[Whole-blood transfusion for hemorrhagic shock resuscitation: two cases in Djibouti].

PubMed

Cordier, P Y; Eve, O; Dehan, C; Topin, F; Menguy, P; Bertani, A; Massoure, P L; Kaiser, E

2012-01-01

Hemorrhagic shock requires early aggressive treatment, including transfusion of packed red blood cells and hemostatic resuscitation. In austere environments, when component therapy is not available, warm fresh whole-blood transfusion is a convenient treatment. It provides red blood cells, clotting factors, and functional platelets. Therefore it is commonly used in military practice to treat hemorrhagic shock in combat casualties. At Bouffard Hospital Center in Djibouti, the supply of packed red blood cells is limited, and apheresis platelets are unavailable. We used whole blood transfusion in two civilian patients with life-threatening non-traumatic hemorrhages. One had massive bleeding caused by disseminated intravascular coagulation due to septic shock; the second was a 39 year-old pregnant woman with uterine rupture. In both cases, whole blood transfusion (twelve and ten 500 mL bags respectively), combined with etiological treatment, enabled coagulopathy correction, hemorrhage control, and satisfactory recovery.

Tactical Damage Control Resuscitation.

PubMed

Fisher, Andrew D; Miles, Ethan A; Cap, Andrew P; Strandenes, Geir; Kane, Shawn F

2015-08-01

Recently the Committee on Tactical Combat Casualty Care changed the guidelines on fluid use in hemorrhagic shock. The current strategy for treating hemorrhagic shock is based on early use of components: Packed Red Blood Cells (PRBCs), Fresh Frozen Plasma (FFP) and platelets in a 1:1:1 ratio. We suggest that lack of components to mimic whole blood functionality favors the use of Fresh Whole Blood in managing hemorrhagic shock on the battlefield. We present a safe and practical approach for its use at the point of injury in the combat environment called Tactical Damage Control Resuscitation. We describe pre-deployment preparation, assessment of hemorrhagic shock, and collection and transfusion of fresh whole blood at the point of injury. By approaching shock with goal-directed therapy, it is possible to extend the period of survivability in combat casualties. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats.

PubMed

Matsuoka, Tadashi; Suzuki, Masaru; Sano, Motoaki; Hayashida, Kei; Tamura, Tomoyoshi; Homma, Koichiro; Fukuda, Keiichi; Sasaki, Junichi

2017-09-01

Mortality of hemorrhagic shock primarily depends on whether or not the patients can endure the loss of circulating volume until radical treatment is applied. We investigated whether hydrogen (H2) gas inhalation would influence the tolerance to hemorrhagic shock and improve survival. Hemorrhagic shock was achieved by withdrawing blood until the mean arterial blood pressure reached 30-35 mm Hg. After 60 minutes of shock, the rats were resuscitated with a volume of normal saline equal to four times the volume of shed blood. The rats were assigned to either the H2 gas (1.3% H2, 26% O2, 72.7% N2)-treated group or the control gas (26% O2, 74% N2)-treated group. Inhalation of the specified gas mixture began at the initiation of blood withdrawal and continued for 2 hours after fluid resuscitation. The survival rate at 6 hours after fluid resuscitation was 80% in H2 gas-treated rats and 30% in control gas-treated rats (p < 0.05). The volume of blood that was removed through a catheter to induce shock was significantly larger in the H2 gas-treated rats than in the control rats. Despite losing more blood, the increase in serum potassium levels was suppressed in the H2 gas-treated rats after 60 minutes of shock. Fluid resuscitation completely restored blood pressure in the H2 gas-treated rats, whereas it failed to fully restore the blood pressure in the control gas-treated rats. At 2 hours after fluid resuscitation, blood pressure remained in the normal range and metabolic acidosis was well compensated in the H2 gas-treated rats, whereas we observed decreased blood pressure and uncompensated metabolic acidosis and hyperkalemia in the surviving control gas-treated rats. H2 gas inhalation delays the progression to irreversible shock. Clinically, H2 gas inhalation is expected to stabilize the subject until curative treatment can be performed, thereby increasing the probability of survival after hemorrhagic shock.

Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function

PubMed Central

Yuxia, Guan; Singh, Khushboo; Reilly, Patrick M.

2017-01-01

Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays a vital role in maintaining vasomotor tone during acute blood loss. We hypothesized that decompensated hemorrhagic shock is associated with decreased AVP stores and supplementation during resuscitation would improve both blood pressure and renal function. Using a decompensated hemorrhagic shock model, male Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and maintained until the MAP could not be sustained without fluid. Once 40% of the shed volume was returned in lactated Ringer’s (Severe Shock), animals were resuscitated over 60 minutes with 4x the shed volume in lactated Ringer’s (LR) or the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6-9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with AVP). Blood samples were taken to measure AVP levels and renal function. Pituitaries were harvested and assayed for AVP. Kidney samples were taken to assess mitochondrial function, histology, and oxidative damage. Baseline pituitary AVP stores (30,364 ± 5311 pg/mg) decreased with severe shock and were significantly depressed post-resuscitation (13,910 ± 3016 pg/ml. p<0.05) and at 18hr (15,592 ±1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher serum AVP levels at 60R (31±8 vs 79±12; p<0.01) with an improved MAP both at 60R (125±3 vs 77±7mmHg; p<0.01) and 18hr (82±6 vs 69±5mmHg;p<0.05). AVP supplementation preserved complex I respiratory capacity at 60R and both complex I and II function at 18hr (p<0.05). AVP was also associated with decreased reactive oxygen species at 60R (856±67 vs 622±48F RFU) and significantly decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9±0.1 vs 1.7±0.1 fold change, p<0.01) and nitrosylation (0.9±0.1 vs 1.4±0.2 fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP levels decrease during severe hemorrhage and may contribute to the development of decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation improves blood pressure, preserves renal mitochondrial function, and mitigates acute kidney injury. PMID:29065123

The outcomes of 1120 severe multiple trauma patients with hemorrhagic shock in an emergency department: a retrospective study.

PubMed

Wen, Yin; Yang, Huang; Wei, Wang; Shan-shou, Liu

2013-01-01

Uncontrolled hemorrhagic shock is a significant factor in death of severe multiple trauma patients. The acute management of injured bleeding in emergency department (ED) may improve patient outcomes. The medical records of severe multiple trauma patients with hemorrhagic shock in our ED were reviewed to summarize an evidence-based approach to the management of critically injured bleeding trauma patients. A retrospective study was carried out from January 2002 to December 2011 in a Chinese tertiary hospital. Clinical data from major trauma patients with hemorrhagic shock admitted to ED were evaluated. The patients were stratified based on the characteristics of traumatic condition and resuscitation strategies. The medical treatments and the outcomes of these severe multiple trauma patients were described. A total of 1120 major trauma patients, consisting of 832 males and 288 females, were enrolled. 906 of the patients (80.9%) were injured in traffic accidents, 104 (9.3%) from falling, and 100 from other reasons. The number of injured sites varied from 2 to 6, 616(55.0%) more than 3. 902 (80.5%) trauma patients have recovered and been discharged from hospital. Uncontrolled hemorrhagic shock is a main reason of trauma patients' death. The resuscitation strategy should center upon permissive hypotension and early hemostatic resuscitation combined identified and corrects coagulopathy. The current approach to the management of critically injured bleeding trauma patients is able to improve patient outcomes.

Inhaled, Nebulized Sodium Nitrite Protects In Murine and Porcine Experimental Models Of Hemorrhagic Shock and Resuscitation by Limiting Mitochondrial Injury

PubMed Central

Kautza, Benjamin; Gomez, Hernando; Escobar, Daniel; Corey, Catherine; Ataya, Bilal; Luciano, Jason; Botero, Ana Maria; Gordon, Lisa; Brumfield, John; Martinez, Silvia; Holder, Andre; Ogundele, Olufunmilayo; Pinsky, Michael; Shiva, Sruti; Zuckerbraun, Brian S.

2015-01-01

Objective The cellular injury that occurs in the setting of hemorrhagic shock and resuscitation (HS/R) affects all tissue types and can drive altered inflammatory responses. Resuscitative adjuncts hold the promise of decreasing such injury. Here we test the hypothesis that sodium nitrite (NaNO2), delivered as a nebulized solution via an inhalational route, protects against injury and inflammation from HS/R. Methods Mice underwent HS/R to a mean arterial pressure (MAP) of 20 or 25 mmHg. Mice were resuscitated with Lactated Ringers after 90–120 minutes of hypotension. Mice were randomized to receive nebulized NaNO2 via a flow through chamber (30mg in 5mL PBS). Pigs (30–35 kg) were anesthetized and bled to a MAP of 30–40 mmHg for 90 minutes, randomized to receive NaNO2 (11 mg in 2.5 mL PBS) nebulized into the ventilator circuit starting 60 minutes into the hypotensive period, followed by initial resuscitation with Hextend. Pigs had ongoing resuscitation and support for up to four hours. Hemodynamic data were collected continuously. Results NaNO2 limited organ injury and inflammation in murine hemorrhagic shock. A nitrate/nitrite depleted diet exacerbated organ injury, as well as mortality, and inhaled NaNO2 significantly reversed this effect. Furthermore, NaNO2 limited mitochondrial oxidant injury. In porcine HS/R, NaNO2 had no significant influence on shock induced hemodynamics. NaNO2 limited hypoxia/reoxia or HS/R-induced mitochondrial injury and promoted mitochondrial fusion. Conclusion NaNO2 may be a useful adjunct to shock resuscitation based on its limitation of mitochondrial injury. PMID:26410351

Bladder mucosa pH and Pco2 as a minimally invasive monitor of hemorrhagic shock and resuscitation.

PubMed

Clavijo-Alvarez, Julio A; Sims, Carrie A; Menconi, Michael; Shim, Inbo; Ochoa, Christian; Puyana, Juan Carlos

2004-12-01

Continuous monitoring of pH, Pco2, and Po2 using fiberoptic sensor technology has been proposed recently as a clinical monitor of the severity of shock and impaired tissue perfusion. Surrogates of gut tissue perfusion such as gastric tonometry, although cumbersome, have been used to indirectly quantify the degree of gut ischemia. The purpose of this study was to demonstrate the feasibility of monitoring bladder mucosa (BM) and to compare urinary bladder mucosa and proximal jejunum mucosa interstitial pH and Pco2 during hemorrhagic shock and resuscitation. Eleven male miniature swine (25-35 kg) (control, n = 4; shock, n = 7) underwent jejunal tonometry and cystostomy. A multisensor probe was placed adjacent to the BM. Urine was diverted. Normocarbia was maintained. Animals were hemorrhaged and kept at a mean arterial pressure of 40 mm Hg. When a constant infusion was required to maintain the mean arterial pressure at 40 mm Hg (decompensation), animals were resuscitated with shed blood plus two times the shed volume in lactated Ringer's solution (20 minutes) and observed for 2 hours. During decompensation, BM pH values decreased significantly from 7.33 +/- 0.08 to 7.01 +/- 0.2 (p < 0.01) and recovered to 7.11 +/- 0.19 at 120 minutes after completion of resuscitation. During decompensation, BM Pco2 values increased significantly compared with baseline (from 49 +/- 6 mm Hg to 71 +/- 19 mm Hg, p < 0.05) and returned to baseline with resuscitation. Jejunum mucosa and BM interstitial Pco2 correlated throughout shock and resuscitation (r = 0.49). Bland-Altman analysis demonstrated significant differences between jejunum mucosa (intramucosal pH) and BM interstitial pH. Shock-induced changes in the Pco2 of the BM are comparable to tonometric changes in the gut. These data suggest that continuous fiberoptic multisensor probe monitoring of the BM could potentially provide a minimally invasive method for the assessment of impaired tissue perfusion of the splanchnic circulation during shock and resuscitation.

Comparisons of Normal Saline and Lactated Ringer’s Resuscitation on Hemodynamics, Metabolic Responses, and Coagulation in Pigs after Severe Hemorrhagic Shock

DTIC Science & Technology

2013-12-11

vasodilator effects and the risks of metabolic acidosis and hyperkalemia . Keywords: Hemorrhagic shock, Oxygen metabolism, Coagulation, Pre-hospital...www.sjtrem.com/content/21/1/86 of hyperchloremic acidosis from NS resuscitation [37]. Consistent with our current results, clinically significant hyperkalemia ...risks of meta- bolic acidosis and hyperkalemia . Currently, military first responders have NS, LR and Hextend available [20]. How- ever, the results from

Myocardial oxygen delivery after experimental hemorrhagic shock.

PubMed Central

Archie, J P; Mertz, W R

1978-01-01

The two components of myocardial oxygen delivery, coronary blood flow to capillaries and diffusion from capillaries to mitochondria, were studied in six dogs, (1) prior to shock, (2) after three hours of hemorrhage shock at a mean systemic arterial pressure of 40 torr, (3) after reinfusion of shed blood, and (4) during the irreversible late posttransfusion stage. There was a maldistribution of left ventricular coronary flow during late shock consistent with subendocardial ischemia. Cardiac performance was significantly impaired after resuscitation and all dogs became irreversible. Total and regional left ventricular coronary blood flow and myocardial oxygen delivery to capillaries were significantly greater than preshock values in (3) but not different from preshock values in (4). However, the myocardial oxygen diffusion area to distance ratio was significantly lower than preshock values in (3), and slightly lower in (4). These data suggest that myocardial oxygen diffusion may be impaired in the early post transfusion period, (3). Accordingly, the probable etiology of left ventricular dysfunction and possibly irreversibility after resuscitation from hemorrhagic shock is subendocardial ischemia during shock with either post-resuscitation impairment of myocardial oxygen diffusion, or in cellular oxygen utilization, or both. PMID:629622

2017 Military Supplement: Dodecafluoropentane Emulsion (Ddfpe) as a Resuscitation Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review.

PubMed

Graham, Kaitlin; Moon-Massat, Paula F; Unger, Evan C

2017-11-15

Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates toxicities exhibited by previous oxygen therapeutics, while anti-inflammatory properties of DDFPe may alleviate damage from ischemia reperfusion injury. This mini-review summarizes our progress in developing a battle-field ready product to prevent combat death due to hemorrhagic shock and/or TBI. Preclinical studies, for both indications, show promising effects of DDFPe as a resuscitation fluid. DDFPe may become a part of the toolkit for tactical healthcare professionals in battlefield and domestic emergency medicine.

The Significance of Splenectomy in Experimental Swine Models of Controlled Hemorrhagic Shock

DTIC Science & Technology

2013-11-01

carefully eval uated in other experimental models of hem orrhage (e.g., uncontrolled hemorrhage, models with concomitant blunt or orthopedic trauma , and...hemorrhagic shock. J Trauma . 2006;61(1):75 81. 3. Pottecher J, Chemla D, Xavier L, et al. The pulse pressure/heart rate ratio as a marker of stroke volume...changes during hemorrhagic shock and resuscitation in anesthetized swine. J Trauma Acute Care Surg. 2013;74(6):1438 1445. 4.Devlin JJ, Kircher SJ

Hepatoprotective Effects of Corilagin Following Hemorrhagic Shock are Through Akt-Dependent Pathway

PubMed Central

Liu, Fu-Chao; Chaudry, Irshad H.; Yu, Huang-Ping

2017-01-01

ABSTRACT Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague–Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin-treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway. PMID:27559697

Adverse Effects of Hemorrhagic Shock Resuscitation with Stored Blood are Ameliorated by Inhaled Nitric Oxide in Lambs

PubMed Central

Baron, David M.; Beloiartsev, Arkadi; Nakagawa, Akito; Martyn, Trejeeve; Stowell, Christopher P.; Malhotra, Rajeev; Mayeur, Claire; Bloch, Kenneth D.; Zapol, Warren M.

2013-01-01

Objectives Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Plasma hemoglobin scavenges nitric oxide (NO), which can cause vasoconstriction, induce inflammation and activate platelets. We hypothesized that transfusion of RBCs stored for prolonged periods would induce adverse effects (pulmonary vasoconstriction, tissue injury, inflammation, and platelet activation) in lambs subjected to severe hemorrhagic shock, and that concurrent inhalation of NO would prevent these adverse effects. Design Animal study. Setting Research laboratory at the Massachusetts General Hospital, Boston, MA. Subjects Seventeen awake Polypay-breed lambs. Interventions Lambs were subjected to 2 h of hemorrhagic shock by acutely withdrawing 50% of their blood volume. Lambs were resuscitated with autologous RBCs stored for 2 h or less (fresh) or 39±2 (mean±SD) days (stored). Stored RBCs were administered with or without breathing NO (80 ppm) during resuscitation and for 21 h thereafter. Measurements and Main Results We measured hemodynamic and oxygenation parameters, markers of tissue injury and inflammation, plasma hemoglobin concentrations, and platelet activation. Peak pulmonary arterial pressure was higher after resuscitation with stored than with fresh RBCs (24±4 vs. 14±2 mmHg, p<0.001) and correlated with peak plasma hemoglobin concentrations (R2=0.56, p=0.003). At 21 h after resuscitation, pulmonary myeloperoxidase activity was higher in lambs resuscitated with stored than with fresh RBCs (11±2 vs. 4±1 U/g, p=0.007). Furthermore, transfusion of stored RBCs increased plasma markers of tissue injury and sensitized platelets to adenosine diphosphate activation. Breathing NO prevented the pulmonary hypertension, and attenuated the pulmonary myeloperoxidase activity, as well as tissue injury and sensitization of platelets to adenosine diphosphate. Conclusions Our data suggest that resuscitation of lambs from hemorrhagic shock with autologous stored RBCs induces pulmonary hypertension and inflammation, which can be ameliorated by breathing NO. PMID:23887236

N-Acetylcysteine and Desferoxamine Reduce Pulmonary Oxidative Stress Caused by Hemorrhagic Shock in a Porcine Model.

PubMed

Mani, Alexandra; Staikou, Chryssoula; Karmaniolou, Iosifina; Orfanos, Nikolaos; Mylonas, Anastassios; Nomikos, Tzortzis; Pafiti, Agathi; Papalois, Apostolos; Arkadopoulos, Nikolaos; Smyrniotis, Vassilios; Theodoraki, Kassiani

2017-02-01

To investigate the pulmonary oxidative stress and possible protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine model subjected to hemorrhagic shock. Twenty-one pigs were randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8) and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were subjected to a 40-min shock period induced by liver trauma, followed by a 60-min resuscitation period. During shock, the mean arterial pressure (MAP) was maintained at 30-40 mmHg. Resuscitation consisted of crystalloids (35 mL/kg) and colloids (18 mL/kg) targeting to MAP normalization (baseline values ± 10%). In addition, Group-C received pretreatment with NAC 200 mg/kg plus DFX 2 g as intravenous infusions. Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyls and glutathione peroxidase (GPx) activity were determined in lung tissue homogenates. Also, histological examination of pulmonary tissue specimens was performed. TBARS were higher in Group-B than in Group-A or Group-C: 2.90 ± 0.47, 0.57 ± 0.10, 1.78 ± 0.47 pmol/μg protein, respectively (p < 0.05). Protein carbonyls content was higher in Group-B than in Group-A or Group-C: 3.22 ± 0.68, 0.89 ± 0.30, 1.95 ± 0.54 nmol/mg protein, respectively (p > 0.05). GPx activity did not differ significantly between the three groups (p > 0.05). Lung histology was improved in Group-C versus Group-B, with less alveolar collapse, interstitial edema and inflammation. NAC plus DFX prevented the increase of pulmonary oxidative stress markers and protein damage after resuscitated hemorrhagic shock and had beneficial effect on lung histology. NAC/DFX combination may be used in the multimodal treatment of hemorrhagic shock, since it may significantly prevent free radical injury in the lung.

Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

PubMed Central

Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.

2015-01-01

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440

N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock.

PubMed

Moreira, Miriam Aparecida; Irigoyen, Maria Claudia; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Koike, Marcia Kiyomi; Montero, Edna Frasson de Souza; Martins, José Luiz

2016-06-01

Renal ischemia/reperfusion injury induced by hemorrhagic shock (HS) and subsequent fluid resuscitation is a common cause of acute renal failure. The objective of this study was to evaluate the effect of combining N-acetylcysteine (NAC) with fluid resuscitation on renal injury in rats that underwent HS. Two groups of male Wistar rats were induced to controlled HS at 35 mm Hg mean arterial pressure for 60 min. After this period, the HS and fluid resuscitation (HS/R) group was resuscitated with lactate containing 50% of the blood that was withdrawn. The HS/R + NAC group was resuscitated with Ringer's lactate combined with 150 mg/kg of NAC and blood. The sham group animals were catheterized but were not subjected to shock. All animals were kept under anesthesia and euthanized after 120 min of fluid resuscitation or observation. Animals treated with NAC presented attenuation of histologic lesions, reduced oxidative stress, and apoptosis markers when compared with animals from the HS/R group. The serum creatinine was similar in all the groups. NAC is a promising drug for combining with fluid resuscitation to attenuate the kidney injury associated with HS. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral effects of resuscitation with hypertonic saline and a new low-sodium hypertonic fluid in hemorrhagic shock and head injury.

PubMed

Sheikh, A A; Matsuoka, T; Wisner, D H

1996-07-01

A 2400-mOsm/L hypertonic solution (isosal) with a lower sodium content, compared with conventional 7.5% hypertonic saline, was formulated using a mixture of sodium chloride, glucose, and mixed amino acids. This solution was developed to minimize hypernatremia during resuscitation. We assessed the effects of isosal on hemodynamics, brain edema, and plasma sodium concentration after head injury associated with hemorrhagic shock. DESIGN. Prospective, randomized laboratory study. University research laboratory. Twenty-one adult female Suffolk sheep, weighing 39 to 49 kg. Animals were subjected to a 2-hr period of hemorrhagic shock to a mean arterial pressure (MAP) of 40 to 45 mm Hg in the presence of a freeze injury to the cerebral cortex. The hemorrhagic shock/head injury phase was followed by 2 hrs of resuscitation with isosal, a new 2400-mosm/L low-sodium hypertonic fluid, 2400 mosm/L of 7.5% hypertonic saline, or lactated Ringer's solution. Initial resuscitation was with a bolus injection of 8 mL/kg of the study solution; subsequent resuscitation in all three groups was with lactated Ringer's solution as needed to maintain baseline cardiac output. Serial hemodynamics, intracranial pressure, electrolytes, and osmolarity were measured. AT the end of resuscitation, the animals were killed and brain water content (mL H2O/g dry weight) of the injured and uninjured areas was determined. Resuscitation volumes were significantly lower in the isosal (19 +/- 5 mL/kg) and 7.5% hypertonic saline (14 +/- 2 mL/mg) groups compared with the lactated Ringer's solution (35 +/- 5 mL/kg) group. Intracranial pressure after 2 hrs of resuscitation was significantly lower in the isosal (7 +/- 1 mm Hg) and hypertonic saline groups (4 +/- 1 mm Hg). Water content in all areas of the brain was significantly lower in the hypertonic saline group compared with the lactated Ringer's solution group. Brain water content in the isosal group was lower than in the lactated Ringer's solution group only in the cerebellum. Plasma sodium content was lower in the isosal group than in the hypertonic saline group. After combined head injury and shock, isosal and 7.5% hypertonic saline have similar effects on hemodynamics and intracranial pressure. Hypertonic saline induces a greater degree of brain dehydration; isosal resuscitation results in smaller increases in plasma sodium.

Minocycline and Doxycycline, but not Tetracycline, Mitigate Liver and Kidney Injury after Hemorrhagic Shock/Resuscitation*

PubMed Central

Kholmukhamedov, Andaleb; Czerny, Christoph; Hu, Jiangting; Schwartz, Justin; Zhong, Zhi; Lemasters, John J.

2014-01-01

Background Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic and oxidative stress. Our Aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation. Methods Mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg) or vehicle. For pre-plus post-treatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h. Results Serum alanine aminotransferase (ALT) increased to 1988 and 1878 U/L after post-treatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline post-treatment decreased ALT to 857 and 863 U/L. Pre-plus post-treatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 279 μM, which minocycline and doxycycline post-treatment decreased to 118 and 112 μM. Minocycline and doxycycline pre- plus post-treatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL and caspase-3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) post-treatment improved 1-week survival from 38%(vehicle) to 69% and 67%, respectively. Conclusion Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore have clinical efficacy to mitigate liver and kidney injury after resuscitated hemorrhage. PMID:24978888

Hepatic and pulmonary apoptosis after hemorrhagic shock in swine can be reduced through modifications of conventional Ringer's solution.

PubMed

Ayuste, Eduardo C; Chen, Huazhen; Koustova, Elena; Rhee, Peter; Ahuja, Naresh; Chen, Zhang; Valeri, C Robert; Spaniolas, Konstantinos; Mehrani, Tina; Alam, Hasan B

2006-01-01

Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in vitro and in small animal experiments, have not been confirmed in large animal models. Our hypothesis was that in a clinically relevant large animal model of hemorrhage, resuscitation with racemic lactated Ringer's solution would induce cellular apoptosis, which can be attenuated by elimination of d-lactate. Yorkshire swine (n = 49, weight 40-58 kg) were subjected to uncontrolled (iliac arterial and venous injuries) and controlled hemorrhage, totaling 40% of estimated blood volume. They were randomized (n = 7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L-LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was identical to LR except for equimolar substitution of lactate with beta-hydroxybutyrate. Resuscitation was performed in three phases, simulating (1) prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood gasses, circulating cytokines (TNF-alpha, IL-1, -6, -10), and markers of organ injury were serially measured. Metabolic activity of brain, and liver, was measured with microdialysis. Four hours postinjury, organs were harvested for Western blotting, ELISA, TUNEL assay, and immunohistochemistry. All resuscitation strategies restored blood pressure, but clearance of lactic acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased during shock and improved with resuscitation, without any significant inter-group differences. Levels of cytokines in circulation were similar, but tissue levels of TNF in liver and lung increased six- and threefolds (p < 0.05) in NR group. In liver, all resuscitation strategies significantly decreased TNF levels compared with the NR group, but in the lung resuscitation with lactated Ringer (DL and L isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation with other solutions. In this large animal model of hemorrhagic shock, resuscitation with conventional (racemic) LR solution increased apoptotic cell death in liver and lung. This effect can be prevented by simple elimination of D-lactate from the Ringer's solution.

Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock.

PubMed

Wu, Feng; Peng, Zhanglong; Park, Pyong Woo; Kozar, Rosemary A

2017-09-01

Syndecan-1 (Sdc1) is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of Sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary Sdc1 and reduction of lung injury, but the precise contribution of Sdc1 to FFPs protection in the lung remains unclear. Human lung endothelial cells were used to assess the time and dose-dependent effect of FFP on Sdc1 expression and the effect of Sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation. Wild-type and Sdc1 mice were subjected to hemorrhagic shock followed by resuscitation with lactated Ringers (LR) or FFP and compared with shock alone and shams. Lungs were harvested after 3 h for analysis of permeability, histology, and inflammation and for measurement of syndecan- 2 and 4 expression. In vitro, FFP enhanced pulmonary endothelial Sdc1 expression in time- and dose-dependent manners and loss of Sdc1 in pulmonary endothelial cells worsened permeability and stress fiber formation by FFP. Loss of Sdc1 in vivo led to equivalency between LR and FFP in restoring pulmonary injury, inflammation, and permeability after shock. Lastly, Sdc1 mice demonstrated a significant increase in pulmonary syndecan 4 expression after hemorrhagic shock and FFP-based resuscitation. Taken together, our findings support a key role for Sdc1 in modulating pulmonary protection by FFP after hemorrhagic shock. Our results also suggest that other members of the syndecan family may at least be contributing to FFP's effects on the endothelium, an area that warrants further investigation.

Small-volume resuscitation from hemorrhagic shock with polymerized human serum albumin.

PubMed

Messmer, Catalina; Yalcin, Ozlem; Palmer, Andre F; Cabrales, Pedro

2012-10-01

Human serum albumin (HSA) is used as a plasma expander; however, albumin is readily eliminated from the intravascular space. The objective of this study was to establish the effects of various-sized polymerized HSAs (PolyHSAs) during small-volume resuscitation from hemorrhagic shock on systemic parameters, microvascular hemodynamics, and functional capillary density in the hamster window chamber model. Polymerized HSA size was controlled by varying the cross-link density (ie, molar ratio of glutaraldehyde to HSA). Hemorrhage was induced by controlled arterial bleeding of 50% of the animal's blood volume (BV), and hypovolemic shock was maintained for 1 hour. Resuscitation was implemented in 2 phases, first, by infusion of 3.5% of the BV of hypertonic saline (7.5% NaCl) then followed by infusion of 10% of the BV of each PolyHSA. Resuscitation provided rapid recovery of blood pressure, blood gas parameters, and microvascular perfusion. Polymerized HSA at a glutaraldehyde-to-HSA molar ratio of 60:1 (PolyHSA(60:1)) provided superior recovery of blood pressure, microvascular blood flow, and functional capillary density, and acid-base balance, with sustained volume expansion in relation to the volume infused. The high molecular weight of PolyHSA(60:1) increased the hydrodynamic radius and solution viscosity. Pharmacokinetic analysis of PolyHSA(60:1) indicates reduced clearance and increased circulatory half-life compared with monomeric HSA and other PolyHSA formulations. In conclusion, HSA molecular size and solution viscosity affect central hemodynamics, microvascular blood flow, volume expansion, and circulation persistence during small-volume resuscitation from hemorrhagic shock. In addition, PolyHSA can be an alternative to HSA in pathophysiological situations with compromised vascular permeability. Copyright © 2012 Elsevier Inc. All rights reserved.

Investigation of Intravenous Hydroxocobalamin Compared to Hextend for Resuscitation in a Swine Model of Uncontrolled Hemorrhagic Shock: A Preliminary Report

DTIC Science & Technology

2017-08-27

TYPE 0812712017 Poster 4. TITLE AND SUBTITLE Investigation of intravenous hydroxocobalamin compared to Hcxtcnd for resuscitation in a S\\vinc...Praleos1onal 7,.0 ApprdvtJ 𔃻Jr ,~1~, re.l14’t. Oi*i~,J;D" i\\ vŕ:~1wJ. Investigation of intravenous Hydroxocobalamin compared to Hextend® for resu...effective as IV Hextend® in improving systolic blood pressure (SBP) in a controlled hemorrhagic shock model. We aimed to compare IV hydroxocobalamin (HOC

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

PubMed

Yang, Long; Dong, Xiujuan

2017-06-01

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock

PubMed Central

Rao, Geeta; Yadav, Vivek R.; Awasthi, Shanjana; Roberts, Pamela R.

2016-01-01

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms. PMID:27288424

Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

DTIC Science & Technology

2004-09-01

hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...hemodynamics and reestablishing inflammatory equilibrium [12]. Various immunoinflammatory alterations have been described in clinical and experimental ...ultimately causing greater morbidity and mortality [4]. Moreover, convincing experimental evidence indicates that conventional large-volume fluid

[Effect of different volumes of fluid resuscitation on hemorrhagic shock with pulmonary edema at high altitude in the unacclimated rat].

PubMed

Liu, Liang-ming; Hu, De-yao; Liu, Jian-cang; Li, Ping; Liu, Hou-dong; Xiao, Nan; Zhou, Xue-wu; Tian, Kun-lun; Huo, Xiao-ping; Shi, Quan-gui; He, Yan-mei; Yin, Zuo-ming

2003-05-01

To study the effects of different volumes of fluid resuscitation on hemorrhagic shock with pulmonary edema at high altitude in the unacclimated rat. One hundred and twenty-six SD rats transported to Lasa, Tibet, 3 760 meters above the sea level, were anesthetized one week later with sodium pentobarbital (30 mg/kg, intraperitoneal). Hemorrhagic shock with pulmonary edema model was induced by hemorrhage (50 mm Hg for 1 hour, 1 mmHg=0.133 kPa) plus intravenous injection of oleic acid (50 microl/kg). Experiments were then conducted in two parts. Sixty-three rats in part I were equally divided into nine groups (n=7): normal control, hemorrhagic shock control, hemorrhagic shock with pulmonary edema (HSPE) without fluid infusion, HSPE plus infusing lactated Ringer's solution (LR) with 0.5-, 1-, 1.5-, 2- or 3- fold volume shed blood, and 1 volume of LR plus mannitol (10 ml/kg). Hemodynamic parameters including mean arterial blood pressure (MAP), left intraventricular systolic pressure (LVSP) and the maximal change rate of intraventricular pressure rise or decline (+/- dp/dt max) were observed at 15, 30, 60 and 120 minutes after infusion, blood gases were measured at 30 and 120 minutes after infusion and the water content of lung and brain was determined at 120 minutes after infusion. In part II, additional 63 rats were used to observe the effect of different volumes of fluid resuscitation on survival time of HSPE rats. 0.5 volume of LR infusion significantly improved MAP, LVSP and +/- dp/dt max, prolonged the survival time of HSPE animals (all P<0.01), while it did not increase the water content of lung and brain and had no marked influence on blood gases. One volume of LR infusion slightly improved hemodynamic parameters, prolonged the survival time and increased the water content of lung. More than 1 volume of LR infusion including 1.5-, 2- and 3- fold volume LR deteriorated the hemodynamic parameters and decreased the survival time of shocked animal, meanwhile they apparently increased the water content of lung. One volume of LR plus mannitol (10 ml/kg) infusion did not improve the hemodynamic parameters and blood gases; also it did not decrease the water content of lung. The tolerance to fluid infusion for the unacclimated animal subjected to hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. 0.5-1 volume of LR infusion appears to be beneficial effect on resuscitation at high altitude, while over 1 volume of LR infusion would aggravate pulmonary edema and exacerbate fluid resuscitation effect.

Experimental Study on the Efficacy of Site-Specific PEGylated Human Serum Albumins in Resuscitation From Hemorrhagic Shock.

PubMed

Song, Xinlei; Zhang, Shu; Cheng, Yanna; Zhao, Ting; Lian, Qianqian; Lu, Lu; Wang, Fengshan

2016-11-01

To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. Laboratory. Male Wistar rats. Prospective study. Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids. The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability. Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.

Development and Resuscitation of a Sedated, Mature Male Miniature Swine Severe Hemorrhage Model

DTIC Science & Technology

2011-07-01

control. Results: Hemorrhage resulted in a characteristic hypotension and metabolic acidosis . Survival time for the control swine was 64 minutes...domestic swine4 and was characteristic of a hemorrhage- induced metabolic acidosis , with a decrease in blood HCO3, and BE and an increase in blood...Hammett M, Asher L, et al. Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock. 2005;24:145–152

Hypertonic/Hyperoncotic Resuscitation from Shock: Reduced Volume Requirement and Lower Intracranial Pressure

DTIC Science & Technology

1989-10-01

in Dogs with Hemorrhagic Shock and an Intracranial Mass. Seventh International Symposium on Intracranial Pressure and Brain Injury , Ann Arbor, Michigan...with Hemorrhagic Shock and an Intracranial Mass. Seventh International Symposium on Intracranial Pressure and Brain Injury . Intracranial Pressure VII...and MCI US groups. Discussion: Following this severe insult a iETTiFMT3-a clinical head injury combined wit6i hemorrha Ic shock, a cobntnc/h rcctc

Changes in lung ultrastructure following heterologous and homologous serum albumin infusion in the treatment of hemorrhagic shock.

PubMed Central

Moss, G S; Das Gupta, T K; Brinkman, R; Sehgal, L; Newsom, B

1979-01-01

The object of this study was to compare the ultrastructure pulmonary effects of the infusion of homologous and heterologous serum albumin solution in the treatment of hemorrhagic shock in baboons. Adult baboons subjected to hemorrhagic shock were resuscitated with either baboon serum albumin, human serum albumin, or Ringer's lactate solution. The lungs were fixed in vivo with potassium pyroantimony, a solution which produces electron dense interstitial precipitation of sodium. The lungs from animals resuscitated with baboon serum albumin showed evidence of interstitial edema, including dispersion of collagen fibers, interstitial smudging and increased interstital sodium concentrations. Similar changes were seen following human serum albumin infusions. Lung tissue from animals treated with Ringer's lactate solution showed minimal changes from normal. These results suggest that interstitial pulmonary edema develops after either homologous or heterologous serum albumin infusion in the treatment of hemorrhagic shock in baboons. Images Figs. 2a and b. Figs. 3a and b. Figs. 4a and b. Figs. 5a and b. Figs. 6a and b. PMID:106780

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT)

DTIC Science & Technology

2013-10-01

proceed with the formal Department of the Army review. 15. SUBJECT TERMS Trauma, hemorrhagic shock, cardiac arrest, cardiopulmonary resuscitation ...n/a Introduction Cardiopulmonary resuscitation (CPR) can save victims of normovolemic cardiac arrest (CA), e.g., ventricular...delayed resuscitation with cardiopulmonary bypass. The primary outcome variable will be survival to hospital discharge with minimal neurologic dysfunction

Novel Resuscitation from Lethal Hemorrhage Suspended Animation for Delayed Resuscitation

DTIC Science & Technology

2005-10-01

hypothermia on rat hippocampal proteomic profiles after 30 minutes of complete cerebral ischemia. American Stroke Association; Fellows’ Research Day, Hilton...well as traumatic brain injury , stroke , hemorrhagic shock, myocardial infarction, hepatic failure, and even pulmonary failure with sepsis. Additional...specific secondary injury 64 Chapter 5 mechanisms, such as local cerebral inflammation, were shown. State-of-the- art reviews by central nervous system

The use of resuscitative endovascular balloon occlusion of the aorta to control hemorrhagic shock during video-assisted retroperitoneal debridement or infected necrotizing pancreatitis.

PubMed

Weltz, Adam S; Harris, Donald G; O'Neill, Natalie A; O'Meara, Lindsay B; Brenner, Megan L; Diaz, Jose J

2015-01-01

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique that has been shown to provide central vascular control to support proximal aortic pressure and minimize hemorrhage in a wide variety of clinic settings, however the role of REBOA for emergency general surgery is less defined. This is a report of a 44 year old man who experienced hemorrhagic shock during video-assisted retroperitoneal debridement (VARD) for necrotizing pancreatitis where REBOA was used to prevent ongoing hemorrhage and death. This is the first documented report REBOA being used during pancreatic debridement in the literature and one of the first times it has been used in emergency general surgery. The use of REBOA is an option for those in hemorrhagic shock whom conventional aortic cross-clamping or supra-celiac aortic exposure is either not possible or exceedingly dangerous. REBOA allows for adequate resuscitation and can be used as a bridge to definitive therapy in a range of surgical subspecialties with minimal morbidity and complications. The risks associated with insertion of wires, sheaths, and catheters into the arterial system, as well as the risk of visceral and spinal cord ischemia due to aortic occlusion mandate that the use of this technique be utilized in only appropriate clinical scenarios. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats.

PubMed

Nassoiy, Sean P; Byron, Kenneth L; Majetschak, Matthias

2017-01-17

Recent evidence suggests that drugs targeting Kv7 channels could be used to modulate vascular function and blood pressure. Here, we studied whether Kv7 channel inhibitors can be utilized to stabilize hemodynamics and reduce resuscitation fluid requirements after hemorrhagic shock. Anesthetized male Sprague-Dawley rats were instrumented with arterial and venous catheters for blood pressure monitoring, hemorrhage and fluid resuscitation. Series 1: Linopirdine (Kv7 channel blocker, 0.1-6 mg/kg) or retigabine (Kv7 channel activator, 0.1-12 mg/kg) were administered to normal animals. Series 2: Animals were hemorrhaged to a MAP of 25 mmHg for 30 min, followed by fluid resuscitation with normal saline (NS) to a MAP of 70 mmHg until t = 75 min. Animals were treated with single bolus injections of vehicle, linopirdine (1-6 mg/kg), XE-991 (structural analogue of linopirdine with higher potency for channel blockade, 1 mg/kg) prior to fluid resuscitation. Series 3: Animals were resuscitated with NS alone or NS supplemented with linopirdine (1.25-200 μg/mL). Data were analyzed with 2-way ANOVA/Bonferroni post-hoc testing. Series 1: Linopirdine transiently (10-15 min) and dose-dependently increased MAP by up to 15%. Retigabine dose-dependently reduced MAP by up to 60%, which could be reverted with linopirdine. Series 2: Fluid requirements to maintain MAP at 70 mmHg were 65 ± 34 mL/kg with vehicle, and 57 ± 13 mL/kg, 22 ± 8 mL/kg and 22 ± 11 mL/kg with intravenous bolus injection of 1, 3 and 6 mg/kg linopirdine, respectively. XE-991 (1 mg/kg), reduced resuscitation requirements comparable to 3 mg/kg linopirdine. Series 3: When resuscitation was performed with linopirdine-supplemented normal saline (NS), fluid requirements to stabilize MAP were 73 ± 12 mL/kg with NS alone and 72 ± 24, 61 ± 20, 36 ± 9 and 31 ± 9 mL/kg with NS supplemented with 1.25, 6.25, 12.5 and 200 μg/mL linopirdine, respectively. Our data suggest that Kv7 channel blockers could be used to stabilize blood pressure and reduce fluid resuscitation requirements after hemorrhagic shock.

Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.

PubMed

Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Rhee, Peter; Rollwagen, Florence M; Olsen, Cara; Keith, James C; Pollack, Matthew

2005-06-01

We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 microg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 microg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 +/- 7.5 mmHg, 71.0 +/- 8.9 mmHg, and 72.9 +/- 12.3 mmHg, respectively) than in group III (59.9 +/- 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 +/- 0.56 L/min) than in group III (2.99 +/- 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This strategy also significantly reduced the extent of third space fluid losses while also having a favorable impact on the intravascular volume status as evidenced by the improved urine output.

An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model.

PubMed

Xu, Yanjie; Dai, Xiongwei; Zhu, Danxia; Xu, Xiaoli; Gao, Cao; Wu, Changping

2015-01-01

Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. Hemorrhagic shock was induced in adult male Sprague-Dawley rats by drawing blood from the femoral artery to maintain the mean arterial pressure at 35-40 mmHg for 1.5 h. The rats were assigned to four groups and the H2S donor, NaHS (28 μmol/kg, i.p.), was injected before the resuscitation in certain groups. After resuscitation the animals were observed and then killed to harvest the hearts. The morphological investigation and ultrastructural analyses were done and apoptotic cells were detected. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. Resuscitated hemorrhagic shock induced heart injury and significantly increased the levels of serum myocardial enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, it caused marked increase of apoptotic cells in heart tissue. Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria-involved pathways.

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-05-01

Intravital Microscopy was successfully employed for investigating EG sheddÍng in hemorrhagic shock/resuscitation for the very first time; 2) Intravital ...during Hemorrhagic Shock in Rats using Intravital Microscopy. Submitted to Microvascular Research, 2012 (under review). FINAL REPORT Laboratory or...Glycocalyx using Intravital Microscopy. In Preparation. IO) PATENT OR COPYRIGHT APPLICATIONS KESULTING FROM NRC ASSOCIATESHIP KESEARCH Provide titles

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-03-01

l) Intravital Microscopy was successfully employed for investigating EG sheddÍng in hemorrhagic shock/resuscitation for the very first time; 2... Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to identify changes and study mechanisms...Glycocalyx during Hemorrhagic Shock in Rats using Intravital Microscopy. Submitted to Microvascular Research, 2012 (under review). FINAL REPORT Laboratory

Complexity and Animal Models

DTIC Science & Technology

2015-01-01

ventricular fibrillation and cardiopulmonary resuscitation . The second presentation will be summarized below. doi:10.1016/j.jcrc.2010.05.013 Neural dynamics...hemorrhagic shock, resuscitation , trauma, inhalation injury, apnea, and other critical states. This research serves as a test bed for discovery

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

PubMed

Georgoff, Patrick E; Nikolian, Vahagn C; Halaweish, Ihab; Chtraklin, Kiril; Bruhn, Peter J; Eidy, Hassan; Rasmussen, Monica; Li, Yongqing; Srinivasan, Ashok; Alam, Hasan B

2017-07-01

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

Intraosseous infusion of blood products and epinephrine in an adult patient in hemorrhagic shock.

PubMed

Burgert, James M

2009-10-01

A 79-year-old woman presented in the postanesthesia care unit with hematemesis following replacement of a jejunostomy tube. Her medical history included recurrent stage IIIC ovarian cancer. The patient rapidly decompensated despite blood products administered through the patient's implanted medication port. The anesthesia service was consulted for resuscitative support. Examination revealed an alert, hypotensive elderly female in hemorrhagic shock. While peripheral intravenous (IV) access was sought, her condition further deteriorated. Attempts at peripheral access were determined futile and central venous access would be required. An intraosseous (IO) catheter was placed in the proximal medial aspect of the left tibia using the EZ-IO device (Vidacare Corp, San Antonio, Texas). Crystalloid and colloid fluids, blood products, and drugs were administered via the IO route, stabilizing the patient's condition during the central access procedure. The IO route was used throughout the resuscitative effort. Hemostasis was achieved, and the patient was admitted to the intensive care unit. Intraosseous infusion is a valuable and underutilized technique in managing patients in hemorrhagic shock with poor IV access. Anesthesia providers should seek education and training from those experienced in IO placement techniques and consider use of the IO route early in the resuscitative process.

Efforts and Programs of the Department of Defense Relating to the Prevention, Mitigation, and Treatment of Blast Injuries

DTIC Science & Technology

2007-01-01

Combat Critical Care Engineering: Evaluation of Closed Loop Control of Ventilation and Oxygen Flow During Resuscitation in the Compensatory and...Decompensatory Phases of Hemorrhagic Shock: This effort evaluated closed loop control of ventilation and oxygen flow during resuscitation in the...Cerebral Injury Volume, Cerebral Edema, Cerebral Blood Flow and Reactivity, and Histopathology in a Rat Model of Traumatic Brain Injury and Hemorrhagic

Lung and Diaphragm Damage at Varying Oxygen Levels and Ventilator Modes Pst Hemorrhagic

DTIC Science & Technology

2011-12-20

scavenging in prenatal neonates (Vento et al., 2009). In addition, Lee et al. found that mice breathing 40% oxygen had elevated tissue levels of...pulmonary mechanics. Another limitation was that we did not administer any fluid resuscitation to correct the hemorrhagic shock during mechanical... resuscitation . Testing only a controlled mode of mechanical ventilation was a limitation to our study. Most mechanical ventilations offer a mixed mode of

Far Forward Treatment of Hemorrhagic Shock

DTIC Science & Technology

2007-02-01

Ringer’s solutions on human leukocytes. J Trauma 52(5):872-878, 2002 6. Alam HB, Punzalan CM, Koustova E, Bowyer MW, Rhee P. Hypertonic Saline: Intraosseous ...Fluid Resuscitation. 17. February 2006- Anesthesia Grand Rounds. Massachusetts General Hospital, Boston, MA. Topic: Trauma Resuscitation: New

δ opioid receptor antagonist, ICI 174,864, is suitable for the early treatment of uncontrolled hemorrhagic shock in rats.

PubMed

Liu, Liangming; Tian, Kunlun; Zhu, Yu; Ding, Xiaoli; Li, Tao

2013-08-01

Fluid resuscitation is the essential step for early treatment of traumatic hemorrhagic shock. However, its implementation is greatly limited before hospital or during evacuation. The authors investigated whether δ opioid receptor antagonist ICI 174,864 was suitable for the early treatment of traumatic hemorrhagic shock. With uncontrolled hemorrhagic-shock rats, the antishock effects of six dosages of ICI 174,864 (0.1, 0.3, 0.5, 1, 3, and 5 mg/kg) infused with or without a small volume of lactated Ringer's solution (LR) before bleeding controlled or bleeding cessation at different times were observed. ICI 174,864 (0.1-3 mg/kg) with or without 1/4 volume of LR infusion showed dose-dependent increase in the mean arterial blood pressure, and significantly prolonged the survival time and 8-h survival rate, as compared with ICI 174,864 plus 1/2 volume of LR infusion. The best effect was shown with 3 mg/kg of ICI 174,864. Bleeding cessation at 1, 2, or 3 h during infusion of ICI 174,864 (3 mg/kg) plus 1/4 volume of LR improved subsequent treatment (70% 24-h survival rate vs. 50 and 10% 24-h survival rate in hypotensive resuscitation and LR group, respectively). There was significant improvement in hemodynamic parameters, oxygen delivery, and tissue perfusion of hemorrhagic-shock rats with 3 mg/kg of ICI 174,864 plus 1/4 volume of LR infusion. δ Opioid receptor antagonist ICI 174,864 alone or with small volume of fluid infusion has good beneficial effect on uncontrolled hemorrhagic shock. Its early application can "buy" time for subsequent treatment of traumatic shock.

Critical role of oxygen radicals in the initiation of hepatic depression after trauma hemorrhage.

PubMed

Jarrar, D; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

2000-11-01

Although depression in hepatocellular function occurs early after trauma and severe hemorrhage and persists despite fluid resuscitation, it remains unknown whether reactive oxygen species (ROS) play any role in the initiation of hepatocellular depression and damage under those conditions. We hypothesized that administration of a ROS scavenger at the beginning of resuscitation will attenuate organ injury after severe shock. Male Sprague-Dawley rats (275-325 g) underwent laparotomy (i.e., induction of soft tissue trauma) and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of maximal bleed-out with RL over 60 minutes. The ROS scavenger 2-mercaptopropionyl glycine (30 mg/kg) or vehicle was administered intravenously as a bolus at the beginning of resuscitation. At 2 hours after the completion of crystalloid resuscitation or the equivalent interval after sham-operation, cardiac index was measured by a dye dilution technique. Hepatocellular function, i.e., the maximum velocity of indocyanine green clearance (Vmax) and the efficiency of the active transport (Km), was determined using an in vivo hemoreflectometer. Serum levels of tumor necrosis factor (TNF)-alpha and alanine aminotransferase were determined with ELISA and colorimetrically, respectively. The results indicate that at 2 hours after trauma hemorrhage and resuscitation, cardiac index and hepatocellular function were markedly depressed with concomitantly increased serum levels of TNF-alpha and alanine aminotransferase (p < 0.05). Administration of 2-mercaptopropionyl glycine, however, restored the depressed cardiac and hepatic function and markedly attenuated liver enzyme release and serum levels of TNF-alpha (p < 0.05). Our data suggest that ROS play a role in producing the depression in organ functions after severe hemorrhagic shock. Thus, adjuncts that attenuate the detrimental effects of ROS may be useful for improving the depressed cardiac and hepatocellular functions after trauma hemorrhage and resuscitation.

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

PubMed

Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

2008-10-01

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

Pyruvate dose response studies targeting the vital signs following hemorrhagic shock

PubMed Central

Sharma, Pushpa; Vyacheslav, Makler; Carissa, Chalut; Vanessa, Rodriguez; Bodo, Mike

2015-01-01

Objectives: To determine the optimal effective dose of sodium pyruvate in maintaining the vital signs following hemorrhagic shock (HS) in rats. Materials and Methods: Anesthetized, male Sprague-Dawley rats underwent computer-controlled HS for 30 minute followed by fluid resuscitation with either hypertonic saline, or sodium pyruvate solutions of 0.5 M, 1.0 M, 2.0 M, and 4.0 M at a rate of 5ml/kg/h (60 minute) and subsequent blood infusion (60 minute). The results were compared with sham and non- resuscitated groups. The animals were continuously monitored for mean arterial pressure, systolic and diastolic pressure, heart rate, pulse pressure, temperature, shock index and Kerdo index (KI). Results: The Sham group remained stable throughout the experiment. Non-resuscitated HS animals did not survive for the entire experiment due to non-viable vital signs and poor shock and KI. All fluids were effective in normalizing the vital signs when shed blood was used adjunctively. Sodium pyruvate 2.0 M was most effective, and 4.0 M solution was least effective in improving the vital signs after HS. Conclusions: Future studies should be directed to use 2.0 M sodium pyruvate adjuvant for resuscitation on multiorgan failure and survival rate in HS. PMID:26229300

Trauma Hemostasis and Oxygenation Research Network position paper on the role of hypotensive resuscitation as part of remote damage control resuscitation.

PubMed

Woolley, Thomas; Thompson, Patrick; Kirkman, Emrys; Reed, Richard; Ausset, Sylvain; Beckett, Andrew; Bjerkvig, Christopher; Cap, Andrew P; Coats, Tim; Cohen, Mitchell; Despasquale, Marc; Dorlac, Warren; Doughty, Heidi; Dutton, Richard; Eastridge, Brian; Glassberg, Elon; Hudson, Anthony; Jenkins, Donald; Keenan, Sean; Martinaud, Christophe; Miles, Ethan; Moore, Ernest; Nordmann, Giles; Prat, Nicolas; Rappold, Joseph; Reade, Michael C; Rees, Paul; Rickard, Rory; Schreiber, Martin; Shackelford, Stacy; Skogran Eliassen, Håkon; Smith, Jason; Smith, Mike; Spinella, Philip; Strandenes, Geir; Ward, Kevin; Watts, Sarah; White, Nathan; Williams, Steve

2018-06-01

The Trauma Hemostasis and Oxygenation Research (THOR) Network has developed a consensus statement on the role of permissive hypotension in remote damage control resuscitation (RDCR). A summary of the evidence on permissive hypotension follows the THOR Network position on the topic. In RDCR, the burden of time in the care of the patients suffering from noncompressible hemorrhage affects outcomes. Despite the lack of published evidence, and based on clinical experience and expertise, it is the THOR Network's opinion that the increase in prehospital time leads to an increased burden of shock, which poses a greater risk to the patient than the risk of rebleeding due to slightly increased blood pressure, especially when blood products are available as part of prehospital resuscitation.The THOR Network's consensus statement is, "In a casualty with life-threatening hemorrhage, shock should be reversed as soon as possible using a blood-based HR fluid. Whole blood is preferred to blood components. As a part of this HR, the initial systolic blood pressure target should be 100 mm Hg. In RDCR, it is vital for higher echelon care providers to receive a casualty with sufficient physiologic reserve to survive definitive surgical hemostasis and aggressive resuscitation. The combined use of blood-based resuscitation and limiting systolic blood pressure is believed to be effective in promoting hemostasis and reversing shock".

The Effect of Infrarenal Aortic Balloon Occlusion on Weaning from Supraceliac Aortic Balloon Occlusion in a Porcine Model (Sus scrofa) of Hemorrhagic Shock

DTIC Science & Technology

2017-06-15

all animals , and continued for six hours. Half of the animals were randomly assigned to Zone-3 REBOA for an additional 45 minutes following Zone-1...concentration or resuscitation requirements.Conclusion: In an animal model of hemorrhagic shock and Zone-1 REBOA, subsequent Zone-3 aortic occlusion did not add

Inhibition of glycogen synthase kinase (GSK)-3-β improves liver microcirculation and hepatocellular function after hemorrhagic shock.

PubMed

Jellestad, Lena; Fink, Tobias; Pradarutti, Sascha; Kubulus, Darius; Wolf, Beate; Bauer, Inge; Thiemermann, Chris; Rensing, Hauke

2014-02-05

Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1 mg/kg), a selective GSK-3β inhibitor, 30 min before induction of hemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function. Copyright © 2013 Elsevier B.V. All rights reserved.

Role of transfused red blood cells for shock and coagulopathy within remote damage control resuscitation.

PubMed

Spinella, Philip C; Doctor, Allan

2014-05-01

The philosophy of damage control resuscitation (DCR) and remote damage control resuscitation (RDCR) can be summarized by stating that the goal is to prevent death from hemorrhagic shock by "staying out of trouble instead of getting out of trouble." In other words, it is preferred to arrest the progression of shock, rather than also having to reverse this condition after significant tissue damage and organ injury cascades are established. Moreover, to prevent death from exsanguination, a balanced approach to the treatment of both shock and coagulopathy is required. This was military doctrine during World War II, but seemed to be forgotten during the last half of the 20th century. Damage control resuscitation and RDCR have revitalized the approach, but there is still more to learn about the most effective and safe resuscitative strategies to simultaneously treat shock and hemorrhage. Current data suggest that our preconceived notions regarding the efficacy of standard issue red blood cells (RBCs) during the hours after transfusion may be false. Standard issue RBCs may not increase oxygen delivery and may in fact decrease it by disturbing control of regional blood flow distribution (impaired nitric oxide processing) and failing to release oxygen, even when perfusing hypoxic tissue (abnormal oxygen affinity). Standard issue RBCs may assist with hemostasis but appear to have competing effects on thrombin generation and platelet function. If standard issue or RBCs of increased storage age are not optimal, then are there alternatives that will allow for an efficacious and safe treatment of shock while also supporting hemostasis? Studies are required to determine if fresh RBCs less than 7 to 10 days provide an outcome advantage. A resurgence in the study of whole blood stored at 4°C for up to 10 days also holds promise. Two randomized controlled trials in humans have indicated that following transfusion with either whole blood stored at 4°C or platelets stored at 4°C there was less clinical bleeding than when blood was reconstituted with components or when platelets were stored at 22°C. Early reversal of shock is essential to prevent exacerbation of coagulopathy and progression of cell death cascades in patients with severe traumatic injuries. Red blood cell storage solutions have evolved to accommodate the needs of non-critically ill patients yet may not be optimal for patients in hemorrhagic shock. Continued focus on the recognition and treatment of shock is essential for continued improvement in outcomes for patients who require damage control resuscitation and RDCR.

Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model.

PubMed

Ranjbaran, Mina; Kadkhodaee, Mehri; Seifi, Behjat; Mirzaei, Reza; Ahghari, Parisa

2018-01-01

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer's lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.

Identification of ideal resuscitation pressure with concurrent traumatic brain injury in a rat model of hemorrhagic shock.

PubMed

Hu, Yi; Wu, Yue; Tian, Kunlun; Lan, Dan; Chen, Xiangyun; Xue, Mingying; Liu, Liangming; Li, Tao

2015-05-01

Traumatic brain injury (TBI) is often associated with uncontrolled hemorrhagic shock (UHS), which contributes significantly to the mortality of severe trauma. Studies have demonstrated that permissive hypotension resuscitation improves the survival for uncontrolled hemorrhage. What the ideal target mean arterial pressure (MAP) is for TBI with UHS remains unclear. With the rat model of TBI in combination with UHS, we investigated the effects of a series of target resuscitation pressures (MAP from 50-90 mm Hg) on animal survival, brain perfusion, and organ function before hemorrhage controlled. Rats in 50-, 60-, and 70-mm Hg target MAP groups had less blood loss and less fluid requirement, a better vital organ including mitochondrial function and better cerebral blood flow, and animal survival (8, 6, and 7 of 10, respectively) than 80- and 90-mm Hg groups. The 70-mm Hg group had a better cerebral blood flow and cerebral mitochondrial function than in 50- and 60-mm Hg groups. In contrast, 80- and 90-mm Hg groups resulted in an excessive hemodilution, a decreased blood flow, an increased brain water content, and more severe cerebral edema. A 50-mm Hg target MAP is not suitable for the resuscitation of TBI combined with UHS. A 70 mm Hg of MAP is the ideal target resuscitation pressure for this trauma, which can keep sufficient perfusion to the brain and keep good organ function including cerebral mitochondrial function. Copyright © 2015 Elsevier Inc. All rights reserved.

Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma.

PubMed

Nikolian, Vahagn C; Dekker, Simone E; Bambakidis, Ted; Higgins, Gerald A; Dennahy, Isabel S; Georgoff, Patrick E; Williams, Aaron M; Andjelkovic, Anuska V; Alam, Hasan B

2018-01-01

Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation. Following controlled traumatic brain injury, hemorrhagic shock, various resuscitation and treatment strategies were evaluated for their association with blood-brain barrier integrity. Analysis of gene expression profiles was performed using Porcine Gene ST 1.1 microarray. Pathway analysis was completed using network analysis tools (Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis). Female Yorkshire swine were subjected to controlled traumatic brain injury and 2 hours of hemorrhagic shock (40% blood volume, mean arterial pressure 30-35 mmHg). Subjects were resuscitated with 1) normal saline, 2) fresh frozen plasma, 3) hetastarch, 4) fresh frozen plasma + valproic acid, or 5) hetastarch + valproic acid (n = 5 per group). After 6 hours of observation, brains were harvested for evaluation. Immunofluoroscopic evaluation of the traumatic brain injury site revealed significantly increased expression of tight-junction associated proteins (zona occludin-1, claudin-5) following combination therapy (fresh frozen plasma + valproic acid and hetastarch + valproic acid). The extracellular matrix protein laminin was found to have significantly improved expression with combination therapies. Pathway analysis indicated that valproic acid significantly modulated pathways involved in endothelial barrier function and cell signaling. Resuscitation with fresh frozen plasma results in improved expression of proteins essential for blood-brain barrier integrity. The addition of valproic acid provides significant improvement to these protein expression profiles. This is likely secondary to activation of key pathways related to endothelial functions.

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT)

DTIC Science & Technology

2014-12-01

SUBJECT TERMS Trauma, hemorrhagic shock, cardiac arrest, cardiopulmonary resuscitation, hypothermia 16. SECURITY CLASSIFICATION OF: 17...EPR) was developed to rapidly preserve the organism during ischemia, using hypothermia , drugs, and fluids, to “buy time” for transport and...resuscitative surgery. The purpose of this study is to test the feasibility of rapidly inducing profound hypothermia (< 10oC) with an aortic flush in trauma

Hypothermia is associated with improved outcomes in a porcine model of hemorrhagic shock.

PubMed

George, Mark E; Mulier, Kristine E; Beilman, Greg J

2010-03-01

: Hypothermia after trauma is, in current medical practice, both avoided and aggressively treated. However, the effects of environmental hypothermia during early resuscitation after hemorrhagic shock have been only poorly characterized. : The objective of our study was to compare normothermia versus mild and severe levels of hypothermia in a porcine model of hemorrhagic shock. In a prospective survival study, we anesthetized 19 juvenile male pigs (Yorkshire-Landrace, 15-25 kg) and caused them to hemorrhage until their systolic blood pressure was 45 mm Hg to 55 mm Hg for a duration of 45 minutes. Then, we randomized them into three groups (all of which underwent an 8-hour limited resuscitation period) as follows: normothermic (39 degrees C), mildly hypothermic (36 degrees C), and severely hypothermic (33 degrees C). We used ice packs to achieve surface cooling that mimicked environmental hypothermia. After 8 hours, we rewarmed the pigs and fully resuscitated them for 16 hours. We extubated the survivors and observed them for an additional 24 hours, before killing them. : Surface cooling resulted in significant reduction in core body temperature. The mortality rate was significantly higher in the normothermic group (60%) than in the two hypothermic groups combined (7%) (p = 0.015) or in the severely hypothermic group (0%) (p = 0.023). Hypothermic animals had significantly lower levels of creatinine kinase, lactate dehydrogenase, and lactate in addition to a lower base deficit after shock. However, severely hypothermic animals required greater volumes of colloid infusion and whole blood transfusion to maintain our target systolic blood pressure and hemoglobin levels when compared with normothermic animals. We saw a strong trend toward decreased oxygen consumption with hypothermia. : In our porcine model, we found that simulating mild and severe levels of environmental hypothermia during early resuscitation after hemorrhage was associated with a significantly decreased mortality rate. Furthermore, markers of cellular stress and organ dysfunction, including lactate levels and the base deficit, were lower in hypothermic animals. Decreasing oxygen consumption with hypothermia may, in part, explain the protective effects observed with hypothermia.

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock.

PubMed

Matheson, Paul J; Hurt, Ryan T; Franklin, Glen A; McClain, Craig J; Garrison, R Neal

2009-10-01

Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

Microwave Processing for Sample Preparation to Evaluate Mitochondrial Ultrastructural Damage in Hemorrhagic Shock

NASA Astrophysics Data System (ADS)

Josephsen, Gary D.; Josephsen, Kelly A.; Beilman, Greg J.; Taylor, Jodie H.; Muiler, Kristine E.

2005-12-01

This is a report of the adaptation of microwave processing in the preparation of liver biopsies for transmission electron microscopy (TEM) to examine ultrastructural damage of mitochondria in the setting of metabolic stress. Hemorrhagic shock was induced in pigs via 35% total blood volume bleed and a 90-min period of shock followed by resuscitation. Hepatic biopsies were collected before shock and after resuscitation. Following collection, biopsies were processed for TEM by a rapid method involving microwave irradiation (Giberson, 2001). Samples pre- and postshock of each of two animals were viewed and scored using the mitochondrial ultrastructure scoring system (Crouser et al., 2002), a system used to quantify the severity of ultrastructural damage during shock. Results showed evidence of increased ultrastructural damage in the postshock samples, which scored 4.00 and 3.42, versus their preshock controls, which scored 1.18 and 1.27. The results of this analysis were similar to those obtained in another model of shock (Crouser et al., 2002). However, the amount of time used to process the samples was significantly shortened with methods involving microwave irradiation.

Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage

PubMed Central

Baker, Todd A.; Romero, Jacqueline; Bach, Harold H.; Strom, Joel A.; Gamelli, Richard L.; Majetschak, Matthias

2011-01-01

Objective To define systemic release kinetics of a panel of cytokines and heat shock proteins (HSP) in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers. Design and Setting Prospective study in a research laboratory. Subjects Twenty-one Yorkshire pigs. Measurements and Main Results Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30mmHg, H), polytrauma plus hemorrhage (P/H) or sham procedure (S). Plasma was obtained at baseline, in 5-15min intervals during a 60min shock period without intervention and in 60-120min intervals during fluid resuscitation for up to 300min. Plasma was assayed for IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-17, IL-18, IFNγ, TGFβ, TNFα, HSP40, HSP70 and HSP90 by ELISA. All animals after S, P and H survived (n=5/group). Three of six animals after P/H died. IL-10 increased during shock after P and this increase was attenuated after H. TNFα increased during the shock period after P, H and also after S. P/H abolished the systemic IL-10 and TNFα release and resulted in 20-30% increased levels of IL-6 during shock. As fluid resuscitation was initiated TNFα and IL-10 levels decreased after P, H and P/H, HSP 70 increased after P, IL-6 levels remained elevated after P/H and also increased after P and S. Conclusions Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/HSP levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/HSPs do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients. PMID:21983369

Creating a “Pro-survival Phenotype” Through Histone Deacetylase Inhibition: Past, Present, and Future

PubMed Central

Halaweish, Ihab; Nikolian, Vahagn; Georgoff, Patrick; Li, Yongqing; Alam, Hasan B

2014-01-01

Traumatic injuries and their sequela represent a major source of mortality in the United States and globally. Initial treatment for shock, traumatic brain injury, and polytrauma is limited to resuscitation fluids to replace lost volume. To date, there are no treatments with inherent pro-survival properties. Our lab has investigated the use of histone deacetylase inhibitors (HDACIs) as pharmacological agents to improve survival. This class of drugs acts through posttranslational protein modifications and is a direct regulator of chromatin structure and function, as well as the function of numerous cytoplasmic proteins. In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a significant survival advantage, even in the absence of fluid resuscitation. Positive results have also been shown in two-hit models of hemorrhage and sepsis and in hemorrhagic shock combined with traumatic brain injury. Accumulating data generated by our group and others continue to support the use of HDACIs for creation of a pro-survival phenotype. With further research and clinical trials, HDACIs have the potential to be an integral tool in treatment of trauma, especially in the pre-hospital phase. PMID:25565645

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Increased circulating D-lactate levels predict risk of mortality after hemorrhage and surgical trauma in baboons.

PubMed

Sobhian, Babak; Kröpfl, Albert; Hölzenbein, Thomas; Khadem, Anna; Redl, Heinz; Bahrami, Soheyl

2012-05-01

Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. Hemorrhagic shock was induced in anesthetized baboons (n = 24) by controlled bleeding (mean arterial pressure, 40 mmHg), base excess (maximum -5 mmol/L), and time (maximum 3 h). To mimic clinical setting more closely, all animals underwent a surgical trauma after resuscitation including midshaft osteotomy stabilized with reamed femoral interlocking nailing and were followed for 7 days. Hemorrhagic shock/surgical trauma resulted in 66% mortality by day 7. In nonsurvivor (n = 16) hemorrhagic shock/surgical trauma baboons, circulating D-lactate levels were significantly increased (2-fold) at 24 h compared with survivors (n = 8), whereas the early increase during hemorrhage and resuscitation declined during the early postresuscitation phase with no difference between survivors and nonsurvivors. Moreover, D-lactate levels remained elevated in the nonsurvival group until death, whereas it decreased to baseline in survivors. Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.

Agreement of Bioreactance Cardiac Output Monitoring With Thermodilution During Hemorrhagic Shock and Resuscitation in Adult Swine.

PubMed

Berlin, David A; Peprah-Mensah, Harrison; Manoach, Seth; Heerdt, Paul M

2017-02-01

The study tests the hypothesis that noninvasive cardiac output monitoring based upon bioreactance (Cheetah Medical, Portland, OR) has acceptable agreement with intermittent bolus thermodilution over a wide range of cardiac output in an adult porcine model of hemorrhagic shock and resuscitation. Prospective laboratory animal investigation. Preclinical university laboratory. Eight ~ 50 kg Yorkshire swine with a femoral artery catheter for blood pressure measurement and a pulmonary artery catheter for bolus thermodilution. With the pigs anesthetized and mechanically ventilated, 40 mL/kg of blood was removed yielding marked hypotension and a rise in plasma lactate. After 60 minutes, pigs were resuscitated with shed blood and crystalloid. Noninvasive cardiac output monitoring and intermittent thermodilution cardiac output were simultaneously measured at nine time points spanning baseline, hemorrhage, and resuscitation. Simultaneous noninvasive cardiac output monitoring and thermodilution measurements of cardiac output were compared by Bland-Altman analysis. A plot was constructed using the difference of each paired measurement expressed as a percentage of the mean of the pair plotted against the mean of the pair. Percent bias was used to scale the differences in the measurements for the magnitude of the cardiac output. Method concordance was assessed from a four-quadrant plot with a 15% zone of exclusion. Overall, noninvasive cardiac output monitoring percent bias was 1.47% (95% CI, -2.5 to 5.4) with limits of agreement of upper equal to 33.4% (95% CI, 26.5-40.2) and lower equal to -30.4% (95% CI, -37.3 to -23.6). Trending analysis demonstrated a 97% concordance between noninvasive cardiac output monitoring and thermodilution cardiac output. Over the wide range of cardiac output produced by hemorrhage and resuscitation in large pigs, noninvasive cardiac output monitoring has acceptable agreement with thermodilution cardiac output.

Recombinant human erythropoietin improves gut barrier function in a hemorrhagic shock and resuscitation rat model.

PubMed

Kao, N Raymond L C; Xenocostas, Anargyros; Driman, David K; Rui, Tao; Huang, Weixiong; Jiao, Xiujun; Martin, Claudio M

2011-11-01

Gut injury and bacterial translocation develop and persist after limited periods of hemorrhagic shock. Erythropoietin (EPO) can exert hemodynamic, anti-inflammatory, and tissue protective effects. We tested the hypothesis that EPO given at the time of resuscitation with saline will reduce functional ileal injury 24 hours after shock. Sprague-Dawley rats (n = 6 per group) were randomized to sham surgery or hemorrhagic shock maintained at mean arterial pressure 40 mm Hg for 60 minutes and then treated with either saline resuscitation (three times the volume of shed blood) or saline + recombinant human EPO (rHuEPO) resuscitation. Intravenous rHuEPO (1,000 U/kg) was given at the start of saline resuscitation, and at 24 hours ileal function was evaluated using quantitative cultures of mesenteric lymph nodes to assess for bacterial translocation (colony-forming units per gram of tissue [CFU/g]), determination of portal vein plasma endotoxin levels and histopathological evaluation using semi-thin plastic sections of the distal ileum. In a second series of animals, fluorescein isothiocyanate-dextran 4000 (FD-4) was used to assess mucosal permeability of the distal ileum to macromolecules. At 24 hours, the saline group had morphologic evidence of intestinal injury when compared with the sham group, and the degree of mucosal injury was less in the saline + rHuEPO when compared with the saline group, which demonstrated significantly reduced bacterial translocation to the mesenteric lymph nodes (383 CFU/g ± 111 CFU/g vs. 1130 CFU/g ± 297 CFU/g; p < 0.05) and decreased terminal ileum permeability to FD-4 (3.08 μg/mL ± 0.31 μg/mL vs. 5.14 μg/mL ± 0.88 μg/mL; p < 0.05). No significant difference was found in the portal vein endotoxin levels between the two groups. Histopathological evaluation demonstrated a trend for decreased enterocyte disarray or disruption and vacuolization in the saline + rHuEPO versus saline group. Using rHuEPO at time of saline resuscitation resulted in decreased bacterial translocation and permeability to macromolecules 24 hours after shock. These observations suggest that rHuEPO can mediate a protective effect on intestinal mucosal barrier function during ischemic injury.

Gradually Increased Oxygen Administration Improved Oxygenation and Mitigated Oxidative Stress after Resuscitation from Severe Hemorrhagic Shock.

PubMed

Luo, Xin; Yin, Yujing; You, Guoxing; Chen, Gan; Wang, Ying; Zhao, Jingxiang; Wang, Bo; Zhao, Lian; Zhou, Hong

2015-11-01

The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid-base status, oxygenation, and oxidative injury were observed and evaluated. Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor-α and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining. GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation.

Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock.

PubMed

Wang, Hao; Guan, Yuxia; Widlund, Anne Lykkegaard; Becker, Lance B; Baur, Joseph A; Reilly, Patrick M; Sims, Carrie A

2014-12-01

Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model Assessment-Insulin Resistance index was used to quantify insulin resistance. RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 ± 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 ± 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 ± 56.6 ng/mL vs. 187.3 ± 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model Assessment-Insulin Resistance index (1.30 ± 0.42 vs. 4.18 ± 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion.

Is gut the "motor" for producing hepatocellular dysfunction after trauma and hemorrhagic shock?

PubMed

Wang, P; Ba, Z F; Cioffi, W G; Bland, K I; Chaudry, I H

1998-02-01

Although studies suggest that the gut may be the "motor" responsible for producing sepsis and multiple organ failure after injury, it is not known whether enterectomy prior to the onset of hemorrhage alters proinflammatory cytokines TNF and IL-6 and, if so, whether hepatocellular dysfunction and damage are prevented or attenuated under such conditions. Under methoxyflurane anesthesia, an enterectomy in the rat was performed by excision of the duodenum, jejunum, and ileum. The rats were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal shed volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 1 h. At 1.5 h after the completion of resuscitation, hepatocellular function [i.e., the maximal velocity (Vmax) and transport efficiency (Km) of indocyanine green (ICG) clearance] was assessed by an in vivo ICG clearance technique. Blood samples were taken for the measurement of TNF, IL-6, and liver enzymes (i.e., SGPT and SGOT). Cardiac output and microvascular blood flow were determined by ICG dilution and laser Doppler flowmetry, respectively. The increase in circulating levels of TNF but not IL-6 was prevented by enterectomy prior to hemorrhage. The reduced Vmax and K(m) and elevated SGPT and SGOT following hemorrhage and resuscitation, however, were not significantly affected by prior enterectomy. Moreover, enterectomy before hemorrhage further reduced hepatic perfusion. Since enterectomy prior to the onset of hemorrhage does not prevent or attenuate the reduced ICG clearance and elevated liver enzymes despite downregulation of TNF production, it appears that the small intestine does not play a significant role in producing hepatocellular dysfunction and injury following trauma and hemorrhagic shock.

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-04-01

Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic shock/resuscitation for the very first time; Contract... Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to identify changes and study...findings in concise form, utilizing key concepts/words. 1) Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic

Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.

PubMed

Hu, Xianwen; Wang, Jingxian; Zhang, Li; Zhang, Qiquan; Duan, Xiaowen; Zhang, Ye

2018-06-02

Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS. Copyright © 2018. Published by Elsevier B.V.

Alcohol abuse and the injured host; Dysregulation of counteregulatory mechanisms Review

PubMed Central

Molina, Patricia E.; Sulzer, Jesse K.; Whitaker, Annie

2013-01-01

Traumatic injury ranks as the number one cause of death for the under 44 year old age group and 5th leading cause of death overall (www.nationaltraumainstitute.org/home/trauma_statistics.html). Although improved resuscitation of trauma patients has dramatically reduced immediate mortality from hemorrhagic shock, long-term morbidity and mortality continue to be unacceptably high during the post-resuscitation period, particularly as a result of impaired host immune responses to subsequent challenges such as surgery or infection. Acute alcohol intoxication (AAI) is a significant risk factor for traumatic injury; with intoxicating blood alcohol levels present in more than 40% of injured patients (1–5). Severity of trauma, hemorrhagic shock and injury is higher in intoxicated individuals than that of sober victims, resulting in higher mortality rates in this patient population. Necessary invasive procedures (surgery, anesthesia) and subsequent challenges (infection) that intoxicated trauma victims are frequently subjected to are additional stresses to an already compromised inflammatory and neuroendocrine milieu and further contribute to their morbidity and mortality. Thus, dissecting the dynamic imbalance produced by AAI during trauma is of critical relevance for a significant proportion of injured victims. This review outlines how AAI at the time of hemorrhagic shock not only prevents adequate responses to fluid resuscitation but also impairs the ability of the host to overcome a secondary infection. Moreover, it discusses the neuroendocrine mechanisms underlying alcohol-induced hemodynamic dysregulation and its relevance to host defense restoration of homeostasis following injury. PMID:23416555

Fluid resuscitation with isotonic or hypertonic saline solution avoids intraneural calcium influx after traumatic brain injury associated with hemorrhagic shock.

PubMed

Balbino, Marcos; Capone Neto, Antonio; Prist, Ricardo; Ferreira, Alice Teixeira; Poli-de-Figueiredo, Luiz F

2010-04-01

Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats.

PubMed

Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye; Johansson, Pär Ingemar

2017-03-01

Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG ® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51 Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.

Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation.

PubMed

Ruan, Xiangcai; Shi, Hanping; Xia, Gengfeng; Xiao, Ying; Dong, Jiaxi; Ming, Feiping; Wang, Shenming

2007-10-01

The aim of the present study was to determine the effects of peroral encapsulated Bifidobacteria on intestinal microflora, bacterial translocation (BT), plasma endotoxin, and ileal villi injury in a rat model of hemorrhagic shock. Sprague-Dawley rats were fed daily with three different diet supplements: phosphate buffered saline, Bifidobacteria (10(9) colon-forming units/day), or microencapsulated Bifidobacteria (10(9) colony-forming units/day). After 7 d of treatment, rats were anesthetized for hemorrhagic or sham shock. Then a laparotomy was performed to determine microbiological analysis of cecal content, BT to mesenteric lymph nodes, plasma endotoxin, and terminal ileal villous damage. In the hemorrhagic-shock model, rats pretreated with Bifidobacteria showed decreases in total aerobes in cecum, magnitude of total aerobes to BT, levels of plasma endotoxin, and percentage of ileal villous damage when compared with rats treated with phosphate buffered saline. Encapsulated Bifidobacteria induced greater decreases than intact Bifidobacteria in this model, except for no difference in percentage of ileal villous damage between the two groups. In addition, the incidence of BT was decreased in hemorrhagic rats pretreated with Bifidobacteria compared with control. However, the magnitude of total anaerobes and Bifidobacteria BT were similar among hemorrhagic-shocked rats receiving three different supplements. Bifidobacteria can be useful in preventing BT in hemorrhagic-shocked rats, and encapsulated Bifidobacteria can augment this effect further. Peroral administration of Bifidobacteria may be a favorable strategy to prevent sepsis and multiple organ dysfunction syndrome in hemorrhagic shock.

HSD is a better resuscitation fluid for hemorrhagic shock with pulmonary edema at high altitude.

PubMed

Liu, Liang-Ming; Hu, De-Yao; Zhou, Xue-Wu; Liu, Jiang-Cang; Li, Ping

2008-12-01

To investigate the fluid tolerance of hemorrhagic shock with pulmonary edema (HSPE) at high altitude in unacclimated rats and the beneficial effect of 7.5% hypertonic saline/6% dextran (HSD). One hundred seventy-six Sprague-Dawley rats, transported to LaSa, Tibet, 3,760 m above the sea level, were anesthetized with sodium pentobarbital (30 mg/kg, i.p.) within 1 week. Hemorrhagic shock with pulmonary edema was induced by bloodletting (50 mmHg for 1 h) plus intravenous injection of oleic acid (50 microL/kg). Seventy-seven rats were equally divided into 11 groups (n = 7/group) including sham-operated control group; hemorrhagic shock control group; HSPE control group; HSPE plus 0.5-, 1.0-, 1.5-, 2.0-, or 3.0-fold volumes of lactated Ringer's solution (LR) groups; and HSPE plus 4, 6, and 8 mL/kg of HSD groups. Hemodynamic parameters including mean arterial blood pressure, left intraventricular systolic pressure, and the maximal change rate of intraventricular pressure rise or decline (+/-dp/dtmax) were observed at baseline and at 15, 30, 60, and 120 min after infusion; blood gases were measured at 30 and 120 min after infusion, and the water content of lung and brain was determined at 120 min after infusion. Additional 99 rats were used to observe the effect of these treatments on the survival time of HSPE rats; 0.5 volume of LR infusion slightly increased the mean arterial blood pressure, left intraventricular systolic pressure, and +/-dp/dtmax and prolonged the survival time of HSPE animals as compared with the HSPE group (P < 0.05 - 0.01); it did not increase the water content of lung and brain and had no marked influences on blood gases. One volume of LR infusion had somewhat improved the hemodynamic parameters for HSPE animals, but had no apparent effect on the survival time and the water content of lung and brain. Lactate Ringer's solution infusion, 1.5, 2, and 3 volumes, significantly deteriorated the hemodynamic parameters, increased the water content of lung, and decreased the survival time of HSPE animals. Hypertonic saline/6% dextran (4 - 8 mL/kg) significantly increased the hemodynamic parameters, improved the blood gases, decreased the water content of lung and brain, and prolonged the survival time of HSPE rats. Among the three dosages of HSD, 6 mL/kg of HSD had the best effect. The tolerance of fluid infusion for hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. More than one volume of LR infusion would aggravate the pulmonary edema and exacerbate the resuscitation effect, but only one volume of LR cannot reach the effective volume resuscitation. Small volume of HSD could better resuscitate hemorrhagic shock with pulmonary edema at high altitude.

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

Hextend and 7.5% hypertonic saline with Dextran are equivalent to Lactated Ringer's in a swine model of initial resuscitation of uncontrolled hemorrhagic shock.

PubMed

Riha, Gordon M; Kunio, Nicholas R; Van, Philbert Y; Hamilton, Gregory J; Anderson, Ross; Differding, Jerome A; Schreiber, Martin A

2011-12-01

The optimal fluid strategy for the early treatment of trauma patients remains highly debated. Our objective was to determine the efficacy of an initial bolus of resuscitative fluids used in military and civilian settings on the physiologic response to uncontrolled hemorrhagic shock in a prospective, randomized, blinded animal study. Fifty anesthetized swine underwent central venous and arterial catheterization followed by celiotomy. Grade V liver injury was performed, followed by 30 minutes of uncontrolled hemorrhage. Then, liver packing was completed, and fluid resuscitation was initiated over 12 minutes with 2 L normal saline (NS), 2 L Lactated Ringer's (LR), 250 mL 7.5% hypertonic saline with 3% Dextran (HTS), 500 mL Hextend (HEX), or no fluid (NF). Animals were monitored for 2 hours postinjury. Blood loss after initial hemorrhage, mean arterial pressure (MAP), tissue oxygen saturation (StO2), hematocrit, pH, base excess, and lactate were measured at baseline, 1 hour, and 2 hours. NF group had less post-treatment blood loss compared with other groups. MAP and StO2 for HEX, HTS, and LR at 1 hour and 2 hours were similar and higher than NF. MAP and StO2 did not differ between NS and NF, but NS resulted in decreased pH and base excess. Withholding resuscitative fluid results in the least amount of posttreatment blood loss. In clinically used volumes, HEX and HTS are equivalent to LR with regard to physiologic outcomes and superior to NF. NS did not provide a measurable improvement in outcome compared with NF and resulted in increased acidosis.

A SOF Damage Control Resuscitation Cocktail

DTIC Science & Technology

2015-05-01

include Hextend for volume resuscitation and tissue perfusion, fibrinogen concentrate for hemostasis, and tranexamic acid for hemostasis. These...for hemostasis, and tranexamic acid for hemostasis. These components are tested in a combat-relevant swine polytrauma model of hemorrhagic shock with...HexVasoCntl HexVasoAlb Ctrl 4 4 would not allow adequate blood loss from the aortic tear, preventing testing of fibrinogen and tranexamic acid as

Thrombelastography is Better Than PT, aPTT, and Activated Clotting Time in Detecting Clinically Relevant Clotting Abnormalities After Hypothermia, Hemorrhagic Shock and Resuscitation in Pigs

DTIC Science & Technology

2008-09-01

hypothermia group using a cold blanket with 4°C circulating water. In the combined group, hemorrhagic shock and LR re- suscitation were induced the same... circulation and a decrease in platelet counts. Fibrinogen levels, in con- trast, were not changed significantly from baseline by hypo- thermia in this...et al. Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg. 1992;104:108–116. The

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-03-01

Luciana 5/18/2011-8/17/2012 1 Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic shock/resuscitation for...05/2013 3/18/2013, 3:21 PM 2 Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to...concise form, utilizing key concepts/words. 1) Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic

THE AMPK ACTIVATOR AICAR AMELIORATES AGE-DEPENDENT MYOCARDIAL INJURY IN MURINE HEMORRHAGIC SHOCK

PubMed Central

Matsiukevich, Dzmitry; Piraino, Giovanna; Klingbeil, Lindsey R.; Hake, Paul W.; Wolfe, Vivian; O’Connor, Michael; Zingarelli, Basilia

2016-01-01

The development of myocardial dysfunction in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of energy homeostasis, which coordinates metabolic recovery after cellular stress. We investigated whether AMPK-regulated pathways are age-dependent in hemorrhage-induced myocardial injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords cardioprotective effects. Anesthetized C57/BL6 young (3–5 months old) and mature male mice (9–12 months old) were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with shed blood and Lactated Ringer’s solution. Mice were sacrificed at 3 hours after resuscitation, and plasma and hearts were harvested for biochemical assays. Vehicle-treated mature mice exhibited higher myocardial injury and higher levels of plasma biomarkers of cardiovascular injury (endocan and follistatin) when compared with young mice. Cardiac cell mitochondrial structure was also markedly impaired in vehicle-treated mature mice when compared to young mice. At molecular analysis, an increase of the phosphorylated catalytic subunit pAMPKα was associated with nuclear translocation of the peroxisome proliferator-activated receptor γ co-activator-α in young, but not mature mice. No changes in autophagy were observed as evaluated by the conversion of the light-chain (LC)3B-I protein to LC3B-II form. Treatment with AICAR ameliorated myocardial damage in both age groups. However, AICAR therapeutic effects were less effective in mature mice compared to young mice and involved distinct mechanisms of action. Thus, our data demonstrate that during hemorrhagic shock AMPK-dependent metabolic mechanisms are important for mitigating myocardial injury. However, these mechanisms are less competent with age. PMID:27513082

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1997-12-01

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

PubMed Central

2010-01-01

Introduction Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses. Methods Thirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2-) were also measured by electron paramagnetic resonance. Results At the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2- release in both aorta and heart (P < 0.05). Conclusions NaHS is protective against the effects of ischemia reperfusion induced by controlled hemorrhage in rats. NaHS also improves hemodynamics in the early resuscitation phase after hemorrhagic shock, most likely as a result of attenuated oxidative stress. The use of NaHS hence appears promising in limiting the consequences of ischemia reperfusion (IR). PMID:20836847

Wound shock: a history of its study and treatment by military surgeons.

PubMed

Hardaway, Robert M

2004-04-01

The treatment of wounds has received considerable attention from the time of the Trojan War. However, it was not until the American Civil War that shock was described as an entity distinct from the wounds themselves and that efforts were directed at more than just treatment of the wound. The need for fluid resuscitation in the treatment of hemorrhagic shock was first recognized in the Spanish American War, as was the association of sepsis with shock. World War I showed the need for blood in the treatment of "wound shock," a lesson that had to be relearned in World War II through bitter experience. Studies in the Korean War described the concept of disseminated intravascular coagulation and multiple organ failure, and the existence of disseminated intravascular coagulation was confirmed by studies in Vietnam. The treatment of hemorrhagic shock is now very effective, but the treatment of traumatic and septic shock remains unsatisfactory.

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

PubMed

Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

2001-05-15

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females. Copyright 2001 Academic Press.

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

PubMed

do Nascimento, Paulo; Vaid, Sumreen U; Hoskins, Stephen L; Espana, Jonathan M; Kinsky, Michael P; Kramer, George C

2007-05-01

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor.

PubMed

Charbonneau, Hélène; Buléon, Marie; Minville, Vincent; Faguer, Stanislas; Girolami, Jean-Pierre; Bascands, Jean-Loup; Tack, Ivan; Mayeur, Nicolas

2016-09-01

Angiotensin-converting enzyme inhibitors are associated with deleterious hypotension during anesthesia and shock. Because the pharmacologic effects of angiotensin-converting enzyme inhibitors are partly mediated by increased bradykinin B2 receptor activation, this study aimed to determine the impact of acute B2 receptor blockade during hemorrhagic shock in angiotensin-converting enzyme inhibitor-treated mice. In vivo study. University research unit. C57/Bl6 mice. The hemodynamic effect of B2 receptor blockade using icatibant (B2 receptor antagonist) was studied using a pressure-targeted hemorrhagic shock and a volume-targeted hemorrhagic shock. Animals were anesthetized with ketamine and xylazine (250 mg/kg and 10 mg/kg, respectively), intubated using intratracheal cannula, and ventilated (9 mL/kg, 150 min). Five groups were studied: 1) sham-operated animals, 2) control shocked mice, 3) shocked mice treated with ramipril for 7 days (angiotensin-converting enzyme inhibitors) before hemorrhagic shock, 4) shocked mice treated with angiotensin-converting enzyme inhibitors and a single bolus of icatibant (HOE-140) immediately before anesthesia (angiotensin-converting enzyme inhibitors + icatibant), and 5) shocked mice treated with a single bolus of icatibant. One hour after volume-targeted hemorrhagic shock, blood lactate was measured to evaluate organ failure. During pressure-targeted hemorrhagic shock, the mean blood volume withdrawn was significantly lower in the angiotensin-converting enzyme inhibitor group than in the other groups (p < 0.001). During volume-targeted hemorrhagic shock, icatibant prevented blood pressure lowering in the angiotensin-converting enzyme inhibitor group (p < 0.001). Blood lactate was significantly higher in the angiotensin-converting enzyme inhibitor group than in the other groups, particularly the HOE groups. During hemorrhagic shock, acute B2 receptor blockade significantly attenuates the deleterious hemodynamic effect of angiotensin-converting enzyme inhibitor treatment in mice. This beneficial effect of B2 receptor blockade is rapidly reached and sustained with a single bolus of icatibant. This benefit could be of interest in angiotensin-converting enzyme inhibitor-treated patients during both emergency anesthesia and resuscitation.

A Prospective, Randomized Investigation of Plasma First Resuscitation for Traumatic Hemorrhage and Attenuation of Acute Coagulopathy of Trauma

DTIC Science & Technology

2016-05-01

TL, Silliman, CC, and Banerjee, A: Tranexamic Acid Inhibited Thromboelastography is a More Sensitive and Rapid Predictor of Hyperfibrinolytic...A: Alpha-enolase, A Glycolytic Enzyme Elevated in Hemorrhagic Shock, Potentiates Fibrinolysis, and is Reversible by Tranexamic Acid (Presented at the...Silliman, CC. Rationale for the Selective Administration of Tranexamic Acid to Inhibit-Fibrinolysis in the Injured Patient. (Presented at Trauma

Systemic Effects of Shock and Resuscitation Monitored by Visible Hyperspectral Imaging

DTIC Science & Technology

2003-01-01

organs. Its causes include hemorrhage, cardiac failure, sepsis, hypoglycemia , and burns; the pathophysiology of these various shock states is quite...different. Depending on the cause of shock, the skin is one organ that readily manifests its ef- fects. The importance of skin oxygenation is well known...attachment of a 7.5-cm-diameter plate to the bolt, was used to cause a blunt right chest injury. A tube thora- costomy was immediately performed. After a

Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation-induced liver injury.

PubMed

Dang, Yangjie; Liu, Ting; Mei, Xiaopeng; Meng, Xiangzhong; Gou, Xingchun; Deng, Bin; Xu, Hao; Xu, Lixian

2017-12-01

It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. HHOS has protective effects against liver injury in a rat model of HSR. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine.

PubMed

Kim, Hubert D; Malinoski, Darren J; Borazjani, Boris; Patel, Madhukar S; Chen, Joseph; Slone, Johnathan; Nguyen, Xuan-Mai T; Steward, Earl; Schmid-Schonbein, Geert W; Hoyt, David B

2010-05-01

Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 +/- 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 +/- 1 with one early death and 2.2 +/- 1.2 with two early deaths, respectively, analysis of variance p < 0.003). The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

Administration of progesterone after trauma and hemorrhagic shock prevents hepatocellular injury.

PubMed

Kuebler, Joachim F; Yokoyama, Yukihiro; Jarrar, Doraid; Toth, Balazs; Rue, Loring W; Bland, Kirby I; Wang, Ping; Chaudry, Irshad H

2003-07-01

Administration of a single dose of progesterone following trauma and hemorrhage in progesterone-deficient rats would ameliorate the inflammatory response and hepatocellular damage. A university laboratory. Ovariectomized female Sprague-Dawley rats (250-350 g; Charles River Laboratories, Wilmington, Mass) underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma), were bled to a mean arterial blood pressure of 35 mm Hg for about 90 minutes, and then were resuscitated using Ringer lactate solution. Progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously at the end of resuscitation. In additional animals, Kupffer cells were isolated following trauma, hemorrhage, and resuscitation and treated in vitro with progesterone, lipopolysaccharide, or both. Six hours following resuscitation, plasma tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) levels and liver myeloperoxidase activity were determined. Hepatocellular function (maximum velocity of indocyanine green clearance [Vmax] and the efficiency of the active transport or Michaelis-Menten constant [Km]) and plasma levels of transaminases were measured 20 hours after resuscitation. Kupffer cell IL-6 and TNF-alpha production were assessed. Plasma levels of TNF-alpha, IL-6, aspartate aminotransferase, and alanine aminotransferase, as well as hepatic myeloperoxidase activity were increased, whereas indocyanine green clearance was depressed in vehicle-treated rats following trauma-hemorrhage. Animals treated with progesterone showed significantly reduced levels of the TNF-alpha, IL-6, and transaminases as well as reduced myeloperoxidase activity in the liver. Progesterone-treated animals showed increased Vmax and Kmax values for indocyanine green. In vitro treatment of Kupffer cells with progesterone decreased TNF-alpha production but did not affect the production of IL-6. Progesterone administration following trauma-hemorrhage ameliorates the proinflammatory response and, subsequently, the hepatocellular injury via direct action on immunocompetent cells.

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

PubMed Central

Patel, Nimesh SA; Nandra, Kiran K; Brines, Michael; Collino, Massimo; Wong, WS Fred; Kapoor, Amar; Benetti, Elisa; Goh, Fera Y; Fantozzi, Roberto; Cerami, Anthony; Thiemermann, Christoph

2011-01-01

Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect—an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB. PMID:21607291

Potential Resuscitation Strategies for Treatment of Hemorrhagic Shock

DTIC Science & Technology

2004-09-01

thrombus (the “pop-clot” pressure); 2) an injectable clot stabilizer (“fix-a-leak”) that is a naturally occurring factor in the clotting cascade (human...recombinant Factor VIIa); and 3) the maximum time up to 24 hours for hypotensive resuscitation below the “pop-the-clot” pressure (“how low for how long...To prevent this blood products are given as soon as possible in the emergency department. Only crystalloids and colloids are currently available on

Closed-Loop Resuscitation of Hemorrhagic Shock: Novel Solutions Infused to Hypotensive and Normotensive Endpoints

DTIC Science & Technology

2007-06-29

Anesthesia & Analgesia 98(4S):SCA 85, 2004. 5. Kramer GC, Brown TLH, Michell MW, Oliveira H, Herndon DN, Muller M, Baker RD: Enteral Resuscitation...Honolulu, Hawaii; Anesth Analg 98(4S):SCA 85, 2004. 10. Bruttig, SPGC, Kramer, GC: Clinical record of emergency vascular access using adult intraosseous ...supplement 1): abstracts 49, 2007. NATO Reports: 1. Bruttig SP, Kramer GC: Clinical record of emergency vascular access using adult intraosseous (10

Osthole attenuates hepatic injury in a rodent model of trauma-hemorrhage.

PubMed

Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.

Damage control: Concept and implementation.

PubMed

Malgras, B; Prunet, B; Lesaffre, X; Boddaert, G; Travers, S; Cungi, P-J; Hornez, E; Barbier, O; Lefort, H; Beaume, S; Bignand, M; Cotte, J; Esnault, P; Daban, J-L; Bordes, J; Meaudre, E; Tourtier, J-P; Gaujoux, S; Bonnet, S

2017-12-01

The concept of damage control (DC) is based on a sequential therapeutic strategy that favors physiological restoration over anatomical repair in patients presenting acutely with hemorrhagic trauma. Initially described as damage control surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic trauma, this concept is articulated in three steps: surgical control of lesions (hemostasis, sealing of intestinal spillage), physiological restoration, then surgery for definitive repair. This concept was quickly adapted for intensive care management under the name damage control resuscitation (DCR), which refers to the modalities of hospital resuscitation carried out in patients suffering from traumatic hemorrhagic shock within the context of DCS. It is based mainly on specific hemodynamic resuscitation targets associated with early and aggressive hemostasis aimed at prevention or correction of the lethal triad of hypothermia, acidosis and coagulation disorders. Concomitant integration of resuscitation and surgery from the moment of admission has led to the concept of an integrated DCR-DCS approach, which enables initiation of hemostatic resuscitation upon arrival of the injured person, improving the patient's physiological status during surgery without delaying surgery. This concept of DC is constantly evolving; it stresses management of the injured person as early as possible, in order to initiate hemorrhage control and hemostatic resuscitation as soon as possible, evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and therapeutic radiological management under the name of radiological DC (DCRad). DCS is applied only to the most seriously traumatized patients, or in situations of massive influx of injured persons, as its universal application could lead to a significant and unnecessary excess-morbidity to injured patients who could and should undergo definitive treatment from the outset. DCS, when correctly applied, significantly improves the survival rate of war-wounded. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Critical care considerations in the management of the trauma patient following initial resuscitation

PubMed Central

2012-01-01

Background Care of the polytrauma patient does not end in the operating room or resuscitation bay. The patient presenting to the intensive care unit following initial resuscitation and damage control surgery may be far from stable with ongoing hemorrhage, resuscitation needs, and injuries still requiring definitive repair. The intensive care physician must understand the respiratory, cardiovascular, metabolic, and immunologic consequences of trauma resuscitation and massive transfusion in order to evaluate and adjust the ongoing resuscitative needs of the patient and address potential complications. In this review, we address ongoing resuscitation in the intensive care unit along with potential complications in the trauma patient after initial resuscitation. Complications such as abdominal compartment syndrome, transfusion related patterns of acute lung injury and metabolic consequences subsequent to post-trauma resuscitation are presented. Methods A non-systematic literature search was conducted using PubMed and the Cochrane Database of Systematic Reviews up to May 2012. Results and conclusion Polytrauma patients with severe shock from hemorrhage and massive tissue injury present major challenges for management and resuscitation in the intensive care setting. Many of the current recommendations for “damage control resuscitation” including the use of fixed ratios in the treatment of trauma induced coagulopathy remain controversial. A lack of large, randomized, controlled trials leaves most recommendations at the level of consensus, expert opinion. Ongoing trials and improvements in monitoring and resuscitation technologies will further influence how we manage these complex and challenging patients. PMID:22989116

Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: definitions, current practice, and knowledge gaps.

PubMed

Jenkins, Donald H; Rappold, Joseph F; Badloe, John F; Berséus, Olle; Blackbourne, Lorne; Brohi, Karim H; Butler, Frank K; Cap, Andrew P; Cohen, Mitchell Jay; Davenport, Ross; DePasquale, Marc; Doughty, Heidi; Glassberg, Elon; Hervig, Tor; Hooper, Timothy J; Kozar, Rosemary; Maegele, Marc; Moore, Ernest E; Murdock, Alan; Ness, Paul M; Pati, Shibani; Rasmussen, Todd; Sailliol, Anne; Schreiber, Martin A; Sunde, Geir Arne; van de Watering, Leo M G; Ward, Kevin R; Weiskopf, Richard B; White, Nathan J; Strandenes, Geir; Spinella, Philip C

2014-05-01

The Trauma Hemostasis and Oxygenation Research Network held its third annual Remote Damage Control Resuscitation Symposium in June 2013 in Bergen, Norway. The Trauma Hemostasis and Oxygenation Research Network is a multidisciplinary group of investigators with a common interest in improving outcomes and safety in patients with severe traumatic injury. The network's mission is to reduce the risk of morbidity and mortality from traumatic hemorrhagic shock, in the prehospital phase of resuscitation through research, education, and training. The concept of remote damage control resuscitation is in its infancy, and there is a significant amount of work that needs to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical in these patients. If shock and coagulopathy can be rapidly identified and minimized before hospital admission, this will very likely reduce morbidity and mortality. This position statement begins to standardize the terms used, provides an acceptable range of therapeutic options, and identifies the major knowledge gaps in the field.

Resuscitation from severe hemorrhagic shock after traumatic brain injury using saline, shed blood, or a blood substitute.

PubMed

Gibson, Jeffrey B; Maxwell, Robert A; Schweitzer, John B; Fabian, Timothy C; Proctor, Kenneth G

2002-03-01

The original purpose of this study was to compare initial resuscitation of hemorrhagic hypotension after traumatic brain injury (TBI) with saline and shed blood. Based on those results, the protocol was modified and saline was compared to a blood substitute, diaspirin cross-linked hemoglobin (DCLHb). Two series of experiments were performed in anesthetized and mechanically ventilated (FiO2 = 0.4) pigs (35-45 kg). In Series 1, fluid percussion TBI (6-8 ATM) was followed by a 30% hemorrhage. At 120 min post-TBI, initial resuscitation consisted of either shed blood (n = 7) or a bolus of 3x shed blood volume as saline (n = 13). Saline supplements were then administered to all pigs to maintain a systolic arterial blood pressure (SAP) of >100 mmHg and a heart rate (HR) of <110 beats/min. In Series 2, TBI (4-5 ATM) was followed by a 35% hemorrhage. At 60 min post-TBI, initial resuscitation consisted of either 500 mL of DCLHb (n = 6) or 500 mL of saline (n = 5). This was followed by saline supplements to all pigs to maintain a SAP of >100 mmHg and a HR of <110 beats/min. In Series 1, most systemic markers of resuscitation (e.g., SAP, HR, cardiac output, filling pressures, lactate, etc.) were normalized, but there were 0/7 vs. 5/13 deaths within 5 h (P = 0.058) with blood vs. saline. At constant arterial O2 saturation (SaO2), mixed venous O2 saturation (SvO2), cerebral perfusion pressure (CPP), and cerebral venous O2 saturation (ScvO2) were all higher, intracranial pressure (ICP) was lower, and CO2 reactivity was preserved with blood vs. saline (all P < 0.05). In Series 2, SAP, ICP, CPP, and lactate were higher with DCLHb vs. saline (all P< 0.05). Cardiac output was lower even though filling pressure was markedly elevated with DCLHb vs. saline (both P< 0.05). Neither SvO2 nor cerebrovascular CO2 reactivity were improved, and ScvO2 was lower with DCLHb vs. saline (P < 0.05). All survived at least 72 h with neuropathologic changes that included sub-arachnoid hemorrhage, midline cerebellar necrosis, and diffuse axonal injury. These changes were similar with DCLHb vs. saline. Thus, whole blood was more effective than saline for resuscitation of TBI, whereas DCLHb was no more, and according to many variables, less effective than saline resuscitation. These experimental results are comparable to those in a recent multicenter trial using DCLHb for the treatment of severe traumatic shock. Further investigations in similar experimental models might provide some plausible explanations why DCLHb unexpectedly increased mortality in patients.

A Sphingosine-1 Phosphate agonist (FTY720) limits trauma/hemorrhagic shock induced multiple organ dysfunction syndrome

PubMed Central

Bonitz, Joyce A.; Son, Julie Y.; Chandler, Benjamin; Tomaio, Jacquelyn N.; Qin, Yong; Prescott, Lauriston M.; Feketeova, Eleonora; Deitch, Edwin A.

2014-01-01

BACKGROUND Trauma/hemorrhagic shock is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1 phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS induced multiple organ dysfunction syndrome (MODS) in a rodent trauma-hemorrhagic shock (T/HS) model. METHODS Rats subjected to trauma/sham-shock (T/SS) or T/HS (30 mm Hg × 90 min), were administered FTY720 (1 mg/kg) post-T/HS during volume resuscitation. Lung injury (permeability to Evans Blue dye), PMN priming (respiratory burst activity), and RBC rigidity were measured. In addition, lymph duct cannulated rats were used to quantify the effect of FTY720 on gut injury (permeability and morphology) and the biologic activity of T/HS vs. T/SS lymph on PMN-RB and RBC deformability. RESULTS T/HS-induced increased lung permeability, PMN priming and RBC rigidity were all abrogated by FTY720. The systemic protective effect of FTY720 was only partially at the gut level, since FTY720 did not prevent T/HS-induced gut injury (morphology or permeability,) however, it did abrogate T/HS lymph-induced increased respiratory burst and RBC rigidity. CONCLUSION FTY720 limited T/HS-induced MODS (lung injury, red cell injury, and neutrophil priming) as well as T/HS lymph bioactivity, although it did not limit gut injury. PMID:25004059

Temporary Percutaneous Aortic Balloon Occlusion to Enhance Fluid Resuscitation Prior to Definitive Embolization of Post-Traumatic Liver Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuoka, Shin; Uchiyama, Katsuhiro; Shima, Hideki

2001-07-15

We successfully stabilized severe hemorrhagic shock following traumatic liver injury by percutaneous transcarotid supraceliac aortic occlusion with a 5 Fr balloon catheter. Then we were able to perform transfemoral embolization therapy of the hepatic arterial bleeding source. Transient aortic occlusion using a balloon catheter appears to be a useful adjunct in select cases where stabilization of the patient is necessary to allow successful selective embolization of the bleeding source.

Abstracts of the International Conference on Hypertonic Resuscitation (5th) Held in Galveston, Texas on 3-5 June 1992

DTIC Science & Technology

1992-08-01

Dextran Metabolism in Dehydrated, Hemorrhaged Sheep Infused with Hypertonic Saline/Dextran (HSD). 3 J. Eaker (Davis, U.S.A.): Small Volume Intraosseous ...S. Majluf (Mexico City, Mexico): Eualuation of an Intraosseous Function versus Intrauenous and Central Catheter in Patients with Hemorrhagic Shock. W...between the traumatized brain parenchyma and the skull bone followed by closure of the cranium by dental cement. At 20 hrs later the animals were

Pre-Hospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsen Hypocoagulation and Hyperfibrinolysis

DTIC Science & Technology

2015-07-01

coagulation defects using fresh plasma and other blood prod- ucts in near equivalent ratios (38), along with prohemostatic agents such as tranexamic ... acid (39). This approach also rec- ommends restricting fluids to limit hemodilution (40) and other deleterious effects of the lethal triad (41). Still

Osthole Attenuates Hepatic Injury in a Rodent Model of Trauma-Hemorrhage

PubMed Central

Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway. PMID:23755293

Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

PubMed

Dickson, J Michael; Wang, Xu; St John, Alexander E; Lim, Esther B; Stern, Susan A; White, Nathan J

2018-03-14

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic Fracture and Intra-Abdominal Hemorrhagic Shock Using Continuous Vital Signs

DTIC Science & Technology

2017-03-01

University of Maryland, Baltimore Baltimore, MD 21201 REPORT DATE: March 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research ...ongoing. After FDA approval of a new novel REBOA catheter (ER-REBOATM (Prytime Medical , Boerne, TX )) in October 2015, we incorporated this catheter into...Scalea, MD 39th Annual CONFERENCE ON SHOCK – June 11-14th, Austin , TX 2. REBOA IMPROVES MEAN BLOOD PRESSURE (MBP) AND SHOCK INDEX (SI) AS MEASURED

A Prospective, Randomized Trial of Intravenous Hydroxocobalamin Versus Whole Blood Transfusion Compared to No Treatment for Class III Hemorrhagic Shock Resuscitation in a Prehospital Swine Model

DTIC Science & Technology

2015-03-01

statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac...increasing blood pressure as well as sys- temic vascular resistance in a hypovolemic hemorrhagic swine model.18 The primary hypothesis of this study is...output, sys- temic vascular resistance , mixed venous oxygen satura- tion, central venous pressure, pulmonary artery pressure, and core temperature. The

Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

PubMed

Chang, Ronald; Holcomb, John B

2016-07-01

Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis.

Abrupt reflow enhances cytokine-induced proinflammatory activation of endothelial cells during simulated shock and resuscitation.

PubMed

Li, Ranran; Zijlstra, Jan G; Kamps, Jan A A M; van Meurs, Matijs; Molema, Grietje

2014-10-01

Circulatory shock and resuscitation are associated with systemic hemodynamic changes, which may contribute to the development of MODS (multiple organ dysfunction syndrome). In this study, we used an in vitro flow system to simulate the consecutive changes in blood flow as occurring during hemorrhagic shock and resuscitation in vivo. We examined the kinetic responses of different endothelial genes in human umbilical vein endothelial cells preconditioned to 20 dyne/cm unidirectional laminar shear stress for 48 h to flow cessation and abrupt reflow, respectively, as well as the effect of flow cessation and reflow on tumor necrosis factor-α (TNF-α)-induced endothelial proinflammatory activation. Endothelial CD31 and VE-cadherin were not affected by the changes in flow in the absence or presence of TNF-α. The messenger RNA levels of proinflammatory molecules E-selectin, VCAM-1 (vascular cell adhesion molecule 1), and IL-8 (interleukin 8) were significantly induced by flow cessation respectively acute reflow, whereas ICAM-1 (intercellular adhesion molecule 1) was downregulated on flow cessation and induced by subsequent acute reflow. Flow cessation also affected the Ang/Tie2 (Angiopoietin/Tie2 receptor tyrosine kinase) system by downregulating Tie2 and inducing its endothelial ligand Ang2, an effect that was further extended on acute reflow. Furthermore, the induction of proinflammatory adhesion molecules by TNF-α under flow cessation was significantly enhanced on subsequent acute reflow. This study demonstrated that flow alterations per se during shock and resuscitation contribute to endothelial activation and that these alterations interact with proinflammatory factors coexisting in vivo such as TNF-α. The abrupt reflow-related enhancement of cytokine-induced endothelial proinflammatory activation supports the concept that sudden regain of flow during resuscitation has an aggravating effect on endothelial activation, which may play a significant role in vascular dysfunction and consequent organ injury. This study implies that the improvement of resuscitation strategies and the pharmacological interference with proinflammatory signaling cascades at the right time of resuscitation of shock patients may be beneficial to regain and/or maintain organ function in patients after circulatory shock.

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

PubMed

Jin, Guang; DeMoya, Marc A; Duggan, Michael; Knightly, Thomas; Mejaddam, Ali Y; Hwabejire, John; Lu, Jennifer; Smith, William Michael; Kasotakis, Georgios; Velmahos, George C; Socrate, Simona; Alam, Hasan B

2012-07-01

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

Peripheral Venous Waveform Analysis for Detecting Hemorrhage and Iatrogenic Volume Overload in a Porcine Model.

PubMed

Hocking, Kyle M; Sileshi, Ban; Baudenbacher, Franz J; Boyer, Richard B; Kohorst, Kelly L; Brophy, Colleen M; Eagle, Susan S

2016-10-01

Unrecognized hemorrhage and unguided resuscitation is associated with increased perioperative morbidity and mortality. The authors investigated peripheral venous waveform analysis (PIVA) as a method for quantitating hemorrhage as well as iatrogenic fluid overload during resuscitation. The authors conducted a prospective study on Yorkshire Pigs (n = 8) undergoing hemorrhage, autologous blood return, and administration of balanced crystalloid solution beyond euvolemia. Intra-arterial blood pressure, electrocardiogram, and pulse oximetry were applied to each subject. Peripheral venous pressure was measured continuously through an upper extremity standard peripheral IV catheter and analyzed with LabChart. The primary outcome was comparison of change in the first fundamental frequency (f1) of PIVA with standard and invasive monitoring and shock index (SI). Hemorrhage, return to euvolemia, and iatrogenic fluid overload resulted in significantly non-zero slopes of f1 amplitude. There were no significant differences in heart rate or mean arterial pressure, and a late change in SI. For the detection of hypovolemia the PIVA f1 amplitude change generated an receiver operator curves (ROC) curve with an area under the curve (AUC) of 0.93; heart rate AUC = 0.61; mean arterial pressure AUC = 0.48, and SI AUC = 0.72. For hypervolemia the f1 amplitude generated an ROC curve with an AUC of 0.85, heart rate AUC = 0.62, mean arterial pressure AUC = 0.63, and SI AUC = 0.65. In this study, PIVA demonstrated a greater sensitivity for detecting acute hemorrhage, return to euvolemia, and iatrogenic fluid overload compared with standard monitoring and SI. PIVA may provide a low-cost, minimally invasive monitoring solution for monitoring and resuscitating patients with perioperative hemorrhage.

248: Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Survival in Lethal Hemorrhage

DTIC Science & Technology

2014-01-01

analyzed to evaluate for nonconvulsvie status epilepticus (NCSE) as defined in previous studies. Results: Out of the thirty patients that underwent...and oxygenation failure in 2,000 (38%) as indications for TI. In univariate analysis, shock status (OR 6.1 95%CI: 3.8-9.7, pɘ.0001) and...attempt, shock status remained associated with CAs (OR 6.2, 95%CI: 3.9-9.7, pɘ.0001) while oxygenation fa lure and resident providers were not (p=0.54

Evaluation of Coagulation Stages of Hemorrhaged Swine: Comparison of Thromboelastography and Rotational Elastometry

DTIC Science & Technology

2010-01-01

this article is prohibited. TEG and ROTEM comparison Tomori et al . 23 Table 2 Blood loss and survival in three Injury models Blood loss at injury...Shock Society, Cologne, Germany; June 2008, Shock 2008; 29:14. 8 Stern S, Rice J, Philbin N, McGwin G, Arnaud F, Johnson T, et al . Resuscitation...commonly used as measures of hemostasis for a variety of 0957·5235 C 2010 Wolters Kluwer Health 1 Lippincott Williams & Wilkins extremely

A fresh frozen plasma to red blood cell transfusion ratio of 1:1 mitigates lung injury in a rat model of damage control resuscitation for hemorrhagic shock.

PubMed

Zhao, Jingxiang; Pan, Guocheng; Wang, Bo; Zhang, Yuhua; You, Guoxing; Wang, Ying; Gao, Dawei; Zhou, Hong; Zhao, Lian

2015-06-01

We aimed to evaluate the effects of resuscitation with different ratios of fresh frozen plasma (FFP) to red blood cells (RBCs) on pulmonary inflammatory injury and to illuminate the beneficial effects of FFP on lung protection compared with lactated ringers (LR) using a rat model of hemorrhagic shock. Rats underwent pressure-controlled hemorrhage for 60 minutes and were then transfused with LR for initial resuscitation. Thereafter, the rats were transfused with varying ratios of FFP:RBC (1:4, 1:2, 1:1, and 2:1) or LR:RBC (1:1) to hold their mean arterial pressure (MAP) at 100 ± 3 mm Hg for 30 minutes. After 4 hours of observation, lung tissue was harvested to determine the wet/dry weight, myeloperoxidase levels, tumor necrosis factor α levels, macrophage inflammatory protein 2 (MIP-2) levels, inducible nitric oxide synthase activity, and the nuclear factor κB p65 DNA-binding activity. With an increase in the FFP:RBC ratio, the volume of required RBC to maintain the target MAP decreased. The MAP value in each group was not significantly different during the whole experiment period. The values of the wet/dry weights and MIP-2 were significantly lower in the FFP:RBC = 1:1 group than the other groups (P < .05). All parameters detected above were predominantly lower in the FFP:RBC = 1:1 group than the FFP:RBC = 1:2 group and the LR:RBC = 1:1 group (P < .05). In addition, all parameter values were lower in the FFP:RBC = 1:1 group than in the FFP:RBC = 2:1 group, but only the wet/dry weight, myeloperoxidase, and MIP-2 values were significantly different (P < .05). Resuscitation with a 1:1 ratio of FFP to RBC results in decreased lung inflammation. Compared with LR, FFP could further mitigate lung inflammatory injury. Copyright © 2015. Published by Elsevier Inc.

Dimethyl Sulfoxide Attenuates Acute Lung Injury Induced by Hemorrhagic Shock/Resuscitation in Rats.

PubMed

Tsung, Yu-Chi; Chung, Chih-Yang; Wan, Hung-Chieh; Chang, Ya-Ying; Shih, Ping-Cheng; Hsu, Han-Shui; Kao, Ming-Chang; Huang, Chun-Jen

2017-04-01

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively (n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression.

Nonhuman primate model of polytraumatic hemorrhagic shock recapitulates early platelet dysfunction observed following severe injury in humans.

PubMed

Schaub, Leasha J; Moore, Hunter B; Cap, Andrew P; Glaser, Jacob J; Moore, Ernest E; Sheppard, Forest R

2017-03-01

Platelet dysfunction has been described as an early component of trauma-induced coagulopathy. The platelet component of trauma-induced coagulopathy remains to be fully elucidated and translatable animal models are required to facilitate mechanistic investigations. We sought to determine if the early platelet dysfunction described in trauma patients could be recapitulated in a nonhuman primate model of polytraumatic hemorrhagic shock. Twenty-four male rhesus macaques weighting 7 to 14 kg were subjected to 60 minutes (min) of severe pressure-targeted controlled hemorrhagic shock (HS) with and without other injuries. After 60 min, resuscitation with 0.9% NaCl and whole blood was initiated. Platelet counts and platelet aggregation assays were performed at baseline (BSLN), end of shock (EOS; T = 60 min), end of resuscitation (EOR; T = 180 min), and T = 360 min on overall cohort. Results are reported as mean ± standard deviation (SD) or median (interquartile range). Statistical analysis was conducted using Spearmen correlation, one-way analysis of variance, two-way repeated-measures analysis of variance, paired t-test or Wilcoxon nonparametric test, with p < 0.05 considered significant. Platelet count in all injury cohorts decreased over time, but no animals developed thrombocytopenia. Correlations were observed between platelet aggregation and platelet count for all agonists: adenosine diphosphate, thrombin recognition-activating peptide-6, collagen, and arachidonic acid. Overall, compared to BSLN, platelet aggregation decreased for all agonist at EOS, EOR, and T = 360 min. When normalized to platelet count, platelet aggregation in response to agonist thrombin recognition-activating peptide-6 demonstrated no change from BSLN at subsequent time points. Aggregation to adenosine diphosphate was significantly less at EOR but not EOS or T = 360 min compared to BSLN. Platelet aggregation to collagen and arachidonic acid was not significantly different at EOS compared to BSLN but was significantly less at EOR and T = 360 min. Nonhuman primates manifest early platelet dysfunction in response to polytraumatic hemorrhagic shock, consistent with that reported in severely injured human patients. Nonhuman primate models potentially are translationally valuable for understanding the mechanisms and pathophysiology of trauma-induced platelet dysfunction.

Diaspirin Cross-Linked Hemoglobin Infusion Did Not Influence Base Deficit and Lactic Acid Levels in Two Clinical Trials of Traumatic Hemorrhagic Shock Patient Resuscitation

DTIC Science & Technology

2010-05-01

Program, University of Illinois School of Public Health (W.G.), Chicago, Illinois. Supported by a contract with the Henry M. Jackson Foundation...fessor Payen (Principal Investigator, Hopiatl Lariboisiere, Paris Cedex 1 0); Docteur Rouvier, MD (Principal Investiga- tor, Hopital Percy , Clamart

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

PubMed Central

Moran, Ana; Thacker, Stephen A.; Arikan, Ayse Akcan; Mastrangelo, Mary-Ann A.; Wu, Yong; Yu, Bi; Tweardy, David J.

2011-01-01

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome. PMID:21738667

Coagulopathy and traumatic shock: Characterizing hemostatic function during the critical period prior to fluid resuscitation

PubMed Central

White, Nathan J.; Martin, Erika J.; Brophy, Donald F.; Ward, Kevin R.

2009-01-01

Aims Identifying early changes in hemostatic clot function as a result of tissue injury and hypoperfusion may provide important information regarding the mechanisms of traumatic coagulopathy. A combat-relevant swine model was used to investigate the development of coagulopathy during trauma by monitoring hemostatic function during increasing severity of shock. Methods Swine were injured (soft tissue + femur fracture) and hemorrhaged while continuously monitoring Oxygen Debt (OD) by indirect calorimetry at the airway. Hemostatic function was assessed by Thrombelastography (TEG), prothrombin time (PT), partial Thromboplastin time (PTT), and fibrinogen concentration and compared before hemorrhage (D0) and during shock when OD= 40 and 80 ml/kg. An instrumented sham group was used for comparison. Results N=23 swine (n=18 hemorrhage, n=5 sham) weighing 45+/−6 Kg were studied after removing an average of 34+/−14% of blood volume during hemorrhage. Hgb, Hct, platelet counts, PT and PTT did not change with increasing OD (p>0.05). Fibrinogen was reduced significantly by OD=40 ml/kg (mean diff =−59.9 mg/dl, 95% CI diff [−95.1, −24.6]). TEG parameters representing clot initiation (R) and polymerization (K and Alpha Angle) did not change with increasing OD during shock (p>0.053). Clot strength (MA) was reduced in the hemorrhage group by OD=80 ml/kg (mean diff = −4.1 mm, 95% CI diff [−7.4, −0.8]). Conclusion In this swine model of traumatic shock, fibrinogen was significantly reduced and an isolated reduction in clot strength (MA) was found with increasing OD. Fibrinogen consumption and altered platelet function may account for the earliest changes in hemostatic function during traumatic shock. PMID:19854556

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2008-05-01

emergency department. Previously we have demonstrated that ICV choline increased basal MABP (+17%) and produced a similar increase in basal MABP in...alcohol intoxicated. However, ICV choline did not alter the initial % decrease in blood pressure nor did it improve MABP throughout hemorrhagic...shock or fluid resuscitation in alcohol-treated animals. These studies showed that intracerebroventricular (ICV) choline (acetylcholine precursor

Protective Effect of Tropisetron on Rodent Hepatic Injury after Trauma-Hemorrhagic Shock through P38 MAPK-Dependent Hemeoxygenase-1 Expression

PubMed Central

Hwang, Tsong-Long; Tsai, Yung-Fong

2012-01-01

Tropisetron can decrease inflammatory cell responses and alleviate organ damage caused by trauma-hemorrhage, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase/hemeoxygenase-1 (p38 MAPK/HO-1) pathway exerts anti-inflammatory effects on different tissues. The aim of this study was to investigate whether p38 MAPK/HO-1 plays any role in the tropisetron-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 min), followed by fluid resuscitation. During resuscitation, several treatment regimens were administered: four doses of tropisetron alone (0.1, 0.3, 1, 3 mg/kg body weight), or a single dose of tropisetron (1 mg/kg body weight) with and without a p38 MAPK inhibitor (SB-203580, 2 mg/kg body weight) or HO antagonist (chromium-mesoporphyrin, 2.5 mg/kg body weight). Various parameters were measured, and the animals were sacrificed at 24 h post-resuscitation. The results showed that trauma-hemorrhage increased the following parameters: plasma concentrations of aspartate (AST) and alanine aminotransferases (ALT), hepatic myeloperoxidase (MPO) activity, and levels of cytokine-induced neutrophil chemoattractant-1 and -3 (CINC-1 and CINC-3), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). These parameters were significantly improved in the tropisetron-treated rats subjected to trauma-hemorrhage. Tropisetron treatment also increased hepatic p38 MAPK and HO-1 expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 or chromium-mesoporphyrin with tropisetron abolished the tropisetron-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of tropisetron administration on alleviation of hepatic injury after trauma-hemorrhage is likely mediated through p38 MAPK-dependent HO-1 expression. PMID:23285267

Protective effect of tropisetron on rodent hepatic injury after trauma-hemorrhagic shock through P38 MAPK-dependent hemeoxygenase-1 expression.

PubMed

Liu, Fu-Chao; Yu, Huang-Ping; Hwang, Tsong-Long; Tsai, Yung-Fong

2012-01-01

Tropisetron can decrease inflammatory cell responses and alleviate organ damage caused by trauma-hemorrhage, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase/hemeoxygenase-1 (p38 MAPK/HO-1) pathway exerts anti-inflammatory effects on different tissues. The aim of this study was to investigate whether p38 MAPK/HO-1 plays any role in the tropisetron-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 min), followed by fluid resuscitation. During resuscitation, several treatment regimens were administered: four doses of tropisetron alone (0.1, 0.3, 1, 3 mg/kg body weight), or a single dose of tropisetron (1 mg/kg body weight) with and without a p38 MAPK inhibitor (SB-203580, 2 mg/kg body weight) or HO antagonist (chromium-mesoporphyrin, 2.5 mg/kg body weight). Various parameters were measured, and the animals were sacrificed at 24 h post-resuscitation. The results showed that trauma-hemorrhage increased the following parameters: plasma concentrations of aspartate (AST) and alanine aminotransferases (ALT), hepatic myeloperoxidase (MPO) activity, and levels of cytokine-induced neutrophil chemoattractant-1 and -3 (CINC-1 and CINC-3), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). These parameters were significantly improved in the tropisetron-treated rats subjected to trauma-hemorrhage. Tropisetron treatment also increased hepatic p38 MAPK and HO-1 expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 or chromium-mesoporphyrin with tropisetron abolished the tropisetron-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of tropisetron administration on alleviation of hepatic injury after trauma-hemorrhage is likely mediated through p38 MAPK-dependent HO-1 expression.

Platelet closure time in anesthetized Greyhounds with hemorrhagic shock treated with hydroxyethyl starch 130/0.4 or 0.9% sodium chloride infusions.

PubMed

McBride, Duana; Hosgood, Giselle; Raisis, Anthea; Smart, Lisa

2016-07-01

To measure platelet closure time (PCT) in dogs during controlled hemorrhagic shock and after fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 or 0.9% sodium chloride. Experimental interventional study. University veterinary teaching hospital. Eleven healthy Greyhounds. Dogs were anesthetized and had 48 mL/kg of blood removed to induce hemorrhagic shock. Dogs received 20 mL/kg of HES 130/0.4 (n = 6) or 80 mL/kg of 0.9% sodium chloride (NaCl; n = 5) intravenously over 20 minutes. PCT was measured using the Platelet Function Analyzer-100 with collagen and adenosine-diphosphate cartridges at: T0 = 60 minutes after induction of anesthesia prior to hemorrhage, T1 = during hemorrhagic shock, and T2 = 40 minutes after completion of fluid bolus. Packed cell volume and platelet count were concurrently measured. Hemorrhagic shock did not significantly change PCT, with no difference between T0 and T1. Both the HES 130/0.4 and 0.9% NaCl group had a significantly increased mean PCT at T2 of 91.4 seconds (95% CI 69.3-113.4) and 95.5 seconds (95% CI 78.2-112.8), respectively, compared to T1. The magnitude of change was significantly greater for the 0.9% NaCl group than the HES 130/0.4 group. There was no difference in the magnitude of change in PCV and platelet count between the 2 groups. The PCV and platelet count were >25% and >100,000/μL, respectively, in all dogs, except for dogs in the HES 130/0.4 group at T2 where platelet counts were <100,000/μL. Controlled hemorrhagic shock in Greyhounds under anesthesia did not cause a significant change in PCT. Both HES 130/0.4 and 0.9% NaCl administration after induction of shock increased PCT. These results do not support that HES 130/0.4 causes relevant platelet dysfunction beyond hemodilution. © Veterinary Emergency and Critical Care Society 2016.

Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

PubMed

Lubitz, Andrea L; Sjoholm, Lars O; Goldberg, Amy; Pathak, Abhijit; Santora, Thomas; Sharp, Thomas E; Wallner, Markus; Berretta, Remus M; Poole, Lauren A; Wu, Jichuan; Wolfson, Marla R

2017-02-01

Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure. A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours. All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group. These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.

Early Treatment in Shock. Addendum

DTIC Science & Technology

2012-08-01

from gardenia root (Gardenia jasminoides Ellis). It is com- monly sold in the United States as an herbal supplement . In terms of crocetin’s fundamental...but results of 14 the available literature collectively allow the conclusion that L-arginine supplementation 15 can be beneficial in ameliorating the...were designed to test two 19 hypotheses. First, L-arginine supplementation during resuscitation will improve survival 20 from lethal hemorrhagic

Diagnostic and Predictive Values of Thirst, Angiotensin II, and Vasopressin During Trauma Resuscitation

DTIC Science & Technology

2010-09-01

and plasma AVP and AT2 levels across a broader spectrum of hemorrhagic shock severity may be warranted. The authors wish to thank the medical, nursing ...301. 2. Olsson K. Central control of vasopressin release and thirst. Acta Paediatr Scand Suppl. 1983;305:36–9. Pr eh os p E m er g C ar e D ow nl oa

Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

PubMed

Hundeshagen, Gabriel; Kramer, George C; Ribeiro Marques, Nicole; Salter, Michael G; Koutrouvelis, Aristides K; Li, Husong; Solanki, Daneshvari R; Indrikovs, Alexander; Seeton, Roger; Henkel, Sheryl N; Kinsky, Michael P

2017-10-01

We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. Experimental human hemorrhage and resuscitation. Clinical research laboratory. Healthy volunteers. Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 ± 3 mL/kg, closed loop: 4.2 ± 2 mL/kg; p < 0.001), plasma volume, extravascular volume (bolus resuscitation: 17 ± 4 mL/kg, decision assist: 3 ± 1 mL/kg, closed loop: -0.3 ± 0.3 mL/kg; p < 0.001), body weight, and urinary output remained stable under decision assist and closed loop and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (-10 mm Hg; p < 0.001) and was lower under bolus resuscitation than closed loop at 20 minutes (bolus resuscitation: 57 ± 2 mm Hg, closed loop: 69 ± 4 mm Hg; p = 0.036). Colloid osmotic pressure (bolus resuscitation: 19.3 ± 2 mm Hg, decision assist, closed loop: 24 ± 0.4 mm Hg; p < 0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration. We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison with formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.

Diffuse optical monitoring of peripheral tissues during uncontrolled internal hemorrhage in a porcine model

PubMed Central

Vishwanath, Karthik; Gurjar, Rajan; Wolf, David; Riccardi, Suzannah; Duggan, Michael; King, David

2018-01-01

Reliable, continuous and noninvasive blood flow and hemoglobin monitoring in trauma patients remains a critical, but generally unachieved goal. Two optical sensing methods - diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) – are used to monitor and detect internal hemorrhage. Specifically, we investigate if cutaneous perfusion measurements acquired using DCS and DRS in peripheral (thighs and ear-lobe) tissues could detect severe hemorrhagic shock in a porcine model. Four animals underwent high-grade hepato-portal injury in a closed abdomen, to induce uncontrolled hemorrhage and were subsequently allowed to bleed for 10 minutes before fluid resuscitation. DRS and DCS measurements of cutaneous blood flow were acquired using fiber optical probes placed on the thigh and earlobe of the animals and were obtained repeatedly starting from 1 to 5 minutes pre-injury, up to several minutes post shock. Clear changes were observed in measured optical spectra across all animals at both sites. DCS-derived cutaneous blood flow decreased sharply during hemorrhage, while DRS-derived vascular saturation and hemoglobin paralleled cardiac output. All derived optical parameters had the steepest changes during the rapid initial hemorrhage unambiguously. This suggests that a combined DCS and DRS based device might provide an easy-to-use, non-invasive, internal-hemorrhage detection system that can be used across a wide array of clinical settings. PMID:29552394

An approach to transfusion and hemorrhage in trauma: current perspectives on restrictive transfusion strategies

PubMed Central

Tien, Homer; Nascimento, Bartolomeu; Callum, Jeannie; Rizoli, Sandro

2007-01-01

Hemorrhagic shock is a leading cause of death in trauma patients. Surgical control of bleeding and fluid resuscitation with both crystalloid and blood products remain the mainstay of therapy for injured patients with bleeding. However, there has been a recent re-evaluation of transfusion practice. Both the fear of transmissible disease and the costs of transfusing blood products have led to increasingly restrictive transfusion practices. A small percentage of trauma patients require massive transfusion. These patients are complex and difficult to manage, and clinicians must act quickly to save them. There is little evidence to help guide clinical transfusion decisions in these patients. A rational approach to using blood products requires an understanding of the end points of resuscitation. Resuscitation with fluids and red cells is necessary to improve perfusion and oxygen delivery to tissues. Avoiding overtransfusion is key, however, because transfusion is also associated with significant risks. This trend toward reducing allogenic blood exposure will likely continue. New technologies that have the potential of reducing blood loss and transfusion requirements in trauma patients with massive bleeding are being developed, and similar old technologies are being reapplied. PMID:17568492

Polyethylene Glycol Polymers in Low Volume Resuscitation

DTIC Science & Technology

2017-10-01

peripheral vascular disease and chronic heart failure, and space medicine. What as the impact on technology transfer? Technology transfer is a very...patterns were almost identical in volunteers and trauma patients. The significantly lower clot strength in blood diluted with 10% PEG-20k could be...lost in the US, compared to cancer (16%), heart disease (12%), and HIV (2%) (1). For all traumatic injuries, hemorrhagic shock is responsible for

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation.

PubMed

Tian, Feng; Gao, Xuejin; Zhang, Li; Wang, Xinying; Wan, Xiao; Jiang, Tingting; Wu, Chao; Bi, Jingcheng; Lei, Qiucheng

2016-09-29

n -3 polyunsaturated fatty acids (PUFAs) can improve the function of the intestinal barrier after damage from ischemia-reperfusion or hemorrhagic shock resuscitation (HSR). However, the effects of n -3 PUFAs on intestinal microbiota and the innate immunity of the intestinal mucosa after HSR remain unclear. In the present study, 40 C57BL/6J mice were randomly assigned to five groups: control, sham, HSR, HSR + n -3 PUFAs and HSR + n -6 PUFAs. Mice were sacrificed 12 h after HSR. Liver, spleen, mesenteric lymph nodes and terminal ileal tissues were collected. Intestinal mucosae were scraped aseptically. Compared with the HSR group, the number of goblet cells increased, expression of mucin 2 was restored and disturbed intestinal microbiota were partly stabilized in the PUFA-administered groups, indicating that both n -3 and n -6 PUFAs reduced overproliferation of Gammaproteobacteria while promoting the growth of Bacteroidetes. Notably, n -3 PUFAs had an advantage over n -6 PUFAs in improving ileal tissue levels of lysozyme after HSR. Thus, PUFAs, especially n -3 PUFAs, partly improved the innate immunity of intestinal mucosa in mice after HSR. These findings suggest a clinical rationale for providing n -3 PUFAs to patients recovering from ischemia-reperfusion.

Non-traumatic hemorrhage is controlled with REBOA in acute phase then mortality increases gradually by non-hemorrhagic causes: DIRECT-IABO registry in Japan.

PubMed

Matsumura, Y; Matsumoto, J; Idoguchi, K; Kondo, H; Ishida, T; Kon, Y; Tomita, K; Ishida, K; Hirose, T; Umakoshi, K; Funabiki, T

2017-08-22

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted. Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001). Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care.

Resuscitation great. George W. Crile: a visionary mind in resuscitation.

PubMed

Soto-Ruiz, Karina M; Varon, Joseph

2009-01-01

George Washington Crile was a successful surgeon who lived at the end of the 19th century. He was born on 11 November 1864 on a farm near Chili, Ohio. He became interested in the study of shock after a close friend died from hemorrhage. Crile dedicated his research years to the study of shock, cardiac arrest, and the use of adrenaline. His research on shock and cardiac arrest led to treatment guidelines that are still used today. He also participated in the Spanish-American War and in World War I as a Navy Surgeon and saved the lives of many soldiers with his principles of blood transfusion and sanitation. He is also known in the surgical world as the grandfather of radical neck dissection and received the Gold Lannelongue Medal and prize. Having written over 400 papers and 24 books, George W. Crile died from complications of bacterial endocarditis on 7th January 1943. Although they were published a long time ago, his contributions to medicine remain fundamental to clinical practice in today's operating rooms and critical care units.

Hemorrhagic Shock and Surgical Stress Alter Distribution of Labile Zinc within High and Low Molecular Weight Plasma Fractions

PubMed Central

Kelly, Edward; Mathew, Jeff; Kohler, Jonathan E.; Blass, Amy L.; Soybel, David I.

2012-01-01

Zinc ions (Zn2+) are essential for tissue repair following injury or stress. We hypothesize that during such stresses Zn2+ is redistributed to labile pools in plasma components. Here we tested this hypothesis utilizing a novel assay to monitor labile Zn2+ in plasma in hemorrhagic shock. Adult rats in the Shock (S) group underwent hemorrhage and resuscitation. Blood samples were drawn at baseline, 1 hr, 4 hrs and 24 hrs. The Surgical Control (SC) group was anesthetized and instrumented, but not bled. Albumin, total Zn2+, and labile Zn2+ levels were assayed in plasma. Binding capacity for Zn2+ was assessed in high (HMW) and low (LMW) molecular weight pools. Significant decreases in total Zn2+ were observed by 24 hrs, in both S and SC groups. Albumin levels were significantly reduced in the S group at 1 hr and 4 hr but restored at 24 hrs; significant changes were not observed in other groups. In whole plasma, labile Zn2+ levels were stable initially in the S and SC groups, but declined at 24 hrs. In the HMW pool, marked and significant impairment of binding was noted throughout all time periods following the shock period in the S group. Such changes were observed in the SC group of less intensity and duration. These experiments suggest that Shock alters affinity of plasma proteins for Zn2+, promoting delivery to peripheral tissues during periods of increased Zn2+ utilization. PMID:22744307

Hemorrhagic shock and surgical stress alter distribution of labile zinc within high- and low-molecular-weight plasma fractions.

PubMed

Kelly, Edward; Mathew, Jeff; Kohler, Jonathan E; Blass, Amy L; Soybel, And David I

2012-08-01

Zinc ions (Zn) are essential for tissue repair following injury or stress. We hypothesize that during such stresses Zn is redistributed to labile pools in plasma components. Here we tested this hypothesis using a novel assay to monitor labile Zn in plasma in hemorrhagic shock. Adult rats in the shock group (S group) underwent hemorrhage and resuscitation. Blood samples were drawn at baseline and at 1, 4, and 24 h. The surgical control group (SC group) was anesthetized and instrumented, but not bled. Albumin, total Zn, and labile Zn levels were assayed in plasma. Binding capacity for Zn was assessed in high- and low-molecular-weight pools. Significant decreases in total Zn were observed by 24 h, in both S and SC groups. Albumin levels were significantly reduced in the S group at 1 and 4 h but restored at 24 h; significant changes were not observed in other groups. In whole plasma, labile Zn levels were stable initially in the S and SC groups, but declined at 24 h. In the high-molecular-weight pool, marked and significant impairment of binding was noted throughout all time periods following the shock period in the S group. Such changes were observed in the SC group of less intensity and duration. These experiments suggest that shock alters affinity of plasma proteins for Zn, promoting delivery to peripheral tissues during periods of increased Zn utilization.

Tranexamic Acid Attenuates The Loss of Lung Barrier Function in a Rat Model of Polytrauma And Hemorrhage With Resuscitation.

PubMed

Wu, Xiaowu; Dubick, Michael A; Schwacha, Martin G; Cap, Andrew P; Darlington, Daniel N

2017-04-01

Severe trauma, hemorrhage, and resuscitation can lead to a trauma-related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage, and resuscitation. Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle, and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10 mg/kg in 0.2 mL). Polytrauma, hemorrhage, and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase, and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.

Pyruvate-Enhanced Resuscitation for Hemorrhagic Shock and Hindlimb Ischemia

DTIC Science & Technology

2015-06-06

Albert Yurvati Albert H Olivencia-Yurvati 611102 c . THIS PAGE The public reporting burden for this collection of information is estimated to average 1...journals (N/A for none) ( c ) Presentations Received Paper TOTAL: Received Paper TOTAL: Number of Non Peer-Reviewed Conference Proceeding publications (other...Mallet . “Surgical management of the goat.” , Lab Animal (06 2011) Devin C . Flaherty, DO, PhD, Besim Hoxha, MD, Shirley Nelson, RLAT, Jie Sun, BS

Evaluation of Resuscitation Fluids on Endothelial Glycocalyx, Venular Blood Flow, and Coagulation Function After Hemorrhagic Shock in Rats

DTIC Science & Technology

2013-10-01

thrombin inhibition, leading to coagulopathy. Using intravital microscopy, we have obtained direct in vivo data showing glycocalyx thickness reduction...collected in 3.2% citrate for coagulation assays (ROTEM, TEM Innovations GmbH, Munich, Germany). Intravital Microscopy The system described in detail...microscopic fields containing venules were randomly selected. The first dye (TR-Dx70) was injected 5 min before baseline. Image sequences of

Early Whole Blood for Patients Requiring Massive Transfusion after Major Trauma

DTIC Science & Technology

2013-03-01

Inflammation and Adiposity after Hemorrhagic Shock and Resuscitation (PI Kozar) Evaluate sarcopenia based on admission CT and compare to BMI and...our collaborator, Dr. Mourtzakis, for calculation of sarcopenia based on muscle mass at the third lumbar vertebrae. There were 58 patients admitted...We are in the process of determining which of the 45 patients had an abdominal CT. We have just completed a retrospective review of elderly trauma

Chronic porcine two-hit model with hemorrhagic shock and Pseudomonas aeruginosa sepsis.

PubMed

Eissner, B; Matz, K; Smorodchenko, A; Röschmann, A; v Specht, B U

2002-01-01

Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as 'first hit' followed by a Pseudomonas aeruginosa infusion as 'second hit'. Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic shock with a 50% reduction of the mean arterial pressure and/or cardiac index for 45 min, followed by resuscitation, while the control group (n = 6) received no pretreatment. All chronically catheterized conscious pigs were challenged with a P. aeruginosa infusion (1.6 x 10(7) CFU/kg/h for the first 24 h followed by 1.6 x 10(6) CFU/kg/h for the next 24 h) and observed for another 48 h. The two-hit group showed the following significant differences to the control group: higher APACHE II scores prior to sepsis induction, increased persisting mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) during bacterial challenge. In contrast, systemic vascular resistance (SVRI) was reduced at the end of the study. Throughout the observation period, the mean arterial pressure (MAP) was significantly reduced. The present study shows that the clinical course and hemodynamic effects of a P. aeruginosa sepsis will be aggravated by a preceding hemorrhagic shock during an observation period of 96 h. This two-hit model represents a valid, clinically relevant experimental protocol in sepsis research. Copyright 2002 S. Karger AG, Basel

Less impairment of hemostasis and reduced blood loss in pigs after resuscitation from hemorrhagic shock using the small-volume concept with hypertonic saline/hydroxyethyl starch as compared to administration of 4% gelatin or 6% hydroxyethyl starch solution.

PubMed

Haas, Thorsten; Fries, Dietmar; Holz, Carmen; Innerhofer, Petra; Streif, Werner; Klingler, Anton; Hanke, Alexander; Velik-Salchner, Corinna

2008-04-01

Small-volume resuscitation using hypertonic saline/hydroxyethyl starch 200/0.62 (HS-HES) has been shown to be an effective alternative to the administration of crystalloids or colloids in trauma patients. All i.v. fluids cause dose-related dilutional coagulopathy and show intrinsic effects on the hemostatic system, but only few data refer to functional consequences after small-volume resuscitation. Using thrombelastometry (ROTEM), we studied 30 pigs (weighing 35-45 kg) after withdrawal of 60% of blood volume [1484 mL (1369-1624 mL)] and receiving 4 mL/kg HS-HES for compensation of blood loss or 4% gelatin or 6% HES 130/0.4 in a 1:1 ratio to lost blood volume. To compare the ROTEM variables (coagulation time, clot formation time, alpha angle, clot firmness, and fibrinogen polymerization) with bleeding tendency, a hepatic incision was made and blood loss was measured. Median (25th, 75th percentile) fibrinogen polymerization was significantly higher after HS-HES infusion [11 mm (10, 11), P = 0.0034] when compared with administration of 4% gelatin [4.5 mm (3.0, 5.8)] or HES 130/0.4 [3.5 mm (2.3, 4.0)]. Median blood loss after liver incision was 725 mL (900, 375) after HS-HES, 1625 mL (1275, 1950) after 4% gelatin, and 1600 mL (1500, 1800) after 6% HES 130/0.4 (P = 0.004). Hemodynamic stabilization was traceable in all groups but showed differences regarding filling pressures. Resuscitation from hemorrhagic shock with HS-HES 200/0.62 results in less impairment of clot formation when compared with compensation of blood loss by administering 6% HES 130/0.4 or 4% gelatin.

Interleukin-6 treatment reverses apoptosis and blunts susceptibility to intraperitoneal bacterial challenge following hemorrhagic shock.

PubMed

Arikan, Ayse Akcan; Yu, Bi; Mastrangelo, Mary-Ann; Tweardy, David J

2006-03-01

Resuscitation from hemorrhagic shock (HS) predisposes to subsequent infections. Susceptibility to infection following sepsis has been attributed to apoptosis. Interleukin (IL)-6 has been shown to have antiapoptotic properties and to decrease postresuscitation inflammation in rodent and porcine models of HS. The objective was to determine if HS increases host susceptibility to infection, if IL-6 administration at resuscitation reduces this susceptibility, and if changes in susceptibility to infection are accompanied by parallel changes in apoptosis. Mice were randomized into three groups-HS, sham, and no-surgery control-and each group was further randomized to receive either IL-6 (3 microg/kg; HS/IL-6) or placebo (HS/P) at the start of resuscitation. In the HS-infection protocol, each mouse was challenged intraperitoneally the next day with a sublethal dose of Staphylococcus aureus (4x107 colony-forming units); 24 hrs later, the peritoneal cavity was lavaged and the major organs were harvested for culture. In the HS-apoptosis protocol, the livers were harvested the next day and analyzed by means of the terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling (TUNEL) assay. HS/P mice had a six- to eight-fold increase in total bacterial counts in comparison with sham and control mice that was attributable to a seven- to nine-fold increase in liver burden. IL-6 treatment reduced total and liver bacterial counts in HS/IL-6 mice by 62% and 69%, respectively, to levels statistically indistinguishable from IL-6-treated sham and control mice. The number of TUNEL-positive liver cells in the HS/P group was increased eight-fold vs. that in the sham group (p=.002); IL-6 resuscitation completely reversed the HS-induced increase in TUNEL-positive cells in the HS/IL-6 group (p=.002). IL-6 treatment at resuscitation eliminated the HS-mediated increase in total and liver bacterial burden and protected the liver from HS-induced apoptosis. Reduced liver apoptosis may explain the ability of IL-6 to blunt the HS-induced increase in susceptibility to bacterial challenge.

Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1.

PubMed

Relja, Borna; Wagner, Nils; Franz, Niklas; Dieteren, Scott; Mörs, Katharina; Schmidt, Julia; Marzi, Ingo; Perl, Mario

2018-03-01

After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R. Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses. EP significantly improved pO 2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections. Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Damage-Associated Molecular Patterns (DAMPs) in Resuscitated Hemorrhagic Shock Are Mitigated by Peritoneal Fluid Administration.

PubMed

Matheson, Paul J; Eid, Mark A; Wilson, Matthew A; Graham, Victoria S; Matheson, Samuel A; Weaver, Jessica Lee; Downard, Cynthia D; Smith, Jason W

2018-05-03

Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is I.V. blood and fluids. CR restores central hemodynamics, but vital organ flow can drop causing hypoperfusion, hypoxia, Damage-Associated Molecular Patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus Direct Peritoneal Resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs. Anesthetized male SD rats were randomized to groups (n=8/group) in one of two sets: 1) Sham (no HS, CR, or DPR); 2) HS/CR (HS=40% MAP for 60min, CR=shed blood + 2 volumes NS); or 3) HS/CR+DPR. First set underwent whole lung blood flow by colorimetric microspheres. Second set underwent tissue collection for Luminex, ELISAs, and histopathology. Lipopolysaccharide (LPS) and DAMPs were measured in serum and/or lung including cytokines, hyaluronic acid (HA), high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), MYD88, and TRIF. Statistics were by ANOVA and Tukey-Kramer test with a priori P<0.05. HS/CR increased serum LPS, HA, HMGB1 and some cytokines (IL-1α, IL-1β, IL-6, and interferon-γ). Lung TLR4 and MYD88 were increased but not TRIF compared to Shams. HS/CR+DPR decreased LPS, HA, cytokines, HMGB1, TLR4, and MYD88 levels but did not alter TRIF compared to HS/CR. Data suggest that gut-derived DAMPs can be modulated by adjunctive DPR to prevent activation of lung TLR-4-mediated processes. Also, DPR improved lung blood flow and reduced lung tissue injury. Adjunctive DPR in HS/CR potentially improves morbidity/mortality by down-regulating the systemic DAMP response.

Granulocyte-Colony Stimulating Factor (G-CSF) Accelerates Wound Healing in Hemorrhagic Shock Rats by Enhancing Angiogenesis and Attenuating Apoptosis

PubMed Central

Huang, Hong; Zhang, Qi; Liu, Jiejie; Hao, Haojie; Jiang, Chaoguang; Han, Weidong

2017-01-01

Background Following severe trauma, treatment of cutaneous injuries is often delayed by inadequate blood supply. The aim of the present study was to determine whether granulocyte-colony stimulating factor (G-CSF) protects endothelial cells (ECs) and enhances angiogenesis in a rat model of hemorrhagic shock (HS) combined with cutaneous injury after resuscitation. Material/Methods The HS rats with full-thickness defects were resuscitated and randomly divided into a G-CSF group (200 μg/kg body weight), a normal saline group, and a blank control group. Histological staining was to used estimate the recovery and apoptosis of skin. Apoptosis- and angiogenesis-related factors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB). Scratch assay, tube formation, and WB experiments were performed to verify the functional effects of G-CSF on HUVECs in vitro. Results H&E staining and Masson trichrome staining showed earlier inflammation resolution and collagen synthesis in the G-CSF-treated group. Angiogenesis-related factors were elevated at mRNA and protein levels. TUNEL staining suggested fewer apoptotic cells in the G-CSF group. The apoptotic-related factors were down-regulated and anti-apoptotic factors were up-regulated in the G-CSF-treated group. Scratch assay and tube formation experiments revealed that G-CSF facilitated migration ability and angiogenic potential of HUVECs. The angiogenic and anti-apoptotic effects were also enhanced in vitro. Conclusions Our results suggest that G-CSF after resuscitation attenuates local apoptosis and accelerates angiogenesis. These findings hold great promise for improving therapy for cutaneous injury in severe trauma and ischemia diseases. PMID:28559534

The Ratio of Blood Products Transfused Affects Mortality in Patients Receiving Massive Transfusions at a Combat Support Hospital

DTIC Science & Technology

2007-10-01

therapy resuscitation, and exacer- bated by hemorrhagic shock, metabolic acidosis, hypother- mia, hyperfibrinolysis, hypocalcemia , and anemia.11,14–19...outcome studies examining the effect of blood product transfusion ratios for trauma patients requiring massive transfusion. Most deaths (80% to 85%) that...calculation of apheresis platelet units transfused, though FWB has previously been shown to be as effective as 10 units of platelet concentrate.33 The

Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1998-01-01

To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

Complement inhibition prevents gut ischemia and endothelial cell dysfunction after hemorrhage/resuscitation.

PubMed

Fruchterman, T M; Spain, D A; Wilson, M A; Harris, P D; Garrison, R N

1998-10-01

Complement, a nonspecific immune response, is activated during hemorrhage/resuscitation (HEM/RES) and is involved in cellular damage. We hypothesized that activated complement injures endothelial cells (ETCs) and is responsible for intestinal microvascular hypoperfusion after HEM/RES. Four groups of rats were studied by in vivo videomicroscopy of the intestine: SHAM, HEM/RES, HEM/RES + sCR1 (complement inhibitor, 15 mg/kg intravenously given before resuscitation), and SHAM + sCR1. Hemorrhage was to 50% of mean arterial pressure for 60 minutes followed by resuscitation with shed blood plus an equal volume of saline. ETC function was assessed by response to acetylcholine. Resuscitation restored central hemodynamics to baseline after hemorrhage. After resuscitation, inflow A1 and premucosal A3 arterioles progressively constricted (-24% and -29% change from baseline, respectively), mucosal blood flow was reduced, and ETC function was impaired. Complement inhibition prevented postresuscitation vasoconstriction and gut ischemia. This protective effect appeared to involve preservation of ETC function in the A3 vessels (SHAM 76% of maximal dilation, HEM/RES 61%, HEM/RES + sCR1 74%, P < .05). Complement inhibition preserved ETC function after HEM/RES and maintained gut perfusion. Inhibition of complement activation before resuscitation may be a useful adjunct in patients experiencing major hemorrhage and might prevent the sequelae of gut ischemia.

Recombinant Factor XIII Mitigates Hemorrhagic Shock-Induced Organ Dysfunction

PubMed Central

Zaets, Sergey B.; Xu, Da-Zhong; Lu, Qi; Feketova, Eleonora; Berezina, Tamara L.; Malinina, Inga V.; Deitch, Edwin A.; Olsen, Eva H.

2012-01-01

Background Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Since FXIII has also been shown to modulate inflammation, endothelial permeability, as well as diminish multiple organ dysfunction (MOD) after gut ischemia-reperfusion injury, we hypothesized that FXIII would reduce MOD caused by trauma-hemorrhagic shock (THS). Materials and methods Rats were subjected to a 90 min THS or trauma sham shock (TSS) and treated with either recombinant human FXIII A2 subunit (rFXIII) or placebo immediately after resuscitation with shed blood or at the end of the TSS period. Lung permeability, lung and gut myeloperoxidase (MPO) activity, gut histology, neutrophil respiratory burst, microvascular blood flow in the liver and muscles, and cytokine levels were measured 3 h after the THS or TSS. FXIII levels were measured before THS or TSS and after the 3-h post-shock period. Results THS-induced lung permeability as well as lung and gut MPO activity was significantly lower in rFXIII-treated than in placebo-treated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and less ileal mucosal injury. rFXIII-treated rats also had a higher liver microvascular blood flow compared with the placebo group. Cytokine response was more favorable in rFXIII-treated animals. Trauma-hemorrhagic shock did not cause a drop in FXIII activity during the study period. Conclusions Administration of rFXIII diminishes THS-induced MOD in rats, presumably by preservation of the gut barrier function, limitation of polymorphonuclear leukocyte (PMN) activation, and modulation of the cytokine response. PMID:21276979

Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic Fracture and Intra Abdominal Hemorrhagic Shock using Continuous Vital Signs

DTIC Science & Technology

2017-11-01

University of Maryland Baltimore, MD 21202 DATE OF REPORT: November 2017 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel...ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5014 11. SPONSOR/MONITOR’S REPORT...Prytime Medical , Boerne, TX )) in October 2015, we incorporated this catheter into our practice in February 2016. Our REBOA training course (Basic

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction Using IL-6 as a Resuscitation Adjuvant

DTIC Science & Technology

2011-12-01

infiltrating PMNs is not merely limited to organs that have been directly injured from trauma. Ischemia - reperfusion injury (which occurs after... injury by facilitating inflammatory cell adhesion in an animal model of myocardial ischemia - reperfusion [61,62]. Fabp2 and Fabp5 have been implicated in...Bauer A, Tweardy DJ (1998) Activation of STAT proteins following ischemia reperfusion injury demonstrates a distinct IL- 6 and G-CSF mediated profile

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction

DTIC Science & Technology

2012-12-01

injury, which they wanted to use to establish if kidney injury occurred in our standard rat T/HS model and to determine whether kidney injury could be...prevented by use of IL-6 as a resuscitation adjuvant. In this experiment, we subjected 6 rats each to either our sham protocol or our standard T/HS...time of accumulation in our standard T/HS protocol. Our results demonstrated that shred blood accumulated sIL-6R over time to concentrations (100 ng

Out-of-hospital Hypertonic Resuscitation After Traumatic Hypovolemic Shock

PubMed Central

Bulger, Eileen M.; May, Susanne; Kerby, Jeffery D.; Emerson, Scott; Stiell, Ian G.; Schreiber, Martin A.; Brasel, Karen J.; Tisherman, Samuel A.; Coimbra, Raul; Rizoli, Sandro; Minei, Joseph P.; Hata, J. Steven; Sopko, George; Evans, David C.; Hoyt, David B.

2011-01-01

Objective To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ≤ 70 mm Hg or systolic blood pressure 71–90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival—HSD: 74.5% (0.1; 95% confidence interval [CI], −7.5 to 7.8); HS: 73.0% (−1.4; 95% CI, −8.7–6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality—HSD: 10% (5.2; 95% CI, 0.4–10.1); HS: 12.2% (7.4; 95% CI, 2.5–12.2); and NS: 4.8%, P < 0.01]. Conclusion Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. PMID:21178763

Hemorrhage-induced hepatic injury and hypoperfusion can be prevented by direct peritoneal resuscitation.

PubMed

Hurt, Ryan T; Zakaria, El Rasheid; Matheson, Paul J; Cobb, Mahoney E; Parker, John R; Garrison, R Neal

2009-04-01

Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes). Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet-dry ratio). Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 +/- 28 microg/mL and aspartate aminotransferase (AST), 234 +/- 24 microg/mL; p < 0.05) compared to group 1 (73 +/- 9 and 119 +/- 10 microg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 +/- 9 microg/mL and AST 150 +/- 17 microg/mL), and tissue edema was similar to sham. CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.

The US Department of Defense Hemorrhage and Resuscitation Research and Development Program.

PubMed

Pusateri, Anthony E; Dubick, Michael A

2015-08-01

Data from recent conflicts demonstrate the continuing need for research and development focusing on hemorrhage control, fluid resuscitation, blood products, transfusion, and pathophysiologic responses to traumatic hemorrhage. The US Department of Defense Hemorrhage and Resuscitation Research and Development Program brings together US Department of Defense efforts and is coordinated with efforts of our other federal government, industry, international, and university-based partners. Military medical research has led to advances in both military and civilian trauma care. A sustained effort will be required to continue to advance the care of severely injured trauma patients.

Fluoroscopy-free Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for controlling life threatening postpartum hemorrhage

PubMed Central

Stensaeth, Knut Haakon; Sovik, Edmund; Haig, Ingrid Natasha Ylva; Skomedal, Erna; Jorgensen, Arve

2017-01-01

Background Severe postpartum hemorrhage occurs in 1/1000 women giving birth. This condition is often dramatic and may be life threatening. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has in recent years been introduced as a novel treatment for hemorrhagic shock. We present a series of fluoroscopy-free REBOA for controlling life threatening postpartum hemorrhage. Methods In 2008 an ‘aortic occlusion kit’ was assembled and used in three Norwegian university hospitals. The on-call interventional radiologist (IR) was to be contacted with a response time < 30 minutes in case of life threatening PPH. Demographics and characteristics were noted from the medical records. Results This retrospective study includes 36 patients treated with fluoroscopy-free REBOA for controlling severe postpartum hemorrhage in the years 2008–2015. The REBOA success rate was 100% and no patients died from REBOA related complications. Uterine artery embolization was performed in 17 (47%) patients and a hysterectomy in 16 (44%) patients. A short (11cm) introducer length was strongly associated with iliac artery thrombus formation (ρ = 0.50, P = 0.002). In addition, there was a strong negative correlation between uterine artery embolization and hysterectomy (ρ = -0.50, P = 0.002). Conclusions Our Norwegian experience indicates the clinical safety and feasibility of REBOA in life threatening PPH. Also, REBOA can be used in an emergency situation without the use of fluoroscopy with a high degree of technical success. It is important that safety implementation of REBOA is established, especially through limited aortic balloon occlusion time and a thorough balloon deflation regime. PMID:28355242

Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma.

PubMed

Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S; Jin, Guang; Jepsen, Cecilie H; Imam, Ayesha; Hwabejire, John O; Deperalta, Danielle; Duggan, Michael; DeMoya, Marc; Velmahos, George C; Alam, Hasan B

2014-04-01

Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS). Twelve swine were subjected to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. ADP-induced platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5 U, p < 0.01) following resuscitation. This was associated with higher fibrinogen levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM-1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ.After 6 hours of observation, ADP-induced platelet aggregation remained higher in the FFP group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153 mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4 ng/mL, p = 0.05), whereas TGF-β levels were higher (2,138 pg/mL vs. 1,802 pg/mL, p = 0.03) in the FFP group. Other markers did not differ. Thromboelastography revealed increased clot strength in the FFP group at both postresuscitation time points. Resuscitation with FFP resulted in an immediate and sustained improvement in platelet function and clot strength compared with high-volume NS resuscitation. This was associated with an increase in fibrinogen levels and an attenuation of endothelial activation.

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

PubMed

Chen, Shuhua; Hoffman, Rosemary A; Scott, Melanie; Manson, Joanna; Loughran, Patricia; Ramadan, Mostafa; Demetris, Anthony J; Billiar, Timothy R

2017-07-01

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1 + cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1 + cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1 + cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1 + cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut. © Society for Leukocyte Biology.

Severe postpartum hemorrhage from uterine atony: a multicentric study.

PubMed

Montufar-Rueda, Carlos; Rodriguez, Laritza; Jarquin, José Douglas; Barboza, Alejandra; Bustillo, Maura Carolina; Marin, Flor; Ortiz, Guillermo; Estrada, Francisco

2013-01-01

Postpartum hemorrhage (PPH) is an important cause of maternal mortality (MM) around the world. Seventy percent of the PPH corresponds to uterine atony. The objective of our study was to evaluate multicenter PPH cases during a 10-month period, and evaluate severe postpartum hemorrhage management. The study population is a cohort of vaginal delivery and cesarean section patients with severe postpartum hemorrhage secondary to uterine atony. The study was designed as a descriptive, prospective, longitudinal, and multicenter study, during 10 months in 13 teaching hospitals. Total live births during the study period were 124,019 with 218 patients (0.17%) with severe postpartum hemorrhage (SPHH). Total maternal deaths were 8, for mortality rate of 3.6% and a MM rate of 6.45/100,000 live births (LB). Maternal deaths were associated with inadequate transfusion therapy. In all patients with severe hemorrhage and subsequent hypovolemic shock, the most important therapy is intravascular volume resuscitation, to reduce the possibility of target organ damage and death. Similarly, the current proposals of transfusion therapy in severe or massive hemorrhage point to early transfusion of blood products and use of fresh frozen plasma, in addition to packed red blood cells, to prevent maternal deaths.

Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway.

PubMed

Hsu, Jun-Te; Le, Puo-Hsien; Lin, Chun-Jung; Chen, Tsung-Hsing; Kuo, Chia-Jung; Chiang, Kun-Chun; Yeh, Ta-Sen

2017-05-01

Although melatonin attenuates the increases in inflammatory mediators and reduces organ injury during trauma-hemorrhage, the mechanisms remain unclear. This study explored whether melatonin prevents liver injury after trauma-hemorrhage through the p38 mitogen-activated protein kinase (MAPK)-dependent, inducible nitrite oxide (iNOS)/hypoxia-inducible factor (HIF)-1α pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), melatonin plus p38 MAPK inhibitor SB203580 (2 mg/kg), or melatonin plus the melatonin receptor antagonist luzindole (2.5 mg/kg). At 2 h after trauma-hemorrhage, histopathology score of liver injury, liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and asparate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the p38 MAPK activation compared with that in the sham-treated animals. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression and attenuated cleaved caspase 3 and receptor interacting protein kinase-1 levels. Coadministration of SB203580 or luzindole abolished the melatonin-mediated attenuation of the trauma-hemorrhage-induced increase of iNOS/HIF-1α protein expression and liver injury markers. Taken together, our results suggest that melatonin prevents trauma-hemorrhage-induced liver injury in rats, at least in part, through melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway. NEW & NOTEWORTHY Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression, which was abolished by coadministration of SB203580 or luzindole. Melatonin prevents trauma-hemorrhage-induced liver injury in rats via the melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway. Copyright © 2017 the American Physiological Society.

A Prospective, Randomized Investigation of Plasma First Resuscitation for Traumatic Hemorrhage and Attenuation of the Acute Coagulopathy of Trauma

DTIC Science & Technology

2013-08-01

Investigation of "Plasma First Resuscitation" for Traumatic Hemorrhage and Attenuation of the Acute Coagulopathy of Trauma PRINCIPAL INVESTIGATOR...34Plasma First Resuscitation" for Traumatic Hemorrhage and Attenuation of the Acute Coagulopathy of Trauma 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...is the most preventable cause of death in trauma patients. Coagulopathy has been documented in up to one third of trauma patients upon arrival to the

Resuscitation of severe uncontrolled hemorrhage: 7.5% sodium chloride/6% dextran 70 vs 0.9% sodium chloride.

PubMed

Stern, S A; Jwayyed, S; Dronen, S C; Wang, X

2000-08-01

Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20 mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

PubMed

Hierholzer, C; Kalff, J C; Chakraborty, A; Watkins, S C; Billiar, T R; Bauer, A J; Tweardy, D J

2001-02-01

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Noninvasive NIR measurement of tissue pH to assess hemorrhagic shock in swine

NASA Astrophysics Data System (ADS)

Soller, Babs R.; Zhang, Songbiao; Micheels, Ronald H.; Puyana, Juan C.

1999-07-01

Body-worn noninvasive physilogical sensors are needed to continuously monitor soldiers for hemorrhage and to provide real-time information for minimally skilled medics to treat the injured. In the hospital intramucosal pHi of the gut is used to monitor shock and its treatment. We hypothesize that abdominal wall muscle (AWM) pH can be measured noninvasively using near infrared (NIR) spectroscopy and partial least squares analysis (PLS) and will correlate with pHi. METHODS: AWM pH was measured with microelectrodes and gastric pHi was measured with a tonometric catheter simultaneously while NIR spectra were collected using prototype LED spectrometers placed on the pig's flanks. Animals were subject to hemorrhagic shock at 45 mm Hg for 45 minutes, then resuscitated with blood and lactated ringers. Relationships between electrode pH, pHi and NIR spectra were developed using PLS with cross validation. RESULTS: NIR spectral changes noninvasively acquired through the skin were shown to be from the muscle, not from changes in skin blood flow. Trending ability (R2) model accuracy (RMSD), and relative error were calculated for individual pigs. Using electrode pH as the reference, average R2 was 0.88 with a predicted accuracy of 0.17 pH units, a 9.3% relative error. Slightly degraded results were observed when pHi was used as a reference. CONCLUSIONS: NIR measurement of tissue pH can be used to noninvasively monitor for shock and guide its treatment in a swine model. These measurements correlate with gastric pHi, a clinically accepted measure of shock, providing an approach to develop similar methodology for humans.

Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local inflammation, NF-kappaB activation and HMGB1 release.

PubMed

Wagner, Nils; Dieteren, Scott; Franz, Niklas; Köhler, Kernt; Mörs, Katharina; Nicin, Luka; Schmidt, Julia; Perl, Mario; Marzi, Ingo; Relja, Borna

2018-01-01

The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored. Female Lewis rats were subjected to TxT followed by hemorrhage/H (60 min, 35±3 mm Hg) and resuscitation/R (TxT+H/R). Reperfusion was performed by either Ringer`s lactated solution (RL) alone or RL supplemented with EP (50 mg/kg). Sham animals underwent all surgical procedures without TxT+H/R. After 2h, blood and liver tissue were collected for analyses, and survival was assessed after 24h. Resuscitation with EP significantly improved haemoglobin levels and base excess recovery compared with controls after TxT+H/R, respectively (p<0.05). TxT+H/R-induced significant increase in alanine aminotransferase levels and liver injury were attenuated by EP compared with controls (p<0.05). Local inflammation as shown by increased gene expression of IL-6 and ICAM-1, enhanced ICAM-1 and HMGB1 protein expression and infiltration of the liver with neutrophils were also significantly attenuated by EP compared with controls after TxT+H/R (p<0.05). EP significantly reduced TxT+H/R-induced p65 activation in liver tissue. Survival rates improved by EP from 50% to 70% after TxT+H/R. These data support the concept that the pronounced local pro-inflammatory response in the liver after blunt chest trauma and hemorrhagic shock is associated with NF-κB. In particular, the beneficial anti-inflammatory effects of ethyl pyruvate seem to be regulated by the HMGB1/NF-κB axis in the liver, thereby, restraining inflammatory responses and liver injury after double hit trauma in the rat.

[Applied studies of structured triglycerides for parenteral nutrition in severe hemorrhagic shock patients after resuscitation].

PubMed

Su, Mao-sheng; He, Lei; Liu, Zhi-wei; Ma, Huan-xian; Zhao, Qing-hua; Zhang, Wen-zhi

2012-03-27

To evaluate the effects of structured triglycerides in parenteral nutrition versus a physical medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture on severe hemorrhagic shock patients after resuscitation. In a randomized trial, we studied 20 critical patients with a total blood loss of over 3000 ml perioperatively and/or intraoperatively. The use of triglycerides started from Day 3 postoperation and parenteral nutrition lasted for no less than 5 days. They were allocated to receive one of two nutrition regiments: structured triglycerides in Group A (n = 10) and MCT/LCT in Group B (n = 10). There were no significant differences of general conditions in two groups. Before the start of parenteral nutrition (d0), d1 d3 and d5 after start of infusion, the following parameters were measured: hemoglobin (Hb), platelet count (Plt), alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), serum triglycerides (TG), prealbumin (PA) and transferrin (TF). And mean artery pressure (MAP), heart rate (HR) and central vein pressure (CVP) were also recorded at the same time-points. Then the post-TG changes of the above data were compared in both groups. After the use of triglycerides, there were no significant differences of MAP, HR, CVP, Hb and Plt in both groups (P > 0.05). At D3 and D5, the serum levels of TG ((2.1 ± 0.4) vs (1.6 ± 0.6) mg/L, (2.3 ± 0.7) vs (1.5 ± 0.3) mg/L) and alanine aminotransferase ((133 ± 58) vs (97 ± 26) U/L; (116 ± 48) vs (77 ± 31) U/L) were significantly higher in Group B versus those receiving structured triglycerides in Group A (P < 0.05). TB ((18 ± 15) vs (18 ± 11) µmol/L) and DB ((8.9 ± 3.2) vs (8.8 ± 2.5) µmol/L) had no significant differences in two groups (P > 0.05). The serum levels of such nutrition markers as PA ((195 ± 55) vs (166 ± 55) mg/L,(245 ± 53) vs (195 ± 58) mg/L) and TF ((2.6 ± 0.5) vs (2.5 ± 0.6) g/L, (3.3 ± 0.8) vs (2.9 ± 0.6) g/L)were significantly higher in Group A than those in Group B (P < 0.05). With regards to lipid metabolism, protein synthesis and hepatocyte protection, structured triglycerides in parenteral nutrition is advantageous to standard MCT/LCT emulsion in severe hemorrhagic shock patients after resuscitation.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

PubMed

Chang, Ronald; Folkerson, Lindley E; Sloan, Duncan; Tomasek, Jeffrey S; Kitagawa, Ryan S; Choi, H Alex; Wade, Charles E; Holcomb, John B

2017-02-01

Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluid Resuscitation for Hemorrhagic Shock in Tactical Combat Casualty Care: TCCC Guidelines Change 14-01 - 2 June 2014

DTIC Science & Technology

2014-06-02

colleagues note that much of the resistance to the use of far-forward fresh whole blood is the perceived risk associated with its use but that this...and hyper-oncotic (e.g., dextrans, hydroxyethyl starches [HESs], and 20% or 25% albumin). The dose of HES used could not exceed 30 mL per kg of body...different types of starch solutions may have different physiologic ef- fects.101 Results after treatment with an assortment of HES options do not

Nitroglycerin Attenuates Vasoconstriction of HBOC-201 during Hemorrhagic Shock Resuscitation

DTIC Science & Technology

2010-01-01

A 00 w 484 LM. Katz ec al. / Resuscicacion 81 (2010) 481-487 45 40 35 ~ 30 E 25 E ll . 20 ct ll . 15 :::= 10 5 0 5!o 0 0...criticised for either being too slow or too fast. EMBO Rep 2002;3:14-6. 35. Knudson MM. Lee s. Erickson V, Morabito D, Derugin N, Manley GT. Tissue oxy...vasodilation with nitrocompounds-is there a maximum? Z Kardiol1989;78:38-40. 40. Noonan PK. Williams Rl.. Benet lL Dose dependent pharmacokinetics of

Gastrointestinal Fluid Resuscitation of Thermally Injured Patients

DTIC Science & Technology

2006-10-01

optimiza- tion of ORT solutions.44–47 Further research on oral fluids for plasma-volume expansion has been performed by NASA . Prolonged space flight is...222 (4.4) 60 44 4 28 370 Burn Jiang’s Burn Drink 252 (5.0) 48 28 0 20 347 Burn Ricelyte (3.0) 50 45 25 34 200 Dehydration AstroAde ( NASA ) 0 164 76 0 40...hemorrhagic shock from gastritis during a trek in Nepal. One liter of double-strength solution followed by 2 liters of standard-strength so- lution were

Evolution de la reanimation transfusionnelle du blesse hemorragique grave au sein des forces militaires americaines (Evolution of US Military Transfusion Support for Resuscitation of Trauma and Hemorrhagic Shock)

DTIC Science & Technology

2013-04-15

Trauma Registry; Fresh whole blood; 1:1:1 component therapy; Platelet:RBC; FFP:RBC; Freeze-dried plasma; Tranexamic acid ∗ Auteur correspondant. Adresse e...Effects of tranexamic acid on death, vascular occlu- sive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a...randomised, placebo-controlled trial. Lancet 2010;376:23–32. [74] Morrison JJ, et al. Military application of tranexamic acid in trauma emer- gency

Is thromboelastography (TEG)-based resuscitation better than empirical 1:1 transfusion?

PubMed Central

Howley, Isaac W; Haut, Elliott R; Jacobs, Lenwoth; Scalea, Thomas M

2018-01-01

Thomboelastography (TEG) is a whole blood measure of coagulation which was originally described in the 1950s. However, it has only been in the last few decades that assays have become accessible and viable as a point-of-care test. Following the observation that hemorrhagic shock is associated with an intrinsic coagulopathy, TEG has been used as a method of diagnosing specific coagulation defects in order to direct individualized blood products resuscitation. An alternative transfusion strategy is the administration of fixed ratio products, a paradigm borne out of military experience. It is unknown which strategy is superior and this topic was debated at the 36th Annual Point/Counterpoint Acute Care Surgery Conference. The following article summarizes the discussants points of view along with a summary of the evidence. Level of evidence Level III. PMID:29766129

American Burn Association Practice Guidelines: Burn Shock Resuscitation

DTIC Science & Technology

2008-02-01

Ann Surg 1979;189: 546–52. 39. Jelenko C III, Williams JB, Wheeler ML, et al. Studies in shock and resuscitation, I: use of a hypertonic, albumin...SUMMARY ARTICLE American Burn Association Practice Guidelines Burn Shock Resuscitation Tam N. Pham, MD,* Leopoldo C . Cancio, MD,† Nicole S. Gibran...practice guidelines burn shock resuscitation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Pham T. N., Cancio L. C

Severe Postpartum Hemorrhage from Uterine Atony: A Multicentric Study

PubMed Central

Montufar-Rueda, Carlos; Rodriguez, Laritza; Jarquin, José Douglas; Barboza, Alejandra; Bustillo, Maura Carolina; Marin, Flor; Ortiz, Guillermo; Estrada, Francisco

2013-01-01

Objective. Postpartum hemorrhage (PPH) is an important cause of maternal mortality (MM) around the world. Seventy percent of the PPH corresponds to uterine atony. The objective of our study was to evaluate multicenter PPH cases during a 10-month period, and evaluate severe postpartum hemorrhage management. Study Design. The study population is a cohort of vaginal delivery and cesarean section patients with severe postpartum hemorrhage secondary to uterine atony. The study was designed as a descriptive, prospective, longitudinal, and multicenter study, during 10 months in 13 teaching hospitals. Results. Total live births during the study period were 124,019 with 218 patients (0.17%) with severe postpartum hemorrhage (SPHH). Total maternal deaths were 8, for mortality rate of 3.6% and a MM rate of 6.45/100,000 live births (LB). Maternal deaths were associated with inadequate transfusion therapy. Conclusions. In all patients with severe hemorrhage and subsequent hypovolemic shock, the most important therapy is intravascular volume resuscitation, to reduce the possibility of target organ damage and death. Similarly, the current proposals of transfusion therapy in severe or massive hemorrhage point to early transfusion of blood products and use of fresh frozen plasma, in addition to packed red blood cells, to prevent maternal deaths. PMID:24363935

The effect of permissive hypotension in combined traumatic brain injury and blunt abdominal trauma: an experimental study in swines.

PubMed

Vrettos, T; Poimenidi, E; Athanasopoulos, P; Balasis, S; Karagiorgos, N; Siklis, T; Gatzounis, G; Fligkou, F

2016-01-01

Optimal hemodynamic resuscitation strategy of the trauma patient with uncontrolled hemorrhage and severe head injury in the pre-hospital setting remains a special challenge. Permissive hypotension prior to definite surgical haemostasis promotes coagulation, decreases blood loss and favors survival. However, hypotension is associated with poor outcome in severe head injury. The purpose of this experimental animal study was to assess the impact of permissive hypotension on survival, hemodynamic profile and brain oxygenation parameters before and/or after definite surgical haemostasis. Six-week-old pigs (n=12) underwent general anesthesia and brain injury was produced by the fluid percussion model. Animals were instrumented to measure hemodynamic parameters and cerebral blood flow. All animals (n=12) were subjected to laparotomy and a surgical knot was placed through the abdominal aorta wall. Uncontrolled hemorrhage was simulated by pulling out the intentionally left protruding free ends of the suture (goal MAP=30 mmHg). Animals were randomly divided into two groups; group A (n=6) was subjected to aggressive fluid resuscitation (goal SAP >80 mmHg) and group B (n=6) was left hypotensive (permissive hypotension). Animals who survived one hour of hypotensive shock underwent definite surgical haemostasis and were resuscitated for one hour. We measured survival, hemodynamic and brain oxygenation parameters at different time points before and after surgical haemostasis. All animals from Group A and 50% from Group B died before surgical haemostasis. In surviving animals (Group B, 50%, p=0.033), MAP, CO, rCBF, SjO2 and AVDO2 were restored to pre-procedural levels. Permissive hypotension by delaying fluid resuscitation up to definite surgical haemostasis improves survival, hemodynamics and allows restoration of cerebral oxygenation in severe head injury.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

PubMed

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-12-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model

PubMed Central

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-01-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. PMID:26232641

Resuscitative Endovascular Balloon Occlusion of the Aorta: A Bridge to Flight Survival.

PubMed

Goforth, Carl; Bradley, Matthew; Pineda, Benilani; See, Suzanne; Pasley, Jason

2018-04-01

Trauma endures as the leading cause of death worldwide, and most deaths occur in the first 24 hours after initial injury as a result of hemorrhage. Historically, about 90% of battlefield deaths occur before the injured person arrives at a theater hospital, and most are due to noncompressible hemorrhage of the torso. Resuscitative endovascular balloon occlusion of the aorta is an evolving technique to quickly place a balloon into the thoracic or abdominal aorta to efficiently block blood flow to distal circulation. Maneuvers, such as resuscitative endovascular balloon occlusion of the aorta, to control endovascular hemorrhage offer a potential intervention to control noncompressible hemorrhage. This technique can be performed percutaneously or open in prehospital environments to restore hemodynamic functions and serve as a survival bridge until the patient is delivered to a treatment facility for definitive surgical hemostasis. This article describes the indications, complications, and application of resuscitative endovascular balloon occlusion of the aorta to military and civilian aeromedical transport. ©2018 American Association of Critical-Care Nurses.

Low-volume binary drug therapy for the treatment of hypovolemia.

PubMed

Bhattacharjee, Himanshu; Nadipuram, Asha; Kosanke, Stanley; Kiani, Mohammad F; Moore, Bob M

2011-06-01

The selective regulation of total peripheral circulation in hypovolemic crisis offers a unique approach for treating and preventing hemorrhagic shock. Ideally, such a therapeutic intervention would require targeting of the striated muscle vascular beds without altering the vascular resistance in vital organ vascular beds. We discovered that a combination of cannabinoid receptor agonist, THC (Δ-tetrahydrocannabinol), and cyclooxygenase 2 inhibitor, NS-398, caused selective microvascular constriction in the mouse cremaster muscle manifested by a pronounced and significant 27.4% ± 7.9% decrease in vessel diameter relative to control (P < 0.01). This observation, and the reported lack of microvascular response in the mesentery and brain, led us to hypothesize that the drug combination could favorably redistribute blood volume in hypovolemia and prolong survival. To test the hypothesis, male Sprague-Dawley rats were subjected to a pressure-controlled hemorrhage (mean arterial pressure reduced to 30 ± 13.73 mmHg) then randomly assigned to one of six treatment groups (n = 6 per group). The untreated, NS-398-treated, and THC-treated groups manifested an insignificant difference in survival between groups after shock. The group treated with a combination of THC and NS-398 manifested a significant increase in mean survival from 53 ± 12 to 227 ± 23 min after shock (P < 0.001). The drug combination significantly reduced IL-1α, IL-1β, IFN-γ, and IL-10 production compared with the group resuscitated with normal saline. In addition, histological evaluation indicated that the therapy protects the lungs and liver against hemorrhagic shock-induced damage. The combination of cannabinoid receptor agonist and cyclooxygenase 2 inhibitor represents a potentially new approach to low-volume therapeutic intervention for hypovolemia.

Mechanism of Salutary Effects of Astringinin on Rodent Hepatic Injury following Trauma-Hemorrhage: Akt-Dependent Hemeoxygenase-1 Signaling Pathways

PubMed Central

Liu, Fu-Chao; Hwang, Tsong-Long; Lau, Ying-Tung; Yu, Huang-Ping

2011-01-01

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35–40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation. PMID:22022464

Mechanism of salutary effects of astringinin on rodent hepatic injury following trauma-hemorrhage: Akt-dependent hemeoxygenase-1 signaling pathways.

PubMed

Liu, Fu-Chao; Hwang, Tsong-Long; Lau, Ying-Tung; Yu, Huang-Ping

2011-01-01

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35-40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation.

Association Between MC-2 Peptide and Hepatic Perfusion and Liver Injury Following Resuscitated Hemorrhagic Shock.

PubMed

Matheson, Paul J; Fernandez-Botran, Rafael; Smith, Jason W; Matheson, Samuel A; Downard, Cynthia D; McClain, Craig J; Garrison, Richard N

2016-03-01

Hemorrhagic shock (HS) due to trauma remains a major cause of morbidity and mortality in the United States, despite continuing progression of advanced life support and treatment. Trauma is the third most common cause of death worldwide and is the leading cause of death in the 1- to 44-year-old age group. Hemorrhagic shock often progresses to multiple organ failure despite conventional resuscitation (CR) that restores central hemodynamics. To examine whether MC-2 would bind glycosaminoglycans to decrease proinflammatory cytokines' influence in the liver, minimize organ edema, prevent liver injury, and improve hepatic perfusion. MC-2, a synthetic octapeptide derived from the heparin-binding domain of murine interferon gamma (IFN-γ), binds glycosaminoglycans to modulate serum and interstitial cytokine levels and activity. A controlled laboratory study of 3y male Sprague-Dawley rats that were randomized to 4 groups of 8 each: sham, sham+MC-2 (50 mg/kg), HS/CR, or HS/CR+MC-2 (HS = 40% of baseline mean arterial pressure for 60 minutes; CR = return of shed blood and 2 volumes of saline). The study began in March, 2013. Effective hepatic blood flow (EHBF) by galactose clearance, wet-dry weights, cytokines, histopathology, complete metabolic panel, and complete blood cell count were performed at 4 hours after CR. MC-2 partially reversed the HS/CR-induced hepatic hypoperfusion at 3 and 4 hours postresuscitation compared with HS/CR alone. Effective hepatic blood flow decreased during the HS period from a mean (SD) of 7.4 (0.3) mL/min/100 g and 7.5 (0.5) mL/min/100g at baseline to 3.7 (0.4) mL/min/100g and 5.9 (0.5) mL/min/100g for the HS/CR and HS/CR+MC-2 groups, respectively (P <.05). Effective hepatic blood flow remained constant in the sham groups throughout the experimental protocol. Organ edema was increased in the ileum and liver in the HS/CR vs sham group, and MC-2 decreased edema in the ileum vs the HS/CR group. MC-2 in HS also decreased levels of alanine aminotransferase, zonula occludens-1, and interleukin-1β compared with HS/CR alone. MC-2 was associated with decreased liver injury, enhanced effective hepatic blood flow, decreased cytokines, and prevention of edema formation in the ileum when administered with CR following HS. These data suggest that the MC-2 peptide could be a potential therapeutic approach to target cytokine and chemokine interactions, which might limit multiple organ failure and decrease mortality in hemorrhagic shock.

Resuscitative Endovascular Balloon Occlusion of the Aorta and Resuscitative Thoracotomy in Select Patients with Hemorrhagic Shock: Early Results from the American Association for the Surgery of Trauma's Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery Registry.

PubMed

Brenner, Megan; Inaba, Kenji; Aiolfi, Alberto; DuBose, Joseph; Fabian, Timothy; Bee, Tiffany; Holcomb, John B; Moore, Laura; Skarupa, David; Scalea, Thomas M

2018-05-01

Aortic occlusion is a potentially valuable tool for early resuscitation in patients nearing extremis or in arrest from severe hemorrhage. The American Association for the Surgery of Trauma's Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery registry identified trauma patients without penetrating thoracic injury undergoing aortic occlusion at the level of the descending thoracic aorta (resuscitative thoracotomy [RT] or zone 1 resuscitative endovascular balloon occlusion of the aorta [REBOA]) in the emergency department (ED). Survival outcomes relative to the timing of CPR need and admission hemodynamic status were examined. Two hundred and eighty-five patients were included: 81.8% were males, with injury due to penetrating mechanisms in 41.4%; median age was 35.0 years (interquartile range 29 years) and median Injury Severity Score was 34.0 (interquartile range 18). Resuscitative thoracotomy was used in 71%, and zone 1 REBOA in 29%. Overall survival beyond the ED was 50% (RT 44%, REBOA 63%; p = 0.004) and survival to discharge was 5% (RT 2.5%, REBOA 9.6%; p = 0.023). Discharge Glasgow Coma Scale score was 15 in 85% of survivors. Prehospital CPR was required in 60% of patients with a survival beyond the ED of 37% and survival to discharge of 3% (all p > 0.05). Patients who did not require any CPR before had a survival beyond the ED of 70% (RT 48%, REBOA 93%; p < 0.001) and survival to discharge of 13% (RT 3.4%, REBOA 22.2%, p = 0.048). If aortic occlusion patients did not require CPR but presented with hypotension (systolic blood pressure <90 mmHg; 9% [65% RT; 35% REBOA]), they achieved survival beyond the ED in 65% (p = 0.009) and survival to discharge of 15% (RT 0%, REBOA 44%; p = 0.008). Overall, REBOA can confer a survival benefit over RT, particularly in patients not requiring CPR. Considerable additional study is required to definitively recommend REBOA for specific subsets of injured patients. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

The US Department of Defense Hemorrhage and Resuscitation Research and Development Program

DTIC Science & Technology

2015-08-01

blood, de- vices for intracavitary bleeding, and new information on how best to use products such as tranexamic acid and plasma in the prehospital...Given MB, et al.: US DoD Hemorrhage and Resuscitation Research and Development Steering Committee: Tranexamic acid and trauma: current status and

COMBAT: Initial experience with a randomized clinical trial of plasma-based resuscitation in the field for traumatic hemorrhagic shock

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Chin, Theresa L; Ghasabyan, Arsen; Chandler, James; Stringham, John; Gonzalez, Eduardo; Moore, Hunter B.; Banerjee, Anirban; Silliman, Christopher C; Sauaia, Angela

2015-01-01

The existing evidence shows great promise for plasma as the first resuscitation fluid in both civilian and military trauma. We embarked on the Control of Major Bleeding After Trauma (COMBAT) trial with the support of the Department of Defense, in order to determine if plasma-first resuscitation yields hemostatic and survival benefits. The methodology of the COMBAT study represents not only three years of development work, but the integration of nearly two-decades of technical experience with the design and implementation of other clinical trials and studies. Herein, we describe the key features of the study design, critical personnel and infrastructural elements, and key innovations. We will also briefly outline the systems engineering challenges entailed by this study. COMBAT is a randomized, placebo controlled, semi-blinded prospective Phase IIB clinical trial, conducted in a ground ambulance fleet based at a Level I trauma center, and part of a multicenter collaboration. The primary objective of COMBAT is to determine the efficacy of field resuscitation with plasma first, compared to standard of care (normal saline). To date we have enrolled 30 subjects in the COMBAT study. The ability to achieve intervention with a hemostatic resuscitation agent in the closest possible temporal proximity to injury is critical and represents an opportunity to forestall the evolution of the “bloody vicious cycle”. Thus, the COMBAT model for deploying plasma in first response units should serve as a model for RCTs of other hemostatic resuscitative agents. PMID:25784527

IDENTIFICATION AND DESCRIPTION OF A NOVEL MURINE MODEL FOR POLYTRAUMA AND SHOCK

PubMed Central

Gentile, Lori F; Nacionales, Dina C; Cuenca, Alex G; Armbruster, Michael; Ungaro, Ricardo F; Abouhamze, Amer S; Lopez, Cecelia; Baker, Henry V; Moore, Frederick A; Ang, Darwin N; Efron, Philip A

2013-01-01

Objective To develop a novel polytrauma model that better recapitulates the immunological response of the severely injured patient by combining long-bone fracture, muscle tissue damage and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically-used murine trauma-hemorrhage models. Design Pre-clinical controlled in vivo laboratory study. Setting Laboratory of Inflammation Biology and Surgical Science. Subjects 6–10 wk old C57BL/6 (B6) mice Interventions Mice underwent 90 minutes of shock (MAP 30 mmHg) and resuscitation via femoral artery cannulation followed by either laparotomy (TH), laparotomy with femur fracture (H+FFx), or laparotomy with cecetomy and femur fracture with muscle tissue damage (PT). Mice were euthanized at two hours, one day and three days post injury. Measurements and Main Results The spleen, bone marrow, blood, and serum were collected from mice for analysis at the above time points. None of the models were lethal. Mice undergoing PT exhibited a more robust inflammatory response with significant elevations in cytokine/chemokine concentrations when compared to traditional models. PT was the only model to induce neutrophilia (Ly6G+CD11b+ cells) on days 1 and 3 (p<0.05). PT, as compared to TH and H+FFx, induced a loss of circulating CD4+ T cell with simultaneous increased cell activation (CD69+ and CD25+), similar to human trauma. There was a prolonged loss of MHCII expression on monocytes in the PT model (p<0.05). Results were confirmed by genome-wide expression analysis which revealed a greater magnitude and duration of blood leukocyte gene expression changes in the PT model than the TH and sham models. Conclusions This novel polytrauma model better replicates the human leukocyte, cytokine, and overall inflammatory response following injury and hemorrhagic shock. PMID:23399937

Re: Coagulation and Fluid Resuscitation by HyperHES in Severe Hemorrhage

DTIC Science & Technology

2013-08-01

aid kit, and we cannot envisage to load them with so much weight. In the context of trauma combat casualty care, fluid resuscitation byHyperHES...coagulation following femur injury and severe hemorrhage in pigs. J Trauma Acute Care Surg. 2013; 74(3):732Y740. 2. Dubick MA, Atkins JL. Small-volume...fluid resuscitation for the far-forward combat envi- ronment: current concepts. J Trauma . 2003;54: S43YS45. 3. Sharma P, Benford B, Karaian JE

[Crisis management during obstetric surgery].

PubMed

Okutomi, Toshiyuki

2009-05-01

Obstetric crisis includes hemorrhagic shock, embolisms and difficult airway. Life will be rapidly threatened with disseminated intravascular coagulation, multiple organ failure or systemic inflammatory response syndrome in these crises. In the face of the crisis, repeated evaluation of parturients and differential diagnosis are necessary along with fetal heart monitoring. For evaluation of bleeding, one should notice that the visual estimation of vaginal bleeding does not reflect the extent of intravascular volume deficit. Treatments for hemorrhagic shock include fluid replacement, blood transfusion as well as fresh frozen plasma, platelet, anticoagulants, anti-thrombin III, and protease inhibitors. When bleeding is still uncontrollable, arterial embolization or hysterectomy will be considered. Embolic disorders are another cause of maternal mortality. The signs and symptoms are all similar (dyspnea, cyanosis and sudden cardiovascular collapse). Strategies against the embolism will be basically symptomatic therapy. The physiological change with pregnancy results in the need of careful pre-anesthetic airway evaluation for parturients. A difficult or failed intubation drill is also extremely important. Recently, laryngeal mask airway has been successfully used in these parturients. During resuscitation of a pregnant woman, left uterine displacement is essential. For a patient who has not responded after 4 to 5 minutes of ACLS, immediate cesarean delivery should be considered.

Incremental balloon deflation following complete resuscitative endovascular balloon occlusion of the aorta results in steep inflection of flow and rapid reperfusion in a large animal model of hemorrhagic shock.

PubMed

Davidson, Anders J; Russo, Rachel M; Ferencz, Sarah-Ashley E; Cannon, Jeremy W; Rasmussen, Todd E; Neff, Lucas P; Johnson, M Austin; Williams, Timothy K

2017-07-01

To avoid potential cardiovascular collapse after resuscitative endovascular balloon occlusion of the aorta (REBOA), current guidelines recommend methodically deflating the balloon for 5 minutes to gradually reperfuse distal tissue beds. However, anecdotal evidence suggests that this approach may still result in unpredictable aortic flow rates and hemodynamic instability. We sought to characterize aortic flow dynamics following REBOA as the balloon is deflated in accordance with current practice guidelines. Eight Yorkshire-cross swine were splenectomized, instrumented, and subjected to rapid 25% total blood volume hemorrhage. After 30 minutes of shock, animals received 60 minutes of Zone 1 REBOA with a low-profile REBOA catheter. During subsequent resuscitation with shed blood, the aortic occlusion balloon was gradually deflated in stepwise fashion at the rate of 0.5 mL every 30 seconds until completely deflated. Aortic flow rate and proximal mean arterial pressure (MAP) were measured continuously over the period of balloon deflation. Graded balloon deflation resulted in variable initial return of aortic flow (median, 78 seconds; interquartile range [IQR], 68-105 seconds). A rapid increase in aortic flow during a single-balloon deflation step was observed in all animals (median, 819 mL/min; IQR, 664-1241 mL/min) and corresponded with an immediate decrease in proximal MAP (median, 30 mm Hg; IQR, 14.5-37 mm Hg). Total balloon volume and time to return of flow demonstrated no correlation (r = 0.016). This study is the first to characterize aortic flow during balloon deflation following REBOA. A steep inflection point occurs during balloon deflation that results in an abrupt increase in aortic flow and a concomitant decrease in MAP. Furthermore, the onset of distal aortic flow was inconsistent across study animals and did not correlate with initial balloon volume or relative deflation volume. Future studies to define the factors that affect aortic flow during balloon deflation are needed to facilitate controlled reperfusion following REBOA.

Lingual, splanchnic, and systemic hemodynamic and carbon dioxide tension changes during endotoxic shock and resuscitation.

PubMed

Guzman, Jorge A; Dikin, Mathew S; Kruse, James A

2005-01-01

Sublingual and intestinal mucosal blood flow and Pco(2) were studied in a canine model of endotoxin-induced circulatory shock and resuscitation. Sublingual Pco(2) (Ps(CO(2))) was measured by using a novel fluorescent optrode-based technique and compared with lingual measurements obtained by using a Stowe-Severinghaus electrode [lingual Pco(2) (Pl(CO(2)))]. Endotoxin caused parallel changes in cardiac output, and in portal, intestinal mucosal, and sublingual blood flow (Q(s)). Different blood flow patterns were observed during resuscitation: intestinal mucosal blood flow returned to near baseline levels postfluid resuscitation and decreased by 21% after vasopressor resuscitation, whereas Q(s) rose to twice that of the preshock level and was maintained throughout the resuscitation period. Electrochemical and fluorescent Pco(2) measurements showed similar changes throughout the experiments. The shock-induced increases in Ps(CO(2)) and Pl(CO(2)) were nearly reversed after fluid resuscitation, despite persistent systemic arterial hypotension. Vasopressor administration induced a rebound of Ps(CO(2)) and Pl(CO(2)) to shock levels, despite higher cardiac output and Q(s), possibly due to blood flow redistribution and shunting. Changes in Pl(CO(2)) and Ps(CO(2)) paralleled gastric and intestinal Pco(2) changes during shock but not during resuscitation. We found that the lingual, splanchnic, and systemic circulations follow a similar pattern of blood flow variations in response to endotoxin shock, although discrepancies were observed during resuscitation. Restoration of systemic, splanchnic, and lingual perfusion can be accompanied by persistent tissue hypercarbia, mainly lingual and intestinal, more so when a vasopressor agent is used to normalize systemic hemodynamic variables.

The clinical effectiveness of permissive hypotension in blunt abdominal trauma with hemorrhagic shock but without head or spine injuries or burns: a systematic review

PubMed Central

Alsawadi, Abdulrahman

2012-01-01

Background Trauma is a major cause of death and disability. The current trend in trauma management is the rapid administration of fluid as per the Advanced Trauma Life Support guidelines, although there is no evidence to support this and even some to suggest it might be harmful. Some guidelines, protocols, and recommendations have been established for the use of permissive hypotension although there is reluctance concerning its application in blunt injuries. Objectives The aim of this review is to determine whether there is evidence of the use of permissive hypotension in the management of hemorrhagic shock in blunt trauma patients. This review also aims to search for any reason for the reluctance to apply permissive hypotension in blunt injuries. Methods This systematic review has followed the steps recommended in the Cochrane Handbook for Systematic Reviews of Interventions. It is also being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement and checklist. Database searches of MEDLINE, EMBASE, the Centre for Reviews and Dissemination databases and the Cochrane Library were made for eligible studies as well as journal searches. Inclusion criteria included systematic reviews that have similar primary questions to this review and randomized controlled trials where patients with blunt torso injuries and hemorrhagic shock were not excluded. Rapid or early fluid administration was compared with controlled or delayed fluid resuscitation and a significant outcome was obtained. Results No systematic reviews attempting to answer similar questions were found. Two randomized controlled trials with mixed types of injuries in the included patients found no significant difference between the groups used in each study. Data concerning the question of this review was sought after these papers were appraised. Conclusion The limited available data are not conclusive. However, the supportive theoretical concept and laboratory evidence do not show any reason for treating blunt injuries differently from other traumatic injuries. Moreover, permissive hypotension is being used for some nontraumatic causes of hemorrhagic shock and in theater. Therefore, this should encourage interested researchers to continue clinical work in this important field. PMID:27147860

Salvage techniques in traumatic cardiac arrest: thoracotomy, extracorporeal life support, and therapeutic hypothermia.

PubMed

Tisherman, Samuel A

2013-12-01

Survival from traumatic cardiac arrest is associated with a very high mortality despite aggressive resuscitation including an Emergency Department thoracotomy (EDT). Novel salvage techniques are needed to improve these outcomes. More aggressive out-of-hospital interventions, such as chest decompression or thoracotomy by emergency physicians or anesthesiologists, seem feasible and show some promise for improving outcomes. For trauma patients who suffer severe respiratory failure or refractory cardiac arrest, there seems to be an increasing role for the use of extracorporeal life support (ECLS), utilizing heparin-bonded systems to avoid systemic anticoagulation. The development of exposure hypothermia is associated with poor outcomes in trauma patients, but preclinical studies have consistently demonstrated that mild, therapeutic hypothermia (34 °C) improves survival from severe hemorrhagic shock. Sufficient data exist to justify a clinical trial. For patients who suffer a cardiac arrest refractory to EDT, induction of emergency preservation and resuscitation by rapid cooling to a tympanic membrane temperature of 10 °C may preserve vital organs long enough to allow surgical hemostasis, followed by resuscitation with cardiopulmonary bypass. Salvage techniques, such as earlier thoracotomy, ECLS, and hypothermia, may allow survival from otherwise lethal injuries.

An update on the use of massive transfusion protocols in obstetrics.

PubMed

Pacheco, Luis D; Saade, George R; Costantine, Maged M; Clark, Steven L; Hankins, Gary D V

2016-03-01

Obstetrical hemorrhage remains a leading cause of maternal mortality worldwide. New concepts involving the pathophysiology of hemorrhage have been described and include early activation of both the protein C and fibrinolytic pathways. New strategies in hemorrhage treatment include the use of hemostatic resuscitation, although the optimal ratio to administer the various blood products is still unknown. Massive transfusion protocols involve the early utilization of blood products and limit the traditional approach of early massive crystalloid-based resuscitation. The evidence behind hemostatic resuscitation has changed in the last few years, and debate is ongoing regarding optimal transfusion strategies. The use of tranexamic acid, fibrinogen concentrates, and prothrombin complex concentrates has emerged as new potential alternative treatment strategies with improved safety profiles. Copyright © 2016 Elsevier Inc. All rights reserved.

Preferential effects of low volume versus high volume replacement with crystalloid fluid in a hemorrhagic shock model in pigs.

PubMed

Ponschab, Martin; Schöchl, Herbert; Keibl, Claudia; Fischer, Henrik; Redl, Heinz; Schlimp, Christoph J

2015-10-06

Fluid resuscitation is a core stone of hemorrhagic shock therapy, and crystalloid fluids seem to be associated with lower mortality compared to colloids. However, as redistribution starts within minutes, it has been suggested to replace blood loss with a minimum of a three-fold amount of crystalloids. The hypothesis was that in comparison to high volume (HV), a lower crystalloid volume (LV) achieves a favorable coagulation profile and exerts sufficient haemodynamics in the acute phase of resuscitation. In 24 anaesthetized pigs, controlled arterial blood loss of 50 % of the estimated blood volume was either (n = 12) replaced with a LV (one-fold) or a HV (three-fold) volume of a balanced, acetated crystalloid solution at room temperature. Hemodynamic parameters, dilution effects and coagulation profile by standard coagulation tests and thromboelastometry at baseline and after resuscitation were determined in both groups. LV resuscitation increased MAP significantly less compared to the HV, 61 ± 7 vs. 82 ± 14 mmHg (p < 0.001) respectively, with no difference between lactate and base excess between groups. Haematocrit after fluid replacement was 0.20 vs. 0.16 (LV vs. HV, p < 0.001), suggesting a grade of blood dilution of 32 vs. 42 % (p < 0.001) compared to baseline values. Compared to LV, HV resulted in decreased core temperature (37.5 ± 0.2 vs. 36.0 ± 0.6 °C, p < 0.001), lower platelet count (318 ± 77 vs. 231 ± 53 K/μL, p < 0.01) and lower plasma fibrinogen levels (205 ± 19 vs. 168 ± 24 mg/dL, p < 0.001). Thromboelastometric measurements showed a significant impairment on viscoelastic clot properties following HV group. While prothrombin time index decreased significantly more in the HV group, activated partial thromboplastin time did not differ between both groups. HV did not result in hyperchloraemic acidosis. Coagulation parameters represented by plasma fibrinogen and ROTEM parameters were also less impaired with LV. With regrad to hematocrit, 60 % of LV remained intracascular , while in HV only 30 % remained in circulation within the first hour of administration. In the acute setting of 50 % controlled blood loss, a one fold LV crystalloid replacement strategy is sufficient to adequately raise blood pressure up to a mean arterial pressure >50 mm Hg. The concept of damage control resuscitation (DCR) with permissive hypotension may be better met by using LV as compared to a three fold HV resuscitation strategy. High volume administration of an acetated balanced crystalloid does not lead to hyperchloraemic acidosis, but may negatively influence clinical parameters, such as higher blood pressure, lower body temperature and impaired coagulation parameters, which could potentially increase bleeding after trauma. Replacement of acute blood loss with just an equal amount of an acetated balanced crystalloid appears to be the preferential treatment strategy in the acute phase after controlled bleeding.

[Role of mesenteric lymph drainage improving the metabolism of red blood cell in hemorrhagic shock rats following fluid resuscitation].

PubMed

Han, Rui; Du, Hui-bo; Lu, Bei; Si, Yong-hua; Zhang, Li-min; Zhang, Yu-pin; Zhao, Zi-gang; Niu, Chun-yu

2012-08-01

To observe the effects of mesenteric lymph drainage on the metabolism of red blood cell (RBC) in hemorrhagic shock (HS) rats following fluid resuscitation. Eighteen male Wistar rats were randomly divided into sham group (n=6), HS group (n=6), HS + drainage group (n=6). After 1.5 hours of HS model prepared, the animals were given fluid resuscitation by lost blood plus equal volume of Ringer solution within 30 minutes in HS and HS + drainage groups, and mesenteric lymph drainage was performed after 1 hour of hypotension in HS + drainage group. At 3 hours after resuscitation or corresponding time, blood samples were obtained from abdominal aorta. Membrane suspensions of RBC prepared from part of whole blood samples were used to measure the activities of adenosine triphosphate ase (ATPase) and contents of ATP and lactic acid (LA), the intracellular fluid of RBC prepared from part of whole blood samples was used to determine the concentration of 2,3-diphosphoglyceric acid (2,3-DPG), Na(+) and K(+), plasma samples isolated from blood by centrifugation were used to determine the concentration of Na(+), K(+), Cl(-) and total Ca. Compared with sham group, the content of ATP (μmol/g), activity of Na(+)-K(+)-ATPase (μmol×mg(-1)×h(-1)) and Ca(2+)-ATPase (μmol×mg(-1)×h(-1)) in RBC membrane and total Ca (mmol/L) in plasma were decreased markedly (ATP: 6.698±0.938 vs. 10.670±1.466, Na(+)-K(+)-ATPase: 0.042±0.010 vs. 0.066±0.019, Ca(2+)-ATPase: 0.054±0.015 vs. 0.081±0.017, total Ca: 2.27±0.18 vs. 2.66±0.21, P<0.05 or P<0.01) in HS group, and the content of LA (mmol/g) in RBC and K(+) (mmol/L), Cl(-) (mmol/L) in plasma were increased observably in HS group (LA: 3.472±0.853 vs. 1.743±0.395, K(+): 5.83±0.34 vs. 5.23±0.37, Cl(-): 113.37±3.63 vs. 106.35±4.99, P<0.05 or P<0.01), there was no significant difference in term of the contents of 2,3-DPG (mmol/L: 2.196±0.609 vs. 2.590±0.574, P>0.05). Compared with HS group, the contents of 2,3-DPG (4.459±0.900) and ATP (8.859±1.189), the activities of Na(+)-K(+)-ATPase (0.089±0.022), Ca(2+)-ATPase (0.082±0.020) of RBC were increased in HS + drainage group, and the level of LA (2.060±0.810) was decreased observably (P<0.05 or P<0.01), there were no significant differences in the other indices. The results indicate that shock mesenteric lymph drainage plays an important role in improving the metabolism of RBC in HS rats following fluid resuscitation, subsequently, may preserve the structure and function of RBC.

Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.

PubMed

Jha, Ruchira M; Molyneaux, Bradley J; Jackson, Travis C; Wallisch, Jessica S; Park, Seo-Young; Poloyac, Samuel; Vagni, Vincent A; Janesko-Feldman, Keri L; Hoshitsuki, Keito; Minnigh, M Beth; Kochanek, Patrick M

2018-06-06

Cerebral edema is critical to morbidity/mortality in traumatic brain injury (TBI) and is worsened by hypotension. Glibenclamide may reduce cerebral edema by inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse cerebral edema exacerbated by hypotension/resuscitation is unknown. We aimed to determine if glibenclamide improves pericontusional and/or diffuse edema in controlled cortical impact (CCI) (5m/sec, 1 mm depth) plus hemorrhagic shock (HS) (35 min), and compare its effects in CCI alone. C57BL/6 mice were divided into five groups (n = 10/group): naïve, CCI+vehicle, CCI+glibenclamide, CCI+HS+vehicle, and CCI+HS+glibenclamide. Intravenous glibenclamide (10 min post-injury) was followed by a subcutaneous infusion for 24 h. Brain edema in injured and contralateral hemispheres was subsequently quantified (wet-dry weight). This protocol brain water (BW) = 80.4% vehicle vs. 78.3% naïve, p < 0.01) but was not reduced by glibenclamide (I%BW = 80.4%). Ipsilateral edema also developed in CCI alone (I%BW = 80.2% vehicle vs. 78.3% naïve, p < 0.01); again unaffected by glibenclamide (I%BW = 80.5%). Contralateral (C) %BW in CCI+HS was increased in vehicle (78.6%) versus naive (78.3%, p = 0.02) but unchanged in CCI (78.3%). At 24 h, glibenclamide treatment in CCI+HS eliminated contralateral cerebral edema (C%BW = 78.3%) with no difference versus naïve. By 72 h, contralateral cerebral edema had resolved (C%BW = 78.5 ± 0.09% vehicle vs. 78.3 ± 0.05% naïve). Glibenclamide decreased 24 h contralateral cerebral edema in CCI+HS. This beneficial effect merits additional exploration in the important setting of TBI with polytrauma, shock, and resuscitation. Contralateral edema did not develop in CCI alone. Surprisingly, 24 h of glibenclamide treatment failed to decrease ipsilateral edema in either model. Interspecies dosing differences versus prior studies may play an important role in these findings. Mechanisms underlying brain edema may differ regionally, with pericontusional/osmolar swelling refractory to glibenclamide but diffuse edema (via Sur1) from combined injury and/or resuscitation responsive to this therapy. TBI phenotype may mandate precision medicine approaches to treat brain edema.

Effects of the Kv7 voltage-activated potassium channel inhibitor linopirdine in rat models of haemorrhagic shock.

PubMed

Nassoiy, Sean P; Babu, Favin S; LaPorte, Heather M; Byron, Kenneth L; Majetschak, Matthias

2018-04-27

Recently, we demonstrated that Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements in short-term rat models of haemorrhagic shock. The aim of the present study was to further delineate the therapeutic potential and side effect profile of the Kv7 channel blocker linopirdine in various rat models of severe haemorrhagic shock over clinically relevant time periods. Intravenous administration of linopirdine, either before (1 or 3 mg/kg) or after (3 mg/kg) a 40% blood volume haemorrhage, did not affect blood pressure and survival in lethal haemorrhage models without fluid resuscitation. A single bolus of linopirdine (3 mg/kg) at the beginning of fluid resuscitation after haemorrhagic shock transiently reduced early fluid requirements in spontaneously breathing animals that were resuscitated for 3.5 hours. When mechanically ventilated rats were resuscitated after haemorrhagic shock with normal saline (NS) or with linopirdine-supplemented (10, 25 or 50 μg/mL) NS for 4.5 hours, linopirdine significantly and dose-dependently reduced fluid requirements by 14%, 45% and 55%, respectively. Lung and colon wet/dry weight ratios were reduced with linopirdine (25/50 μg/mL). There was no evidence for toxicity or adverse effects based on measurements of routine laboratory parameters and inflammation markers in plasma and tissue homogenates. Our findings support the concept that linopirdine-supplementation of resuscitation fluids is a safe and effective approach to reduce fluid requirements and tissue oedema formation during resuscitation from haemorrhagic shock. © 2018 John Wiley & Sons Australia, Ltd.

Direct vascular control results in less physiologic derangement than proximal aortic clamping in a porcine model of noncompressible extrathoracic torso hemorrhage.

PubMed

White, Joseph M; Cannon, Jeremy W; Stannard, Adam; Burkhardt, Gabriel E; Spencer, Jerry R; Williams, Ken; Oh, John S; Rasmussen, Todd E

2011-11-01

The optimal method of vascular control and resuscitation in patients with life-threatening, extrathoracic torso hemorrhage remains debated. Guidelines recommend emergency department thoracotomy (EDT) with aortic clamping, although transabdominal aortic clamping followed by vascular control and direct vascular control (DVC) without aortic clamping are alternatives. The objective of this study is to compare the effectiveness of three approaches to extrathoracic torso hemorrhage in a large animal model. Adolescent swine (Sus Scrofa) (mean weight = 80.9 kg) were randomized into three groups all of which had class IV shock established by hemorrhage from an iliac artery injury. Group 1: EDT with thoracic aortic clamping (N = 6); group 2: transabdominal supraceliac aortic clamping (SCC; N = 6); and group 3: DVC of bleeding site without aortic clamping (N = 6). After hemorrhage, EDT or SCC was performed in groups 1 and 2, respectively, with subsequent exploration of the bleeding site and placement of a temporary vascular shunt (TVS). Group 3 (DVC) underwent direct exploration of the injury and placement of a TVS. All groups were resuscitated to predefined physiologic endpoints over 6 hours with repeated measures of central and cerebral perfusion and end-organ function at standardized time points. Postmortem tissue analysis was performed to quantify injury to critical tissue beds. There was no difference in mortality among the groups and no TVS failures. Central aortic pressure, carotid flow, and partial pressure brain tissue oximetry, all demonstrated increases in EDT and SCC after application of the aortic clamp relative to DVC (p < 0.05). During resuscitation, serum lactate levels were higher in EDT compared with SCC and DVC (6.85 vs. 3.08 and 2.15, respectively; p < 0.05) and serum pH in EDT reflected greater acidosis than SCC and DVC (7.24 vs. 7.36 and 7.39, respectively; p < 0.05). EDT and SCC required more intravenous fluid than DVC (2,166 mL and 2,166 mL vs. 667 mL, respectively; p < 0.05) and more vasopressors were used in EDT and SCC compared with DVC (52.1 μg and 43.5 μg vs. 12.4 μg, respectively; p < 0.05). Brain and myocardial tissue stains demonstrated the same degree of acute ischemic changes in all groups. Although aortic clamping increases central and cerebral perfusion, DVC results in less physiologic derangement. The optimal method of aortic control would incorporate the benefits of maintained central pressure with less associated morbidity. Clinical studies evaluating DVC are warranted.

Early identification of patients requiring massive transfusion, embolization, or hemostatic surgery for traumatic hemorrhage: a systematic review protocol.

PubMed

Tran, Alexandre; Matar, Maher; Steyerberg, Ewout W; Lampron, Jacinthe; Taljaard, Monica; Vaillancourt, Christian

2017-04-13

Hemorrhage is a major cause of early mortality following a traumatic injury. The progression and consequences of significant blood loss occur quickly as death from hemorrhagic shock or exsanguination often occurs within the first few hours. The mainstay of treatment therefore involves early identification of patients at risk for hemorrhagic shock in order to provide blood products and control of the bleeding source if necessary. The intended scope of this review is to identify and assess combinations of predictors informing therapeutic decision-making for clinicians during the initial trauma assessment. The primary objective of this systematic review is to identify and critically assess any existing multivariable models predicting significant traumatic hemorrhage that requires intervention, defined as a composite outcome comprising massive transfusion, surgery for hemostasis, or angiography with embolization for the purpose of external validation or updating in other study populations. If no suitable existing multivariable models are identified, the secondary objective is to identify candidate predictors to inform the development of a new prediction rule. We will search the EMBASE and MEDLINE databases for all randomized controlled trials and prospective and retrospective cohort studies developing or validating predictors of intervention for traumatic hemorrhage in adult patients 16 years of age or older. Eligible predictors must be available to the clinician during the first hour of trauma resuscitation and may be clinical, lab-based, or imaging-based. Outcomes of interest include the need for surgical intervention, angiographic embolization, or massive transfusion within the first 24 h. Data extraction will be performed independently by two reviewers. Items for extraction will be based on the CHARMS checklist. We will evaluate any existing models for relevance, quality, and the potential for external validation and updating in other populations. Relevance will be described in terms of appropriateness of outcomes and predictors. Quality criteria will include variable selection strategies, adequacy of sample size, handling of missing data, validation techniques, and measures of model performance. This systematic review will describe the availability of multivariable prediction models and summarize evidence regarding predictors that can be used to identify the need for intervention in patients with traumatic hemorrhage. PROSPERO CRD42017054589.

Combat Casualties Undergoing Lifesaving Interventions Have Decreased Heart Rate Complexity at Multiple Time Scales

DTIC Science & Technology

2013-01-01

almost half of the cases, related to delays in hemorrhage control during transportation or in resuscitation efforts. Earlier detection of hemorrhagic...restored to normal values with fluid resuscitation [311. On further analysis, we found that SampEn retained its ability to discriminate survivors from...information about HR dynamics in the neonatal ICU setting. They have developed a real time index, termed HR characteristics, which takes into

[Assistenza cardiocircolatoria. (Cardio-circulatory care)].

PubMed

Cogo, P E

2010-06-01

Mortality in pediatric cardiovascular failure is markedly improved with the advent of neonatal and pediatric intensive care and with the implementation of treatment guidelines. In 2002 the American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Shock reported mortality rates of 0%-5% in previously healthy and 10% in chronically ill children with septic shock associated with implementation of "best clinical practices". Early recognition of shock is the key to successful resuscitation in critically ill children. Often, shock results in or co-exists with myo-cardial dysfunction or acute lung injury. Recognition and appropriate management of these insults is crucial for successful outcomes. Resuscitation should be directed to restoration of tissue perfusion and normalization of cardiac and respiratory function. The underlying cause of shock should also be addressed urgently. The physiological response of individual children to shock resuscitation varies and is often unpredictable. Therefore, repeated assessments of vital parameters are needed for taking appropriate decisions. Global indices of tissue oxygen delivery help in targeting therapies more accurately. Isotonic fluids form the cornerstone of treatment and the amount required for resuscitation is based on etiologies and therapeutic response. After resuscitation has been initiated, targeted history and clinical evaluation must be performed to ascertain the cause of shock and management of co-morbidities should be implemented simultaneously. While the management of shock can be protocol based, the treatment needs to be individualized depending on the suspected etiology and therapeutic response particularly for children who suffer from congenital heart disease.

The impact of post-resuscitation feedback for paramedics on the quality of cardiopulmonary resuscitation.

PubMed

Bleijenberg, Eduard; Koster, Rudolph W; de Vries, Hendrik; Beesems, Stefanie G

2017-01-01

The Guidelines place emphasis on high-quality cardiopulmonary resuscitation (CPR). This study aims to measure the impact of post-resuscitation feedback on the quality of CPR as performed by ambulance personnel. Two ambulances are dispatched for suspected cardiac arrest. The crew (driver and paramedic) of the first arriving ambulance is responsible for the quality of CPR. The crew of the second ambulance establishes an intravenous access and supports the first crew. All resuscitation attempts led by the ambulance crew of the study region were reviewed by two research paramedics and structured feedback was given based on defibrillator recording with impedance signal. A 12-months period before introduction of post-resuscitation feedback was compared with a 19-months period after introduction of feedback, excluding a six months run-in interval. Quality parameters were chest compression fraction (CCF), chest compression rate, longest peri-shock pause and longest non-shock pause. In the pre-feedback period 55 cases were analyzed and 69 cases in the feedback period. Median CCF improved significantly in the feedback period (79% vs 86%, p<0.001). The mean chest compression rate was within the recommended range of 100-120/min in 87% of the cases in the pre-feedback period and in 90% of the cases in the feedback period (p=0.65). The duration of longest non-shock pause decreased significantly (40s vs 19s, p<0.001), the duration of the longest peri-shock pause did not change significantly (16s vs 13s, p=0.27). Post-resuscitation feedback improves the quality of resuscitation, significantly increasing CCF and decreasing the duration of longest non-shock pauses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fluid therapy for septic shock resuscitation: which fluid should be used?

PubMed

Corrêa, Thiago Domingos; Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Silva, Eliézer; de Assuncao, Murillo Santucci Cesar

2015-01-01

Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients.

[Damage control resuscitation of severe multiple trauma in the pelvic fractures].

PubMed

Fu, Chang-guo

2015-05-01

To discuss the clinical effects of damage control resuscitation (DCR) in treating severe multiple trauma in the pelvic fractures. From March 2009 to September 2013, a restrospective analysis was conducted on the clinical data of 28 patients with multiple trauma in the pelvic fractures, including 19 males and 9 females, ranging in age from 21 to 51 years old with an average of 32.5 years old. According to Tile classification of pelvic fractures, 16 cases were type B and 12 cases were type C. Injury severity score (ISS) averaged 32.0±3.4. All cases were treated with damage contral orthopaedics and DCR strategy, namely that used immediately with small capacity of balanced salt solution on admission so as to maintain the blood pressure between 80 to 90 mmHg. At the same time, emergency phase I simple debridement plus external fixator or bundled with fixed pelvic was done, and the chest or abdomen combined injury was treated at first. And limbs fracture was temporary dealing with bone traction or plaster external fixation, etc. After bleeding was controlled by operation, fluid resuscitation was done as fast as possible and the plasma was transfused early according to the proportion of plasma and red cell suspension (2 U:1 U-3 U:2 U). Dosage of balanced salt solution and blood before remedy shock was recorded, and the removal of time of lactic acid and coagulation were observed. Five cases were died after 4 to 15 hours into hospital (3 cases died for severe trauma-hemorrhagic shock and 2 cases for acute respiratory distress syndrome). Twenty-three cases were remedy shock at 1.6 to 4.3 hours after injury with an average of 2.4 hours. Period I operation duration was (78.2±10.3) minutes. Dosage of balanced salt solution was (3,798±340) ml and red cell suspension was 14 to 18 U, fresh frozen plasma (FFP) was (1,267±58) ml (1U FFP=100 ml), blood platelet was 8 to 12 U for 9 patients. The removal time of lactic acid and PT-APTT was (11.4±2.1) hours and (4.3±0.8) hours. Measures were taken to correct electrolyte and acid-base imbalance was normal. The success rat of recovery was 82.2% (23/28). Damage control resuscitation (DCR) integrates the main links such as damage control operation and allowable low blood pressure (or limited liquid resuscitation) and hemostatic control resuscitation, was early effective treatment measures for the patients with severe multiple trauma in the pelvic fractures.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

PubMed

Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph

2017-03-10

To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

Pharmacological targeting of chemokine (C-X-C motif) receptor 4 in porcine polytrauma and hemorrhage models

PubMed Central

Bach, Harold H.; Wong, Yee M.; LaPorte, Heather M.; Gamelli, Richard L.; Majetschak, Matthias

2016-01-01

BACKGROUND Recent evidence suggests that chemokine receptor CXCR4 regulates vascular α1-adrenergic receptor function and that the noncognate CXCR4 agonist ubiquitin has therapeutic potential after trauma/hemorrhage. Pharmacologic properties of ubiquitin in large animal trauma models, however, are poorly characterized. Thus, the aims of the present study were to determine the effects of CXCR4 modulation on resuscitation requirements after polytrauma, to assess whether ubiquitin influences survival times after lethal polytrauma-hemorrhage, and to characterize its dose-effect profile in porcine models. METHODS Anesthetized pigs underwent polytrauma (PT, femur fractures/lung contusion) alone (Series 1) or PT/hemorrhage (PT/H) to a mean arterial blood pressure of 30 mmHg with subsequent fluid resuscitation (Series 2 and 3) or 40% blood volume hemorrhage within 15 minutes followed by 2.5% blood volume hemorrhage every 15 minutes without fluid resuscitation (Series 4). In Series 1, ubiquitin (175 and 350 nmol/kg), AMD3100 (CXCR4 antagonist, 350 nmol/kg), or vehicle treatment 60 minutes after PT was performed. In Series 2, ubiquitin (175, 875, and 1,750 nmol/kg) or vehicle treatment 60 minutes after PT/H was performed. In Series 3, ubiquitin (175 and 875 nmol/kg) or vehicle treatment at 60 and 180 minutes after PT/H was performed. In Series 4, ubiquitin (875 nmol/kg) or vehicle treatment 30 minutes after hemorrhage was performed. RESULTS In Series 1, resuscitation fluid requirements were significantly reduced by 40% with 350-nmol/kg ubiquitin and increased by 25% with AMD3100. In Series 2, median survival time was 190 minutes with vehicle, 260 minutes with 175-nmol/kg ubiquitin, and longer than 420 minutes with 875-nmol/kg and 1,750-nmol/kg ubiquitin (p < 0.05 vs. vehicle). In Series 3, median survival time was 288 minutes with vehicle and 336 minutes and longer than 420 minutes (p < 0.05 vs. vehicle) with 175-nmol/kg and 875-nmol/kg ubiquitin, respectively. In Series 4, median survival time was 147.5 minutes and 150 minutes with vehicle and ubiquitin, respectively (p > 0.05). CONCLUSION These findings further suggest CXCR4 as a drug target after PT/H. Ubiquitin treatment reduces resuscitation fluid requirements and provides survival benefits after PT/H. The pharmacological effects of ubiquitin treatment occur dose dependently. PMID:26683396

Assessment of Correlation of Distal Mean Arterial Pressure with Aortic Blood Flow during Partial Resuscitative Endovascular Balloon Aortic Occlusion (P-REBOA) in a Swine (Sus scrofa) Controlled Hemorrhage Model

DTIC Science & Technology

2017-11-06

60th Medical Group (AMC), Travis AFB, CA INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) FINAL REPORT SUMMARY (Please type all information. Use...Pressure with Aortic Blood Flow during Partial Resuscitative Endovascular Balloon Aortic Occlusion (P-REBOA) in a Swine (Sus scrofa) Controlled Hemorrhage...to Date Sus scrofa 8 8 2. PROTOCOL TYPE /CHARACTERISTICS: (Check all applicable terms in EACH column) _ Training: Live Animal Medical Readiness

Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

NASA Technical Reports Server (NTRS)

Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

2004-01-01

Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure < 70 mmHg, head trauma, and penetrating injury requiring surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC unloading. We analyzed one volunteer study, 15 intraoperative trials, and 3 trauma studies using HBOCs. Perioperative studies generally suggest ability to deliver oxygen, but one trauma trial using HBOCs (HemAssist) for treatment of trauma resulted in a dramatic increase in mortality, while an intraoperative trauma study using Polyheme demonstrated reductions in blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of different small volume strategies are warranted.

Nontraumatic Retroperitoneal Hematoma After Warfarin Administration: Fatal Case Report and Review of the Literature.

PubMed

Hosseini, Marzieh; Hosseinzadeh, Amin; Raufian, Kasra; Hedjazi, Arya

2015-12-01

Spontaneous retroperitoneal hematoma after warfarin therapy is an extremely rare event. Here, we report a 25-year-old man who was brought in to the emergency service with confusion. On arrival, the patient had hypotension, tachycardia, tachypnea, low-grade fever, and Glasgow Coma Scale score of 12. Abdominal examination revealed distention and mild tenderness in the right upper quadrant of the abdomen. The patient had a history of aortic valve replacement surgery and was on warfarin treatment at an international normalized ratio of 2.4. Our patient progressed to cardiorespiratory arrest. The resuscitation was initiated promptly. Despite all resuscitation measures, including transfusion and administration of high doses of catecholamine, the patient died of hypovolemic shock 3 hours after admission. At autopsy, the external surface of the abdominal great vessels (descending aorta and mesenteric vessels) showed scattered petechial hemorrhages without any visible site of perforation. After comprehensive exploration of the abdomen, no evidence of traumatic event was identified and the cause of internal blood loss was noted as warfarin adverse effect.

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

PubMed Central

Hwang, Tsong-Long; Shen, Hsin-I; Liu, Fu-Chao; Tsai, Hsin-I; Wu, Yang-Chang; Chang, Fang-Rong; Yu, Huang-Ping

2014-01-01

Neutrophil activation is associated with the development of organ injury after trauma–hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma–hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma–hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma–hemorrhagic shock-induced organ injury in rats. PMID:25360589

Effect of Fluid Resuscitation on Acute Skeletal Muscle Ischemia-Reperfusion Injury after Hemorrhagic Shock in Rats

DTIC Science & Technology

2006-06-01

b . ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std...1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 suimencortsaG laideMroiretnA silaibiT T o u rn iq u e t L im b / C o n tr a la te ra l L im b W et W e ig h t R...0.6 0.7 suimencortsaG laideMroiretnA silaibiT T o u rn iq u e t L im b / C o n tr a la te ra l L im b V ia b ili ty R

CE: Assessing Patients During Septic Shock Resuscitation.

PubMed

Bridges, Elizabeth

2017-10-01

: In 2015, the Surviving Sepsis Campaign six-hour bundle was updated. The revised version now recommends documenting the reassessment of volume status and tissue perfusion after initial fluid resuscitation through a repeated focused examination. This article addresses the practice and interpretation of two components of this examination in adults: capillary refill time and skin mottling score. It further discusses how to best integrate these noninvasive parameters into the care of patients undergoing resuscitation for septic shock.

Examining platelet-fibrin interactions during traumatic shock in a swine model using platelet contractile force and clot elastic modulus.

PubMed

White, Nathan J; Martin, Erika J; Brophy, Donald F; Ward, Kevin R

2011-07-01

A significant proportion of severely injured patients develop early coagulopathy, characterized by abnormal clot formation, which impairs resuscitation and increases mortality. We have previously demonstrated an isolated decrease in clot strength by thrombelastography in a swine model of nonresuscitated traumatic shock. In order to more closely examine platelet-fibrin interactions in this setting, we define the observed decrease in clot strength in terms of platelet-induced clot contraction and clot elastic modulus using the Hemostasis Analysis System (HAS) (Hemodyne Inc., Richmond, Virginia, USA). Whole blood was sampled for HAS measurements, metabolic measurements, cell counts, and fibrinogen concentration at baseline prior to injury and again at a predetermined level of traumatic shock defined by oxygen debt. Male swine (N=17) received femur fracture and controlled arterial hemorrhage to achieve an oxygen debt of 80 ml/kg. Platelet counts were unchanged, but fibrinogen concentration was reduced significantly during shock (167.6 vs. 66.7 mg/dl, P=0.0007). Platelet contractile force generated during clot formation did not change during shock (11.7 vs. 10.4 kdynes, P=0.41), but clot elastic modulus was dynamically altered, resulting in a lower final value (22.9 vs. 17.3 kdynes/cm, P<0.0001). In this model of traumatic shock, platelet function was preserved, whereas terminal clot elastic modulus was reduced during shock in a manner most consistent with early changes in the mechanical properties of the developing fibrin fiber network.

Survival without sequelae after prolonged cardiopulmonary resuscitation after electric shock.

PubMed

Motawea, Mohamad; Al-Kenany, Al-Sayed; Hosny, Mostafa; Aglan, Omar; Samy, Mohamad; Al-Abd, Mohamed

2016-03-01

"Electrical shock is the physiological reaction or injury caused by electric current passing through the human body. It occurs upon contact of a human body part with any source of electricity that causes a sufficient current through the skin, muscles, or hair causing undesirable effects ranging from simple burns to death." Ventricular fibrillation is believed to be the most common cause of death after electrical shock. "The ideal duration of cardiac resuscitation is unknown. Typically prolonged cardiopulmonary resuscitation is associated with poor neurologic outcomes and reduced long term survival. No consensus statement has been made and traditionally efforts are usually terminated after 15-30 minutes." The case under discussion seems worthy of the somewhat detailed description given. It is for a young man who survived after 65 minutes after electrical shock (ES) after prolonged high-quality cardiopulmonary resuscitation (CPR), multiple defibrillations, and artificial ventilation without any sequelae. Early start of adequate chest compressions and close adherence to advanced cardiac life support protocols played a vital role in successful CPR.

Pharmacologic Suppression of Inflammation by a Diphenyldifluoroketone, EF24, in a Rat Model of Fixed-Volume Hemorrhage Improves Survival

PubMed Central

Yadav, Vivek R.; Sahoo, Kaustuv; Roberts, Pamela R.

2013-01-01

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)–mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase–1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2–mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1β were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies. PMID:23995597

Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study.

PubMed

Ko, Byuk Sung; Kim, Kyuseok; Choi, Sung-Hyuk; Kang, Gu Hyun; Shin, Tae Gun; Jo, You Hwan; Ryoo, Seung Mok; Beom, Jin Ho; Kwon, Woon Yong; Han, Kap Su; Choi, Han Sung; Chung, Sung Phil; Suh, Gil Joon; Lim, Tae Ho; Kim, Won Young

2018-02-24

Septic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation. This observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level <2 mmol/L after volume resuscitation) and those who were not (≥2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors. Other outcome variables such as in-hospital mortality, intensive care unit (ICU) stay (days), Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. Of 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (either initially or after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation. Thus, these 49 patients were excluded by the new definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all p < 0.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p = 0.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (p = 0.03, both). It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted.

Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.

PubMed

Xu, Jing-Yuan; Chen, Qi-Hong; Xie, Jian-Feng; Pan, Chun; Liu, Song-Qiao; Huang, Li-Wei; Yang, Cong-Shan; Liu, Ling; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Yi; Qiu, Hai-Bo

2014-12-15

The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

PubMed

Braga, D; Barcella, M; D'Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, M H; DeLano, F A; Baselli, G; Schmid-Schönbein, G W; Kistler, E B; Aletti, F; Barlassina, C

2017-08-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Uncontrolled Hemorrhage Differs From Volume- or Pressure-Matched Controlled Hemorrhage in Swine

DTIC Science & Technology

2007-10-01

differences between these models, we evaluated the relationship between blood volume loss and blood pressure in controlled versus uncontrolled hemorrhage...aortotomy; (2) group P, controlled hemorrhage matched to the blood pressure profile of group U; or (3) group V, controlled hemorrhage matched to the...hemorrhage and received no fluid resuscitation. Group U resulted in a blood loss of 17.6 T 0.7 mL kgj1 and a reduction in blood pressure to 28 T 3 mmHg at

Wide variation in cardiopulmonary resuscitation interruption intervals among commercially available automated external defibrillators may affect survival despite high defibrillation efficacy.

PubMed

Snyder, David; Morgan, Carl

2004-09-01

Recent studies have associated interruptions of cardiopulmonary resuscitation imposed by automated external defibrillators (AEDs) with poor resuscitation outcome. In particular, the "hands-off" interval between precordial compressions and subsequent defibrillation shock has been implicated. We sought to determine the range of variation among current-generation AEDs with respect to this characteristic. Seven AEDs from six manufacturers were characterized via stopwatch and arrhythmia simulator with respect to the imposed hands-off interval. All AEDs were equipped with new batteries, and measurements were repeated five times for each AED. A wide variation in the hands-off interval between precordial compressions and shock delivery was observed, ranging from 5.2 to 28.4 secs, with only one AED achieving an interruption of <10 secs. Laboratory and clinical data suggest that this range of variation could be responsible for a more than two-fold variation in patient resuscitation success, an effect that far exceeds any defibrillation efficacy differences that may hypothetically exist. In addition to defibrillation waveform and dose, researchers should consider the hands-off cardiopulmonary resuscitation interruption interval between cardiopulmonary resuscitation and subsequent defibrillation shock to be an important covariate of outcome in resuscitation studies. Defibrillator design should minimize this interval to avoid potential adverse consequences on patient survival.

Monitoring peripheral perfusion and microcirculation.

PubMed

Dubin, Arnaldo; Henriquez, Elizabeth; Hernández, Glenn

2018-06-01

Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation. Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time. Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.

Mechanism of the beneficial effects of ATP-MgCl2 following trauma-hemorrhage and resuscitation: downregulation of inflammatory cytokine (TNF, IL-6) release.

PubMed

Wang, P; Ba, Z F; Morrison, M H; Ayala, A; Dean, R E; Chaudry, I H

1992-04-01

Although ATP-MgCl2 improves hepatocellular function in a nonheparinized model of trauma-hemorrhage and crystalloid resuscitation, it remains unknown whether the beneficial effects of this agent are due to downregulation of the release of the inflammatory cytokines, tumor necrosis factor (TNF), and interleukin-6 (IL-6) under those conditions. To study this, rats underwent a 5-cm laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with four times the volume of shed blood with RL over 60 min. ATP-MgCl2 (50 mumoles/kg body weight each) or an equivalent volume of normal saline was infused intravenously for 95 min. This infusion was started during the last 15 min of RL resuscitation. Plasma levels of TNF and IL-6 were measured at 1.5 hr after the completion of resuscitation by cytokine-dependent cellular assays. Hepatic blood flow was determined by in vivo indocyanine green clearance (corrected by hepatic extraction ratio for indocyanine green), radioactive microspheres, and [3H]-galactose clearance techniques. The results indicate that the levels of circulating TNF and IL-6 increased significantly in the hemorrhaged-resuscitated animals. ATP-MgCl2 treatment, however, markedly decreased the synthesis and/or release of these cytokines to levels similar to the sham group. The markedly decreased hepatic blood flow (as determined by three different methods) and hepatic extraction ratio for indocyanine green were also restored by ATP-MgCl2 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Enteral tranexamic acid attenuates vasopressor resistance and changes in α1-adrenergic receptor expression in hemorrhagic shock.

PubMed

Santamaria, Marco Henry; Aletti, Federico; Li, Joyce B; Tan, Aaron; Chang, Monica; Leon, Jessica; Schmid-Schönbein, Geert W; Kistler, Erik B

2017-08-01

Irreversible hemorrhagic shock is characterized by hyporesponsiveness to vasopressor and fluid therapy. Little is known, however, about the mechanisms that contribute to this phenomenon. Previous studies have shown that decreased intestinal perfusion in hemorrhagic shock leads to proteolytically mediated increases in gut permeability, with subsequent egress of vasoactive substances systemically. Maintenance of blood pressure is achieved in part by α1 receptor modulation, which may be affected by vasoactive factors; we thus hypothesized that decreases in hemodynamic stability and vasopressor response in shock can be prevented by enteral protease inhibition. Rats were exposed to experimental hemorrhagic shock (35 mm Hg mean arterial blood pressure for 2 hours, followed by reperfusion for 2 hours) and challenged with phenylephrine (2 μg/kg) at discrete intervals to measure vasopressor responsiveness. A second group of animals received enteral injections with the protease inhibitor tranexamic acid (TXA) (127 mM) along the small intestine and cecum 1 hour after induction of hemorrhagic shock. Blood pressure response (duration and amplitude) to phenylephrine after reperfusion was significantly attenuated in animals subjected to hemorrhagic shock compared with baseline and control nonshocked animals and was restored to near baseline by enteral TXA. Arteries from shocked animals also displayed decreased α1 receptor density with restoration to baseline after enteral TXA treatment. In vitro, rat shock plasma decreased α1 receptor density in smooth muscle cells, which was also abrogated by enteral TXA treatment. Results from this study demonstrate that experimental hemorrhagic shock leads to decreased response to the α1-selective agonist phenylephrine and decreased α1 receptor density via circulating shock factors. These changes are mitigated by enteral TXA with correspondingly improved hemodynamics. Proteolytic inhibition in the lumen of the small intestine improves hemodynamics in hemorrhagic shock, possibly by restoring α1 adrenergic functionality necessary to maintain systemic blood pressure and perfusion.

Initial resuscitation and management of pediatric septic shock

PubMed Central

Martin, Kelly; Weiss, Scott L.

2015-01-01

The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function, 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications, and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock. PMID:25604591

Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding.

PubMed

Safaei, Mansour; Takami, Hassan Mousavi

2011-10-01

The most common cause of shock in the surgical or trauma patient is hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood transfusion, such as risk of transmission of infectious diseases, and access and maintenance limitations, treatment of shock with autologous blood seems to be a decent solution. Autologous blood accumulated in body cavities in traumatic bleeding (such hemothorax), and bloodshed in operation field during open heart or vascular surgeries, and similar situations, can be utilized again. In this study, autotransfusion effects compared with crystalloid fluid in the treatment of hemorrhagic shock was investigated. After induction of hemorrhagic shock in dogs by Wiggers type controlled bleeding, treating them in a group with autologous blood and another group with Ringer lactate were performed, and the results of treatment were studied. There was no mortality in both treatment approaches. Immediately after treatment, crystalloid positive effects such as renormalized vital signs and appropriate consciousness were more noticeable than autotransfusion, while twenty-four hours after, the desired effects of autologous blood were more pronounced like decreased metabolic acidosis and improvement of diuresis. Crystalloid during the first hours after treatment of hemorrhagic shock may be better than autologous blood as preferred treatment, while autotransfusion showed its benefits some hours after. This finding can be used to develop better strategies for treatment of hemorrhagic shock.

Shock Duration after Resuscitation Is Associated with Occurrence of Post-Cardiac Arrest Acute Kidney Injury

PubMed Central

2015-01-01

This retrospective observational study investigated the clinical course and predisposing factors of acute kidney injury (AKI) developed after cardiac arrest and resuscitation. Eighty-two patients aged over 18 yr who survived more than 24 hr after cardiac arrest were divided into AKI and non-AKI groups according to the diagnostic criteria of the Kidney Disease/Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI. Among 82 patients resuscitated from cardiac arrest, AKI was developed in 66 (80.5%) patients (AKI group) leaving 16 (19.5%) patients in the non-AKI group. Nineteen (28.8%) patients of the AKI group had stage 3 AKI and 7 (10.6%) patients received renal replacement therapy during admission. The duration of shock developed within 24 hr after resuscitation was shorter in the non-AKI group than in the AKI group (OR 1.02, 95% CI 1.01-1.04, P < 0.05). On Multiple logistic regression analysis, the only predisposing factor of post-cardiac arrest AKI was the duration of shock. In conclusion, occurrence and severity of post-cardiac arrest AKI is associated with the duration of shock after resuscitation. Renal replacement therapy is required for patients with severe degree (stage 3) post-cardiac arrest AKI. PMID:26028935

AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits.

PubMed

Huang, Yi; Ratz, Paul H; Miner, Amy S; Locke, Victoria A; Chen, Grace; Chen, Yang; Barbee, Robert W

2017-01-01

Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO 2 ), while fewer have been used to in an attempt to reduce oxygen demand (VO 2 ). The cellular energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK) has the potential to modulate both whole-body DO 2 and VO 2 . Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside) given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits. Methods: Chronically treated animals received AICAR (40 mg/kg/day, IV) for 10 days prior to hemorrhage, while rabbits in the acute study were infused with AICAR (7.5 mg/kg bolus, 2 mg/kg/min infusion) or vehicle (0.3 ml/kg saline bolus, 0.03 ml/kg/min infusion) IV for 2 h prior to severe hemorrhage. Both acutely and chronically treated animals were sedated (ketamine/xylazine cocktail) the morning of the terminal experiment and surgically prepared for hemorrhage, including the implantation of arterial and venous catheters (for blood removal/sampling and drug/vehicle administration) and thoracotomy for implantation of transit-time flow transducers (for cardiac output determination). Results: AICAR given acutely lowered arterial blood glucose and increased blood lactate levels before hemorrhage, and abolished the well-documented hemorrhage-induced hyperglycemia seen in vehicle treated animals. Animals given AICAR chronically had blunted hemorrhage-induced hyperglycemia without prior baseline changes. Chronically treated AICAR animals showed significantly lower lactate levels during hemorrhage. Rabbits receiving AICAR both acutely and chronically experienced similar falls in mean arterial pressure, cardiac output and hence DO 2 to their vehicle counterparts throughout the hemorrhage period. However, rabbits treated either acutely or chronically with AICAR accumulated lower oxygen deficits and debt during hemorrhage compared to vehicle-infused controls. Conclusions: The oxygen debt data suggest that AMPK activation could decrease trauma associated morbidity and mortality, perhaps by mechanisms related to increased glucose utilization. Additional studies are needed to investigate the effects of AICAR and associated mechanisms of action when given during resuscitation from hemorrhage.

Earlier Endpoints Are Required for Hemorrhagic Shock Trials among Severely Injured Patients

PubMed Central

Fox, Erin E.; Holcomb, John B.; Wade, Charles E.; Bulger, Eileen M.; Tilley, Barbara C.

2016-01-01

Background Choosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-hour and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints. Methods The goal of this project was to determine the optimal endpoint for hemorrhage control trials using existing literature and new analyses of previously published data. Results Recent studies among bleeding trauma patients show that hemorrhagic deaths occur rapidly, at a high rate, and in a consistent pattern. Early preventable deaths among trauma patients are largely due to hemorrhage and the median time to hemorrhagic death from admission is 2.0-2.6 hours. Approximately 85% of hemorrhagic deaths occur within 6 hours. The hourly mortality rate due to traumatic injury decreases rapidly after enrollment from 4.6% per hour at 1 hour post-enrollment to 1% per hour at 6 hours to <0.1% per hour by 9 hours and thereafter. Early primary endpoints (within 6 hours) have critically important benefits for hemorrhage control trials, including being congruent with the median time to hemorrhagic death, biologic plausibility, and enabling the use of all-cause mortality, which is definitive and objective. Conclusions Primary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-cause mortality evaluated within the first 6 hours is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 hour and 30 day all-cause mortality as well as the customary safety endpoints. PMID:28207628

A Novel Fluoroscopy-free, Resuscitative Endovascular Aortic Balloon Occlusion System in a Model of Hemorrhagic Shock

DTIC Science & Technology

2013-07-01

group (7.7 [1.5] mmol/L vs. 6.1 [3.3] mmol/L, p = 0.007) and a higher creatine kinase level in PBS than in CBS (144,290 [138,363] U/L vs. 68,876 [57,291...5,423) 0.452 Creatinine , mg/dL 2.3 (1.2) 1.7 (0.4) 0.029 1.7 (0.8) 1.5 (0.2) 0.418 K+, mmol/L 7.49 (1.72) 7.60 (1.28) 0.845 7.66 (1.45) 6.10 (3.27...0.007 CK, U/L 47,031 (14,109) 70,152 (32,362) 0.228 68,876 (57,291) 144,290 (138,363) G0.001 AST, aspartate aminotransferase; CK, creatine kinase; K

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

PubMed Central

Braga, D; Barcella, M; D’Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, MH; DeLano, FA; Baselli, G; Schmid-Schönbein, GW; Kistler, EB; Aletti, F

2017-01-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger’s shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients. PMID:28661205

Beta-blockade prevents hematopoietic progenitor cell suppression after hemorrhagic shock.

PubMed

Elhassan, Ihab O; Hannoush, Edward J; Sifri, Ziad C; Jones, Eyone; Alzate, Walter D; Rameshwar, Pranela; Livingston, David H; Mohr, Alicia M

2011-08-01

Severe injury is accompanied by sympathetic stimulation that induces bone marrow (BM) dysfunction by both suppression of hematopoietic progenitor cell (HPC) growth and loss of cells via HPC mobilization to the peripheral circulation and sites of injury. Previous work demonstrated that beta-blockade (BB) given prior to tissue injury both reduces HPC mobilization and restores HPC colony growth within the BM. This study examined the effect and timing of BB on BM function in a hemorrhagic shock (HS) model. Male Sprague-Dawley rats underwent HS via blood withdrawal, maintaining the mean arterial blood pressure at 30-40 mm Hg for 45 min, after which the extracted blood was reinfused. Propranolol (10 mg/kg) was given either prior to or immediately after HS. Blood pressure, heart rate, BM cellularity, and death were recorded. Bone marrow HPC growth was assessed by counting colony-forming unit-granulocyte-, erythrocyte-, monocyte-, megakaryocyte (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E) cells. Administration of BB prior to injury restored HPC growth to that of naïve animals (CFU-GEMM 59 ± 11 vs. 61 ± 4, BFU-E 68 ± 9 vs. 73 ± 3, and CFU-E 81 ± 35 vs. 78 ± 14 colonies/plate). Beta-blockade given after HS increased the growth of CFU-GEMM, BFU-E, and CFU-E significantly and improved BM cellularity compared with HS alone. The mortality rate was not increased in the groups receiving BB. Administration of propranolol either prior to injury or immediately after resuscitation significantly reduced post-shock BM suppression. After HS, BB may improve BM cellularity by decreasing HPC mobilization. Therefore, the early use of BB post-injury may play an important role in attenuating the BM dysfunction accompanying HS.

Acute resuscitation of the unstable adult trauma patient: bedside diagnosis and therapy

PubMed Central

Kirkpatrick, Andrew W.; Ball‡, Chad G.; D'Amours, Scott K.; Zygun, David

2008-01-01

Traumatic injury remains the leading cause of potentially preventable death in Canadians under age 40 years. Although only a minority of patients present with hemodynamic instability, these patients have a significant chance of dying. The causes of instability must be recognized and corrected quickly by using a systematic approach. To allow key supportive interventions to be undertaken swiftly, it is more important to identify and prioritize systemic compromise than to confirm specific diagnoses. Most potentially preventable trauma death relates to airway obstruction, hemopneumothorax, intracranial hemorrhage and intracavitary bleeding. Definitive airway control should be assured as a first priority. Hemopneumothoraces are typically addressed by chest tube insertion, although thoracic exploration will occasionally be urgently required. Hemorrhage control is much more important than fluid resuscitation and mandates the earliest possible definitive management. Unstable patients nearing physiological exhaustion require abbreviated or “damage-control” surgical tactics. This should be recognized early in the resuscitation rather than late in an operative procedure. The management of expanding intracranial hemorrhage requires optimization of oxygenation, ventilation and circulatory support while urgent CT and expert neurosurgical care are provided. Polytrauma presenting with head injury challenges the most developed of trauma systems, necessitating thoughtful prioritization of care and taking into consideration local capabilities. Bedside trauma sonography is an evolving tool that complements the physical examination during an initial survey. Future breakthroughs in trauma resuscitation may involve procoagulant medications, imaging technology, circulatory assist techniques and the use of inflammatory modulators. The greatest future challenge in trauma care, though, will be the provision of basic organized resuscitative care to the global community. PMID:18248707

Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

PubMed

Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

2015-01-01

Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing to curtail transcapillary albumin leakage and resulting in increasingly positive net fluid balances. GIPS may represent a third hit after the initial insult and the ischaemia reperfusion injury. Novel markers like the capillary leak index, extravascular lung water and pulmonary permeability index may help the clinician in guiding appropriate fluid management. Capillary leak is an inflammatory condition with diverse triggers that results from a common pathway that includes ischaemia-reperfusion, toxic oxygen metabolite generation, cell wall and enzyme injury leading to a loss of capillary endothelial barrier function. Fluid overload should be avoided in this setting.

Walter B. Cannon's World War I experience: treatment of traumatic shock then and now.

PubMed

Ryan, Kathy L

2018-06-01

Walter B. Cannon (1871-1945), perhaps America's preeminent physiologist, volunteered for service with the Army Expeditionary Force (AEF) during World War I. He initially served with Base Hospital No. 5, a unit made up of Harvard clinicians, before moving forward to the front lines to serve at a casualty clearing station run by the British. During his time there, he performed research on wounded soldiers to understand the nature and causes of traumatic shock. Subsequently, Cannon performed animal experimentation on the causes of traumatic shock in the London laboratory of Dr. William Bayliss before being assigned to the AEF Central Medical Laboratory in Dijon, France, where he continued his experimental studies. During this time, he also developed and taught a curriculum on resuscitation of wounded soldiers to medical providers. Although primarily a researcher and teacher, Cannon also performed clinical duties throughout the war, serving with distinction under fire. After the war, Cannon wrote a monograph entitled Traumatic Shock (New York: Appleton, 1923), which encapsulated the knowledge that had been gained during the war, both from direct observation of wounded soldiers, as well as laboratory experimentation on the causes and treatment of traumatic shock. In his monograph, Cannon elucidates a number of principles concerning hemorrhagic shock that were later forgotten, only to be "rediscovered" during the current conflicts in Iraq and Afghanistan. This paper summarizes Cannon's wartime experiences and the knowledge gained concerning traumatic shock during World War I, with a comparison of current combat casualty care practices and knowledge to that which Cannon and his colleagues understood a century ago.

Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding*

PubMed Central

Safaei, Mansour; Takami, Hassan Mousavi

2011-01-01

BACKGROUND: The most common cause of shock in the surgical or trauma patient is hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood transfusion, such as risk of transmission of infectious diseases, and access and maintenance limitations, treatment of shock with autologous blood seems to be a decent solution. Autologous blood accumulated in body cavities in traumatic bleeding (such hemothorax), and bloodshed in operation field during open heart or vascular surgeries, and similar situations, can be utilized again. In this study, autotransfusion effects compared with crystalloid fluid in the treatment of hemorrhagic shock was investigated. METHODS: After induction of hemorrhagic shock in dogs by Wiggers type controlled bleeding, treating them in a group with autologous blood and another group with Ringer lactate were performed, and the results of treatment were studied. RESULTS: There was no mortality in both treatment approaches. Immediately after treatment, crystalloid positive effects such as renormalized vital signs and appropriate consciousness were more noticeable than autotransfusion, while twenty-four hours after, the desired effects of autologous blood were more pronounced like decreased metabolic acidosis and improvement of diuresis. CONCLUSIONS: Crystalloid during the first hours after treatment of hemorrhagic shock may be better than autologous blood as preferred treatment, while autotransfusion showed its benefits some hours after. This finding can be used to develop better strategies for treatment of hemorrhagic shock. PMID:22973328

Clonidine Reduces Norepinephrine and Improves Bone Marrow Function in a Rodent Model of Lung Contusion, Hemorrhagic Shock and Chronic Stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Ramos, Harry; Loftus, Tyler J.; Efron, Philip A.; Mohr, Alicia M.

2016-01-01

Background Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Methods Male Sprague-Dawley rats underwent six days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75μg/kg) after the restraint stress. On post-injury day seven, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor (G-CSF), and peripheral blood mobilization of hematopoietic progenitor cells (HPC), as well as bone marrow cellularity and erythroid progenitor cell growth. Results The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress, significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1±0.6 vs. 10.8±0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased HPC mobilization and restored G-CSF levels. Conclusions After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. PMID:27742030

Low hemorrhage-related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography-directed hemostatic resuscitation with plasma and platelets.

PubMed

Johansson, Pär I; Sørensen, Anne Marie; Larsen, Claus F; Windeløv, Nis A; Stensballe, Jakob; Perner, Anders; Rasmussen, Lars S; Ostrowski, Sisse R

2013-12-01

Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated. This was a prospective study of adult trauma patients admitted to a Level I trauma center. Demography, Injury Severity Score (ISS), transfusion therapy, and mortality were registered. Hemostatic resuscitation was based on a massive transfusion protocol encompassing transfusion packages and thromboelastography (TEG)-guided therapy. A total of 182 patients were included (75% males, median age 43 years, ISS of 17, 92% with blunt trauma). Overall 28-day mortality was 12% with causes of death being exsanguinations (14%), traumatic brain injury (72%, two-thirds expiring within 24 hr), and other (14%). One-fourth, 16 and 15% of the patients, received red blood cells (RBCs), plasma, or platelets (PLTs) within 2 hours from admission and 68, 71, and 75%, respectively, of patients transfused within 24 hours received the respective blood products within the first 2 hours. In patients transfused within 24 hours, the median number of blood products at 2 hours was 5 units of RBCs, 5 units of plasma, and 2 units of PLT concentrates. Nonsurvivors had lower clot strength by kaolin-activated TEG and TEG functional fibrinogen and lower kaolin-tissue factor-activated TEG α-angle and lysis after 30 minutes compared to survivors. None of the TEG variables were independent predictors of massive transfusion or mortality. Three-fourths of the patients transfused with plasma or PLTs within 24 hours received these in the first 2 hours. Hemorrhage caused 14% of the deaths. We introduced transfusion packages and early TEG-directed hemostatic resuscitation at our hospital 10 years ago and this may have contributed to reducing hemorrhagic trauma deaths. © 2013 American Association of Blood Banks.

Effects of Stomach Inflation on Cardiopulmonary Function and Survival During Hemorrhagic Shock: A Randomized, Controlled, Porcine Study.

PubMed

Braun, Patrick; Putzer, Gabriel; Strapazzon, Giacomo; Wimmer, Angela; Schnell, Hermann; Arnold, Henrik; Neururer, Sabrina; Brugger, Hermann; Wenzel, Volker; Paal, Peter

2016-07-01

Ventilation of an unprotected airway may result in stomach inflation. The purpose of this study was to evaluate the effect of clinically realistic stomach inflation on cardiopulmonary function during hemorrhagic shock in a porcine model. Pigs were randomized to a sham control group (n = 9), hemorrhagic shock (35 mL kg over 15 min [n = 9]), and hemorrhagic shock combined with stomach inflation (35 mL kg over 15 min and 5 L stomach inflation [n = 10]). When compared with the control group, hemorrhagic shock (n = 9) increased heart rate (103 ± 11 vs. 146 ± 37 beats min; P = 0.002) and lactate (1.4 ± 0.5 vs. 4.0 ± 1.9 mmol L; P < 0.001), and decreased mean arterial blood pressure (81.3 ± 12.8 vs. 35.4 ± 8.1 mmHg; P < 0.001) and stroke-volume index (38.1 ± 6.4 vs. 13.6 ± 4.8 mL min m; P < 0.001). Hemorrhagic shock combined with stomach inflation (n = 10) versus hemorrhagic shock only (n = 9) increased intra-abdominal pressure (27.0 ± 9.3 vs. 1.1 ± 1.0 mmHg; P < 0.001), and decreased stroke-volume index (9.9 ± 6.0 vs. 20.8 ± 8.5 mL min m; P = 0.007), and dynamic respiratory system compliance (10.8 ± 4.5 vs. 38.1 ± 6.1 mL cmH2O; P < 0.001). Before versus after stomach evacuation during hemorrhagic shock, intra-abdominal pressure decreased (27.0 ± 9.3 vs. 9.8 ± 5.4 mmHg; P = 0.042). Survival in the sham control and hemorrhagic shock group was 9 of 9, respectively, and 3 of 10 after hemorrhagic shock and stomach inflation (P < 0.001). During hemorrhagic shock stomach inflation caused an abdominal compartment syndrome and thereby impaired cardiopulmonary function and aerobic metabolism, and increased mortality. Subsequent stomach evacuation partly reversed adverse stomach-inflation triggered effects.

Multicenter retrospective study of noncompressible torso hemorrhage: Anatomic locations of bleeding and comparison of endovascular versus open approach.

PubMed

Chang, Ronald; Fox, Erin E; Greene, Thomas J; Eastridge, Brian J; Gilani, Ramyar; Chung, Kevin K; DeSantis, Stacia M; DuBose, Joseph J; Tomasek, Jeffrey S; Fortuna, Gerald R; Sams, Valerie G; Todd, S Rob; Podbielski, Jeanette M; Wade, Charles E; Holcomb, John B

2017-07-01

Rational development of technology for rapid control of noncompressible torso hemorrhage (NCTH) requires detailed understanding of what is bleeding. Our objectives were to describe the anatomic location of truncal bleeding in patients presenting with NCTH and compare endovascular (ENDO) management versus open (OPEN) management. This is a retrospective study of adult trauma patients with NCTH admitted to four urban Level I trauma centers in the Houston and San Antonio metropolitan areas in 2008 to 2012. Inclusion criteria include named axial torso vessel disruption, Abbreviated Injury Scale chest or abdomen score of 3 or higher with shock (base excess, <-4) or truncal operation in 90 minutes or less, or pelvic fracture with ring disruption. Exclusion criteria include isolated hip fractures, falls from standing, or prehospital cardiopulmonary resuscitation. After dichotomizing into OPEN, ENDO, and resuscitative thoracotomy (RT) groups based on the initial approach to control NCTH, a mixed-effects Poisson regression with robust error variance (controlling for age, mechanism, Injury Severity Score, shock, hypotension, and severe head injury as fixed effects and site as a random effect) was used to test the hypothesis that ENDO was associated with reduced in-hospital mortality in NCTH patients. Five hundred forty-three patients with NCTH underwent ENDO (n = 166, 31%), OPEN (n = 309, 57%), or RT (n = 68, 12%). Anatomic bleeding locations were 25% chest, 41% abdomen, and 31% pelvis. ENDO was used to treat relatively few types of vascular injuries, whereas OPEN and RT injuries were more diverse. ENDO patients had more blunt trauma (95% vs. 34% vs. 32%); severe injuries (median Injury Severity Score, 34 vs. 27 vs. 21), and increased time to intervention (median, 298 vs. 92 vs. 51 minutes) compared with OPEN and RT. Mortality was 15% versus 20% versus 79%. ENDO was associated with decreased mortality compared to OPEN (relative risk, 0.58; 95% confidence interval, 0.46-0.73). Although ENDO may reduce mortality in NCTH patients, significant group differences limit the generalizability of this finding. Therapeutic, level V.

Activation of sirtuin 1/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage

PubMed Central

Li, Pengyun; Meng, Xianzhong; Bian, Huining; Burns, Nana; Zhao, Ke-seng; Song, Rui

2015-01-01

Vascular hyporeactivity is one of the major causes responsible for refractory hypotension and associated mortality in severe hemorrhagic shock. Mitochondrial permeability transition (mPT) pore opening in arteriolar smooth muscle cells (ASMCs) is involved in the pathogenesis of vascular hyporeactivity. However, the molecular mechanism underlying mitochondrial injury in ASMCs during hemorrhagic shock is not well understood. Here we produced an in vivo model of severe hemorrhagic shock in adult Wistar rats. We found that sirtuin (SIRT)1/3 protein levels and deacetylase activities were decreased in ASMCs following severe shock. Immunofluorescence staining confirmed reduced levels of SIRT1 in the nucleus and SIRT3 in the mitochondria, respectively. Acetylation of cyclophilin D (CyPD), a component of mPT pore, was increased. SIRT1 activators suppressed mPT pore opening and ameliorated mitochondrial injury in ASMCs after severe shock. Furthermore, administration of SIRT1 activators improved vasoreactivity in rats under severe shock. Our data suggest that epigenetic mechanisms, namely histone post-translational modifications, are involved in regulation of mPT by SIRT1/SIRT3- mediated deacetylation of CyPD. SIRT1/3 is a promising therapeutic target for the treatment of severe hemorrhagic shock. PMID:26473372

Albumin in Burn Shock Resuscitation: A Meta-Analysis of Controlled Clinical Studies.

PubMed

Navickis, Roberta J; Greenhalgh, David G; Wilkes, Mahlon M

2016-01-01

Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07-0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed.

The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock.

PubMed

Kellum, John A; Chawla, Lakhmir S; Keener, Christopher; Singbartl, Kai; Palevsky, Paul M; Pike, Francis L; Yealy, Donald M; Huang, David T; Angus, Derek C

2016-02-01

Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy. To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes. Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock. We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3. In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.

Effects of fibrinogen concentrate after shock/resuscitation – A comparison between in vivo microvascular clot formation and thromboelastometry

PubMed Central

Martini, Judith; Cabrales, Pedro; Fries, Dietmar; Intaglietta, Marcos; Tsai, Amy G.

2014-01-01

Objective Dilutional coagulopathy after resuscitation with crystalloids/colloids clinically often appears as diffuse microvascular bleeding. Administration of fibrinogen reduces bleeding and increases maximum clot firmness (MCF), measured by thromboelastometry. Study objective was to implement a model where microvascular bleeding can be directly assessed by visualizing clot formation in microvessels, and correlations can be made to thromboelastometry. Design Randomized animal study. Setting University research laboratory. Subjects Male Syrian Golden hamsters. Interventions Microvessels of Syrian Golden hamsters fitted with a dorsal window chamber were studied using videomicroscopy. After 50% hemorrhage followed by 1 hr of hypovolemia resuscitation with 35% of blood volume using a high molecular weight (MW) HES solution (Hextend®, Hospira, MW 670 kD) occurred. Animals were then treated with 250 mg/kg fibrinogen iv (Laboratoire français du Fractionnement et des Biotechnologies (LFB), Paris, France) or an equal volume of saline before venular vessel wall injuries were made by directed laser irradiation and the ability of microthrombus formation was assessed. Measurements and main results Thromboelastometric measurements of MCF were performed at the beginning and at the end of the experiment. Resuscitation with HES and sham treatment significantly decreased FIBTEM MCF from 32 ± 9 at baseline vs. 13 ± 5 mm after sham treatment (p < 0.001). Infusion of fibrinogen concentrate significantly increased MCF, restoring baseline levels (baseline 32 ± 9 mm; after fibrinogen administration 29 ± 2 mm). In vivo microthrombus formation in laser injured vessels significantly increased in fibrinogen treated animals compared with sham (77% vs. 18%). Conclusions Fibrinogen treatment leads to increased clot firmness in dilutional coagulopathy as measured with thromboelastometry. At the microvascular level this increased clot strength, corresponds to an increased incidence of thrombus formation in vessels injured by focused laser irradiation. PMID:23978812

Damage Control Resuscitation: A New Paradigm for Fluid Resuscitation of Severely Injured Soldiers

DTIC Science & Technology

2006-11-01

Chughtai , 2006). Its use in treating hemorrhaging trauma patients is attractive because it offers a site-specific therapy for controlling...L., 2006: The use of fresh whole blood in massive transfusion. J Trauma, 60, S59- 69. Rizoli, S. B. and Chughtai , T., 2006: The emerging role of

Acute Management of the Traumatically Injured Pelvis.

PubMed

Skitch, Steven; Engels, Paul T

2018-02-01

Severe pelvic trauma is a challenging condition. The pelvis can create multifocal hemorrhage that is not easily compressible nor managed by traditional surgical methods such as tying off a blood vessel or removing an organ. Its treatment often requires reapproximation of bony structures, damage control resuscitation, assessment for associated injuries, and triage of investigations, as well as multimodality hemorrhage control (external fixation, preperitoneal packing, angioembolization, REBOA [resuscitative endovascular balloon occlusion of the aorta]) by multidisciplinary trauma specialists (general surgeons, orthopedic surgeons, endovascular surgeons/interventional radiologists). This article explores this complex clinical problem and provides a practical approach to its management. Copyright © 2017 Elsevier Inc. All rights reserved.

Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

2017-03-01

Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in rats subjected to hemorrhagic shock].

PubMed

Zhou, X; Hu, D; Liu, L; Wu, Z; Qin, J; Cai, S

2001-12-01

We have studied the effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in hemorrhage-shocked rats using micropippette aspiration technique. Wistar rats were randomly divided into three groups of 0.9% NaCl(NS), 7.5% NaCl (HS) and 5% NaCl-3.5% NaAc (HSA), respectively. The animals were bled to reach a mean arterial pressure of 5.3 kPa in 10 minutes and maintained in shock for 90 minutes. 4 ml/kg NS, HS and HSA was given intravenously and respectively in 5 minutes following hemorrhagic shock. The blood was collected to determine the viscoelasticities of erythrocyte membrane at baseline, shock and after treatment. The results showed that the elastic moduli and viscous coefficients of erythrocyte membrane were increased obviously following hemorrhagic shock. HS raised elastic moduli and reduced viscous coefficients significantly compared with NS after treatment. The elastic moduli and viscous coefficients of erythrocyte membrane were decreased remarkably in HSA group than in NS and HS group. These data suggested that HSA could improve the viscoelasticities of erythrocyte membrane significantly in rats subjected to hemorrhagic shock.

The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

PubMed

Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

2008-10-01

To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

PubMed

Hernández, Glenn; Cavalcanti, Alexandre Biasi; Ospina-Tascón, Gustavo; Zampieri, Fernando Godinho; Dubin, Arnaldo; Hurtado, F Javier; Friedman, Gilberto; Castro, Ricardo; Alegría, Leyla; Cecconi, Maurizio; Teboul, Jean-Louis; Bakker, Jan

2018-04-23

Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

A Clinical Series of Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhage Control and Resuscitation

DTIC Science & Technology

2013-01-01

required to demonstrate proficiency through completion of a pretest and posttest including examination of hand- on skills with both animal and simulator...With available technology, this method of resuscitation can be performed by trauma and acute care surgeons who have benefited from instruction on a...the right posterior axillary line at the level of the eighth rib (Table 1). On arrival, his pulse was 119 beats per minute (bpm) and his blood pressure

Comparisons of Lactated Ringer’s and Hextend Resuscitation on Hemodynamics and Coagulation following Femur Injury and Severe Hemorrhage in Pigs

DTIC Science & Technology

2013-01-01

resuscitation but not with Hextend. The lack of recovery after Hextend is likely caused by greater hemodilution and possible effects of starches on...coagulation substrates and further documents the need to restrict the use of high-molecular-weight starch in resuscitation fluids for bleeding casualties. (J...inex- pensive and have been widely used at prehospital and hospital settings. Colloids, such as albumin, gelatin, and hydroxyethyl starch (HES), are

Accuracy of continuous noninvasive hemoglobin monitoring for the prediction of blood transfusions in trauma patients.

PubMed

Galvagno, Samuel M; Hu, Peter; Yang, Shiming; Gao, Cheng; Hanna, David; Shackelford, Stacy; Mackenzie, Colin

2015-12-01

Early detection of hemorrhagic shock is required to facilitate prompt coordination of blood component therapy delivery to the bedside and to expedite performance of lifesaving interventions. Standard physical findings and vital signs are difficult to measure during the acute resuscitation stage, and these measures are often inaccurate until patients deteriorate to a state of decompensated shock. The aim of this study is to examine a severely injured trauma patient population to determine whether a noninvasive SpHb monitor can predict the need for urgent blood transfusion (universal donor or additional urgent blood transfusion) during the first 12 h of trauma patient resuscitation. We hypothesize that trends in continuous SpHb, combined with easily derived patient-specific factors, can identify the immediate need for transfusion in trauma patients. Subjects were enrolled if directly admitted to the trauma center, >17 years of age, and with a shock index (heart rate/systolic blood pressure) >0.62. Upon admission, a Masimo Radical-7 co-oximeter sensor (Masimo Corporation, Irvine, CA) was applied, providing measurement of continuous non-invasive hemoglobin (SpHb) levels. Blood was drawn and hemoglobin concentration analyzed and conventional pulse oximetry photopletysmograph signals were continuously recorded. Demographic information and both prehospital and admission vital signs were collected. The primary outcome was transfusion of at least one unit of packed red blood cells within 24 h of admission. Eight regression models (C1-C8) were evaluated for the prediction of blood use by comparing area under receiver operating curve (AUROC) at different time intervals after admission. 711 subjects had continuous vital signs waveforms available, to include heart rate (HR), SpHb and SpO2 trends. When SpHb was monitored for 15 min, SpHb did not increase AUROC for prediction of transfusion. The highest ROC was recorded for model C8 (age, sex, prehospital shock index, admission HR, SpHb and SpO2) for the prediction of blood products within the first 3 h of admission. When data from 15 min of continuous monitoring were analyzed, significant improvement in AUROC occurred as more variables were added to the model; however, the addition of SpHb to any of the models did not improve AUROC significantly for prediction of blood use within the first 3 h of admission in comparison to analysis of conventional oximetry features. The results demonstrate that SpHb monitoring, accompanied by continuous vital signs data and adjusted for age and sex, has good accuracy for the prediction of need for transfusion; however, as an independent variable, SpHb did not enhance predictive models in comparison to use of features extracted from conventional pulse oximetry. Nor was shock index better than conventional oximetry at discriminating hemorrhaging and prediction of casualties receiving blood. In this population of trauma patients, noninvasive SpHb monitoring, including both trends and absolute values, did not enhance the ability to predict the need for blood transfusion.

Defibrillation and resuscitation in a piglet model of pediatric ventricular fibrillation following AHA 2005 guidelines.

PubMed

Zhou, Zhengyu; Wang, Yubin; Zhou, Huiying; Huang, Meng; Liu, Huiting; Hsieh, Chengtai; Xue, Zhimou

2010-08-01

To evaluate the efficacy and safety of defibrillation on children according to AHA 2005 recommendations Pig resembles human in the chest configuration, anatomy and physiology of the cardiovascular and pulmonary systems. Piglets weighing 7.0 Kg ± 1.4kg, 14.0kg ± 2.8kg, 25.0kg ± 5.0kg respectively, which represented children 1 to 8 yr old were induced ventricular fibrillation (VF). An adult biphasic AED was used in conjunction with pediatric attenuating electrodes which could deliver 50-J shock for 2 min and two min of cardiopulmonary resuscitation (CPR) immediately followed it. If VF did not reverse, 70-J shock combined with CPR was used, and the protocol was repeated five times. If an organized cardiac rhythm with mean aortic pressure more than 60 mmHg persisted for an interval of 5 minutes, the animal was regarded as successfully resuscitated. If the AED recognized a "non-shockable" rhythm, CPR was also performed immediately for 2 min. The same resuscitation program was exercised on piglets of manual defibrillator group. Neurologic alertness score, hemodynamic and myocardial functions were evaluated, autopsy was routinely performed to document possible injuries. In the AED group, 14 out of 15 animals, were successfully resuscitated, among them 11 piglets were resuscitated by 50-J defibrillation combined with cardiopulmonary resuscitation, and other three recovered to normal by 1 or 2 times of 70-J shocks and CPR. All animals in manual defibrillator group were successfully resuscitated by 50-J shocks and CPR. Left ventricular ejection fraction and fractional area change were reduced significantly during 3-4 hr post-resuscitation (P<0.05) and returned to baseline ranges at the end of 72 hr. There was no evidence of myocardial and pulmonary damage during autopsy, and neurologic recovery was also normal. Data of blood gas analysis, blood electrolytes and myocardial enzymes does not show any statistically significant difference (P> 0.05) in the groups. 50 J biphasic dose defibrillation combined with effective CPR, successfully terminated VF without adverse effects on myocardial function and survival in a piglet defibrillation model for young children 1 to 8 yr of age. The new guidelines recommendation that one shock immediately followed by CPR is reasonable. Adults AED combined with pediatric electrodes is feasible to the diagnosis and treatment of pediatric VF model. But the user should not rely too much on AED's "automatic" function, but should accumulate and integrate his experience with AED technology.

HIF-1α regulates Cx40-dependent vasodilatation following hemorrhagic shock in rats

PubMed Central

Duan, Chenyang; Chen, Ken; Yang, Guangming; Li, Tao; Liu, Liangming

2017-01-01

HIF-1α plays an essential role in hemorrhagic shock-induced vasoconstriction. However, the underlying mechanisms remain poorly understood. Here, we studied both the role of HIF-1α in regulating vasodilatation, and the involvement of Cx40 in this process. We found that endothelium-dependent vasodilatation exhibited an overall decline after hemorrhagic shock: at the beginning of shock vasodilatation reactivity significantly decreased, followed by a slight increase from 0.5 h to 2 h after shock. After 2 h vasodilatation dropped again. Throughout this process, protein levels of HIF-1α gradually increased. In the late period of shock, vasodilatation reactivity was enhanced by oligomycin, an HIF-1α inhibitor, suggesting that HIF-1α may promote vasoconstriction. Moreover, in the late period of shock Cx40 levels gradually increased and exhibited a negative correlation with endothelium-dependent vasoconstriction reactivity. Furthermore, Cx40 AODN significantly improved vasoconstriction reactivity and could be regulated by either an HIF-1α inhibitor or an agonist. Together, these data suggest that HIF-1α may inhibit endothelium-dependent vasodilatation reactivity following hemorrhagic shock by up-regulating Cx40, especially in the late period of shock. PMID:28386353

Noncompressible Torso Hemorrhage: A Review with Contemporary Definitions and Management Strategies

DTIC Science & Technology

2012-01-01

Criteria 1. Thoracic cavity (including lung ) 2. Solid organ injury grade 4 (liver, kidney, spleen) Hemorrhagic shocka; or need for immediate operation 3...resuscitation and warming in the intensive care unit. DCS is an extreme surgical strategy that carries a risk of infection; intra-abdominal abscess ...depending on location. Injury to the periphery Noncompressible Torso Hemorrhage 849 of the lung can be stapled off in a nonanatomic fashion using a linear

The Effect of Hypothermia on Prolonged Distal Aortic Balloon Occlusion in a Porcine Model (Sus scrofa) of Hemorrhage

DTIC Science & Technology

2017-06-12

REBOA.Methods: 12 swine were anesthetized, instrumented, then underwent 15 blood volume hemorrhage. Animals were randomized to hypothermia or...normothermia followed by 4 hours of zone III REBOA, resuscitation with shed blood , and 3 hours of critical care. Physiologic parameters were continuously...significant differences between groups at baseline or after hemorrhage. No histologic differences were observed in hind limb skeletal muscle. Maximum

Causes of death after fluid bolus resuscitation: new insights from FEAST.

PubMed

Myburgh, John; Finfer, Simon

2013-03-14

The Fluid Expansion as Supportive Therapy (FEAST study) was an extremely well conducted study that gave unexpected results. The investigators had reported that febrile children with impaired perfusion treated in low-income countries without access to intensive care are more likely to die if they receive bolus resuscitation with albumin or saline compared with no bolus resuscitation at all. In a secondary analysis of the trial, published in BMC Medicine, the authors found that increased mortality was evident in patients who presented with clinical features of severe shock in isolation or in conjunction with features of respiratory or neurological failure. The cause of excess deaths was primarily refractory shock and not fluid overload. These features are consistent with a potential cardiotoxic or ischemia-reperfusion injury following resuscitation with boluses of intravenous fluid. Although these effects may have been amplified by the absence of invasive monitoring, mechanical ventilation or vasopressors, the results provide compelling insights into the effects of intravenous fluid resuscitation and potential adverse effects that extend beyond the initial resuscitation period. These data add to the increasing body of literature about the safety and efficacy of intravenous resuscitation fluids, which may be applicable to management of other populations of critically ill patients.

Evaluation of Prehospital Blood Products to Attenuate Acute Coagulopathy of Trauma in a Model of Severe Injury and Shock in Anesthetized Pigs

PubMed Central

Watts, Sarah; Nordmann, Giles; Brohi, Karim; Midwinter, Mark; Woolley, Tom; Gwyther, Robert; Wilson, Callie; Poon, Henrietta; Kirkman, Emrys

2015-01-01

ABSTRACT Acute trauma coagulopathy (ATC) is seen in 30% to 40% of severely injured casualties. Early use of blood products attenuates ATC, but the timing for optimal effect is unknown. Emergent clinical practice has started prehospital deployment of blood products (combined packed red blood cells and fresh frozen plasma [PRBCs:FFP], and alternatively PRBCs alone), but this is associated with significant logistical burden and some clinical risk. It is therefore imperative to establish whether prehospital use of blood products is likely to confer benefit. This study compared the potential impact of prehospital resuscitation with (PRBCs:FFP 1:1 ratio) versus PRBCs alone versus 0.9% saline (standard of care) in a model of severe injury. Twenty-four terminally anesthetised Large White pigs received controlled soft tissue injury and controlled hemorrhage (35% blood volume) followed by a 30-min shock phase. The animals were allocated randomly to one of three treatment groups during a 60-min prehospital evacuation phase: hypotensive resuscitation (target systolic arterial pressure 80 mmHg) using either 0.9% saline (group 1, n = 9), PRBCs:FFP (group 2, n = 9), or PRBCs alone (group 3, n = 6). Following this phase, an in-hospital phase involving resuscitation to a normotensive target (110 mmHg systolic arterial blood pressure) using PRBCs:FFP was performed in all groups. There was no mortality in any group. A coagulopathy developed in group 1 (significant increase in clot initiation and dynamics shown by TEG [thromboelastography] R and K times) that persisted for 60 to 90 min into the in-hospital phase. The coagulopathy was significantly attenuated in groups 2 and 3 (P = 0.025 R time and P = 0.035 K time), which were not significantly different from each other. Finally, the volumes of resuscitation fluid required was significantly greater in group 1 compared with groups 2 and 3 (P = 0.0067) (2.8 ± 0.3 vs. 1.9 ± 0.2 and 1.8 ± 0.3 L, respectively). This difference was principally due to a greater volume of saline used in group 1 (P = 0.001). Prehospital PRBCs:FFP or PRBCs alone may therefore attenuate ATC. Furthermore, the amount of crystalloid may be reduced with potential benefit of reducing the extravasation effect and later tissue edema. PMID:26177017

Polydatin Alleviates Small Intestine Injury during Hemorrhagic Shock as a SIRT1 Activator

PubMed Central

Zeng, Zhenhua; Chen, Zhongqing; Xu, Siqi; Song, Rui; Yang, Hong; Zhao, Ke-seng

2015-01-01

Objective. To evaluate the role of SIRT1 in small intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment. Research Design and Methods. The severe hemorrhagic shock model was reproduced in Sprague Dawley rats. Main Outcome Measures. Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection. Results. Bleeding and swelling appeared in the small intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1. Conclusions. The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small intestine injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment. PMID:26301045

Systemic and Microvascular Effects of Resuscitation with Blood Products After Severe Hemorrhage in Rats

DTIC Science & Technology

2014-01-01

thickness, blood flow, and microvascular permeability were studied using intravital microscopy. Hemodynamics and coagulation tests (rotational...Microcirculation; packed red blood cells; intravital microscopy; ROTEM; plasma proteins; rats. Current US military guidance for the resuscitation of warfighters...was used for coagulation assays (rotational thromboelast- ometry [ROTEM], TEM Innovations GmbH, Germany). Intravital Microscopy and Animal Preparation

[The influence of lactate Ringer solution versus hydroxyethyl starch on coagulation and fibrinolytic system in patients with septic shock].

PubMed

Lv, Jie; Zhao, Hui-ying; Liu, Fang; An, You-zhong

2012-01-01

To investigate the influence of lactate Ringer solution (RL) versus hydroxyethyl starch 130/0.4 (HES130/0.4) solution on coagulation and fibrinolytic system in the patients with septic shock. Forty-two consecutive patients with septic shock diagnosed between September 2009 and June 2011 were randomized to two study groups: RL resuscitation group (RL group) with 20 patients, and HES130/0.4 resuscitation group (HES group) with 22 patients. In all of them peripheral blood was collected at four points of time: before resuscitation, 6, 12, 24 hours after resuscitation, and then prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of plasma tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI) were determined. Meanwhile, the patients' outcome and the length of intensive care unit stay (ICU-LOS) were recorded. ICU-LOS (days) in HES group was significantly shorter than the RL group (12.5 ± 8.8 vs. 17.1 ± 16.6, P < 0.01). Meanwhile, the volume of fluid (L: 2.77 ± 0.59) as well as vasoactive drugs [μg×kg(-1)×min(-1): 0.56 ± 0.15] used in the HES group were significantly lower than RL group (3.46 ± 0.73, 0.81 ± 0.41, both P < 0.01). In RL group, 12 patients died and 8 patients survived, while in HES group, 7 patients died and 15 patients survived, showing no difference between two groups. PT, APTT and the levels of t-PA showed no significant differences between two groups at different time points, but the levels of plasma PAI (μg/L) of the HES group decreased gradually, and was significantly lower than that before resuscitation and RL group at 24 hours after resuscitation (41.76 ± 25.95 vs. 89.11 ± 14.27, 55.08 ± 35.43, both P < 0.05). Both RL and HES130/0.4 fluid resuscitation did not affect the outcome of the patients with septic shock, but the resuscitation efficiency of HES130/0.4 is much better than RL. Both type of fluids did not show the effect on coagulability of the septic patients, but colloid fluid resuscitation may protect the vascular endothelial cell, reduce the inhibition of fibrinolytic system, and alleviate hypercoagulability state of patients in early stage.

Extracorporeal cardiopulmonary resuscitation outcomes in term and premature neonates*.

PubMed

McMullan, David Michael; Thiagarajan, Ravi R; Smith, Kendra M; Rycus, Peter T; Brogan, Thomas V

2014-01-01

Extracorporeal cardiopulmonary resuscitation appears to improve survival in patients with acute refractory cardiopulmonary failure. This analysis was performed to determine survival outcomes and predictors of in-hospital mortality for term and preterm neonates who received extracorporeal cardiopulmonary resuscitation. Retrospective review of data from the Extracorporeal Life Support Organization international registry. Pediatric and neonatal ICUs. Infants less than or equal to 30 days. Extracorporeal cardiopulmonary resuscitation. Demographic, clinical, and survival data from patients who received extracorporeal cardiopulmonary resuscitation between 1998 and 2010 were analyzed to determine factors that affect in-hospital mortality. Overall survival to hospital discharge for the 641 neonates who received extracorporeal cardiopulmonary resuscitation was 39%. In univariate analysis, gestational age correlated inversely with stroke (odds ratio, 0.84 [95% CI, 0.75-0.95]; p = 0.006) and death (odds ratio, 0.87 [95% CI, 0.78-0.96]; p = 0.005) as did corrected gestational age (odds ratio, 0.89 [95% CI, 0.81-0.97]; p = 0.006) and birth weight (odds ratio, 0.53 [95% CI, 0.38-0.74]; p < 0.001). Dysrhythmia as the primary diagnosis had significantly lower odds of death than single-ventricle cardiac disease (odds ratio, 0.24 [95% CI, 0.06-0.95]; p = 0.04). Higher pre-extracorporeal cardiopulmonary resuscitation oxygenation decreased the odds of death (odds ratio, 0.996 [95% CI, 0.994-0.999]; p = 0.01), whereas complications occurring on extracorporeal life support increased the odds of death. In the multivariate analysis, lower birth weight and pre-extracorporeal cardiopulmonary resuscitation oxygenation, as well as complications including CNS hemorrhage, pulmonary hemorrhage, acidosis, renal replacement therapy, and mechanical complications, increased the odds of death. Overall survival for neonates receiving extracorporeal cardiopulmonary resuscitation is similar to older pediatric patients but decreases with lower gestational age and weight. Despite this, many low-birth weight neonates survive to hospital discharge.

The focused abdominal sonography for trauma examination can reliably identify patients with significant intra-abdominal hemorrhage in life-threatening pelvic fractures.

PubMed

Christian, Nicole Townsend; Burlew, Clay Cothren; Moore, Ernest E; Geddes, Andrea E; Wagenaar, Amy E; Fox, Charles J; Pieracci, Fredric M

2018-06-01

The focused abdominal sonography for trauma (FAST) examination has been reported to be unreliable in pelvic fracture patients. Additionally, given the advent of new therapeutic interventions, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), rapid identification of intra-abdominal hemorrhage compared with Zone III hemorrhage may guide different therapeutic strategies. We hypothesized that FAST is reliable for detecting clinically significant intra-abdominal hemorrhage in the face of complex pelvic fractures. Our pelvic fracture database of all hemodynamically unstable patients requiring intervention from January 1, 2005, to July 1, 2015, was reviewed. The FAST examination was compared with operative and computed tomography (CT) scan findings. Confirmatory evaluation for FAST(-) patients was considered positive if therapeutic intervention was required. During the study period, 81 patients in refractory shock with FAST imaging in our emergency department (ED) underwent pelvic packing. Mean age was 45 ± 2 years and Injury Severity Score was 50 ± 1.5. The FAST examination was negative in 53 patients; 52 patients did not require operative intervention for abdominal bleeding while one patient required splenectomy. The FAST examination was positive in 28 patients; 26 had findings confirmed by CT or laparotomy while two patients did not have intra-abdominal hemorrhage on further evaluation. The sensitivity and specificity for FAST in this population was 96% and 96%, respectively, positive predictive value was 93%, and negative predictive value was 98%. The false-negative and -positive rates for FAST were 2% and 7%. Focused abdominal sonography for trauma examination reliably identifies clinically significant hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The incidence of a false-negative FAST in this unstable pelvic fracture population was 2%. FAST results may be used when determining the role of REBOA in these multisystem trauma patients and requires further study. REBOA placement should be considered in hemodynamically unstable pelvic fracture patients who are FAST(-), while laparotomy should be used in FAST(+) patients. Therapeutic, level IV.

Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating inferior vena cava injury in coagulopathic swine.

PubMed

Koko, Kiavash R; McCauley, Brian M; Gaughan, John P; Nolan, Ryan S; Fromer, Marc W; Hagaman, Ashleigh L R; Choron, Rachel L; Brown, Spencer A; Hazelton, Joshua P

2017-07-01

Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone. Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant. There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05). These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model. This is basic science research based on a large animal model, level V.

Prevention of Hypovolemic Circulatory Collapse by IL-6 Activated Stat3

PubMed Central

Tsimelzon, Anna I.; Mastrangelo, Mary-Ann A.; Hilsenbeck, Susan G.; Poli, Valeria; Tweardy, David J.

2008-01-01

Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT) 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3β, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients. PMID:18270592

Fixed-energy biphasic waveform defibrillation in a pediatric model of cardiac arrest and resuscitation.

PubMed

Tang, Wanchun; Weil, Max Harry; Jorgenson, Dawn; Klouche, Kada; Morgan, Carl; Yu, Ting; Sun, Shijie; Snyder, David

2002-12-01

For adults, 150-J fixed-energy, impedance-compensating biphasic truncated exponential (ICBTE) shocks are now effectively used in automated defibrillators. However, the high energy levels delivered by adult automated defibrillators preclude their use for pediatric patients. Accordingly, we investigated a method by which adult automated defibrillators may be adapted to deliver a 50-J ICBTE shock for pediatric defibrillation. Prospective, randomized study. A university-affiliated research institution. Domestic piglets. We initially investigated four groups of anesthetized mechanically ventilated piglets weighing 3.8, 7.5, 15, and 25 kg. Ventricular fibrillation was induced with an AC current delivered to the right ventricular endocardium. After 7 mins of untreated ventricular fibrillation, a conventional manual defibrillator was used to deliver up to three 50-J ICBTE shocks. If ventricular fibrillation was not reversed, a 1-min interval of precordial compression preceded a second sequence of up to three shocks. The protocol was repeated until spontaneous circulation was restored, or for a total of 15 mins. In a second set of experiments, we evaluated a 150-J biphasic adult automated defibrillator that was operated in conjunction with energy-reducing electrodes such as to deliver 50-J shocks. The same resuscitation protocol was then exercised on piglets weighing 3.7, 13.5, and 24.2 kg. All animals were successfully resuscitated. Postresuscitation hemodynamic and myocardial function quickly returned to baseline values in both experimental groups, and all animals survived. An adaptation of a 150-J biphasic adult automated defibrillator in which energy-reducing electrodes delivered 50-J shocks successfully resuscitated animals ranging from 3.7 to 25 kg without compromise of postresuscitation myocardial function or survival.

Investigation of Intravenous Hydroxocobalamin Compared to Hextend for Resuscitation in a Swine Model of Uncontrolled Hemorrhagic Shock: A Preliminary Report

DTIC Science & Technology

2017-06-16

Iy Dlrec~ b. Is not ~j’lnll I’cr ~pport. res, ~ es or otollr~phs for pu -.. 2. Pilnt your ~me, r~nk;;. l ~Ge. sllln dll~ tt. ’brm In tt.e ~utho(s block...or e eledronl: slgnal1Jre. :> ..••• 1t21 a COP)’of the S9 [e.O.=e report, QA’ DWIR:E> IAC\\JC sl1JGY,progr ev~1 ~ the r8~arch ~ l ". ed l .1udy. If this...a ~chnl~1 U! l caU:,"!IJ~SCI’l~3I1on,~e the ~pe rn~DtlTllI.llon report. eft< , etc.) In the "P~co Tltee" t: x. 4 ..•••1tll a copy of your b’WIlc1

The Noninvasive Carbon Dioxide Gradient (NICO2G) during Hemorrhagic Shock

DTIC Science & Technology

2014-07-01

as well as a tPCO2- PaCO2 gap more than 16 mmHg were reported to be associated with poor outcomes in patients with septic shock (18). Previously, our...shortcomings, which include the need for frequent calibration with a tank of standardized cali- bration gas (24), relative bulk, need for a heated sensor, and...hemorrhagic, septic , and cardiogenic shock (27). Van der Linden et al. (28) demonstrated a venous-arterial gradient for PCO2 in hemorrhaged dogs. There was

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

PubMed

Moreno, Daniel H; Cacione, Daniel G; Baptista-Silva, Jose C C

2016-05-13

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mm Hg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 to 100 mm Hg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (April 2016) and the Cochrane Register of Studies (CENTRAL (2016, Issue 3)). Clinical trials databases were searched (April 2016) for details of ongoing or unpublished studies. We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms. Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions. We identified no RCTs that met the inclusion criteria. We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured abdominal aortic aneurysm.

PubMed

Moreno, Daniel H; Cacione, Daniel G; Baptista-Silva, Jose Cc

2018-06-13

An abdominal aortic aneurysm (AAA) is the pathological enlargement of the aorta and can develop in both men and women. Progressive aneurysm enlargement can lead to rupture. The rupture of an AAA is frequently fatal and accounts for the death from haemorrhagic shock of at least 45 people per 100,000 population. The outcome of people with ruptured AAA varies among countries and healthcare systems, with mortality ranging from 53% to 90%. Definitive treatment for ruptured AAA includes open surgery or endovascular repair. The management of haemorrhagic shock is crucial for the person's outcome and aims to restore organ perfusion and systolic blood pressure above 100 mmHg through immediate and aggressive fluid replacement. This rapid fluid replacement is known as the normotensive resuscitation strategy. However, evidence suggests that infusing large volumes of cold fluid causes dilutional and hypothermic coagulopathy. The association of these factors may exacerbate bleeding, resulting in a 'lethal triad' of hypothermia, acidaemia, and coagulopathy. An alternative to the normotensive resuscitation strategy is the controlled (permissive) hypotension resuscitation strategy, with a target systolic blood pressure of 50 mmHg to 100 mmHg. The principle of controlled or hypotensive resuscitation has been used in some management protocols for endovascular repair of ruptured AAA. It may be beneficial in preventing blood loss by avoiding the clot disruption caused by the rapid increase in systolic blood pressure; avoiding dilution of clotting factors, platelets and fibrinogen; and by avoiding the temperature decrease that inhibits enzyme activity involved in platelet and clotting factor function. This is an update of a review first published in 2016. To compare the effects of controlled (permissive) hypotension resuscitation and normotensive resuscitation strategies for people with ruptured AAA. The Cochrane Vascular Information Specialist searched the Specialised Register (August 2017), the Cochrane Register of Studies (CENTRAL (2017, Issue 7)) and EMBASE (August 2017). The Cochrane Vascular Information Specialist also searched clinical trials databases (August 2017) for details of ongoing or unpublished studies. We sought all published and unpublished randomised controlled trial (RCTs) that compared controlled hypotension and normotensive resuscitation strategies for the management of shock in patients with ruptured abdominal aortic aneurysms. Two review authors independently assessed identified studies for potential inclusion in the review. We used standard methodological procedures in accordance with the Cochrane Handbook for Systematic Review of Interventions. We identified no RCTs that met the inclusion criteria. We found no RCTs that compared controlled hypotension and normotensive resuscitation strategies in the management of haemorrhagic shock in patients with ruptured abdominal aortic aneurysm that assessed mortality, presence of coagulopathy, intensive care unit length of stay, and the presence of myocardial infarct and renal failure. High quality studies that evaluate the best strategy for managing haemorrhagic shock in ruptured abdominal aortic aneurysms are required.

Prognostic value of relative adrenal insufficiency after out-of-hospital cardiac arrest.

PubMed

Pene, Frédéric; Hyvernat, Hervé; Mallet, Vincent; Cariou, Alain; Carli, Pierre; Spaulding, Christian; Dugue, Marie-Annick; Mira, Jean-Paul

2005-05-01

To assess the prevalence of relative adrenal insufficiency in patients successfully resuscitated after cardiac arrest, and its prognostic role in post-resuscitation disease. A prospective observational single-center study in a medical intensive care unit. 64 patients hospitalised in the intensive care unit after successful resuscitation for out-of-hospital cardiac arrest. A corticotropin-stimulation test was performed between 12 and 24 h following admission: serum cortisol level was measured before and 60 min after administration of tetracosactide 250 microg. Patients with an incremental response less than 9 microg/dl were considered to have relative adrenal insufficiency (non-responders). Variables were expressed as medians and interquartile ranges. 33 patients (52%) had relative adrenal insufficiency. Baseline cortisol level was higher in non-responders than in responders (41 [27.2-55.5] vs. 22.8 [15.7-35.1] microg/dl respectively, P=0.001). A long interval before initiation of cardiopulmonary resuscitation was associated with relative adrenal insufficiency (5 [3-10] vs. 3 [3-5] min, P=0.03). Of the 38 patients with post-resuscitation shock, 13 died of irreversible multiorgan failure. The presence of relative adrenal insufficiency was identified as a poor prognostic factor of shock-related mortality (log-rank P=0.02). A trend towards higher mortality in non-responders was identified in a multivariate logistic regression analysis (odds ratio 6.77, CI 95% 0.94-48.99, P=0.058). Relative adrenal insufficiency occurs frequently after successful resuscitation of out-of-hospital cardiac arrest, and appears to be associated with a poor prognosis in cases of post-resuscitation shock. The role of corticosteroid supplementation should be evaluated in this setting.

Noninvasive optical cytochrome c oxidase redox state measurements using diffuse optical spectroscopy

PubMed Central

Lee, Jangwoen; Kim, Jae G.; Mahon, Sari B.; Mukai, David; Yoon, David; Boss, Gerry R.; Patterson, Steven E.; Rockwood, Gary; Isom, Gary; Brenner, Matthew

2014-01-01

Abstract. A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166  mg/min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes. PMID:24788369

Noninvasive optical cytochrome c oxidase redox state measurements using diffuse optical spectroscopy

NASA Astrophysics Data System (ADS)

Lee, Jangwoen; Kim, Jae G.; Mahon, Sari B.; Mukai, David; Yoon, David; Boss, Gerry R.; Patterson, Steven E.; Rockwood, Gary; Isom, Gary; Brenner, Matthew

2014-05-01

A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166 mg/min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes.

In vivo analysis of intestinal permeability following hemorrhagic shock

PubMed Central

Alsaigh, Tom; Chang, Marisol; Richter, Michael; Mazor, Rafi; Kistler, Erik B

2015-01-01

AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate (FITC)-labeled dextrans 20, to semi-quantitatively verify the ability of bowel-derived low-molecular weight molecules (< 20 kD) to access the central circulation. RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage (1.11 ± 0.19 vs 0.86 ± 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls (1.2 ± 0.18 vs 0.97 ± 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 ± 6.52 vs 3.38 ± 1.11 fluorescent intensity units (× 105, P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability. CONCLUSION: Increased small bowel permeability in hemorrhagic shock may allow for systemic absorption of otherwise retained proteolytically-generated peptides, with consequent hemodynamic instability and remote organ failure. PMID:26557479

Myocardial Dysfunction and Shock after Cardiac Arrest

PubMed Central

Jentzer, Jacob C.; Chonde, Meshe D.; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies. PMID:26421284

Myocardial Dysfunction and Shock after Cardiac Arrest.

PubMed

Jentzer, Jacob C; Chonde, Meshe D; Dezfulian, Cameron

2015-01-01

Postarrest myocardial dysfunction includes the development of low cardiac output or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired left ventricular systolic function is reported in nearly two-thirds of patients resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor support are similarly common after cardiac arrest. Whereas shock requiring vasopressor support is consistently associated with an adverse outcome after cardiac arrest, the association between myocardial dysfunction and outcomes is less clear. Myocardial dysfunction and shock after cardiac arrest develop as the result of preexisting cardiac pathology with multiple superimposed insults from resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion injury and cardiovascular toxicity from excessive levels of inflammatory cytokine activation and catecholamines, among other contributing factors. Similar mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after resuscitation from cardiac arrest involves restoration of preload, vasopressors to support arterial pressure, and inotropic support if needed to reverse the effects of myocardial dysfunction and improve systemic perfusion. Further research is needed to define the role of postarrest myocardial dysfunction on cardiac arrest outcomes and identify therapeutic strategies.

Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

PubMed

Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Chi-Hsun; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

2007-10-01

Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estradiol (E2) prevents organ damage following trauma-hemorrhage, it remains unknown whether Akt/HO-1 plays any role in E2-mediated attenuation of hepatic injury following trauma-hemorrhage. To study this, male rats underwent trauma-hemorrhage (mean blood pressure, approximately 40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI-3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma-hemorrhage, plasma alpha-GST and hepatic tissue myeloperoxidase (MPO) activity, IL-6, TNF-alpha, ICAM-1, cytokine-induced neutrophil chemoattractant-1, and MIP-2 levels were measured. Hepatic Akt and HO-1 protein levels were also determined. Trauma-hemorrhage increased hepatic injury markers (alpha-GST and MPO activity), cytokines, ICAM-1, and chemokine levels. These parameters were markedly improved in the E2-treated rats following trauma-hemorrhage. E2 treatment also increased hepatic Akt activation and HO-1 expression compared with vehicle-treated, trauma-hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma-hemorrhage are in part mediated via an ER-related, Akt-dependent up-regulation of HO-1.

Embolization of Rectal Arteries: An Alternative Treatment for Hemorrhagic Shock Induced by Traumatic Intrarectal Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pichon, Nicolas, E-mail: nicolas.pichon@unilim.fr, E-mail: nicolas.pichon@chu-limoges.fr; Francois, Bruno; Pichon-Lefievre, Florence

2005-05-15

Rectal injuries caused by foreign bodies or iatrogenic insertions may lead to severe complications whose therapeutic management remains controversial. At times, both the rapid identification and treatment of subsequent active rectal bleeding may be challenging, especially when endoscopy fails to locate and control the arterial hemorrhage. We present the first two successful cases of middle rectal artery embolization in patients presenting with sustained bleeding and hemorrhagic shock.

Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock.

PubMed

Taylor, Stephanie Parks; Karvetski, Colleen H; Templin, Megan A; Heffner, Alan C; Taylor, Brice T

2018-02-01

The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups. Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016. 1293 (31.3%) patients were obese (BMI≥30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3h than did patients with lower BMI (p≤0.001). In obese patients, fluid given at 3h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]). Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research. Copyright © 2017 Elsevier Inc. All rights reserved.

Causes of death after fluid bolus resuscitation: new insights from FEAST

PubMed Central

2013-01-01

The Fluid Expansion as Supportive Therapy (FEAST study) was an extremely well conducted study that gave unexpected results. The investigators had reported that febrile children with impaired perfusion treated in low-income countries without access to intensive care are more likely to die if they receive bolus resuscitation with albumin or saline compared with no bolus resuscitation at all. In a secondary analysis of the trial, published in BMC Medicine, the authors found that increased mortality was evident in patients who presented with clinical features of severe shock in isolation or in conjunction with features of respiratory or neurological failure. The cause of excess deaths was primarily refractory shock and not fluid overload. These features are consistent with a potential cardiotoxic or ischemia-reperfusion injury following resuscitation with boluses of intravenous fluid. Although these effects may have been amplified by the absence of invasive monitoring, mechanical ventilation or vasopressors, the results provide compelling insights into the effects of intravenous fluid resuscitation and potential adverse effects that extend beyond the initial resuscitation period. These data add to the increasing body of literature about the safety and efficacy of intravenous resuscitation fluids, which may be applicable to management of other populations of critically ill patients. PMID:23497460

The AED in resuscitation: it's not just about the shock.

PubMed

Page, Richard L

2011-01-01

The automated external defibrillator (AED), in combination with effective cardiopulmonary resuscitation (CPR), is a critical part of the American Heart Association's "Chain of survival." Newer guidelines have simplified resuscitation and emphasized the importance of CPR in providing rapid and deep compressions with minimal interruptions; in fact, CPR should resume immediately after the shock given by the AED, without the delay entailed in checking for pulse or rhythm conversion. Our experience with the AED aboard aircraft, showing 40% long-term survival with the AED in ventricular fibrillation, demonstrated the safety and efficacy of the device. Despite this and other reports of successful AED deployment, AEDs are not yet available at all public locations. Prospective research, as undertaken by the Resuscitation Outcomes Consortium, will be the key to future refinements of the guidelines and enhanced survival with use of the AED in sudden cardiac arrest.

Defining Dogma: Quantifying Crystalloid Hemodilution in a Prospective Randomized Control Trial with Blood Donation as a Model for Hemorrhage.

PubMed

Ross, Samuel Wade; Christmas, A Britton; Fischer, Peter E; Holway, Haley; Seymour, Rachel; Huntington, Ciara R; Heniford, B Todd; Sing, Ronald F

2018-06-04

The concept of hemodilution after blood loss and crystalloid infusion is a surgical maxim that remains unproven in humans. We sought to quantify the effect of hemodilution after crystalloid administration in voluntary blood donors as a model for acute hemorrhage. A prospective, randomized control trial was conducted in conjunction with community blood drives. Donors were randomized to receive no IV fluid(noIVF), two liters normal saline(NS), or two liters lactated ringers(LR) after blood donation. Blood samples were taken before donation of 500 mL of blood, immediately after donation, and following IV fluid administration. Hemoglobin(Hgb) was measured at each time point. Hgb between time points were compared between groups using standard statistical tests and the Bonferroni correction for multiple comparisons. Statistical significance was set at p≤0.0167. Of 165 patients consented, 157 patients completed the study. Average pre-donation Hgb was 14.3 g/dL. There was no difference in the mean Hgb levels after blood donation between the three groups(p>0.05). Compared to the control group, there was a significant drop in Hgb in the crystalloid infused groups from the post-donation level to post-resuscitation(13.2 vs 12.1 vs 12.2 g/dL, p<0.0001). A formula was created to predict hemoglobin levels from a given estimated blood loss(EBL) and volume replacement(VR): Hemodilution Hgb=(MeanPre-donation Hgb - hemorrhage Hgb drop - equilibration hemoglobin drop - resuscitation Hgb drop)=MeanPre-donation Hgb - [(EBL/TBV)*l] - [(EBL/TBV)*h] - [(VR/TBV)*r], l = 5.111g/dL = blood loss coefficient, h=6.722 g/dL=equilibration coefficient, r= 2.617g/dL= resuscitation coefficient. This study proves the concept of hemodilution and derived a mathematical relationship between blood loss and resuscitation. This data may help to estimate response of hemoglobin levels to blood loss and fluid resuscitation in clinical practice. Copyright © 2018. Published by Elsevier Inc.

Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy.

PubMed

Malbrain, Manu L N G; Van Regenmortel, Niels; Saugel, Bernd; De Tavernier, Brecht; Van Gaal, Pieter-Jan; Joannes-Boyau, Olivier; Teboul, Jean-Louis; Rice, Todd W; Mythen, Monty; Monnet, Xavier

2018-05-22

In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.

Pelvic fracture in multiple trauma: A 67-case series.

PubMed

Caillot, M; Hammad, E; Le Baron, M; Villes, V; Leone, M; Flecher, X

2016-12-01

Severe pelvic trauma remains associated with elevated mortality, largely due to hemorrhagic shock. The main study objective was to test for correlation between fracture type and mortality. The secondary objective was to assess the efficacy in terms of mortality of multidisciplinary management following a decision-tree in multiple trauma victims admitted to a level 1 trauma center. Between July 2011 and July 2013, 534 severe trauma patients were included in a single-center continuous prospective observational study. All patients with hemorrhagic shock received early treatment by pelvic binder. Patients with active bleeding on full-body CT or persisting hemorrhagic shock underwent arteriography with or without embolization. Pelvic trauma was graded on the Tile classification. The principle end-point was mortality. Median age was 40 years (range, 26-48 years), with a 79% male/female sex ratio. Thirty-two of the 67 patients with pelvic trauma (48%) were in hemorrhagic shock at admission. Median injury severity score (ISS) was 36 (range, 24-43). On the Tile classification, 22 patients (33%) were grade A, 33 (49%) grade B and 12 (18%) grade C. Overall mortality was 19%, and 42% in case of hemorrhagic shock. Mortality was significantly higher with Tile C than A or B (58% vs. 9.1% and 12.1%, respectively; P=0.001). Vertical shear fracture (Tile C) was associated with greater mortality from hemorrhagic shock. IV, case series. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

4-Phenylbutyrate Benefits Traumatic Hemorrhagic Shock in Rats by Attenuating Oxidative Stress, Not by Attenuating Endoplasmic Reticulum Stress.

PubMed

Yang, Guangming; Peng, Xiaoyong; Hu, Yi; Lan, Dan; Wu, Yue; Li, Tao; Liu, Liangming

2016-07-01

Vascular dysfunction such as vascular hyporeactivity following severe trauma and shock is a major cause of death in injured patients. Oxidative stress and endoplasmic reticulum stress play an important role in vascular dysfunction. The objective of the present study was to determine whether or not 4-phenylbutyrate can improve vascular dysfunction and elicit antishock effects by inhibiting oxidative and endoplasmic reticulum stress. Prospective, randomized, controlled laboratory experiment. State key laboratory of trauma, burns, and combined injury. Five hundred and fifty-two Sprague-Dawley rats. Rats were anesthetized, and a model of traumatic hemorrhagic shock was established by left femur fracture and hemorrhage. The effects of 4-phenylbutyrate (5, 20, 50, 100, 200, and 300 mg/kg) on vascular reactivity, animal survival, hemodynamics, and vital organ function in traumatic hemorrhagic shock rats and cultured vascular smooth muscle cells, and the relationship to oxidative stress and endoplasmic reticulum stress was observed. Lower doses of 4-phenylbutyrate significantly improved the vascular function, stabilized the hemodynamics, and increased the tissue blood flow and vital organ function in traumatic hemorrhagic shock rats, and markedly improved the survival outcomes. Among all dosages observed in the present study, 20 mg/kg of 4-phenylbutyrate had the best effect. Further results indicated that 4-phenylbutyrate significantly inhibited the oxidative stress, decreased shock-induced oxidative stress index such as the production of reactive oxygen species, increased the antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione, and improved the mitochondrial function by inhibiting the opening of the mitochondrial permeability transition pore in rat artery and vascular smooth muscle cells. In contrast, 4-phenylbutyrate did not affect the changes of endoplasmic reticulum stress markers following traumatic hemorrhagic shock. Furthermore, 4-phenylbutyrate increased the nuclear levels of nuclear factor-E2-related factor 2, and decreased the nuclear levels of nuclear factor κB in hypoxic vascular smooth muscle cells. 4-phenylbutyrate has beneficial effects for traumatic hemorrhagic shock including improving animal survival and protecting organ function. These beneficial effects of 4-phenylbutyrate in traumatic hemorrhagic shock result from its vascular function protection via attenuation of the oxidative stress and mitochondrial permeability transition pore opening. Nuclear factor-E2-related factor 2 and nuclear factor-κB may be involved in 4-phenylbutyrate-mediated inhibition of oxidative stress.

Alterations of Mg2+ After Hemorrhagic Shock.

PubMed

Lee, Mun-Young; Yang, Dong Kwon; Kim, Shang-Jin

2017-11-01

Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg 2+ levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg 2+ as the physiologically active form. The aim of this study was to determine changes in blood Mg 2+ and tMg after hemorrhage in rats identifying mechanism and origin of the changes in blood Mg 2+ . Hemorrhagic shock produced significant increases in blood Mg 2+ , plasma tMg, Na + , K + , Cl - , anion gap, partial pressures of oxygen, glucose, and blood urea nitrogen but significant decreases in RBC tMg, blood Ca 2+ , HCO 3 - , pH, partial pressures of carbon dioxide, hematocrit, hemoglobin, total cholesterol, and plasma/RBC ATP. During hemorrhagic shock, K + , anion gap, and BUN showed significant positive correlations with changes in blood Mg 2+ level, while Ca 2+ , pH, and T-CHO correlated to Mg 2+ in a negative manner. In conclusion, hemorrhagic shock induced an increase in both blood-free Mg 2+ and tMg, resulted from Mg 2+ efflux from metabolic damaged cell with acidosis and ATP depletion.

STUDIES IN RESUSCITATION: I. THE GENERAL CONDITIONS AFFECTING RESUSCITATION, AND THE RESUSCITATION OF THE BLOOD AND OF THE HEART

PubMed Central

Pike, F. H.; Guthrie, C. C.; Stewart, G. N.

1908-01-01

Our results may be briefly summarized: 1. Blood, when defibrinated, soon loses its power to maintain the activity of the higher nervous centers, and its nutritive properties for all tissues quickly diminish. 2. Artificial fluids, as a substitute for blood, are not satisfactory. 3. The proper oxygenation of the blood is an indispensable adjunct in the resuscitation of an animal. 4. The heart usually continues to beat for some minutes after it ceases to affect a mercury manometer, and resuscitation of it within this period by extra-thoracic massage and artificial respiration is sometimes successful. 5. Resuscitation of the heart by direct massage is the most certain method at our command. 6. A proper blood-pressure is an indispensable condition for the continued normal activity of the heart. 7. Anæsthetics, hemorrhage and induced currents applied to the heart render resuscitation more difficult than asphyxia alone. PMID:19867138

[Beneficial effect of thyrotropin-releasing hormone in combination with HSD on hemorrhagic shock with pulmonary edema at high altitude in the rat].

PubMed

Hu, De-yao; Liu, Liang-ming; Li, Ping; Liu, Jian-cang; Liu, Hou-dong; He, Yan-mei; Huo, Xiao-ping; Tian, Kun-lun; Shi, Quan-gui; Xiao, Nan; Zhou, Xue-wu

2003-05-01

To study the effects of thyrotropin-releasing hormone (TRH) in combination with hypertonic saline/dextran (7.5% NaCl + 6% Dextran 40, HSD ) on hemorrhagic shock with pulmonary edema in the rats which were recently brought to high altitude. Forty-nine SD rats, transported to Lasa, Tibet, which was 3,760 meters above the sea level, were anesthetized one week later with sodium pentobarbital (30 mg/kg, intraperitoneal). Hemorrhagic shock with pulmonary edema was induced by hemorrhage (50 mm Hg maintained for 1 hour,1 mm Hg=0.133 kPa) plus intravenous injection of oleic acid (50 microl/kg). They were equally divided into seven groups (n=7): normal control, hemorrhagic shock, hemorrhagic shock with pulmonary edema (HSPE), HSPE plus TRH (5 mg/kg), HSPE plus HSD (4 ml/kg), and HEPE plus TRH and HSD in combination. Hemodynamic parameters including mean arterial blood pressure(MAP), left intraventricular systolic pressure (LVSP) and the maximal change rate of intraventricular pressure rise or decline (+/- dp/dt max) were observed at 15, 30, 60 and 120 minutes, blood gases were analyzed at 30 and 120 minutes, and the water content of lung and brain was determined at 120 minutes after drug administration. TRH or HSD used alone or in combination significantly increased MAP, LVSP and +/- dp/dt max (P<0.05 or P<0.01 ), ameliorated acid-base imbalance, and decreased the water content of lung and brain. The effect of the two in combination was superior to either drug used alone. TRH in combination with HSD can be used in the treatment of hemorrhagic shock with pulmonary edema at high altitude.

Is Survival Time After Hemorrhage a Heritable, Quantitative Trait?: An Initial Assessment

DTIC Science & Technology

2008-06-01

The epidemiology of traumatic death. A population-based analysis. Arch Surg 128:571Y575, 1993. 5. Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R...therapeutic goals and early warning of death. Arch Surg 106:630Y636, 1973. 752 SHOCK VOL. 29, NO. 6 KLEMCKE ET AL. Copyright @ 200 by the Shock...Hemorrhagic shock in rats. Measured blood volumes as the basis for the extent of hemorrhage. Arch Surg 99:484Y488, 1969. 19. Nose H, Morita M, Yawata T

Time- and fluid-sensitive resuscitation for hemodynamic support of children in septic shock: barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support Guidelines in a pediatric intensive care unit in a developing world.

PubMed

Oliveira, Cláudio F; Nogueira de Sá, Flávio R; Oliveira, Débora S F; Gottschald, Adriana F C; Moura, Juliana D G; Shibata, Audrey R O; Troster, Eduardo J; Vaz, Flávio A C; Carcillo, Joseph A

2008-12-01

To analyze mortality rates of children with severe sepsis and septic shock in relation to time-sensitive fluid resuscitation and treatments received and to define barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support guidelines in a pediatric intensive care unit in a developing country. Retrospective chart review and prospective analysis of septic shock treatment in a pediatric intensive care unit of a tertiary care teaching hospital. Ninety patients with severe sepsis or septic shock admitted between July 2002 and June 2003 were included in this study. Of the 90 patients, 83% had septic shock and 17% had severe sepsis; 80 patients had preexisting severe chronic diseases. Patients with septic shock who received less than a 20-mL/kg dose of resuscitation fluid in the first hour of treatment had a mortality rate of 73%, whereas patients who received more than a 40-mL/kg dose in the first hour of treatment had a mortality rate of 33% (P < 0.05). Patients treated less than 30 minutes after diagnosis of severe sepsis and septic shock had a significantly lower mortality rate (40%) than patients treated more than 60 minutes after diagnosis (P < 0.05). Controlling for the risk of mortality, early fluid resuscitation was associated with a 3-fold reduction in the odds of death (odds ratio, 0.33; 95% confidence interval, 0.13-0.85). The most important barriers to achieve adequate severe sepsis and septic shock treatment were lack of adequate vascular access, lack of recognition of early shock, shortage of health care providers, and nonuse of goals and treatment protocols. The mortality rate was higher for children older than 2 years, for those who received less than 40 mL/kg in the first hour, and for those whose treatment was not initiated in the first 30 minutes after the diagnosis of septic shock. The acknowledgment of existing barriers to a timely fluid administration and the establishment of objectives to overcome these barriers may lead to a more successful implementation of the American College of Critical Care Medicine guidelines and reduced mortality rates for children with septic shock in the developing world.

Use of artificial intelligence to identify cardiovascular compromise in a model of hemorrhagic shock.

PubMed

Glass, Todd F; Knapp, Jason; Amburn, Philip; Clay, Bruce A; Kabrisky, Matt; Rogers, Steven K; Garcia, Victor F

2004-02-01

To determine whether a prototype artificial intelligence system can identify volume of hemorrhage in a porcine model of controlled hemorrhagic shock. Prospective in vivo animal model of hemorrhagic shock. Research foundation animal surgical suite; computer laboratories of collaborating industry partner. Nineteen, juvenile, 25- to 35-kg, male and female swine. Anesthetized animals were instrumented for arterial and systemic venous pressure monitoring and blood sampling, and a splenectomy was performed. Following a 1-hr stabilization period, animals were hemorrhaged in aliquots to 10, 20, 30, 35, 40, 45, and 50% of total blood volume with a 10-min recovery between each aliquot. Data were downloaded directly from a commercial monitoring system into a proprietary PC-based software package for analysis. Arterial and venous blood gas values, glucose, and cardiac output were collected at specified intervals. Electrocardiogram, electroencephalogram, mixed venous oxygen saturation, temperature (core and blood), mean arterial pressure, pulmonary artery pressure, central venous pressure, pulse oximetry, and end-tidal CO(2) were continuously monitored and downloaded. Seventeen of 19 animals (89%) died as a direct result of hemorrhage. Stored data streams were analyzed by the prototype artificial intelligence system. For this project, the artificial intelligence system identified and compared three electrocardiographic features (R-R interval, QRS amplitude, and R-S interval) from each of nine unknown samples of the QRS complex. We found that the artificial intelligence system, trained on only three electrocardiographic features, identified hemorrhage volume with an average accuracy of 91% (95% confidence interval, 84-96%). These experiments demonstrate that an artificial intelligence system, based solely on the analysis of QRS amplitude, R-R interval, and R-S interval of an electrocardiogram, is able to accurately identify hemorrhage volume in a porcine model of lethal hemorrhagic shock. We suggest that this technology may represent a noninvasive means of assessing the physiologic state during and immediately following hemorrhage. Point of care application of this technology may improve outcomes with earlier diagnosis and better titration of therapy of shock.

Acute Hemorrhage into Adrenal Pseudocyst Presenting with Shock: Diagnostic Dilemmas — Report of Three Cases and Review of Literature

PubMed Central

Sivasankar, Amarapathy; Jeswanth, Sathyanesan; Johnson, Maria Antony; Ravichandran, Palaniappan; Rajendran, Shanmugasundaram; Kannan, Devy Gounder; Surendran, Rajagopal

2006-01-01

We report three cases of acutely bleeding adrenal pseudocysts presenting as hemorrhagic shock. Pregnancy was associated in two cases. The diagnostic dilemmas are discussed with special reference to their unusual presentations, diagnosis, and treatment. We believe that our cases, complicated by intracystic hemorrhage, may be related to pregnancy. PMID:17619705

Interleukin-6 infusion blunts proinflammatory cytokine production without causing systematic toxicity in a swine model of uncontrolled hemorrhagic shock.

PubMed

Brundage, Susan I; Zautke, N A; Holcomb, J B; Spain, D A; Lam, J C; Mastrangelo, M A; Macaitis, J M; Tweardy, D J

2004-11-01

Serum elevations of interleukin-6 (IL-6) correlate with multiple organ dysfunction syndrome and mortality in critically injured trauma patients. Data from rodent models of controlled hemorrhage suggest that recombinant IL-6 (rIL-6) infusion protects tissue at risk for ischemia-reperfusion injury. Exogenous rIL-6 administered during shock appears to abrogate inflammation, providing a protective rather than a deleterious influence. In an examination of this paradox, the current study aimed to determine whether rIL-6 decreases inflammation in a clinically relevant large animal model of uncontrolled hemorrhagic shock, (UHS), and to investigate the mechanism of protection. Swine were randomized to four groups (8 animals in each): (1) sacrifice, (2) sham (splenectomy followed by hemodilution and cooling to 33 degrees C), (3) rIL-6 infusion (sham plus UHS using grade 5 liver injury with packing and resuscitation plus blinded infusion of rIL-6 [10 mcg/kg]), and (4) placebo (UHS plus blinded vehicle). After 4 hours, blood was sampled, estimated blood loss determined, animals sacrificed, and lung harvested for RNA isolation. Quantitative reverse transcriptase-polymerase chain reaction was used to assess granulocyte colony-stimulating factor (G-CSF), IL-6, and tumor necrosis factor-alpha (TNFalpha) messenger ribonucleic acid (mRNA) levels. Serum levels of IL-6 and TNFalpha were measured by enzyme-linked immunoassay (ELISA). As compared with placebo, IL-6 infusion in UHS did not increase estimated blood loss or white blood cell counts, nor decrease hematocrit or platelet levels. As compared with the sham condition, lung G-CSF mRNA production in UHS plus placebo increased eightfold (*p < 0.05). In contrast, rIL-6 infusion plus UHS blunted G-CSF mRNA levels, which were not significantly higher than sham levels (p = 0.1). Infusion of rIL-6 did not significantly affect endogenous production of either lung IL-6 or mRNA. As determined by ELISA, rIL-6 infusion did not increase final serum levels of IL-6 or TNFalpha over those of sham and placebo conditions. Exogenous rIL-6 blunts lung mRNA levels of the proinflammatory cytokine G-CSF. The administration of rIL-6 does not increase the local expression of IL-6 nor TNFalpha mRNA in the lung. Additionally, rIL-6 infusion does not appear to cause systemic toxicity.

Acute transfusion-related abdominal injury in trauma patients: a case report.

PubMed

Michel, P; Wähnert, D; Freistühler, M; Laukoetter, M G; Rehberg, S; Raschke, M J; Garcia, P

2016-10-19

Secondary abdominal compartment syndrome is well known as a life-threatening complication in critically ill patients in an intensive care unit. Massive crystalloid fluid resuscitation has been identified as the most important risk factor. The time interval from hospital admittance to the development of manifest abdominal compartment syndrome is usually greater than 24 hours. In the absence of any direct abdominal trauma, we observed a rapidly evolving secondary abdominal compartment syndrome shortly after hospital admittance associated with massive transfusion of blood products and only moderate crystalloid resuscitation. We report the case of an acute secondary abdominal compartment syndrome developing within 3 to 4 hours in a 74-year-old polytraumatized white woman. Although multiple fractures of her extremities and a B-type pelvic ring fracture were diagnosed by a full body computed tomography scan, no intra-abdominal injury could be detected. Hemorrhagic shock with a drop in her hemoglobin level to 5.7 g/dl was treated by massive transfusion of blood products and high doses of catecholamines. Shortly afterwards, her pulmonary gas exchange progressively deteriorated and mechanical ventilation became almost impossible with peak airway pressures of up to 60 cmH 2 O. Her abdomen appeared rigid and tense accompanied by a progressive hemodynamic decompensation necessitating mechanic cardiopulmonary resuscitation. Although preoperative computed tomography scans showed no signs of intra-abdominal fluid, a decompressive laparotomy under cardiopulmonary resuscitation conditions was performed and 2 liters of ascites-like fluid disgorged. Her hemodynamics and pulmonary ventilation improved immediately. This case report describes for the first time acute secondary abdominal compartment syndrome in a trauma patient, evolving in a very short time period. We hypothesize that the massive transfusion of blood products along with high doses of catecholamines triggered the acute development of abdominal compartment syndrome. Trauma teams need to consider a rapidly developing secondary abdominal compartment syndrome to be a potential cause of hemodynamic decompensation not only in the later phase of treatment but also in the emergency phase of treatment.

Evaluation of a novel closed-loop fluid-administration system based on dynamic predictors of fluid responsiveness: an in silico simulation study.

PubMed

Rinehart, Joseph; Alexander, Brenton; Le Manach, Yannick; Hofer, Christoph; Tavernier, Benoit; Kain, Zeev N; Cannesson, Maxime

2011-01-01

Dynamic predictors of fluid responsiveness have made automated management of fluid resuscitation more practical. We present initial simulation data for a novel closed-loop fluid-management algorithm (LIR, Learning Intravenous Resuscitator). The performance of the closed-loop algorithm was tested in three phases by using a patient simulator including a pulse-pressure variation output. In the first phase, LIR was tested in three different hemorrhage scenarios and compared with no management. In the second phase, we compared LIR with 20 practicing anesthesiologists for the management of a simulated hemorrhage scenario. In the third phase, LIR was tested under conditions of noise and artifact in the dynamic predictor. In the first phase, we observed a significant difference between the unmanaged and the LIR groups in moderate to large hemorrhages in heart rate (76 ± 8 versus 141 ± 29 beats/min), mean arterial pressure (91 ± 6 versus 59 ± 26 mm Hg), and cardiac output (CO; (6.4 ± 0.9 versus 3.2 ± 1.8 L/min) (P < 0.005 for all comparisons). In the second phase, LIR intervened significantly earlier than the practitioners (16.0 ± 1.3 minutes versus 21.5 ± 5.6 minutes; P < 0.05) and gave more total fluid (2,675 ± 244 ml versus 1,968 ± 644 ml; P < 0.05). The mean CO was higher in the LIR group than in the practitioner group (5.9 ± 0.2 versus 5.2 ± 0.6 L/min; P < 0.05). Finally, in the third phase, despite the addition of noise to the pulse-pressure variation value, no significant difference was found across conditions in mean, final, or minimum CO. These data demonstrate that LIR is an effective volumetric resuscitator in simulated hemorrhage scenarios and improved physician management of the simulated hemorrhages.

[Observation of therapeutic effect by combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng on late hemorrhagic shock of rabbits].

PubMed

Wang, Z W; Gao, S Z; Cheng, B C

1997-05-01

To explore the therapeutic mechanism of Salvia miltiorrhize, ligustrazine and Panax notoginseng in treating late hemorrhagic shock in rabbit. Rabbit hemorrhagic shock models (MPA 5.3 kPa) were set up according to Wiggers' method and administrated Salvia miltiorrhiza, ligustrazine, Panax notoginseng. The values of blood RBC superoxide dismutase (SOD) and blood lactate (BL), plasma malondialdehyde (MDA) and magnesium (Mg++) were continuously monitored before shock, 120 minutes after shock, 60 and 120 minutes after hydraulic dilatation. (1) In 120 minutes after shock, the level of SOD decreased and the concentrations of MDA, BL, Mg++ were markedly increased, which indicated that the cell membrane damage caused by oxygen free radicals in rabbit hemorrhagic shock. (2) Salvia miltiorrhiza, Ligustrazine or Panax notoginseng could alleviate lipidperoxidation injury to tissue. Compared with the single drug administration groups, the effects of oxygen free radicals scavangers by combined administration with half dose of 2 drugs were better than the single drug with full dose alone and the side effects such as depression of blood pressure and heart rates would be alleviated. Combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng would half the dosage, the blood pressure depression and heart rate reduction alleviated and better result obtained.

A Comparison of Vasopressin, Terlipressin, and Lactated Ringers for Resuscitation of Uncontrolled Hemorrhagic Shock in an Animal Model

PubMed Central

Lee, Chien-Chang; Lee, Meng-Tse Gabriel; Chang, Shy-Shin; Lee, Si-Huei; Huang, Yu-Chi; Yo, Chia-Hung; Lee, Shih-Hao; Chen, Shyr-Chyr

2014-01-01

Aim The aim of this study is to compare the effect of lactated ringer (LR), vasopressin (Vaso) or terlipressin (Terli) on uncontrolled hemorrhagic shock (UHS) in rats. Methods 48 rats were divided into four treatment groups for UHS study. Vaso group was given bolus vasopressin (0.8 U/kg); the Terli group was given bolus terlipressin (15 mcg/kg); LR group was given LR and the sham group was not given anything. Mean arterial pressure (MAP), serum lactate level, plasma cytokine levels, lung injury and mortality are investigated for these different treatment groups. Results Compared with LR group, vasopressin and terlipressin-treated groups were associated with higher MAP, lowered mortality rates, less lung injury, lowered serum lactate level, less proinflammatory and more anti-inflammatory cytokine production at certain time points. Comparing between vasopressin and terlipressin treated groups, there is no statistical difference in mortality rates, lung injury, serum lactate level and cytokine level. However, there is a difference in the length of time in maintaining a restored level of MAP (80 to 110 mmHg). The terlipressin treated rats can maintain this restored level of MAP for 45 minutes, but the vasopressin treated rats can only maintain this restored level of MAP for 5 minutes before decreasing gradually to the MAP observed in LR group (40 mmHg). Conclusion Early optimization of hemodynamics with terlipressin or vasopressin in an animal model of UHS was associated with improved hemodynamics and inflammatory cytokine profile than the LR control. Compared with vasopressin, terlipressin has the advantage of ease of use and sustained effects. PMID:24759799

Clinical presentation and management of severe Ebola virus disease.

PubMed

West, T Eoin; von Saint André-von Arnim, Amélie

2014-11-01

Clinicians caring for patients infected with Ebola virus must be familiar not only with screening and infection control measures but also with management of severe disease. By integrating experience from several Ebola epidemics with best practices for managing critical illness, this report focuses on the clinical presentation and management of severely ill infants, children, and adults with Ebola virus disease. Fever, fatigue, vomiting, diarrhea, and anorexia are the most common symptoms of the 2014 West African outbreak. Profound fluid losses from the gastrointestinal tract result in volume depletion, metabolic abnormalities (including hyponatremia, hypokalemia, and hypocalcemia), shock, and organ failure. Overt hemorrhage occurs infrequently. The case fatality rate in West Africa is at least 70%, and individuals with respiratory, neurological, or hemorrhagic symptoms have a higher risk of death. There is no proven antiviral agent to treat Ebola virus disease, although several experimental treatments may be considered. Even in the absence of antiviral therapies, intensive supportive care has the potential to markedly blunt the high case fatality rate reported to date. Optimal treatment requires conscientious correction of fluid and electrolyte losses. Additional management considerations include searching for coinfection or superinfection; treatment of shock (with intravenous fluids and vasoactive agents), acute kidney injury (with renal replacement therapy), and respiratory failure (with invasive mechanical ventilation); provision of nutrition support, pain and anxiety control, and psychosocial support; and the use of strategies to reduce complications of critical illness. Cardiopulmonary resuscitation may be appropriate in certain circumstances, but extracorporeal life support is not advised. Among other ethical issues, patients' medical needs must be carefully weighed against healthcare worker safety and infection control concerns. However, meticulous attention to the use of personal protective equipment and strict adherence to infection control protocols should permit the safe provision of intensive treatment to severely ill patients with Ebola virus disease.

Does selective beta-1 blockade provide bone marrow protection after trauma/hemorrhagic shock?

PubMed

Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C; Kotamarti, Srinath; Calderon, Gabriel M; Alzate, Walter D; Livingston, David H; Mohr, Alicia M

2012-09-01

Previously, nonselective beta-blockade (BB) with propranolol demonstrated protection of the bone marrow (BM) after trauma and hemorrhagic shock (HS). Because selective beta-1 blockers are used commonly for their cardiac protection, the aim of this study was to more clearly define the role of specific beta adrenergic receptors in BM protection after trauma and HS. Male Sprague-Dawley rats underwent unilateral lung contusion (LC) followed by HS for 45 minutes. After resuscitation, animals were injected with a selective beta-blocker, atenolol (B1B), butoxamine (B2B), or SR59230A (B3B). Animals were killed at 3 hours or 7 days. Heart rate and blood pressure were measured throughout the study period. BM cellularity, growth of hematopoietic progenitor cells (HPCs) in BM, and hemoglobin levels (Hb) were assessed. Treatment with a B2B or B3B after LCHS restored both BM cellularity and BM HPC colony growth at 3 hours and 7 days. In contrast, treatment with a B1B had no effect on BM cellularity or HPC growth but did decrease heart effectively rate throughout the study. Treatment with a B3B after LCHS increased Hb as compared with LCHS alone. After trauma and HS, protection of BM for 7 days was seen with use of either a selective beta-2 or beta-3 blocker. Use of a selective beta-1 blocker was ineffective in protecting the BM despite a physiologic decrease in heart rate. Therefore, the protection of BM is via the beta-2 and beta-3 receptors and it is not via a direct cardiovascular effect. Published by Mosby, Inc.

Of hemorrhagic shock, spherical cows and Aloe vera

PubMed Central

Gutierrez, Guillermo; Fuller, Stephanie P

2004-01-01

The central question explored in this commentary is whether the beneficial effects of an Aloe vera derived drag-reducing polymer during hemorrhagic shock is due to its O2 radical scavenging properties or to changes in blood rheology. PMID:15566601

Intraosseous vascular access in disasters and mass casualty events: A review of the literature.

PubMed

Burgert, James M

2016-01-01

The intraosseous (IO) route of vascular access has been increasingly used to administer resuscitative fluids and drugs to patients in whom reliable intravenous (IV) access could not be rapidly or easily obtained. It is unknown that to what extent the IO route has been used to gain vascular access during disasters and mass casualty events. The purpose of this review was to examine the existing literature to answer the research question, "What is the utility of the IO route compared to other routes for establishing vascular access in patients resulting from disasters and mass casualty events?" Keyword-based online database search of PubMed, CINAHL, and the Cochrane Database of Systematic Reviews. University-based academic research cell. Included evidence were randomized and nonrandomized trials, systematic reviews with and without meta-analysis, case series, and case reports. Excluded evidence included narrative reviews and expert opinion. Not applicable. Of 297 evidence sources located, 22 met inclusion criteria. Located evidence was organized into four categories including chemical agent poisoning, IO placement, while wearing chemical protective clothing (PPE), military trauma, and infectious disease outbreak. Evidence indicates that the IO route of infusion is pharmacokinetically equal to the IV route and superior to the intramuscular (IM) and endotracheal routes for the administration of antidotal drugs in animal models of chemical agent poisoning while wearing full chemical PPE. The IO route is superior to the IM route for antidote administration during hypovolemic shock. Civilian casualties of explosive attacks and mass shootings would likely benefit from expanded use of the IO route and military resuscitation strategies. The IO route is useful for fluid resuscitation in the management of diarrheal and hemorrhagic infectious disease outbreaks.

In vivo Evaluation of Venular Glycocalyx during Hemorrhagic Shock in Rats using Intravital Microscopy

DTIC Science & Technology

2013-01-01

Brief Communication In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using intravital microscopy☆,☆☆ Ivo Torres Filho...pathophysiology and tested the hypothesis that hemorrhage causes glycocalyx degrada- tion in cremaster muscle microvessels. We utilized intravital microscopy...bound (Reitsma et al., 2007; Weinbaum et al., 2007). Intravital microscopy has been an invaluable resource for in vivo measurements of critically

Damage control resuscitation: history, theory and technique

PubMed Central

Ball, Chad G.

2014-01-01

Damage control resuscitation (DCR) represents the natural evolution of the initial concept of damage control surgery. It currently includes early blood product transfusion, immediate arrest and/or temporization of ongoing hemorrhage (i.e., temporary intravascular shunts and/or balloon tamponade) as well as restoration of blood volume and physiologic/hematologic stability. As a result, DCR addresses the early coagulopathy of trauma, avoids massive crystalloid resuscitation and leaves the peritoneal cavity open when a patient approaches physiologic exhaustion without improvement. This concept also applies to severe injuries within anatomical transition zones as well as extremities. This review will discuss each of these concepts in detail. PMID:24461267

Novel Measures of Volume Status and Cardiac Function in Traumatic Shock

DTIC Science & Technology

2016-06-01

cardio -protective, fluid-limited method of resuscitation. In addition to providing insight into fluid management and cardiac function, the data indicate... cardio -protective method of resuscitation. 8.0 REFERENCES 1. Marik PE, Monnet X, Teboul JL. Hemodynamic parameters to guide fluid therapy. Ann

Prognostic value of extravascular lung water and its potential role in guiding fluid therapy in septic shock after initial resuscitation.

PubMed

Wang, Hao; Cui, Na; Su, Longxiang; Long, Yun; Wang, Xiaoting; Zhou, Xiang; Chai, Wenzhao; Liu, Dawei

2016-06-01

To explore whether extravascular lung water (EVLW) provides a valuable prognostic tool guiding fluid therapy in septic shock patients after initial resuscitation. We performed a retrospective study of septic shock patients who achieved adequate initial fluid resuscitation with extended hemodynamic monitoring, analyzing the prognostic value of EVLW and whether fluid therapy for 24 (T24) or 24-48 hours (T24-48) after initial resuscitation with a recommended value of EVLW yielded a 28-day mortality advantage. One hundred five patients with septic shock were included in this study, 60 (57.1%) of whom died after 28 days. For 48 hours after initial resuscitation, the daily fluid balance (DFB; T24: 2494 ± 1091 vs 1965 ± 964 mL [P = .011] and T24-48: 2127 ± 783 vs 1588 ± 665 mL [P < .001]) and daily maximum values of the EVLW index (EVLWImax; T24: 13.9 ± 3.7 vs 11.5 ± 3.2 mL/kg [P < .001] and T24-48: 14.4 ± 5.3 vs 12.0 ± 4.4 mL/kg [P < .001]) were significantly higher in nonsurvivors than in survivors. In multivariate regression analysis, the DFB (T24: odds ratio [OR] 1.001 [P = .016] and T24-48: OR 1.001 [P = .008]), EVLWImax (T24: OR 2.158 [P = .002] and T24-48: OR 3.277 [P = .001]), blood lactate (T24: OR 1.368 [P = .021] and T24-48: OR 4.112 [P < .001]), and central venous blood oxygen saturation (T24: OR 0.893 [P = .013] and T24-48: OR 0.780 [P = .004]) were all independently associated with the 28-day mortality. A receiver operating characteristic analysis revealed that area under the curve values of 0.82 (95% confidence interval, 0.74-0.91; P < .001) and 0.90 (95% confidence interval, 0.83-0.96; P < .001) for EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) predicted a 28-day mortality with sensitivities of 88% (80%-96%) and 95% (90%-100%) and specificities of 60% (46%-74%) and 76% (63%-89%).The EVLWImax was correlated with DFB with Spearman ρ values of 0.497 (T24: P < .001) and 0.650 (T24-48: P < .001). Cox survival and regression analyses demonstrated that EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) was associated with higher risk and increased mortality, with adjusted ORs of 4.77 (P < .001) and 10.86 (P < .001). A higher EVLW in septic shock patients after initial resuscitation was associated with a more positive fluid balance and increased mortality, which is an independent predictor of the 28-day mortality in septic shock patients after initial resuscitation. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamic Contrast-Enhanced Ultrasound Identifies Microcirculatory Alterations in Sepsis-Induced Acute Kidney Injury.

PubMed

Lima, Alexandre; van Rooij, Tom; Ergin, Bulent; Sorelli, Michele; Ince, Yasin; Specht, Patricia A C; Mik, Egbert G; Bocchi, Leonardo; Kooiman, Klazina; de Jong, Nico; Ince, Can

2018-05-15

We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. Prospective controlled animal experiment study. Hospital-affiliated animal research institution. Fifteen female pigs. The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular hypoperfusion was quantified by decreased peak enhancement and an increased ratio of the final plateau intensity to peak enhancement. Reduced intrarenal blood flow could be estimated by measuring the microbubble transit times between the interlobar arteries and capillary vessels in the renal cortex. Sublingual microcirculation measured using the Cytocam in a fixed area showed decreased functional capillary density associated with plugged sublingual capillary vessels that persisted during and after fluid resuscitation. In our lipopolysaccharide model, with resuscitation targeted at blood pressure, the contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation.

Initiation and Termination of Massive Transfusion Protocols: Current Strategies and Future Prospects.

PubMed

Foster, John C; Sappenfield, Joshua W; Smith, Robert S; Kiley, Sean P

2017-12-01

The advent of massive transfusion protocols (MTP) has had a significant positive impact on hemorrhaging trauma patient morbidity and mortality. Nevertheless, societal MTP guidelines and individual MTPs at academic institutions continue to circulate opposing recommendations on topics critical to MTPs. This narrative review discusses up-to-date information on 2 such topics, the initiation and termination of an MTP. The discussion for each begins with a review of the recommendations and supporting literature presented by MTP guidelines from 3 prominent societies, the American Society of Anesthesiologists, the American College of Surgeons, and the task force for Advanced Bleeding Care in Trauma. This is followed by an in-depth analysis of the main components within those recommendations. Societal recommendations on MTP initiation in hemorrhaging trauma patients emphasize the use of retrospectively validated massive transfusion (MT) prediction score, specifically, the Assessment of Blood Consumption and Trauma-Associated Severe Hemorrhage scores. Validation studies have shown that both scoring systems perform similarly. Both scores reliably identify patients that will not require an MT, while simultaneously overpredicting MT requirements. However, each scoring system has its unique advantages and disadvantages, and this review discusses how specific aspects of each scoring system can affect widespread applicability and statistical performance. In addition, we discuss the often overlooked topic of initiating MT in nontrauma patients and the specific tools physicians have to guide the MT initiation decision in this unique setting. Despite the serious complications that can arise with transfusion of large volumes of blood products, there is considerably less research pertinent to the topic of MTP termination. Societal recommendations on MTP termination emphasize applying clinical reasoning to identify patients who have bleeding source control and are adequately resuscitated. This review, however, focuses primarily on the recommendations presented by the Advanced Bleeding Care in Trauma's MTP guidelines that call for prompt termination of the algorithm-guided model of resuscitation and rapidly transitioning into a resuscitation model guided by laboratory test results. We also discuss the evidence in support of laboratory result-guided resuscitation and how recent literature on viscoelastic hemostatic assays, although limited, highlights the potential to achieve additional benefits from this method of resuscitation.

Molecular weight and molar substitution are more important in HES-induced renal impairment than concentration after hemorrhagic and septic shock.

PubMed

Simon, T P; Thiele, C; Schuerholz, T; Fries, M; Stadermann, F; Haase, G; Amann, K U; Marx, G

2015-06-01

Clinical studies have raised concerns about the safety of 6% hydroxyethylstarch (HES) 130/0.42, but the pathomechanisms of this renal impairment remain unknown. To evaluate the effects of different HES concentrations, molar substitutions and molecular weights in HES-induced renal impairment, we used a porcine two-hit model that combined haemorrhagic and septic shock. We conducted a prospective, randomised, double-blinded, controlled study in a university animal laboratory. Thirty anaesthetised and ventilated pigs were randomised to receive volume replacement therapy using 6% HES130/0.42, 6% HES200/0.5, 10% HES130/0.42 or 10% HES200/0.5, all dissolved in 0.9% NaCl rather than 0.9% NaCl alone. First, we bled the animals until they reached half of their baseline mean arterial pressure (MAP) for 45 minutes followed by fluid resuscitation. As a second hit, sepsis was induced using an Escherichia coli-laden clot 6 hours after haemorrhagic shock. Volume resuscitation started with a delay of two hours and a central venous pressure goal of 12 mmHg. At the end of the study, the groups showed no difference in cardiac output or MAP, but the volume balance (mL/kg BW) was significantly higher in the 0.9% NaCl group (346±90; P≤0.05) than in the other groups (6% HES130, 125±26; 6% HES200, 105±15; 10% HES130, 114±17; 10% HES200, 96±23). Creatinine clearance (mL/min) was significantly lower in the 6% HES200 (26±33) and 10% HES200 (15±18) groups compared to the 0.9% NaCl group (104±46; P≤0.05) but not in the HES 130 formulations (6% HES130: 64±51; 10% HES130: 58±38) at the end of the study. In this porcine two-hit shock model, treatment with 0.9% NaCl, HES 130/0.42 or HES 200/0.5 led to a similar maintenance of haemodynamic values. Despite this similar maintenance of the haemodynamic values, volume replacement with 6% and 10% HES 200/0.5 led to an accumulation of HES, higher colloid osmotic pressure and significantly reduced renal function after haemorrhagic and septic shock. These facts support the presumption that not the concentration but the degree of substitution and the molecular weight play a decisive role in HES-induced renal impairment.

Hypertonic lactated saline resuscitation reduces the risk of abdominal compartment syndrome in severely burned patients.

PubMed

Oda, Jun; Ueyama, Masashi; Yamashita, Katsuyuki; Inoue, Takuya; Noborio, Mitsuhiro; Ode, Yasumasa; Aoki, Yoshiki; Sugimoto, Hisashi

2006-01-01

Secondary abdominal compartment syndrome is a lethal complication after resuscitation from burn shock. Hypertonic lactated saline (HLS) infusion reduces early fluid requirements in burn shock, but the effects of HLS on intraabdominal pressure have not been clarified. Patients admitted to our burn unit between 2002 and 2004 with burns > or =40% of the total body surface area without severe inhalation injury were entered into a fluid resuscitation protocol using HLS (n = 14) or lactated Ringer's solution (n = 22). Urine output was monitored hourly with a goal of 0.5 to 1.0 mL/kg per hour. Hemodynamic parameters, blood gas analysis, intrabladder pressure as an indicator of intraabdominal pressure (IAP), and the peak inspiratory pressure were recorded. Pulmonary compliance and the abdominal perfusion pressure were also calculated. In the HLS group, the amount of intravenous fluid volume needed to maintain adequate urine output was less at 3.1 +/- 0.9 versus 5.2 +/- 1.2 mL/24 h per kg per percentage of total body surface area, and the peak IAP and peak inspiratory pressure at 24 hours after injury were significantly lower than those in the lactated Ringer's group. Two of 14 patients (14%) in the HLS group and 11 of 22 patients (50%) developed IAH within 20.8 +/- 7.2 hours after injury. In patients with severe burn injury, a large intravenous fluid volume decreases abdominal perfusion during the resuscitative period because of increased IAP. Our data suggest that HLS resuscitation could reduce the risk of secondary abdominal compartment syndrome with lower fluid load in burn shock patients.

Temporary arterial shunts to maintain limb perfusion after arterial injury: an animal study

NASA Technical Reports Server (NTRS)

Dawson, D. L.; Putnam, A. T.; Light, J. T.; Ihnat, D. M.; Kissinger, D. P.; Rasmussen, T. E.; Bradley, D. V. Jr

1999-01-01

BACKGROUND: Temporary shunt placement can quickly restore perfusion after extremity arterial injury. This study examined the adequacy of limb blood flow with shunt use, non-heparin-bonded shunt patency over prolonged periods, and the safety of this technique. METHODS: Common iliac arteries were divided and 4.0-mm Silastic Sundt shunts placed in 16 anesthetized pigs. Eight (group I) had shunts placed immediately; eight others (group II) were shunted after an hour of limb ischemia and hemorrhagic shock. Physiologic parameters and femoral artery blood flow in both hindlimbs were continuously monitored. Limb lactic acid generation, oxygen utilization, and hematologic and metabolic effects were serially evaluated for 24 hours. RESULTS: Shunts remained patent in 13 of 16 pigs. Shunts thrombosed in two group I animals because of technical errors, but functioned well after thrombectomy and repositioning. Patency could not be maintained in one animal that died from shock. Flow in group I shunted limbs was 57 (+/-11 SD) % of control. For group II animals in shock, shunted limb flow initially averaged 46 +/- 15% of control, but 4 hours after shunt placement, the mean limb blood flow was the same as in group I. Increased oxygen extraction compensated for the lower flow. Lactic acid production was not increased in comparison to control limbs. CONCLUSION: Shunts provided adequate flow in this model of extremity trauma. Correctly placed shunts stayed patent for 24 hours, without anticoagulation, if shunt placement followed resuscitation.

Hemorrhagic shock as a sequela of splenic rupture in a patient with infectious mononucleosis: focus on the potential role of salicylates.

PubMed

Bouliaris, Konstantinos; Karangelis, Dimos; Daskalopoulos, Marios; Spanos, Konstantinos; Fanariotis, Michael; Giaglaras, Anargyros

2012-01-01

Despite the fact that the vast majority of splenic ruptures are traumatic, infectious mononucleosis has been incriminated as a major predisposing factor that affects the integrity of the spleen, thus causing atraumatic ruptures and life-threatening hemorrhages. Herein we present a case of a 23-year-old Caucasian male who underwent an emergency laparotomy for acute abdomen and hemorrhagic shock, caused by spontaneous splenic rupture secondary to infectious mononucleosis. The potential role of salicylates in the development of a hemorrhagic complication in a patient with infectious mononucleosis is discussed.

Definitive studies on pole-top resuscitation. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, A.S.; Ridolpho, P.F.; Cole, J.E.

1983-02-01

This report summarizes the history of the application of cardiopulmonary resuscitation to the electric shock victim located at the top of a utility pole. This dramatic and urgent situation requires that rescue be attempted with procedures which are thoroughly understood and effective. Questions related to the use of resuscitation and precordial thump at the pole top were subjected to experimental testing, both in animals and in humans. Results of this study clearly demonstrate the advantages of postponing resuscitation until the victim has been lowered to the ground. The author concludes with seven recommendations for emergency treatment at the scene.

The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

PubMed

Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

2017-09-01

The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p < 0.001) and mortality (29% vs 14%; p < 0.001). Subgroup analysis of 127 patients meeting only the old definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice.

PubMed

Shein, Steven L; Shellington, David K; Exo, Jennifer L; Jackson, Travis C; Wisniewski, Stephen R; Jackson, Edwin K; Vagni, Vincent A; Bayır, Hülya; Clark, Robert S B; Dixon, C Edward; Janesko-Feldman, Keri L; Kochanek, Patrick M

2014-08-15

Secondary insults, such as hemorrhagic shock (HS), worsen outcome from traumatic brain injury (TBI). Both TBI and HS modulate levels of inflammatory mediators. We evaluated the addition of HS on the inflammatory response to TBI. Adult male C57BL6J mice were randomized into five groups (n=4 [naïve] or 8/group): naïve; sham; TBI (through mild-to-moderate controlled cortical impact [CCI] at 5 m/sec, 1-mm depth), HS; and CCI+HS. All non-naïve mice underwent identical monitoring and anesthesia. HS and CCI+HS underwent a 35-min period of pressure-controlled hemorrhage (target mean arterial pressure, 25-27 mm Hg) and a 90-min resuscitation with lactated Ringer's injection and autologous blood transfusion. Mice were sacrificed at 2 or 24 h after injury. Levels of 13 cytokines, six chemokines, and three growth factors were measured in serum and in five brain tissue regions. Serum levels of several proinflammatory mediators (eotaxin, interferon-inducible protein 10 [IP-10], keratinocyte chemoattractant [KC], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1alpha [MIP-1α], interleukin [IL]-5, IL-6, tumor necrosis factor alpha, and granulocyte colony-stimulating factor [G-CSF]) were increased after CCI alone. Serum levels of fewer proinflammatory mediators (IL-5, IL-6, regulated upon activation, normal T-cell expressed, and secreted, and G-CSF) were increased after CCI+HS. Serum level of anti-inflammatory IL-10 was significantly increased after CCI+HS versus CCI alone. Brain tissue levels of eotaxin, IP-10, KC, MCP-1, MIP-1α, IL-6, and G-CSF were increased after both CCI and CCI+HS. There were no significant differences between levels after CCI alone and CCI+HS in any mediator. Addition of HS to experimental TBI led to a shift toward an anti-inflammatory serum profile--specifically, a marked increase in IL-10 levels. The brain cytokine and chemokine profile after TBI was minimally affected by the addition of HS.

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

Battlefield trauma care then and now: a decade of Tactical Combat Casualty Care.

DTIC Science & Technology

2012-01-01

use of tranexamic acid to help prevent death from noncompressible hemorrhage35 37 The use of the Combat Ready Clamp to control junctional...hemorrhage38 The use as described for fentanyl lozenges, tranexamic acid , moxifloxacin, ertapenem, and cefotetan is unlabeled use of Food and Drug Administration...2011;377:1096 1101. 35. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military appli- cation of tranexamic acid in trauma emergency resuscitation

Association of Fluid Resuscitation Initiation Within 30 Minutes of Severe Sepsis and Septic Shock Recognition With Reduced Mortality and Length of Stay.

PubMed

Leisman, Daniel; Wie, Benjamin; Doerfler, Martin; Bianculli, Andrea; Ward, Mary Frances; Akerman, Meredith; D'Angelo, John K; Zemmel D'Amore, Jason A

2016-09-01

We evaluate the association of intravenous fluid resuscitation initiation within 30 minutes of severe sepsis or septic shock identification in the emergency department (ED) with inhospital mortality and hospital length of stay. We also compare intravenous fluid resuscitation initiated at various times from severe sepsis or septic shock identification's association with the same outcomes. This was a review of a prospective, observational cohort of all ED severe sepsis or septic shock patients during 13 months, captured in a performance improvement database at a single, urban, tertiary care facility (90,000 ED visits/year). The primary exposure was initiation of a crystalloid bolus at 30 mL/kg within 30 minutes of severe sepsis or septic shock identification. Secondary analysis compared intravenous fluid initiated within 30, 31 to 60, or 61 to 180 minutes, or when intravenous fluid resuscitation was initiated at greater than 180 minutes or not provided. Of 1,866 subjects, 53.6% were men, 72.5% were white, mean age was 72 years (SD 16.6 years), and mean initial lactate level was 2.8 mmol/L. Eighty-six percent of subjects were administered intravenous antibiotics within 180 minutes; 1,193 (64%) had intravenous fluid initiated within 30 minutes. Mortality was lower in the within 30 minutes group (159 [13.3%] versus 123 [18.3%]; 95% confidence interval [CI] 1.4% to 8.5%), as was median hospital length of stay (6 days [95% CI 6 to 7] versus 7 days [95% CI 7 to 8]). In multivariate regression that included adjustment for age, lactate, hypotension, acute organ dysfunction, and Emergency Severity Index score, intravenous fluid within 30 minutes was associated with lower mortality (odds ratio 0.63; 95% CI 0.46 to 0.86) and 12% shorter length of stay (hazard ratio=1.14; 95% CI 1.02 to 1.27). In secondary analysis, mortality increased with later intravenous fluid resuscitation initiation: 13.3% (≤30 minutes) versus 16.0% (31 to 60 minutes) versus 16.9% (61 to 180 minutes) versus 19.7% (>180 minutes). Median hospital length of stay also increased with later intravenous fluid initiation: 6 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 7 days) versus 7 days (95% CI 6 to 8 days) versus 8 days (95% CI 7 to 9 days). The time of intravenous fluid resuscitation initiation was associated with improved mortality and could be used as an easier obtained alternative to intravenous fluid completion time as a performance indicator in severe sepsis and septic shock management. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Novel Resuscitation from Lethal Hemorrhage - Suspended Animation for Delayed Resuscitation

DTIC Science & Technology

2002-09-01

para la inducci6n rApida de hipotermia leve en perros , usando un equipo simple de bomba enfriadora. Se anetesiaron superficialmente dies perros de caza...21 - 28 kg) y se pusieron en ventilaci6n mecAnica. En cinco perros , se insertaron dos cat~teres en las venas femorales, uno perif~rico y el otro hacia...gasto cardiaco). En los otros 5 perros (grvpo control) se realiz6 un enfriamiento con m6todo dlinico externo, usando alcohol sobre ]a piel del tronco

Urgent care in gynaecology: resuscitation and management of sepsis and acute blood loss.

PubMed

Fischerova, Daniela

2009-10-01

Sepsis and/or acute blood loss can be encoutered as an emergency condition in gynaecology, especially in women with ectopic pregnancy/miscarriage, acute pelvic inflammatory disease (PID)/tuboovarian abscesses, post-puerperal sepsis/haemorrhage and even in postoperative scenarios. If underestimated or suboptimally treated, both can lead to an inadequate tissue perfusion (defined as shock) and the development of multi-organ failure. Morbidity and mortality after development of one of the shock syndromes (septic or haemorrhagic) correlates directly with the duration and severity of the malperfusion. The patient's prognosis depends on a prompt diagnosis of the presence of shock and immediate resuscitation to predefined physiological end-points, often before the cause of the shock has been identified. In septic shock, hypotension is primarily treated with fluid administration and eventually vasopressors, if required, in order to improve the circulation. Timely administration of antibiotics, control of infectious foci, appropriate use of corticoids and recombinant human activated protein C, tight glucose control, prophylaxis of deep vein thrombosis and stress ulcer prevention complete the therapy of septic shock. In haemorrhagic shock, the treatment primarily involves controlling haemorrhage, reversal of possible coagulopathy and administration of sufficient volumes of fluids and blood products to restore normal tissue perfusion.

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock.

PubMed

Assadi, A; Desebbe, O; Kaminski, C; Rimmelé, T; Bénatir, F; Goudable, J; Chassard, D; Allaouchiche, B

2008-01-01

We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

[The clinical significance of microcirculation and oxygen metabolism evaluation in acute kidney injury assessment in patients with septic shock after resuscitation].

PubMed

Yu, C; Liu, D W; Wang, X T; He, H W; Pan, P; Xing, Z Q

2018-02-01

Objective: To evaluate the value of microcirculation and oxygen metabolism evaluation (MicrOME) in acute kidney injury(AKI) evaluation in patients with septic shock after resuscitation. Methods: Consecutive patients with septic shock after resuscitation and mechanical ventilation were enrolled from October 2016 to February 2017 in ICU at Peking Union Medical College Hospital.Patients were divided into 3 groups based on 10 min transcutaneous oxygen challenge test transcutaneous partial pressure of oxygen(PtcO(2))and venoarterial pressure of carbon dioxide difference (Pv-aCO(2)) /arteriovenous O(2) content difference (Ca-vO(2)) by blood gas analysis, i.e. group A [ΔPtcO(2)>66 mmHg(1 mmHg=0.133 kPa) and Pv-aCO(2)/Ca-vO(2)≤1.23], group B (ΔPtcO(2)≤66 mmHg), group C (ΔPtcO(2)>66 mmHg and Pv-aCO(2)/Ca-vO(2)>1.23). Heart rate,mean arterial pressure,central venous pressure,noradrenaline dose,lactate,Pv-aCO(2),Ca-vO(2), lactate clearance, central venous oxygen saturation(ScvO(2)) and liquid equilibrium were assessed after resuscitation.AKI staging based on Kidney Disease Global Improving Outcomes (KDIGO) clinical practice guideline was analyzed. The predictive value of lactate, ScvO(2), Pv-aCO(2)/Ca-vO(2) to progression of AKI after resuscitation was determined using receiver operating characteristic(ROC)curve analysis. Results: A total of 49 septic shock patients were enrolled including 30 males and 19 females with mean age of (61.10±17.10)years old.There were 19 patients in group A,21 patients in group B, and 9 patients in group C. Acute physiology and chronic health evaluation Ⅱ score was 20.92±7.19 and sequential organ failure assessment score 12.02±3.28. There were 4 patients with AKI and 1 progressed in group A, 11 patients with AKI and 2 progressed in group B, 6 patients with AKI and 4 progressed in group C. The cutoff value of Pv-aCO(2)/Ca-vO(2) was equal or more than 2.20 for predicting progression of AKI, resulting in a sensitivity of 85.7% and a specificity of 73.8%. Conclusion: MicrOME is a significant parameter to predict the progression of AKI in patients with septic shock after resuscitation. Pv-aCO(2)/Ca-vO(2) is also a good predictive factor.

Evaluation of hemodynamic effects of xenon in dogs undergoing hemorrhagic shock

PubMed Central

Franceschi, Ruben C.; Malbouisson, Luiz; Yoshinaga, Eduardo; Auler, José Otavio Costa; de Figueiredo (in memoriam), Luiz Francisco Poli; Carmona, Maria José C.

2013-01-01

OBJECTIVES: The anesthetic gas xenon is reported to preserve hemodynamic stability during general anesthesia. However, the effects of the gas during shock are unclear. The objective of this study was to evaluate the effect of Xe on hemodynamic stability and tissue perfusion in a canine model of hemorrhagic shock. METHOD: Twenty-six dogs, mechanically ventilated with a fraction of inspired oxygen of 21% and anesthetized with etomidate and vecuronium, were randomized into Xenon (Xe; n = 13) or Control (C; n = 13) groups. Following hemodynamic monitoring, a pressure-driven shock was induced to reach an arterial pressure of 40 mmHg. Hemodynamic data and blood samples were collected prior to bleeding, immediately after bleeding and 5, 20 and 40 minutes following shock. The Xe group was treated with 79% Xe diluted in ambient air, inhaled for 20 minutes after shock. RESULT: The mean bleeding volume was 44 mL.kg−1 in the C group and 40 mL.kg−1 in the Xe group. Hemorrhage promoted a decrease in both the cardiac index (p<0.001) and mean arterial pressure (p<0.001). These changes were associated with an increase in lactate levels and worsening of oxygen transport variables in both groups (p<0.05). Inhalation of xenon did not cause further worsening of hemodynamics or tissue perfusion markers. CONCLUSIONS: Xenon did not alter hemodynamic stability or tissue perfusion in an experimentally controlled hemorrhagic shock model. However, further studies are necessary to validate this drug in other contexts. PMID:23525321

THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK

PubMed Central

Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.

2012-01-01

The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149

Dengue Hemorrhagic Fever at 60 Years: Early Evolution of Concepts of Causation and Treatment

PubMed Central

Cohen, Sanford N.

2015-01-01

SUMMARY During the decade of the 1960s, the epidemiology of a new dengue disease, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), was described by collaborative research performed by Thai scientists from many institutions and by workers at the U.S. Army's SEATO Medical Research Laboratory in Bangkok, Thailand. Careful clinical and physiological studies provided the initial description of DSS. DSS cases were caused by each of the four dengue viruses (DENV) and not chikungunya (CHIK) virus or DENV 5 and 6, were associated with a secondary-type dengue antibody response in children over the age of 1 year, were associated with a primary antibody response in infants less than 1 year old whose mothers had neutralizing antibodies to all four DENV, were associated more frequently with secondary DENV 2 infections than those due to DENV 1 and 3, and were more common in females than males over the age of 3 years. Robust laboratory methods for growth and recovery of DENV in tissue cultures were introduced. In addition, life-saving principles of fluid and plasma protein resuscitation of hypovolemia were described. Most epidemiological observations made during the decade of the 1960s have been confirmed in the succeeding 45 years. Much contemporary research on pathogenesis fails to address the two distinct immunological antecedents of DHF/DSS. PMID:26085471

Restrictive Versus Massive Fluid Resuscitation Strategy (REFILL study), influence on blood loss and hemostatic parameters in obstetric hemorrhage: study protocol for a randomized controlled trial.

PubMed

de Lange, Natascha; Schol, Pim; Lancé, Marcus; Woiski, Mallory; Langenveld, Josje; Rijnders, Robbert; Smits, Luc; Wassen, Martine; Henskens, Yvonne; Scheepers, Hubertina

2018-03-06

Postpartum hemorrhage (PPH) is associated with maternal morbidity and mortality and has an increasing incidence in high-resource countries, despite dissemination of guidelines, introduction of skills training, and correction for risk factors. Current guidelines advise the administration, as fluid resuscitation, of almost twice the amount of blood lost. This advice is not evidence-based and could potentially harm patients. All women attending the outpatient clinic who are eligible will be informed of the study; oral and written informed consent will be obtained. Where there is more than 500 ml blood loss and ongoing bleeding, patients will be randomized to care as usual, fluid resuscitation with 1.5-2 times the amount of blood loss or fluid resuscitation with 0.75-1.0 times the blood loss. Blood loss will be assessed by weighing all draping. A blood sample, for determining hemoglobin concentration, hematocrit, thrombocyte concentration, and conventional coagulation parameters will be taken at the start of the study, after 60 min, and 12-18 h after delivery. In a subgroup of women, additional thromboelastometric parameters will be obtained. Our hypothesis is that massive fluid administration might lead to a progression of bleeding due to secondary coagulation disorders. In non-pregnant individuals with massive blood loss, restrictive fluid management has been shown to prevent a progression to dilution coagulopathy. These data, however, cannot be extrapolated to women in labor. Our objective is to compare both resuscitation protocols in women with early, mild PPH (blood loss 500-750 ml) and ongoing bleeding, taking as primary outcome measure the progression to severe PPH (blood loss > 1000 ml). Netherlands Trial Register, NTR 3789 . Registered on 11 January 2013.

Implementation and execution of military forward resuscitation programs.

PubMed

Hooper, Timothy J; Nadler, Roy; Badloe, John; Butler, Frank K; Glassberg, Elon

2014-05-01

Through necessity, military medicine has been the driver of medical innovation throughout history. The battlefield presents challenges, such as the requirement to provide care while under threat, resource limitation, and prolonged evacuation times, which must be overcome to improve casualty survival. Focus must also be placed on identifying the causes, and timing, of death within the battlefield. By doing so, military medical doctrine can be shaped, appropriate goals set, new concepts adopted, and relevant technologies investigated and implemented. The majority of battlefield casualties still die in the prehospital environment, before reaching a medical treatment facility, and hemorrhage remains the leading cause of potentially survivable death. Many countries have adopted policies that push damage control resuscitation forward into the prehospital setting, while understanding the need for timely medical evacuation. Although these policies vary according to country, the majority share many common principles. These include the need for early catastrophic hemorrhage control at point-of-wounding, judicious use of fluid resuscitation, use of blood products as far forward as possible, and early evacuation to a surgical facility. Some countries place medical providers with the ability, and resources, for advanced resuscitation with the forward fighting units (perhaps at company level), whereas others have established en route resuscitation capabilities. If we are to continue to improve battlefield casualty survival, we must continue to work together and learn from each other. We must also carry on working alongside our civilian colleagues so that the benefits of translational experience are not lost. This review describes several countries current military approaches to prehospital trauma care. These approaches, refined through a decade of experience, merit consideration for integration into civilian prehospital care practice.

Clinical Characteristics of Dengue Shock Syndrome in Vietnamese Children: A 10-Year Prospective Study in a Single Hospital

PubMed Central

Lam, Phung Khanh; Tam, Dong Thi Hoai; Diet, Tran Vinh; Tam, Cao Thi; Tien, Nguyen Thi Hanh; Kieu, Nguyen Tan Thanh; Simmons, Cameron; Farrar, Jeremy; Nga, Nguyen Thi Ngoc; Qui, Phan Tu; Dung, Nguyen Minh; Wolbers, Marcel; Wills, Bridget

2013-01-01

Background. Dengue shock syndrome (DSS) is a severe manifestation of dengue virus infection that particularly affects children and young adults. Despite its increasing global importance, there are no prospective studies describing the clinical characteristics, management, or outcomes of DSS. Methods. We describe the findings at onset of shock and the clinical evolution until discharge or death, from a comprehensive prospective dataset of 1719 Vietnamese children with laboratory-confirmed DSS managed on a single intensive care unit between 1999 and 2009. Results. The median age of patients was 10 years. Most cases had secondary immune responses, with only 6 clear primary infections, and all 4 dengue virus serotypes were represented during the 10-year study. Shock occurred commonly between days 4 and 6 of illness. Clinical signs and symptoms were generally consistent with empirical descriptions of DSS, although at presentation 153 (9%) were still febrile and almost one-third had no bleeding. Overall, 31 (2%) patients developed severe bleeding, primarily from the gastrointestinal tract, 26 of whom required blood transfusion. Only 8 patients died, although 123 of 1719 (7%) patients had unrecordable blood pressure at presentation and 417 of the remaining 1596 (26%) were hypotensive for age. The majority recovered well with standard crystalloid resuscitation or following a single colloid infusion. All cases were classified as severe dengue, while only 70% eventually fulfilled all 4 criteria for the 1997 World Health Organization classification of dengue hemorrhagic fever. Conclusions. With prompt intervention and assiduous clinical care by experienced staff, the outcome of this potentially fatal condition can be excellent. PMID:24046311

Time to achieve target mean arterial pressure during resuscitation from experimental anaphylactic shock in an animal model. A comparison of adrenaline alone or in combination with different volume expanders.

PubMed

Tajima, K; Zheng, F; Collange, O; Barthel, G; Thornton, S N; Longrois, D; Levy, B; Audibert, G; Malinovsky, J M; Mertes, P M

2013-11-01

Anaphylactic shock is a rare, but potentially lethal complication, combining life-threatening circulatory failure and massive fluid shifts. Treatment guidelines rely on adrenaline and volume expansion by intravenous fluids, but there is no solid evidence for the choice of one specific type of fluid over another. Our purpose was to compare the time to achieve target mean arterial pressure upon resuscitation using adrenaline alone versus adrenaline with different resuscitation fluids in an animal model and to compare the tissue oxygen pressures (PtiO2) with the various strategies. Twenty-five ovalbumin-sensitised Brown Norway rats were allocated to five groups after anaphylactic shock induction: vehicle (CON), adrenaline alone (AD), or adrenaline with isotonic saline (AD+IS), hydroxyethyl starch (AD+HES) or hypertonic saline (AD+HS). Time to reach a target mean arterial pressure value of 75 mmHg, cardiac output, skeletal muscle PtiO2, lactate/pyruvate ratio and cumulative doses of adrenaline were recorded. Non-treated rats died within 15 minutes. The target mean arterial pressure value was reached faster with AD+HES (median: 10 minutes, range: 7.5 to 12.5 minutes) and AD+IS (median: 17.5 minutes, range: 5 to 25 minutes) versus adrenaline alone (median: 25 minutes, range: 20-30 minutes). There were also reduced adrenaline requirements in these groups. The skeletal muscle PtiO2 was restored only in the AD+HES group. Although direct extrapolation to humans should be made with caution, our results support the combined use of adrenaline and volume expansion for resuscitation from anaphylactic shock. When used with adrenaline the most effective fluid was hydroxyethyl starch, whereas hypertonic saline was the least effective.

Hemorrhagic Shock as a Sequela of Splenic Rupture in a Patient with Infectious Mononucleosis: Focus on the Potential Role of Salicylates

PubMed Central

Bouliaris, Konstantinos; Karangelis, Dimos; Daskalopoulos, Marios; Spanos, Konstantinos; Fanariotis, Michael; Giaglaras, Anargyros

2012-01-01

Despite the fact that the vast majority of splenic ruptures are traumatic, infectious mononucleosis has been incriminated as a major predisposing factor that affects the integrity of the spleen, thus causing atraumatic ruptures and life-threatening hemorrhages. Herein we present a case of a 23-year-old Caucasian male who underwent an emergency laparotomy for acute abdomen and hemorrhagic shock, caused by spontaneous splenic rupture secondary to infectious mononucleosis. The potential role of salicylates in the development of a hemorrhagic complication in a patient with infectious mononucleosis is discussed. PMID:22431933

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-09-01

Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol may be a future therapeutic target to improve healing after severe injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Muscle oxygenation as an early predictor of shock severity in trauma patients

PubMed Central

Arakaki, Lorilee S. L.; Bulger, Eileen M.; Ciesielski, Wayne A.; Carlbom, David J.; Fisk, Dana M.; Sheehan, Kellie L.; Asplund, Karin M.; Schenkman, Kenneth A.

2016-01-01

Introduction We evaluated the potential utility of a new prototype noninvasive muscle oxygenation (MOx) measurement for the identification of shock severity in a population of patients admitted to the trauma resuscitation rooms of a Level I regional trauma center. The goal of this project was to correlate MOx with shock severity as defined by standard measures of shock: systolic blood pressure, heart rate, and lactate. Methods Optical spectra were collected from subjects by placement of a custom-designed optical probe over the first dorsal interosseous muscles on the back of the hand. Spectra were acquired from trauma patients as soon as possible upon admission to the trauma resuscitation room. Patients with any injury were eligible for study. MOx was determined from the collected optical spectra with a multi-wavelength analysis that used both visible and near-infrared regions of light. Shock severity was determined in each patient by a scoring system based on combined degrees of hypotension, tachycardia, and lactate. MOx values of patients in each shock severity group (mild, moderate, and severe) were compared using two-sample t-tests. Results In 17 healthy control patients, the mean MOx value was 91.0 ± 5.5%. A total of 69 trauma patients were studied. Patients classified as having mild shock had a mean MOx of 62.5 ± 26.2% (n = 33), those classified as in moderate shock had a mean MOx of 56.9 ± 26.9% (n = 25) and those classified as in severe shock had a MOx of 31.0 ± 17.1% (n = 11). Mean MOx for each of these groups was statistically different from the healthy control group (p<0.05). Receiver operating characteristic (ROC) analyses show that MOx and shock index (heart rate/systolic blood pressure) identified shock similarly well (area under the curves (AUC) = 0.857 and 0.828, respectively). However, MOx identified mild shock better than shock index in the same group of patients (AUC = 0.782 and 0.671, respectively). Conclusions The results obtained from this pilot study indicate that MOx correlates with shock severity in a population of trauma patients. Noninvasive and continuous MOx holds promise to aid in patient triage and to evaluate patient condition throughout the course of resuscitation. PMID:27820776

Shock progression and survival after use of a condom uterine balloon tamponade package in women with uncontrolled postpartum hemorrhage.

PubMed

Burke, Thomas F; Danso-Bamfo, Sandra; Guha, Moytrayee; Oguttu, Monica; Tarimo, Vincent; Nelson, Brett D

2017-10-01

To examine the outcomes of women in advanced shock from uncontrolled postpartum hemorrhage (PPH) who underwent placement of an Every Second Matters for Mothers and Babies Uterine Balloon Tamponade (ESM-UBT) device. In a prospective case series, data were collected for women who received an ESM-UBT device at healthcare facilities in Kenya, Senegal, Sierra Leone, and Tanzania between September 1, 2012, and September 30, 2016. Shock class was assigned on the basis of recorded blood pressures and mental status at the time of UBT placement. Data for 306 women with uncontrolled PPH from uterine atony across 117 facilities were analyzed. Normal vital signs or class I/II shock were reported for 166 (54.2%). In this group, one death occurred and was attributed to PPH (survival rate 99.4%). There were no cases of shock progression. One hundred and eleven (36.3%) were in class III shock and 29 (9.5%) in class IV shock; the respective survival rates were 97.3% (n=108) and 86.2% (n=25). The ESM-UBT device arrests hemorrhage, prevents shock progression, and is associated with high survival rates among women with uncontrolled PPH from uterine atony. © 2017 International Federation of Gynecology and Obstetrics.

Comparative analysis of survival between elderly and non-elderly severe sepsis and septic shock resuscitated patients

PubMed Central

Palomba, Henrique; Corrêa, Thiago Domingos; Silva, Eliézer; Pardini, Andreia; de Assuncao, Murillo Santucci Cesar

2015-01-01

Objective To compare outcomes between elderly (≥65 years old) and non-elderly (<65 years old) resuscitated severe sepsis and septic shock patients and determine predictors of death among elderly patients. Methods Retrospective cohort study including 848 severe sepsis and septic shock patients admitted to the intensive care unit between January 2006 and March 2012. Results Elderly patients accounted for 62.6% (531/848) and non-elderly patients for 37.4% (317/848). Elderly patients had a higher APACHE II score [22 (18-28) versus 19 (15-24); p<0.001], compared to non-elderly patients, although the number of organ dysfunctions did not differ between the groups. No significant differences were found in 28-day and in-hospital mortality rates between elderly and non-elderly patients. The length of hospital stay was higher in elderly compared to non-elderly patients admitted with severe sepsis and septic shock [18 (10-41) versus 14 (8-29) days, respectively; p=0.0001]. Predictors of death among elderly patients included age, site of diagnosis, APACHE II score, need for mechanical ventilation and vasopressors. Conclusion In this study population early resuscitation of elderly patients was not associated with increased in-hospital mortality. Prospective studies addressing the long-term impact on functional status and quality of life are necessary. PMID:26313436

The Stop-Only-While-Shocking algorithm reduces hands-off time by 17% during cardiopulmonary resuscitation - a simulation study.

PubMed

Koch Hansen, Lars; Mohammed, Anna; Pedersen, Magnus; Folkestad, Lars; Brodersen, Jacob; Hey, Thomas; Lyhne Christensen, Nicolaj; Carter-Storch, Rasmus; Bendix, Kristoffer; Hansen, Morten R; Brabrand, Mikkel

2016-12-01

Reducing hands-off time during cardiopulmonary resuscitation (CPR) is believed to increase survival after cardiac arrests because of the sustaining of organ perfusion. The aim of our study was to investigate whether charging the defibrillator before rhythm analyses and shock delivery significantly reduced hands-off time compared with the European Resuscitation Council (ERC) 2010 CPR guideline algorithm in full-scale cardiac arrest scenarios. The study was designed as a full-scale cardiac arrest simulation study including administration of drugs. Participants were randomized into using the Stop-Only-While-Shocking (SOWS) algorithm or the ERC2010 algorithm. In SOWS, chest compressions were only interrupted for a post-charging rhythm analysis and immediate shock delivery. A Resusci Anne HLR-D manikin and a LIFEPACK 20 defibrillator were used. The manikin recorded time and chest compressions. Sample size was calculated with an α of 0.05 and 80% power showed that we should test four scenarios with each algorithm. Twenty-nine physicians participated in 11 scenarios. Hands-off time was significantly reduced 17% using the SOWS algorithm compared with ERC2010 [22.1% (SD 2.3) hands-off time vs. 26.6% (SD 4.8); P<0.05]. In full-scale cardiac arrest simulations, a minor change consisting of charging the defibrillator before rhythm check reduces hands-off time by 17% compared with ERC2010 guidelines.

Pediatric defibrillation after cardiac arrest: initial response and outcome

PubMed Central

Rodríguez-Núñez, Antonio; López-Herce, Jesús; García, Cristina; Domínguez, Pedro; Carrillo, Angel; Bellón, Jose María

2006-01-01

Introduction Shockable rhythms are rare in pediatric cardiac arrest and the results of defibrillation are uncertain. The objective of this study was to analyze the results of cardiopulmonary resuscitation that included defibrillation in children. Methods Forty-four out of 241 children (18.2%) who were resuscitated from inhospital or out-of-hospital cardiac arrest had been treated with manual defibrillation. Data were recorded according to the Utstein style. Outcome variables were a sustained return of spontaneous circulation (ROSC) and one-year survival. Characteristics of patients and of resuscitation were evaluated. Results Cardiac disease was the major cause of arrest in this group. Ventricular fibrillation (VF) or pulseless ventricular tachycardia (PVT) was the first documented electrocardiogram rhythm in 19 patients (43.2%). A shockable rhythm developed during resuscitation in 25 patients (56.8%). The first shock (dose, 2 J/kg) terminated VF or PVT in eight patients (18.1%). Seventeen children (38.6%) needed more than three shocks to solve VF or PVT. ROSC was achieved in 28 cases (63.6%) and it was sustained in 19 patients (43.2%). Only three patients (6.8%), however, survived at 1-year follow-up. Children with VF or PVT as the first documented rhythm had better ROSC, better initial survival and better final survival than children with subsequent VF or PVT. Children who survived were older than the finally dead patients. No significant differences in response rate were observed when first and second shocks were compared. The survival rate was higher in patients treated with a second shock dose of 2 J/kg than in those who received higher doses. Outcome was not related to the cause or the location of arrest. The survival rate was inversely related to the duration of cardiopulmonary resuscitation. Conclusion Defibrillation is necessary in 18% of children who suffer cardiac arrest. Termination of VF or PVT after the first defibrillation dose is achieved in a low percentage of cases. Despite a sustained ROSC being obtained in more than one-third of cases, the final survival remains low. The outcome is very poor when a shockable rhythm develops during resuscitation efforts. New studies are needed to ascertain whether the new international guidelines will contribute to improve the outcome of pediatric cardiac arrest. PMID:16882339

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial

PubMed Central

2013-01-01

Background Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Methods Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Results Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. Conclusions Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. Trial registration ISRCTN69856593 PMID:23496872

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

PubMed

Maitland, Kathryn; George, Elizabeth C; Evans, Jennifer A; Kiguli, Sarah; Olupot-Olupot, Peter; Akech, Samuel O; Opoka, Robert O; Engoru, Charles; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Brent, Bernadette; Nteziyaremye, Julius; Mpoya, Ayub; Prevatt, Natalie; Dambisya, Cornelius M; Semakula, Daniel; Ddungu, Ahmed; Okuuny, Vicent; Wokulira, Ronald; Timbwa, Molline; Otii, Benedict; Levin, Michael; Crawley, Jane; Babiker, Abdel G; Gibb, Diana M

2013-03-14

Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. ISRCTN69856593.

Computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in endotoxin-induced shock.

PubMed

Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Sugimachi, Masaru

2017-10-23

Hemodynamic resuscitation in septic shock requires aggressive fluid replacement and appropriate use of vasopressors to optimize arterial pressure (AP) and cardiac output (CO). Because responses to these drugs vary between patients and within patient over time, strict monitoring of patient condition and repetitive adjustment of drug dose are required. This task is time and labor consuming, and is associated with poor adherence to resuscitation guidelines. To overcome this issue, we developed a computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in septic shock, and evaluated the performance of the system in a canine model of endotoxin shock. Our system monitors AP, CO and central venous pressure, and computes arterial resistance (R), stressed blood volume (V) and Frank-Starling slope of left ventricle (S). The system controls R with noradrenaline (NA), and V with Ringer's acetate solution (RiA), thereby controlling AP and CO. In 4 dogs, AP and CO were measured invasively. In another 4 dogs, AP and CO were measured less invasively using clinically acceptable modalities, aiming to make the system clinically feasible. In all 8 dogs, endotoxin shock was induced by injecting Escherichia coli lipopolysaccharide, which significantly decreased AP from 95 (91-108) to 43 (39-45) mmHg, and CO from 112 (104-142) to 62 (51-73) ml·min -1 ·kg -1 . The system was then connected to the dogs, and activated. System performance was observed over a period of 4 h. Our system immediately started infusions of NA and RiA. Within 40 min, RiA increased V to target level, and NA maintained R at target level, while S was concomitantly increased. These resulted in restoration of AP to 70 (69-71) mmHg and CO to 130 (125-138) ml·min -1 ·kg -1 . Median of absolute performance error, an index of precision of control, was small in AP [2.5 (2.1-4.5) %] and CO [2.4 (1.4-5.5) %], which were not increased even when the variables were measured less invasively. In a canine model of endotoxin shock, our system automatically improved and maintained AP and CO at their target values with small performance error. Our system is potentially an attractive clinical tool for rescuing patients with septic shock.

STUDIES IN RESUSCITATION: IV. THE RETURN OF FUNCTION IN THE CENTRAL NERVOUS SYSTEM AFTER TEMPORARY CEREBRAL ANÆMIA

PubMed Central

Pike, F. H.; Guthrie, C. C.; Stewart, G. N.

1908-01-01

The experiments on cerebral anæmia have enabled us to duplicate, by an entirely different method, many of the results obtained by anatomical division or removal of parts of the central nervous system. In some respects the method of anæmia permits of greater precision than the method of division or excision, and avoids, in great measure, the disturbances due to the wound and to the hemorrhage caused by the latter method. The method of general anæmia, as Couty pointed out long ago, leaves something to be desired in the matter of exact localization, but this objection may be met, in some degree at least, by appropriate methods of investigation. It is desirable that the results obtained by the method of section should be duplicated by some other method in order to eliminate as much as possible the effects due to the irritation produced by the anatomical lesion. Our results show, as we believe, that, of the bulbar mechanisms studied, the respiratory is the most automatic, the vasomotor in part automatic, and the cardiac like the swallowing mechanism, almost wholly dependent upon afferent impulses for the arousal and discharge of its normal activity. The eye reflexes return during the resuscitation period in the animals in which the cerebral anæmia has not been too prolonged. The motor cortex loses its excitability during anæmia, but may regain it after the reëstablishment of the circulation. The pilomotor mechanism is disturbed during the spasms which occur at a certain stage in the resuscitation. The temperature falls during the occlusion period, but rises again, often to far above normal, in the days following the anæmia. So many disturbing factors, such as the violent muscular contractions during spasms, enter into the problem that it is impossible to say that there is an actual disturbance of the temperature regulating mechanism although we are inclined to believe that this is the case. All the senses return, following cerebral anæmia, but sight and hearing may afterwards fail without causing the death of the animal. The mental processes may return without any apparent deficiency, if the period of anæmia has been short. After longer occlusion, apparent insanity has been seen, and in one case, apparent total loss of mental processes occurred. The reflex excitability of the cord returns rather early in the resuscitation period. Reflexes from the anterior part of the cord first involve muscles on the same side as the stimulus, and later cross to involve muscles of the opposite side. The spinal cord sometimes falls into much the same condition as that following spinal transection, and the scratch reflex appears. Spinal transection, when these reflexes have appeared, does not produce shock. Practically all phenomena of spinal shock may be reproduced without section of the cord. We conclude, therefore, that spinal shock is due more to the cutting off of the reflex pathways through the higher centers of the nervous system than to the stimulation of inhibitory fibers by the anæmia. PMID:19867144

Obstetric hemorrhage and shock management: using the low technology Non-pneumatic Anti-Shock Garment in Nigerian and Egyptian tertiary care facilities.

PubMed

Miller, Suellen; Fathalla, Mohamed M F; Ojengbede, Oladosu A; Camlin, Carol; Mourad-Youssif, Mohammed; Morhason-Bello, Imran O; Galadanci, Hadiza; Nsima, David; Butrick, Elizabeth; Al Hussaini, Tarek; Turan, Janet; Meyer, Carinne; Martin, Hilarie; Mohammed, Aminu I

2010-10-18

Obstetric hemorrhage is the leading cause of maternal mortality globally. The Non-pneumatic Anti-Shock Garment (NASG) is a low-technology, first-aid compression device which, when added to standard hypovolemic shock protocols, may improve outcomes for women with hypovolemic shock secondary to obstetric hemorrhage in tertiary facilities in low-resource settings. This study employed a pre-intervention/intervention design in four facilities in Nigeria and two in Egypt. Primary outcomes were measured mean and median blood loss, severe end-organ failure morbidity (renal failure, pulmonary failure, cardiac failure, or CNS dysfunctions), mortality, and emergency hysterectomy for 1442 women with ≥750 mL blood loss and at least one sign of hemodynamic instability. Comparisons of outcomes by study phase were assessed with rank sum tests, relative risks (RR), number needed to treat for benefit (NNTb), and multiple logistic regression. Women in the NASG phase (n = 835) were in worse condition on study entry, 38.5% with mean arterial pressure <60 mmHg vs. 29.9% in the pre-intervention phase (p = 0.001). Despite this, negative outcomes were significantly reduced in the NASG phase: mean measured blood loss decreased from 444 mL to 240 mL (p < 0.001), maternal mortality decreased from 6.3% to 3.5% (RR 0.56, 95% CI 0.35-0.89), severe morbidities from 3.7% to 0.7% (RR 0.20, 95% CI 0.08-0.50), and emergency hysterectomy from 8.9% to 4.0% (RR 0.44, 0.23-0.86). In multiple logistic regression, there was a 55% reduced odds of mortality during the NASG phase (aOR 0.45, 0.27-0.77). The NNTb to prevent either mortality or severe morbidity was 18 (12-36). Adding the NASG to standard shock and hemorrhage management may significantly improve maternal outcomes from hypovolemic shock secondary to obstetric hemorrhage at tertiary care facilities in low-resource settings.

Optimization of Lyophilized Plasma for Use in Combat Casualties

DTIC Science & Technology

2015-01-01

respiratory distress syndrome and multiple organ failure in combat casualties. This model was developed at Oregon Health & Science University (OHSU) and...during the controlled hemorrhage to induce acidosis and coagulopathy. This reflects current civilian pre-hospital resuscitative practices. Operative

MitoQ modulates oxidative stress and decreases inflammation following hemorrhage.

PubMed

Powell, Rebecca D; Swet, Jacob H; Kennedy, Kenneth L; Huynh, Toan T; Murphy, Michael P; Mckillop, Iain H; Evans, Susan L

2015-03-01

Oxidative stress associated with hemorrhagic shock and reperfusion (HSR) results in the production of superoxide radicals and other reactive oxygen species, leading to cell damage and multiple-organ dysfunction. We sought to determine if MitoQ, a mitochondria-targeted antioxidant, reduces morbidity in a rat model of HSR by limiting oxidative stress. HSR was achieved in male rats by arterial blood withdrawal to a mean arterial pressure of 25 ± 2 mm Hg for 1 hour before resuscitation. MitoQ (5 mg/kg), TPP (triphenylphosphonium, 5 mg/kg) or saline (0.9% vol./vol.) was administered intravenously 30 minutes before resuscitation, followed by an intraperitoneal administration (MitoQ, 20 mg/kg) immediately after resuscitation (n = 5 per group). Morbidity was assessed based on cumulative markers of animal distress (0-10 scale). Rats were sacrificed 2 hours after procedure completion, and liver tissue was collected and processed for histology or assayed for lipid peroxidation (thiobarbituric acid reactive substance [TBARS]) or endogenous antioxidant (catalase, glutathione peroxidase [GPx], and superoxide dismutase) activity. HSR significantly increased morbidity as well as TBARS and catalase activities versus sham. Conversely, no difference in GPx or superoxide dismutase activity was measured between sham, HSR, and TPP, MitoQ administration reduced morbidity versus HSR (5.8 ± 0.3 vs. 7.6 ± 0.3; p < 0.05), while TPP administration significantly reduced hepatic necrosis versus both HSR and HSR-MitoQ (1.2 ± 0.1 vs. 2.0 ± 0.2 vs. 1.9 ± 0.2; p < 0.05, n = 5). Analysis of oxidative stress demonstrated increased TBARS and GPx in HSR-MitoQ versus sham (12.0 ± 1.1 μM vs. 6.2 ± 0.5 μM and 37.9 ± 3.0 μmol/min/mL vs. 22.9 ± 2.7 μmol/min/mL, TBARS and GPx, respectively, n = 5; p < 0.05). Conversely, catalase activity in HSR-MitoQ was reduced versus HSR (1.96 ± 1.17 mol/min/mL vs. 2.58 ± 1.81 mol/min/mL; n = 5; p < 0.05). Finally, MitoQ treatment decreased tumor necrosis factor α (0.66 ± 0.07 pg/mL vs. 0.92 ± 0.08 pg/mL) and interleukin 6 (7.3 ± 0.8 pg/mL vs. 11 ± 0.9 pg/mL) versus HSR as did TPP alone (0.58 ± 0.05 pg/mL vs. 0.92 ± 0.08 pg/mL; 6.7 ± 0.6 pg/mL vs. 11 ± 0.9 pg/mL; n = 5; p < 0.05). Our data demonstrate that MitoQ treatment following hemorrhage significantly limits morbidity and decreases hepatic tumor necrosis factor α and interleukin 6. In addition, MitoQ differentially modulates oxidative stress and hepatic antioxidant activity.

Pressure threshold for shock wave induced renal hemorrhage.

PubMed

Mayer, R; Schenk, E; Child, S; Norton, S; Cox, C; Hartman, C; Cox, C; Carstensen, E

1990-12-01

Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism.

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

PubMed Central

Rudd, Penny A.; Wilson, Jane; Gardner, Joy; Larcher, Thibaut; Babarit, Candice; Le, Thuy T.; Anraku, Itaru; Kumagai, Yutaro; Loo, Yueh-Ming; Gale, Michael; Akira, Shizuo; Khromykh, Alexander A.

2012-01-01

Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/− mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/− mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome. PMID:22761364

Coenzyme Q10: A New Treatment for Hemorrhagic Shock

DTIC Science & Technology

2014-10-29

SUBJECT TERMS hemorrhagic shock, ubiquinol, Coenzyme Q10, patient outcome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...o leo& to tboOigllll failure. The < Iota fur AlM •1 ha"’ boon ._...runym.,..,; •• ted in p=en~atlons and publiobed tn Expu""’""" P/u<llology. Tho

Analysis of bystander CPR quality during out-of-hospital cardiac arrest using data derived from automated external defibrillators.

PubMed

Fernando, Shannon M; Vaillancourt, Christian; Morrow, Stanley; Stiell, Ian G

2018-07-01

Little is known regarding the quality of cardiopulmonary resuscitation (CPR) performed by bystanders in out-of-hospital cardiac arrest (OHCA). We sought to determine quality of bystander CPR provided during OHCA using CPR quality data stored by Automated External Defibrillators (AEDs). We used the Resuscitation Outcomes Consortium database to identify OHCA cases of presumed cardiac etiology where an AED was utilized. We then matched AED data to each case identified. AED data was analyzed using manufacturer software in order to determine overall measures of bystander CPR quality, changes in bystander CPR quality over time, and adherence to existing 2010 Resuscitation Quality Guidelines. 100 cases of OHCA of presumed cardiac etiology involving bystander CPR and with corresponding AED data. Mean age was 62.3 years, and 75% were male. Bystanders demonstrated high-quality CPR over all minutes of resuscitation, with a chest compression fraction of 76%, a compression depth of 5.3 cm, and a compression rate of 111.2 compressions/min. Mean perishock pause was 26.8 s. Adherence rates to 2010 Resuscitation Guidelines for compression rate and depth were found to be 66% and 55%, respectively. CPR quality was lowest in the first minute, resulting from increased delay to rhythm analysis (mean 40.7 s). In cases involving shock delivery, latency from initiation of AED to shock delivery was 59.2 s. We found that bystanders perform high-quality CPR, with strong adherence rates to existing Resuscitation Guidelines. High-quality CPR is maintained over the first five minutes of resuscitation, but was lowest in the first minute. Copyright © 2018 Elsevier B.V. All rights reserved.

Fluid resuscitation of the trauma patient: How much is enough?

PubMed Central

Hamilton, Stewart M.; Breakey, Pat

1996-01-01

Patient management in the prehospital resuscitative phase after trauma is vitally important to the outcome. Early definitive care remains the essential element in improving morbidity and mortality. In Canada, where a large proportion of trauma occurs at sites distant from a trauma centre, the prehospital resuscitative phase is long and has even greater potential to affect outcome. Conventional teaching about the end points of resuscitation has promoted the concept of normalization of hemodynamic parameters with maintenance of end-organ perfusion, as measured by the hourly urine output. Recent work in patients with a closed head injury and in patients with penetrating torso trauma challenge the notion that trauma patients are homogeneous with respect to these end points. In the Canadian setting of blunt injury, where a closed head injury is usually suspected and often present, the evidence from clinical studies suggests that an aggressive approach to maintaining blood pressure is warranted. In penetrating torso injury in an urban setting, there is evidence to suggest that delaying resuscitation until hemorrhage is controlled is beneficial. More Canadian clinical trials are required in this area. In the meantime, the priorities of resuscitation must be carefully assessed for each patient and pattern of injury. PMID:8599784

A tourniquet assisted cardiopulmonary resuscitation augments myocardial perfusion in a porcine model of cardiac arrest.

PubMed

Yang, Zhengfei; Tang, David; Wu, Xiaobo; Hu, Xianwen; Xu, Jiefeng; Qian, Jie; Yang, Min; Tang, Wanchun

2015-01-01

During cardiopulmonary resuscitation (CPR), myocardial blood flow generated by chest compression rarely exceeds 35% of its normal level. Cardiac output generated by chest compression decreases gradually with the prolongation of cardiac arrest and resuscitation. Early studies have demonstrated that myocardial blood flow during CPR is largely dependent on peripheral vascular resistance. In this study, we investigated the effects of chest compression in combination with physical control of peripheral vascular resistance assisted by tourniquets on myocardial blood flow during CPR. Ventricular fibrillation was induced and untreated for 7 min in ten male domestic pigs weighing between 33 and 37 kg. The animals were then randomized to receive CPR alone or a tourniquet assisted CPR (T-CPR). In the CPR alone group, chest compression was performed by a miniaturized mechanical chest compressor. In the T-CPR group, coincident with the start of resuscitation, the thin elastic tourniquets were wrapped around the four limbs from the distal end to the proximal part. After 2 min of CPR, epinephrine (20 μg/kg) was administered via the femoral vein. After 5 min of CPR, defibrillation was attempted by a single 150 J shock. If resuscitation was not successful, CPR was resumed for 2 min before the next defibrillation. The protocol was continued until successful resuscitation or for a total of 15 min. Five minutes after resuscitation, the elastic tourniquets were removed. The resuscitated animals were observed for 2h. T-CPR generated significantly greater coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow. There was no difference in both intrathoracic positive and negative pressures between the two groups. All animals were successfully resuscitated with a single shock in both groups. There were no significant changes in hemodynamics observed in the animals treated in the T-CPR group before-and-after the release of tourniquets at post-resuscitation 5 min. T-CPR improves myocardial and cerebral perfusion during CPR. It may provide a new and convenient method for augmenting myocardial and cerebral blood flow during CPR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Intraoperative stroke volume optimization using stroke volume, arterial pressure, and heart rate: closed-loop (learning intravenous resuscitator) versus anesthesiologists.

PubMed

Rinehart, Joseph; Chung, Elena; Canales, Cecilia; Cannesson, Maxime

2012-10-01

The authors compared the performance of a group of anesthesia providers to closed-loop (Learning Intravenous Resuscitator [LIR]) management in a simulated hemorrhage scenario using cardiac output monitoring. A prospective cohort study. In silico simulation. University hospital anesthesiologists and the LIR closed-loop fluid administration system. Using a patient simulator, a 90-minute simulated hemorrhage protocol was run, which included a 1,200-mL blood loss over 30 minutes. Twenty practicing anesthesiology providers were asked to manage this scenario by providing fluids and vasopressor medication at their discretion. The simulation program was also run 20 times with the LIR closed-loop algorithm managing fluids and an additional 20 times with no intervention. Simulated patient weight, height, heart rate, mean arterial pressure, and cardiac output (CO) were similar at baseline. The mean stroke volume, the mean arterial pressure, CO, and the final CO were higher in the closed-loop group than in the practitioners group, and the coefficient of variance was lower. The closed-loop group received slightly more fluid (2.1 v 1.9 L, p < 0.05) than the anesthesiologist group. Despite the roughly similar volumes of fluid given, the closed-loop maintained more stable hemodynamics than the practitioners primarily because the fluid was given earlier in the protocol and CO optimized before the hemorrhage began, whereas practitioners tended to resuscitate well but only after significant hemodynamic change indicated the need. Overall, these data support the potential usefulness of this closed-loop algorithm in clinical settings in which dynamic predictors are not available or applicable. Published by Elsevier Inc.

The pattern of early lung parenchymal and air space injury following acute blood loss.

PubMed

Younger, J G; Taqi, A S; Jost, P F; Till, G O; Johnson, K J; Stern, S A; Hirschl, R B

1998-07-01

Acute lung injury is a frequent clinical occurrence following blood loss and trauma. The nature of this injury remains poorly understood. To examine the relative parenchymal and intra-alveolar distribution of inflammation in a rat model of hemorrhage and resuscitation. Rats were anesthetized and subjected to hemorrhage followed by resuscitation with shed blood and saline. Myeloperoxidase activity of lung homogenates and cytology of bronchoalveolar lavage fluid were used to measure total lung and intra-alveolar neutrophil invasion. Extravasation of i.v.-administered [125I]-albumin was used to determine total lung and alveolar permeability. Permeability results were analyzed using their base-10 logarithmic transformations. 86 animals were studied. Whole-lung myeloperoxidase activity was increased (control = 0.34 +/- 0.16 units, injured = 0.84 +/- 0.43 units, p < 0.01), while there was no difference in intra-alveolar leukocyte counts (injured = 1.85 +/- 1.30 x 10(5)/mL, control = 2.44 +/- 1.75 x 10(5)/mL, p = 0.40), suggesting that the cellular component of the injury was more severe in the intravascular and interstitial spaces. There was a strong trend toward increased permeability in the interstitial compartment, and a significant increase in permeability in the intra-alveolar compartment (whole-lung permeability: control = -0.27 +/- 0.19 units, injured = 0.10 +/- 0.55 units, p = 0.06; alveolar permeability: control = -2.00 +/- 0.47 units, injured = -1.32 +/- 0.49 units, p < 0.01), suggesting that the loss of integrity to macromolecules was not limited to the interstitium. Hemorrhage and resuscitation resulted in an acute lung injury characterized by extravasation of intravascular protein into both the interstitium and the intra-alveolar space. Neutrophil invasion of the lung was demonstrable only in the interstitial compartment.

Bronchospasm and anaphylactic shock following lidocaine aerosol inhalation in a patient with butane inhalation lung injury.

PubMed

Lee, Min-Young; Park, Kyong Ah; Yeo, So-Jeong; Kim, Shin-Hee; Goong, Hyeun-Jeong; Jang, An-Soo; Park, Choon-Sik

2011-10-01

Allergic reactions to local anesthetics are very rare and represent <1% of all adverse local anesthetics reactions. A 54-year-old man was admitted to the hospital in the winter because of shortness of breath. The patient reportedly had an inhalation lung injury due to butane gas fuel. On the fifth day, he developed an asthmatic attack and anaphylactic shock immediately after lidocaine aerosol administration to prepare for bronchoscopy to confirm an acute inhalational lung injury diagnosis. Cardiopulmonary resuscitation was performed immediately after respiratory arrest, and the patient was admitted to the intensive care unit intubated and on a ventilator. He was extubated safely on the third post-cardiopulmonary resuscitation day. These observations suggest that aerosol lidocaine anesthesia may cause airway narrowing and anaphylactic shock. Practitioners should be aware of this potential complication. We report on this case with a brief review of the literature.

Shock in the Nonhuman Primate. Volume 2. Abstracts of the Published Literature, 1974-1977

DTIC Science & Technology

1977-06-01

primates from hemorrhagic and septic shock. Trunkey, D., J. Holcroft, and M. A. Carpenter ... ........... .... 42 Calcium flux during hemorrhagic...virtually absent. In vitro endotoxin-leukocyte interaction reproduced all changes seen in sequestered PMN-leukocytes with the exception of leukocyte...Although there is no pre- sently known clinical state referable to lead-endotoxin interaction and since our experimental conditions were not

[Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous oxygen saturation in patients with sepsis].

PubMed

Yu, Bin; Tian, Hui-yan; Hu, Zhen-jie; Zhao, Chai; Liu, Li-xia; Zhang, Yong; Zhu, Gui-jun; Wang, Lan-tao; Wu, Xin-hui; Li, Juan

2013-10-01

To compare the efficacy of fluid resuscitation as guided by lactate clearance rate (LCR) and central venous oxygen saturation (ScvO2) in patients with sepsis. A prospective randomized control study was conducted. Fifty patients diagnosed with severe sepsis or septic shock from January 2011 to February 2012 in department of critical care medicine of Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were randomly divided into two groups according to the sequence (each n=25): ScvO2 group and LCR group. After ICU admission, the patients were treated symptomatically timely, and fluid resuscitation was started as early as possible according to Surviving Sepsis Campaign guidance for management of severe sepsis and septic shock 2008. Central venous pressure (CVP)≥8 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure (MAP)≥65 mm Hg and ScvO2≥0.70 served as goal values to accomplish the fluid resuscitation therapy in ScvO2 group, while CVP≥8 mm Hg, MAP≥65 mm Hg, LCR≥10% served as goal value to accomplish the fluid resuscitation therapy in LCR group. The general condition and clinical characteristics on arrival in ICU, changes in CVP, MAP, ScvO2, lactate level and/or LCR before (0 hour) and 3, 6, 72 hours after the start of fluid resuscitation and the other related conditions during the therapy were recorded. There was no significant difference in general data or clinical characteristics before the start of therapy, occurrence of organ dysfunction, or treatment measures during different time periods after start of fluid resuscitation. Compared with the condition immediately before fluid resuscitation, at 3 hours after start of fluid resuscitation, CVP were improved in LCR and ScvO2 groups (8.58±1.17 mm Hg vs. 6.33±1.21 mm Hg, 9.08±2.43 mm Hg vs. 5.33±0.98 mm Hg, both P<0.05); at 6 hours after start of fluid resuscitation, heart rate (HR) and respiratory rate (RR) were lowered in LCR and ScvO2 groups (HR: 96±18 bpm vs. 127±13 bpm, 98±13 bpm vs. 116±19 bpm, RR: 23±3 times/min vs. 33±9 times/min, 24±5 times/min vs. 35±6 times/min, all P<0.05), oxygenation index (PaO2/FiO2) was increased in LCR and ScvO2 groups (179±41 mm Hg vs. 86±21 mm Hg, 202±33 mm Hg vs. 95±17 mm Hg, both P<0.05), and there was no significant difference in MAP in both groups. There was no significant difference in all indexes between two groups. In LCR group, 3 hours after start of fluid resuscitation, lactate level was significantly decreased (2.81±0.18 mmol/L vs. 3.43±1.31 mmol/L, P<0.05). Compared with the value 3 hours after start of fluid resuscitation, LCR was significantly improved at 6 hours and 72 hours after start of fluid resuscitation in LCR group [(42.69±8.75)%, (48.87±9.69)% vs. (20.32±4.58)%, both P<0.05]. Compared with that immediately before fluid resuscitation, ScvO2 was significant improved in ScvO2 group at 3 hours after start of fluid resuscitation (0.65±0.04 vs. 0.53±0.06, P<0.05). There was no significant difference in success rate of fluid resuscitation comparing that of 6 hours and that of 72 hours [6 hours: 72% (18/25) vs. 64% (16/25), χ(2)=0.368, P=0.762; 72 hours: 88% (22/25) vs. 88% (22/25) ,χ(2)=0.000, P=1.000], length of ICU stay (8±3 days vs. 10±4 days, t=0.533, P=0.874), length of hospital stay (29±11 days vs. 35±16 days, t=0.692, P=0.531), improvement rate [84% (21/25) vs. 76%(19/25), χ(2)=0.500, P=0.480] or 28-day mortality [20% (5/25) vs. 28% (7/25), χ(2)=0.439, P=0.742] between LCR and ScvO2 groups. Both LCR and ScvO2 can be taken as the index in confirming the endpoint of fluid resuscitation for patients with severe sepsis and septic shock. Fluid resuscitation therapy under the guidance of LCR is accurate and reliable in patients with severe sepsis and septic shock.

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage.

PubMed

Patton, J H; Lyden, S P; Ragsdale, D N; Croce, M A; Fabian, T C; Proctor, K G

1998-05-01

Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

Early resuscitation with polymerized bovine hemoglobin reverses acidosis, but not peripheral tissue oxygenation, in a severe hamster shock model.

PubMed

Wettstein, Reto; Tsai, Amy G; Harder, Yves; Erni, Dominique; Intaglietta, Marcos

2006-11-01

Awake hamsters equipped with the dorsal window chamber preparation were subjected to hemorrhage of 50% of the estimated blood volume. Initial resuscitation (25% of estimated blood volume) with polymerized bovine hemoglobin (PBH) or 10% hydroxyethyl starch (HES) occurred in concert with an equivolumetric bleeding to simulate the early, prehospital setting (exchange transfusion). Resuscitation (25% of estimated blood volume) without bleeding was performed with PBH, HES, or autologous red blood cells (HES-RBCs). Peripheral microcirculation, tissue oxygenation, and systemic hemodynamic and blood gas parameters were assessed. After exchange transfusion, base deficit was -8.6 +/- 3.7 mmol/L (PBH) and -5.1 +/- 5.3 mmol/L (HES) (not significant). Functional capillary density was 17% +/- 6% of baseline (PBH) and 31% +/- 11% (HES) (P < 0.05) and arteriolar diameter 73% +/- 3% of baseline (PBH) and 90% + 5% (HES) (P < 0.01). At the end, hemoglobin levels were 3.7 +/- 0.3 g/dL with HES, 8.2 +/- 0.6 g/dL with PBH, and 10.4 +/- 0.8 g/dL with HES-RBCs (P < 0.01 HES vs. PBH and HES-RBCs, P < 0.05 PBH vs. HES-RBCs). Base excess was restored to baseline with PBH and HES-RBCs, but not with HES (P < 0.05). Functional capillary density was 46% +/- 5% of baseline (PBH), 62% + 20% (HES-RBCs), and 36% +/- 19% (HES) (P < 0.01 HES-RBCs vs. HES). Peripheral oxygen delivery and consumption was highest with HES-RBCs, followed by PBH (P < 0.05 HES-RBCs vs. PBH, P < 0.01 HES-RBCs and PBH vs. HES). In conclusion, the PBH led to a correction of base deficit comparable to blood transfusion. However, oxygenation of the peripheral tissue was inferior with PBH. This was attributed to its negative impact on the peripheral microcirculation caused by arteriolar vasoconstriction.

Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

PubMed

Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Tan, Jermaine C K; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

2015-11-01

Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Fifty-six NHS hospitals in England. A total of 1260 patients who presented at EDs with septic shock. EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced cardiovascular support days in critical care for the EGDT group. At 1 year, the incremental net benefit for EGDT versus usual resuscitation was negative at -£725 (95% CI -£3000 to £1550). The probability that EGDT was more cost-effective than usual resuscitation was below 30%. There were no significant differences in any other secondary outcomes, including health-related quality of life, or adverse events. Recruitment was lower at weekends and out of hours. The intervention could not be blinded. There was no significant difference in all-cause mortality at 90 days for EGDT compared with usual resuscitation among adults identified with early septic shock presenting to EDs in England. On average, costs were higher in the EGDT group than in the usual-resuscitation group while quality-adjusted life-years were similar in both groups; the probability that it is cost-effective is < 30%. The ProMISe (Protocolised Management In Sepsis) trial completes the planned trio of evaluations of EGDT across the USA, Australasia and England; all have indicated that EGDT is not superior to usual resuscitation. Recognising that each of the three individual, large trials has limited power for evaluating potentially important subgroups, the harmonised approach adopted provides the opportunity to conduct an individual patient data meta-analysis, enhancing both knowledge and generalisability. Current Controlled Trials ISRCTN36307479. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 97. See the NIHR Journals Library website for further project information.

Hemorrhage and Hemorrhagic Shock in Swine: A Review

DTIC Science & Technology

1989-11-01

17 Temperature Regulation ....................... 18 Blood Gas and Acid- Base Status ....................... 18 Electrolyte...22 Renal Function .................................. 23 Hepatic Function ................................ 24 Central Nervous System Function...MODELS Most porcine hemorrhage models are based on concepts and procedures previously developed in other species, especially the dog. As a consequence

Cardiorespiratory interactions and blood flow generation during cardiac arrest and other states of low blood flow.

PubMed

Sigurdsson, Gardar; Yannopoulos, Demetris; McKnite, Scott H; Lurie, Keith G

2003-06-01

Recent advances in cardiopulmonary resuscitation have shed light on the importance of cardiorespiratory interactions during shock and cardiac arrest. This review focuses on recently published studies that evaluate factors that determine preload during chest compression, methods that can augment preload, and the detrimental effects of hyperventilation and interrupting chest compressions. Refilling of the ventricles, so-called ventricular preload, is diminished during cardiovascular collapse and resuscitation from cardiac arrest. In light of the potential detrimental effects and challenges of large-volume fluid resuscitations, other methods have increasing importance. During cardiac arrest, active decompression of the chest and impedance of inspiratory airflow during the recoil of the chest work by increasing negative intrathoracic pressure and, hence, increase refilling of the ventricles and increase cardiac preload, with improvement in survival. Conversely, increased frequency of ventilation has detrimental effects on coronary perfusion pressure and survival rates in cardiac arrest and severe shock. Prolonged interruption of chest compressions for delivering single-rescuer ventilation or analyzing rhythm before shock delivery is associated with decreased survival rate. Cardiorespiratory interactions are of profound importance in states of cardiovascular collapse in which increased negative intrathoracic pressure during decompression of the chest has a favorable effect and increased intrathoracic pressure with ventilation has a detrimental effect on survival rate.

Amelioration of Ischemia/Reperfusion Injury During Resuscitation from Hemorrhage by Induction of Heme Oxygenase-1 (HO-1) in a Conscious Mouse Model of Uncontrolled Hemorrhage

DTIC Science & Technology

2013-10-01

gauze. For bioluminescence imaging, mice were anes1hetized with isoflurane/a1r and injected ,v; th I 00 µ I of lucifcnn (dissolved m phosphate...buffered salme mto the peritoneal cavity. F1\\ e min after luciferin injection , mice "’ere imaged for 1-5 minutes. Photons emitted from specific regions...kidney. spleen, duodenum, jejunum, ileum, stomach, brain. salivary gland, skeletal muscle, and testes) were removed 5 min following injection of

Clindamycin-induced anaphylactic shock during general anesthesia.

PubMed

Chiou, Chiuan-Shiou; Lin, Su-Man; Lin, Shih-Pin; Chang, Wen-Guei; Chan, Kwok-Hon; Ting, Chien-Kun

2006-11-01

Clindamycin-related anaphylactic reaction is rarely reported. We report a male patient with buccal cancer who was undergoing radical neck dissection when life-threatening anaphylactic shock developed soon after intravenous infusion of clindamycin. Immediate cardiopulmonary resuscitation was performed, and the patient recovered uneventfully. Perioperative anaphylactic shock is a serious problem due to the difficulty of judgment and potentially disastrous outcome. Immediate diagnosis and halting of drug infusion should be the first actions taken.

Technique Development for a Polytrauma Model to Study Partial Resuscitative Endovascular Balloon Occlusion of the Aorta (P-REBOA) in Swine (Sus scrofa)

DTIC Science & Technology

2016-06-01

widely in literature, limiting comparisons. Methods: Yorkshire-cross swine were anesthetized, instrumented, and splenectomized. A simple liver...applicable injury in swine . Use of the tourniquet allowed for consistent liver injury and precise control over hemorrhage.

Prehospital Use of Plasma for Traumatic Hemorrhage

DTIC Science & Technology

2013-06-01

Treatment Trials Network which h as trialed pre-hospital use of midazolam autoinjection for status epilepticus and is tria ling the use of in travenous...history and current status . J Trauma 2011; 70:811-12. 48. Ogilvie MP, Ryan ML, Proctor KG. Hetastarch during initial resuscitation from trauma. J

Current Treatment of Lower Gastrointestinal Hemorrhage

PubMed Central

Raphaeli, Tal; Menon, Raman

2012-01-01

Massive lower gastrointestinal bleeding is a significant and expensive problem that requires methodical evaluation, management, and treatment. After initial resuscitation, care should be taken to localize the site of bleeding. Once localized, lesions can then be treated with endoscopic or angiographic interventions, reserving surgery for ongoing or recurrent bleeding. PMID:24294124

Mesenchymal Stem Cells for the Prevention of Acute Respiratory Distress Syndrome after Pulmonary Contusion and Hemorrhagic Shock

DTIC Science & Technology

2017-10-01

Contusion and Hemorrhagic Shock PRINCIPAL INVESTIGATOR: Martin Schreiber, MD CONTRACTING ORGANIZATION: Oregon Health & Science University Portland, OR...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Oregon Health & Science University 3181 SW Sam Jackson Park Road, Portland, OR 97239 Blood Systems...extubated the animals was not logistically or physically feasible. To improve the welfare of the animal and consistency in the model, we revised our model

Arterioureteral Fistula: Treatment of a Hemorrhagic Shock with Massive Hematuria by Placing a Balloon Catheter.

PubMed

Merzeau, Nicolas; Riquet, Hervé; Nicolacopoulos, Ioannis; Alame, Abbas; Larré, Stéphane

2017-01-01

Arterioureteral fistulas (AUF) are serious diseases with increasing incidence. This case report relates the management of AUF in a patient with a history of abdominal oncological surgery, pelvic radiotherapy, and a double J stent in place. The fistula was discovered during a hemorrhagic shock with massive hematuria. The bleeding was controlled by a balloon catheter which led to endovascular treatment consisting of a covered stent.

Arterioureteral Fistula: Treatment of a Hemorrhagic Shock with Massive Hematuria by Placing a Balloon Catheter

PubMed Central

Riquet, Hervé; Nicolacopoulos, Ioannis; Alame, Abbas

2017-01-01

Arterioureteral fistulas (AUF) are serious diseases with increasing incidence. This case report relates the management of AUF in a patient with a history of abdominal oncological surgery, pelvic radiotherapy, and a double J stent in place. The fistula was discovered during a hemorrhagic shock with massive hematuria. The bleeding was controlled by a balloon catheter which led to endovascular treatment consisting of a covered stent. PMID:28465857

The role of lymph factors in lung injury, bone marrow suppression, and endothelial cell dysfunction in a primate model of trauma-hemorrhagic shock.

PubMed

Deitch, Edwin A; Forsythe, Raquel; Anjaria, Dev; Livingston, David H; Lu, Qi; Xu, Da-Zhong; Redl, Heinz

2004-09-01

Studies in rodent models of trauma-hemorrhagic shock (T/HS) have shown that factors contained in the intestinal lymph are responsible for acute lung injury and bone marrow suppression, and that they contribute to a systemic inflammatory state. Because results observed in rodent T/HS models may not fully reflect the response of injured patients, it is necessary to determine if these results can be replicated in primates before the institution of invasive studies in humans. Thus, the three goals of this study were to determine if diversion of thoracic duct lymph reduced T/HS-induced lung injury; to compare the biologic activity of thoracic duct lymph from baboons subjected to T/HS or trauma sham-shock (T/SS); and to compare the biologic activity and composition of plasma from baboons subjected to T/SS, T/HS, and T/HS with thoracic duct lymph drainage. Three groups of baboons were studied: T/SS plus lymph diversion via a thoracic duct catheter, T/HS, and T/HS plus lymph diversion (T/HS-LD). The trauma component consisted of a neck dissection with resection of the proximal clavicle plus a laparotomy. HS was to a mean arterial pressure of 40 mmHg and was maintained at 40 mmHg until the base excess reached -5 mEq or the total shock period reached 3 h. Volume resuscitation was carried out by reinfusing the shed blood plus crystalloids. Before, during, and after the T/HS or T/SS period, blood and lymph samples were obtained for analysis, and lung samples were harvested for measurement of lung wet-to-dry ratio at 5 h after the end of the shock period. Diversion of thoracic duct lymph prevented T/HS-induced lung injury as reflected in lung wet-to-dry weight ratios (T/SS = 4.6 +/- 0.5; T/HS+LD = 4.8 +/- 0.7; T/HS = 5.4 +/- 0.6; P < 0.05). Lymph from the T/HS group collected during the early postshock period was cytotoxic for human endothelial cells (HUVECs; 16% vs. 100% survival in T/SS lymph) and increased HUVEC monolayer permeability almost 2-fold (P < 0.01). T/HS lymph and plasma also suppressed red blood cell (erythroid burst-forming unit) and white blood cell (granulocyte-monocyte colony-forming unit) progenitor cell growth of human bone marrow to approximately 50% of control, whereas T/SS lymph and plasma were not suppressive (P < 0.05). Plasma cytokine levels were increased to a similar degree in the two T/HS groups. Thus, in a primate model of T/HS, gut-derived factors carried in the lymph potentiates lung injury and endothelial dysfunction, and suppresses bone marrow progenitor cell growth.

Lyophilized plasma attenuates vascular permeability, inflammation and lung injury in hemorrhagic shock.

PubMed

Pati, Shibani; Peng, Zhanglong; Wataha, Katherine; Miyazawa, Byron; Potter, Daniel R; Kozar, Rosemary A

2018-01-01

In severe trauma and hemorrhage the early and empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity and mortality. However, utilization of FFP comes with the significant burden of shipping and storage of frozen blood products. Dried or lyophilized plasma (LP) can be stored at room temperature, transported easily, reconstituted rapidly with ready availability in remote and austere environments. We have previously demonstrated that FFP mitigates the endothelial injury that ensues after hemorrhagic shock (HS). In the current study, we sought to determine whether LP has similar properties to FFP in its ability to modulate endothelial dysfunction in vitro and in vivo. Single donor LP was compared to single donor FFP using the following measures of endothelial cell (EC) function in vitro: permeability and transendothelial monolayer resistance; adherens junction preservation; and leukocyte-EC adhesion. In vivo, using a model of murine HS, LP and FFP were compared in measures of HS- induced pulmonary vascular inflammation and edema. Both in vitro and in vivo in all measures of EC function, LP demonstrated similar effects to FFP. Both FFP and LP similarly reduced EC permeability, increased transendothelial resistance, decreased leukocyte-EC binding and persevered adherens junctions. In vivo, LP and FFP both comparably reduced pulmonary injury, inflammation and vascular leak. Both FFP and LP have similar potent protective effects on the vascular endothelium in vitro and in lung function in vivo following hemorrhagic shock. These data support the further development of LP as an effective plasma product for human use after trauma and hemorrhagic shock.

Trial of early, goal-directed resuscitation for septic shock.

PubMed

Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

2015-04-02

Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).

Resuscitation of severe but brief haemorrhagic shock with PFC in rabbits restores skeletal muscle oxygen delivery and does not alter skeletal muscle metabolism.

PubMed

Audonnet-Blaise, Sandra; Krafft, Marie-Pierre; Smani, Younes; Mertes, Paul-Michel; Marie, Pierre-Yves; Labrude, Pierre; Longrois, Dan; Menu, Patrick

2006-07-01

Studies have demonstrated that perfluorocarbon (PFC) emulsions associated with hyperoxia improved whole body oxygen delivery during resuscitation of acute haemorrhagic shock (HS). Nevertheless the microcirculatory effects of PFC and the potential deleterious effects of hyperoxic reperfusion are still of concern. We investigated (i) the ability of a newly formulated, small sized and highly stable PFC emulsion to increase skeletal muscle oxygen delivery and (ii) the effect of hyperoxic reperfusion on skeletal muscle metabolism after a brief period of ischaemia using an original, microdialysis-based method that allowed simultaneous measurement tissue oxygen pressure (PtiO2) and interstitial lactate and pyruvate. These measurements were carried out in anaesthetised and ventilated (FiO2 = 1) rabbits subjected to acute HS (50% of blood volume withdrawal) and either resuscitated with a PFC emulsion diluted with a 5% albumin solution (16.2 g PFC per kg body weight) (n = 10) or with a modified fluid gelatin solution (Gelofusine) (n = 10). We found no difference between the two groups for the haemodynamic and haematological variables (except for the venous oxygen partial pressure). However, a significant difference was observed in the slope of the regression linear relationship exhibited between the mean arterial pressure (MAP) and the PtiO2, PFC group showing a much steeper slope than Gelofusine group. In addition, PtiO2 values increased linearly with decreasing haematocrit (Hct) values in PFC-resuscitated animals and decreased linearly with decreasing Hct values in Gelofusine-resuscitated animals. There were no differences between the two groups concerning the blood and interstitial lactate/pyruvate ratios suggesting no deleterious effect of hyperoxic resuscitation in skeletal muscle. In conclusion these results suggest that resuscitation of severe, but brief, HS with PFC increased skeletal muscle oxygen delivery without measurable deleterious effects.

Instrument to detect syncope and the onset of shock

NASA Astrophysics Data System (ADS)

McAdams, Daniel R.; Kolodziejski, Noah J.; Stapels, Christopher J.; Fernandez, Daniel E.; Podolsky, Matthew J.; Farkas, Dana; Christian, James F.; Joyner, Michael J.; Johnson, Christopher P.; Paradis, Norman A.

2016-03-01

Currently the diagnosis of hemorrhagic shock is essentially clinical, relying on the expertise of nurses and doctors. One of the first measurable physiological changes that marks the onset of hemorrhagic shock is a decrease in capillary blood flow. Diffuse correlation spectroscopy (DCS) quantifies this decrease. DCS collects and analyzes multiply scattered, coherent, near infrared light to assess relative blood flow. This work presents a preliminary study using a DCS instrument with human subjects undergoing a lower body negative pressure (LBNP) protocol. This work builds on previous successful DCS instrumentation development and we believe it represents progress toward understanding how DCS can be used in a clinical setting.

Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest.

PubMed

Spinelli, Elena; Davis, Ryan P; Ren, Xiaodan; Sheth, Parth S; Tooley, Trevor R; Iyengar, Amit; Sowell, Brandon; Owens, Gabe E; Bocks, Martin L; Jacobs, Teresa L; Yang, Lynda J; Stacey, William C; Bartlett, Robert H; Rojas-Peña, Alvaro; Neumar, Robert W

2016-02-01

To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. Laboratory investigation. University laboratory. Pigs. Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation. A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats.

PubMed Central

Pannen, B H; Köhler, N; Hole, B; Bauer, M; Clemens, M G; Geiger, K K

1998-01-01

Maintenance of hepatic microcirculatory flow after ischemia of the liver is essential to prevent hepatic dysfunction. Thus, we determined the differential role of carbon monoxide (CO) and nitric oxide (NO) in the intrinsic control of sinusoidal perfusion, mitochondrial redox state, and bile production in the isolated perfused rat liver after hemorrhagic shock. Administration of tin protoporphyrin-IX (50 microM), a specific inhibitor of the CO generating enzyme heme oxygenase, caused a decrease in sinusoidal flow that was more pronounced after shock compared with sham shock, as determined by in situ epifluorescence microscopy. This was associated with a shift in hepatocellular redox potential to a more reduced state (increased fluorescence intensity of reduced pyridine nucleotides in hepatocytes, decreased acetoacetate/beta-hydroxybutyrate ratio in the perfusate) and a profound reduction in bile flow. In sharp contrast, the preferential inhibitor of the inducible isoform of NO synthase S-methylisothiourea sulfate (100 microM) did not affect sinusoidal flow, hepatic redox state, or function. This indicates that 1.) endogenously generated CO preserves sinusoidal perfusion after hemorrhagic shock, 2.) protection of the hepatic microcirculation by CO may serve to limit shock-induced liver dysfunction, and 3.) in contrast to CO, inducible NO synthase-derived NO is of only minor importance for the intrinsic control of hepatic perfusion and function under these conditions. PMID:9739056

Different Recovery Profiles of Coagulation Factors, Thrombin Generation, and Coagulation Function After Hemorrhagic Shock in Pigs

DTIC Science & Technology

2012-06-06

Different recovery profiles of coagulation factors, thrombin generation, and coagulation function after hemorrhagic shock in pigs Wenjun Z. Martini ...Defense. Address for reprints: Wenjun Z. Martini , PhD, The US Army Institute of Surgical Research, 3698 Chambers Pass, Ft. Sam Houston, San Antonio, TX...control number 1. REPORT DATE 01 SEP 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Different recovery profiles of

Hemodynamic coherence and the rationale for monitoring the microcirculation.

PubMed

Ince, Can

2015-01-01

This article presents a personal viewpoint of the shortcoming of conventional hemodynamic resuscitation procedures in achieving organ perfusion and tissue oxygenation following conditions of shock and cardiovascular compromise, and why it is important to monitor the microcirculation in such conditions. The article emphasizes that if resuscitation procedures are based on the correction of systemic variables, there must be coherence between the macrocirculation and microcirculation if systemic hemodynamic-driven resuscitation procedures are to be effective in correcting organ perfusion and oxygenation. However, in conditions of inflammation and infection, which often accompany states of shock, vascular regulation and compensatory mechanisms needed to sustain hemodynamic coherence are lost, and the regional circulation and microcirculation remain in shock. We identify four types of microcirculatory alterations underlying the loss of hemodynamic coherence: type 1, heterogeneous microcirculatory flow; type 2, reduced capillary density induced by hemodilution and anemia; type 3, microcirculatory flow reduction caused by vasoconstriction or tamponade; and type 4, tissue edema. These microcirculatory alterations can be observed at the bedside using direct visualization of the sublingual microcirculation with hand-held vital microscopes. Each of these alterations results in oxygen delivery limitation to the tissue cells despite the presence of normalized systemic hemodynamic variables. Based on these concepts, we propose how to optimize the volume of fluid to maximize the oxygen-carrying capacity of the microcirculation to transport oxygen to the tissues.

Impact of plasma viscosity on microcirculatory flow after traumatic haemorrhagic shock: A prospective observational study.

PubMed

Naumann, David N; Hazeldine, Jon; Bishop, Jon; Midwinter, Mark J; Harrison, Paul; Nash, Gerard; Hutchings, Sam D

2018-05-19

Preclinical studies report that higher plasma viscosity improves microcirculatory flow after haemorrhagic shock and resuscitation, but no clinical study has tested this hypothesis. We investigated the relationship between plasma viscosity and sublingual microcirculatory flow in patients during resuscitation for traumatic haemorrhagic shock (THS). Sublingual video-microscopy was performed for 20 trauma patients with THS as soon as feasible in hospital, and then at 24 h and 48 h. Values were obtained for total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index (MFI), microcirculatory heterogeneity index (MHI), and Point of Care Microcirculation (POEM) scores. Plasma viscosity was measured using a Wells-Brookfield cone and plate micro-viscometer. Logistic regression analyses examined relationships between microcirculatory parameters and plasma viscosity, adjusting for covariates (systolic blood pressure, heart rate, haematocrit, rate and volume of fluids, and rate of noradrenaline). Higher plasma viscosity was not associated with improved microcirculatory parameters. Instead, there were weakly significant associations between higher plasma viscosity and lower (poorer) MFI (p = 0.040), higher (worse) MHI (p = 0.033), and lower (worse) POEM scores (p = 0.039). The current study did not confirm the hypothesis that higher plasma viscosity improves microcirculatory flow dynamics in patients with THS. Further clinical investigations are warranted to determine whether viscosity is a physical parameter of importance during resuscitation of these patients.

[Fluid management and cause of death during shock period in patients with severe burns or burns complicated by inhalation injury].

PubMed

Zhang, Ming-liang; Li, Chi; Ma, Chun-xu

2003-11-01

To explore fluid management and cause of death during shock period in severe burns or burns with inhalation injury. One hundred and twelve patients with severe burns or burn complicated by inhalation injury admitted to our hospital from 1991 to 2000 were analyzed. The fluid management and death conditions during shock period were discussed. The fluid volume for resuscitation could be described as follows: the total fluid volume was 2.2 ml/(%TBSA.kg) including colloid fluid 0.5 ml/(%TBSA.kg), crystalloid fluid 1 ml/(%TBSA.kg)and water 0.7 ml/(%TBSA.kg) during first 24 hours. The total fluid volume was 1.8 ml/(%TBSA.kg) including colloid fluid 0.4 ml/(%TBSA.kg), crystalloid fluid 0.7 ml/(%TBSA.kg) and water 0.7 ml/(%TBSA.kg) during second 24 hours. There were no difference in fluid management between burns and burns with inhalation injury. Seven patients died due to respiratory failure during shock period. Many fluid formula can provide guidance for resuscitation and it is very important that early fluid therapy should accord with concrete clinical conditions of patients in order to pass smoothly through shock period. Early fluid management is not different between burns and burns with inhalation injury.

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

PubMed

Kleber, Christian; Becker, Christopher A; Malysch, Tom; Reinhold, Jens M; Tsitsilonis, Serafeim; Duda, Georg N; Schmidt-Bleek, Katharina; Schaser, Klaus D

2015-07-01

Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Large-Volume Crystalloid Fluid Is Associated with Increased Hyaluronan Shedding and Inflammation in a Canine Hemorrhagic Shock Model.

PubMed

Smart, Lisa; Boyd, C J; Claus, M A; Bosio, E; Hosgood, G; Raisis, A

2018-05-04

Shedding of the endothelial glycocalyx precedes leukocyte activation and adherence in acute inflammation. Rapid administration of crystalloid or colloid fluids for treating hemorrhagic shock may cause endothelial glycocalyx shedding, thereby increasing inflammation. This study aimed to compare the effect of different fluid treatments in a canine shock model on glycocalyx biomarker, hyaluronan, and inflammatory biomarkers. Greyhound dogs under general anesthesia subject to hemorrhage for 60 min were given 20 mL kg -1 of either fresh whole blood (FWB), hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg -1 of isotonic crystalloid (CRYST) over 20 min (n = 6 per group). Plasma biomarkers hyaluronan, interleukin (IL) 6, 8, 10, tumor necrosis factor-α, monocyte chemoattractant protein-1, keratinocyte chemokine-like, and atrial natriuretic peptide were measured at baseline, end of hemorrhage (Shock), end of fluid administration (T20), and then 40 (T60), 100 (T120), and 160 (T180) minutes later. Biomarker concentrations were compared between groups using the Kruskal-Wallis test or Fisher's exact test (measurable versus unmeasurable) (significance set at P < 0.05). Hyaluronan concentration peaked early in the CRYST group at T20, compared to HES (P = 0.005) and GELO (P = 0.018), and later in the GELO group at T60, compared to FWB (P < 0.001). The CRYST group had significantly more samples with measurable IL6 at T180 (P = 0.015), compared to GELO, and IL10 at T60, T120, and T180 (all P = 0.015), compared to FWB. There were no significant differences in other biomarker concentrations. In conclusion, rapid large-volume crystalloid administered for hemorrhagic shock was associated with increased hyaluronan and a greater inflammatory response.

Resuscitation from Hypovolemia in Swine with Intraosseous Infusion of a Saturated Salt-Dextran Solution (SSD)

DTIC Science & Technology

1992-10-01

marrow and the proximal tibia is often used for emergency vascular access (3-5). In adults, however, avascular yellow marrow replaces the red marrow of...for histological evaluation of acute lesions, presence or absence of thrombi, fat or bone emboli, necrosis or hemorrhage to the lung, and decreased

Decay-accelerating Factor Limits Hemorrhage-instigated Tissue Injury and Improves Resuscitation Clinical Parameters

DTIC Science & Technology

2012-10-29

thicknesswithacryostat andfixed incoldmethanol for 20min. The fixed sections were permeabilized with 0.2% Triton X-100 in PBS for 10min, then blockedwith 2% bovine ...J Inflamm 1998;48:13. [31] Garratty G. Blood group antigens as tumor markers, parasitic /bacterial/viral receptors, and their association with

Point-of-care optical tool to detect early stage of hemorrhage and shock

NASA Astrophysics Data System (ADS)

Gurjar, Rajan S.; Riccardi, Suzannah L.; Johnson, Blair D.; Johnson, Christopher P.; Paradis, Norman A.; Joyner, Michael J.; Wolf, David E.

2014-02-01

There is a critical unmet clinical need for a device that can monitor and predict the onset of shock: hemorrhagic shock or bleeding to death, septic shock or systemic infection, and cardiogenic shock or blood flow and tissue oxygenation impairment due to heart attack. Together these represent 141 M patients per year. We have developed a monitor for shock based on measuring blood flow in peripheral (skin) capillary beds using diffuse correlation spectroscopy, a form of dynamic light scattering, and have demonstrated proof-of-principle both in pigs and humans. Our results show that skin blood flow measurement, either alone or in conjunction with other hemodynamic properties such as heart rate variability, pulse pressure variability, and tissue oxygenation, can meet this unmet need in a small self-contained patch-like device in conjunction with a hand-held processing unit. In this paper we describe and discuss the experimental work and the multivariate statistical analysis performed to demonstrate proof-of-principle of the concept.

Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency.

PubMed

Ayala, Alfred; Chung, Chun-Shiang; Lomas, Joanne L; Song, Grace Y; Doughty, Lesley A; Gregory, Stephen H; Cioffi, William G; LeBlanc, Brian W; Reichner, Jonathan; Simms, H Hank; Grutkoski, Patricia S

2002-12-01

Acute lung injury (ALI) leading to respiratory distress is a common sequela of shock/trauma, however, modeling this process in mice with a single shock or septic event is inconsistent. One explanation is that hemorrhage is often just a "priming insult," thus, secondary stimuli may be required to "trigger" ALI. To test this we carried out studies in which we assessed the capacity of hemorrhage alone or hemorrhage followed by septic challenge (CLP) to induce ALI. Lung edema, bronchoalveolar lavage interleukin (IL)-6, alveolar congestion, as well as lung IL-6, macrophage inflammatory protein (MIP)-2, and myeloperoxidase (MPO) activity were all increased in mice subjected to CLP at 24 but not 72 hours following hemorrhage. This was associated with a marked increase in the susceptibility of these mice to septic mortality. Peripheral blood neutrophils derived from 24 hours post-hemorrhage, but not Sham animals, exhibited an ex vivo decrease in apoptotic frequency and an increase in respiratory burst capacity, consistent with in vivo "priming." Subsequently, we observed that adoptive transfer of neutrophils from hemorrhaged but not sham-hemorrhage animals to neutropenic recipients reproduce ALI when subsequently septically challenged, implying that this priming was mediated by neutrophils. We also found marked general increases in lung IL-6, MIP-2, and MPO in mice deficient for toll-like receptor (TLR-4) or the combined lack of TLR-4/FasL. However, the TLR-4 defect markedly attenuated neutrophil influx into the lung while not altering the change in local cytokine/chemokine expression. Alternatively, the combined loss of FasL and TLR-4 did not inhibit the increase in MPO and exacerbated lung IL-6/MIP-2 levels even further.

Effect of gender and sex hormones on immune responses following shock.

PubMed

Angele, M K; Schwacha, M G; Ayala, A; Chaudry, I H

2000-08-01

Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

Arterial Blood Gases, Electrolytes and Metabolic Indices Associated with Hemorrhagic Shock: Inter-and Intrainbred Rat Strain Variation

DTIC Science & Technology

2013-03-07

hyperkalemia can also have adverse effects on car- diovascular and neuromuscular function (42, 58, 66). Hence, at least in some inbred rat strains such as BN...to know to interpret arterial blood gases. Philadelphia: Lippincott Williams and Wilkins, 1999. 42. Mazze RI, Escue HM, Houston JB. Hyperkalemia and...MC, Carmona MJ, Auler Júnior JO. Hyperkalemia accompanies hemorrhagic shock and correlates with mor- tality. Clinics (Sao Paulo) 64: 591–597, 2009. 56

A Hemoglobin Based Oxygen Carrier, Bovine Polymerized Hemoglobin (HBOC-201) versus Hetastarch (HEX) in an Uncontrolled Liver Injury Hemorrhagic Shock Swine Model with Delayed Evacuation

DTIC Science & Technology

2004-10-01

A Hemoglobin Based Oxygen Carrier, Bovine Polymerized Hemoglobin (HBOC-201) versus Hetastarch (HEX) in an Uncontrolled Liver Injury Hemorrhagic Shock...Transcutaneous tis- sue oxygenation was restored more rap- idly in HBOC-201 pigs, there was a trend to lower lactic acid, and base deficit was less...lactic acidosis and base deficit (BD) abnormalities, indicating on-going hypoperfusion.2–4 As these abnormalities measured upon hospital arrival

Intramuscular Tranexamic Acid in Tactical and Combat Settings.

PubMed

Vu, Erik N; Wan, Wilson C Y; Yeung, Titus C; Callaway, David W

Uncontrolled hemorrhage remains a leading cause of preventable death in tactical and combat settings. Alternate routes of delivery of tranexamic acid (TXA), an adjunct in the management of hemorrhagic shock, are being studied. A working group for the Committee for Tactical Emergency Casualty Care reviewed the available evidence on the potential role for intramuscular (IM) administration of TXA in nonhospital settings as soon as possible from the point of injury. EMBASE and MEDLINE/PubMed databases were sequentially searched by medical librarians for evidence of TXA use in the following contexts and/or using the following keywords: prehospital, trauma, hemorrhagic shock, optimal timing, optimal dose, safe volume, incidence of venous thromboembolism (VTE), IM bioavailability. A total of 183 studies were reviewed. The strength of the available data was variable, generally weak in quality, and included laboratory research, case reports, retrospective observational reviews, and few prospective studies. Current volume and concentrations of available formulations of TXA make it, in theory, amenable to IM injection. Current bestpractice guidelines for large-volume injection (i.e., 5mL) support IM administration in four locations in the adult human body. One case series suggests complete bioavailability of IM TXA in healthy patients. Data are lacking on the efficacy and safety of IM TXA in hemorrhagic shock. There is currently insufficient evidence to support a strong recommendation for or against IM administration of TXA in the combat setting; however, there is an abundance of literature demonstrating efficacy and safety of TXA use in a broad range of patient populations. Balancing the available data and risk- benefit ratio, IM TXA should be considered a viable treatment option for tactical and combat applications. Additional studies should focus on the optimal dose and bioavailability of IM dosing of patients in hemorrhagic shock, with assessment of potential downstream sequelae. 2018.

The impact of manual defibrillation technique on no-flow time during simulated cardiopulmonary resuscitation.

PubMed

Perkins, Gavin D; Davies, Robin P; Soar, Jasmeet; Thickett, David R

2007-04-01

Rapid defibrillation is the most effective strategy for establishing return of spontaneous circulation following cardiac arrest due to ventricular fibrillation. The aim of this study is to measure the delay due to of charging the defibrillator during chest compression in an attempt to reduce the duration of the pre-shock pause in between cessation of chest compressions and shock delivery as advocated by the American Heart Association (AHA) guidelines compared to charging the defibrillator immediately following rhythm analysis without resuming chest compressions as recommended by the European Resuscitation Council (ERC). This was a randomised controlled cross over trial comparing pre-shock pause times when defibrillation was performed on a manikin according to the AHA and ERC guidelines using paddles and hands free defibrillation systems. The pre-shock pause between cessation of chest compression and shock delivery was significantly different between techniques (Friedman test, P<0.0001). ERC paddles technique had the greatest pre-shock pause (7.4 s [6.7-11.2]) followed by ERC hands free (7.0 s [6.5-8.5]) and AHA paddles (1.6 s [1.1-2.3]). AHA hands free took the least amount of time (1.5 s [0.8-1.5]). Extrapolating these data to older defibrillators with longer charge times saw pre-shock pause intervals of 9 s (Codemaster XL) and 12 s (Lifepak 20) with the ERC approach. This study demonstrated clinically significant delays to defibrillation by analysing and charging the defibrillator without performing concurrent chest compressions. In a simulated scenario, charging the defibrillator whilst performing chest compressions was perceived as safe and significantly reduced the pre-shock pause between cessation of chest compression and shock delivery.

Comparison of continuous compression with regular ventilations versus 30:2 compressions-ventilations strategy during mechanical cardiopulmonary resuscitation in a porcine model of cardiac arrest.

PubMed

Yang, Zhengfei; Liu, Qingyu; Zheng, Guanghui; Liu, Zhifeng; Jiang, Longyuan; Lin, Qing; Chen, Rui; Tang, Wanchun

2017-09-01

A compression-ventilation (C:V) ratio of 30:2 is recommended for adult cardiopulmonary resuscitation (CPR) by the current American Heart Association (AHA) guidelines. However, continuous chest compression (CCC) is an alternative strategy for CPR that minimizes interruption especially when an advanced airway exists. In this study, we investigated the effects of 30:2 mechanical CPR when compared with CCC in combination with regular ventilation in a porcine model. Sixteen male domestic pigs weighing 39±2 kg were utilized. Ventricular fibrillation was induced and untreated for 7 min. The animals were then randomly assigned to receive CCC combined with regular ventilation (CCC group) or 30:2 CPR (VC group). Mechanical chest compression was implemented with a miniaturized mechanical chest compressor. At the same time of beginning of precordial compression, the animals were mechanically ventilated at a rate of 10 breaths-per-minute in the CCC group or with a 30:2 C:V ratio in the VC group. Defibrillation was delivered by a single 150 J shock after 5 min of CPR. If failed to resuscitation, CPR was resumed for 2 min before the next shock. The protocol was stopped if successful resuscitation or at a total of 15 min. The resuscitated animals were observed for 72 h. Coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow in the VC group were similar to those achieved in the CCC group during CPR. No significant differences were observed in arterial blood gas parameters between two groups at baseline, VF 6 min, CPR 4 min and 30, 120 and 360 min post-resuscitation. Although extravascular lung water index of both groups significantly increased after resuscitation, no distinct difference was found between CCC and VC groups. All animals were successfully resuscitated and survived for 72 h with favorable neurologic outcomes in both groups. However, obviously more numbers of rib fracture were observed in CCC animals in comparison with VC animals. There was no difference in hemodynamic efficacy and gas exchange during and after resuscitation, therefore identical 72 h survival with intact neurologic function was observed in both VC and CCC groups. However, the incidence of rib fracture increases during the mechanical CPR strategy of CCC combined with regular ventilations.

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

PubMed

Self, Wesley H; Semler, Matthew W; Bellomo, Rinaldo; Brown, Samuel M; deBoisblanc, Bennett P; Exline, Matthew C; Ginde, Adit A; Grissom, Colin K; Janz, David R; Jones, Alan E; Liu, Kathleen D; Macdonald, Stephen P J; Miller, Chadwick D; Park, Pauline K; Reineck, Lora A; Rice, Todd W; Steingrub, Jay S; Talmor, Daniel; Yealy, Donald M; Douglas, Ivor S; Shapiro, Nathan I

2018-05-09

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock.

PubMed

Ida, K K; Chisholm, K I; Malbouisson, L M S; Papkovsky, D B; Dyson, A; Singer, M; Duchen, M R; Smith, K J

2018-06-01

During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

[Mild therapeutic hypothermia in cardiogenic shock : Retrospective analysis of 80 patients with preclinical cardiac arrest due to cardiac causes].

PubMed

Adler, C; Pfister, R; Baldus, S; Reuter, H

2017-02-01

The mortality in patients with cardiogenic shock after out-of-hospital cardiac arrest (OHCA) remains high despite advances in resuscitation and early revascularization strategies. The use of mild therapeutic hypothermia (MTH) for improvement of survival and neurological outcome in patients with cardiogenic shock is currently subject to renewed discussion. The aim of this study was the detection of risk factors for mortality and morbidity in patients under MTH in cardiogenic shock following preclinical resuscitation for OHCA. A total of 80 consecutive patients in cardiogenic shock after successful resuscitation (mean age 60 ± 3.2 years) treated with MTH were retrospectively analyzed. Patients were cooled to 33 °C for 24 h using an endovascular cooling device. Neurological outcome was assessed after 2 months based on the Glasgow-Pittsburgh cerebral performance category (CPC) and correlated with various blood parameter values. After 2 months 31 patients (39 %) showed a good neurological recovery with CPC scores of 1-2, 20 patients (25 %) had a poor neurological outcome with CPC scores of 3-4 and 29 (36 %) patients enrolled in the trial died (CPC 5). Patients with a poor outcome showed significantly higher mean serum levels for lactate, creatinine and urea. In addition, these patients showed a continuous increase of serum neuron-specific enolase (NSE) values in contrast to patients with a good outcome (∆ NSE from admission to day 1, CPC 1 and 2: - 10.6 ± 3 µg/l and CPC 3-5: 33 ± 12 µg/l, p = 0.02). Changes in the course of serum creatinine, urea and NSE levels within the first 72 h after OHCA could provide valuable additional information for the early assessment of the neurological prognosis in patients treated with MTH.

Battlefield Tourniquets: Lessons Learned in Moving Current Care Toward Best Care in an Army Medical Department at War.

PubMed

Kragh, John F; Dubick, Michael A

2016-01-01

Bleeding prevention and control by tourniquet use by out-of-hospital caregivers is a major breakthrough in military medicine of current wars. The present review documents developments in tourniquet practices since 2001 among the US military services for aid in improving doctrine, policy, and especially care in wars to come. Tourniquets are an adjunct for resuscitation in self-care and buddy aid and today are issued to all military servicepersons who deploy into a combat zone. In the US Army, virtually every Soldier is trained in first aid tourniquet use; since 2009 they are instructed early and often to use them early and often. Despite substantial knowledge gains among the services in tourniquet use and resulting improvements in casualty survival, current evidence shows persistent difficulties in achieving best care with tourniquet use for individual trauma patients. Nevertheless, contemporary tourniquet use incorporates key lessons learned over the last 14 years of war that include: (1) tourniquet use reliably stops bleeding from limb wounds and prevents mortality in prehospital settings; and (2) brief tourniquet use appears to be safe. These 2 lessons have become so evident that civilian emergency medical systems have begun using them, albeit unevenly. Collection and interpretation of data of casualties with tourniquet use have showed that such intervention has lifesaving benefit through 2 mechanisms: control of both ongoing hemorrhage and shock severity. The next generation of interventions in bleeding control involves developing the skill sets, education, and standards of tourniquet users which may improve hemorrhage control in wars to come.

Early structural changes of the heart after experimental polytrauma and hemorrhagic shock

PubMed Central

Halbgebauer, Rebecca; Eisele, Philipp; Messerer, David A. C.; Weckbach, Sebastian; Schultze, Anke; Braumüller, Sonja; Gebhard, Florian

2017-01-01

Evidence is emerging that systemic inflammation after trauma drives structural and functional impairment of cardiomyocytes and leads to cardiac dysfunction, thus worsening the outcome of polytrauma patients. This study investigates the structural and molecular changes in heart tissue 4 h after multiple injuries with additional hemorrhagic shock using a clinically relevant rodent model of polytrauma. We determined mediators of systemic inflammation (keratinocyte chemoattractant, macrophage chemotactic protein 1), activated complement component C3a and cardiac troponin I in plasma and assessed histological specimen of the mouse heart via standard histomorphology and immunohistochemistry for cellular and subcellular damage and ongoing apoptosis. Further we investigated spatial and quantitative changes of connexin 43 by immunohistochemistry and western blotting. Our results show significantly increased plasma levels of both keratinocyte chemoattractant and cardiac troponin I 4 h after polytrauma and 2 h after induction of hypovolemia. Although we could not detect any morphological changes, immunohistochemical evaluation showed increased level of tissue high-mobility group box 1, which is both a damage-associated molecule and actively released as a danger response signal. Additionally, there was marked lateralization of the cardiac gap-junction protein connexin 43 following combined polytrauma and hemorrhagic shock. These results demonstrate a molecular manifestation of remote injury of cardiac muscle cells in the early phase after polytrauma and hemorrhagic shock with marked disruption of the cardiac gap junction. This disruption of an important component of the electrical conduction system of the heart may lead to arrhythmia and consequently to cardiac dysfunction. PMID:29084268

Effects of Synthetic Versus Natural Colloid Resuscitation on Inducing Dilutional Coagulopathy and Increasing Hemorrhage in Rabbits

DTIC Science & Technology

2008-05-01

hemostasis, and plasma expanders: a quarter century enigma. Fed Proc. 1975;34:1429–1440. 23. Bergqvist D. Dextran and haemostasis. a review. Acta Chir ...eds. Blood Substitutes and Plasma Expanders. Prog Clin Biol Res. 1978;19:293–298. 57. Kovalik SG, Ledgewood AM, Lucas CE, Higgins RF. The cardiac

Destination Healthcare Facility of Shocked Trauma Patients in Scotland: Analysis of Transfusion and Surgical Capability of Receiving Hospitals

DTIC Science & Technology

2013-01-01

earlier use of balanced blood component transfusion7,8 and the use of adjuncts such as tranexamic acid ,9,10 collec- tively termed damage control...K. Early fluid resuscitation in severe trauma. Br Med J 2012;345:5752. 9. CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular...23e32. 10. Morrison JJ, DuBose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs

Red Tides: Mass casualty and whole blood at sea Red Tides.

PubMed

Miller, Benjamin T; Lin, Andrew H; Clark, Susan C; Cap, Andrew P; Dubose, Joseph J

2018-02-13

The U.S. Navy's casualty-receiving ships provide remote damage control resuscitation (RDCR) platforms to treat injured combatants deployed afloat and ashore. We report a significant mass casualty incident aboard the USS Bataan, and the most warm fresh whole blood (WFWB) transfused at sea for traumatic hemorrhagic shock since the Vietnam War. Casualty-receiving ships have robust medical capabilities, including a frozen blood bank with packed red blood cells (pRBC) and fresh frozen plasma (FFP). The blood supply can be augmented with WFWB collected from a "walking blood bank" (WBB). Following a helicopter crash, six patients were transported by MV-22 Osprey to the USS Bataan. Patient 1 had a pelvic fracture, was managed with a pelvic binder, and received 4 units of pRBC, 2 units of FFP, and 6 units of WFWB. Patient 2, with a comminuted tibia and fibula fracture, underwent lower extremity four-compartment fasciotomy, and received 4 units of WFWB. Patient 3 underwent several procedures, including left anterior thoracotomy, aortic cross-clamping, exploratory laparotomy, small bowel resection, and tracheostomy. He received 8 units of pRBC, 8 units of FFP, and 28 units of WFWB. Patients 4 and 5 had suspected spine injuries and were managed non-operatively. Patient 6, with open tibia and fibula fractures, underwent lower extremity four-compartment fasciotomy with tibia external fixation and received 1 unit of WFWB. All patients survived aeromedical evacuation to a Role 4 medical facility and subsequent transfer to local hospitals. Maritime military mass casualty incidents are challenging, but the U.S. Navy's casualty-receiving ships are ready to perform RDCR at sea. Activation of the ship's WBB to transfuse WFWB is essential for hemostatic resuscitations afloat. V STUDY TYPE: Case series.

Induced hypothermia does not impair coagulation system in a swine multiple trauma model.

PubMed

Mohr, Juliane; Ruchholtz, Steffen; Hildebrand, Frank; Flohé, Sascha; Frink, Michael; Witte, Ingo; Weuster, Matthias; Fröhlich, Matthias; van Griensven, Martijn; Keibl, Claudia; Mommsen, Philipp

2013-04-01

Accidental hypothermia, acidosis, and coagulopathy represent the lethal triad in severely injured patients. Therapeutic hypothermia however is commonly used in transplantations, cardiac and neurosurgical surgery, or after cardiac arrest. However, the effects of therapeutic hypothermia on the coagulation system following multiple trauma need to be elucidated. In a porcine model of multiple trauma including blunt chest injury, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of therapeutic hypothermia on coagulation was evaluated. A total of 40 pigs were randomly assigned to sham (only anesthesia) or trauma groups receiving either hypothermia or normothermia. Each group consisted of 10 pigs. Analyzed parameters were cell count (red blood cells, platelets), pH, prothrombin time (PT), fibrinogen concentration, and analysis with ROTEM and Multiplate. Trauma and consecutive fluid resuscitation resulted in impaired coagulation parameters (cell count, pH, PT, fibrinogen, ROTEM, and platelet function). During hypothermia, coagulation parameters measured at 37°C, such as PT, fibrinogen, thrombelastometry measurements, and platelet function, showed no significant differences between normothermic and hypothermic animals in both trauma groups. Additional analyses of thrombelastometry at 34°C during hypothermia showed significant differences for clotting time and clot formation time but not for maximum clot firmness. We were not able to detect macroscopic or petechial bleeding in both trauma groups. Based on the results of the present study we suggest that mild hypothermia can be safely performed after stabilization following major trauma. Mild hypothermia has effects on the coagulation system but does not aggravate trauma-induced coagulopathy in our model. Before hypothermic treatment can be performed in the clinical setting, additional experiments with prolonged and deeper hypothermia to exclude detrimental effects are required.

Freeze-dried plasma enhances clot formation and inhibits fibrinolysis in the presence of tissue plasminogen activator similar to pooled liquid plasma.

PubMed

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Sauaia, Angela; Stettler, Gregory; Dzieciatkowska, Monika; Hansen, Kirk; Banerjee, Anirban; Silliman, Christopher C

2017-08-01

Systemic hyperfibrinolysis is an integral part of trauma-induced coagulopathy associated with uncontrolled bleeding. Recent data suggest that plasma-first resuscitation attenuates hyperfibrinolysis; however, the availability, transport, storage, and administration of plasma in austere environments remain challenging and have limited its use. Freeze-dried plasma (FDP) is a potential alternative due to ease of storage, longer shelf life, and efficient reconstitution. FDP potentially enhances clot formation and resists breakdown better than normal saline (NS) and albumin and similar to liquid plasma. Healthy volunteers underwent citrated blood draw followed by 50% dilution with NS, albumin, pooled plasma (PP), or pooled freeze-dried plasma (pFDP). Citrated native and tissue plasminogen activator (t-PA)-challenge (75 ng/mL) thrombelastography were done. Proteins in PP, pFDP, and albumin were analyzed by mass spectroscopy. pFDP and PP had superior clot-formation rates (angle) and clot strength (maximum amplitude) compared with NS and albumin in t-PA-challenge thrombelastographies (angle: pFDP, 67.9 degrees; PP, 67.8 degrees; NS, 40.6 degrees; albumin, 35.8 degrees; maximum amplitude: pFDP, 62.4 mm; PP, 63.5 mm; NS, 44.8 mm; albumin, 41.1 mm). NS and albumin dilution increased susceptibility to t-PA-induced hyperfibrinolysis compared with pFDP and PP (NS, 62.4%; albumin, 62.6%; PP, 8.5%; pFDP, 6.7%). pFDP was similar to PP in the attenuation of t-PA-induced fibrinolysis. Most proteins (97%) were conserved during the freeze-dry process, with higher levels in 12% of pFDP proteins compared with PP. pFDP enhances clot formation and attenuates hyperfibrinolysis better than NS and albumin and is a potential alternative to plasma resuscitation in the treatment of hemorrhagic shock. © 2017 AABB.

Initial Assessment and Resuscitation in Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Simon, Tracey G; Travis, Anne C; Saltzman, John R

2015-07-01

Acute nonvariceal upper gastrointestinal bleeding remains an important cause of hospital admission with an associated mortality of 2-14%. Initial patient evaluation includes rapid hemodynamic assessment, large-bore intravenous catheter insertion and volume resuscitation. A hemoglobin transfusion threshold of 7 g/dL is recommended, and packed red blood cell transfusion may be necessary to restore intravascular volume and improve tissue perfusion. Patients should be risk stratified into low- and high-risk categories, using validated prognostic scoring systems such as the Glasgow-Blatchford, AIMS65 or Rockall scores. Effective early management of acute, nonvariceal upper gastrointestinal hemorrhage is critical for improving patient outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Implementation of automated external defibrillators on merchant ships.

PubMed

Oldenburg, Marcus; Baur, Xaver; Schlaich, Clara

2011-01-01

In contrast to cruise ships, ferries and merchant ships are rarely equipped with automated external defibrillators (AEDs). Germany is the first flag state worldwide that legally requires to carry AEDs on seagoing merchant vessels by September 2012 at the latest. The aim of this study was to investigate the effect of training ship officers in the handling of AEDs and to explore their perceptions concerning the user-friendliness of currently available defibrillators. Using four different AEDs, 130 nautical officers performed a total of 400 resuscitation drills. One group (n = 60) used only one device before and after resuscitation training; the other group (n = 70) used all four AEDs in comparison after training. The officers' performances were timed and they were asked by questionnaire about the user-friendliness of each AED. Without resuscitation training, 81.7% of the first mentioned group delivered an effective defibrillation shock. After a 7-hour resuscitation training with special regard to defibrillation, all ship officers (n = 130) used the AED correctly. Among all AEDs, the mean time until start of analysis decreased from 72.4 seconds before to 60.4 seconds after resuscitation training (Wilcoxon test; p < 0.001). The results of the questionnaire and the differences in time to first shock indicated a different user-friendliness of the AEDs. The voice prompts and the screen messages of all AEDs were well understood by all participants. In the second mentioned group, 57.1% regarded feedback information related to depths and frequency of thorax compression as helpful. Nautical officers are able to use AEDs in a timely and effective way with proper training. However, to take advantage of all wanted features of the device (monitoring and resuscitation), the ship management has to observe practical questions of storage, maintenance, signing, training, data management, and transmission. Thus, implementation of the regulations requires proper instructions for the maritime industry by responsible bodies. © 2011 International Society of Travel Medicine.

Ruptured superior gluteal artery pseudoaneurysm with hemorrhagic shock: Case report.

PubMed

Corbacioglu, Kerem Seref; Aksel, Gokhan; Yildiz, Altan

2016-03-01

Pseudoaneurysm of the superior gluteal artery (SGA) is very rare and the most common causes are blunt or penetrating pelvic traumas. Although pseudoaneurysm can be asymptomatic at the time of initial trauma, it can be symptomatic weeks, months, even years after initial trauma. We present a case of a ruptured superior gluteal artery pseudoaneurysm with hemorrhagic shock twenty days after a bomb injury in the Syria civil war. In addition, we review the anatomy of the SGA, clinical presentation and pitfalls of pseudoaneurysm, and imaging and treatment options.

[New recommendations on the use of human albumin solutions in patients with severe sepsis and septic shock. A critical evaluation of the literature].

PubMed

Latour-Pérez, J

2013-01-01

The third edition of the Surviving Sepsis Campaign guidelines opens the door to the use of albumin for fluid resuscitation in patients with severe sepsis and septic shock. This recommendation is based on a recent meta-analysis that included studies with evidence of insufficient plasma expansion in the control group and studies performed in children with malaria with clear statistical heterogeneity (P for interaction=.02). After excluding pediatric studies, the confidence interval of the effect estimate was consistent with a mortality excess in the group treated with albumin (OR=.87 [95%CI: .71 to 1.07]). Two new randomized studies reported after publication of the meta-analysis found no benefit in patients treated with albumin. Given the uncertainty about the true effect of albumin (due to the existence of indirectness and imprecision) and its cost considerations, it is suggested not to use albumin in the initial resuscitation of patients with severe sepsis and septic shock (GRADE2C). Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

PubMed Central

DeLano, Frank A.; Hoyt, David B.; Schmid-Schönbein, Geert W.

2015-01-01

Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate di-methanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multi-organ failure, which can be treated with protease inhibitors that are currently available for use in the clinic. PMID:23345609

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique

PubMed Central

Lamoureux, Lorissa; Radhakrishnan, Jeejabai; Gazmuri, Raúl J.

2015-01-01

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes – but is not limited to – hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation. PMID:25938619

Do all β-blockers attenuate the excess hematopoietic progenitor cell mobilization from the bone marrow following trauma/hemorrhagic shock?

PubMed

Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C; Alzate, Walter D; Livingston, David H; Mohr, Alicia M

2014-04-01

Severe injury results in increased mobilization of hematopoietic progenitor cells (HPC) from the bone marrow (BM) to sites of injury, which may contribute to persistent BM dysfunction after trauma. Norepinephrine is a known inducer of HPC mobilization, and nonselective β-blockade with propranolol has been shown to decrease mobilization after trauma and hemorrhagic shock (HS). This study will determine the role of selective β-adrenergic receptor blockade in HPC mobilization in a combined model of lung contusion (LC) and HS. Male Sprague-Dawley rats were subjected to LC, followed by 45 minutes of HS. Animals were then randomized to receive atenolol (LCHS + β1B), butoxamine (LCHS + β2B), or SR59230A (LCHS + β3B) immediately after resuscitation and daily for 6 days. Control groups were composed of naive animals. BM cellularity, %HPCs in peripheral blood, and plasma granulocyte-colony stimulating factor levels were assessed at 3 hours and 7 days. Systemic plasma-mediated effects were evaluated in vitro by assessment of BM HPC growth. Injured lung tissue was graded histologically by a blinded reader. The use of β2B or β3B following LCHS restored BM cellularity and significantly decreased HPC mobilization. In contrast, β1B had no effect on HPC mobilization. Only β3B significantly reduced plasma G-CSF levels. When evaluating the plasma systemic effects, both β2B and β3B significantly improved BM HPC growth as compared with LCHS alone. The use of β2 and β3 blockade did not affect lung injury scores. Both β2 and β3 blockade can prevent excess HPC mobilization and BM dysfunction when given after trauma and HS, and the effects seem to be mediated systemically, without adverse effects on subsequent healing. Only treatment with β3 blockade reduced plasma G-CSF levels, suggesting different mechanisms for adrenergic-induced G-CSF release and mobilization of HPCs. This study adds to the evidence that therapeutic strategies that reduce the exaggerated sympathetic stimulation after severe injury are beneficial and reduce BM dysfunction.

Management of traumatic hemipelvectomy: an institutional experience on four consecutive cases

PubMed Central

2013-01-01

Background and objective The incidence of traumatic hemipelvectomy is rare, but it is a devastating injury. Recently, an increasing number of patients with traumatic hemipelvectomy are admitted to trauma centers alive due to improvements of the pre-hospital care. Successful management requires prompt recognition of the nature of this injury and meticulous surgical technique. We present our successful experiences on four cases of traumatic hemipelvectomy in the past nine years. Patients and methods Four cases with traumatic hemipelvectomy were admited to our hospital from June 21, 2002 to September 3, 2011. All injuries occurred due to vehicle accident and all patients were in a state of severe hypotension, with two of them having anal lacerations. These four cases were treated immediately with resuscitation, control of hemorrhage, early amputation, repeated debridement and closure of the wounds. An angiographic embolization was given to control hemorrhage in two of the cases preoperatively. One case underwent fecal diversion. Wound infection occurred in all of cases which was successfully controlled by repeated debridements, effective anti-biotic regimen, split-thickness skin grafts. Results All four cases were saved successfully with well-healed wounds during follow up from 1 to 7 years. They were able to walk by themself using crutches. Conclusion Adhering to the surgery principles of damage control including appropriate resuscitation, hemorrhage control, coagulopathy correction and multiple debridements and closure of the wounds in reasonable period of time can save the life of cases suffering from severe pelvic ring injury. PMID:23953033

Effects of brief training on use of automated external defibrillators by people without medical expertise.

PubMed

Mitchell, K Blake; Gugerty, Leo; Muth, Eric

2008-04-01

This study examined the effect of three types of brief training on the use of automatic external defibrillators (AEDs) by 43 lay users. Because AEDs were recently approved for home use, brief training for nonprofessional users needs investigation. During training, the exposure training group read an article about AEDs that provided no information on how to operate them; the low-training group inspected the AED and read the operating instructions in the paper-based manual but was not allowed to use the device; and the high-training group watched a training video and performed a mock resuscitation using the AED but no manikin. All participants returned 2 weeks later and performed a surprise simulated AED resuscitation on a manikin. Most participants in each training group met criteria of minimally acceptable performance during the simulated manikin resuscitation, as measured by time to first shock, pad placement accuracy, and safety check performance. All participants who committed errors were able to successfully recover from them to complete the resuscitation. Compared with exposure training, the low and high training had a beneficial effect on time to first shock and errors. Untrained users were able to adequately use this AED, demonstrating walk-up-and-use usability, but additional brief training improved user performance. This study demonstrated the importance of providing high-quality but brief training for home AED users. In conjunction with other findings, the current study helps demonstrate the need for well-designed training for consumer medical devices.

The Mechanism of Microcirculatory Failure in Shock.

DTIC Science & Technology

1979-05-01

response to regional and systemic shock. Surgery 77:268, 1975. 10. Weksler BB, et al: Synthesis of PGI2 (prostacyclin) by cultured human and bovine ... bovine blood platelets. J Biol Chem 252:5871, 1977. -. . Q •( 14. Roth GJ and Mejerus PW: Acetylation of prostaglandin synthetase by aspirin. Proc Natl...gases were determined every 30 minutes and metabolic acidosis was treated with sodium bicarbonate. After 90 minutes the animals were resuscitated by

Approach to the critically ill camelid.

PubMed

Bedenice, Daniela

2009-07-01

The estimation of fluid deficits in camelids is challenging. However, early recognition and treatment of shock and hypovolemia is instrumental to improve morbidity and mortality of critically ill camelids. Early goal-directed fluid therapy requires specific knowledge of clinical indicators of hypovolemia and assessment of resuscitation endpoints, but may significantly enhance the understanding, monitoring, and safety of intravenous fluid therapy in South American camelids (SAC). It is important to recognize that over-aggressive fluid resuscitation is just as detrimental as under resuscitation. Nonetheless, a protocol of conservative fluid management is often indicated in the treatment of camelids with pulmonary inflammation, to counteract edema formation. The early recognition of lung dysfunction is often based on advanced diagnostic techniques, including arterial blood gas analysis, diagnostic imaging, and noninvasive pulmonary function testing.

PNU-282987 improves the hemodynamic parameters by alleviating vasopermeability and tissue edema in dogs subjected to a lethal burns shock.

PubMed

Hu, Quan; Du, Ming-Hua; Hu, Sen; Chai, Jia-ke; Luo, Hong-Min; Hu, Xiao-Han; Zhang, Lin; Lin, Zhi-Long; Ma, Li; Wang, Huan; Sheng, Zhi-Yong

2014-01-01

Excessive inflammation and high vasopermeability can lead to blood volume loss and tissue edema, which can affect the resuscitation and prognosis for serious burn patients. In this experiment, we investigated the effect of PNU-282987, an α7 nicotine cholinergic receptor agonist on the hemodynamic parameters and survival rate by inhibiting vasopermeability and tissue edema during the fluid resuscitation for lethal burn shock. Forty Beagle dogs with intubation of the carotid artery and jugular vein 24 hours before the injury were subjected to 50% TBSA full-thickness burns, and were randomly divided into following four groups: no resuscitation group (group NR), venous fluid resuscitation group (group R), PNU-282987 treatment group (group P), and fluid resuscitation group plus PNU-282987 group (group RP), with 10 dogs in each group. Hemodynamic variables and biochemical parameters were determined with animals in a conscious and cooperative state. The plasma volume and the vasopermeability were determined by indocyanine green and fluorescein isothiocyanate-dextran, respectively. The level of tumor necrosis factor-α and interleukin-1β in plasma, and the water content of different organs were also determined. The mean arterial pressure, cardiac output, and plasma volume of all dogs decreased significantly, and the lung extravascular water index and pulmonary vascular permeability index increased remarkably after burn. The hemodynamic parameters deteriorated continually in group N dogs, and then anuria, hyperlactacidemia, and multiple organ dysfunctions developed. The mean arterial pressure and cardiac output of dogs in group R and group RP returned to preinjury levels at 48 hours postburn. The lung extravascular water index and pulmonary vascular permeability in group R were higher than those before preinjury. The dogs in group RP were found to have a significant increase in plasma volume and urine output, and a remarkable decrease in the levels of tumor necrosis factor-α, interleukin-1α, lactic acid, and organ functions compared with those of group R (P <.05). The survival rate of RP group (100%; 10/10) was significantly higher than that of group N (0; 0/10), group P (20%; 2/10), and group R (60%; 6/10). PNU-282987 combined with intravenous fluid resuscitation significantly improved hemodynamics and the survival rate in the early period after this lethal burn shock. The mechanism may be attributable to the lowering of the level of proinflammatory mediators, amelioration of vasopermeability-induced visceral edema, less of blood volume loss, and protection of vital organs through activation of cholinergic anti-inflammatory pathway.

Mitochondrial Permeability Transition in Pathogenesis of Hemorrhagic Injury: Targeted Therapy with Minocycline

DTIC Science & Technology

2012-03-01

minocy- cline treatment (Figures 1-4). Minocycline also improved mitochondrial function as assessed by intravital multiphoton imaging of the...will make direct measurements by intravital multiphoton microscopy to determine whether onset of the mitochondrial permeability transition and...oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization were assessed by intravital microscopy. After H/R with vehicle or

Angiotensin (1-7) contributes to nitric oxide tonic inhibition of vasopressin release during hemorrhagic shock in acute ethanol intoxicated rodents

PubMed Central

Whitaker, Annie M.; Molina, Patricia E.

2013-01-01

Aims Acute ethanol intoxication (AEI) attenuates the arginine vasopressin (AVP) response to hemorrhage leading to impaired hemodynamic counter-regulation and accentuated hemodynamic stability. Previously we identified that the ethanol-induced impairment of circulating AVP concentrations in response to hemorrhage was the result of augmented central nitric oxide (NO) inhibition. The aim of the current study was to examine the mechanisms underlying ethanol-induced up-regulation of paraventricular nucleus (PVN) NO concentration. Angiotensin (ANG) (1-7) is an important mediator of NO production through activation of the Mas receptor. We hypothesized that Mas receptor inhibition would decrease central NO concentration and thus restore the rise in circulating AVP levels during hemorrhagic shock in AEI rats. Main Methods Conscious male Sprague Dawley rats (300-325 g) received a 15h intra-gastric infusion of ethanol (2.5g/kg + 300mg/kg/h) or dextrose prior to a fixed-pressure (~40mmHg) 60 minute hemorrhage. The Mas receptor antagonist A-779 was injected through an intracerebroventricular (ICV) cannula 15 min prior to hemorrhage. Key Findings PVN NOS activity and NO were significantly higher in AEI compared to DEX-treated controls at the completion of hemorrhage. ICV A-779 administration decreased NOS activity and NO concentration, partially restoring the rise in circulating AVP levels completion of hemorrhage in AEI rats. Significance These results suggest that Mas receptor activation contributes to the NO-mediated inhibitory tone of AVP release in the ethanol-intoxicated hemorrhaged host. PMID:24002017

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

PubMed

Truse, Richard; Hinterberg, Jonas; Schulz, Jan; Herminghaus, Anna; Weber, Andreas; Mettler-Altmann, Tabea; Bauer, Inge; Picker, Olaf; Vollmer, Christian

2017-01-01

Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function. © 2017 S. Karger AG, Basel.

The Shock Index revisited – a fast guide to transfusion requirement? A retrospective analysis on 21,853 patients derived from the TraumaRegister DGU®

PubMed Central

2013-01-01

Introduction Isolated vital signs (for example, heart rate or systolic blood pressure) have been shown unreliable in the assessment of hypovolemic shock. In contrast, the Shock Index (SI), defined by the ratio of heart rate to systolic blood pressure, has been advocated to better risk-stratify patients for increased transfusion requirements and early mortality. Recently, our group has developed a novel and clinical reliable classification of hypovolemic shock based upon four classes of worsening base deficit (BD). The objective of this study was to correlate this classification to corresponding strata of SI for the rapid assessment of trauma patients in the absence of laboratory parameters. Methods Between 2002 and 2011, data for 21,853 adult trauma patients were retrieved from the TraumaRegister DGU® database and divided into four strata of worsening SI at emergency department arrival (group I, SI <0.6; group II, SI ≥0.6 to <1.0; group III, SI ≥1.0 to <1.4; and group IV, SI ≥1.4) and were assessed for demographics, injury characteristics, transfusion requirements, fluid resuscitation and outcomes. The four strata of worsening SI were compared with our recently suggested BD-based classification of hypovolemic shock. Results Worsening of SI was associated with increasing injury severity scores from 19.3 (± 12) in group I to 37.3 (± 16.8) in group IV, while mortality increased from 10.9% to 39.8%. Increments in SI paralleled increasing fluid resuscitation, vasopressor use and decreasing hemoglobin, platelet counts and Quick’s values. The number of blood units transfused increased from 1.0 (± 4.8) in group I to 21.4 (± 26.2) in group IV patients. Of patients, 31% in group III and 57% in group IV required ≥10 blood units until ICU admission. The four strata of SI discriminated transfusion requirements and massive transfusion rates equally with our recently introduced BD-based classification of hypovolemic shock. Conclusion SI upon emergency department arrival may be considered a clinical indicator of hypovolemic shock in respect to transfusion requirements, hemostatic resuscitation and mortality. The four SI groups have been shown to equal our recently suggested BD-based classification. In daily clinical practice, SI may be used to assess the presence of hypovolemic shock if point-of-care testing technology is not available. PMID:23938104

Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock.

PubMed

Yang, Guangming; Peng, Xiaoyong; Wu, Yue; Li, Tao; Liu, Liangming

2017-10-01

We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin 43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed that AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia. AVP restored hypoxia-induced decrease of Cx43 phosphorylation at Ser 262 and gap junctional communication in VSMCs. Activation of RhoA with U-46619 increased the contractile effect of AVP. This effect was antagonized by the ROCK inhibitor Y27632 and the Cx43-mimetic peptide. In contrast, neither an agonist nor an inhibitor of PKC had significant effects on AVP-induced contraction after hemorrhagic shock. In addition, silencing of Cx43 with siRNA blocked the AVP-induced increase of ROCK activity in hypoxic VSMCs. In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser 262 play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process. Copyright © 2017 the American Physiological Society.

Accurate recognition and effective treatment of ventricular fibrillation by automated external defibrillators in adolescents.

PubMed

Atkins, D L; Hartley, L L; York, D K

1998-03-01

To evaluate the accuracy and efficacy of automated external defibrillators (AEDs) in patients <16 years old. AEDs are standard therapy in out-of-hospital resuscitation of adults and have led to higher success rates. Their use in children and adolescents has never been evaluated, despite recommendations from the American Heart Association that they be used in children >8 years of age. This was a retrospective cohort study of children <16 years old who underwent out-of-hospital cardiac resuscitation and on whom an AED was used during the resuscitation. The setting was rural and urban prehospital emergency medical systems. Patients were identified by review of a database of cardiac arrests maintained by a large surveillance program of these services. AEDs were used to assess cardiac rhythm in 18 patients with a mean age of 12.1 +/- 3.7 years. The cardiac rhythms were analyzed 67 times and included ventricular fibrillation (25), asystole/pulseless electrical activity (32), sinus bradycardia (6), and sinus tachycardia (4). The AEDs recognized all nonshockable rhythms accurately and advised no shock. Ventricular fibrillation was recognized accurately in 22 (88%) of 25 episodes and advised or administered a shock 22 times. Sensitivity and specificity for accurate rhythm analysis were 88% and 100%, respectively. One patient with a nonshockable rhythm survived, whereas 3 of 9 patients with ventricular fibrillation survived. These data furnish evidence that AEDs provide accurate rhythm detection and shock delivery to children and young adolescents. AED use is potentially as effective for children as it is for adults.

Shock Wave-Stimulated Periosteum for Cartilage Repair

DTIC Science & Technology

2015-03-01

Abscess Hemorrhage was graded with the following scores: 0: No hemorrhage 1: 1 or more small (barely visible through 10x objective) hematomas 2...1-3 or more medium (visible through 10x objective) hematomas 3: >3 or more medium (immediately visible in 10x objective) hematomas 4: 1 or more...large (immediately visible in 10x objective) hematomas The results are shown in Table 3 Table 3. Scores for the degree of inflammation and hemorrhage

Management of massive diffuse alveolar hemorrhage in a child with systemic lupus erythematosus.

PubMed

Kimura, Dai; Shah, Samir; Briceno-Medina, Mario; Sathanandam, Shyam; Haberman, Brent; Zhang, Jie; Myers, Linda; Kumar, Tk Susheel; Knott-Craig, Christopher

2015-01-01

Diffuse alveolar hemorrhage (DAH) from systemic lupus erythematosus (SLE) is a rare but potentially life-threatening condition. We report the case of a 14-year-old female with SLE who developed hypoxia and shock secondary to severe alveolar hemorrhage. She was successfully managed by placement on extracorporeal membrane oxygenation (ECMO) followed by emergent pulmonary lobectomy and medical treatment including high-dose methylprednisolone, cyclophosphamide, intravenous immunoglobulin, and plasmapheresis.

Use of freeze-dried plasma in French intensive care unit in Afghanistan.

PubMed

Martinaud, Christophe; Ausset, Sylvain; Deshayes, Anne Virginie; Cauet, Amandine; Demazeau, Nicolas; Sailliol, Anne

2011-12-01

Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Massive hemorrhage management includes transfusion of red blood cells and plasma in a 1:1 ratio. Fresh frozen plasma requires thawing and badly fits the emergency criteria. Since 1994, the French Military Blood Bank has been producing freeze-dried plasma (FDP) and providing it for overseas operation. The aim of our study was to evaluate the use of FDP in war settings and to assess its clinical efficiency and safety. We performed a prospective study of the FDP delivered at the International Security Assistance Force Role 3 Military Medical Treatment Facility in the Kabul Afghanistan International Airport between February 2010 and February 2011. We included every patient who received at least one unit of FDP. Basic clinical data were recorded at admission. Transfusion requirements were monitored. Biological testing were performed before and after administration of FDP including hemoglobin concentration, platelets count, fibrinogen level, prothrombin time (PT), and thromboelastography. Eighty-seven casualties received FDP during 93 episodes of transfusion. On average, 3.5 FDP units were transfused per episodes of transfusion. Of the 87 patients studied, 7 died because of nonsurvivable injuries and outcomes were unavailable for 11. The other 59 patients survived. PT significantly declined by an average of 3.3 seconds after FDP transfusion. This moderate decrease in PT reflects continued bleeding and resuscitation. It nevertheless suggests improvement in hemostasis before surgical control of bleeding. All FDP users reported ease of use, clinically observed efficacy equivalent to fresh frozen plasma and the absence of adverse effects associated with FDP. Our results provide evidence of the effectiveness of FDP for the prevention or correction of coagulopathy and hemorrhage in combat casualties.

Neuroendocrine Derangements in Early Septic Shock: Pharmacotherapy for Relative Adrenal and Vasopressin Insufficiency.

PubMed

Schurr, James W; Szumita, Paul M; DeGrado, Jeremy R

2017-09-01

Septic shock is a leading cause of mortality in intensive care units throughout the world. While this disease state represents a highly complex pathophysiology involving numerous organ systems, the early approach to care includes adequate hemodynamic support traditionally achieved via infusions of vasoactive medications after adequate fluid resuscitation. Relative adrenal and vasopressin deficiencies are a common feature of septic shock that contribute to impaired hemodynamics. Hydrocortisone and vasopressin are endocrine system hormone analogues that target the acute neuroendocrine imbalance associated with septic shock. This clinically focused annotated review describes the pathophysiological mechanisms behind their use and explores the potential clinical roles of early administration and synergy when combined.

Influence of Asymptomatic Pneumonia on the Response to Hemorrhage and Resuscitation in Swine

DTIC Science & Technology

2010-01-01

and complete blood count (Pentra-120 Hemato- logy Analyzer, ABX Diagnostics, Irvine, CA); 3) total plasma protein, glucose, creatinine , lactate...dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), amylase and lactate (Vitros Chemistry System...CK. Creatinine increased at 15 min in both groups and remained elevated throughout the study. Mean total protein, amylase and ALT decreased similarly

Low Volume Resuscitation with Cell Impermeants

DTIC Science & Technology

2016-04-01

to rise) and a fall in peripheral vascular resistance . In this model, hemorrhage and blood loss was controlled so any changes in hemoglobin...appealing. The increase in capillary filling together with reduced resistance to flow in these peripheral beds leads to increased blood flow and oxygen...delivery. The low resistance , compared to saline controls, likely represents a physical decompression of the capillary beds by controlling cell and

The Effect Of Supraphysiologic Blood Pressure on Traumatic Brain Injury and Proximal Tissue Beds During Resuscitative Balloon Occlusion of the Aorta and Variable Aortic Control in a Porcine Model (Sus scrofa) of Polytrauma.

DTIC Science & Technology

2017-04-27

Control In A Porcine Model (Sus Scrofa) Of Polytrauma. PRINCIPAL INVESTIGATOR (PI) / TRAINING COORDINATOR (TC): Lt Col Timothy Williams DEPARTMENT... controlled cortical impact followed by 25% total blood volume rapid hemorrhage. After 30 minutes of hypotension, animals were randomized to 60

Prognostic Value of Venous to Arterial Carbon Dioxide Difference during Early Resuscitation in Critically Ill Patients with Septic Shock.

PubMed

Helmy, Tamer Abdallah; El-Reweny, Ehab Mahmoud; Ghazy, Farahat Gomaa

2017-09-01

The partial pressure of venous to arterial carbon dioxide gradient (PCO 2 gap) is considered as an alternative marker of tissue hypoperfusion and has been used to guide treatment for shock. The aim of this study was to investigate the prognostic value of venous-to-arterial carbon dioxide difference during early resuscitation of patients with septic shock and compared it with that of lactate clearance and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. Forty patients admitted to one Intensive Care Unit were enrolled. APACHE-II score was calculated on admission. An arterial blood gas, central venous, and lactate samples were obtained on admission and after 6 h, and lactate clearance was calculated. Patients were classified retrospectively into Group I (survivors) and Group II (nonsurvivors). Pv-aCO 2 difference in the two groups was evaluated. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. At T0, Group II showed high PCO 2 gap (8.37 ± 1.36 mmHg) than Group I (7.55 ± 0.95 mmHg) with statistically significant difference ( P = 0.030). While at T6, Group II showed higher PCO 2 gap (9.48 ± 1.47 mmHg) with statistically significant difference ( P < 0.001) and higher mean lactate values (62.71 ± 23.66 mg/dl) with statistically significant difference ( P < 0.001) than Group I where PCO 2 gap and mean lactate values became much lower, 5.91 ± 1.12 mmHg and 33.61 ± 5.80 mg mg/dl, respectively. Group I showed higher lactate clearance (25.42 ± 6.79%) with statistically significant difference ( P < 0.001) than Group II (-69.40-15.46%). High PCO 2 gap >7.8 mmHg after 6 h from resuscitation of septic shock patients is associated with high mortality.

Detection of ventricular fibrillation in the presence of cardiopulmonary resuscitation artefacts.

PubMed

Aramendi, Elisabete; de Gauna, Sofia Ruiz; Irusta, Unai; Ruiz, Jesus; Arcocha, M Fe; Ormaetxe, Jose Miguel

2007-01-01

Providing cardiopulmonary resuscitation (CPR) to a patient in cardiac arrest introduces artefacts into the electrocardiogram (ECG), corrupting the diagnosis of the underlying heart rhythm. CPR must therefore be discontinued for reliable shock advice analysis by an automated external defibrillator (AED). Detection of ventricular fibrillation (VF) during CPR would enable CPR to continue during AED rhythm analysis, thereby increasing the likelihood of resuscitation success. This study presents a new adaptive filtering method to clean the ECG. The approach consists of a filter that adapts its characteristics to the spectral content of the signal exclusively using the surface ECG that commercial AEDs capture through standard patches. A set of 200 VF and 25 CPR artefact samples collected from real out-of-hospital interventions were used to test the method. The performance of a shock advice algorithm was evaluated before and after artefact removal. CPR artefacts were added to the ECG signals and four degrees of corruption were tested. Mean sensitivities of 97.83%, 98.27%, 98.32% and 98.02% were achieved, producing sensitivity increases of 28.44%, 49.75%, 59.10% and 64.25%, respectively, sufficient for ECG analysis during CPR. Although satisfactory and encouraging sensitivity values have been obtained, further clinical and experimental investigation is required in order to integrate this type of artefact suppressing algorithm in current AEDs.

Pharmacology of pediatric resuscitation.

PubMed

Ushay, H M; Notterman, D A

1997-02-01

The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Shankar-Hari, Manu; Phillips, Gary S; Levy, Mitchell L; Seymour, Christopher W; Liu, Vincent X; Deutschman, Clifford S; Angus, Derek C; Rubenfeld, Gordon D; Singer, Mervyn

2016-02-23

Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. To develop a new definition and clinical criteria for identifying septic shock in adults. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28,150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1,309,025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1,847,165) electronic health record (EHR) data sets. Evidence for and agreement on septic shock definitions and criteria. The systematic review identified 44 studies reporting septic shock outcomes (total of 166,479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock-associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.

Feasibility of blind aortic catheter placement in the prehospital environment to guide resuscitation in cardiac arrest.

PubMed

Manning, James E

2013-08-01

Aortic catheter-based resuscitation therapies are emerging with laboratory investigations showing benefit in models of trauma-related noncompressible torso hemorrhage and nontraumatic cardiac arrest. For these investigational aortic catheter-based therapies to reach their greatest potential clinical benefit, the ability to initiate them in the prehospital setting will be important. Feasibility of prehospital aortic catheterization without imaging capability supports this potential and is described in this report. A physician prehospital response system was created in cooperation with the local emergency medical services system to provide invasive hemodynamic monitoring during cardiac arrest. Physicians were dispatched to all known or suspected prehospital cardiac arrests covered by the emergency medical services system. Physicians responded with a specialized vascular catheterization pack and a monitor with invasive pressure monitoring capability. The physicians performed blind thoracic aortic and central venous catheterizations in cardiac arrest patients in the prehospital setting to measure coronary perfusion pressure, to optimize closed-chest cardiopulmonary resuscitation technique, and to administer intra-aortic epinephrine. During a 2-year period, 22 medical cardiac arrest patients underwent prehospital invasive hemodynamic monitoring to guide resuscitation. Most patients had both aortic and central venous catheters inserted. The combination of intra-aortic epinephrine and adjustments in closed-chest cardiopulmonary resuscitation technique resulted in improved coronary perfusion pressure. Return of spontaneous circulation with survival to hospital admission was achieved in 50% (11 of 22) of these patients. This report demonstrates the feasibility of successful blind aortic and central venous catheterizations in the prehospital environment and supports the potential feasibility of other emerging aortic catheter-based resuscitation therapies.

Plasma transfusion for patients with severe hemorrhage: what is the evidence?

PubMed

Callum, Jeannie L; Rizoli, Sandro

2012-05-01

The following review will detail the current knowledge in massive hemorrhage with regard to the pathophysiology of the coagulation disturbance, the role of plasma, the role of alternatives to plasma, and the clinical value of having a massive transfusion protocol. The coagulation disturbance in trauma patients is more than just the result of consumption of clotting factors at sites of injury and dilution from the infusion of intravenous fluids and red blood cells (RBCs). Even before substantial amounts of fluid resuscitation and RBC transfusion, one-quarter of trauma patients already have abnormal coagulation variables. There is an apparent role for the activation of protein C, hypofibrinogenemia, and fibrin(gen)olysis in the coagulation disturbance after trauma and massive hemorrhage. None of these three disturbances would be completely mitigated by the use of plasma alone, suggesting that there may be an opportunity to improve care of these patients with alternative strategies, such as fibrinogen concentrates and antifibrinolytics. Despite numerous retrospective cohort studies evaluating 1:1 plasma to RBC formula-driven resuscitation, the overall clinical value of this approach is unclear. Studies have even raised concerns regarding a potential increase in morbidity associated with this approach, particularly for patients overtriaged to 1:1 where a massive transfusion is unlikely. We also do not have sufficient evidence to recommend either goal-directed therapy with thromboelastography or early use of fibrinogen replacement, with either cryoprecipitate or fibrinogen concentrates. We have high-quality data that argue against the role for recombinant Factor VIIa that should prompt removal of this strategy from existing protocols. In contrast, we have high-level evidence that all bleeding trauma patients should receive tranexamic acid as soon as possible after injury. This therapy must be included in hemorrhage protocols. If we are to improve the care of massively bleeding patients on a firm scientific ground, we will need large-scale randomized trials to delineate the role of coagulation replacement and the utility of laboratory monitoring. But even until these trials are completed, it is clear that a massive transfusion protocol is needed in all hospitals that manage bleeding patients, to ensure a prompt and coordinated response to hemorrhage. © 2012 American Association of Blood Banks.

Vagal nerve stimulation modulates the dendritic cell profile in posthemorrhagic shock mesenteric lymph.

PubMed

Morishita, Koji; Costantini, Todd W; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul

2014-03-01

Previous studies have established that posthemorrhagic shock mesenteric lymph (PHSML) contains proinflammatory mediators, while the cellular basis of PHSML is less well characterized in acute models of injury. CD103 dendritic cells (DCs) have been identified in the mesenteric lymph (ML) in models of chronic intestinal inflammation, suggesting an important role in the gut response to injury. We have previously demonstrated the ability of vagal nerve stimulation (VNS) to prevent gut barrier failure after trauma/hemorrhagic shock (T/HS); however, the ability of VNS to alter ML DCs is unknown. We hypothesized that the CD103 MHC-II DC population would change in PHSML and that VNS would prevent injury-induced changes in this population in PHSML. Male Sprague-Dawley rats were randomly assigned to trauma/sham shock or T/HS. T/HS was induced by midline laparotomy and 60 minutes of HS (blood pressure, 35 mm Hg), followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. Gut tissue was harvested at 2 hours after injury for histologic analysis. ML was collected during the pre-HS, HS, and post-HS phase. For flow cytometric analysis, ML cells were subjected to staining with CD103 and MHC-II antibodies, and this cell population was compared in the pre-HS and post-HS phase from the same animal. The CD4Foxp3 cell (T reg) population in the ML node (MLN) was also tested to determine effects of CD103 DC modulation in the ML. VNS reduced histologic gut injury and ML flow seen after injury. The CD103 MHC-II DC population in the PHSML was significantly decreased compared with pre-HS and was associated with decreased T reg expression in the MLN. VNS prevented the injury-induced decrease in the CD103 MHC-II+ DC population in the ML and restored the T reg population in the MLN. These findings suggest that VNS mediates the inflammatory responses in ML DCs and MLN T reg cells by affecting the set point of T/HS responsiveness.

Mesenchymal Stem Cells Enhance Lung Recovery After Injury, Shock, and Chronic Stress

PubMed Central

Gore, Amy V.; Bible, Letitia E.; Livingston, David H.; Mohr, Alicia M.; Sifri, Ziad C.

2016-01-01

Background Normal lung healing is impaired when lung contusion (LC) is followed by hemorrhagic shock (HS) and chronic stress (CS). Mesenchymal stem cells (MSCs) are immunomodulatory, pluripotent cells that are under investigation for use in wound healing and tissue regeneration. We hypothesized that treatment with MSCs can reverse the impaired healing seen after LC combined with HS and CS (LCHS/CS). Methods Male Sprague-Dawley (SD) rats (n=6/group) underwent LCHS with or without a single iv dose of 5 × 106 SD rat MSCs following resuscitation. Thereafter, rats were subjected to two hours of CS daily on days 1–6 and were killed on day 7. Lung histology was scored according to a well-established lung injury score (LIS) that included interstitial and pulmonary edema, alveolar integrity, and inflammatory cells. Scoring ranges from 0 (normal lung) to 11 (most severely injured). Whole blood was analyzed for the presence of CD4+CD25+FoxP3+ T regulatory cells (Treg) by flow cytometry. Results Seven days after isolated LC, LIS had returned to 0.8 ± 0.4, however, after LCHS/CS healing is significantly delayed (7.2 ± 2.2; p<0.05). Addition of MSC to LCHS/CS decreased LIS to 2.0 ± 1.3 (p<0.05) and decreased all subgroup scores (inflammatory cells, interstitial and pulmonary edema, and alveolar integrity) significantly as compared to LCHS/CS (p<0.05). The percentage of Tregs found in the peripheral blood of animals undergoing LCHS/CS did not significantly change from LC alone (10.5 ± 3.3% vs 6.7 ± 1.7%; p>0.05). Treatment with MSCs significantly increased the Treg population as compared to LCHS/CS alone (11.7 ± 2.7% vs 6.7 ± 1.7%; p<0.05) Conclusion In this model, the severe impairment of wound healing observed one week after LCHS/CS is reversed by a single treatment with MSCs immediately after resuscitation. This improvement in lung healing is associated with a decrease in the number of inflammatory cells and lung edema and a significant increase in peripheral Tregs. Further study into timing of administration and mechanisms by which cell-based therapy using MSCs modulate the immune system and improve wound healing is warranted. PMID:26830071

A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome.

PubMed

Selvi, Subramanian Kalaivani; Kar, Rakhee; Vadivelan, Mehalingam; Subrahmanyam, Dharanipragada Krishna Suri

2012-01-01

Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.

Recombinant Factor VIIa Reduces Rebleed Hemorrhage Volume in a Swine Aortotomy Model: A Randomized Double-Blinded Study

DTIC Science & Technology

2008-06-01

Bpops,[ a dose of 90 Hg kgj1 will produce serum concentrations of factor VII high enough to reduce hemorrhage by accelerating thrombin production and...interaction is species-specific, and human FVII seems to have only between 5% and 50% activity when exposed to porcine tissue factor (15). The results...Copyright @ 200 by the Shock Society. Unauthorized reproduction of this article is prohibited.8 RECOMBINANT FACTOR VIIA REDUCES REBLEED HEMORRHAGE

Effects of Bovine Polymerized Hemoglobin in Coagulation in Controlled Hemorrhagic Shock in Swine

DTIC Science & Technology

2005-01-01

continuous blood pressure monitoring. A pulmonary artery catheter was also inserted. To mimic soft tissue injury, the rectus abdominus muscle was crushed in...volume by catheter withdrawal of blood over 15 min (;1.7 mL/kg/min). Time 0 designated initiation of the rectus abdominus crush and concomitant hemorrhage

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

PubMed

Ma, Hu-Sai; Ma, Ju-Hua; Xue, Feng-Lai; Fu, Xiang-Ning; Zhang, Ni

2016-12-01

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

“Post partum hemorrhage: causes and management”

PubMed Central

2013-01-01

Background Post partum hemorrhage is defined as blood loss of 500 ml or above. It is the most common cause of pre-mature mortality of women world wide. Our objective was to evaluate the most common etiology and method of management of Post partum Hemorrhage in a tertiary care hospital of Karachi. Findings It was a cross sectional study conducted at Liaquat National Hospital Karachi, during the period of July 2011 to May 2012. Review include mode of delivery, possible cause of postpartum hemorrhage, supportive, medical and surgical interventions. All the women admitted with post partum hemorrhage or develop PPH in hospital after delivery were included in our study. Bleeding disorder and use of anticoagulants were set as exclusion criteria. Diagnosis was made on the basis of blood loss assessment which was made via subjective and objective evaluation. During the targeted months, out of total 1493 deliveries (26/1493 = 1.741%) 26 cases of post partum hemorrhage were reported with a mean age of 26.153 ± 7.37. No deaths were reported and all cases were referred and unbooked cases. All Patients were conscious, tachycardiac and hypotensive. Most of the women were suffering from hemorrhage during or after the birth of their 1st child. Primary post partum hemorrhage emerge as the most common type of post partum hemorrhage and uterine atony was detected as the most common cause of primary post partum hemorrhage. Retained products of conception was the most common cause of secondary post partum hemorrhage and hysterectomy was found to be the most frequent method of management of post partum hemorrhage. Conclusion This study highlights the existing variable practices for the management of postpartum hemorrhage. Hemorrhage associated morbidity and mortality can be prevented by critical judgment, early referral and resuscitation by attendants. Introduction of an evidence-based management model can potentially reduce the practice variability and improve the quality of care. PMID:23773785

CPR Induced Consciousness During Out-of-Hospital Cardiac Arrest: A Case Report on an Emerging Phenomenon.

PubMed

Pound, Joshua; Verbeek, P Richard; Cheskes, Sheldon

2017-01-01

High quality cardiopulmonary resuscitation (CPR) has produced a relatively new phenomenon of consciousness in patients with vital signs absent. Further research is necessary to produce a viable treatment strategy during and post resuscitation. To provide a case study done by paramedics in the field illustrating the need for sedation in a patient whose presentation was consistent with CPR induced consciousness. Resuscitative challenges are provided as well as potential future treatment options to minimize harm to both patients and prehospital providers. A 52-year-old male presented as a witnessed out-of-hospital cardiac arrest (OHCA). During CPR the patient began to exhibit signs of life including severe agitation and thrashing of his limbs while CPR was ongoing for ventricular fibrillation prior to defibrillation. Resuscitation became considerably more complicated due to the violent and counterintuitive motions done by the patient during their own resuscitation. Despite the atypical presentation of cardiac arrest the patient was successfully resuscitated employing high quality CPR, standard advanced life support (ALS) care as well as two double sequential external defibrillation shocks. The patient underwent emergency percutaneous coronary intervention (PCI) for a 100% occlusion of his left anterior descending artery (LAD). The patient returned home 3 days later fully recovered with a Cerebral Performance Score of 1. CPR induced consciousness is emerging as a new phenomenon challenging providers of high quality CPR during cardiac arrest resuscitation. Our case report describes the manifestations of CPR induced consciousness as well as the resuscitative challenges which occur during resuscitation. Further research is required to determine the true frequency of this condition as well as treatment algorithms that would allow for appropriate and safe management for both the patient and EMS providers.

Resuscitation quality assurance for out-of-hospital cardiac arrest--setting-up an ambulance defibrillator telemetry network.

PubMed

Lyon, R M; Clarke, S; Gowens, P; Egan, G; Clegg, G R

2010-12-01

Out-of-hospital cardiac arrest (OHCA) is a leading cause of pre-hospital mortality. Chest compressions performed during cardiopulmonary resuscitation aim to provide adequate perfusion to the vital organs during cardiac arrest. Poor resuscitation technique and the quality of pre-hospital CPR influences outcome from OHCA. Transthoracic impedance (TTI) measurement is a useful tool in the assessment of the quality of pre-hospital resuscitation by ambulance crews but TTI telemetry has not yet been performed in the United Kingdom. We describe a pilot study to implement a data network to collect defibrillator TTI data via telemetry from ambulances. Prospective, observational pilot study over a 5-month period. Modems were fitted to 40 defibrillators on ambulances based in Edinburgh. TTI data was sent to a receiving computer after resuscitation attempts for OHCA. 58 TTI traces were transmitted during the pilot period. Compliance with the telemetry system was high. The mean ratio of chest compressions was 73% (95% CI 69-77%), the mean chest compression rate was 128 (95% CI 122-134). The mean time interval from chest compression interruption to shock delivery was 27 s (95% CI 22-32 s). Trans-thoracic impedance analysis is an effective means of recording important measures of resuscitation quality including the hands-on-the-chest time, compression rate and defibrillation interval time. TTI data transmission via telemetry is straightforward, efficient and allows resuscitation data to be captured and analysed from a large geographical area. Further research is warranted on the impact of post-resuscitation reporting on the quality of resuscitation delivered by ambulance crews. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Helicopter In-flight Resuscitation with Freeze-dried Plasma of a Patient with a High-velocity Gunshot Wound to the Neck in Afghanistan - A Case Report.

PubMed

Gellerfors, Mikael; Linde, Joacim; Gryth, Dan

2015-10-01

Massive hemorrhage with coagulopathy is one of the leading causes of preventable death in the battlefield. The development of freeze-dried plasma (FDP) allows for early treatment with coagulation-optimizing resuscitation fluid in the prehospital setting. This report describes the first prehospital use of FDP in a patient with carotid artery injury due to a high-velocity gunshot wound (HVGSW) to the neck. It also describes in-flight constitution and administration of FDP in a Medevac Helicopter. Early administration of FDP may contribute to hemodynamic stabilization and reduction in trauma-induced coagulopathy and acidosis. However, large-scale studies are needed to define the prehospital use of FDP and other blood products.

Adherence to AHA Guidelines When Adapted for Augmented Reality Glasses for Assisted Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial

PubMed Central

Gervaix, Alain; Haddad, Kevin; Lacroix, Laurence; Schrurs, Philippe; Sahin, Ayhan; Lovis, Christian; Manzano, Sergio

2017-01-01

Background The American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) are nowadays recognized as the world’s most authoritative resuscitation guidelines. Adherence to these guidelines optimizes the management of critically ill patients and increases their chances of survival after cardiac arrest. Despite their availability, suboptimal quality of CPR is still common. Currently, the median hospital survival rate after pediatric in-hospital cardiac arrest is 36%, whereas it falls below 10% for out-of-hospital cardiac arrest. Among emerging information technologies and devices able to support caregivers during resuscitation and increase adherence to AHA guidelines, augmented reality (AR) glasses have not yet been assessed. In order to assess their potential, we adapted AHA Pediatric Advanced Life Support (PALS) guidelines for AR glasses. Objective The study aimed to determine whether adapting AHA guidelines for AR glasses increased adherence by reducing deviation and time to initiation of critical life-saving maneuvers during pediatric CPR when compared with the use of PALS pocket reference cards. Methods We conducted a randomized controlled trial with two parallel groups of voluntary pediatric residents, comparing AR glasses to PALS pocket reference cards during a simulation-based pediatric cardiac arrest scenario—pulseless ventricular tachycardia (pVT). The primary outcome was the elapsed time in seconds in each allocation group, from onset of pVT to the first defibrillation attempt. Secondary outcomes were time elapsed to (1) initiation of chest compression, (2) subsequent defibrillation attempts, and (3) administration of drugs, as well as the time intervals between defibrillation attempts and drug doses, shock doses, and number of shocks. All these outcomes were assessed for deviation from AHA guidelines. Results Twenty residents were randomized into 2 groups. Time to first defibrillation attempt (mean: 146 s) and adherence to AHA guidelines in terms of time to other critical resuscitation endpoints and drug dose delivery were not improved using AR glasses. However, errors and deviations were significantly reduced in terms of defibrillation doses when compared with the use of the PALS pocket reference cards. In a total of 40 defibrillation attempts, residents not wearing AR glasses used wrong doses in 65% (26/40) of cases, including 21 shock overdoses >100 J, for a cumulative defibrillation dose of 18.7 Joules per kg. These errors were reduced by 53% (21/40, P<.001) and cumulative defibrillation dose by 37% (5.14/14, P=.001) with AR glasses. Conclusions AR glasses did not decrease time to first defibrillation attempt and other critical resuscitation endpoints when compared with PALS pocket cards. However, they improved adherence and performance among residents in terms of administering the defibrillation doses set by AHA. PMID:28554878

Transfusion Practice in Military Trauma

DTIC Science & Technology

2008-01-01

al., 1969; Faringer et al., 1993; Brohi et al., 2003; MacLeod et al., 2003). All these findings suggest that there is a need for the early use of...fre- quency and serious implications for survival had not been widely appreciated (Simmons et al., 1969; Faringer et al., 1993). Coagulopathy had...Scalea, T.M. (2002) Hypotensive resuscitation during active hemorrhage: its impact on in hospital mortality. Journal of Trauma, 52, 1141 1146. Faringer

Disseminated viridians streptococcus (Streptococcus mitis) infection presenting with toxic shock-like syndrome.

PubMed

Intalapaporn, Poj; Wongcharoen, Sunee; Chinapha, Anongnart; Jariyasethpong, Tavatchai

2013-03-01

The authors report a case of a 35-year-old man with no known underlying disease who presented with fever, cellulitis with hemorrhagic blebs on the left leg, monoarthricular left knee arthritis, multiple organ failure and septic shock. His clinical syndrome was compatible with toxic shock syndrome and his blood grew alpha hemolytic (viridians) Streptococcus mitis. To our knowledge, there are few reported cases of toxic shock syndrome cause by Streptococcus mitis in immune-competent adults.

Extracorporeal Cardiopulmonary Resuscitation Among Patients with Structurally Normal Hearts.

PubMed

Conrad, Stephanie J; Bridges, Brian C; Kalra, Yuvraj; Pietsch, John B; Smith, Andrew H

Extracorporeal cardiopulmonary resuscitation (eCPR) has been well described as a rescue therapy in refractory cardiac arrest among patients with congenital heart disease. The purpose of this retrospective analysis of data from the Extracorporeal Life Support Organization was to evaluate outcomes of eCPR in patients with structurally normal hearts and to identify risk factors that may contribute to mortality. During the study period, 1,431 patients met inclusion criteria. Median age was 16 years. Overall survival to hospital discharge was 32%. Conditional logistic regression demonstrated an independent survival benefit among smaller patients, patients with a lower partial pressure of carbon dioxide (PaCO2) on cannulation, and those with a shorter duration from intubation to eCPR cannulation. A diagnosis of sepsis was independently associated with a nearly threefold increase in odds of mortality, whereas the diagnosis of myocarditis portended a more favorable outcome. Neurologic complications, pulmonary hemorrhage, disseminated intravascular coagulation, CPR, pH less than 7.20, and hyperbilirubinemia after eCPR cannulation were independently associated with an increase in odds of mortality. When utilizing eCPR in patients with structurally normal hearts, a diagnosis of sepsis is independently associated with mortality, whereas a diagnosis of myocarditis is protective. Neurologic complications and pulmonary hemorrhage while on extracorporeal membrane oxygenation (ECMO) are independently associated with mortality.

Effects of C1 Inhibitor on Tissue Damage in a Porcine Model of Controlled Hemorrhage

DTIC Science & Technology

2012-07-01

and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups...damage in a dose-dependent man- ner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis ... acidosis , reduced circulating tumor necrosis factor !, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on

In-Hospital Quality-of-Care Measures for Pediatric Sepsis Syndrome.

PubMed

Odetola, Folafoluwa O; Freed, Gary; Shevrin, Caroline; Madden, Brian; McCormick, Julie; Dombkowski, Kevin

2017-07-24

Sepsis syndrome, comprising sepsis, severe sepsis, and septic shock, is a leading cause of child mortality and morbidity, for which the delivery of time-sensitive care leads to improved survival. We aimed to describe the development and testing of quality measures for in-hospital care of pediatric sepsis syndrome. Seven measures of quality of care for children hospitalized with sepsis syndrome were developed by using an iterative process including literature review, development of concepts and candidate measures, and selection of measures for feasibility and importance by 2 panels of experts. The measures were tested for reliability and validity among children 0 to 18 years of age hospitalized with sepsis syndrome from January 1, 2012, to June 30, 2013. Of 27 hospitals, 59% had no protocol for the identification and treatment of pediatric sepsis syndrome. Blood culture was performed in only 70% of patients with pediatric sepsis syndrome. Antibiotics were administered within 1 hour of diagnosis in 70% of patients with pediatric severe sepsis or septic shock, and timely fluid resuscitation was performed in 50% of patients with severe sepsis or septic shock. Documentation of heart rate during fluid resuscitation of children with severe sepsis or septic shock was observed in 18% of cases. Two measures could not be rigorously tested for validity and reliability given the rarity of septic shock and were deemed infeasible. This multisite study to develop and validate measures of the quality of hospital care of children with sepsis syndrome highlights the existence of important gaps in delivery of care. Copyright © 2017 by the American Academy of Pediatrics.

Captopril and the intestinal response to hemorrhagic shock.

PubMed

Rosenfeld, L M; Cooper, H S

1982-09-01

In order to help clarify the role of the renin-angiotensin system in the evolution of the post-hemorrhagic circulatory shock syndrome, captopril, a potent inhibitor of the conversion of angiotensin I to angiotensin II, was infused into a hemorrhagic shock model in the cat. The hemorrhage protocol had arterial blood withdrawn until a mean arterial blood pressure (MABP) of 40 mm Hg developed. Oligemia was maintained for a period of 2.5 hr, after which time, all remaining shed blood was reinfused and the cats observed for an additional 2 hr. Coincident with the large reduction in MABP, superior mesenteric artery flow (SMAF) was similarly reduced as recorded by a noncannulating electromagnetic flow probe fitted around the artery. Post-oligemic plasma activities of cathepsin D (CD) and alkaline phosphatase (AP) were elevated 11-fold and 3-fold respectively; intestinal morphological damage was graded at 2.8 +/- 0.6 on a 0-4 scale of increasing severity (control: 0.03 +/- 0.02). Captopril was administered at an initial priming dose of 0.5 mg/kg followed by a continuous infusion of 0.5 mg/kg/hr. Improved post-reinfusion maintenance of MABP and SMAF was noted. Plasma elevations in enzyme activity were more moderate: 8-fold for CD, 1.5-fold for AP. Intestinal morphologic damage was graded at 2.5 +/- 0.3. Blockade of angiotensin II formation by captopril thus demonstrated beneficial effects on post-oligemic hemodynamic status and on the degree of cellular enzyme release without significant improvement in intestinal morphology.

A Novel Swine Model for Evaluation of Potential Intravascular Hemostatic Agents

DTIC Science & Technology

2007-06-01

bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24:145–152. 2. Bellamy RF. 1984. The causes of death in...WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. 2005. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J

Red blood cell transfusion in the resuscitation of septic patients with hematological malignancies.

PubMed

Mirouse, Adrien; Resche-Rigon, Matthieu; Lemiale, Virginie; Mokart, Djamel; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Renault, Anne; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Jourdain, Mercé; Darmon, Michaël; Azoulay, Elie; Pène, Frédéric

2017-12-01

Indications for red blood cell (RBC) transfusion in septic acute circulatory failure remain unclear. We addressed the practices and the prognostic impact of RBC transfusion in the early resuscitation of severe sepsis and septic shock in patients with hematological malignancies. We performed a retrospective analysis of a prospectively collected database of patients with hematological malignancies who required intensive care unit (ICU) admission in 2010-2011. Patients with a main admission diagnosis of severe sepsis or septic shock were included in the present study. We assessed RBC transfusion during the first two days as part of initial resuscitation. Among the 1011 patients of the primary cohort, 631 (62.4%) were admitted to the ICU for severe sepsis (55%) or septic shock (45%). Among them, 210 (33.3%) patients received a median of 2 [interquartile 1-3] packed red cells during the first 48 h. Hemoglobin levels were lower in transfused patients at days 1 and 2 and became similar to those of non-transfused patients at day 3. Early RBC transfusion was more likely in patients with myeloid neoplasms and neutropenia. Transfused patients displayed more severe presentations as assessed by higher admission SOFA scores and blood lactate levels and the further requirements for organ failure supports. RBC transfusion within the first two days was associated with higher day 7 (20.5 vs. 13.3%, p = 0.02), in-ICU (39 vs. 25.2%, p < 0.001) and in-hospital (51 vs. 36.6%, p < 0.001) mortality rates. RBC transfusion remained independently associated with increased in-hospital mortality in multivariate logistic regression (OR 1.52 [1.03-2.26], p = 0.03) and propensity score-adjusted (OR 1.64 [1.05-2.57], p = 0.03) analysis. RBC transfusion is commonly used in the early resuscitation of septic patients with hematological malignancies. Although it was preferentially provided to the most severe patients, we found it possibly associated with an increased risk of death.

Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article.

PubMed

Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Nejabatian, Arezu; Alavian, Seyed Moayed

2015-10-01

Liver as an important organ has a vital role in physiological processes in the body. Different causes can disrupt normal function of liver. Factors such as hypo-perfusion, hypoxemia, infections and some others can cause hepatic injury and hepatic shock. Published research resources from 2002 to May 2015 in some databases (PubMed, Scopus, Index Copernicus, DOAJ, EBSCO-CINAHL, Science direct, Cochrane library and Google scholar and Iranian search database like SID and Iranmedex) were investigated for the present study. Different causes can lead to hepatic shock. Most of these causes can be prevented by early resuscitation and treatment of underlying factors. Hepatic shock is detected in ill patients, especially those with hemodynamic disorders. It can be prevented by early treatment of underlying disease. There is no definite treatment for hepatic shock and should be managed conservatively. Hepatic shock in patients can increase the mortality rate.

Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article

PubMed Central

Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Nejabatian, Arezu; Alavian, Seyed Moayed

2015-01-01

Context: Liver as an important organ has a vital role in physiological processes in the body. Different causes can disrupt normal function of liver. Factors such as hypo-perfusion, hypoxemia, infections and some others can cause hepatic injury and hepatic shock. Evidence Acquisition: Published research resources from 2002 to May 2015 in some databases (PubMed, Scopus, Index Copernicus, DOAJ, EBSCO-CINAHL, Science direct, Cochrane library and Google scholar and Iranian search database like SID and Iranmedex) were investigated for the present study. Results: Different causes can lead to hepatic shock. Most of these causes can be prevented by early resuscitation and treatment of underlying factors. Conclusions: Hepatic shock is detected in ill patients, especially those with hemodynamic disorders. It can be prevented by early treatment of underlying disease. There is no definite treatment for hepatic shock and should be managed conservatively. Hepatic shock in patients can increase the mortality rate. PMID:26587034

Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

PubMed Central

Mommsen, Philipp; Pfeifer, Roman; Mohr, Juliane; Ruchholtz, Steffen; Flohé, Sascha; Fröhlich, Matthias; Keibl, Claudia; Seekamp, Andreas; Witte, Ingo

2015-01-01

Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia. PMID:26170533

Hypovolemic Shock and Hemoperitoneum from Spontaneous Avulsion of a Large Pedunculated Uterine Leiomyoma.

PubMed

Mizrahi, Daniel J; Kaushik, Chhavi; Adamo, Robert

2017-03-01

Hemoperitoneum with hypovolemic shock from avulsion of a pedunculated leiomyoma is a rare but highly fatal condition that can occur spontaneously or as a result of trauma. We report a case of hemoperitoneum and hypovolemic shock secondary to a bleeding leiomyoma detected via computed tomography (CT) scan in a 39 year old premenopausal, gravida 0 female that presented with abdominal pain and became hemodynamically unstable in the emergency department. A preoperative bimanual exam revealed a mass consistent with a 20 week gestational uterus. Following fluid resuscitation, the patient underwent emergent myomectomy and ligation of the right uterine artery and was discharged home in good condition.

The apelinergic system as an alternative to catecholamines in low-output septic shock.

PubMed

Coquerel, David; Sainsily, Xavier; Dumont, Lauralyne; Sarret, Philippe; Marsault, Éric; Auger-Messier, Mannix; Lesur, Olivier

2018-01-19

Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the "maintaining blood pressure" paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

Ion Movements in Shock in Relation to Survival and Its Modifications

DTIC Science & Technology

1985-01-01

from normal to irreversibly injured are initiated and modified by primary and/or secondary effects of ion redistributions taking place between the...reactions to injury by the shock state has become possible. However, spcclflc aspects concerning effects at the cellular and subcellular levels need...to be further clarified. Therefore, the aim of this study was to characterize the cellular and subcellular effects of hemorrhagic and bacteremic shock

Clinical and clinical laboratory correlates in sea otters dying unexpectedly in rehabilitation centers following the Exxon Valdez oil spill

USGS Publications Warehouse

Rebar, A.H.; Lipscomb, T.P.; Harris, R.K.; Ballachey, Brenda E.

1995-01-01

Following the Exxon Valdez oil spill, 347 oiled sea otters (Enhydra lutris) were treated in rehabilitation centers. Of these, 116 died, 94 within 10 days of presentation. Clinical records of 21 otters dying during the first 10 days of rehabilitation were reviewed to define the laboratory abnormalities and clinical syndromes associated with these unexpected deaths. The most common terminal syndrome was shock characterized by hypothermia, lethargy, and often hemorrhagic diarrhea. In heavily and moderately oiled otters, shock developed within 48 hours of initial presentation, whereas in lightly oiled otters shock generally occurred during the second week of captivity. Accompanying laboratory abnormalities included leukopenia with increased numbers of immature neutrophils (degenerative left shift), lymphopenia, anemia, azotemia (primarily prerenal), hyperkalemia, hypoproteinemia/hypoalbuminemia, elevations of serum transaminases, and hypoglycemia. Shock associated with hemorrhagic diarrhea probably occurred either as a direct primary effect of oiling or as an indirect effect secondary to confinement and handling in the rehabilitation centers. Lightly oiled otters were less likely to die from shock than were heavily oiled otters (22% vs. 72%, respectively). Heavily oiled otters developed shock more rapidly and had greater numbers of laboratory abnormalities, suggesting that exposure to oil was an important contributing factor.

[Effects of granulocyte-macrophage colony stimulating factor on nuclear factor-KappaB activation in multiple organs of hemorrhage-induced acute lung injury in mice].

PubMed

Wang, Qian; Song, Yong; Shi, Yi

2007-05-01

To investigate the effects of nuclear factor-KappaB (NF-KappaB) activation in multiple organs of hemorrhage-induced acute lung injury (ALI) by the specific granulocyte-macrophage colony stimulating factor (GM-CSF)-neutralizing antibody (22E9) and dexamethasone (DEX) in mice. Twenty male C57BL/6 mice were used to reproduce a model of hemorrhagic shock by cardiac puncture. Before cardiac puncture, mice in different groups were transnasally administered with phosphate buffered solution (PBS, PCG group), PBS plus 1 microg 22E9 (HS1 group), PBS plus 10 microg 22E9 (HS10 group) and PBS plus 20 microg DEX (DEX group), respectively. In negative control group (NCG group) received cardiac puncture without shock followed by transnasal administration with PBS without shock. Lungs, hearts, livers and kidneys tissues of mice were harvested at 4 hours after hemorrhagic shock. The activities of NF-KappaB in different organs was determined by electrophoretic mobility shift assay (EMSA). The tumor necrosis factor-alpha (TNF-alpha) in lung and heart were determined by enzyme-linked immunosorbent assay (ELISA). 22E9 in both low or high doses could significantly inhibit NF-KappaB activities in lung, heart and liver, and elevated NF-KappaB activity in kidney compared with those of PCG group (all P<0.05). The effect of 22E9 was much better in HS1 group than in HS10 group (all P<0.05). DEX significantly strengthened NF-KappaB activity in kidney (P<0.05) and didn't significantly inhibit NF-KappaB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF-alpha in lung and heart, while DEX significantly inhibited TNF-alpha in heart (all P<0.05). 22E9 can inhibit the NF-KappaB activation and inflammatory reaction in multiple organs after hemorrhage-induced ALI and reduce injury in multiple organs, while DEX has no significant effect.

The Role of Post-Resuscitation Electrocardiogram in Patients With ST-Segment Changes in the Immediate Post-Cardiac Arrest Period.

PubMed

Kim, Youn-Jung; Min, Sun-Yang; Lee, Dong Hun; Lee, Byung Kook; Jeung, Kyung Woon; Lee, Hui Jai; Shin, Jonghwan; Ko, Byuk Sung; Ahn, Shin; Nam, Gi-Byoung; Lim, Kyoung Soo; Kim, Won Young

2017-03-13

The authors aimed to evaluate the role of post-resuscitation electrocardiogram (ECG) in patients showing significant ST-segment changes on the initial ECG and to provide useful diagnostic indicators for physicians to determine in which out-of-hospital cardiac arrest (OHCA) patients brain computed tomography (CT) should be performed before emergency coronary angiography. The usefulness of immediate brain CT and ECG for all resuscitated patients with nontraumatic OHCA remains controversial. Between January 2010 and December 2014, 1,088 consecutive adult nontraumatic patients with return of spontaneous circulation who visited the emergency department of 3 tertiary care hospitals were enrolled. After excluding 245 patients with obvious extracardiac causes, 200 patients were finally included. The patients were categorized into 2 groups: those with ST-segment changes with spontaneous subarachnoid hemorrhage (SAH) (n = 50) and those with OHCA of suspected cardiac origin group (n = 150). The combination of 4 ECG characteristics including narrow QRS (<120 ms), atrial fibrillation, prolonged QTc interval (≥460 ms), and ≥4 ST-segment depressions had a 66.0% sensitivity, 80.0% specificity, 52.4% positive predictive value, and 87.6% negative predictive value for predicting SAH. The area under the receiver-operating characteristic curves in the post-resuscitation ECG findings was 0.816 for SAH. SAH was observed in a substantial number of OHCA survivors (25.0%) with significant ST-segment changes on post-resuscitation ECG. Resuscitated patients with narrow QRS complex and any 2 ECG findings of atrial fibrillation, QTc interval prolongation, or ≥4 ST-segment depressions may help identify patients who need brain CT as the next diagnostic work-up. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Developing a New Definition and Assessing New Clinical Criteria for Septic Shock

PubMed Central

Shankar-Hari, Manu; Phillips, Gary S.; Levy, Mitchell L.; Seymour, Christopher W.; Liu, Vincent X.; Deutschman, Clifford S.; Angus, Derek C.; Rubenfeld, Gordon D.; Singer, Mervyn

2016-01-01

IMPORTANCE Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE To develop a new definition and clinical criteria for identifying septic shock in adults. DESIGN, SETTING, AND PARTICIPANTS The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005–2010; n = 28 150), University of Pittsburgh Medical Center (UPMC) (2010–2012; n = 1 309 025), and Kaiser Permanente Northern California (KPNC) (2009–2013; n = 1 847 165) electronic health record (EHR) data sets. MAIN OUTCOMES AND MEASURES Evidence for and agreement on septic shock definitions and criteria. RESULTS The systematic review identified 44 studies reporting septic shock outcomes (total of 166 479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock–associated crude mortality was 46.5% (95%CI, 42.7%–50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3%[95%CI, 41.2%–43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets. CONCLUSIONS AND RELEVANCE Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation. PMID:26903336

Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

PubMed Central

Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

2013-01-01

Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

Mesenchymal Stem Cells Reverse T/HS Induced Bone Marrow Dysfunction

PubMed Central

Gore, Amy V.; Bible, Letitia E.; Livingston, David H.; Mohr, Alicia M.; Sifri, Ziad C.

2015-01-01

Intro Lung contusion (LC) followed by hemorrhagic shock (HS) causes persistent bone marrow (BM) dysfunction lasting up to seven days after injury. Mesenchymal stem cells (MSC) are multipotent cells that can hasten healing as well as exert protective immunomodulatory effects. We hypothesize that MSC can attenuate BM dysfunction following combined LCHS. Materials and Methods Male Sprague-Dawley (SD) rats (n=5-6/group) underwent LC+45 minutes of HS (MAP of 30-35). Allogeneic MSCs (5 × 106 cells) were injected IV following resuscitation. At seven days, BM was analyzed for cellularity and growth of hematopoetic progenitor cell (HPC) colonies (CFU-E, BFU-E, CFU-GEMM). Flow cytometry measured %HPCs in peripheral blood (PB); plasma G-CSF levels were measured via ELISA. Data was analyzed by one-way ANOVA followed by Tukey's multiple comparison test. Results As previously shown, at seven days, LCHS resulted in 22, 30, and 24% decreases in CFU-GEMM, BFU-E and CFU-E colony growth respectively vs. naïve. Treatment with MSCs returned all BM parameters to naïve levels. There was no difference in %HPCs in PB between groups, however, G-CSF remained elevated up to seven days following LCHS. MSCs returned G-CSF to naïve levels. Plasma from animals receiving MSCs was not suppressive to the BM. Conclusion One week following injury, the persistent BM dysfunction seen in animals undergoing LCHS is reversed by treatment with MSCs with an associated return of plasma G-CSF levels to normal. Plasma from animals undergoing LCHS+MSCs was not suppressive to BM cells in vitro. Treatment with MSCs following injury and shock reverses BM suppression and returns plasma G-CSF levels to normal. PMID:26193832

Why do some studies find that CPR fraction is not a predictor of survival?

PubMed

Wik, Lars; Olsen, Jan-Aage; Persse, David; Sterz, Fritz; Lozano, Michael; Brouwer, Marc A; Westfall, Mark; Souders, Chris M; Travis, David T; Herken, Ulrich R; Lerner, E Brooke

2016-07-01

An 80% chest compression fraction (CCF) during resuscitation is recommended. However, heterogeneous results in CCF studies were found during the 2015 Consensus on Science (CoS), which may be because chest compressions are stopped for a wide variety of reasons including providing lifesaving care, provider distraction, fatigue, confusion, and inability to perform lifesaving skills efficiently. The effect of confounding variables on CCF to predict cardiac arrest survival. A secondary analysis of emergency medical services (EMS) treated out-of-hospital cardiac arrest (OHCA) patients who received manual compressions. CCF (percent of time patients received compressions) was determined from electronic defibrillator files. Two Sample Wilcoxon Rank Sum or regression determined a statistical association between CCF and age, gender, bystander CPR, public location, witnessed arrest, shockable rhythm, resuscitation duration, study site, and number of shocks. Univariate and multivariate logistic regressions were used to determine CCF effect on survival. Of 2132 patients with manual compressions 1997 had complete data. Shockable rhythm (p<0.001), public location (p<0.004), treatment duration (p<0.001), and number of shocks (p<0.001) were associated with lower CCF. Univariate logistic regression found that CCF was inversely associated with survival (OR 0.07; 95% CI 0.01-0.36). Multivariate regression controlling for factors associated with survival and/or CCF found that increasing CCF was associated with survival (OR 6.34; 95% CI 1.02-39.5). CCF cannot be looked at in isolation as a predictor of survival, but in the context of other resuscitation activities. When controlling for the effects of other resuscitation activities, a higher CCF is predictive of survival. This may explain the heterogeneity of findings during the CoS review. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of timing and duration of a single chest compression pause on short-term survival following prolonged ventricular fibrillation.

PubMed

Walcott, Gregory P; Melnick, Sharon B; Walker, Robert G; Banville, Isabelle; Chapman, Fred W; Killingsworth, Cheryl R; Ideker, Raymond E

2009-04-01

Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome. Part A: 48 swine were anesthetized, fibrillated for 7min and randomized. Chest compressions were initiated for 90s followed by defibrillation and then resumption of chest compressions. Four groups were studied-G2000: 40s pause beginning 20s before, and ending 20s after defibrillation, A1: a 20s pause just before defibrillation, A2: a 20s pause ending 30s prior to defibrillation, and group A3: a 10s pause ending 30s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4h. The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p<0.05). Survival did not differ significantly among groups A1, A2, A3, and B. These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit.

Effect of timing and duration of a single chest compression pause on short-term survival following prolonged ventricular fibrillation☆

PubMed Central

Walcott, Gregory P.; Melnick, Sharon B.; Walker, Robert G.; Banville, Isabelle; Chapman, Fred W.; Killingsworth, Cheryl R.; Ideker, Raymond E.

2014-01-01

Background Pauses during chest compressions are thought to have a detrimental effect on resuscitation outcome. The Guidelines 2005 have recently eliminated the post-defibrillation pause. Previous animal studies have shown that multiple pauses of increasing duration decrease resuscitation success. We investigated the effect of varying the characteristics of a single pause near defibrillation on resuscitation outcome. Methods Part A: 48 swine were anesthetized, fibrillated for 7 min and randomized. Chest compressions were initiated for 90 s followed by defibrillation and then resumption of chest compressions. Four groups were studied—G2000: 40 s pause beginning 20 s before, and ending 20 s after defibrillation, A1: a 20 s pause just before defibrillation, A2: a 20 s pause ending 30 s prior to defibrillation, and group A3: a 10 s pause ending 30 s prior to defibrillation. Part B: 12 swine (Group B) were studied with a protocol identical to Part A but with no pause in chest compressions. Primary endpoint was survival to 4 h. Results The survival rate was significantly higher for groups A1, A2, A3, and B (5/12, 7/12, 5/12, and 5/12 survived) than for the G2000 group (0/12, p < 0.05). Survival did not differ significantly among groups A1, A2, A3, and B. Conclusions These results suggest that the Guidelines 2005 recommendation to omit the post-shock pulse check and immediately resume chest compressions may be an important resuscitation protocol change. However, these results also suggest that clinical maneuvers further altering a single pre-shock chest compression pause provide no additional benefit. PMID:19185411

Patient-centric blood pressure-targeted cardiopulmonary resuscitation improves survival from cardiac arrest.

PubMed

Sutton, Robert M; Friess, Stuart H; Naim, Maryam Y; Lampe, Joshua W; Bratinov, George; Weiland, Theodore R; Garuccio, Mia; Nadkarni, Vinay M; Becker, Lance B; Berg, Robert A

2014-12-01

Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure-targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9-13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0-12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0-3] vs. 2 [range, 2-2]; P = 0.003). Blood pressure-targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest.

Patient-centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest

PubMed Central

Friess, Stuart H.; Naim, Maryam Y.; Lampe, Joshua W.; Bratinov, George; Weiland, Theodore R.; Garuccio, Mia; Nadkarni, Vinay M.; Becker, Lance B.; Berg, Robert A.

2014-01-01

Rationale: Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. Objectives: To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF). Methods: After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure–targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival. Measurements and Main Results: The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9–13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0–12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0–3] vs. 2 [range, 2–2]; P = 0.003). Conclusions: Blood pressure–targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest. PMID:25321490

Strategies of experiment standardization and response optimization in a rat model of hemorrhagic shock and chronic hypertension.

PubMed

Reynolds, Penny S; Tamariz, Francisco J; Barbee, Robert Wayne

2010-04-01

Exploratory pilot studies are crucial to best practice in research but are frequently conducted without a systematic method for maximizing the amount and quality of information obtained. We describe the use of response surface regression models and simultaneous optimization methods to develop a rat model of hemorrhagic shock in the context of chronic hypertension, a clinically relevant comorbidity. Response surface regression model was applied to determine optimal levels of two inputs--dietary NaCl concentration (0.49%, 4%, and 8%) and time on the diet (4, 6, 8 weeks)--to achieve clinically realistic and stable target measures of systolic blood pressure while simultaneously maximizing critical oxygen delivery (a measure of vulnerability to hemorrhagic shock) and body mass M. Simultaneous optimization of the three response variables was performed though a dimensionality reduction strategy involving calculation of a single aggregate measure, the "desirability" function. Optimal conditions for inducing systolic blood pressure of 208 mmHg, critical oxygen delivery of 4.03 mL/min, and M of 290 g were determined to be 4% [NaCl] for 5 weeks. Rats on the 8% diet did not survive past 7 weeks. Response surface regression model and simultaneous optimization method techniques are commonly used in process engineering but have found little application to date in animal pilot studies. These methods will ensure both the scientific and ethical integrity of experimental trials involving animals and provide powerful tools for the development of novel models of clinically interacting comorbidities with shock.

Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock.

PubMed

Du, Wei; Liu, Da-Wei; Wang, Xiao-Ting; Long, Yun; Chai, Wen-Zhao; Zhou, Xiang; Rui, Xi

2013-12-01

Central venous oxygen saturation (Scvo2) is a useful therapeutic target when treating septic shock. We hypothesized that combining Scvo2 and central venous-to-arterial partial pressure of carbon dioxide difference (△Pco2) may provide additional information about survival. We performed a retrospective analysis of 172 patients treated for septic shock. All patients were treated using goal-directed therapy to achieve Scvo2 ≥ 70%. After 6 hours of treatment, we divided patients into 4 groups based on Scvo2 (<70% or ≥ 70%) and △Pco2 (<6 mm Hg or ≥ 6 mm Hg). Overall, 28-day mortality was 35.5%. For patients in whom the Scvo2 target was not achieved at 6 hours, mortality was 50.0%, compared with 29.5% in those in whom Scvo2 exceeded 70% (P = .009). In patients with Scvo2 ≥ 70%, mortality was lower if △Pco2 was <6 mm Hg than if △Pco2 was ≥ 6 mm Hg (56.1% vs 16.1%, respectively; P < .001) and 6-hour lactate clearance was superior (0.01 ± 0.61 vs 0.21 ± 0.31, respectively; P = .016). The combination of Scvo2 and △Pco2 appears to predict outcome in critically ill patients resuscitated from septic shock better than Scvo2 alone. Patients who meet both targets appear to clear lactate more efficiently. © 2013.

[Case study with a gunshot fracture of lower extremities and damage of popliteal artery (case report)].

PubMed

Orakhelashvili, G A; Kapanadze, L P; Bregadze, G I; Kacharava, B D; Dzagnidze, E B

2011-12-01

Severe vascular gunshot injury (popliteal artery damage) and fractures of both low extremities are causes traumatic shock (stage III) and anemia in a 32 years female patient. Being the victim of crime, the patient for 5 hours was in a life-threatening condition that could develop the multiple organ system failure (MOSF) as a result of tissue ischemia and reperfusion and acute irreversible shock. There was an urgent necessity to perform three immediate operations at the same time. Successful recovery required rapid control of the inciting event (i.e., maintenance of effective hemodynamic stability and the body's ability to protect its vital organs, choice of the type of anesthesia with certain anesthetics) facilitated by resuscitative therapy directed toward minimizing the overall "dose" of shock. Oxybutirate sodium (a GABA analog, the only one narcotic drug and a natural metabolite of body) administered intravenously as a hypnotic agent and an important component of intensive care as well have had clearly anti-shock and antihypoxant effects. Rapid improving of circulation and using of medications with wide range of anti-stress action (such as oxybutirate sodium, dexamethazone and glucose) assisted successful resuscitation and possibility to perform three operations (duration: 6 hours and 45 minutes). An increasing emphasis was being placed on prevention of MOSF, including 1) maintenance of tissue oxygenation; 2) using above-mentioned anti-stress and antihypoxant medicines with mutually supportive effects and 3) infection control.

Fibrinogen Availability and Coagulation Function After Hemorrhage and Resuscitation in Pigs

DTIC Science & Technology

2011-08-01

Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to...that reduced clot formation rate and clot strength by ROTEM are indicative of transfusion re- quirements (14). The purpose of this study was to inves...administration and to reduce the usage of blood products (15,16). In this study, we observed a parallel changing pattern between fibrinogen concentration

A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume

PubMed Central

Bian, Yuzhu; Chang, Thomas Ming Swi

2015-01-01

Abstract We crosslink hemoglobin (Hb), superoxide dismutase (SOD), catalase (CAT), and carbonic anhydrase (CA) to form a soluble polyHb-SOD-CAT-CA nanobiotechnological complex. The obtained product is a soluble complex with three enhanced red blood cell (RBC) functions and without blood group antigens. In the present study, 2/3 of blood volume was removed to result in 90-min hemorrhagic shock at mean arterial blood pressure (MAP) of 30 mmHg. This was followed by the reinfusion of different resuscitation fluids, then followed for another 60 min. PolyHb-SOD-CAT-CA maintained the MAP at 87.5 ± 5 mmHg as compared with 3 volumes of lactated Ringer's solution, 43.3 ± 2.8 mmHg; blood, 91.3 ± 3.6 mmHg; polyHb-SOD-CAT, 86.0 ± 4.6 mmHg; poly stroma-free hemolysate (polySFHb), 85.0 ± 2.5 mmHg; and polyHb, 82.6 ± 3.5 mmHg. PolyHb-SOD-CAT-CA was superior to the blood and other fluids based on the following criteria. PolyHb-SOD-CAT-CA reduced tissue pCO2 from 98 ± 4.5 mmHg to 68.6 ± 3 mmHg. This was significantly (p < 0.05) more effective than lactated Ringer's solution (98 ± 4.5 mmHg), polyHb (90.1 ± 4.0 mmHg), polyHb-SOD-CAT (90.9 ± 1.4 mmHg), blood (79.1 ± 4.7 mmHg), and polySFHb (77 ± 5 mmHg). PolyHb-SOD-CAT-CA reduced the elevated ST level to 21.7 ± 6.7% and is significantly (< 0.05) better than polyHb (57.7 ± 8.7%), blood (39.1 ± 1.5%), polySFHb (38.3% ± 2.1%), polyHb-SOD-CAT (27.8 ± 5.6%), and lactated Ringer's solution (106 ± 3.1%). The plasma cardiac troponin T (cTnT) level of polyHb-SOD-CAT-CA group was significantly (P < 0.05) lower than that of all the other groups. PolyHb-SOD-CAT-CA reduced plasma lactate level from 18 ± 2.3 mM/L to 6.9 ± 0.3 mM/L. It was significantly more effective (P < 0.05) than lactated Ringer's solution (12.4 ± 0.6 mM/L), polyHb (9.6 ± 0.7 mM/L), blood (8.1 ± 0.2 mM/L), polySFHb (8.4 ± 0.1 mM/L), and polyHb-SOD-CAT (7.6 ± 0.3 mM/L). PolyHb-SOD-CAT-CA can be stored for 320 days at room temperature. Lyophilized poly-Hb-SOD-CAT-CA can be heat pasteurized at 68F for 2 h. This can be important if there is a need to inactivate human immunodeficiency virus, Ebola virus, and other infectious organisms. PMID:25297052

Initial fractal exponent of heart-rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study

PubMed Central

Brown, Samuel M.; Tate, Quinn; Jones, Jason P.; Knox, Daniel; Kuttler, Kathryn G.; Lanspa, Michael; Rondina, Matthew T.; Grissom, Colin K.; Behera, Subhasis; Mathews, V.J.; Morris, Alan

2013-01-01

Introduction Heart-rate variability reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in heart-rate variability upon ICU admission would be associated with unsuccessful early resuscitation of sepsis. Methods We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of EKG, sampled at 500 Hz, at ICU admission and calculated heart-rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality. Results We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (p=0.04) after controlling for mean heart rate. In the optimal model, SOFA score and the long-term fractal alpha parameter were associated with vasopressor independence. Conclusions Loss of complexity in heart rate variability is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of heart rate variability (HRV) could guide treatment in sepsis. PMID:23958243

Colloid normalizes resuscitation ratio in pediatric burns.

PubMed

Faraklas, Iris; Lam, Uyen; Cochran, Amalia; Stoddard, Gregory; Saffle, Jeffrey

2011-01-01

Fluid resuscitation of burned children is challenging because of their small size and intolerance to over- or underresuscitation. Our American Burn Association-verified regional burn center has used colloid "rescue" as part of our pediatric resuscitation protocol. With Institutional Review Board approval, the authors reviewed children with ≥15% TBSA burns admitted from January 1, 2004, to May 1, 2009. Resuscitation was based on the Parkland formula, which was adjusted to maintain urine output. Patients requiring progressive increases in crystalloid were placed on a colloid protocol. Results were expressed as an hourly resuscitation ratio (I/O ratio) of fluid infusion (ml/kg/%TBSA/hr) to urine output (ml/kg/hr). We reviewed 53 patients; 29 completed resuscitation using crystalloid alone (lactated Ringer's solution [LR]), and 24 received colloid supplementation albumin (ALB). Groups were comparable in age, gender, weight, and time from injury to admission. ALB patients had more inhalation injuries and larger total and full-thickness burns. LR patients maintained a median I/O of 0.17 (range, 0.08-0.31), whereas ALB patients demonstrated escalating ratios until the institution of albumin produced a precipitous return of I/O comparable with that of the LR group. Hospital stay was lower for LR patients than ALB patients (0.59 vs 1.06 days/%TBSA, P = .033). Twelve patients required extremity or torso escharotomy, but this did not differ between groups. There were no decompressive laparotomies. The median resuscitation volume for ALB group was greater than LR group (9.7 vs 6.2 ml/kg/%TBSA, P = .004). Measuring hourly I/O is a helpful means of evaluating fluid demands during burn shock resuscitation. The addition of colloid restores normal I/O in pediatric patients.

Hemorrhagic Shock-Induced Vascular Hyporeactivity in the Rat: Relationship to Gene Expression of Nitric Oxide Synthase, Endothelin-1, and Select Cytokines in Corresponding Organs

DTIC Science & Technology

2005-01-01

the Selected Genes Sense Antisense Product length (bp) G3PDH 5=-TCCTGCACCACCAACTGCTTAG-3= 5=-TGCTTCACCACCTTCTTGATGTC-3= 341 iNOS 5...GAPDH, as a housekeeping gene, was not affected significantly by the hemorrhage protocol. The results showed that mRNA levels of all enzymes and

Defining hypotension in moderate to severely injured trauma patients: raising the bar for the elderly.

PubMed

Edwards, Meghan; Ley, Eric; Mirocha, James; Hadjibashi, Anoushiravan Amini; Margulies, Daniel R; Salim, Ali

2010-10-01

Hypotension, defined as systolic blood pressure less than 90 mm Hg, is recognized as a sign of hemorrhagic shock and is a validated prognostic indicator. The definition of hypotension, particularly in the elderly population, deserves attention. We hypothesized that the systolic blood pressure associated with increased mortality resulting from hemorrhagic shock increases with increasing age. The Los Angeles County Trauma Database was queried for all moderate to severely injured patients without major head injuries admitted between 1998 and 2005. Several fit statistic analyses were performed for each systolic blood pressure from 50 to 180 mm Hg to identify the model that most accurately defined hypotension for three age groups. The optimal definition of hypotension for each group was determined from the best fit model. A total of 24,438 patients were analyzed. The optimal definition of hypotension was systolic blood pressure of 100 mm Hg for patients 20 to 49 years, 120 mm Hg for patients 50 to 69 years, and 140 mm Hg for patients 70 years and older. The optimal systolic blood pressure for improved mortality in hemorrhagic shock increases significantly with increasing age. Elderly trauma patients without major head injuries should be considered hypotensive for systolic blood pressure less than 140 mm Hg.

Optimal Surgical Therapy in a Porcine (Sus scrofa) Model of Extra-Thoracic Penetrating Trauma Resulting in Hemorrhagic Shock: ED Thoracotomy vs. Immediate Trans-Abdominal Vascular Control. A Porcine Model for Evaluating the Management of Non-Compressible Torso Hemorrhage

DTIC Science & Technology

2010-11-08

celiac aortic clamping (n=6), direct vascular control (n=6), and endovascular aortic occlusion n=6). This study presents a large animal model of class...including thoracic aortic clamping, supra- celiac aortic clamping, direct vascular control, and proximal endovascular balloon occlusion. Following vascular...subsequently underwent non-compressible hemorrhage with thoracic aortic clamping (n=6), supra- celiac aortic clamping (n=6), direct vascular control (n=6

Deployable, Field-Sustainable, Reverse Transcription-Polymerase Chain Reaction Assays for Rapid Screening and Serotype Identification of Dengue Virus in Mosquitoes

DTIC Science & Technology

2007-03-01

C, Gottig S, Schiiiing S, et ai: Rapid detection and quantiilcation of RNA of Eboia and Marburg viruses, L.assa virus, Crimean - Congo hemorrhagic fever ...the past two decades, dengue fever (DF) and the poten- tially fatal forms ofthe disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome, have...Viroi 2003; 77: i 1436-47. 5. Gubler DJ: Dengue and dengue hemorrhagic fever . Ciin Microbiol Rev 1998; 11: 480-96. 6. Fonseca BA, Fonseca SN: Dengue virus

Saved by focused echo evaluation in resuscitation

PubMed Central

Hollister, N; Bond, R; Donovan, A; Nicholls, B

2011-01-01

A 74-year-old woman received thrombolysis for pericarditis. She subsequently developed shock and cardiac arrest. The case report describes the events of how a simple immediate bedside focused echo proved to be a life saving assessment. Current availability and training issues in focused transthoracic echo are discussed. PMID:22707666

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage.

PubMed

Baylis, James R; St John, Alexander E; Wang, Xu; Lim, Esther B; Statz, Matthew L; Chien, Diana; Simonson, Eric; Stern, Susan A; Liggins, Richard T; White, Nathan J; Kastrup, Christian J

2016-09-01

Hemorrhage is the leading cause of preventable death in trauma, and hemorrhage from noncompressible junctional anatomic sites is particularly difficult to control. The current standard is QuikClot Combat Gauze packing, which requires 3 min of compression. We have created a novel dressing with calcium carbonate microparticles that can disperse and self-propel upstream against flowing blood. We loaded these microparticles with thrombin and tranexamic acid and tested their efficacy in a swine arterial bleeding model without wound compression. Anesthetized immature female swine received 5 mm femoral arteriotomies to induce severe junctional hemorrhage. Wounds were packed with kaolin-based QuikClot Combat Gauze (KG), propelled thrombin-microparticles with protonated tranexamic acid (PTG), or a non-propelling formulation of the same thrombin-microparticles with non-protonated tranexamic acid (NPTG). Wounds were not compressed after packing. Each animal then received one 15 mL/kg bolus of hydroxyethyl starch solution followed by Lactated Ringer as needed for hypotension (maximum: 100 mL/kg) for up to 3 h. Survival was improved with PTG (3-h survival: 8/8, 100%) compared with KG (3/8, 37.5%) and NPTG (2/8, 25%) (P <0.01). PTG animals maintained lower serum lactate and higher hemoglobin concentrations than NPTG (P <0.05) suggesting PTG decreased severity of subsequent hemorrhagic shock. However, total blood loss, Lactated Ringer infusion volumes, and mean arterial pressures of surviving animals were not different between groups (P >0.05). Thus, in this swine model of junctional arterial hemorrhage, gauze with self-propelled, prothrombotic microparticles improved survival and 2 indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds.