Honore', P M; Joannes-Boyau, O; Merson, L; Boer, W; Piette, V; Galloy, A-C; Janvier, G
2006-07-01
Since the last decade, hemofiltration and especially high volume hemofiltration has rapidly evolved from a somewhat experimental treatment towards a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine resistant hypodynamic septic shock. Nevertheless, this approach lacks prospective randomized studies (PRT'S) evaluating the critical role of early hemofiltration in sepsis. An important step forward which could be called the 'big bang' in term of hemofiltration was the publication of a PRT in patients with acute renal failure (ARF) (1). Before this study (2), nobody believed that hemofiltration could change the survival rate in intensive care. Since that big bang, many physicians consider that hemofiltration at a certain dose can change the survival rate in intensive care. So the world of hemofiltration in ICU is not a definitive world, it is still in expansion. Indeed, we now have to try to define what will be the exact dose we need in septic acute renal failure. This dose might well be 'higher' than 35 ml/kg/hour in the septic acute renal failure 'group' as suggested by many studies (2-5). At present, it is the issue of continuous dose of high volume hemofiltration that has to be tested in future randomized studies. Since the Vicenza study (2) has shown that 35 ml/kg/h is the best dose in terms of survival, dealing with non septic acute renal failure in ICU, several studies from different groups have shown that, in septic acute renal failure, a higher dose might correlate with better survival. This has also been shown in some way by the study of the 'Vicenza group' but not with a statistically significant value (2). New PRT'S have just started in Europe like the IVOIRE study (hIgh VOlume in Intensive caRE) (6) and the RENAL study. Another large study is looking more basically at dose in non septic acute renal failure in Australasia and is led by the group of Rinaldo Bellomo in Melbourne (7) as well as the ATN study (8) led by Palevsky and colleagues in the USA, also testing the importance of dose in the treatment for ARF. Nevertheless, 'early goal-directed hemofiltration therapy' like early goal directed therapy (9) has to be studied in our critical ill patients. Regarding this issue, fewer studies, mainly retrospective exist, but again the IVOIRE study (6) will address this issue by studying septic patients with acute renal injury according to the Rifle classification (10). So, this review focuses on the early application and on the adequate dose of continuous high volume hemofiltration in septic shock in order to improve not only hemodynamics, but survival in this very severely ill cohort of patients. This could well be called the 'big bang of hemofiltration' as one could never have anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of ICU-septic acute renal failure patients. On top of the use of early and adequate dose of hemofiltration in sepsis, a higher dose could also provide better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this paper also reviews 'brand' new theories regarding the rationale for hemofiltration in sepsis. Finally, this paper also addresses the so-called negative studies as well anticipated side effects.
Moriyama, Brad; Henning, Stacey A.; Jin, Haksong; Kolf, Mike; Rehak, Nadja N.; Danner, Robert L.; Walsh, Thomas J.; Grimes, George J.
2011-01-01
PURPOSE To assess the physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded bicarbonate-buffered hemofiltration solution used at the National Institutes of Health Clinical Center (http://www.cc.nih.gov). METHODS Two hemofiltration fluid formulations with a bicarbonate of 50 mEq/L and a magnesium of 1.5 mEq/L or 15 mEq/L were prepared in triplicate with an automated compounding device. The hemofiltration solution with a bicarbonate of 50 mEq/L and a magnesium of 1.5 mEq/L contains the maximum concentration of additives that we use in clinical practice. The hemofiltration solution of 15 mEq/L of magnesium and 50 mEq/L of bicarbonate was used to study the physicochemical properties of this interaction. The solutions were stored without light protection at 22 to 25 °C for 48 hours. Physical compatibility was assessed by visual inspection and microscopy. The pH of the solutions was assayed at 3 to 4 hours and 52 to 53 hours after compounding. In addition, electrolyte and glucose concentrations in the solutions were assayed at two time points after preparation: 3 to 4 hours and 50 to 51 hours. RESULTS No particulate matter was observed by visual and microscopic inspection in the compounded hemofiltration solutions at 48 hours. Electrolyte and glucose concentrations and pH were similar at both time points after solution preparation. CONCLUSION Magnesium sulfate (1.5 mEq/L) and sodium bicarbonate (50 mEq/L) were physically compatible in a pharmacy-compounded bicarbonate-buffered hemofiltration solution at room temperature without light protection at 48 hours. PMID:20237384
Tapia, Pablo; Lillo, Felipe; Soto, Dagoberto; Escobar, Leslie; Simon, Felipe; Hernández, Karina; Alegría, Leyla; Bruhn, Alejandro
2016-01-01
A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol·kg-1·h-1 coupled to hemofiltration (THAM+HF group) at 100 mL·kg-1·h-1. After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm·kg H2O-1 at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis. PMID:27648139
2009-05-01
to result in any extra- renal effects. In the CVVH group the initial prescribed dose was variable based on hemo- dynamic compromise and perceived...associated with a decrease in 28-day and hospital mortality when compared with a historical control group, which largely did not receive any form of renal ...BUN: blood urea nitrogen; CVVH: continuous venovenous hemofiltration; CVVHDF: continuous venovenous hemodiafiltration; ESRD: end-stage renal disease
Faucheux, F.; L'Huillier, J.P.; Rouillion, P.; Yvroud, E.; Kessler, M.; Huriet, C.
1982-01-01
The extranephric cleaning by means of hemofiltration and generally operations in extracorporal circulation requires the blood derivation towards a treatment apparatus: filtration by means of hemodialysis, oxygenation. The working principle of the treatment apparatuses does not simply allow to connect the blood flow taken from the patient. A control of the patient is therefore necessary to have a treatment performed in good conditions. The method that we propose consists in weighting the variable containing unit of the apparatus and in subjecting this weight to a value determined by the physician. This value is programmed on the machine before the treatment session. The control is performed by means of an action on the differential flow and allow a precise control of the weight loss of the patient during a treatment in extranephric cleaning by means of hemofiltration.
Temporary metabolic support by extracorporeal blood therapy for liver failure after surgery.
Matsubara, S; Okabe, K; Ouchi, K; Sato, T; Matsuno, S
1988-01-01
With the aim of temporarily assisting deterioration of liver function developing after surgery, extracorporeal blood purification therapy (EBPT) (plasma exchange and/or hemofiltration) was carried out in 26 postoperative patients. Initiation of EBPT was instituted according to the criteria of either a serum bilirubin greater than 15 mg/dl or Grade 2 or more coma. Plasma exchange was carried out 235 times in 23 patients and hemofiltration was performed 28 times for seven patients. In addition, hemodialysis and CAPD were linked in eight cases. Plasma exchange was found to control the progression of DIC and endotoxemia. Nine patients (35%) were weaned from EBPT. In the survivors the levels of blood ammonia and number of major complications were significantly lower compared to the nonsurvivors. Three patients treated only with hemofiltration were all lost. Among co-morbid factors present, incidences of renal failure, respiratory failure, and associated liver cirrhosis significantly increased poor clinical outcome on EBPT for postoperative liver failure.
Bourquin, Vincent; Ponte, Belén; Hirschel, Bernard; Pugin, Jérôme; Martin, Pierre-Yves; Saudan, Patrick
2011-01-01
Background. Leptospirosis is a spirochetal zoonosis with complex clinical features including renal and liver failure. Case report. We report the case of a Swiss fisherman presenting with leptospirosis. After initial improvement, refractory septic shock and severe liver and kidney failure developed. The expected mortality was estimated at 90% with clinical scores. The patient underwent plasma exchanges and high-volume hemofiltration (HVHF) with complete recovery of hepatic and kidney functions. Discussion. Plasma exchanges and HVHF may confer survival benefit on patients with severe leptospirosis, refractory septic shock, and multiple-organ failure.
Rousseau, Anne-Françoise; Damas, Pierre; Renwart, Ludovic; Amand, Théo; Erpicum, Marie; Morimont, Philippe; Dubois, Bernard; Massion, Paul B
2014-11-01
Acute respiratory distress syndrome management is currently based on lung protective ventilation. Such strategy may lead to hypercapnic acidosis. We report a case of refractory hypercapnia in a severe burn adult, treated with simplified veno-venous extracorporeal carbon dioxide removal technique. We integrated a pediatric oxygenator in a continuous veno-venous hemofiltration circuit. This technique, used during at least 96h, was feasible, sure and efficient with carbon dioxide removal rate up to 32%. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.
[Application of improved regional citrate anticoagulation in continuous hemofiltration in children].
Bai, K; Liu, C J; Fu, Y Q; Xu, F
2017-05-04
Objective: To investigate the application of regional citrate anticoagulation with calcium hemofiltration basic solution in continuous hemofiltration in children. Method: The clinical data of 18 patients with citrate anticoagulation in continuous hemofiltration in children, excluding the hepatic failure and septic shock cases, were analyzed retrospectively, from September 2015 to August 2016 in Intensive Care Unit of the Children's Hospital of Chongqing Medical University.The commercial calcium hemofiltration basic solution was used as displacement liquid . The blood gas analysis, electrolyte, four coagulation tests during the treatment and the corresponding relations of quantity of blood flow(QB), quantity of citrate flow(QCi), quantity of sodium bicarbonate flow(QSB), quantity of calcium flow(QCa), quantity of filtered solution flow (Qf) were monitored. Meanwhile, the blood gas analysis, electrolyte, four coagulation tests, useful life of filter, bleeding and clotting events internal and external before, during and after the treatments were monitored, too. And the common complications of citrate anticoagulation, such as hypocalcaemia, metabolic alkalosis, citrate accumulation and hypernatremia were observed. Result: Continuous hemofiltration was applied in 18 patients for 734.5 hours, and the average useful life of filter was (25±11)h.There was no obvious clotting event. There were 168 groups of datum of the blood gas analysis, electrolyte, four coagulation tests during the treatment and the relationships of QB, QCi, QSB, QCa, Qf had been collected. The relationships of the initial parameter settings of QB, QCi, QSB, QCa and Qf were concluded as QCi=1.8×QB, QCa=0.12×QB, QSB=0.01×Qf . There were 150 times(89.3%)of extracorporeal ionized calcium(iCa(E)(2+)) and 162 times(96.4%) of intracorporal ionized calcium(iCa(I)(2+)) reached the anticoagulation target. Although all the comparisons of Na(+) ((136.2±4.1) vs .(138.2±2.4) vs .(138.5±3.9)mmol/L), iCa(2+) ((1.07±0.11) vs .(1.21±0.12) vs .(1.17±0.09)mmol/L), HCO(3)(-) ((22±4) vs .(28±5) vs . (26±4)mmol/L) among before, during and after treatment had significant difference( F =6.414, 18.950, 19.151; P =0.002, 0.000, 0.000). Each mean parameter was within the nearly normal range, except that the HCO(3)(-) increased slightly. High HCO(3)(-) was the most common complications, which happened 87 times (51.8%) during the treatment and 11 cases(37.9%) after the treatment. There was none with refractory hypocalcemia and total ionized calcium(TCa(2+) )/iCa(2+) above 2.5, which hints the accumulation of citrate. Conclusion: The commercialized displacement liquid containing calcium can be used in RCA-CHF in children safely and simply.
de Pont, Anne-Cornélie J M; Bouman, Catherine S C; Bakhtiari, Kamran; Schaap, Marianne C L; Nieuwland, Rienk; Sturk, Augueste; Hutten, Barbara A; de Jonge, Evert; Vroom, Margreeth B; Meijers, Joost C M; Büller, Harry R
2006-01-01
During continuous venovenous hemofiltration, predilution can prolong circuit survival time, but the underlying mechanism has not been elucidated. The aim of the present study was to compare predilution with postdilution, with respect to circuit thrombogenesis. Eight critically ill patients were treated with both predilutional and postdilutional continuous venovenous hemofiltration in a crossover fashion. A filtration flow of 60 ml/min was used in both modes. We chose blood flows of 140 and 200 ml/min during predilution and postdilution, respectively, to keep the total flow through the hemofilter constant. Extracorporeal circuit pressures were measured hourly, and samples of blood and ultrafiltrate were collected at five different time points. Thrombin-antithrombin complexes and prothrombin fragments F1 + 2 were measured by ELISA, and platelet activation was assessed by flow cytometry. No signs of thrombin generation or platelet activation were found during either mode. During postdilution, baseline platelet count and maximal prefilter pressure had a linear relation, whereas both parameters were inversely related with circuit survival time. In summary, predilution and postdilution did not differ with respect to extracorporeal circuit thrombogenesis. During postdilution, baseline platelet count and maximal prefilter pressure were inversely related with circuit survival time.
Sun, Zhao-Xi; Huang, Hai-Rong; Zhou, Hong
2006-01-01
AIM: To study the effect of combined indwelling catheter, hemofiltration, respiration support and traditional Chinese medicine (e.g. Dahuang) in treating abdominal compartment syndrome of fulminant acute pancreatitis. METHODS: Patients with fulminant acute pancreatitis were divided randomly into 2 groups of combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring and routine conservative measures group (group 1) and control group (group 2). Routine non-operative conservative treatments including hemofiltration, respiration support, gastrointestinal TCM ablution were also applied in control group patients. Effectiveness of the two groups was observed, and APACHE II scores were applied for analysis. RESULTS: On the second and fifth days after treatment, APACHE II scores of group 1 and 2 patients were significantly different. Comparison of effectiveness (abdominalgia and burbulence relief time, hospitalization time) between groups 1 and 2 showed significant difference, as well as incidence rates of cysts formation. Mortality rates of groups 1 and 2 were 10.0% and 20.7%, respectively. For patients in group 1, celiac drainage quantity and intra-abdominal pressure, and hospitalization time were positively correlated (r = 0.552, 0.748, 0.923, P < 0.01) with APACHE II scores. CONCLUSION: Combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring, short veno-venous hemofiltration (SVVH), gastrointestinal TCM ablution, respiration support have preventive and treatment effects on abdominal compartment syndrome of fulminant acute pancreatitis. PMID:16937509
Musaeva, T S; Berdnikov, A P; Goncharenko, S I; Denisova, E A
2014-01-01
We performed a retrospective study in 68 patients (144 procedures) with severe sepsis and intracranial hypertension measured by the pressure in the central retinal vein. The patients underwent high-volume hemofiltration (HV-HF) for extrarenal indications. Increased pressure in the central retinal vein was accompanied by critical points of cerebral perfusion pressure and the growth of neurological deficit with inhibition level of consciousness to coma 1. In this case, IHV-HF may be associated with the formation of the critical points of cerebral perfihsion and severe disorders of microcirculation and the lack of resolution of tissue hypoperfusion. In case of intracranial hypertension IHV-HF is not effective in the category of patients where there is a combination ΔpCO2 > 5.9 mm Hg level and GCS <10 points.
Brummelhuis, Walter J; Joles, Jaap A; Stam, Jord C; Adams, Hendrik; Goldschmeding, Roel; Detmers, Frank J; El Khattabi, Mohamed; Maassen, Bram T; Verrips, C Theo; Braam, Branko
2010-08-01
Staphylococcus aureus produces the superantigen toxic shock syndrome toxin 1 (TSST-1). When the bacterium invades the human circulation, this toxin can induce life-threatening gram-positive sepsis. Current sepsis treatment does not remove bacterial toxins. Variable domains of llama heavy-chain antibodies (VHH) against toxic shock syndrome toxin 1 ([alpha]-TSST-1 VHH) were previously found to be effective in vitro. We hypothesized that removing TSST-1 with [alpha]-TSST-1 VHH hemofiltration filters would ameliorate experimental sepsis in pigs. After assessing in vitro whether timely removing TSST-1 interrupted TSST-1-induced mononuclear cell TNF-[alpha] production, VHH-coated filters were applied in a porcine sepsis model. Clinical course, survival, plasma interferon [gamma], and TSST-1 levels were similar with and without VHH-coated filters as were TSST-1 concentrations before and after the VHH filter. Plasma TSST-1 levels were much lower than anticipated from the distribution of the amount of infused TSST-1, suggesting compartmentalization to space or adhesion to surface not accessible to hemofiltration or pheresis techniques. Removing TSST-1 from plasma was feasible in vitro. However, the [alpha]-TSST-1 VHH adsorption filter-based technique was ineffective in vivo, indicating that improvement of VHH-based hemofiltration is required. Sequestration likely prevented the adequate removal of TSST-1. The latter warrants further investigation of TSST-1 distribution and clearance in vivo.
Peng, Zhi-Yun; Chang, Ping; Wang, Hua; Cen, Zhong-Ran; Zhou, Jian; Liu, Zhan-Guo
2015-10-01
A 20-year-old male patient was admitted in our department 14 h after paraquat poisoning at the dose of about 50 mL. The patient underwent intensive hemoperfusion for 2 h (3 times a day) for 9 consecutive days and received continuous renal replacement therapy (CRRT) in the mode of continuous veno-venous hemofiltration (CVVH) for 10 consecutive days in addition to routine medications. The biochemical indexes were monitored during the therapy. After the treatment, paraquat concentrations in the blood and urine were decreased, and the patient's urine volume (UV) increased, serum creatinine (Cr) level decreased, and the oxygenation index became normal. Dynamic CT scan showed no obvious pulmonary fibrosis. The patient was followed up for 6 months after discharge and no complaint of discomforts was reported. This case suggests that early intensive hemoperfusion and long-term CVVH may help improve the prognosis after paraquat poisoning.
Liver transplantation for fulminant hepatitis at Stanford University.
Lu, Amy; Monge, Humberto; Drazan, Kenneth; Millan, Maria; Esquivel, Carlos O
2002-01-01
To review the clinical characteristics and outcomes of 26 patients evaluated for liver transplantation for fulminant hepatic failure at Stanford University and Lucile Packard Children's Hospital in an attempt to identify risk factors and prognostic predictors of survival. A retrospective review of the records of 26 consecutive patients who were evaluated for possible liver transplantation for acute liver failure from May 1, 1995, to January 1, 2000. Pretransplant patient demographics and clinical characteristics were collected, and the data were analyzed by univariate and multivariate analysis. Clinical assessment of encephalopathy did not predict outcome. Patients with abnormal computed tomography (CT) of the brain had a twofold increase in mortality compared with those patients with normal studies (p = 0.03). Patients requiring mechanical ventilation and continuous venovenous hemofiltration (CVVH) also had a poor prognosis. Predictors of poor outcome after fulminant hepatic failure include abnormal CT scan, mechanical ventilation, and requirement for hemofiltration.
Hernandez, Stephanie H; Howland, Maryann; Schiano, Thomas D; Hoffman, Robert S
2015-01-01
Acetaminophen-induced fulminant hepatic failure is associated with acute kidney injury, metabolic acidosis, and fluid and electrolyte imbalances, requiring treatment with renal replacement therapies. Although antidote, acetylcysteine, is potentially extracted by renal replacement therapies, pharmacokinetic data are lacking to guide potential dosing alterations. We aimed to determine the extracorporeal removal of acetylcysteine by various renal replacement therapies. Simultaneous urine, plasma and effluent specimens were serially collected to measure acetylcysteine concentrations in up to three stages: before, during and upon termination of renal replacement therapy. Alterations in pharmacokinetics were determined by applying standard pharmacokinetic equations. Over 2 years, 10 critically ill patients in fulminant hepatic failure requiring renal replacement therapy coincident with acetylcysteine were consecutively enrolled. All 10 patients required continuous venovenous hemofiltration (n = 10) and 2 of the 10 also required hemodialysis (n = 2). There was a significant alteration in the pharmacokinetics of acetylcysteine during hemodialysis; the area under the curve (AUC) decreased 41%, the mean extraction ratio was 51%, the mean hemodialytic clearance was 114.01 ml/kg/h, and a mean 166.75 mg/h was recovered in the effluent or 41% of the hourly dose. Alteration in the pharmacokinetics of acetylcysteine during continuous venovenous hemofiltration did not appear to be significant: the AUC decreased 13%, the mean clearance was 31.77 ml/kg/h and a mean 62.12 mg/h was recovered in the effluent or 14% of the hourly dose. There was no significant extraction of acetylcysteine from continuous venovenous hemofiltration. In contrast, there was significant extracorporeal removal of acetylcysteine during hemodialysis. A reasonable dose adjustment may be to double the IV infusion rate or possibly supplement with oral acetylcysteine during hemodialysis.
[Combination of hemodialysis and hemofiltration in severe caffeine intoxication].
Colin-Benoit, Eugénie; Friolet, Raymond; Rusca, Marco; Teta, Daniel; Gobin, Niels
2017-05-01
A 21-year-old man ingested 75g of pure caffeine, in an attempt to commit suicide. This represents 7.5 times the minimal lethal dose. Caffeine, 1,3,7-trimethylxanthine, is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet. Mechanisms of action are dose-dependent. When caffeine overdosing occurs, neurologic, cardiovascular and renal systems are mainly affected. Severe intoxication can be fatal. No antidote is available and treatment is purely symptomatic. Hemoperfusion has previously been carried out in the 1990's to treat patients with caffeine intoxication. Since 2009, hemodialysis and hemofiltration have proposed as well. Our patient was successfully treated with a combination of hemodiafiltration, intermittent and then continuous. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.
Mol, Meriel; van Kan, Hendrikus J M; Schultz, Marcus J; de Jonge, Evert
2008-05-01
To study whether selective decontamination of the digestive tract (SDD) results in detectable serum tobramycin concentrations in intensive care unit (ICU) patients with acute renal failure treated with continuous venovenous hemofiltration (CVVH). Prospective, observational, single-center study in a mixed medical-surgical ICU. Adult ICU patients receiving SDD for at least 3 days and being treated with CVVH because of acute renal failure. Tobramycin serum concentrations were measured at the 3rd day after start of CVVH and every 3 days thereafter. Detectable serum concentrations of tobramycin were found in 12 (63%) of 19 patients and in 15 (58%) of the 26 samples. With a toxic tobramycin concentration defined as more than 2.0 mg/l, we found one patient with a toxic concentration of 3.0 mg/l. In three other patients tobramycin concentrations of >or=1.0 mg/l were found. In patients with acute renal failure treated with CVVH, administration of SDD with tobramycin can lead to detectable and potentially toxic serum tobramycin concentrations.
[Severe Legionella micdadei pneumonia effectively treated with hemofiltration therapy].
Matsubara, S; Akashi, S; Naitoh, K; Nakahara, Y; Hayashi, S
1998-10-01
A 42-year-old man was admitted because of fever, productive cough, and progressive dyspnea. Chest x-ray films and computed tomographic scans disclosed dense consolidation in the left and right lung fields. No pathogenic agent was found despite extensive bacteriological examinations. Based on serological findings, the patient was given a diagnosis of acute pneumonia caused by Legionella micdadei. It has been reported that Legionnaire's disease is easily complicated by fatal systemic illnesses such as disseminated intravascular coagulation (DIC) and multiple organ failure. In fact, the patient suffered from severe hypotension and DIC on admission. Treatments against systemic complications were started together with intravenous administration of antibiotics including erythromycin. Continuous intravenous cathecolamin, however, failed to alleviate the patient's shock. We therefore applied endotoxin eliminating therapy using a polymyxin-B-column (PMX) and continuous hemofiltration (CHF). The patient recovered from critical shock immediately after the start of PMX, which together with CHF, alleviated his systemic complications. Although the factors responsible for fatal systemic complications in Legionnare's disease are not well-documented, our findings suggested that some substances removable by PMX and CHF play an important role in pathogenesis.
Bosch, T; Wendler, T; Maschke, H
2003-06-01
DALI (direct adsorption of lipids) is the first LDL-apheresis technique able to adsorb low-density lipoprotein (LDL) and lipoproteina) directly from whole blood. In the standard procedure, acid citrate dextrose (ACD-A) is used as anticoagulation and the adsorber is rinsed with a specially manufactured priming solution (PS). Using neutral trisodium citrate (TSC) instead of ACD-A might improve the acid-base homeostasis during DALI apheresis; moreover, applying wholesale hemofiltration solutions instead of the special PS might avoid the use of two separate solutions for both priming before and reinfusion after the treatment, thus simplifiying the procedure. The present study was performed to test the effect of neutral (TSC) anticoagulation and of two different commercially available hemofiltration (HF) priming solutions on the efficacy and biocompatibility of DALI apheresis. Five hypercholesterolemic chronic DALI patients were treated prospectively, on a weekly or biweekly basis, 3 times each by standard DALI-apheresis (A). by DALI using 4% TSC and bicarbonate-buffered HF BIC35-210 priming (B). as well as by DALI using 4% TSC and lactate-buffered HF 23 priming (C). After the sessions, the extracorporeal circuit (ECC) was rinsed with saline in study arm A and with the corresponding HF solutions in study arms B and C, respectively. Acute LDL-cholesterol reductions in the study arms A/B/C averaged 64/64/63%, for Lp(a) 62/64/62%, respectively (n=15). Clinically, all sessions were essentially uneventful and no clots were observed in the ECC. No major differences were found between the 3 study arms with respect to biocompatibility (elastase, C3a, thrombin-antithrombin, beta-thromboglobulin, bradykinin). DALI apheresis using TSC anticoagulation and HF solutions for both priming and reinfusion proved to be as safe and effective as the standard DALI apheresis. These modifications, however, further simplify the procedure.
Pichaiwong, Warangkana; Leelahavanichkul, Asada; Eiam-ong, Somchai
2006-08-01
To compare the clearance performances and biocompatibility between the modified cellulose membrane and the standard synthetic membrane in continuous renal replacement therapy (CRRT). Seventeen patients with acute renal failure (ARF) were treated with separated continuous veno venous hemofiltration (CVVH) system conducted with the pre-dilution mode. The modified cellulose used was a Sureflux150E (cellulose triacetate) and the standard synthetic membranes used was an AV-400. Blood and replacement flow rate were kept at 100 and 20 mL/min, respectively. Ultrafiltraion rate was 1,200 mL/hr. Samplings of blood and ultrafiltrate were collected at baseline, 2, 8, 16, and 24 hr. Patients in both methods could similarly tolerate CRRT with only minor complications. Sureflux 150E and AV-400 provided comparable values of sieving coefficients and clearances of small solutes. The albumin loss in ultrafiltrate by Sureflux 150E was greater than AV-400. The values of life span and biocompatability of both hemofilters were not different. Because of the excellent efficacy and the much cheaper cost, the modified cellulose membrane could be an appropriate alternative to standard synthetic membrane in CRRT.
Clinical Study on Acute Pancreatitis in Pregnancy in 26 Cases
Qihui, Cheng; Xiping, Zhang; Xianfeng, Ding
2012-01-01
Aim. This paper investigated the pathogenesis and treatment strategies of acute pancreatitis (AP) in pregnancy. Methods. We analyzed retrospectively the characteristics, auxiliary diagnosis, treatment strategies, and clinical outcomes of 26 cases of patients with AP in pregnancy. Results. All patients were cured finally. (1) Nine cases of 22 mild acute pancreatitis (MAP) patients selected automatic termination of pregnancy because of the unsatisfied therapeutic efficacy or those patients' requirements. (2) Four cases of all patients were complicated with severe acute pancreatitis (SAP); 2 cases underwent uterine incision delivery while one of them also received cholecystectomy, debridement and drainage of pancreatic necrosis, and percutaneous jejunostomy. One case had a fetal death when complicated with SAP; she had to receive extraction of bile duct stones and drainage of abdominal cavity after induced abortion. The other one case with hyperlipidemic pancreatitis was given induced abortion and hemofiltration. Conclusions. The first choice of MAP in pregnancy is the conventional therapy. Apart from the conventional therapy, we need to terminate pregnancy as early as possible for patients with SAP. Removing biliary calculi and drainage is supposed to be considered for acute biliary pancreatitis. Lowering blood lipids treatment should be applied to hyperlipidemic pancreatitis or given to hemofiltration when necessary. PMID:23213326
Once-Daily Amikacin Dosing in Burn Patients Treated with Continuous Venovenous Hemofiltration
2011-10-01
previously documented inaccuracies with the Vitek 2 instrument (1), all Acinetobacter baumannii isolates reported as susceptible to amikacin were confirmed...to the analysis. Bacteriology. Amikacin MICs were determined for Gram-negative blood- stream isolates using the Vitek 2 instrument (bioMérieux...al. 2010. Aminoglycoside resistance and susceptibility testing errors in Acinetobacter baumannii-calcoaceticus complex. J. Clin. Microbiol. 48:1132
Colistin Use in Patients With Reduced Kidney Function.
Fiaccadori, Enrico; Antonucci, Elio; Morabito, Santo; d'Avolio, Antonio; Maggiore, Umberto; Regolisti, Giuseppe
2016-08-01
Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Franquiz, Miguel J; Kalaria, Shamir N; Armahizer, Michael J; Gopalakrishnan, Mathangi; McCarthy, Paul J; Badjatia, Neeraj
2018-02-01
Lacosamide is a new-generation antiepileptic drug (AED) that is eliminated by both hepatic and renal mechanisms. Lacosamide elimination by continuous renal replacement therapy (CRRT) has never been studied. The objective of this case report was to describe lacosamide pharmacokinetics in the setting of CRRT. We describe a single patient admitted to the study center with status epilepticus and multiorgan failure. The patient required both continuous venovenous hemofiltration (CVVH) and several AEDs. He was receiving intravenous lacosamide 200 mg twice/day at steady state prior to sampling. Plasma lacosamide concentrations were derived using a validated high-performance liquid chromatography method. Parameters were calculated using Phoenix WinNonlin 7.1 software. The peak concentration at steady state was 7.7 mg/L, the trough concentration was 5.9 mg/L (goal 5-12 mg/L). The volume of distribution was 0.7 L/kg, the elimination half-life was 21 hours, and the sieving coefficient was 0.8 (± 0.06). Lacosamide was cleared by CVVH as demonstrated by the sieving coefficient, but plasma concentrations remained within goal range throughout the dosing interval. These results may suggest that lacosamide 200 mg twice/day is a useful dosing strategy for critically ill patients who require CVVH. © 2017 Pharmacotherapy Publications, Inc.
Colistin Pharmacokinetics in Burn Patients During Continuous Venovenous Hemofiltration
2015-01-01
NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION...Materials. All drugs and chemicals were reagent grade and were obtained from Sigma (St. Louis, MO) unless otherwise noted. Pharmacokinetic sampling...Chemother 50: 1953 –1958. http://dx.doi.org/10.1128/AAC .00035-06. 4. Zavascki AP. 2014. Polymyxins for the treatment of extensively-drug- resistant Gram
Daily hemofiltration with a simplified method of delivery.
Zimmerman, Deborah L; Swedko, Peter J; Posen, Gerald A; Burns, Kevin D
2003-01-01
Observational studies of daily hemodialysis (HD) and intermittent hemofiltration (HF) therapy have been associated with improved outcomes for patients with endstage renal disease. We conducted a prospective study to evaluate the feasibility of daily HF as an alternative to intermittent HD using a simplified HF system (NxStage Medical). Each patient received 1 week of intermittent HD followed by 4 weeks of daily HF. Ringers lactate was used as the initial replacement solution; however, Hemosol LG2/L0 was used subsequently to simplify patient management. Changes in quality of life, nutrition, and laboratory values were assessed. Seven patients have completed 168 HF treatments with Hemosol. Their treatment time on HD was 232 minutes 3 days per week, and 132 minutes on HF 6 days per week. Single pool Kt/V per treatment for HD was 1.69 compared with 0.44 for HF (standard Kt/V 2.38 vs 1.93). Despite these weekly differences in urea clearance, potassium, calcium, phosphate, and nutrition remained stable. Beta-2 microglobulin tended to decline. All parameters of the Kidney Disease Quality of Life Instrument Short Form (KDQOL-SF) either remained stable or improved. In addition, blood pressure declined, allowing for a reduction in the number of antihypertensive medications. In summary, these preliminary data suggest that daily HF with this system is safe, simple, efficacious, and could potentially be used as a home based renal replacement therapy.
2013-05-17
wide range of clinical presentations from mild to life threatening. We present a case of a 34 year old woman in the Burn Intensive Care Unit , who...P., Lundy J. B., Renz E. M., Chung K. K., 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...ES) United States Army Institute of Surgical Research, JBSA Fort Sam Houston, TX 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING
[Star fruit (Averrhoa carambola) toxic encephalopathy].
Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D
2009-03-01
Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.
Very high volume hemofiltration with the Cascade system in septic shock patients.
Quenot, Jean-Pierre; Binquet, Christine; Vinsonneau, Christophe; Barbar, Saber-David; Vinault, Sandrine; Deckert, Valerie; Lemaire, Stéphanie; Hassain, Ali Ait; Bruyère, Rémi; Souweine, Bertrand; Lagrost, Laurent; Adrie, Christophe
2015-12-01
We compared hemodynamic and biological effects of the Cascade system, which uses very high volume hemofiltration (HVHF) (120 mL kg(-1) h(-1)), with those of usual care in patients with septic shock. Multicenter, prospective, randomized, open-label trial in three intensive care units (ICU). Adults with septic shock with administration of epinephrine/norepinephrine were eligible. Patients were randomized to usual care plus HVHF (Cascade group), or usual care alone (control group). Primary end point was the number of catecholamine-free days up to 28 days after randomization. Secondary end points were number of days free of mechanical ventilation, renal replacement therapy (RRT) or ICU up to 90 days, and 7-, 28-, and 90-day mortality. We included 60 patients (29 Cascade, 31 usual care). Baseline characteristics were comparable. Median number of catecholamine-free days was 22 [IQR 11-23] vs 20 [0-25] for Cascade vs control; there was no significant difference even after adjustment. There was no significant difference in number of mechanical ventilation-free days or ICU requirement. Median number of RRT-free days was 85 [46-90] vs 74 [0-90] for Cascade vs control groups, p = 0.42. By multivariate analysis, the number of RRT-free days was significantly higher in the Cascade group (up to 25 days higher after adjustment). There was no difference in mortality at 7, 28, or 90 days. Very HVHF using the Cascade system can safely be used in patients presenting with septic shock, but it was not associated with a reduction in the need for catecholamines during the first 28 days.
Jamal, Janattul-Ain; Udy, Andrew A; Wallis, Steven C; Ranganathan, Dwarakanathan; McWhinney, Brett C; Ungerer, Jacobus P J; Lipman, Jeffrey; Roberts, Jason A
2015-08-01
To determine the adsorption and elimination characteristics of meropenem and piperacillin during simulated continuous renal replacement therapy (CRRT), and to compare the observed data from this ex vivo study with previous data from clinical studies. This was an experimental study utilizing a modified CRRT circuit and polysulfone membrane (1.2 m2), circulated with a blood-crystalloid mixture. Adsorption onto the CRRT circuit was tested over a 4-h period, and clearance was assessed separately using variable continuous hemofiltration settings. A rapid 9% reduction in circulating meropenem and piperacillin concentrations was observed at approximately 0.5 and 1.0 h for each antibiotic, respectively. The post-dilution setting was associated with a significantly higher sieving coefficient (Sc) and filter clearance (CLfilter) (mean ± SD) (Sc 1.14 ± 0.10 versus 1.06 ± 0.04; CLfilter 19.05 ± 1.63 versus 17.59 ± 0.62 ml/min, P values < 0.05) for meropenem. No significant differences were observed for piperacillin pharmacokinetics. Clinically comparable Sc data were observed between data obtained from the ex vivo study and data from previous clinical studies, for both antibiotics. Meropenem and piperacillin appear to be rapidly adsorbed into the CRRT circuit, and the delivery site of fluid replacement significantly influences meropenem pharmacokinetics. However, these findings are likely to be clinically insignificant and not affect dosing requirements. This ex vivo method could be a surrogate for future clinical pharmacokinetic studies of CRRT. Further research is required to explore the applicability of the ex vivo method to further characterize antibiotic pharmacokinetics during CRRT.
Minar, E; Zazgornik, J; Bayer, P M; Lanschützer, H; Mengele, K; Marosi, L
1984-01-14
The incidence of macrocytic anemia has been investigated in 32 patients on maintenance hemodialysis (mean age 46 years, mean duration of dialysis treatment 27.5 months), in 18 patients with combined hemodialysis (HD) and hemofiltration (HF) treatment (mean age 42 years, mean duration of combined HD and HF treatment 6.3 months) and in 32 patients after renal transplantation (mean age 41 years, mean observation period since successful renal transplantation 55.2 months). Also investigated were serum levels of vitamin B12 (radioassay kit 57Co) and folic acid (radioassay kit 125J). Macrocytosis (MCV greater than 96 fl) was observed in 38% of the patients on maintenance hemodialysis, in 44% of the patients with combined HD and HF treatment, and in 47% of the renal transplant recipients. In the chronically dialysed patients, in contrast to the patients with combined HD and HF treatment, the mean serum folic acid level was significantly lower (p less than 0.005) than that of healthy controls. Serum levels of vitamin B12 were within the normal range in all patients. There were no significant differences in serum levels of folic acid and vitamin B12 between the patients with MCV greater than 96 fl and MCV less than or equal to 96 fl. Nor was there a correlation between the serum levels of folic acid or vitamin B12 and mean corpuscular volume. These results suggest that folic acid deficiency is of minor importance in the complex pathogenesis of anemia in hemodialysed patients.
Colistin Pharmacokinetics in Burn Patients during Continuous Venovenous Hemofiltration
Rowan, Matthew P.; Niece, Krista L.; Stewart, Ian J.; Mende, Katrin; Cota, Jason M.; Murray, Clinton K.; Chung, Kevin K.
2014-01-01
While colistin is considered a last resort for the treatment of multidrug-resistant Gram-negative bacterial infections, there has been an increase in its use due to the increasing prevalence of drug-resistant infections worldwide. The pharmacology of colistin is complex, and pharmacokinetic data are limited, especially in patients requiring renal replacement therapy. As a result, dosing for patients who require renal replacement remains a challenge. Here, we present pharmacokinetic data for colistin from two burn patients (37 and 68 years old) infected with colistin-susceptible isoclonal Acinetobacter baumannii and receiving continuous venovenous hemofiltration (CVVH). To our knowledge, we are the first to examine data from before and during CVVH (for one patient), allowing analysis of the effect of CVVH on colistin pharmacokinetics. Pharmacokinetic/pharmacodynamic analysis indicated that a dose increase from 1.5 to 2.2 mg/kg of body weight colistin base activity on CVVH was insufficient to satisfy the target parameter of an AUC24/MIC (area under the concentration-time curve over 24 h in the steady state divided by the MIC) of ≥60 at an MIC of ≥1 μg/ml in one patient with residual endogenous renal function. Plasma concentrations of colistin ranged from 0 to 15 μg/ml, with free colistin levels ranging from 0.4 to 2.2 μg/ml. While both patients resolved their clinical infections and survived to discharge, colistin-resistant colonizing isolates resulted from therapy in one patient. The variabilities observed in colistin concentrations and pharmacokinetic characteristics highlight the importance of pharmacokinetic monitoring of antibiotics in patients undergoing renal replacement therapy. PMID:25313211
Yang, Yi; Zhang, Ping; Cui, Yu; Lang, Xia; Yuan, Jing; Jiang, Hua; Lei, Wen; Lv, Rong; Zhu, Yi; Lai, En; Chen, Jiang
2013-09-19
The primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI). 760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia. The Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103-1.910, p = 0.008). Hypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate.
Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.
Nilsson, Tobias; Hansson, Christoffer; Wallinder, Andreas; Malm, Carl-Johan; Silverborn, Martin; Ricksten, Sven-Erik; Dellgren, Göran
2016-02-01
Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Beşişik, Sevgi Kalayoğlu; Oztürk, Gülistan Bahat; Calişkan, Yaşar; Sargin, Deniz
2005-03-01
Transplantation-associated thrombotic microangiopathy has been associated with significantly reduced survival following allogeneic bone marrow transplantation. We describe here the course of Transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease, and response to plasma exchange therapy. A 19-year-old male patient underwent hematopoietic stem cell transplantation (HSCT) from his HLA-matched brother for lymphoblastic lymphoma in the first complete remission. Transplantation-associated thrombotic microangiopathy was diagnosed 17 days after transplantation. At that time, neurological abnormalities were not present. Cyclosporin A (CsA) was discontinued. Hematological stabilization was recorded. On day +20, abdominal distention, painful hepatomegaly and ascites complicated the clinical picture. With a high hepatic venous pressure gradient (18mmH20), veno-occlusive disease of the liver was diagnosed and defibrotide was started, which resulted in a dramatic cessation of pain and increase in urinary output. However, transplantation-associated thrombotic microangiopathy-related symptoms progressed and plasma exchange was instituted, which resulted in worsening of veno-occlusive disease symptoms. He was referred to the Intensive Care Unit due to respiratory compromise and was intubated. Plasma exchange was continued in order after hemofiltration. In three days, fever resolved, hemofiltration could be stopped, and ventilator dependence ended. After 19 aphereses, serum LDH level returned to normal and schistocytes were minimal on microscopic examination of the blood film. Platelet count increase was more gradual. Plasma exchange was discontinued. On the 40th day of defibrotide, all symptoms related with veno-occlusive disease were resolved and defibrotide was stopped. We think that our case is important to establish the relation and management strategy of these two small vessel complications of HSCT.
Ruggero, M A; Argento, A C; Heavner, M S; Topal, J E
2013-04-01
The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS(®)). The patient was a 32-year-old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin-enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein-bound toxins. In addition to protein-bound waste, MARS removes water-soluble, low molecular-weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k(e)) for the removal of piperacillin in this patent was 0.453 h(-1) and the half-life (λ) was 1.53 h. The k(e) was 2.9-fold higher than with CVVHD alone and the λ was 3.7-fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations. © 2012 John Wiley & Sons A/S.
Study on the treatment of acute thallium poisoning.
Zhang, Hong-Tao; Qiao, Bao-Ping; Liu, Bao-Ping; Zhao, Xian-Guo
2014-05-01
Acute thallium poisoning rarely occurs but is a serious and even fatal medical condition. Currently, patients with acute thallium poisoning are usually treated with Prussian blue and blood purification therapy. However, there are few studies about these treatments for acute thallium poisoning. Nine patients with acute thallium poisoning from 1 family were treated successfully with Prussian blue and different types of blood purification therapies and analyzed. Prussian blue combined with sequential hemodialysis, hemoperfusion and/or continuous veno-venous hemofiltration were effective for the treatment of patients with acute thallium poisoning, even after delayed diagnosis. Blood purification therapies help in the clearance of thallium in those with acute thallium poisoning. Prussian blue treatment may do the benefit during this process.
Dose determinants in continuous renal replacement therapy.
Clark, William R; Turk, Joseph E; Kraus, Michael A; Gao, Dayong
2003-09-01
Increasing attention is being paid to quantifying the dose of dialysis prescribed and delivered to critically ill patients with acute renal failure (ARF). Recent trials in both the intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) realms have suggested that a direct relationship between dose and survival exists for both of these therapies. The purpose of this review, first, is to analyze critically the above-mentioned dose/outcome studies in acute dialysis. Subsequently, the factors influencing dose prescription and delivery are discussed, with the focus on continuous venovenous hemofiltration (CVVH). Specifically, differences between postdilution and predilution CVVH will be highlighted, and the importance of blood flow rate in dose delivery for these therapies will be discussed.
High pressure rotating reverse osmosis for long term space missions
NASA Astrophysics Data System (ADS)
Christensen Pederson, Cynthia Lynn
Rotating reverse osmosis, which uses reverse osmosis to purify water and rotating filtration to improve the efficacy of filtration, has great potential for wastewater recycling on a long term space mission. Previous investigations of a proof-of-concept device indicated that the most efficient method to improve rotating reverse osmosis performance is to increase the operational pressure. Thus, a second generation device and fluid circuit were designed, fabricated, and tested to permit high pressure operation for long time periods. The design overcame several obstacles including membrane attachment, rotating seal design, and fluid and pressure management. A theoretical model of rotating reverse osmosis was modified to properly account for the flow conditions in the new design. Tests lasting a week were conducted with a variety of model wastewaters. Significant fouling and a decrease in flux were observed after three days of testing regardless of the operational parameters. A semi-empirical model, the fouling potential, was added to the theoretical model to account for the fouling. This allowed the simulation of 48 hour cleaning cycles that significantly increased the flux of the device. Experimental investigation of the rotational speed and concentrate flow rate indicated that an increase in either parameter decreased the fouling slightly. A week long test of a wastewater ersatz with a biocide did not exhibit a decrease in flux around day three that otherwise occurred. Therefore, biofouling was identified as the primary mechanism of fouling. Rotating reverse osmosis was compared with conventional spiral wound reverse osmosis and displayed increased rejection under dead end filtration conditions. The rotating device exhibited similar rejection and increased flux compared to a tubular reverse osmosis device previously used in a NASA wastewater recovery system. The integration of the rotating device into a NASA water recovery management system was evaluated. Lastly, a theoretical model of rotating hemofiltration was developed that demonstrated that the device is not clinically feasible given the permeability of available hemofiltration membranes.
2013-01-01
Introduction The primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI). Methods 760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia. Results The Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103–1.910, p = 0.008). Conclusions Hypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate. PMID:24050634
Clinical CVVH model removes endothelium-derived microparticles from circulation
Abdelhafeez, Abdelhafeez H.; Jeziorczak, Paul M.; Schaid, Terry R.; Hoefs, Susan L.; Kaul, Sushma; Nanchal, Rahul; Jacobs, Elizabeth R.; Densmore, John C.
2014-01-01
Background Endothelium-derived microparticles (EMPs) are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI) in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH) reduces serum EMP levels and may be adapted as a potential therapeutic intervention. Materials and methods EMPs were generated from plasminogen activation inhibitor-1 (PAI-1)-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL) was circulated through a standard CVVH filter (pore size 200 μm, flow rate 250 mL/hr) for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs. Results A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate) from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration. Conclusion These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI. PMID:24596654
Iodinated contrast media and the role of renal replacement therapy.
Weisbord, Steven D; Palevsky, Paul M
2011-05-01
Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.
Guo, Wanli; Lei, Jin; Duan, Peng; Ma, Xiaoming
2015-08-01
To investigate the effects of application of intermittent hemofiltration combined with hemoperfusion (HP) in the early stage of severe burn in the prevention and treatment of sepsis. Forty severely burned patients, admitted to our burn ward from June 2011 to March 2013, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and blood purification group (BP, n=20) according to the random number table. Patients in group CT received CT according to the accepted principles of treatment for a severe burn. Patients in group BP received CT and intermittent hemofiltration combined with HP once respectively on post injury day (PID) 3, 5, and 7, spanning 6 to 8 hours for each treatment. On PID 3, 5, 7, 10, and 14, body temperature, heart rate, and respiratory rate were recorded; white blood cell count (WBC), neutrophil granulocytes, blood urea nitrogen (BUN), and creatinine were determined; levels of IL-1, IL-6, TNF-α, and high-mobility group box 1 (HMGB1) in serum were determined by ELISA; level of LPS in serum was determined with the chromogenic substrate limulus amebocyte lysate method; level of procalcitonin (PCT) in serum was determined by double antibody sandwich immune chemiluminescence method. The symptoms and signs of sepsis were observed during the treatment. Data were processed with Fisher's exact test, chi-square test, analysis of variance for repeated measurement, and LSD-t test. (1) Except for that on PID 5, the mean body temperature of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.87 to 2.97, P values below 0.05). The heart rate was significantly slower in patients of group BP than in group CT from PID 3 to 14 (with t values from 1.78 to 3.59, P values below 0.05). Except for that on PID 3, the respiratory rate of patients in group BP was significantly slower than that of group CT at each of the rest time points (with t values from 1.93 to 2.85, P values below 0.05). (2) The levels of WBC, neutrophil granulocytes, BUN, and creatinine of patients in group BP were significantly lower than those of group CT (with t values from 1.78 to 4.23, P values below 0.05). (3) Except for that on PID 3, the level of IL-1 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.97 to 4.16, P values below 0.05). Except for that on PID 7, the level of IL-6 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 2.11 to 6.34, P values below 0.05). The levels of TNF-α and HMGB1 of patients in group BP were significantly lower than those of group CT from PID 3 to 14 (with t values from 1.98 to 5.29, P values below 0.05). (4) On PID 3, 5, 7, 10, and 14, the levels of LPS and PCT of patients in group BP were respectively (0.23 ± 0.07), (0.27 ± 0.09), (0.22 ± 0.06), (0.20 ± 0.08), (0.15 ± 0.07) EU/mL, and (0.44 ± 0.12), (0.67 ± 0.13), (0.74 ± 0.13), (0.64 ± 0.12), (0.71 ± 0.10) ng/mL, and they were lower than those of group CT [(0.37 ± 0.08), (0.45 ± 0.09), (0.56 ± 0.09), (0.48 ± 0.08), (0.40 ± 0.08) EU/mL, and (0.74 ± 0.11), (1.16 ± 0.12), (1.40 ± 0.13), (1.55 ± 0.15), (1.49 ± 0.14) ng/mL, with t values from 1.88 to 3.43, P values below 0.05]. (5) The incidence of sepsis of patients in group BP was obviously lower than that of group CT (χ² = 6.94, P<0.01). Intermittent hemofiltration combined with HP can effectively improve blood biochemical indexes and vital signs and reduce the occurrence of burn sepsis by decreasing the levels of proinflammatory cytokines, LPS, and PCT.
Hopf, H-B; Hochscherf, M; Jehmlich, M; Leischik, M; Ritter, J
2007-07-01
This paper describes the introduction of a single-pass batch hemodialysis system for renal replacement therapy in a 14 bed intensive care unit. The goals were to reduce the workload of intensive care unit physicians using an alternative and simpler method compared to continuous veno-venous hemodiafiltration (CVVHDF) and to reduce the costs of hemofiltrate solutions (80,650 EUR per year in our clinic in 2005). We describe and evaluate the process of implementation of the system as well as the achieved and prospective savings. We conclude that a close cooperation of all participants (physicians, nurses, economists, technicians) of a hospital can achieve substantial benefits for patients and employees as well as reduce the economic burden of a hospital.
Continuous venovenous hemofiltration in the management of paraquat poisoning
Lin, Guodong; Long, Jianhai; Luo, Yuan; Wang, Yongan; Zewu, Qiu
2017-01-01
Abstract Background: Paraquat (PQ) poisoning is a widespread occurrence, especially in underdeveloped areas. The treatment of PQ poisoning has always been difficult, and there is currently no definite effective treatment. Continuous venovenous hemofiltration (CVVH) treatment for PQ poisoning has been widely used in clinical practice; however, its effect remains uncertain. Accordingly, the purpose of this meta-analysis was to evaluate the efficacy of CVVH in the treatment of PQ poisoning. Methods: We searched for relevant trials using PubMed, Embase, the Cochrane Library, and 3 Chinese databases, the Chinese BioMedical Literature Database, National Knowledge Infrastructure Database, and Wanfang Database. We included all qualified randomized controlled trials (RCTs) of CVVH treatment for patients with PQ poisoning. The primary outcome was mortality, while the secondary outcomes included the survival time and constituent ratios of death due to respiratory failure and circulatory failure. Results: Three RCTs involving 290 patients were included. The mortality rates of the intervention and control groups were 57.9% and 61.0%, respectively. Pooled analysis demonstrated no significant difference in mortality between the CVVH treatment and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.78–1.15, P = .56), with a low level of heterogeneity (X2 = 1.75, I2 = 0%). However, the CVVH group was associated with a longer survival time compared to the control group (weighted mean difference 1.73, 95% CI: 0.56–2.90, P = .004). Respiratory failure as the cause of death was more common in the CVVH group, as compared with the control group (RR 1.66, 95% CI: 1.24–2.23, P = .0008), whereas patients in the control group were more likely to die from circulatory failure than in the CVVH group (RR 0.56, 95% CI: 0.40–0.81, P = .002). Conclusion: Although CVVH treatment might not noticeably reduce mortality for patients with PQ poisoning, it can prolong the survival time of the patients and improve the stability of the circulatory system, thereby enabling further treatment. PMID:28514303
Boucher, Bradley A; Hudson, Joanna Q; Hill, David M; Swanson, Joseph M; Wood, G Christopher; Laizure, S Casey; Arnold-Ross, Angela; Hu, Zhe-Yi; Hickerson, William L
2016-12-01
High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. Prospective clinical pharmacokinetic study. Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CL T otal ), CL by CVVH (CL HF ), half-life during CVVH, volume of distribution at steady state (Vd ss ), and the percentage of drug eliminated by CVVH. In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CL HF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CL T otal (14.74 ± 4.75 L/hr). Cilastatin CL HF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CL T otal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vd ss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen. © 2016 Pharmacotherapy Publications, Inc.
[Is the time ripe for cytosorb].
Gehling, Markus; Tryba, Michael
2016-03-01
Hemofiltration with Cytosorb can reduce cytokines in sepsis. Since cytokines are involved in the development of vasodilatatory shock in sepsis, their reduction might improve the chance of survival in this condition. In spite of the CE-approval of Cytosorb clinical efficacy has not been proved so far. Other techniques reducing cytokines by direct or indirect manners failed to prove an influence on sepsis mortality. Moreover, the nonspecific elimination of pro- and anti-inflammatory cytokines may result in different clinical effects. Benefits and risks of nonspecific cytokine elimination may be determined by the interaction of pro- and anti-inflammatory cytokines. Therefore, the usefulness of cytokine elimination using Cytosorb cannot be estimated without clinical data. The application of cytosorb in life threatening septic shock should be accompanied by a critical discussion of the limits of these curing trials. © Georg Thieme Verlag KG Stuttgart · New York.
Köse, Melis; Canda, Ebru; Kagnici, Mehtap; Uçar, Sema Kalkan; Çoker, Mahmut
2017-01-01
In treatment of metabolic imbalances caused by maple syrup urine disease (MSUD), peritoneal dialysis, and hemofiltration, pharmacological treatments for elimination of toxic metabolites can be used in addition to basic dietary modifications. Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate (NaPB) in urea-cycle disorder cases has been associated with a reduction in branched-chain amino acid (BCAA) concentrations when the patients are on adequate dietary protein intake. Moreover, NaPB in treatment of MSUD patients is also associated with reduction of BCAA levels in a limited number of cases. However, there are not enough studies in the literature about application and efficacy of this treatment. Our case report sets an example of an alternative treatment's efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease.
Transfer of endogenous pyrogens across artificial membranes?
Lonnemann, G; Linnenweber, S; Burg, M; Koch, K M
1998-05-01
Synthetic high-flux dialyzer membranes used in continuous veno-venous hemofiltration are permeable to middle molecular size endogenous pyrogens, the pro-inflammatory cytokines IL-1 beta and TNF-alpha. The quantities removed by sieving are, however, negligible in vitro as well as in vivo. Adsorption of cytokines to the membrane polymer is the major mechanism of pyrogen removal. Adsorption seems to be semispecific for pro-inflammatory cytokines because levels of anti-inflammatory mediators were not changed or even increased during CVVH. Thus, CVVH may change cytokine profiles in septic patients supporting the predominance of anti-inflammatory over pro-inflammatory activity in plasma. It remains to be demonstrated whether modifications of extracorporeal blood purification systems (high-volume CVVH, plasma separation + adsorption) are able to amplify the change in cytokine profiles and whether this change influences outcome of septic patients.
Canda, Ebru; Kagnici, Mehtap; Uçar, Sema Kalkan; Çoker, Mahmut
2017-01-01
In treatment of metabolic imbalances caused by maple syrup urine disease (MSUD), peritoneal dialysis, and hemofiltration, pharmacological treatments for elimination of toxic metabolites can be used in addition to basic dietary modifications. Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate (NaPB) in urea-cycle disorder cases has been associated with a reduction in branched-chain amino acid (BCAA) concentrations when the patients are on adequate dietary protein intake. Moreover, NaPB in treatment of MSUD patients is also associated with reduction of BCAA levels in a limited number of cases. However, there are not enough studies in the literature about application and efficacy of this treatment. Our case report sets an example of an alternative treatment's efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease. PMID:28589054
Shahbazov, Rauf; Fox, Michael; Alejo, Jennifer L; Anjum, Malik A; Azari, Feredun; Doyle, Alden; Agarwal, Avinash; Brayman, Kenneth L
2018-04-01
Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two. Perhaps CVVHF is a better modality compared to HD in this setting to prevent further insult from pigment nephropathy to an allograft. A combination of early diagnosis and intensive continuous renal replacement therapy can be used for allograft salvage in a patient with rhabdomyolysis in the immediate post-kidney transplant period.
Frydrychowicz, Clara; Pasieka, Bastian; Pierer, Matthias; Mueller, Wolf; Petros, Sirak; Weidhase, Lorenz
2017-01-04
Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure. We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored. Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.
Extracorporeal methods of blood glutamate scavenging: a novel therapeutic modality.
Zhumadilov, Agzam; Boyko, Matthew; Gruenbaum, Shaun E; Brotfain, Evgeny; Bilotta, Federico; Zlotnik, Alexander
2015-05-01
Pathologically elevated glutamate concentrations in the brain's extracellular fluid are associated with several acute and chronic brain insults. Studies have demonstrated that by decreasing the concentration of glutamate in the blood, thereby increasing the concentration gradient between the brain and the blood, the rate of brain-to-blood glutamate efflux can be increased. Blood glutamate scavengers, pyruvate and oxaloacetate have shown great promise in providing neuroprotection in many animal models of acute brain insults. However, glutamate scavengers' potential systemic toxicity, side effects and pharmacokinetic properties may limit their use in clinical practice. In contrast, extracorporeal methods of blood glutamate reduction, in which glutamate is filtered from the blood and eliminated, may be an advantageous adjunct in treating acute brain insults. Here, we review the current evidence for the glutamate-lowering effects of hemodialysis, peritoneal dialysis and hemofiltration. The evidence reviewed here highlights the need for clinical trials.
He, Wen-Hua; Yu, Min; Zhu, Yin; Xia, Liang; Liu, Pi; Zeng, Hao; Zhu, Yong; Lv, Nong-Hua
2016-10-01
To compare the value of emergent triglyceride (TG)-lowering therapies between early high-volume hemofiltration (HVHF) and low-molecular-weight heparin (LMWH) combined with insulin (LMWH+insulin) as well as their effects on the outcomes of hypertriglyceridemic pancreatitis (HTGP) patients. In this randomized controlled trial, 66 HTGP patients presenting within 3 days after the onset of symptoms from August 2011 to October 2013 were assigned randomly to receive either HVHF or LMWH+insulin as an emergent TG-lowering therapy. Thirty-three patients were included in each group, and the therapy was started as soon as possible after admission. TG levels, clinical outcomes, and inflammatory biomarkers were compared between the 2 groups. Thirty-two individuals in the HVHF group and 34 in the LMWH+insulin group were included in the final analysis. Characteristics of the patients in both groups were roughly comparable. HVHF could remove TG from the plasma and achieve its target (<500 mg/dL) in approximately 9 hours, whereas the target was not achieved within 48 hours in patients receiving the LMWH+insulin treatment (P<0.05). However, no differences were found in terms of the majority of the clinical outcomes, including local pancreatic complications (P>0.05), the requirement of surgical intervention (P=0.49), mortality (P=0.49), and the duration of hospitalization (P=0.144). Furthermore, an unexpectedly higher incidence of persistent organ failure was observed in the HVHF group compared with the LMWH+insulin group (risk ratio with HVHF, 2.42; 95% confidence interval, 1.15-5.11; P=0.01). Hospital charges for patients in the HVHF group were approximately 2-fold higher than those for patients in the LMWH+insulin group (5.20±4.90 vs. 2.92±3.21, P=0.03). We selected a systemic inflammatory response syndrome score of at least 2 at baseline as a predictor of SAP patients, and the subgroup analyses showed that HVHF cannot improve the prognosis of the predicted SAP patients compared with the LMWH+insulin group. HVHF can lower TG levels more efficiently than LMWH+insulin therapy, but it is not superior in terms of clinical outcomes and costs. Further multicenter studies with large samples are required to clarify the feasibility of administering the HVHF treatment to HTGP patients (ChiCTR-TRC-13003274).
Albumin Apheresis for Artificial Liver Support: In Vitro Testing of a Novel Filter.
Piatek, Tomasz; Giebultowicz, Joanna; Rüth, Marieke; Lemke, Horst-Dieter; Bonn, Florian; Wroczynski, Piotr; Malkowski, Piotr; Rozga, Jacek
2018-05-16
Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof-of-concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin-leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large-pore filter for similar clinical application is described. The performance of the filter was studied in vitro; it was found to effectively remove a wide spectrum of pathogenic factors implicated in the pathophysiology of hepatic failure, including protein bound toxins and defective forms of circulating albumin. Data on mass transport characteristics and functionality using various modes of filtration and dialysis provide rationale for clinical evaluation of the filter for artificial liver support using albumin apheresis. © 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.
Historical milestones of a long pathway.
Roy, Thomas
2011-01-01
Hemodiafiltration (HDF), developed from the combination of hemodialysis and hemofiltration, is considered to be the most effective current procedure to remove uremic toxins from the blood of kidney patients. Historically, the clinical use of HDF was for many years limited due to the cost burden related to the large amount of sterile volume replacement fluid needed. The solution offered was on-line preparation of replacement fluid from standard dialysate by means of membrane filtration. Industry opened to this concept quite early and worked on various technical solutions between the early 1980s and the late 1990s before real state-of-the-art systems became commercially available on a broad basis. This article reviews in particular the activities of initially Fresenius and later Fresenius Medical Care in this field and identifies major concepts and prototypes up to today's commercially available high-end product--the 5008 therapy system--where on-line HDF finally became integrated as a standard component. Copyright © 2011 S. Karger AG, Basel.
Clark, William R; Turk, Joseph E
2004-01-01
Given the results of recent randomized controlled trials as well as staffing and budget challenges that today face many institutions across North America, a novel therapeutic approach is likely necessary to enable improvements in clinical outcomes for renal failure patients. The NxStage System One was developed to address these challenges. The system is an innovative, flexible device that delivers hemodialysis, hemofiltration, and/or ultrafiltration therapies to patients with renal failure or fluid overload. The unique characteristics of this system include a highly automated system design with a drop-in cartridge to facilitate training and simple operation; portable size and independence from dedicated infrastructure to minimize practical barriers to where therapy may be administered; use of high-quality premixed treatment fluids to enable capture of the potential clinical benefits of fluid purity without the hassles of local water treatment; and wide operating ranges to allow clinician flexibility in patient therapy prescriptions. In both the chronic and acute care environments, the System One presents clinicians with a new platform for delivering patient therapy improvements within real-world constraints.
Moeslein, Fred M; McAndrew, Elizabeth G; Appling, William M; Hryniewich, Nicole E; Jarvis, Kevin D; Markos, Steven M; Sheets, Timothy P; Uzgare, Rajneesh P; Johnston, Daniel S
2014-06-01
A new melphalan hemoperfusion filter (GEN 2) was evaluated in a simulated-use porcine model of percutaneous hepatic perfusion (PHP). The current study evaluated melphalan filtration efficiency, the transfilter pressure gradient, and the removal of specific blood products. A porcine PHP procedure using the GEN 2 filter was performed under Good Laboratory Practice conditions to model the 60-min clinical PHP procedure. The mean filter efficiency for removing melphalan in six filters was 99.0 ± 0.4 %. The transfilter pressure gradient across the filter averaged 20.9 mmHg for the 60-min procedure. Many blood components, including albumin and platelets, decreased on average from 3.55 to 2.02 g/dL and from 342 to 177 × 10.e3/μL, respectively, during the procedure. The increased melphalan extraction efficiency of the new filter is expected to decrease systemic melphalan exposure. In addition, the low transfilter pressure gradient resulted in low resistance to blood flow in the GEN 2 filter, and the changes to blood components are expected to be clinically manageable.
Sanchez-Izquierdo Riera, J A; Montoiro Allué, R; Tomasa Irriguible, T; Palencia Herrejón, E; Cota Delgado, F; Pérez Calvo, C
2016-10-01
We maintain a dynamic position on extracorporeal blood purification therapies (EBPT). Continuous therapies are of choice in the hemodynamically unstable patient. We recommend their early introduction in the course of the disease, and starting with a dose of 30-35mL/kg/h. Above all, however, daily re-evaluation is required of the hemodynamic and metabolic situation and water balance of our patients in order to allow dynamic dose adjustment. Some data suggest that continuous EBPT can favorably influence the clinical course of our patients, even in the absence of acute kidney injury. The potential usefulness of hemofiltration at doses higher than the conventional doses (continuous ultrafiltration >50mL/kg/h or pulses of at least 4h a day to more than 100dosesmL/kg/h) for achieving blood purification has also been commented. We review the possible indications of this technique, together with the peculiarities of implementing these therapies in children. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.
Post-partum streptococcal toxic shock syndrome associated with necrotizing fasciitis.
Chua, Wei Chuan; Mazlan, Mohd Zulfakar; Ali, Saedah; Che Omar, Sanihah; Wan Hassan, Wan Mohd Nazaruddin; Seevaunnantum, S Praveena; Mohd Zaini, Rhendra Hardy; Hassan, Mohd Hasyizan; Muhd Besari, Alwi; Abd Rahman, Zaidah; Salmuna Ayub, Zeti Norfidiyati; Abd Ghani, Sabrina; Yaacob, Normalinda; Wan Rosli, Wan Rosilawati
2017-01-01
We report a fatal case of post-partum streptococcal toxic shock syndrome in a patient who was previously healthy and had presented to the emergency department with an extensive blistering ecchymotic lesions over her right buttock and thigh associated with severe pain. The pregnancy had been uncomplicated, and the mode of delivery had been spontaneous vaginal delivery with an episiotomy. She was found to have septicemic shock requiring high inotropic support. Subsequently, she was treated for necrotizing fasciitis, complicated by septicemic shock and multiple organ failures. A consensus was reached for extensive wound debridement to remove the source of infection; however, this approach was abandoned due to the patient's hemodynamic instability and the extremely high risks of surgery. Both the high vaginal swab and blister fluid culture revealed Group A beta hemolytic streptococcus infection. Intravenous carbapenem in combination with clindamycin was given. Other strategies attempted for streptococcal toxic removal included continuous veno-venous hemofiltration and administration of intravenous immunoglobulin. Unfortunately, the patient's condition worsened, and she succumbed to death on day 7 of hospitalization.
Zirconium: biomedical and nephrological applications.
Lee, David B N; Roberts, Martin; Bluchel, Christian G; Odell, Ross A
2010-01-01
Recent years have witnessed a rapid increase in the use of zirconium (Zr)-containing compounds in artificial internal organs. Examples include dental implants and other restorative practices, total knee and hip replacement, and middle-ear ossicular chain reconstruction. In nephrological practice, Zr-containing sorbents have been used in hemofiltration, hemodialysis, peritoneal dialysis, and in the design and construction of wearable artificial kidneys. Zr compounds continue to be widely and extensively used in deodorant and antiperspirant preparations. In the public health arena, Zr compounds have been studied or used in controlling phosphorus pollution and in the reclamation of poison and bacteria-contaminated water. Experimental and clinical studies support the general consensus that Zr compounds are biocompatible and exhibit low toxicity. Reports on possible Zr-associated adverse reactions are rare and, in general, have not rigorously established a cause-and-effect relationship. Although publications on the use of Zr compounds have continued to increase in recent years, reports on Zr toxicity have virtually disappeared from the medical literature. Nevertheless, familiarity with, and continued vigilant monitoring of, the use of these compounds are warranted. This article provides an updated review on the biomedical use of Zr compounds.
See, Kay Choong; Lee, Margaret; Mukhopadhyay, Amartya
2009-01-01
Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group), received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020). When calcium-containing replacement solution was used, more citrate was required (mean 280 ml/h, CI 227.2-332.8 vs. 265 ml/h, CI 203.4-326.6, P = 0.069), but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6 ml/h, CI 26.8-76.4, P < or = 0.0001).
Massive naproxen overdose with serial serum levels.
Al-Abri, Suad A; Anderson, Ilene B; Pedram, Fatehi; Colby, Jennifer M; Olson, Kent R
2015-03-01
Massive naproxen overdose is not commonly reported. Severe metabolic acidosis and seizure have been described, but the use of renal replacement therapy has not been studied in the context of overdose. A 28-year-old man ingested 70 g of naproxen along with an unknown amount of alcohol in a suicidal attempt. On examination in the emergency department 90 min later, he was drowsy but had normal vital signs apart from sinus tachycardia. Serum naproxen level 90 min after ingestion was 1,580 mg/L (therapeutic range 25-75 mg/L). He developed metabolic acidosis requiring renal replacement therapy using sustained low efficiency dialysis (SLED) and continuous venovenous hemofiltration (CVVH) and had recurrent seizure activity requiring intubation within 4 h from ingestion. He recovered after 48 h. Massive naproxen overdose can present with serious toxicity including seizures, altered mental status, and metabolic acidosis. Hemodialysis and renal replacement therapy may correct the acid base disturbance and provide support in cases of renal impairment in context of naproxen overdose, but further studies are needed to determine the extraction of naproxen.
Wu, Yunzhen; Wang, Chunting
2015-05-01
To establish a mathematical formula for choosing the manner of replacement fluid infusion in continuous renal replacement therapy (CRRT), so as to provide the basis for improving the treatment effect. A mathematical formula for choosing the manner of replacement fluid infusion with continuous veno-venous hemofiltration (CVVH) was taken as an example, and it was compared with the result of standard replacement fluid in order to analyze the effect of different manners of infusion. (1) Comparison parameters: the plasma volume ("Vreturn") and some electrolyte concentration ("Creturn") in back way of CRRT ( if other thing was solute, filter coefficient should be 1.0). (2) Research objects: the actual replacement fluid (for example, the most complex should be sorted into A and B type) mode (pre or post) was compared with the standard replacement fluid (the A and B in one). (3) Based on the formula of standard replacement, four equations in different conditions were derived: pre-dilution and post-dilution mode; same direction and same ratio; same direction and different ratio; different direction and same ratio; different direction and different ratio. The calculated results of "Vreturn" (except hematocrit) and "Creturn" were same to the standard only following the rule of same direction and ratio for A and B no matter pre-dilution mode or post-dilution mode, and it was different from the standard in others. In pre-dilution mode and post-dilution mode, it showed: (1) A and B in same direction and different ratio: "Vreturn" and "Creturn" were different from the standard for the alterative ratio of B. (2) A and B in different direction and same ratio: "Vreturn" was same to the standard, but "Creturn" was different from the standard for the completely different and more complex computational formula. (3) A and B in different direction and different ratio: both "Vreturn" and "Creturn" were different from the standard. The different "Vreturn" was due to the different ratio of B. The different "Creturn" was caused by different ratio of B and the completely different computational formula. (1) For parts of replacement fluid which must be separated (for example, bicarbonate formula), the result is same to the standard, and is predicted and mastered only following the rule of same direction and ratio. Otherwise, we need to calculate the two parameters over and over again. The result will run out of our judgment. The wrongness of losing water and electrolyte disorders maybe come out. (2) Accordingly,the formula could be used to analyze the same case like the separated replacement infusion, for example, a large number of citrates as regional anticoagulation were infused only in the front of filter, while the replacement fluid can be done in varied forms.
Tomescu, Dana R; Olimpia Dima, Simona; Ungureanu, Daniela; Popescu, Mihai; Tulbure, Dan; Popescu, Irinel
2016-05-16
Emergency transplantation of a donor liver that is not matched for the major blood antigens can produce marked immune-mediated cytokine release that can cause donor graft loss. Control of the inflammatory response may be a key element in treatment. We present the case of a 46-year-old man with primary graft nonfunction after liver transplantation who underwent emergency retransplantation with an ABO-incompatible graft. A severe inflammatory response syndrome (SIRS) was noted in the perioperioperative period of retransplantation. The patient was successfully treated for this condition with a new hemoadsorption column (CytoSorb®), in combination with continuous venovenous hemofiltration (CVVH) throughout the intraoperative and early postoperative period. During and after each treatment a significant and rapid decrease of pro- and anti-inflammatory cytokines was observed, especially for interleukin-6 (IL-6), IL-10 and monocyte chemotactic protein 1 (MCP-1). Reduction of cytokines was associated with normalization of cardiac output and systemic vascular resistance, and improved liver function. We believe this is the first case in which hemoadsorptionin combination with CVVH has been used to manage SIRS in a patient with primary graft nonfunction undergoing emergency retransplantation.
Successful outcome after intravenous gasoline injection.
Domej, Wolfgang; Mitterhammer, Heike; Stauber, Rudolf; Kaufmann, Peter; Smolle, Karl Heinz
2007-12-01
Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.
Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L
2015-01-01
Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.
Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H.; Roy, Shuvo
2015-01-01
Silicon nanopore membranes (SNM) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here we present an initial evaluation of the SNM’s mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200ml/min) and pressures (1,448mmHg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4-hours in an extra-corporeal porcine model. The pressure drop across the flow cell was 4.6mmHg at 200ml/min. Mechanical testing showed that SNM could withstand up to 775.7mmHg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extra-corporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1 fold increase and 1.8 fold increase over polyethylene-glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD-41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy. PMID:26692401
The use of renal replacement therapy in acute decompensated heart failure.
Udani, Suneel M; Murray, Patrick T
2009-01-01
The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.
Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study.
Li, An; Li, Wenxiong; Hao, Fengtong; Wang, Haishi
2016-01-01
To evaluate the efficacy of conservative treatment vs. hemoperfusion (HP) vs. HP + continuous veno-venous hemofiltration (CVVH) for acute Paraquat (PQ) poisoning. This was a multicenter retrospective study of patients with PQ poisoning between January 2013 and June 2014. Clinical data and PQ serum levels were collected at baseline and after 24, 48, and 72 h of treatment. Seventy-five, 65, and 43 underwent conservative treatment only (conservative treatment group), conservative treatment + HP (HP group), and conservative treatment + HP + CVVH (HP + CVVH group), respectively. PQ serum levels decreased in all groups after 72 h of treatment (p < 0.001); meanwhile, these values decreased faster in the HP and HP + CVVH groups compared with the conservative treatment group. More importantly, PQ blood levels were significantly lower in the HP + CVVH group compared with the HP group at 24 h (p < 0.05). Sequential organ failure assessment (ΔSOFA) values in the HP and HP + CVVH groups were significantly lower compared with that obtained for the conservative treatment group (p < 0.05). The 60-day survival rates were 21.3, 43.1 and 46.5%, respectively. Multivariate analysis indicated that age, PQ dose, admission PQ levels, and admission SOFA score were independently associated with mortality. HP and HP + CVVH were protective factors. Early HP or HP + CVVH after PQ poisoning could decrease PQ blood levels, alleviate organ damage, and increase survival. © 2016 S. Karger AG, Basel.
Advanced glycation end products in clinical nephrology.
Kalousová, M; Zima, T; Tesar, V; Stípek, S; Sulková, S
2004-01-01
As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists). Copyright 2004 S. Karger AG, Basel
Silicon nanoporous membranes as a rigorous platform for validation of biomolecular transport models
Feinberg, Benjamin J.; Hsiao, Jeff C.; Park, Jaehyun; Zydney, Andrew L.; Fissell, William H.; Roy, Shuvo
2017-01-01
Microelectromechanical systems (MEMS), a technology that resulted from significant innovation in semiconductor fabrication, have recently been applied to the development of silicon nanopore membranes (SNM). In contrast to membranes fabricated from polymeric materials, SNM exhibit slit-shaped pores, monodisperse pore size, constant surface porosity, zero pore overlap, and sub-micron thickness. This development in membrane fabrication is applied herein for the validation of the XDLVO (extended Derjaguin, Landau, Verwey, and Overbeek) theory of membrane transport within the context of hemofiltration. In this work, the XDLVO model has been derived for the unique slit pore structure of SNM. Beta-2-microglobulin (B2M), a clinically relevant “middle molecular weight” solute in kidney disease, is highlighted in this study as the solute of interest. In order to determine interaction parameters within the XDLVO model for B2M and SNM, goniometric measurements were conducted, yielding a Hamaker constant of 4.61× 10−21 J and an acid-base Gibbs free energy at contact of 41 mJ/m2. The XDLVO model was combined with existing models for membrane sieving, with predictions of the refined model in good agreement with experimental data. Furthermore, the results show a significant difference between the XDLVO model and the simpler steric predictions typically applied in membrane transport. The refined model can be used as a tool to tailor membrane chemistry and maximize sieving or rejection of different biomolecules. PMID:28936029
Bioengineered Renal Cell Therapy Device for Clinical Translation
Pino, Christopher J.; Westover, Angela J.; Buffington, Deborah A.; Humes, H. David
2016-01-01
The Bioartificial Renal Epithelial Cell System (BRECS), is a cell-based device to treat acute kidney injury through renal cell therapy from an extracorporeal circuit. To enable widespread implementation of cell therapy, the BRECS was designed to be cryopreserved as a complete device, cryostored, cryoshipped to an end-use site, thawed as a complete device, and employed in a therapeutic extracorporeal hemofiltration circuit. This strategy overcomes storage and distribution issues that have been previous barriers to cell therapy. Previous BRECS housings produced by Computer Numerical Control (CNC) machining, a slow process taking hours to produce one bioreactor, was also prohibitively expensive (>$600/CNC-BRECS); major obstacles to mass production. The goal of this study was to produce a BRECS to be mass produced by injection molding (IM-BRECS), decreasing cost (<$20/unit) and improving manufacturing speed (hundreds of units/hr), while maintaining the same cell therapy function as the previous CNC-BRECS, first evaluated through prototypes produced by stereolithography (SLA-BRECS). The finalized IM-BRECS design had a significantly lower fill volume (10 mL), mass (49 g) and footprint (8.5 cm×8.5 cm×1.5 cm), and was demonstrated to outperform the previous BRECS designs with respect to heat transfer, significantly improving control of cooling during cryopreservation and reducing thaw times during warming. During in vitro culture, IM-BRECS performed similarly to previous CNC-BRECS with respect to cell metabolic activity (lactate production, oxygen consumption and glutathione metabolism) and amount of cells supported. PMID:27922886
Li, Ming Xin; Liu, Jun Feng; Lu, Jian Da; Zhu, Ying; Kuang, Ding Wei; Xiang, Jian Bing; Sun, Peng; Wang, Wei; Xue, Jun; Gu, Yong; Hao, Chuan Ming
2016-12-01
The object of this study is to explore whether the plasmadiafiltration (PDF) is more effective in improving the intestinal mucosal barrier function by removing more key large molecular inflammatory mediators and then prolonging the survival time. Totally, 24 porcine sepsis models induced by cecal ligation and puncture (CLP) operation were randomly divided into three groups: PDF group, high-volume hemofiltration (HVHF) group, and control group, and received 8 h treatment, respectively. The expression of ZO-1 and occludin in intestinal mucosal epithelial cells were detected by immunohistochemistry, and apoptotic protein caspase-3-positive lymphocytes were signed in mesenteric lymph nodes by TUNEL staining. The hemodynamic parameters were measured by invasive cavity detection. The tumor necrosis factor alpha (TNFα) and high-mobility group protein 1 (HMGB1) were tested by ELISA method. And then, the survival curves with all-cause death were compared with three groups. PDF led to a superior reversal of sepsis-related hemodynamic impairment and serum biochemistry abnormalities and resulted in longer survival time compared with HVHF and control (p < 0.01). Definitive protection from excessive TNF-α and HMGB1 response were only achieved by PDF. A more regular distribution pattern of ZO-1 and occludin along the epithelium was found in PDF animals (p < 0.01). The presence of apoptotic lymphocytes was significantly reduced in the PDF animals (p < 0.01). PDF can effectively eliminate more pivotal inflammatory mediators of TNFα and HMGB1 and reduce the inflammation damage of the intestinal mucosal barrier and apoptosis of lymphocyte then improve the circulation function and prolong the survival time.
Doripenem Treatment during Continuous Renal Replacement Therapy
Wenisch, J. M.; Maier-Salamon, A.; Fritsch, A.; Saria, K.; Zuba, C.; Jilch, S.; Lemmerer, R.; Unger, M.; Jaehde, U.; Jäger, W.; Thalhammer, F.
2015-01-01
Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa. While the initial dosing recommendation for renally competent patients and patients undergoing continuous renal replacement therapy (cRRT) was 500 mg every 8 h (q8h), the dose for renally competent patients was updated to 1 g q8h in June 2012. There are no updated data for the dosing of patients on continuous renal replacement therapy. The original dosing regimen for cRRT patients was based on nonseptic patients, while newer publications chose comparatively low target concentrations for a carbapenem. Thus, there is an urgent need for updated recommendations for dosing during cRRT. In the trial presented here, we included 13 oliguric septic patients undergoing cRRT in an intensive care setting. Five patients each were treated with hemodiafiltration or hemodialysis, while three patients received hemofiltration treatment. All patients received 1 g doripenem every 8 h. Doripenem concentrations in the plasma and ultrafiltrate were measured over 48 h. The mean hemofilter clearance was 36.53 ml/min, and the mean volume of distribution was 59.26 liters. The steady-state trough levels were found at 8.5 mg/liter, with no considerable accumulation. Based on pharmacokinetic and pharmacodynamic considerations, we propose a regimen of 1 g q8h, which may be combined with a loading dose of 1.5 to 2 g for critically ill patients. (This study has been registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.) PMID:26711775
Acute metformin intoxication: 2012 experience of Emergency Departement of Lodi, Italy.
Acquistapace, Giulia; Rossi, Marco; Garbi, Mara; Cosci, Pablo; Canetta, Ciro; Manelli, Anna; Ricevuti, Giovanni
2014-10-01
Background: Metformin is a biguanide antihyperglycemic agent that decreases insulin resistance. It is removed through renal mechanisms and its clearance is reduced in renal failure. Metformin ingestion should always be considered in the differential diagnosis of any patient with metabolic acidosis and increased lactate level. Hemodialysis and continuous veno-venous hemofiltration (CVVH) are both efficient methods to treat metformin intoxication and correct metabolic abnormalities. Patient 1: A 63-year-old man with type 2 diabetes mellitus presented to emergency department (ED) of Lodi (Italy) for dyspnea. He also reported having diarrhea for 10 days. Initial investigations revealed metabolic acidosis with hyperlactatemia and hypoglycemia (54 mg/dL), metformin concentration was 41 μg/mL (normal value <4 μg/mL). His hemodynamic condition became rapidly unstable and hypotension worsened despite CVVH being performed. Death occurred in 24 h. Patient 2: A 76-year-old man with type 2 diabetes mellitus presented to ED of Lodi for dyspnea. He referred a recent surgery amputation of the left foot's fifth phalanx for osteomyelitis, in levofloxacin therapy. Initial investigations revealed metabolic acidosis with hyperlactatemia and severe hypoglycemia (20 mg/dL). Two hemodialysis sessions were performed with complete normalization of the serum concentration of metformin. In our two cases the genesis of metformin intoxication was clear, powered by acute renal failure, but less obvious was the etiology of acute renal damage responsible for metformin accumulation. Damage due to renal hypoperfusion or the direct toxic effect of metformin should be considered. Additionally, for the second patient, we can also hypothesize that interstitial nephritis was exacerbated by levofloxacin.
Recent Advances in the Treatment of Organophosphorous Poisonings
Balali-Mood, Mahdi; Saber, Hamidreza
2012-01-01
Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of organophosphorous poisoning poisonings. PMID:23115436
John, Harald; Hierer, Jessica; Haas, Olga; Forssmann, Wolf-Georg
2007-03-01
Chemerin is a chemoattractive protein acting as a ligand for the G-protein-coupled receptor ChemR23/CMKLR1 and plays an important role in the innate and adaptive immunity. Proteolytic processing of its C terminus is essential for receptor binding and physiological activity. Therefore, we investigated the plasma stability of the decapeptide chemerin 145-154 (P(145)-F(154)) corresponding to the C terminus of the physiologically active chemerin variant E(21)-F(154) from human hemofiltrate. For monitoring concentration-time profiles and degradation products we developed a novel matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry procedure using an internal peptide standard (hemorphin LVV-H7) for quantification. The linear range covers 2.5 orders of magnitude in the lower micromolar concentration range (lower limit of quantification 0.312 microg/ml, 0.25 microM) characterized by satisfactory reproducibility (CV < or =9%), accuracy (< or =10%), ruggedness, and recovery (98%). We found that chemerin 145-154 is C-terminally truncated in human citrate plasma by the cleavage of the penultimate dipeptidyl residue. N-terminal truncation was not observed. In contrast to citrate plasma, no degradation was detected in ethylenediammetetraacetate (EDTA) plasma. We identified angiotensin-converting-enzyme (ACE) to be responsible for C-terminal truncation, which could be completely inhibited by EDTA and captopril. These results are relevant to clarify the natural processing of chemerin and the potential involvement of ACE in mediating the immune response.
Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury
Zhu, Qiuyu; Liu, Junfeng; Qian, Jing; You, Huaizhou; Gu, Yong; Hao, Chuanming; Jiao, Zheng; Ding, Feng
2013-01-01
Introduction Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA. Methods Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients’ CVVH sessions with citrate anticoagulation. Results Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements. Conclusions Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation. Trial Registration ClinicalTrials.gov Identifier NCT00948558 PMID:23824037
Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study.
Chung, Kevin K; Coates, Elsa C; Hickerson, William L; Arnold-Ross, Angela L; Caruso, Daniel M; Albrecht, Marlene; Arnoldo, Brett D; Howard, Christina; Johnson, Laura S; McLawhorn, Melissa M; Friedman, Bruce; Sprague, Amy M; Mosier, Michael J; Conrad, Peggie F; Smith, David J; Karlnoski, Rachel A; Aden, James K; Mann-Salinas, Elizabeth A; Wolf, Steven E
2018-06-20
Acute kidney injury (AKI) after severe burns is historically associated with a high mortality. Over the past two decades, various modes of renal replacement therapy (RRT) have been utilized in this population. The purpose of this multicenter study was to evaluate demographic, treatment and outcomes data among severe burn patients treated with RRT collectively at various burn centers around the United States. After institutional review board approval, a multicenter observational study was conducted. All adult patients 18 or older, admitted with severe burns who were placed on RRT for acute indications but not randomized into a concurrently enrolling interventional trial were included. Across 8 participating burn centers, 171 subjects were enrolled during a 4 year period. Complete data was available in 170 subjects with a mean age of 51±17, percent total body surface area (TBSA) burn of 38±26% and Injury Severity Score of 27±21. 80% of subjects were male and 34% were diagnosed with smoke inhalation injury. The preferred mode of therapy was continuous venovenous hemofiltration at a mean delivered dose of 37±19 (mL/kg/hr) and a treatment duration of 13±24 days. Overall, in hospital mortality was 50%. Among survivors, 21% required RRT upon discharge from the hospital while 9% continued to require RRT 6 months after discharge. This is the first multi-center cohort of burn patients who underwent RRT reported to date. Overall mortality is comparable to other critically ill populations who undergo RRT. Most patients who survive to discharge eventually recover renal function.
Extracorporeal blood treatment (EBT) methods in SIRS/Sepsis.
Bellomo, R; Honoré, P M; Matson, J; Ronco, C; Winchester, J
2005-05-01
Extracorporeal blood purification treatment (EBT) methods have been used in the treatment of experimental and human SIRS/Sepsis in a variety of settings and with variable reports of efficacy and safety. Their role in the management of SIRS/Sepsis remains controversial. To develop consensus statements regarding important aspects of research, practice and technical management concerning EBT. Systematic review of published study. Evidence-based grading of information available. Consensus development regarding fundamental questions about EBT. Consensus was achieved on all questions posed during the conference. It was agreed that there is currently a clear biological rational for EBT in SIRS and Sepsis. It was agreed that conventional CVVH has sufficiently been shown not to be effective in SIRS/Sepsis in the absence of concomitant ARF and that other therapies such as plasmapheresis or high-volume hemofiltration or coupled plasma filtration adsorption appear more promising and should be tested in multicentre randomized controlled trials. Patients with ARF and SIRS/Sepsis should be treated differently from those with ARF alone even though current practice in this field is not well known. Patients with refractory septic shock should be considered for EBT. Appropriate end points for clinical trials can be defined and chosen according to the goals of the trial. Different technologies exist for EBT and better understanding of the merits and safety of each is needed as well as better standardization of methodology and dose. Broad consensus can be achieved on several aspects of EBT and can be used to inform clinical practice and to help guide the establishment of a future research agenda.
The future of the artificial kidney: moving towards wearable and miniaturized devices.
Ronco, C; Davenport, A; Gura, V
2011-01-01
New directions in dialysis research include cheaper treatments, home based therapies and simpler methods of blood purification. These objectives may be probably obtained with innovations in the field of artificial kidney through the utilization of new disciplines such as miniaturization, microfluidics, nanotechnology. This research may lead to a new era of dialysis in which the new challenges are transportability, wearability and why not the possibility to develop implantable devices. Although we are not there yet, a new series of papers have recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable artificial kidneys (WAK). Some of them use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality (ViWAK and AWAK.) A special mention deserves the wearable/portable ultrafiltration system for the therapy of overhydration and congestive heart failure (WAKMAN). This system will allow dehospitalization and treatment of patients with less comorbidity and improved tolerance. On the way to the wearable artificial kidney, new discoveries have been made such as a complete system for hemofiltration in newborns (CARPEDIEM). The neonate in fact is the typical patient who may benefit from miniaturization of the dialysis circuit. This review analyzes the rationale for such endeavour and the challenges to overcome in order to make possible a true ambulatory dialysis treatment. Some initial results with these new devices are presented. We would like to stimulate a collaborative effort to make a quantum leap in technology making the wearable artificial kidney a reality rather than a dream.
Human albumin: old, new, and emerging applications.
Rozga, Jacek; Piątek, Tomasz; Małkowski, Piotr
2013-05-10
Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function. In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications has increased in recent years. This, along with increased costs of manufacturing and lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices. This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional and governmental organizations. Results reflect current knowledge about the role of albumin in health and disease and relevance of albumin therapy in specific clinical settings. Albumin therapy is currently recommended in spontaneous bacterial peritonitis with ascites, refractory ascites not responsive to diuretics, large-volume paracentesis, post-paracentesis syndrome, and the treatment of hepatorenal syndrome as an adjunct to vasoconstrictors. New indications for albumin therapy are linked to the antioxidant activity of albumin and its effects on capillary integrity. In recent years, large-pore hemofiltration and albumin exchange have emerged as promising liver support therapies for liver failure and other toxic syndromes. They are designed to remove a broad range of blood-borne toxins and to restore normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules saturated with toxins with normal albumin. In view of the ongoing worldwide shortage and high cost of human albumin (native and recombinant), new usage criteria, protocols, and guidelines for appropriate utilization of albumin are needed.
Yin, Zehua; Cheng, Chong; Qin, Hui; Nie, Chuanxiong; He, Chao; Zhao, Changsheng
2015-01-01
Researches on blood purification membranes are fuelled by diverse clinical needs, such as hemodialysis, hemodiafiltration, hemofiltration, plasmapheresis, and plasma collection. To approach high-performance dialyzer, the integrated antifouling and antithrombotic properties are highly necessary for the design/modification of advanced artificial membranes. In this study, we propose and demonstrate that the physical blend of triblock polyurethane (PU) and polyethersulfone (PES) may advance the performance of hemodialysis membranes with greatly enhanced blood compatibility. It was found that the triblock PU could be blended with PES at high ratio owing to their excellent miscibility. The surfaces of the PES/PU composite membranes were characterized using attenuated total reflectance-Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, water contact angle measurement, and surface ζ-potentials. The results indicated that the membrane surfaces were assembled with hydrophilic segregation layer owing to the migration of amphiphilic PU segments during membrane preparation, which might confer the composite membranes with superior hemocompatibility. The cross-section scanning electron microscopy images of the composite membranes exhibited structure transformation from finger-like structure to sponge-like structure, which indicated that the composite membrane had tunable porosity and permeability. The further ultrafiltration experiments indicated that the composite membranes showed increased permeability and excellent antifouling ability. The blood compatibility observation indicated that PES/PU composite membranes owned decreased protein adsorption, suppressed platelet adhesion, and prolonged plasma recalcification time. These results indicated that the PES/PU composite membranes exhibited enhanced antifouling and antithrombotic properties than the pristine PES membrane. The strategy may forward the fabrication of blood compatible composite membranes for clinical blood dialysis by using the various functional miscible polymers. © 2014 Wiley Periodicals, Inc.
Kashani, Kianoush; Thongprayoon, Charat; Cheungpasitporn, Wisit; Iacovella, Gina M; Akhoundi, Abbasali; Albright, Robert C
2017-01-01
Given the known deleterious effects seen with bicarbonate supplementation for acidemia, we hypothesized that utilizing high bicarbonate concentration replacement solution in continuous venovenous hemofiltration (CVVH) would be independently associated with higher mortality. In a propensity score-matched historical cohort study conducted at a single tertiary care center from December 9, 2006, through December 31, 2009, a total of 287consecutive adult critically ill patients with Stage III acute kidney injury (AKI) requiring CVVH were enrolled. We excluded patients on maintenance dialysis, those who received other modalities of continuous renal replacement therapies, and patients that received a mixed of 22 and 32 mEq/L bicarbonate solution pre- and post-filter. The primary outcome was in-hospital and 90-day mortality rates. Among enrollees, 68 were used 32 mEq/L bicarbonate solution, and 219 received 22mEq/L bicarbonate solution for CVVH. Patients on 32 mEq/L bicarbonate solution were more often non-surgical, had lower pH and bicarbonate level but had higher blood potassium and phosphorus levels in comparison with those on 22 mEq/L bicarbonate solution. After adjustment for the baseline characteristics, the use of 32 bicarbonate solution was significantly associated with increased in-hospital (HR = 1.94; 95% CI 1.02-3.79) and 90-day mortality (HR = 1.50; 95% CI 1.03-2.14). There was a significant increase in the hospital (p = .03) and 90-day (p = .04) mortality between the 22 vs. 32 mEq/L bicarbonate solution groups following propensity matching. Our data showed there is a strong association between using high bicarbonate solution and mortality independent of severity of illness and comorbid conditions. These findings need to be evaluated further in prospective studies.
Sodium thiosulfate treatment for calcific uremic arteriolopathy in children and young adults.
Araya, Carlos E; Fennell, Robert S; Neiberger, Richard E; Dharnidharka, Vikas R
2006-11-01
In adult patients with ESRD, calcific uremic arteriolopathy (CUA) is an uncommon but life-threatening complication. No effective therapy exists, although anecdotal case reports highlight the use of sodium thiosulfate (STS), a calcium-chelating agent with antioxidant properties. CUA is rare in children, and STS use has not been reported. The objective of this study was to determine the influence of STS treatment on three patients with CUA in a pediatric chronic dialysis unit. The patients were between 12 and 21 yr of age; two were male; and primary diagnoses were obstructive uropathy, renal dysplasia, and calcineurin nephrotoxicity. Time from ESRD to CUA diagnosis was 1, 9, and 20 yr. Diagnosis was made by tissue biopsy and three-phase bone scan. Pain was the presenting symptom. Initial treatment included discontinuation of calcitriol and use of non-calcium-based phosphate binders and low-calcium dialysate concentration. STS dosage was 25 g/1.73 m(2) per dose intravenously after each hemodialysis session. For optimization of removal of calcium deposits, patient three received a combination of STS and continuous venovenous hemofiltration for the first 10 d. All patients demonstrated rapid pain relief. Within weeks, skin induration and joint mobility of the extremities improved. Radiographic evidence of reduction in the calcium deposits occurred within 3 mo of initiation of STS. The only complication was prolonged QT interval in one patient as a result of hypocalcemia, who was resolved by use of a higher dialysate calcium concentration. STS seems well tolerated in children and young adults with CUA and has mild adverse effects. For determination of its efficacy, optimum dosage, duration of therapy, and dialysis modality, controlled trials are needed.
Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients
Malone, Rebecca S.; Fish, Douglas N.; Abraham, Edward; Teitelbaum, Isaac
2001-01-01
The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m2 polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 ± 13.0 years [standard deviation]; mean weight, 96.7 ± 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CLS) and elimination half-life (t1/2) of cefepime were 35.9 ± 6.0 ml/min and 12.9 ± 2.6 h during CVVH versus 46.8 ± 12.4 ml/min and 8.6 ± 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CLS, respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CLS of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC ≤ 8 μg/ml) during CVVH or CVVHDF. PMID:11600370
Stem cells: The Next Therapeutic Frontier
Humes, H. David
2005-01-01
Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine, and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders. Blood transfusions and bone marrow transplantation are prime examples of the successful application of cell-based therapeutics; but recent advances in cellular and molecular biology have expanded the potential applications of this approach. Although recombinant genetic engineering to produce a variety of therapeutics such as human erythropoietin and insulin has proven successful, these treatments are unable to completely correct or reverse disease states, because most common disease processes are not due to the deficiency of a single protein but develop due to alterations in the complex interactions of a variety of cell components. In these complex situations, cell-based therapy may be a more successful strategy by providing a dynamic, interactive, and individualized therapeutic approach that responds to the pathophysiological condition of the patient. In this regard, cells may provide innovative methods for drug delivery of biologics, immunotherapy, and tissue regenerative or replacement engineering (1,2). The translation of this discipline to medical practice has tremendous potential, but in many applications technological issues need to be overcome. Since many cell-based indications are already being evaluated in the clinic, the field appears to be on the threshold of a number of successes. This review will focus on our group's use of human stem/progenitor cells in the treatment of acute and chronic renal failure as extensions to the current successful renal substitution processes of hemodialysis and hemofiltration. PMID:16555613
Limiting excessive postoperative blood transfusion after cardiac procedures. A review.
Ferraris, V A; Ferraris, S P
1995-01-01
Analysis of blood product use after cardiac operations reveals that a few patients (< or = 20%) consume the majority of blood products (> 80%). The risk factors that predispose a minority of patients to excessive blood use include patient-related factors, transfusion practices, drug-related causes, and procedure-related factors. Multivariate studies suggest that patient age and red blood cell volume are independent patient-related variables that predict excessive blood product transfusion after cardiac procedures. Other factors include preoperative aspirin ingestion, type of operation, over- or underutilization of heparin during cardiopulmonary bypass, failure to correct hypothermia after cardiopulmonary bypass, and physician overtransfusion. A survey of the currently available blood conservation techniques reveals 5 that stand out as reliable methods: 1) high-dose aprotinin therapy, 2) preoperative erythropoietin therapy when time permits adequate dosage before operation, 3) hemodilution by harvest of whole blood immediately before cardiopulmonary bypass, 4) autologous predonation of blood, and 5) salvage of oxygenator blood after cardiopulmonary bypass. Other methods, such as the use of epsilon-aminocaproic acid or desmopressin, cell saving devices, reinfusion of shed mediastinal blood, and hemofiltration have been reported to be less reliable and may even be harmful in some high-risk patients. Consideration of the available data allows formulation of a 4-pronged plan for limiting excessive blood transfusion after surgery: 1) recognize the causes of excessive transfusion, including the importance of red blood cell volume, type of procedure being performed, preoperative aspirin ingestion, etc.; 2) establish a quality management program, including a survey of transfusion practices that emphasizes physician education and availability of real-time laboratory testing to guide transfusion therapy; 3) adopt a multimodal approach using institution-proven techniques; and 4) continually reassess blood product use and analyze the cost-benefits of blood conservation interventions. PMID:7580359
Procalcitonin as a marker of micro-inflammation in hemodialysis.
Conti, Giovanni; Amore, Alessandro; Chiesa, Monica; Mancuso, Domenico; Cirina, Paola; Mengozzi, Giulio; Santoro, Antonio; Coppo, Rosanna
2005-01-01
In searching for a rapid and sensitive test to detect micro-inflammation in patients on hemodialysis (HD), we measured serum procalcitonin (PCT) levels and made a comparison with other traditional markers such as C-reactive protein (CRP), serum amyloid (SAA) and homocysteine, considered related to vascular damage. We investigated 51 HD patients, without signs of infection, in basal conditions (during standard bicarbonate dialysis and unselected filters: X) and after 4 months of possibly more biocompatible treatments (on-line hemofiltration (HF) or HD with ultra-pure dialysate and biocompatible membranes: Y). Serum PCT (measured by immunoluminometric assay), CRP and SAA (nephelometric assay) and plasma homocysteine (measured by high performance liquid chromatography) concentrations were assessed at the beginning of dialysis (T0) and after 4 hr (T4). Patients on unselected dialysis displayed mean PCT values significantly increased after 4 hr of dialysis in comparison to those at the start of the sessions (XT4 1.56 +/- 3.93 vs. XT0 0.4 +/- 0.34 ng/mL; p < 0.05). The PCT levels detected after 4 hr of biocompatible treatments were significantly lower than those detected after 4 hr of unselected treatments (YT4 0.78 +/- 0.34 ng/mL; p < 0.05), even though the percentage of patients with positive PCT values (> 0.5 ng/mL) remained almost unchanged. No significant modification in mean levels or in the frequency of positive values was observed for CRP, SAA and homocysteine. After 4 months of highly biocompatible treatments, a reduction in intradialytic enhancements of all inflammation markers was detected. Our data support the conclusion that PCT is a more precise marker than other traditional tests to evaluate micro-inflammation and biocompatibility in HD.
Belbrik, S; Marie, A; Boudailliez, B; Morinière, P; Sébert, J L; Solal, M C; Westeel, P F; Roche, D; Fournier, A
1990-01-01
To assess the prevalence of histologic bone disease in our center where Al(OH)3 intake is restricted, we reviewed 42 bone biopsies performed between 1975 and 1985 in patients dialyzed more than 29 months. Bone biopsies were performed systematically (2/3 of the cases) or because of a mild hypercalcemia (1/3 of the cases). Seventeen of these patients had been dialyzed before 1978 with softened water moderately contaminated by aluminum. Fifteen had always been dialyzed with reverse osmosis treated water and 10 had been exclusively treated by hemofiltration. The prevalence of osteitis fibrosa was 76%, that of osteomalacia null and that of adynamic bone disease 24% (but only 9.5% with positive Aluminon staining). When the 17 patients dialyzed with aluminum contaminated water before 1978 were excluded, only one patient among 25 had an aluminum adynamic bone disease (4%). This low prevalence can probably be explained by the restricted intake of Al(OH)3 thanks to the systematic administration of Ca CO3 and in a few cases of Mg (OH). The adynamic bone disease group has lower serum concentration of PTH and shorter duration on dialysis whereas the serum levels of calcium, phosphorus, magnesium and aluminum and daily dose of Ca CO3, Mg (OH)2 and Al(OH)3 do not differ. The frequency of the positivity of aluminum staining is not statistically different in the 2 groups. In 4 cases, adynamic bone disease without aluminum or iron intoxications is found, associated with a relative hypoparathyroidism. It is not explained by previous parathyroidectomy, diabetes or steroid therapy. 1) Restriction of aluminum intake and dialysis with reverse osmosis treated water lead to a low prevalence of aluminum bone disease. 2) A new bone disease in uremia is described: the idiopathic adynamic bone disease associated with a relative hypoparathyroidism.
Matejka, Jan; Varvarovsky, Ivo; Vojtisek, Petr; Herman, Ales; Rozsival, Vladimir; Borkova, Veronika; Kvasnicka, Jiri
2010-11-01
Although the optimal strategy for preventing contrast-induced acute kidney injury (CI-AKI) has not yet been established, the current strategy focuses on adequate periprocedural hydration, the use of a low amount of low or iso-osmolar contrast medium, and the application of adjunctive therapies, including hemofiltration, hemodialysis and drugs. Previous trials and meta-analyses concerning the use of the adenosine antagonist theophylline have revealed contradictory results. We sought to evaluate the effect of theophylline in CI-AKI prevention in well-hydrated elderly patients with chronic kidney disease. We therefore conducted a randomized, double-blind, placebo-controlled trial involving 56 patients who had been referred for cardiac coronary angiography and/or angioplasty. 31 of these patients were randomly assigned to 200 mg theophylline IV before the procedure, and 25 to a placebo. The iso-osmolar contrast medium iodixanol was used. The primary endpoint was an increase in serum creatinine at study termination 48 h after contrast medium administration. Baseline characteristics in the placebo and theophylline groups were similar in terms of median age (75 years), estimated glomerular filtration rate (33 ± 10 vs. 33 ± 10 ml/min/1.73 m²; p = 0.87), diabetes mellitus (80 vs. 71%; p = 0.54), and amount of contrast used (94 ± 35 vs. 95 ± 38 ml; p = 0.89). There was no difference in serum creatinine at baseline (2.06 ± 0.59 vs. 2.02 ± 0.45 mg/dl; p = 0.62) or study termination (2.06 ± 0.68 vs. 2.10 ± 0.53; p = 0.79). A prophylactic effect of theophylline was not observed. The incidence of renal impairment following exposure to the contrast medium was low. This fact can be attributed to adequate parenteral hydratation and the use of the minimum amount of contrast medium necessary.
Kellum, John A; Song, Mingchen; Venkataraman, Ramesh
2004-03-01
Previous studies have shown that inflammatory mediators can be removed from the circulation with hemofiltration and that adsorption plays an important role. Because adsorptive capacity of hollow-fiber dialyzers is limited, we sought to determine whether hemoadsorption using high surface area beads would result in greater mediator removal and improved survival in experimental sepsis. Randomized controlled laboratory experiment. University laboratory. Sixty-six adult Sprague-Dawley rats. We conducted two ex vivo and two in vivo experiments. For in vivo experiments, we administered Escherichia coli endotoxin (20 mg/kg) by intravenous infusion and then randomized each animal to receive either hemoadsorption or a sham circuit for 4 hrs. Hemoadsorption was performed for 4 hrs using an arterial-venous circuit and a CytoSorb cartridge containing 10 g of polystyrene divinyl benzene copolymer beads with a biocompatible polyvinylpyrrolidone coating. Survival time was measured to a maximum of 12 hrs. In a separate set of experiments, we studied 12 animals using the same protocol except that we killed all animals at 4 hrs and removed standardized sections of liver for analysis of nuclear factor-kappaB DNA binding. Mean survival time among hemoadsorption-treated animals was 629+/-114 vs. 518+/-120 mins for sham-treated animals (p <.01). Overall survival (defined at 12 hrs) was also significantly better in the hemoadsorption group, seven of 20 vs. one of 20 (p <.05). Plasma interleukin-6 and interleukin-10 concentrations and liver nuclear factor-kappaB DNA binding were significantly reduced by hemoadsorption. Ex vivo experiments showed no endotoxin adsorption but strengthened our in vivo observations by showing rapid adsorption of tumor necrosis factor, interleukin-6, and interleukin-10. Hemoadsorption was associated with reduced inflammation and improved survival in this murine model of septic shock.
Thongprayoon, Charat; Cheungpasitporn, Wisit; Iacovella, Gina M.; Akhoundi, Abbasali; Albright, Robert C.
2017-01-01
Background Given the known deleterious effects seen with bicarbonate supplementation for acidemia, we hypothesized that utilizing high bicarbonate concentration replacement solution in continuous venovenous hemofiltration (CVVH) would be independently associated with higher mortality. Methods In a propensity score-matched historical cohort study conducted at a single tertiary care center from December 9, 2006, through December 31, 2009, a total of 287consecutive adult critically ill patients with Stage III acute kidney injury (AKI) requiring CVVH were enrolled. We excluded patients on maintenance dialysis, those who received other modalities of continuous renal replacement therapies, and patients that received a mixed of 22 and 32 mEq/L bicarbonate solution pre- and post-filter. The primary outcome was in-hospital and 90-day mortality rates. Results Among enrollees, 68 were used 32 mEq/L bicarbonate solution, and 219 received 22mEq/L bicarbonate solution for CVVH. Patients on 32 mEq/L bicarbonate solution were more often non-surgical, had lower pH and bicarbonate level but had higher blood potassium and phosphorus levels in comparison with those on 22 mEq/L bicarbonate solution. After adjustment for the baseline characteristics, the use of 32 bicarbonate solution was significantly associated with increased in-hospital (HR = 1.94; 95% CI 1.02–3.79) and 90-day mortality (HR = 1.50; 95% CI 1.03–2.14). There was a significant increase in the hospital (p = .03) and 90-day (p = .04) mortality between the 22 vs. 32 mEq/L bicarbonate solution groups following propensity matching. Conclusion Our data showed there is a strong association between using high bicarbonate solution and mortality independent of severity of illness and comorbid conditions. These findings need to be evaluated further in prospective studies. PMID:28957333
Urodilatin, a natriuretic peptide with clinical implications.
Meyer, M; Richter, R; Forssmann, W G
1998-02-21
Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also profit from URO treatment, as it increases stroke volume and PCWP. Moreover, preliminary results from recent studies indicate that URO may also be effective in patients suffering from hepato-renal syndrome.
Zhang, Jian; Li, Yi; Tao, Gui-Zhou; Chen, Yun-Dai; Hu, Tao-Hong; Cao, Xue-Bin; Jing, Quan-Min; Wang, Xiao-Zeng; Ma, Ying-Yan; Wang, Geng; Liu, Hai-Wei; Wang, Bin; Xu, Kai; Li, Jing; Deng, Jie; Han, Ya-Ling
2015-03-20
Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown. In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200-300 ml, n = 712) or (high contrast volume [HCV], ≥ 300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days. Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273). Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.
Herrera-Gutiérrez, Manuel E; Seller-Pérez, Gemma; Arias-Verdú, Dolores; Granados, Maria M; Dominguez, Juan M; Navarrete, Rocío; Morgaz, Juán; Gómez-Villamandos, Rafael
2012-10-01
Replacement therapies based on the use of convection have value for the removal of inflammatory mediators. Such therapies have been proposed for the management of septic shock, but diffusion has not proved useful in this scenario, unless high-flow membranes are used. The exact role of diffusion in these cases remains to be clarified because continuous replacement therapies are usually delivered with low-flow membranes and mixed convection-diffusion modalities. However, studies specifically addressing this problem have not been performed. Our aim was to define the efficacy of hemofiltration (convection) and hemodialysis (diffusion) in cytokine clearance and hemodynamic improvement in an experimental model of septic shock. Shock was induced in 15 beagle dogs (weight 10-15 kg) by infusion of 1 mg/kg of ultrapure Escherichia coli lipopolysaccharide diluted in 20 mL saline for 10 minutes. Five animals were followed without interventions (controls), five animals were treated with convection (100 mL kg h) for 6 hours, and five animals were treated with diffusion (100 mL kg h) for 6 hours. All subjects in the control group died during the study, whereas all treated subjects survived. Mean arterial pressure, cardiac output, systolic variability volume, systemic vascular resistances, dPMax, and pulmonary compliance improved in treated subjects. However, the differences in mean arterial pressure and cardiac output were significant only in the convection group and not in the diffusion-treated group.Tumor necrosis factor α rose equally in all groups and decreased only in treated subjects. Interleukin 6 rose in the three groups but decreased only in the convection group and remained unchanged in the control and diffusion groups. Convection and diffusion improved survival and hemodynamic parameters in a septic shock model. Improvement was more pronounced with convection, a difference that may be explained by convective clearance of cytokines.
Nguyen, A; Pozzi, M; Mastroianni, C; Léger, P; Loisance, D; Pavie, A; Leprince, P; Kirsch, M
2015-06-01
Biventricular support can be achieved using paracorporeal ventricular assist devices (p-BiVAD) or the Syncardia temporary total artificial heart (t-TAH). The purpose of the present study was to compare survival and morbidity between these devices. Data from 2 French neighboring hospitals were reviewed. Between 1996 and 2009, 148 patients (67 p-BiVADs and 81 t-TAH) underwent primary, planned biventricular support. There were 128 (86%) males aged 44±13 years. Preoperatively, p-BiVAD recipients had significantly lower systolic and diastolic blood pressures, more severe hepatic cytolysis and higher white blood cell counts than t-TAH recipients. In contrast, t-TAH patients had significantly higher rates of pre-implant ECLS and hemofiltration. Mean support duration was 79±100 days for the p-BiVAD group and 71±92 for t-TAH group (P=0.6). Forty two (63%) p-BiVAD recipients were bridged to transplantation (39, 58%) or recovery (3, 5%), whereas 51 (63%) patients underwent transplantation in the t-TAH group. Death on support was similar between groups (p-BiVAD, 26 (39%); t-TAH, 30 (37%); P=0.87). Survival while on device was not significantly different between patient groups and multivariate analysis showed that only preimplant diastolic blood pressure and alanine amino-transferase levels were significant predictors of death. Post-transplant survival in the p-BiVAD group was 76±7%, 70±8%, and 58±9% at 1, 3, and 5 years after transplantation, respectively, and was similar to that of the t-TAH group (77±6%, 72±6%, and 70±7%, P=0.60). Survival while on support and up to 5 years after heart transplantation was not significantly different in patients supported by p-BiVADs or t-TAH. Multivariate analysis revealed that survival while on transplantation was not affected by the type of device implanted.
Predictive relevance of clinical scores and inflammatory parameters in secondary peritonitis.
Zügel, Nikolaus P; Kox, Martin; Lichtwark-Aschoff, Michael; Gippner-Steppert, Cornelia; Jochum, Marianne
2011-01-01
To measure and evaluate clinical scores and various inflammation parameters for providing a better outcome assessment of patients with secondary peritonitis. Prospective study. ICU of a university and a university affiliated hospital. Fifty-six patients with severe secondary peritonitis were enrolled in this study executed within 4 years. Blood samples were taken preoperatively and 2, 6, 8, 12, 18, 24, 30, 36, 42 and 48 hours post operation, thereafter every 12th hour until day 5 respectively once daily until day 14. Etiology of peritonitis, clinical score systems (APACHE II, MOF and SOFA), and 27 mainly with activity tests or enzyme-immunoassays measurable inflammation parameters were simultaneously analyzed and stratified into lethal outcome (n = 11) or survival (n = 45), respectively. The etiological distribution of peritonitis was identical among both groups. Proportion of intraperitoneal fungi, E. coli, and bacteroids was substantially higher during the primary operation in the group with lethal outcome. With increasing significance initial and follow-up APACHE II, MOF and SOFA scores provided higher values in this group. Various plasma/serum parameters of hemostasis, leukocyte proteolytic system, acute phase reaction, cytokine system, cell adhesion, opsonization, and main organ functions showed significantly different values between both groups at the preoperative stage and/or during observation period I (day 0-4). Logistic regression analysis revealed the SOFA score and neopterin concentration as the combination with the best sensitivity (63.6%) and specificity (93.2%) for predicting the patients' survival even at the preoperative stage. For the observation period I, the combination of SOFA score and TNF receptor II showed the highest predictive sensitivity (72.7%) and specificity (95.6%). Evaluation of the severity of secondary peritonitis using a scoring system with high prognostic relevance could conceivably result in an earlier and adequate application of intensive care such as hemofiltration, administration of immunoglobulins and serial abdominal lavage to improve successful outcome.
[Continuous Veno-venous Hemofiltration in Goat Model with Crush Syndrome].
Tang, Yi; Zhang, Ling; Yang, Ying-ying; Zhao, Yu-liang; Fu, Ping
2016-01-01
Crush syndrome (CS) is a common critical condition. This study aimed to establish crush syndrome goat model through muscle injection of glycerol and test the effect of continuous veno-venous hemofiltraion (CVVH). 12 male goats at 12-15 months age were randomly assigned into control, model, and CVVH groups. After 2 weeks of normal feeding, the goats were weighed and stripped off foods for 24 h. Goats in the model and CVVH groups were then injected with 50% glycerol athind legs. Diagnosis of CS was established based on serum creatine kinase (CK) > 1 000 U/L and serum creatinine (sCr) > 2 times of standard. No intervention was given to goats in the control group. A catheter was planted to get blood access. CVVH was administered using a Prisma-flex machine, with blood flow being set at 100 mL/min and replacement fluid with predilution at 35 mL/(kg x h). After 23 h of treatment, the goats were sacrificed. Plasma and kidney samples were taken. Bloody urine hyperkalemia and decrease of urine volume were found in all of the goats injected with glycerol. Serum CK and sCr increased 1 h after the injection compared with the controls. After 23 h of CVVH treatment, serum CK and sCr decreased compared with goats in the model group. The light microscope revealed manifestation of tubular necrosis and interstitial edema, but the glomeruli were almost normal. The electronic microscope found prominent signs of cell apoptosis, such as chromatin aggregation, mitochondrial swelling, and endoplasmic reticulum expansion. Caspase12 expression in the goats with CS was significantly higher than that in the controls. The CVVH treated goats had lower level of expression than those in the model group (P < 0.05). TUNEL staining identified a higher proportion of renal cell apoptosis in the goats in the model group compared with those in the CVVH group. Muscle injection with glycerol can induce CS in goats. Early CVVH intervention improves renal function and alleviates renal tubular cell apoptosis.
[Resuscitation principles in severe acute pancreatitis complicated by multiple organ dysfunctions].
Purcaru, F; Ghelase, F; Gugilă, I; Curcă, T; Nemeş, R; Georgescu, I; Chiuţu, L; Surlin, V
1997-01-01
The first part renders very synthetically a few of the principal pathogenetical mechanisms implicated in PA, as well as general data about MODS, and then tackles therapeutical principles of great organic disfunction, the therapy of septic states and nutrition in PA. Hemodynamics dysfunction--the therapeutical objectives are correlated with the principal mechanisms implicated in cardio-vascular disfunction (the grown level of some myocardial depressive factors, the shortcoming of peripheral vascular resistance, a.s.o.). The therapeutical principles covets the volemic restoration, inotropic therapy, the correction of hydro-ionic and acido-basic disorders, the vasomotor therapy, the CID's correction, the myocardium protection against the free radicals of oxygen. The therapy is recommended to be individualized depending on the clinical data and the monitoring of some parameters (T.A, P.V.C., intrapulmonary pressure, EKG, hematocrit value, a.s.o.). Pulmonary disfunction--includes the therapy of some clinical forms of pulmonary complications, the restrictive syndrome, infections, the pulmonary shunt, the atelectasis and insists on ARDS which is a complication with vital implications. The therapy of curdling disorders--recommends blood, derivatives, antiprotease, the substitution of the consumed curdling factors, as well as the removal of the pathogenic factors which disturb the coagulation-coagulolysis equilibrium. Purge proceedings--covet the elimination from the organism of the toxic agents which generate cell-organic lesions. That's why it is moot the elimination of the pancreatic toxins before reaching the circulation (the thoracic tube draining and peritoneal lavage) as well as extrarenal purge proceedings (hemodialysis, hemofiltration and hemodiafiltration) with their benefits and limits. The sepsis and the immunotherapy--are tackled based on recent data from literature which besides antibiotherapy insists on the neutralization of various toxins and mediators by means of monoclonal and polyclonal antibodies, anti TFL antibodies, IL, a.s.o. Nutrition--is different presented, parenterally and enterally, each of them with their benefits and limits and with the recommendation to be used by means of the clinical form. There are mentioned some other additional treatments (pain removing, antagonisms of H2 receptors, inflammation and cytotoxicity inhibition, gastric decompression, a.s.o.).
Severe lactic acidosis after an iatrogenic propylene glycol overdose.
Zosel, Amy; Egelhoff, Elizabeth; Heard, Kennon
2010-02-01
Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died. Although the patient's outcome was death, his lactic acidosis was treated successfully with fomepizole and CVVH. Clinicians should be aware that an iatrogenic overdose of lorazepam may result in severe propylene glycol toxicity, which may be treated with fomepizole and CVVH.
Effect of Frequent or Extended Hemodialysis on Cardiovascular Parameters: A Meta-analysis
Susantitaphong, Paweena; Koulouridis, Ioannis; Balk, Ethan M.; Madias, Nicolaos E.; Jaber, Bertrand L.
2012-01-01
Background Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Study Design Meta-analysis. Setting & Population MEDLINE literature search (inception-April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms “short daily HD”, “daily HD”, “quotidian HD”, “frequent HD”, “intensive HD”, “nocturnal HD”, and “home HD”. Selection Criteria for Studies Single-arm cohort studies (with pre- and post-study evaluations) and randomized controlled trials examining the effect of frequent or extended HD on cardiac morphology and function, and blood pressure parameters. Studies of hemofiltration, hemodiafiltration and peritoneal dialysis were excluded. Intervention Frequent (2–8 hours,> thrice weekly) or extended (>4 hours, thrice weekly) HD as compared with conventional (≤ 4 hours, thrice weekly) HD. Outcomes Absolute changes in cardiac morphology and function, including LV mass index (LVMI) (primary), and blood pressure parameters (secondary). Results We identified 38 single-arm studies, 5 crossover trials and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (−31.2 g/m2, 95% CI, −39.8 to −22.5; P<0.001).The 3 randomized trials found a less pronounced net reduction in LVMI (−7.0 g/m2; 95% CI, −10.2 to −3.7; P<0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6 to 11.9; P=0.01). Other cardiac morphological parameters displayed similar improvements. There were also significant decreases in systolic, diastolic, and mean blood pressure, and mean number of anti-hypertensive medications. Limitations Paucity of randomized controlled trials. Conclusions Conversion from conventional to frequent or extended HD is associated with an improvement in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and in several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed. PMID:22370022
Prowle, John R; Molan, Maurice P; Hornsey, Emma; Bellomo, Rinaldo
2012-06-01
In septic patients, decreased renal perfusion is considered to play a major role in the pathogenesis of acute kidney injury. However, the accurate measurement of renal blood flow in such patients is problematic and invasive. We sought to overcome such obstacles by measuring renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. Pilot observational study. University-affiliated general adult intensive care unit. Ten adult patients with established septic acute kidney injury and 11 normal volunteers. Cine phase-contrast magnetic resonance imaging measurement of renal blood flow and cardiac output. The median age of the study patients was 62.5 yrs and eight were male. At the time of magnetic resonance imaging, eight patients were mechanically ventilated, nine were on continuous hemofiltration, and five required vasopressors. Cine phase-contrast magnetic resonance imaging examinations were carried out without complication. Median renal blood flow was 482 mL/min (range 335-1137) in septic acute kidney injury and 1260 mL/min (range 791-1750) in healthy controls (p = .003). Renal blood flow indexed to body surface area was 244 mL/min/m2 (range 165-662) in septic acute kidney injury and 525 mL/min/m2 (range 438-869) in controls (p = .004). In patients with septic acute kidney injury, median cardiac index was 3.5 L/min/m2 (range 1.6-8.7), and median renal fraction of cardiac output was only 7.1% (range 4.4-10.8). There was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury (r = .26, p = .45). Cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion during critical illness in man. Near-simultaneous accurate measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. Renal blood flow seems consistently reduced as a fraction of cardiac output in established septic acute kidney injury. Cine phase-contrast magnetic resonance imaging may be a valuable tool to further investigate renal blood flow and the effects of therapies on renal blood flow in critical illness.
Lu, Hai-Yang; Ning, Xin-Yu; Chen, Ying-Qi; Han, Shu-Jun; Chi, Ping; Zhu, Sai-Nan; Yue, Yun
2018-05-05
As a major complication after orthotopic liver transplantation (OLT), the occurrence of acute kidney injury (AKI) is frequently defined by serum creatinine (Cr); however, the accuracy of commonly used blood urea nitrogen (BUN), uric acid (UA), and β 2 -microglobulin (β 2 -MG) remains to be explored. This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation. Patients who underwent OLT in three centers between July 2003 and December 2013 were enrolled. The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and classified by stage. Measurement data were analyzed using the t-test or Wilcoxon rank-sum test; enumerated data were analyzed using the Chi-square test or Fisher's exact test. Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic (ROC) curve analysis. This study excluded 976 cases and analyzed 697 patients (578 men and 119 women); the post-OLT AKI incidence was 0.409. Compared with the no-AKI group, the AKI group showed very significant differences in Model for End-stage Liver Disease score (14.74 ± 9.91 vs. 11.07 ± 9.54, Z = 5.404; P < 0.001), hepatic encephalopathy (45 [15.8%] vs. 30 [7.3%], χ 2 = 12.699; P < 0.001), hemofiltration (28 [9.8%] vs. 0 [0.0%], χ 2 = 42.171; P < 0.001), and 28-day mortality (23 [8.1%] vs. 9 [2.2%], χ 2 = 13.323; P <0.001). Moreover, mean values of Cr, BUN, UA, and β 2 -MG in the AKI group differed significantly at postoperative days 1, 3, and 7 (all P < 0.001). ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 (sensitivity 80.1%, specificity 75.7%, cutoff value 88.23 μmol/L), 0.916 for Stage 2 (sensitivity 87.6%, specificity 82.6%, cutoff value 99.9 μmol/L), and 0.972 for Stage 3 (sensitivity 94.1%, specificity 88.2%, cutoff value 122.90 μmol/L). The sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.
Álvarez-Lerma, Francisco; Marín-Corral, Judith; Vila, Clara; Masclans, Joan Ramón; González de Molina, Francisco Javier; Martín Loeches, Ignacio; Barbadillo, Sandra; Rodríguez, Alejandro
2016-10-23
Patients infected with influenza A (H1N1)pdm09 virus requiring admission to the ICU remain an important source of mortality during the influenza season. The objective of the study was to assess the impact of a delay in diagnosis of community-acquired influenza A (H1N1)pdm09 virus infection on clinical outcome in critically ill patients admitted to the ICU. A prospective multicenter observational cohort study was based on data from the GETGAG/SEMICYUC registry (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU in which diagnosis of influenza A (H1N1)pdm09 virus infection had been established within the first week of hospitalization were included. Patients were classified into two groups according to the time at which the diagnosis was made: early (within the first 2 days of hospital admission) and late (between the 3rd and 7th day of hospital admission). Factors associated with a delay in diagnosis were assessed by logistic regression analysis. In 2059 ICU patients diagnosed with influenza A (H1N1)pdm09 virus infection within the first 7 days of hospitalization, the diagnosis was established early in 1314 (63.8 %) patients and late in the remaining 745 (36.2 %). Independent variables related to a late diagnosis were: age (odds ratio (OR) = 1.02, 95 % confidence interval (CI) 1.01-1.03, P < 0.001); first seasonal period (2009-2012) (OR = 2.08, 95 % CI 1.64-2.63, P < 0.001); days of hospital stay before ICU admission (OR = 1.26, 95 % CI 1.17-1.35, P < 0.001); mechanical ventilation (OR = 1.58, 95 % CI 1.17-2.13, P = 0.002); and continuous venovenous hemofiltration (OR = 1.54, 95 % CI 1.08-2.18, P = 0.016). The intra-ICU mortality was significantly higher among patients with late diagnosis as compared with early diagnosis (26.9 % vs 17.1 %, P < 0.001). Diagnostic delay was one independent risk factor for mortality (OR = 1.36, 95 % CI 1.03-1.81, P < 0.001). Late diagnosis of community-acquired influenza A (H1N1)pdm09 virus infection is associated with a delay in ICU admission, greater possibilities of respiratory and renal failure, and higher mortality rate. Delay in diagnosis of flu is an independent variable related to death.
Bordalo, Alvaro D B; Nobre, Angelo L; Silva, Fernanda; Serpa, Carlos; Cravino, João
2011-01-01
In spite of the strong criticism elicited thereafter, the results of a multicentric study on the consequences of several perioperative anti-hemorrhagic strategies in cardiac surgery, published five years ago, led to the aprotinin (Aprot) withdrawal from the market and its progressive replacement by tranexamic acid (TrAc) in many surgical departments. To evaluate the hemostatic effects and clinical consequences of TrAc use or non-use in off-pump coronary bypass surgery (CABG) and compare them with those of Aprot use or non-use in conventional (conv) CABG. Retrospective analysis of 2 groups (Gr) of patients (pts): GrA - 252 pts undergoing isolated conv CABG (GrA1 - 185 pts submitted to an intra-operative full-dose Aprot protocol; GrA2 - 67 pts operated without Aprot); GrB - 383 pts undergoing isolated off-pump CABG (GrB1 - 136 pts submitted to an intra-operative low-dose TrAc protocol; GrB2 - 247 pts operated in absence of TrAc). Pre-operative clinical characteristics (GrA1 vs GrA2, GrB1 vs GrB2): mean age (years) - 65 vs 64 (NS), 64 vs 64; female gender - 20% vs 21% (NS), 23% vs 20% (NS); logistic Euroscore - 5.1% vs 6.2% (NS), 6.3% vs 5.5% (NS); chronic renal failure - 21% vs 27% (NS), 27% vs 25% (NS); diffuse coronary artery disease - 34% vs 42% (NS), 36% vs 30% (NS); pre-operative betablocker treatment - 64% vs 55% (NS), 74% vs 71% (NS); statin therapy for > 3 months - 78% vs 82% (NS), 81% vs 85% (NS). Pts have been operated by 4 surgeons largely experienced in both CABG modalities. Antiplatelet therapy was stopped => 4 days prior to surgery (but aspirin was maintained in high-risk pts). Results (GrA1 vs GrA2, GrB1 vs GrB2): 1) Bleeding (mL/pt - mean): 783 vs 1375 (p < 0.001), 1061 vs 1368 (p < 0.001); blood loss > 1500 mL (%pts) - 5.4% vs 34% (p < 0.0001), 12% vs 28% (p < 0.001); surgical re-exploration for bleeding - 1.1% vs 3.0% (NS), 2.2% vs 2.0% (NS). 2) Transfusion of blood products (U/pt - mean): plasma - 0.56 vs 2.19 (p < 0.001), 1.45 vs 1.03 (p < 0.05); platelets - 0.09 vs 0.22 (p < 0.02), 0.24 vs 0.15 (NS). 3) Renal function (%pts): increased serum cre- atinine - 56% vs 56%, 55% vs 38% (p < 0.001); hemofiltration use - 1.1% vs 1.5% (NS), 1.5% vs 0.4% (NS). 4) Perioperative myocardial infarction - 21.6% vs 17.9% (NS), 17.6% vs 14.6% (NS); other ischemic events - 3.2% vs 3.0% (NS), 1.5% vs 1.2% (NS). 5) Hospital mortality: 4.8% vs 4.5% (NS), 4.4% vs 1.6% (NS). 1) TrAc does not reduce the risk of surgical re-exploration for bleeding. 2) Taking into account the differences between conv CABG and off-pump CABG, TrAc hemostatic effect seems to be inferior to that of Aprot, without offering a better safety profile in terms of lesser renal or ischemic risk as a counterpart.
Yu, Bin; Liu, Lixia; Xing, Dong; Zhao, Congcong; Hu, Zhenjie
2015-05-01
To investigate the extracorporeal clearance rate of imipenem in severe infection patients in the mode of continuous vena-venous hemofiltration (CVVH) during continuous renal replacement therapy (CRRT), in order to approach if the concentration of imipenem in plasma could achieve effective levels of anti-infection, and to explore the effect of time and anticoagulation measure on imipenem clearance during CRRT treatment. A prospective observational study was conducted. All adult severe infection patients complicating acute kidney injury (AKI) in the Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University from March 2013 to September 2014, who were prescribed imipenem as part of their required medical care, and CRRT for treatment of AKI were enrolled. 0.5 g doses of imipenem was administered intravenously every 6 hours or 8 hours according to random number table, and infused over 0.5 hour. The unfractionated heparin was used for anticoagulation in the patients without contraindications, and no anticoagulation strategy was used in the patients with high risk of bleeding. At 24 hours after first time of administration, postfilter venous blood and ultrafiltrate samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 5, 6, and 8 hours after imipenem administration. The concentration of imipenem in above samples was determined with liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS). A total of 25 patients were enrolled. Thirteen patients received imipenem intravenously every 6 hours, and 12 patients, every 8 hours. The anticoagulation was conducted with heparin in 13 cases, and 12 cases without anticoagulation. The intra-day precision, inter-day precision, matrix effect, and recovery rate in low, medium, and high concentration of plasma and ultrafiltrate, and the stability of samples under different conditions showed a good result, the error of accuracy was controlled in the range of ±15%. With the application of Prismaflex blood filtration system and AN69-M100 filter, under the mode with CVVH, the total clearance rate of imipenem was (8.874±2.828) L/h when the actual dose of replacement fluid was (31.63±1.48) mL×kg⁻¹×h⁻¹, the total CRRT clearance rate of imipenem in vitro was (2.211±0.539) L/h, which accounting for (30.1±15.7)% of the total drug clearance. In 6 hours interval dosage regimen, the percentages of the time > 4× minimum inhibitory concentration (MIC) at specific 4×MIC of 2, 4, 6, and 8 μg/mL of imipenem were more than 40% of the dosing interval. But in the 8 hours interval dosage regimen, when the level was above the 4×MIC of 4 μg/mL, maintaining time would drop below 40% of the dosing interval, with significant differences compared with that in 6 hours interval dosage regimen [4×MIC = 2 μg/mL: (60.84±20.25)% vs. (94.01±12.46)%, t = 4.977, P = 0.001; 4×MIC = 4 μg/mL: (39.85±15.88)% vs. (68.74±9.57)%, t = 5.562, P = 0.000; 4×MIC = 6 g/mL: (27.58±13.70)% vs. (53.97±8.36)%, t = 5.867, P = 0.000; 4×MIC = 8 μg/mL: ( 8.87±12.43)% vs. (43.48±7.83)%, t = 5.976, P = 0.000]. No significant change in sieving coefficient of imipenem was found within a short time (6 hours), which indicated that there was no effect of anticoagulation on clearance of imipenem by AN69-M100 filter, and no statistical significance was found with repeated measure analysis (F = 0.186, P > 0.05 ). The clearance rate of imipenem is increased significantly in vitro under the mode of CVVH with the actual dose of replacement fluid was (31.63±1.48) mL×kg⁻¹×h⁻¹ in severe infective patients with severe sepsis complicating AKI, affecting the level of plasma drug concentration, need to adjust the dosage regimen. When the time of the dosing interval was shortened, the concentration of imipenem in patients' plasma could be increased significantly. In a short period of time, the sieving coefficient of imipenem through AN69 filter is not affected by anticoagulation measures and time cleaning efficiency will not decline.
Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis
2007-01-01
Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients. PMID:18058085
Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui
2013-02-01
To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) <150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are >180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.
Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui
2013-02-01
To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.