Polymyxin-B immobilized column-direct hemoperfusion for adolescent toxic shock syndrome.

PubMed

Nanishi, Etsuro; Hirata, Yuichirou; Lee, Sooyoung; Kaku, Noriyuki; Momii, Kenta; Kubota, Kensuke; Nishio, Hisanori; Maehara, Yoshihiko; Hara, Toshiro

2016-10-01

Toxic shock syndrome (TSS) is a critical illness associated with toxin from Staphylococcus aureus. Despite recent advances in critical care, mortality remains high and additional effective therapy is required. We report an adolescent case of TSS successfully treated with direct hemoperfusion using polymyxin-B immobilized fiber (PMX-DHP). The patient with spina bifida also had ischial pressure ulcer, and developed TSS associated with methicillin-resistant S. aureus. Despite conventional treatment, the patient developed refractory shock, which was immediately improved with PMX-DHP. PMX-DHP has been widely used for the treatment of sepsis to remove circulating endotoxins produced by Gram-negative bacteria, but beneficial effects have also been reported for Gram-positive bacterial infection. To our knowledge, this is the first report on PMX-DHP for TSS in an adolescent patient, and we propose that PMX-DHP could be a new treatment strategy for severe TSS in children as well. © 2016 Japan Pediatric Society.

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.

PubMed

Schädler, Dirk; Pausch, Christine; Heise, Daniel; Meier-Hellmann, Andreas; Brederlau, Jörg; Weiler, Norbert; Marx, Gernot; Putensen, Christian; Spies, Claudia; Jörres, Achim; Quintel, Michael; Engel, Christoph; Kellum, John A; Kuhlmann, Martin K

2017-01-01

We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Curative effect of neutral macroporous resin hemoperfusion on treating hemodialysis patients with refractory uremic pruritus.

PubMed

Li, Wen-Hong; Yin, Yu-Min; Chen, Hao; Wang, Xiao-Dan; Yun, He; Li, Hui; Luo, Jie; Wang, Jin-Wen

2017-03-01

This study aims to investigate the efficacy and safety of neutral macroporous resin hemoperfusion in treating maintenance hemodialysis (MHD) patients with refractory uremic pruritus (RUP).Ninety patients were enrolled and were randomly divided into 3 groups: control group, experiment 1 group, and experiment 2 group. Clinical symptom scores of skin itching were recorded before and at 4 and 8 weeks after the treatment. In addition, serum parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and C-reactive protein (CRP) were detected; and the calcium-phosphorus product ([Ca] × [P]) was calculated to compare the curative effect.VSA score, modified Duo pruritus score, and CRP: these indices decreased to some extent at 4 and 8 weeks after treatment in the 2 experiment groups, compared with pretreatment (P < 0.05); and differences among these 3 groups were statistically significant (P < 0.05). PTH, P, and [Ca] × [P]: these indices decreased to some extent at 4 and 8 weeks after treatment in the 2 experiment groups, compared with pretreatment (P < 0.05); and differences between the control and experiment 1 groups, as well as between the control and experiment 2 groups, were statistically significant (P < 0.05). However, the difference between the experiment 1 and experiment 2 groups were not statistically significant (P < 0.05).The effects of HA330 and HA130 resin hemoperfusion apparatus on secondary hyperparathyroidism and the disorder of calcium and phosphorus metabolism are similar. The mechanism may be related to its strong adsorption effect, and its capacity to widely remove inflammatory mediators, immune mediators, and endotoxins.

Curative effect of neutral macroporous resin hemoperfusion on treating hemodialysis patients with refractory uremic pruritus

PubMed Central

Li, Wen-Hong; Yin, Yu-Min; Chen, Hao; Wang, Xiao-Dan; Yun, He; Li, Hui; Luo, Jie; Wang, Jin-Wen

2017-01-01

Abstract This study aims to investigate the efficacy and safety of neutral macroporous resin hemoperfusion in treating maintenance hemodialysis (MHD) patients with refractory uremic pruritus (RUP). Ninety patients were enrolled and were randomly divided into 3 groups: control group, experiment 1 group, and experiment 2 group. Clinical symptom scores of skin itching were recorded before and at 4 and 8 weeks after the treatment. In addition, serum parathyroid hormone (PTH), calcium (Ca2+), phosphorus (P3+), and C-reactive protein (CRP) were detected; and the calcium–phosphorus product ([Ca] × [P]) was calculated to compare the curative effect. VSA score, modified Duo pruritus score, and CRP: these indices decreased to some extent at 4 and 8 weeks after treatment in the 2 experiment groups, compared with pretreatment (P < 0.05); and differences among these 3 groups were statistically significant (P < 0.05). PTH, P3+, and [Ca] × [P]: these indices decreased to some extent at 4 and 8 weeks after treatment in the 2 experiment groups, compared with pretreatment (P < 0.05); and differences between the control and experiment 1 groups, as well as between the control and experiment 2 groups, were statistically significant (P < 0.05). However, the difference between the experiment 1 and experiment 2 groups were not statistically significant (P < 0.05). The effects of HA330 and HA130 resin hemoperfusion apparatus on secondary hyperparathyroidism and the disorder of calcium and phosphorus metabolism are similar. The mechanism may be related to its strong adsorption effect, and its capacity to widely remove inflammatory mediators, immune mediators, and endotoxins. PMID:28328802

Biocompatibility and Cytotoxic Evaluation of New Sorbent Cartridges for Blood Hemoperfusion.

PubMed

Pomarè Montin, Diego; Ankawi, Ghada; Lorenzin, Anna; Neri, Mauro; Caprara, Carlotta; Ronco, Claudio

2018-06-08

The use of adsorption cartridges for hemoperfusion (HP) is rapidly evolving. For these devices, the potential induced cytotoxicity is an important issue. The aim of this study was to investigate potential in vitro cytotoxic effects of different sorbent cartridges, HA130, HA230, HA330, HA380 (Jafron, China), on U937 monocytes. Monocytes were exposed to the sorbent material in static and dynamic manners. In static test, cell medium samples were collected after 24 h of incubation in the cartridges. In dynamic test, HP modality has been carried out and samples at 30, 60, 90, and 120 min were collected. Compared to control samples, there was no evidence of increased necrosis or apoptosis in monocytes exposed to the cartridges both in the static and dynamic tests. Our in vitro testing suggests that HA cartridges carry an optimal level of biocompatibility and their use in HP is not associated with adverse reactions or signs of cytotoxicity. © 2018 S. Karger AG, Basel.

Polymyxin-B-immobilized-fiber column hemoperfusion with oseltamivir treatment for ARDS due to influenza H1N1/09.

PubMed

Binh, Nguyen Gia; Manabe, Toshie; Co, Dao Xuan; Tuan, Nguyen Dang; Thach, Pham The; Kudo, Koichiro

2015-06-01

Acute respiratory distress syndrome (ARDS) is one of the severe complications of influenza H1N1/09 infection, resulting in high mortality. Effective treatment strategies for ARDS are needed. This report presents two cases of ARDS due to influenza in Vietnam. Both cases were similar in terms of starting symptoms, the rapid progression to ARDS, and the treatment strategy, direct hemoperfusion with a polymyxin-B-immobilized fiber column (PMX-DHP) and oseltamivir. However, the clinical course of disease and the outcomes were different. For case 1, treatment was initiated on day 4 following the onset of hypoxemia due to ARDS. Symptoms improved rapidly after treatment and the patient was discharged on day 12. For case 2, treatment was initiated on day 9 after the onset of symptoms. Despite intensive therapy, the patient died on day 18. In conclusion, treatment with PMX-DHP and oseltamivir is effective on ARDS due to influenza but only if initiated early.

Sequential use of hemoperfusion and single-pass albumin dialysis can safely reverse methotrexate nephrotoxicity.

PubMed

Chan, Winnie Kwai Yu; Hui, Wun Fung

2016-10-01

High-dose methotrexate therapy (HDMTX) is a common form of chemotherapy used in children with high-grade malignancy such as osteosarcoma. Treatment with HDMTX requires careful monitoring of drug levels with folinic acid (leucovorin) rescue therapy. Toxicity from methotrexate is not uncommon and sometimes causes significant morbidity and mortality. We report an 11-year-old child whose 24-h post-HDMTX serum level was 651.8 μmol/L (recommended level <20 μmol/L), which was complicated by septic shock and progressive renal and liver failure. As carboxypeptidase (glucarpidase) was not available locally, she was treated with the sequential use of charcoal hemoperfusion (CHP) and single-pass albumin dialysis (SPAD). The patient recovered without complications. Both liver and renal function recovered with no significant late sequelae. CHP and SPAD are effective extracorporeal methods of removing methotrexate. They provide alternative treatment options for critical care nephrologists in the management of methotrexate toxicity.

A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia.

PubMed

Itai, Junji; Ohshimo, Shinichiro; Kida, Yoshiko; Ota, Kohei; Iwasaki, Yasumasa; Hirohashi, Nobuyuki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki; Tanigawa, Koichi

2015-01-05

Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.

21 CFR 876.5870 - Sorbent hemoperfusion system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... extracorporeal blood system. The device is used in the treatment of poisoning, drug overdose, hepatic coma, or... the treatment of poisoning and drug overdose. The special controls for this device are: (i) The device... electrical components, appropriate analysis and testing must be conducted to verify electrical safety and...

78 FR 25747 - Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-02

... committee information line to learn about possible modifications before coming to the meeting. Agenda: On... extracorporeal blood system. Sorbent hemoperfusion systems may also include the machine or instrument used to... from the patient, delivery to a hemodialysis machine for filtering, and return of filtered blood to the...

77 FR 9610 - Gastroenterology-Urology Devices; Reclassification of Sorbent Hemoperfusion Devices for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

..., substances. and drugs (e.g., adsorption of glucose, unspecific removal characteristics, drop in patients... Sec. 860.130 of the regulations. XIV. Environmental Impact The Agency has determined under 21 CFR 25... impact statement is required. XV. Analysis of Impacts FDA has examined the impacts of the proposed rule...

Influence of combination hemodialysis/hemoperfusion against score of depression in regular hemodialysis patients

NASA Astrophysics Data System (ADS)

Permatasari, T. D.; Thamrin, A.; Hanum, H.

2018-03-01

Patients with chronic kidney disease, have a higher risk for psychological distress such as anxiety, depression and cognitive decline. Combination of Hemodialysis (HD)/hemoperfusion (HP) regularly able to eliminate uremic toxin with mild-to-large molecular weight better. HD/HP can remove metabolites, toxin, and pathogenic factors and regulate the water, electrolyte and acid-base balance to improve the quality of patient’s sleep and appetite also reduces itching of the skin, which in turn improve the quality and life expectancy. This research was a cross sectional research with a pre-experimental design conducted from July to September 2015 with 17 regular hemodialysis patients as samples. Inclusion criteria were regular hemodialysis patients and willingly participated in the research. The assessmentwas conducted using BDI to assess depression. To obtained the results, data were analyzed using T-Test and showed that that the average BDI score before the combination of HD/HP 18.59±9 to 8.18±2.83 after the combination (p<0.001). In conclusion, combination HD/HP can lower depression scores in patients with regular HD.

Bilirubin and bile acids removal by haemoperfusion through synthetic resin "Persorb".

PubMed

Filip, K; Malý, J; Horký, J; Tlustáková, M; Kálal, J; Vrána, M

1990-01-01

A new type of styrene-divinylbenzene copolymer coated with polyhema was tested for biocompatibility and ability to remove bile acid, bilirubin, phenols and cholesterol in dogs with surgically induced biliary obstruction. After 4-hr hemoperfusion through a polypropylene column containing 325 g of resin, performed 7-10 days after the ligature of the cystic and common bile duct, the serum levels of bile acids, bilirubin, phenols and cholesterol decreased by 60.9 +/- 30.3% (p less than 0.001), 34.8 +/- 12.2% (p less than 0.001), 19.4 +/- 15.6% (p less than 0.001) and 15.3 +/- 4.2% (p less than 0.05), respectively. The procedure was well tolerated, no bleeding or other adverse reactions occurred. The average platelet count decreased by 19.4 +/- 15.6% (p less than 0.05). Hemoperfusion through the Czechoslovak resin coated with polyhema is safe and efficient for removal of bile acids and other protein-bound and lipid-soluble substances which accumulate in cholestatic syndromes and hepatic failure. Thus, it may play an important role in the treatment of such events as a method of artificial liver support.

Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

PubMed

Saito, Nobuyuki; Sugiyama, Kazuhiro; Ohnuma, Testu; Kanemura, Takashi; Nasu, Michitaka; Yoshidomi, Yuya; Tsujimoto, Yuta; Adachi, Hiroshi; Koami, Hiroyuki; Tochiki, Aito; Hori, Kota; Wagatsuma, Yukiko; Matsumoto, Hisashi

2017-01-01

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).

Hemoperfusion in the treatment of acute clozapine intoxication in China.

PubMed

He, Jia-Li; Xiang, Yu-Tao; Li, Wen-Biao; Cai, Zhuo-Ji; Ungvari, Gabor Sandor

2007-12-01

No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP). In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered. One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP. A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.

Clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning and prognosis analysis after rescue.

PubMed

Dong, Hui; Weng, Yi-Bing; Zhen, Gen-Shen; Li, Feng-Jie; Jin, Ai-Chun; Liu, Jie

2017-06-01

This study reports the clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning, and analyzes the prognosis after rescue.The general data of 68 patients with severe organophosphorus poisoning treated in our hospital were retrospectively analyzed. These patients were divided into 2 groups: treatment group, and control group. Patients in the control group received routine emergency treatment, while patients in the treatment group additionally received hemoperfusion plus hemodialysis on the basis of routine emergency treatment. The curative effects in these 2 groups and the prognosis after rescue were compared.Compared with the control group, atropinization time, recovery time of cholinesterase activity, recovery time of consciousness, extubation time, and length of hospital stay were shorter (P < .05); the total usage of atropine was significantly lower (P < .05); Glasgow Coma Score was significantly higher (P < .05); acute physiology and chronic health score (APACHE II) was significantly lower (P < .05); and mortality and poisoning rebound rate was significantly lower (P < .05) in the treatment group.Hemoperfusion and hemodialysis on the basis of routine emergency treatment for critical patients with organophosphorus poisoning can improve rescue outcomes and improve the prognosis of patients, which should be popularized.

Some results of hemosorption columns development and usage in Czechoslovakia.

PubMed

Kálal, J; Tlustáková, M

Hemoperfusion columns packed with active charcoal and a synthetic resin have been manufactured in Czechoslovakia since 1983. In both cases the sorption packings are coated with a layer of poly(2-hydroxyethyl methacrylate). The columns are manufactured in two sizes: for adults (800 ml) and for children (400 ml). The manufacturer is OPS Kolín: the number of columns manufactured so far is 3400.

[Comparison study on adsorption of middle molecular substances with multiwalled carbon nanotubes and activated carbon].

PubMed

Li, Guifeng; Wan, Jianxin; Huang, Xiangqian; Zeng, Qiao; Tang, Jing

2011-08-01

In recent years, multi-walled carbon nanotubes (MWCTs) are very favorable to the adsorption of middle molecular substances in the hemoperfusion because of their multiporous structure, large surface area and high reactivity, which are beneficial to the excellent absorption properties. The purpose of this study was to study the MWCTs on the adsorption capacity of the middle molecular substances. Vitamin B12 (VB12) was selected as a model of the middle molecular substances. The morphologies of MWCTs and activated carbon from commercial "carbon kidney" were observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The adsorption behavior of VB12 was compared to each other with UV-visible absorption spectra. The MWCTs formed a sophistaicate gap structure, and compared to the activated carbon, MWCTs had a larger surface area. By Langmuir equation and Freundlich equation fitting analysis, VB12 adsorption on MWCTs is fit for multi-molecular layer adsorption, and the adsorption type of activated carbon is more inclined to the model corresponding to Langmuir monolayer adsorption. The adsorption rate of MWCTs is faster than that of the activated carbon and the adsorption capacity is greater, which could be expected to become the new adsorbent in the hemoperfusion.

A Novel Perfusion System for Damage Control of Hyperkalemia in Swine (Sus scrofa)

DTIC Science & Technology

2018-03-20

randomized to the control or treatment group . In both groups , blood was pumped through an extracorporeal circuit (EC) with an in-line hemodialyzer. In...Results:Serum potassium concentration was significantly lower in the treatment than in the control group over time (P = 0.02). There was no difference...environments. We hypothesized that a simplified hemoperfusion system could control serum potassium concentration in a swine model of acute

A Novel Perfusion System for Damage Control of Hyperkalemia in Swine (Sus scrofa)

DTIC Science & Technology

2018-03-20

randomized to the control or treatment group . In both groups , blood was pumped through an extracorporeal circuit (EC) with an in-line hemodialyzer. In...Results: Serum potassium concentration was significantly lower in the treatment than in the control group over time (P = 0.02). There was no...austere environments. We hypothesized that a simplified hemoperfusion system could control serum potassium concentration in a swine model of acute

Clearance Rate and BP-ANN Model in Paraquat Poisoned Patients Treated with Hemoperfusion

PubMed Central

Hu, Lufeng; Hong, Guangliang; Ma, Jianshe; Wang, Xianqin; Lin, Guanyang; Zhang, Xiuhua; Lu, Zhongqiu

2015-01-01

In order to investigate the effect of hemoperfusion (HP) on the clearance rate of paraquat (PQ) and develop a clearance model, 41 PQ-poisoned patients who acquired acute PQ intoxication received HP treatment. PQ concentrations were determined by high performance liquid chromatography (HPLC). According to initial PQ concentration, study subjects were divided into two groups: Low-PQ group (0.05–1.0 μg/mL) and High-PQ group (1.0–10 μg/mL). After initial HP treatment, PQ concentrations decreased in both groups. However, in the High-PQ group, PQ levels remained in excess of 0.05 μg/mL and increased when the second HP treatment was initiated. Based on the PQ concentrations before and after HP treatment, the mean clearance rate of PQ calculated was 73 ± 15%. We also established a backpropagation artificial neural network (BP-ANN) model, which set PQ concentrations before HP treatment as input data and after HP treatment as output data. When it is used to predict PQ concentration after HP treatment, high prediction accuracy (R = 0.9977) can be obtained in this model. In conclusion, HP is an effective way to clear PQ from the blood, and the PQ concentration after HP treatment can be predicted by BP-ANN model. PMID:25695058

A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney.

PubMed

Kuan, Kean Guan; Wee, Mau Nam; Chung, Wen Yuan; Kumar, Rohan; Mees, Soeren Torge; Dennison, Ashley; Maddern, Guy; Trochsler, Markus

2017-05-01

Normothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ. Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters. The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid-base environment in this small series. In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid-base environment. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Nanofibrous polymeric beads from aramid fibers for efficient bilirubin removal.

PubMed

Peng, Zihang; Yang, Ye; Luo, Jiyue; Nie, Chuanxiong; Ma, Lang; Cheng, Chong; Zhao, Changsheng

2016-08-16

Polymer based hemoperfusion has been developed as an effective therapy to remove the extra bilirubin from patients. However, the currently applied materials suffer from either low removal efficiency or poor blood compatibility. In this study, we report the development of a new class of nanofibrous absorbent that exhibited high bilirubin removal efficiency and good blood compatibility. The Kevlar nanofiber was prepared by dissolving micron-sized Kevlar fiber in proper solvent, and the beads were prepared by dropping Kevlar nanofiber solutions into ethanol. Owing to the nanofiborous structure of the Kevlar nanofiber, the beads displayed porous structures and large specific areas, which would facilitate the adsorption of toxins. In the adsorption test, it was noticed that the beads possessed an adsorption capacity higher than 40 mg g(-1) towards bilirubin. In plasma mimetic solutions, the beads still showed high bilirubin removal efficiency. Furthermore, after incorporating with carbon nanotubes, the beads were found to have increased adsorption capacity for human degradation waste. Moreover, the beads showed excellent blood compatibility in terms of a low hemolysis ratio, prolonged clotting times, suppressed coagulant activation, limited platelet activation, and inhibited blood related inflammatory activation. Additionally, the beads showed good compatibility with endothelial cells. In general, the Kevlar nanofiber beads, which integrated with high adsorption capacity, good blood compatibility and low cytotoxicity, may have great potential for hemoperfusion and some other applications in biomedical fields.

Evaluation of vibrated fluidized bed techniques in coating hemosorbents.

PubMed

Morley, D B

1991-06-01

A coating technique employing a vibrated fluidized bed was used to apply an ultrathin (2 microns) cellulose nitrate coating to synthetic bead activated charcoal. In vitro characteristics of the resulting coated sorbent, including permeability to model small and middle molecules, and mechanical integrity, were evaluated to determine the suitability of the process in coating granular sorbents used in hemoperfusion. Initial tests suggest the VFB-applied CN coating is both highly uniform and tightly adherent and warrants further investigation as a hemosorbent coating.

Polymyxin B-immobilized fiber column hemoperfusion removes endotoxin throughout a 24-hour treatment period.

PubMed

Mitaka, Chieko; Fujiwara, Naoto; Yamamoto, Mamoru; Toyofuku, Takahiro; Haraguchi, Go; Tomita, Makoto

2014-10-01

The purpose of this study was to evaluate the extent of endotoxin adsorption by polymyxin B-immobilized fiber column hemoperfusion (PMX) performed for a 24-hour treatment period in patients with septic shock. Nineteen patients with septic shock were retrospectively studied. The plasma endotoxin concentrations of blood drawn from the radial artery and from the outlet circuit of the PMX column were measured by kinetic turbidimetric limulus assay using an MT-358 Toxinometer (Wako Pure Chemical Industries, Ltd, Osaka, Japan) after 24 hours of PMX treatment. The endotoxin removal rate was defined by the following equation: ([radial artery endotoxin concentration - outlet circuit of PMX column endotoxin concentration]/radial artery endotoxin concentration) × 100%. The patients had a median Acute Physiology and Chronic Health Evaluation II score of 29 at intensive care unit admission and a 28-day mortality of 47%. Before the start of the PMX treatment, the median radial arterial plasma endotoxin concentration was 16.48 pg/mL. After 24 hours of PMX treatment, the median radial plasma endotoxin concentration had decreased to 1.857 pg/mL, and the concentration at the outlet circuit of the PMX column was further decreased to 0.779 pg/mL. The median endotoxin removal rate was 74.4%. These findings suggest that 24-hour PMX treatment was effective in removing endotoxin continuously throughout the entire treatment period. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of resin adsorbents for blood purification at Nankai University in China.

PubMed

Wang, Yong-Jian; Yu, Yao-Ting

2011-04-01

Various types of porous resin adsorbents based on polystyrene, agarose, and cellulose as matrixes coupling with DNA, amino acids and other biological active molecules as ligands were extensively studied in China. Molecular recognition between the ligand and pathogenic molecule was investigated. Several commercialized products are now widely used in hospitals all over China. Whole blood hemoperfusion is used to treat patients suffering from autoimmune diseases, uremia acute intoxication, and hyperbilirubinemia. Clinical performances of hundreds and thousands of patients treated by whole blood sorption therapy show that the therapy is safe, efficient, and cost-effective.

Effects of hemoperfusion and continuous renal replacement therapy on patient survival following paraquat poisoning.

PubMed

Wang, Yadong; Chen, Yao; Mao, Lu; Zhao, Guangju; Hong, Guangliang; Li, Mengfang; Wu, Bin; Chen, Xiaorong; Tan, Meng; Wang, Na; Lu, Zhongqiu

2017-01-01

Mortality in patients with paraquat (PQ) poisoning is related to plasma PQ levels. Concentrations lower than 5,000 ng/mL are considered critical but curable. This study assessed the effects of hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the survival of PQ-poisoned patients with plasma PQ levels below 5,000ng/mL. We analyzed the records of 164 patients with PQ poisoning who were treated at the First Affiliated Hospital of Wenzhou Medical University in China between January 2011 and May 2015. We divided these patients into six sub-groups based on baseline plasma PQ levels and treatment, compared their clinical characteristics, and analyzed their survival rates. Patient sub-groups did not differ in terms of age, sex, time between poisoning and hospital admission, or time to first gavage. Biochemical indicators improved over time in all sub-groups following treatment, and the combined HP and CRRT treatment yielded better results than HP or CRRT alone. Fatality rates in the three treatment sub-groups did not differ among patients with baseline plasma PQ levels of 50-1,000 ng/mL, but in patients with 1,000-5,000 ng/mL levels, the mortality rate was 59.2% (HP treatment group), 48% (CRRT treatment group), and 37.9% (combined treatment group). Mortality rates were higher 10-30 days after hospitalization than in the first 10 days after admission. In the early stages of PQ poisoning, CRRT is effective in reducing patient fatality rates, particularly when combined with HP. Our data could be useful in increasing survival in acute PQ poisoning patients.

Clinical preparedness for severe pneumonia with highly pathogenic avian influenza A (H5N1): experiences with cases in Vietnam.

PubMed

Kudo, Koichiro; Binh, Nguyen Gia; Manabe, Toshie; Co, Dao Xuan; Tuan, Nguyen Dang; Izumi, Shinyu; Takasaki, Jin; Minh, Dang Hung; Thuy, Pham Thi Phuong; Van, Vu Thi Tuong; Hanh, Tran Thuy; Chau, Ngo Quy

2012-12-01

Avian influenza A (H5N1) in human presents a global pandemic threat, and preparedness is urgently required in high-risk countries. A retrospective chart review was conducted on 8 patients with H5N1 infection (aged 2-30 years; 3 fatal) who were hospitalized in Bach Mai Hospital (BMH), Vietnam, or in affiliated hospitals with consultation by physicians in BMH between 2007 and 2010. Demographic background, chest radiographs, and clinical and laboratory data were evaluated to determine the critical issues in relation to clinical outcomes. Treatment of 4 patients with acute respiratory distress syndrome (ARDS) (2 fatal) was assessed for renal replacement therapy using continuous hemodiafiltration (CHDF), polymyxin B-immobilized (PMX) hemoperfusion, or their combination. Patients had direct contact with dead/sick poultry infected with H5N1 virus or lived in areas where H5N1 poultry outbreaks had been reported at the same time as their illness. Time to initiation of oseltamivir from symptom onset was 2-6 days for survivors and 7-9 days for non-survivors. All patients except one had infiltrative shadows on chest radiographs on admission. Patients with delayed treatment developed ARDS. Renal replacement therapy contributed to patient survival, with improvement of oxygenation and a dramatic decrease in serum cytokine levels if initiated earlier. Understanding local H5N1 poultry outbreaks and chest radiography assist early diagnosis and initiation of antiviral treatment. Developing a network among local and tertiary care hospitals can reduce the time to initiation of treatment. CHDF and PMX hemoperfusion are possible candidates for effective treatment of ARDS with H5N1 if applied earlier. Copyright © 2012 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Study on the treatment of acute thallium poisoning.

PubMed

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.

Life-threatening urethral hemorrhage after placement of a Foley catheter in a patient with uroseptic disseminated intravascular coagulation due to chronic urinary retention induced by untreated benign prostatic hyperplasia.

PubMed

Ikegami, Yukihiro; Yoshida, Keisuke; Imaizumi, Tsuyoshi; Isosu, Tsuyoshi; Kurosawa, Shin; Murakawa, Masahiro

2016-10-01

A 77-year-old man with severe septic disseminated intravascular coagulation following urinary infection was transported to our hospital. He had developed urinary retention induced by untreated prostatic hyperplasia. Immediate drainage with a Foley catheter was successfully carried out, but the hematuria progressed to life-threatening hemorrhage. Complete hemostasis was impossible by surgical treatment because the tissue around the prostatic urethra was very fragile and hemorrhagic. Organized treatments (continuous hemodiafiltration combined with polymyxin-B immobilized fiber column hemoperfusion and systemic treatment with antibiotics and coagulation factors) were commenced soon after the operation. The patient eventually recovered from the septic disseminated intravascular coagulation. This case report illustrates the risk of placement of Foley catheters in patients with severe septic disseminated intravascular coagulation.

Evaluation of efficacy of resin hemoperfusion in patients with acute 2,4-dinitrophenol poisoning by dynamic monitoring of plasma toxin concentration.

PubMed

Zhao, Xue-hong; Jiang, Jiu-kun; Lu, Yuan-qiang

2015-08-01

The intoxications caused by 2,4-dinitrophenol (2,4-DNP), even death, have been frequently reported in recent years. This study aims to investigate the dynamic changes of plasma toxin concentration and explore the clinical value of resin hemoperfusion (HP) in the treatment of patients with acute 2,4-DNP poisoning. We reported 16 cases of acute 2,4-DNP poisoning through occupational exposure due to ignoring the risk of poisoning. The blood samples were collected from the 14 survivors. According to the different treatments of resin HP, the survivors were divided into routine HP (n=5) and intensive HP (n=9) groups. Ultra high performance liquid chromatography/ tandem mass spectroscopy (UPLC-MS/MS) was used to detect the 2,4-DNP concentration in plasma in this study. The 14 survivors recovered very well after treatment. The initial plasma 2,4-DNP concentrations (C1) of survivors ranged from 0.25 to 41.88 µg/ml (mean (12.56±13.93) µg/ml). A positive correlation existed between initial plasma 2,4-DNP concentration (C1) and temperature. The elimination of 2,4-DNP was slow and persistent, and the total clearance rates of plasma toxin from the 1st to 3rd day (R3), the 3rd to 7th day (R3-7), and the 1st to 7th day (R7), were only (53.03±14.04)%, (55.25±10.50)%, and (78.29±10.22)%, respectively. The plasma toxin was cleared up to 25 d after poisoning in most of the patients. The R3, R3-7, and R7 in the intensive HP group were all apparently higher than those in the routine HP group, with statistical significance (P<0.05). Simultaneously, the elimination half-life (t1/2) of 2,4-DNP in the intensive HP group was apparently shorter than that in the routine HP group, with statistical significance (P<0.05). The clinicians should be aware of this slow and persistent process in the elimination of plasma 2,4-DNP. Higher initial plasma toxin concentration resulted in a more severe fever for the patient. According to the limited data, longer and more frequent resin HP may accelerate to eliminate the poison.

[Combination of hemodialysis and hemofiltration in severe caffeine intoxication].

PubMed

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.

Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review.

PubMed

Honore, Patrick M; Jacobs, Rita; Joannes-Boyau, Olivier; De Regt, Jouke; De Waele, Elisabeth; van Gorp, Viola; Boer, Willem; Verfaillie, Lies; Spapen, Herbert D

2013-01-01

In recent years, after all the attention has been focused on the dose for continuous renal replacement therapy (CRRT) in sepsis and systemic inflammation response syndrome (SIRS), the relatively negative results of all those studies did urge our expectations on new approaches regarding CRRT in sepsis and SIRS. So far, after the failure of the major randomized studies on dose, attention is now drawn to new membranes that could better eliminate massive amounts of unbound mediators in wider spectrum and also in greater magnitude Nevertheless, for septic acute kidney injury, the recommended dose will remain 35 ml/kg/h until the IVOIRE (hIgh VOlume in Intensive Care) study will be published. In this new armamentarium, we have distinguished the first tools that can still be called membranes ranging from AN69 Surface Treated (ST), SEPTEX, polymethylmetacrylate, to Oxiris that can still run with a CRRT device. Polymyxin B is still a kind of membrane although it has a larger surface, but it can run in a hemoperfusion system and is also much more selective. Adsorptive columns and sorbents are not anymore membranes but are seen as cartridges as the surface is extremely huge when compared with that of membranes (more than 500 m). They can still run in a hemoperfusion device. At the very end, we do have apheresis or selective plasma exchange (also very close to sorbents and columns) but we have very few data up to now regarding sepsis. Regarding spectrum, CytoSorb seems to be very promising although it is not able to capture endotoxin and IL-10. Oxiris is also promising as it can capture endotoxin and cytokines. AN69 ST is very powerful to capture numerous cytokines and especially high-mobility group box 1 protein (a very upstream cytokine). Polymethylmetacrylate has also the power to capture endotoxin and numerous other cytokines probably with a larger magnitude than Oxiris although this is not proven. Lastly, high-porosity membranes (Septex) may play a role especially when used in continuous venovenous hemodialysis mode. At the end, if we look for a more enlarged spectrum and a higher magnitude, CytoSorb might be seen as the most promising although not having the ability to fix endotoxin. Future studies will tell us which membrane or sorbent will be most useful in the adjunctive treatment for sepsis.

In vitro comparison of the adsorption of inflammatory mediators by blood purification devices.

PubMed

Malard, Benjamin; Lambert, Corine; Kellum, John A

2018-05-04

Septic shock, a leading cause of acute kidney injury, induces release of pro-/anti-inflammatory mediators, leading to increased mortality and poor renal recovery. This is the first in vitro study directly comparing three single-use blood purification devices in terms of removing sepsis-associated mediators and endotoxins. In vitro hemoperfusion was performed using oXiris ® , CytoSorb ® , and Toraymyxin ® . Heparinized human plasma from healthy volunteers was pre-incubated with pathologic quantities of inflammatory mediators and filtered in a closed-loop circulation model for 2 h. For each device, the removal of 27 inflammatory mediators was measured over time. Endotoxin removal mediated by oXiris and Toraymyxin was assessed using hemoperfusion over 6 h. Endotoxin (lipopolysaccharide) removal was most rapid with Toraymyxin; mean adsorptive clearance over the first 30 min was ~ 20 ml/min vs ~ 8 ml/min with oXiris (p < 0.05). There was minimal endotoxin removal with CytoSorb (1 ml/min). At 120 min, there was no significant difference between the endotoxin removal rates using oXiris (mean ± standard deviation, 68.0 ± 4.4%) and Toraymyxin (83.4 ± 3.8%); both were significantly higher vs CytoSorb (- 6.3 ± 4.9%; p < 0.05). Total removal with oXiris was 6.9 μg vs 9.7 μg for Toraymyxin, where the total lipopolysaccharide quantity introduced was approximately 15.8 μg. Removal rates of pro-/anti-inflammatory cytokines and other inflammatory mediators were similar between oXiris and CytoSorb and were higher with CytoSorb and oXiris vs Toraymyxin. Granulocyte colony-stimulating factor was only effectively adsorbed by CytoSorb (99.4%). Differences were detected between the adsorption mechanism of the devices; binding to oXiris was mainly ionic, while CytoSorb was hydrophobic. No specific protein adsorption was found qualitatively with Toraymyxin. Adsorption rate kinetics varied for individual inflammatory mediators using the three blood purification devices. Mechanisms of adsorption differed between the devices. oXiris was the only device tested that showed both endotoxin and cytokine removal. oXiris showed similar endotoxin adsorption to Toraymyxin and similar adsorption to CytoSorb for the removal of other inflammatory mediators. Differences in device removal capacities could enable treatment to be more tailored to patients.

Evaluation of Delcath Systems' Generation 2 (GEN 2) melphalan hemofiltration system in a porcine model of percutaneous hepatic perfusion.

PubMed

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.

Emerging drugs in sepsis.

PubMed

Leone, Marc; Textoris, Julien; Michel, Fabrice; Wiramus, Sandrine; Martin, Claude

2010-03-01

Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited. The literature was analyzed with Pubmed() during the 2008 - 2009 period. If required, seminal articles published before 2008 were cited. Clinical trials focusing on 'sepsis' were first assessed. Next, relevant experimental data in this field were reported. The goal of the review is to determine the role for new licensed antibiotics, to give an insight into the conflict on adjuvant therapies and to disclose new experimental concepts. New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.

Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry.

PubMed

Cutuli, Salvatore Lucio; Artigas, Antonio; Fumagalli, Roberto; Monti, Gianpaola; Ranieri, Vito Marco; Ronco, Claudio; Antonelli, Massimo

2016-12-01

In 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice. The EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP. Septic shock was diagnosed in 305 (85.4 %) patients. The most common source of infection was abdominal (44.0 %) followed by pulmonary (17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16 ± 1.77 from 3.32 ± 1.29, p < 0.0001), respiratory (1.95 ± 0.95 from 2.40 ± 1.06, p < 0.001) and renal (1.84 ± 1.77 from 2.23 ± 1.62, p = 0.013). Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5 %. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75 % in comparison to the 39 % of patients who did not (p < 0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %, p = 0.003), ICU (59 vs. 36.7 %, p = 0.006) and hospital survival rate (53.2 vs. 35 %, p = 0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission. The EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique.

[Successful hemodialysis for life-threatening carbamazepine drug overdose: Case-based introduction of new guidelines].

PubMed

Drick, N; Patecki, M; Arelin, V; Schmidt, J J; Wahl, O; Kielstein, J T

2015-10-01

Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

From artificial red blood cells, oxygen carriers, and oxygen therapeutics to artificial cells, nanomedicine, and beyond

PubMed Central

Chang, Thomas M. S.

2013-01-01

The first experimental artificial red blood cells have all three major functions of red blood cells (rbc). However, the first practical one is a simple polyhemoglobin (PolyHb) that only has an oxygen-carrying function. This is now in routine clinical use in South Africa and Russia. An oxygen carrier with antioxidant functions, PolyHb-catalase-superoxide dismutase, can fulfill two of the three functions of rbc. Even more complete is one with all three functions of rbc in the form of PolyHb-catalase-superoxide dismutase-carbonic anhydrase. The most advanced ones are nanodimension artificial rbc with either PEG-lipid membrane or PEG-PLA polymermembrane. Extensions in to oxygen therapeutics include a PolyHb-tyrosinase that suppresses the growth of melanoma in a mice model. Another is a PolyHb-fibrinogen that is an oxygen carrier with platelet-like function. Research has now extended well beyond the original research on artificial rbc into many areas of artificial cells. These include nanoparticles, nanotubules, lipid vesicles, liposomes, polymer-tethered lipid vesicles, polymersomes, microcapsules, bioencapsulation, nanocapules, macroencapsulation, synthetic cells, and others. These are being used in nanotechnology, nanomedicine, regenerative medicine, enzyme/gene therapy, cell/stem cell therapy, biotechnology, drug delivery, hemoperfusion, nanosensers, and even by some groups in agriculture, industry, aquatic culture, nanocomputers, and nanorobotics. PMID:22409281

Nanoporous biomaterials for uremic toxin adsorption in artificial kidney systems: A review.

PubMed

Cheah, Wee-Keat; Ishikawa, Kunio; Othman, Radzali; Yeoh, Fei-Yee

2017-07-01

Hemodialysis, one of the earliest artificial kidney systems, removes uremic toxins via diffusion through a semipermeable porous membrane into the dialysate fluid. Miniaturization of the present hemodialysis system into a portable and wearable device to maintain continuous removal of uremic toxins would require that the amount of dialysate used within a closed-system is greatly reduced. Diffused uremic toxins within a closed-system dialysate need to be removed to maintain the optimum concentration gradient for continuous uremic toxin removal by the dialyzer. In this dialysate regenerative system, adsorption of uremic toxins by nanoporous biomaterials is essential. Throughout the years of artificial kidney development, activated carbon has been identified as a potential adsorbent for uremic toxins. Adsorption of uremic toxins necessitates nanoporous biomaterials, especially activated carbon. Nanoporous biomaterials are also utilized in hemoperfusion for uremic toxin removal. Further miniaturization of artificial kidney system and improvements on uremic toxin adsorption capacity would require high performance nanoporous biomaterials which possess not only higher surface area, controlled pore size, but also designed architecture or structure and surface functional groups. This article reviews on various nanoporous biomaterials used in current artificial kidney systems and several emerging nanoporous biomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1232-1240, 2017. © 2016 Wiley Periodicals, Inc.

[Influence of high-voltage electric burn on the microcirculation of heart in rabbit].

PubMed

Zhang, Qing-fu; Zhou, Hui-min; Wang, Che-jiang; Shao, Hong-bo

2012-06-01

To study the influence of high-voltage electric burn on the microcirculation of heart in rabbit. One-hundred and twenty New Zealand rabbits of clean grade were divided into control group (C) and electric burn group (EB) according to the random number table, with 60 rabbits in each group. Rabbits in EB group were subjected to high-voltage electric burn (the electrical current flow into the left foreleg at the lateral side of proximal end and out from the corresponding site of the right hind leg) with voltage regulator and experimental transformer. Rabbits in C group were sham injured with the same devices without electrification. At 15 minutes before injury, and 5 minutes, 1, 2, 4, 8 hour (s) post injury (PIM or PIH), ten rabbits in each group were chosen to examine the cardiac apex microcirculation hemoperfusion (CAMH) with laser Doppler hemoperfusion image instrument. The morphologic changes of microvessels of left ventricular wall tissues of 2 rabbits from each of the 10 rabbits collected at above-mentioned time points were observed with light microscope and transmission electron microscope. Auricular vein blood of rabbit was harvested at above-mentioned time points for the determination of aspartate amino transferase (AST), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK), and creatine kinase isozyme MB (CK-MB) by full-automatic biochemical analyzer. Data were processed with two-factor analysis of variance and LSD test. (1) The differences between C group and EB group in detection results were statistically significant, with F values from 425.991 to 3046.834, P values all below 0.01. Only the data within EB group were comparable. (2) At PIM 5, the CAMH value of rabbits in EB group was (1.96 ± 0.09) V, which was lower than that at 15 minutes before injury [(4.34 ± 0.35) V, P < 0.01]. The CAMH value of rabbits in EB group was increased at PIH 1 [(3.43 ± 0.30) V], and then it showed a tendency of decrease. (3) Bleeding and microthrombus formation were observed in venule and capillary vessel of rabbits in EB group at PIH 8. Breakage of basement membrane of capillary endothelial cells, mitochondrial swelling, and severe degranulation from damaged endoplasmic reticulum were observed in rabbits of EB group at PIH 8. (4) Levels of AST, LDH, HBDH, CK, and CK-MB in rabbits of EB group were significantly higher at PIH 1, 2, 4, 8 than at 15 minutes before injury (with P values all below 0.01). The AST level peaked at PIH 2 [(164 ± 39) U/L]. Levels of LDH and HBDH peaked at PIH 4, which were respectively (1016 ± 246) U/L and (487 ± 54) U/L. The CK level peaked at PIH 8 [(7799 ± 738) U/L]. The CK-MB level peaked at PIH 2 [(1848 ± 65) U/L]. High-voltage electric burn can bring damage to the microvessels of heart in rabbits and change blood flow of microcirculation, which should be given adequate attention during the treatment.

Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study.

PubMed

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.

Acute exacerbation of interstitial pneumonia associated with rheumatoid arthritis during the course of treatment for Pneumocystis jirovecii pneumonia: a case report.

PubMed

Kuroda, Takeshi; Takeuchi, Hiroyuki; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Moriyama, Hiroshi; Nakano, Masaaki; Narita, Ichiei

2016-04-26

Pneumocystis jirovecii pneumonia (PCP) is potentially fatal infectious complication in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. Hospital survival due to human immunodeficiency virus-unrelated PCP reaches to 60%. The high mortality rate results from difficulties in establishing an early diagnosis, concurrent use of prophylactic drugs, possible bacterial coinfection. We herein report a case of PCP in RA patients who developed the architectural distortions of lung in spite of combined modality therapy. A 73-year-old Japanese woman with RA was admitted with shortness of breath. Five weeks previously, she had been started on etanercept in addition to methotrexate (MTX). Chest computed tomography (CT) demonstrated diffuse ground glass opacities distributed throughout the bilateral middle to lower lung fields, and serum β-D-glucan was elevated. Bronchoalveolar lavage fluid revealed no P. jirovecii, but the organism was detected by polymerase chain reaction method. Trimethoprim/sulfamethoxazole was administered with methylprednisolone pulse therapy. However, the follow-up chest X-ray and chest CT demonstrated aggravation of the pneumonia with architectural distortions. Additional direct hemoperfusion with polymyxin B-immobilized fibers and intravenous cyclophosphamide therapy were insufficiently effective, and the patient died on day 25. The architectural distortions of lung should be considered as a cause of death of PCP. For this reason, a high suspicion of this infectious complication must be kept in mind in order to establish an early diagnosis and treatment in patients with RA managed with MTX and biologics.

Hemostatic Effects of Microbubble-Enhanced Low-Intensity Ultrasound in a Liver Avulsion Injury Model

PubMed Central

Feng, Guiying; Liu, Jianhua; Zhao, Xiaochen; Wei, Jinglu; Ou, Wencai; Xiao, Shuyi; Hu, Zhiwen; Wei, Hongqin; Liu, Zheng

2014-01-01

Objectives Microbubble-enhanced therapeutic ultrasound (MEUS) can block the blood flow in the organs. The aim of this study was to evaluate the hemostatic effect of microbubble-enhanced pulsed, low-intensity ultrasound in a New Zealand White rabbit model of avulsion trauma of the liver. The therapeutic ultrasound (TUS) transducer was operated with the frequency of 1.2 MHz and an acoustic pressure of 3.4 MPa. Microbubble-(MB) enhanced ultrasound (MEUS) (n = 6) was delivered to the distal part of the liver where the avulsion was created. Livers were treated by TUS only (n = 4) or MB only (n = 4) which served as controls. Bleeding rates were measured and contrast enhanced ultrasound (CEUS) was performed to assess the hemostatic effect, and liver hemoperfusion before and after treatment. Generally, bleeding rates decreased more than 10-fold after the treatment with MEUS compared with those of the control group (P<0.05). CEUS showed significant declines in perfusion. The peak intensity value and the area under the curve also decreased after insonation compared with those of the control group (P<0.05). Histological examination showed cloudy and swollen hepatocytes, dilated hepatic sinusoids, perisinusoidal spaces with erythrocyte accumulation in small blood vessels, obvious hemorrhage around portal areas and scattered necrosis in liver tissues within the insonation area of MEUS Group. In addition, necrosis was found in liver tissue 48 h after insonation. We conclude that MEUS might provide an effective hemostatic therapy for serious organ trauma such as liver avulsion injury. PMID:24788757

Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series.

PubMed

Träger, Karl; Skrabal, Christian; Fischer, Guenther; Datzmann, Thomas; Schroeder, Janpeter; Fritzler, Daniel; Hartmann, Jan; Liebold, Andreas; Reinelt, Helmut

2017-05-29

Infective endocarditis is a serious disease condition. Depending on the causative microorganism and clinical symptoms, cardiac surgery and valve replacement may be needed, posing additional risks to patients who may simultaneously suffer from septic shock. The combination of surgery bacterial spreadout and artificial cardiopulmonary bypass (CPB) surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyperinflammatory state frequently associated with compromised hemodynamic and organ function. Hemoadsorption might represent a potential approach to control the hyperinflammatory systemic reaction associated with the procedure itself and subsequent clinical conditions by reducing a broad range of immuno-regulatory mediators. We describe 39 cardiac surgery patients with proven acute infective endocarditis obtaining valve replacement during CPB surgery in combination with intraoperative CytoSorb hemoadsorption. In comparison, we evaluated a historical group of 28 patients with infective endocarditis undergoing CPB surgery without intraoperative hemoadsorption. CytoSorb treatment was associated with a mitigated postoperative response of key cytokines and clinical metabolic parameters. Moreover, patients showed hemodynamic stability during and after the operation while the need for vasopressors was less pronounced within hours after completion of the procedure, which possibly could be attributed to the additional CytoSorb treatment. Intraoperative hemoperfusion treatment was well tolerated and safe without the occurrence of any CytoSorb device-related adverse event. Thus, this interventional approach may open up potentially promising therapeutic options for critically-ill patients with acute infective endocarditis during and after cardiac surgery, with cytokine reduction, improved hemodynamic stability and organ function as seen in our patients.

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

PubMed

Marchioni, Alessandro; Tonelli, Roberto; Ball, Lorenzo; Fantini, Riccardo; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Malerba, Mario; Pelosi, Paolo; Clini, Enrico

2018-03-23

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

[Curative effect of paraquat detoxification recipe combined with continuous hemoperfusion in the treatment of patients with APP and clinical value of Presepsin].

PubMed

Wang, Weizhan; Li, Jing; Zhu, Baoyue; Gao, Xun; Xiao, Qingmian; Qi, Hongna; Ye, Yanqiao; Liu, Yongjian; Han, Yongyan; Ma, Gongying; Wang, Pu

2017-11-01

To investigate the clinical effect of paraquat (PQ) detoxification recipe combined with continuous hemoperfusion (HP) in the treatment of patients with acute paraquat poisoning (APP) and clinical significance of soluble CD14 subtype (sCD14-st, Presepsin). A prospective randomized controlled trial was conducted. 152 patients with moderate APP admitted to Department of Emergency Medicine of Harrison International Peace Hospital Affiliated to Hebei Medical University from July 2013 to June 2017 were enrolled, and they were randomly divided into three groups. The patients in HP group (group A, n = 35) only received 2-hour HP for 3 times, 8 hours each time, those in PQ detoxification recipe combined with HP group (group B, n = 50) received PQ detoxification recipe 1 (once per 2 hours until no PQ component was found in faeces) and 2 (3 times a day for 14 days) beside HP. The others in PQ detoxification recipe combined with persistent HP group (group C, n = 67) received continuous HP until the PQ component in serum was not detected. The parameters of organ function and inflammatory factor, and blood Presepsin and PQ contents were determined before and after treatment. The curative effect and 28-day mortality were recorded. The correlations between serum Presepsin level and PQ content as well as 28-day mortality were analyzed with Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of Presepsin on prognosis. The total effective rate of group C was significantly higher than that of groups A and B [70.1% (47/67) vs. 34.3% (12/35), 54.0% (27/50)], and 28-day mortality was significantly lowered [29.8% (20/67) vs. 65.7% (23/35), 46.0% (23/50), both P < 0.05]. There was no significant difference in alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukins (IL-6 and IL-10) before treatment among the three groups. Five days after treatment, the above parameters in the three groups were increased as compared with those before treatment, but the increase degree in group C was the lowest. At 7 days after treatment, the parameters were decreased, especially in group C. There was no significant difference in serum Presepsin and PQ levels before treatment among the three groups. With the prolongation of treatment time, the Prespsin levels in groups A, B, and C were increased, and peaked at 12 hours (μg/L: 4.28±0.20, 3.87±0.25, 3.53±0.23), then gradually decreased,and the PQ contents were lower than those before treatment from 8 hours (mg/L: 1.76±0.12 vs. 2.12±0.17, 1.57±0.08 vs. 2.24±0.16, 1.25±0.10 vs. 2.14±0.18), with a time dependence pattern, especially in group C (all P < 0.05) . Correlation analysis showed that blood Presepsin level was positively correlated with PQ content and 28-day mortality (r 1 = 0.917, r 2 = 0.864, both P = 0.001), suggesting that the higher the PQ content was, the higher the Presepsin level, and the higher the 28-day mortality was. ROC curve analysis showed that the area under ROC curve (AUC) of Presepsin predicting 28-day mortality was 0.863; when the cut-off value was 1.22 μg/L, the sensitivity was 83.3%, the specificity was 81.4%, the positive predictive value was 77.46%, and the negative predictive value was 86.42%. Early administration of PQ detoxification recipe combined with continuous HP treatment can effectively reduce Presepsin level, decrease the mortality of patients with moderate APP, improve the prognosis. Presepsin can assess the prognosis of patients with APP.

A case of acute onset postoperative gas gangrene caused by Clostridium perfringens.

PubMed

Takazawa, Tomonori; Ohta, Jou; Horiuchi, Tatsuo; Hinohara, Hiroshi; Kunimoto, Fumio; Saito, Shigeru

2016-08-03

Gas gangrene is a necrotic infection of soft tissue associated with high mortality rates. We report a case of postoperative gas gangrene with very acute onset and rapid progression of symptoms. To our knowledge, this case is the most acute onset of postoperative gas gangrene ever reported. A 65-year-old Japanese female patient developed a shock state 16 h after radical cystectomy with ileal conduit reconstruction. Two days after the operation, she was transferred to the intensive care unit because of deterioration in her respiratory and circulatory condition. Soon after moving her to the ICU, a subcutaneous hemorrhage-like skin rash appeared and extended rapidly over her left side. Blood tests performed on admission to the ICU indicated severe metabolic acidosis, liver and renal dysfunction, and signs of disseminated intravascular coagulation. Suspecting necrotizing fasciitis or gas gangrene, we performed emergency fasciotomy. Subsequently, multidisciplinary treatment, including empirical therapy using multiple antibiotics, mechanical ventilation, hyperbaric oxygen therapy, polymyxin B-immobilized fiber column direct hemoperfusion, and continuous hemodiafiltration, was commenced. Culture of the debris from a wound abscess removed by emergency fasciotomy detected the presence of Clostridium perfringens. We hypothesized that the source of infection in this case may have been the ileum used for bladder reconstruction. Although the initial treatment prevented further clinical deterioration, she developed secondary infection from the 3rd week onward, due to infection with multiple pathogenic bacteria. Despite prompt diagnosis and intensive therapy, the patient died 38 days after the operation. Although the patient did not have any specific risk factors for postsurgical infection, she developed a shock state only 16 h after surgery due to gas gangrene. Our experience highlights the fact that physicians should be aware that any patient could possibly develop gas gangrene postoperatively.

Advances in toxicology and medical treatment of chemical warfare nerve agents

PubMed Central

2012-01-01

Organophosphorous (OP) Nerve agents (NAs) are known as the deadliest chemical warfare agents. They are divided into two classes of G and V agents. Most of them are liquid at room temperature. NAs chemical structures and mechanisms of actions are similar to OP pesticides, but their toxicities are higher than these compounds. The main mechanism of action is irreversible inhibition of Acetyl Choline Esterase (AChE) resulting in accumulation of toxic levels of acetylcholine (ACh) at the synaptic junctions and thus induces muscarinic and nicotinic receptors stimulation. However, other mechanisms have recently been described. Central nervous system (CNS) depression particularly on respiratory and vasomotor centers may induce respiratory failure and cardiac arrest. Intermediate syndrome after NAs exposure is less common than OP pesticides poisoning. There are four approaches to detect exposure to NAs in biological samples: (I) AChE activity measurement, (II) Determination of hydrolysis products in plasma and urine, (III) Fluoride reactivation of phosphylated binding sites and (IV) Mass spectrometric determination of cholinesterase adducts. The clinical manifestations are similar to OP pesticides poisoning, but with more severity and fatalities. The management should be started as soon as possible. The victims should immediately be removed from the field and treatment is commenced with auto-injector antidotes (atropine and oximes) such as MARK I kit. A 0.5% hypochlorite solution as well as novel products like M291 Resin kit, G117H and Phosphotriesterase isolated from soil bacterias, are now available for decontamination of NAs. Atropine and oximes are the well known antidotes that should be infused as clinically indicated. However, some new adjuvant and additional treatment such as magnesium sulfate, sodium bicarbonate, gacyclidine, benactyzine, tezampanel, hemoperfusion, antioxidants and bioscavengers have recently been used for OP NAs poisoning. PMID:23351280

Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup.

PubMed

Anseeuw, Kurt; Mowry, James B; Burdmann, Emmanuel A; Ghannoum, Marc; Hoffman, Robert S; Gosselin, Sophie; Lavergne, Valery; Nolin, Thomas D

2016-02-01

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Advances in toxicology and medical treatment of chemical warfare nerve agents.

PubMed

Moshiri, Mohammd; Darchini-Maragheh, Emadodin; Balali-Mood, Mahdi

2012-11-28

Organophosphorous (OP) Nerve agents (NAs) are known as the deadliest chemical warfare agents. They are divided into two classes of G and V agents. Most of them are liquid at room temperature. NAs chemical structures and mechanisms of actions are similar to OP pesticides, but their toxicities are higher than these compounds. The main mechanism of action is irreversible inhibition of Acetyl Choline Esterase (AChE) resulting in accumulation of toxic levels of acetylcholine (ACh) at the synaptic junctions and thus induces muscarinic and nicotinic receptors stimulation. However, other mechanisms have recently been described. Central nervous system (CNS) depression particularly on respiratory and vasomotor centers may induce respiratory failure and cardiac arrest. Intermediate syndrome after NAs exposure is less common than OP pesticides poisoning. There are four approaches to detect exposure to NAs in biological samples: (I) AChE activity measurement, (II) Determination of hydrolysis products in plasma and urine, (III) Fluoride reactivation of phosphylated binding sites and (IV) Mass spectrometric determination of cholinesterase adducts. The clinical manifestations are similar to OP pesticides poisoning, but with more severity and fatalities. The management should be started as soon as possible. The victims should immediately be removed from the field and treatment is commenced with auto-injector antidotes (atropine and oximes) such as MARK I kit. A 0.5% hypochlorite solution as well as novel products like M291 Resin kit, G117H and Phosphotriesterase isolated from soil bacterias, are now available for decontamination of NAs. Atropine and oximes are the well known antidotes that should be infused as clinically indicated. However, some new adjuvant and additional treatment such as magnesium sulfate, sodium bicarbonate, gacyclidine, benactyzine, tezampanel, hemoperfusion, antioxidants and bioscavengers have recently been used for OP NAs poisoning.

Endotoxin Elimination in Patients with Septic Shock: An Observation Study.

PubMed

Adamik, Barbara; Zielinski, Stanislaw; Smiechowicz, Jakub; Kübler, Andrzej

2015-12-01

To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66-0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43-0.77), (p = 0.005); MAP increased from 69 (62-80) to 80 mm Hg (68-88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15-0.80) to 0.1 μg/kg/min (0.00-0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9-15) to 9 (7-14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA -2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.

Technical considerations in percutaneous hepatic perfusion--a multi-center experience.

PubMed

Antoine, Radcliffe A

2011-03-01

Patients diagnosed with primary or metastatic liver cancer face a daunting future that is complicated by limited treatment options. Percutaneous hepatic perfusion is a novel approach to chemotherapy delivery that offers significant benefits over contemporary modalities. Percutaneous hepatic perfusion is a procedure in which a chemotherapeutic agent is administered at high doses via the hepatic artery where it perfuses the liver, is extracted and filtered using a veno-veno bypass circuit, a fenestrated multi-lumen double-balloon catheter, and two biocompatible hemoperfusion filters. Venous access is gained at the groin through the femoral vein after which the catheter is advanced and positioned in the inferior vena cava just below the right atrium.The catheter's proximal and distal balloons are inflated to occlude the inferior vena cava above and below the hepatic veins. The occlusion isolated the chemo-rich venous outflow of the liver from the systemic venous circulation. This maneuver also diverts venous blood returning to the heart from lower extremities of the azygos vein. Once the patient is on bypass, the agent is infused through the hepatic artery where it saturates the liver. The chemo-rich venous outflow is extracted through the double-balloon catheter by the bypass circuit. The blood is continuously filtered and cleared of the agent as it passes through the filters and returned to the patient through a catheter placed in the right internal jugular vein. A phase I study demonstrated efficacy with an overall radiographic response rate of 30% observed in treated patients. In 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. The technique is minimally invasive and can be performed safely by a well-trained multi-disciplinary team. It offers significant benefits including multiple procedures without risks commonly associated with open abdominal surgery.

Technical Considerations in Percutaneous Hepatic Perfusion—A Multi-Center Experience

PubMed Central

Antoine, Radcliffe A.

2011-01-01

Abstract: Patients diagnosed with primary or metastatic liver cancer face a daunting future that is complicated by limited treatment options. Percutaneous hepatic perfusion is a novel approach to chemotherapy delivery that offers significant benefits over contemporary modalities. Percutaneous hepatic perfusion is a procedure in which a chemotherapeutic agent is administered at high doses via the hepatic artery where it perfuses the liver, is extracted and filtered using a veno-veno bypass circuit, a fenestrated multi-lumen double-balloon catheter, and two biocompatible hemoperfusion filters. Venous access is gained at the groin through the femoral vein after which the catheter is advanced and positioned in the inferior vena cava just below the right atrium. The catheter’s proximal and distal balloons are inflated to occlude the inferior vena cava above and below the hepatic veins. The occlusion isolated the chemo-rich venous outflow of the liver from the systemic venous circulation. This maneuver also diverts venous blood returning to the heart from lower extremities of the azygos vein. Once the patient is on bypass, the agent is infused through the hepatic artery where it saturates the liver. The chemorich venous outflow is extracted through the double-balloon catheter by the bypass circuit. The blood is continuously filtered and cleared of the agent as it passes through the filters and returned to the patient through a catheter placed in the right internal jugular vein. A phase I study demonstrated efficacy with an overall radiographic response rate of 30% observed in treated patients. In 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. The technique is minimally invasive and can be performed safely by a well-trained multi-disciplinary team. It offers significant benefits including multiple procedures without risks commonly associated with open abdominal surgery. PMID:21449232

Imaging characteristics and pathogenesis of intracranial artery stenosis in patients with acute cerebral infarction

PubMed Central

Xu, Wenyuan; Xie, Ning; Zhang, Cheng; Huang, Qin

2018-01-01

The current study aimed to investigate the imaging characteristics and pathogenesis of intracranial artery stenosis in patients with acute cerebral infarction. In total, 84 patients diagnosed with acute cerebral infarction were recruited. Magnetic resonance angiography was performed to detect the existence of intracranial artery stenosis or occlusion. In addition, magnetic resonance imaging and diffusion weighted imaging were employed to analyze the infarction types and characteristics. In the majority of patients, the infarction resulted from internal carotid stenosis (77 cases; 91.7%), while it was caused by vertebral artery stenosis in a small number of cases (7 cases; 8.3%). Multiple infarction was identified the most common type of infarction among all cases (69.0%). The most common types of infarctions in the internal carotid system were multiple infarction implicating both the cortex and centrum ovale (23.4%), and internal watershed infarction (22.1%). Although the number of cases was relatively small, multiple infarction was observed to have a high incidence in the vertebral artery system. Bedside electrocardiogram was also recorded to determine the sinus rhythm and examine the abnormal hemodynamics. The sinus bradycardia rate of patients with multiple infarction was markedly greater in comparison with that in single infarction patients (χ2=0.01, P<0.05). Transcranial Doppler plus microembolus monitoring was utilized to explore the possible pathogenesis of all types of infarctions, such as arterial embolization. As compared with the single infarction patients, the embolus rate in patients with multiple infarction was notably increased by ~3.7-fold (χ2=8.65, P<0.05). In conclusion, the cerebral infarction was common in the internal carotid system, with multiple infarction observed in the majority of cases. The pathogenesis of cerebral infarction included arterial embolization and inadequate hemoperfusion. PMID:29725389

Effects of different blood purification methods on serum cytokine levels and prognosis in patients with acute severe organophosphorus pesticide poisoning.

PubMed

Liu, Lunzhi; Ding, Guohua

2015-04-01

The aim of the present study was to investigate the impact of three different blood purification methods, hemoperfusion (HP), continuous blood purification (CBP), and on-line high-volume hemodiafiltration (OL-HDF), on the survival rate of patients with acute severe organophosphorus pesticide poisoning (ASOPP), as well as on major pro-inflammatory (interleukin [IL]-1, IL-6, tumor necrosis factor-α [TNF-α]) and anti-inflammatory (IL-10) cytokines in the serum. Eighty-one ASOPP patients were randomly divided into three groups: HP (N = 23), HP + CBP (N = 26), HP + OL-HD (N = 32). Serum IL-1, IL-6, TNF-α, and IL-10 levels were assessed by ELISA before treatment and at 24 and 48 h post-treatment and survival rates were determined. Patient survival rate was significantly higher in OL-HDF and CBP treated patients compared with HP group (P < 0.05). A significantly greater clearance effect in serum IL-1, IL-6, and TNF-α levels at 24 and 48 h post-treatment was observed in CBP and OL-HDF groups compared with the HP group (P < 0.05). The levels of serum anti-inflammatory cytokine IL-10 increased significantly in CBP and OL-HDF groups compared with the HP group (P < 0.05 at 48 h post-treatment). In addition, OL-HDF treatment achieved similar changes in serum TNF-α, IL-1, IL-6 and IL-10 levels as CBP (P > 0.05). Compared with the HP method, CBP or OL-HDF combined with HP can rapidly clear inflammatory cytokines, reduce systemic inflammatory response syndrome, and improve the survival of ASOPP patients. Compared with CBP, OL-HDF is an economical and effective method to treat ASOPP with less technical difficulty and more suitability for rural areas and primary hospitals. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

[Charcoal, cocaine and rattlesnakes: evidence-based treatment of poisoning].

PubMed

Schaper, A

2013-10-01

Since ancient times poisoning has been treated medicinally. Clinical toxicology, in the narrow sense of the term, developed from the foundation of specialized medical treatment units for poisoning and the formation of the first poison information centers in the second half of the twentieth century. Historically, the first poison information centers were often localized at pediatric clinics or departments of internal medicine. It became increasingly more obvious that this pooling of competences made sense. This article gives a general introduction in clinical toxicology and presents the functions and key activities of emergency poison centers. The organisation and work of a poisons centre is demonstrated on the basis of the Poisons Information Center (GIZ) North annual report for 2011. In a short summary the basic principles of clinical toxicology are elucidated: the primary removal of poisons by gastric lavage and administration of activated charcoal, secondary removal of poisons by enhanced elimination using hemodialysis, hemoperfusion, multi-dose activated charcoal and molecular adsorbent recirculating systems (MARS) and the indications for administration of specific antidotes or antivenins (antisera against poisoning by poisonous animals). Gastric lavage is indicated within 1 h after ingestion of a potentially life-threatening dose of a poison. In cases of poisoning with substances which penetrate the central nervous system (CNS) gastric lavage should be performed only after endotracheal intubation due to the risk of aspiration. The basic management of poisoned patients by emergency medicine personnel out of hospital and on the way to hospital is presented. The Bremen list, a compilation of the five antidotes, atropine, 4-dimethylaminophenol (4-DMAP), tolonium chloride, naloxone and activated charcoal for out of hospital treatment by emergency doctors is presented. In all, even questionable cases of poisoning consultation at emergency poison centers is recommended. An extensive list of all German speaking poison information centers is available on the homepage of GIZ-Nord (http://www.giz-nord.de).

[Clinical study on application of intermittent hemofiltration combined with hemoperfusion in the early stage of severe burn in the prevention and treatment of sepsis].

PubMed

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.

Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup

PubMed Central

Ghannoum, Marc; Yates, Christopher; Galvao, Tais F.; Sowinski, Kevin M.; Vo, Thi Hai Vân; Coogan, Andrew; Gosselin, Sophie; Lavergne, Valery; Nolin, Thomas D.; Hoffman, Robert S.

2014-01-01

Abstract Context. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Objectives. To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning. Methods. After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results. Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous renal replacement therapies (3D) are alternatives if hemodialysis is not available. MDAC therapy should be continued during ECTR (1D). Conclusion. Despite the low quality of the available clinical evidence and the high protein binding capacity of carbamazepine, the workgroup suggested extracorporeal removal in cases of severe carbamazepine poisoning. PMID:25355482

Extracorporeal treatment for valproic acid poisoning: systematic review and recommendations from the EXTRIP workgroup.

PubMed

Ghannoum, Marc; Laliberté, Martin; Nolin, Thomas D; MacTier, Robert; Lavergne, Valery; Hoffman, Robert S; Gosselin, Sophie

2015-06-01

The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning. The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations. The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350-700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative. VPA is moderately dialyzable in the setting of overdose. ECTR is indicated for VPA poisoning if at least one of the above criteria is present. Intermittent hemodialysis is the preferred ECTR modality in VPA poisoning.

Extracorporeal treatment for theophylline poisoning: systematic review and recommendations from the EXTRIP workgroup.

PubMed

Ghannoum, Marc; Wiegand, Timothy J; Liu, Kathleen D; Calello, Diane P; Godin, Melanie; Lavergne, Valery; Gosselin, Sophie; Nolin, Thomas D; Hoffman, Robert S

2015-05-01

The Extracorporeal Treatments in Poisoning workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Here, the workgroup presents its systematic review and recommendations for theophylline. After a systematic review of the literature, a subgroup reviewed articles, extracted data, summarized findings, and proposed structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed. A second vote determined the final recommendations. 141 articles were included: 6 in vitro studies, 4 animal studies, 101 case reports/case series, 7 descriptive cohorts, 4 observational studies, and 19 pharmacokinetic studies, yielding a low-to-very-low quality of evidence for all recommendations. Data on 143 patients were reviewed, including 10 deaths. The workgroup concluded that theophylline is dialyzable (level of evidence = A) and made the following recommendations: ECTR is recommended in severe theophylline poisoning (1C). Specific recommendations for ECTR include a theophylline concentration [theophylline] > 100 mg/L (555 μmol/L) in acute exposure (1C), the presence of seizures (1D), life-threatening dysrhythmias (1D) or shock (1D), a rising [theophylline] despite optimal therapy (1D), and clinical deterioration despite optimal care (1D). In chronic poisoning, ECTR is suggested if [theophylline] > 60 mg/L (333 μmol/L) (2D) or if the [theophylline] > 50 mg/L (278 μmol/L) and the patient is either less than 6 months of age or older than 60 years of age (2D). ECTR is also suggested if gastrointestinal decontamination cannot be administered (2D). ECTR should be continued until clinical improvement is apparent or the [theophylline] is < 15 mg/L (83 μmol/L) (1D). Following the cessation of ECTR, patients should be closely monitored. Intermittent hemodialysis is the preferred method of ECTR (1C). If intermittent hemodialysis is unavailable, hemoperfusion (1C) or continuous renal replacement therapies may be considered (3D). Exchange transfusion is an adequate alternative to hemodialysis in neonates (2D). Multi-dose activated charcoal should be continued during ECTR (1D). Theophylline poisoning is amenable to ECTRs. The workgroup recommended extracorporeal removal in the case of severe theophylline poisoning.

Systemic Immunomodulating Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

PubMed Central

Zimmermann, Stefanie; Sekula, Peggy; Venhoff, Moritz; Motschall, Edith; Knaus, Jochen; Schumacher, Martin

2017-01-01

Importance Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare but severe adverse reactions with high mortality. There is no evidence-based treatment, but various systemic immunomodulating therapies are used. Objectives To provide an overview on possible immunomodulating treatments for SJS/TEN and estimate their effects on mortality compared with supportive care. Data Sources A literature search was performed in December 2012 for articles published in MEDLINE, MEDLINE Daily, MEDLINE Inprocess, Web of Science, EMBASE, Scopus, and the Cochrane Library (Central) from January 1990 through December 2012, and updated in December 2015, in the English, French, Spanish, and German languages looking for treatment proposals for SJS/TEN. Other sources were screened manually. Study Selection Initially, 157 randomized and nonrandomized studies on therapies (systemic immunomodulating therapies or supportive care) for SJS/TEN were selected. Data Extraction and Synthesis Relevant data were extracted from articles. Authors were contacted for further information. Finally, 96 studies with sufficient information regarding eligibility and adequate quality scores were considered in the data synthesis. All steps were performed independently by 2 investigators. Meta-analyses on aggregated study data (random-effects model) and individual patient data (IPD) (logistic regression adjusted for confounders) were performed to assess therapeutic efficacy. In the analysis of IPD, 2 regression models, stratified and unstratified by study, were fitted. Main Outcomes and Measures Therapy effects on mortality were expressed in terms of odds ratios (ORs) with 95% CIs. Results Overall, 96 studies (3248 patients) were included. Applied therapies were supportive care or systemic immunomodulating therapies, including glucocorticosteroids, intravenous immunoglobulins, cyclosporine, plasmapheresis, thalidomide, cyclophosphamide, hemoperfusion, tumor necrosis factor inhibitors, and granulocyte colony-stimulating factors. Glucocorticosteroids were associated with a survival benefit for patients in all 3 analyses but were statistically significant in only one (aggregated data: OR, 0.5; 95%% CI, 0.3-1.01; IPD, unstratified: OR, 0.7; 95% CI, 0.5-0.97; IPD, stratified: OR, 0.8; 95% CI, 0.4-1.3). Despite the low patient size, cyclosporine was associated with a promising significant result in the only feasible analysis of IPD (unstratified model) (OR, 0.1; 95% CI, 0.0-0.4). No beneficial findings were observed for other therapies, including intravenous immunoglobulins. Conclusions and Relevance Although all analyses, including the unstratified model, had limitations, glucocorticosteroids and cyclosporine were the most promising systemic immunomodulating therapies for SJS/TEN. Further evaluation in prospective studies is required. However, this work provides a comprehensive overview on proposed systemic immunomodulating treatments for SJS/TEN, which is of great relevance for treating physicians. PMID:28329382

Aconite poisoning.

PubMed

Chan, Thomas Y K

2009-04-01

Aconitine and related alkaloids found in the Aconitum species are highly toxic cardiotoxins and neurotoxins. The wild plant (especially the roots and root tubers) is extremely toxic. Severe aconite poisoning can occur after accidental ingestion of the wild plant or consumption of an herbal decoction made from aconite roots. In traditional Chinese medicine, aconite roots are used only after processing to reduce the toxic alkaloid content. Soaking and boiling during processing or decoction preparation will hydrolyze aconite alkaloids into less toxic and non-toxic derivatives. However, the use of a larger than recommended dose and inadequate processing increases the risk of poisoning. A Medline search (1963-February 2009) was conducted. Key articles with information on the use of aconite roots in traditional medicine, active (toxic) ingredients, mechanisms of toxicity, toxicokinetics of Aconitum alkaloids, and clinical features and management of aconite poisoning were reviewed. The cardiotoxicity and neurotoxicity of aconitine and related alkaloids are due to their actions on the voltage-sensitive sodium channels of the cell membranes of excitable tissues, including the myocardium, nerves, and muscles. Aconitine and mesaconitine bind with high affinity to the open state of the voltage-sensitive sodium channels at site 2, thereby causing a persistent activation of the sodium channels, which become refractory to excitation. The electrophysiological mechanism of arrhythmia induction is triggered activity due to delayed after-depolarization and early after-depolarization. The arrhythmogenic properties of aconitine are in part due to its cholinolytic (anticholinergic) effects mediated by the vagus nerve. Aconitine has a positive inotropic effect by prolonging sodium influx during the action potential. It has hypotensive and bradycardic actions due to activation of the ventromedial nucleus of the hypothalamus. Through its action on voltage-sensitive sodium channels in the axons, aconitine blocks neuromuscular transmission by decreasing the evoked quantal release of acetylcholine. Aconitine, mesaconitine, and hypaconitine can induce strong contractions of the ileum through acetylcholine release from the postganglionic cholinergic nerves. Patients present predominantly with a combination of neurological, cardiovascular, and gastrointestinal features. The neurological features can be sensory (paresthesia and numbness of face, perioral area, and the four limbs), motor (muscle weakness in the four limbs), or both. The cardiovascular features include hypotension, chest pain, palpitations, bradycardia, sinus tachycardia, ventricular ectopics, ventricular tachycardia, and ventricular fibrillation. The gastrointestinal features include nausea, vomiting, abdominal pain, and diarrhea. The main causes of death are refractory ventricular arrhythmias and asystole and the overall in-hospital mortality is 5.5%. Management of aconite poisoning is supportive, including immediate attention to the vital functions and close monitoring of blood pressure and cardiac rhythm. Inotropic therapy is required if hypotension persists and atropine should be used to treat bradycardia. Aconite-induced ventricular arrhythmias are often refractory to direct current cardioversion and antiarrhythmic drugs. Available clinical evidence suggests that amiodarone and flecainide are reasonable first-line treatment. In refractory cases of ventricular arrhythmias and cardiogenic shock, it is most important to maintain systemic blood flow, blood pressure, and tissue oxygenation by the early use of cardiopulmonary bypass. The role of charcoal hemoperfusion to remove circulating aconitine alkaloids is not established. Aconite roots contain aconitine, mesaconitine, hypaconitine, and other Aconitum alkaloids, which are known cardiotoxins and neurotoxins. Patients present predominantly with neurological, cardiovascular, and gastrointestinal features. Management is supportive; the early use of cardiopulmonary bypass is recommended if ventricular arrhythmias and cardiogenic shock are refractory to first-line treatment.

Treatment for calcium channel blocker poisoning: A systematic review

PubMed Central

Dubé, P.-A.; Gosselin, S.; Guimont, C.; Godwin, J.; Archambault, P. M.; Chauny, J.-M.; Frenette, A. J.; Darveau, M.; Le sage, N.; Poitras, J.; Provencher, J.; Juurlink, D. N.; Blais, R.

2014-01-01

Context Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. Objective To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. Methods Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. Results The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5–2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. Conclusions The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality. PMID:25283255

[Effect of rhubarb as the main composition of sequential treatment in patients with acute paraquat poisoning: a prospective clinical research].

PubMed

Wang, Weizhan; Li, Jing; Ma, Guoying; Li, Na; Wang, Pu; Xiao, Qingmian; Li, Baiyan; Liu, Yongjian; Gao, Xun; Li, Wei

2015-04-01

To observe the effect of rhubarb as the main composition in the therapy for patients with acute paraquat poisoning (AP). A prospective randomized controlled trial was conducted. 128 patients with APP admitted to Harrison International Peace Hospital from March 2011 to December 2013 were randomly divided into western medicine control group (n = 64) and western medicine and traditional Chinese medicine (TCM) combination group (n = 64). All the patients were treated with repeated gastric lavage and oral kaolin. The patients in western medicine control group were given 20% mannitol and (or) magnesium sulfate for catharsis, early ( within 8 hours of admission ) hemoperfusion HP), and also given the routine combined therapy. In TCM combination group, in addition to the above treatment patients were given oral paraquat poisoning detoxification prescription No.1 every 2 hours for catharsis, which was composed of rhubarb 10 g, glauber salt 12 g, agrimony 12 g, and licorice 6 g. When green stool disappeared, detoxification therapy was changed to No. 2 compound once a day for 14 days, which was consisted of rhubarb 10 g, ginseng 6 g, agrimony 15 g, rhizoma chuanxiong 10 g, licorice 6 g. The poison volume, first dose of oral drug, time for the first HP, time of the first defecation, the time of last green stool, decontamination time, white blood cell count ( WBC ), C-reactive protein ( CRP ), arterial blood gas analysis, blood lactic acid ( Lac ), liver and kidney functions, myocardial enzyme spectrum, chest CT, adverse reaction, days of hospitalization, and mortality rate were observed in both groups. The levels of paraquat in plasma and urine were determined before treatment and 12 hours after poisoning in both groups. Sixty days after discharge, chest CT was taken for observation of pulmonary fibrosis. There were no significant differences in the poison volume, ingestion time and the time for the first HP between the two groups. Compared with western medicine control group, the first defecation time (hours: 3.94 ± 1.14 vs. 6.17 ± 1.52), the last time of green stool (hours: 36.90 ± 4.10 vs. 51.6 3 ± 4.91), and poison clean-up time from plasma (hours: 19.48 ± 3.63 vs. 23.84 ± 3.29) in combination with TCM group were significantly earlier (all P < 0.01). WBC, CRP, alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels were gradually increased after admission in combination with TCM group, and they peaked on 5th day [WBC ( × 10⁹/L) : 15.35 ± 2.17 vs. 17.47 ± 2.09, CRP (mg/L): 32.62 ± 2.76 vs. 39.51 ± 2.45, ALT (U/L): 270.88 ± 11.06 vs. 334.67 ± 7.85, BUN (mmol/L): 13.29 ± 1.90 vs. 17.63 ± 1.42, SCr (μmol/L): 203.54 ± 18.40 vs. 251.53 ± 14.38, all P < 0.05 ], and then they declined; Lac after admission was gradually increased, and peaked at 7 days (mmol/L: 3.53 ± 0.21 vs. 3.82 ± 0.14, P < 0.05 ), and then it was decreased. Myocardial enzyme spectrum was increased after admission, and peaked on 3rd day [creatine kinase (CK, U/L): 192.09 ± 16.26 vs. 216.20 ± 11.96, creatine kinase isoenzyme enzyme ( K-MB, U/L): 39.03 ± 3.75 vs. 47.22 ± 5.84, both P < 0.05 ), and then they declined gradually. Arterial partial pressure of oxygen (PaO₂) and base excess (E) were gradually decreased after admission, down to trough on the 7th day after admission [PaO₂(mmHg, 1 mmHg = 0.133 kPa): 87.04 ± 2.37 vs. 84.93 ± 2.44, BE (mmol/L): -7.31 ± 2.31 vs. -9.18 ± 2.49, both P < 0.05 ], and then they were increased. At 12 hours after poisoning, paraquat contents in plasma and urine in combination with TCM group were significantly lower than those of the western medicine control group [plasma (ng/L): 0.83 ± 0.08 vs. 0.96 ± 0.10, urine (ng/L): 0.88 ± 0.09 vs. 0.97 ± 011, both P < 0.05]. The injury to lung tissue was significantly improved in combination with TCM group compared with that in the western medicine control group, and no serious adverse reactions was found, and the hospital stay time (days: 20.46 ± 6.07 vs. 29.73 ± 9.16) was significantly shortened (P < 0.01), and the mortality rate [ 35.9% (23/64) vs. 45.3% (29/64) ] was significantly lowered compared with western medicine control group (P < 0.05). In the combination with TCM group pulmonary fibrosis was lighter than that in the western medicine control group during the 60-day follow-up. The sequential treatment of No. 1 and No. 2 detoxification of APP, using rhubarb as the main drug, can effectively eliminate paraquat, reduce absorption of the toxin, prevent the development of multiple organ dysfunction syndrome (MODS) induced by the toxin, shorten the hospital stay days, and improve the prognosis of APP.