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The EXTRIP (EXtracorporeal Treatments In Poisoning) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians and nephrologists reviewing all available evidence in extracorporeal procedures for the treatment of intoxications in a standardized way to distill treatment recommendations for the physician at the bedside. The second round of guidelines will include recommendations for ethylenglycol intoxication. The case reported here is of a 60-year old man with a body weight of 65 kg who ingested approximately half a bottle (500 mL) of Aral Antifreeze in a suicidal attempt and presented around 12 h later with severe metabolic acidosis (venous blood gas analysis: pH 7.13; lactate 30 mmol/l, anion gap 23.3 mmol/l). As fomepizole, the inhibitor of the alcohol dehydrogenase, was not readily available, therapy with intermittent hemodialysis was started, as well as ethanol infusion. The first available ethylenglycol concentration before prolonged intermittent hemodialysis was 1230 mg/L. The total removed amount of ethylenglycol during intermittent hemodialysis, as well as following prolonged intermittent renal replacement therapy, was quantified (102 and 65 g). Based on this case report, the new EXRIP recommendations for the role of extracorporeal treatment in the case of ethylenglycol intoxication are discussed., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: 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., Extrip Guidelines: 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., Case Report: 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.

Background: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP)., Methods: After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose 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. Following discussion, a second vote determined the final recommendations., Results: Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D)., Conclusion: APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated.

High-flux hemodialysis is the method of choice for the treatment of many life threatening intoxications. Reports on intoxication with pentoxifylline are rare, and although pharmacokinetic properties of the drug suggest a potential role for hemodialysis, there are no published reports on extracorporeal treatment attempts. We report the first case of successful treatment of potentially life-threatening pentoxifylline intoxication by high-flux hemodialysis. Based on this single case, dialysis should be considered, especially in anuric patients with pentoxifylline intoxication.

Guided by the idea of providing a stable electrolyte composition of the dialysate, the late Bernd Tersteegen designed a machine ingeniously combining the advantages of a closed tank hemodialysis system with the efficacy and bacteriological safety of a single-pass system. Several thousand dialysis sessions have been performed with this system in the chronic hemodialysis population. Recently, highly efficient (i.e. high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit as extended dialysis. Furthermore, they can also be a safer, more effective and less costly alternative to traditional extracorporeal techniques in the treatment of severe intoxication. In a case-based approach, we review the increasing use of such a system., (Copyright 2004 S. Karger AG, Basel)

Recently, highly efficient (i.e., high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit. They also can be a safer, more effective, and less costly alternative to traditional extracorporal techniques in the treatment of severe intoxication. This holds true even if the substance to be eliminated is believed to be a poor candidate for dialysis treatment. We report a case of successful treatment of potentially life-threatening intoxication, with valproic acid (VPA) using a GENIUS batch dialysis system for combined standard and extended high-volume hemodialysis therapy. Concentration of VPA in the total collected dialysate were measured.

Carbamazepine intoxication is associated with seizures, coma, arrhythmias and death. In acute intoxication, charcoal hemoperfusion is employed for removal of the drug. This can be associated with thrombocytopenia, coagulopathy, hypothermia and hypocalcemia. Alternatively, we used high-efficiency hemodialysis with a batch dialysis system (Genius), lowering not only serum levels of carbamazepine but removing a considerable amount of the drug as measured in the dialysate. This treatment regimen was compared to treatment by hemoperfusion. A 3.5-hour high-flux hemodialysis was as effective as a 2-hour hemoperfusion. We conclude that high-efficiency hemodialysis is a safe and effective alternative for treating life-threatening carbamazepine intoxication.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In addition, ADMA is degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which hydrolyzes ADMA to L-citrulline and dimethylamine. Activity of DDAH is decreased by oxidized low density lipoprotein (LDL) or tumor necrosis factor-alpha (TNF-alpha) in vitro yielding increased levels of ADMA. Furthermore, plasma levels of ADMA are elevated in hyperhomocyst(e)inemia and in hypertensive patients on a high salt diet. Data from several experimental studies suggest that ADMA concentrations in a pathophysiologically high range (3 to 10 micromol/L) significantly inhibit vascular NO formation by NO synthase in the presence of L-arginine in isolated human blood vessels, cultured macrophages, and in cultured endothelial cells. It has been well demonstrated that ADMA accumulates in chronic renal failure. Although there is controversy concerning the absolute concentration of ADMA, all authors found a two- to sixfold increase in ADMA levels in patients in chronic renal failure as compared to controls. Different dialysis treatment strategies differentially affect ADMA levels. The presence of atherosclerosis is associated with higher ADMA levels in patients with normal renal function as well as in dialysis patients, but this phenomenon may be unrelated to renal handling of ADMA. Reduced NO elaboration secondary to accumulation of ADMA may be an important pathogenic factor for atherosclerosis in chronic renal failure and ADMA may be a new uremic toxin. Clinical studies on the effect of ADMA are needed to further elucidate its pathophysiological role in atherosclerosis and uremia.

Background: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions., Methods: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session., Results: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes. The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected., Conclusion: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.