Extracorporeal Treatments In Poisoning Research Articles

Predictors of prolonged supratherapeutic serum lithium concentrations: a retrospective chart review

Introduction The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup suggests hemodialysis in severe lithium poisoning if specific criteria are met. One criterion is if the expected time to obtain a lithium concentration <1.0 mEq/L with optimal management is >36 h. There are a lack of data regarding which patient characteristics are associated with the rate at which patients achieve a lithium concentration <1.0 mEq/L. Methods We conducted a retrospective chart review analyzing hospital electronic medical records. Inclusion criteria consisted of a lithium concentration >1.2 mEq/L during hospitalization. We excluded patients who received extracorporeal treatment before 36 h elapsed from time of initial lithium concentration >1.2 mEq/L. The primary analysis consisted of a Cox regression and a secondary analysis evaluated the nomogram method described by Buckley and colleagues for predicting prolonged supratherapeutic lithium concentration. Results One hundred and one patients were included in the study. The median time to reach a lithium concentration <1.0 mEq/L was 42.5 h (IQR: 33.8–51.1). Older patients, patients taking a thiazide, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, patients with a higher initial lithium concentration, and patients with higher sodium concentrations achieved a lithium concentration <1 mEq/L at a slower rate. For the nomogram analysis, sensitivity (61.5%) and specificity (54.5%) were moderate, the positive predictive value (16.7%) was poor, and the negative predictive value (90.6%) was excellent. Discussion The results from our primary analysis suggest that identifying higher serum sodium concentration and use of certain antihypertensives that decrease glomerular filtration rate as predictors of an increased time to reach a therapeutic lithium concentration may help identify patients who meet the Extracorporeal Treatments in Poisoning criteria for hemodialysis. The nomogram method performed similarly to prior validation studies. Conclusions In this retrospective chart review of patients with supratherapeutic lithium concentrations, we identified several risk factors for prolonged supratherapeutic lithium concentrations.

Extracorporeal treatment in poisoning

In rare cases, intoxicated patients may require an extracorporeal procedure for enhanced toxin elimination. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup provides consensus- and evidence-based recommendations regarding the use of extracorporeal procedures in the management of critically ill, poisoned patients, with ongoing updates. Extracorporeal clearance is highest for low molecular weight substances with low volume of distribution, low plasma protein binding, and high water-solubility. To maximize the effect of extracorporeal clearance, blood and dialysate flow rates should be as high as possible, and the membrane with the largest surface area should be utilized. Intermittent hemodialysis is the most commonly employed extracorporeal procedure due to its highest effectiveness, while hemodynamically compromised patients can benefit from acontinuous procedure.

Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study

Introduction: Metformin, a commonly used oral antihyperglycemic drug, poses a rare risk related to the development of metformin-associated lactic acidosis (MALA). The Extracorporeal Treatments in Poisoning (EXTRIP) group recommended intermittent haemodialysis (IHD) as a primary elimination therapy in case of severe metformin poisoning. However, in haemodynamically unstable patients, our previous observations suggested that continuous venovenous haemofiltration (CVVH) might be more effective. This retrospective cohort study aimed to contribute evidence on the use of IHD and CVVH in patients with severe MALA, particularly in haemodynamically unstable patients. Methods: Data from January 2015 to December 2020 were collected from the Leuven University Hospital. Two separate search methods, based on hospital activity records and laboratory criteria, were used to identify patients with MALA. Patients diagnosed with MALA, receiving extracorporeal treatment within 24 h of admission, were included. Patients were categorized into the IHD and CVVH groups. Patient characteristics, treatment details, and outcomes were analysed. Results: Among 358,148 patient records, 35 MALA cases were identified. IHD was chosen as the initial elimination technique in 13 cases, whereas 22 patients were first commenced on CVVH. Patients treated with CVVH were sicker, had more comorbidities and had higher ventilation and vasopressor requirements. CVVH group had longer vasopressor use, longer ICU stays, and higher in-hospital mortality. Discussion: CVVH rather than IHD seems to be the preferred elimination technique in the more critically ill patients with MALA. Due to its retrospective design, this study failed to identify the superior elimination technique in terms of efficacy. Poorer outcomes in the CVVH group are likely attributed to the severity of illness rather than the inferiority of the elimination therapy. We acknowledge the diagnostic challenges regarding MALA. Using metformin assays could be beneficial in managing these patients. Conclusions: This study suggests clinicians’ preference for CVVH in severe cases of MALA with haemodynamic instability.

Retrospective evaluation of management guidelines for extracorporeal treatment of metformin poisoning

Introduction: The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup defined criteria for extracorporeal toxin removal in patients with metformin poisoning. The primary objective of this study was to determine the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria. The secondary objective was to determine the performance characteristics of the EXTRIP criteria. Methods: This was a single-center retrospective analysis of metformin poisoned patients. Inclusion criteria were: suspicion of metformin poisoning with at least one of the following present: lactate concentration >5 mmol/L; pH < 7.35; or impaired kidney function. Patient data were extracted by reviewers who were unaware of the study hypothesis. Cases were analyzed based on EXTRIP criteria, whether extracorporeal toxin removal was performed, and survival. Sensitivity, specificity, negative predictive value and positive predictive value were calculated with respect to the EXTRIP criteria and survival. Results: Of 201 patients studied, 145 patients met recommended EXTRIP criteria (EXTRIP positive) and 56 patients did not (EXTRIP negative). Among patients who met recommended EXTRIP criteria, 96 received extracorporeal toxin removal and 49 did not. There was no difference in survival between these groups: 75.0% versus 73.5%, respectively (P >0.05). All 56 patients who did not meet EXTRIP criteria, survived (negative predictive value = 100%). Discussion: The study did not demonstrate a survival benefit for extracorporeal toxin removal in those meeting EXTRIP criteria. Conclusion: In this retrospective analysis, the recommended EXTRIP criteria had a negative predictive value for death of 100%. Further study is needed to evaluate the benefit of extracorporeal toxin removal in patients meeting EXTRIP criteria for metformin poisoning.

正常腎機能患者のプレガバリン中毒に対する血液浄化療法の効果(Effects of blood purification therapy for pregabalin intoxication in patients with normal kidney function)

要旨 プレガバリンを過量服薬した正常腎機能患者に対してextracorporeal treatment（ECTR）を施行し，経過中の血中プレガバリン濃度を液体クロマトグラフィー質量分析法（LC–MS）で測定した2例を経験したため報告する。症例1は49歳の女性。プレガバリン5,750mg，ベニジピン160mgなどを過量服用し救急搬送された。来院時，舌根沈下あり気管挿管した。洞停止が頻回にみられ，循環不全進行のためノルアドレナリン，ドブタミンを開始した。来院後11時間より血液濾過透析（hemodiafiltration: HDF）を開始し5時間施行した。プレガバリンの半減期はHDF前22.8時間，HDF中2.3時間であった。症例2は41歳の女性。プレガバリン3,225mg，アムロジピン65mgなどを過量服薬し救急搬送された。ICU入室後に意識レベルが低下したため，気管挿管した。来院後5時間より血液透析（hemodialysis: HD）を開始し4時間施行した。HD終了後に意識レベルの改善がみられた。正常腎機能患者のプレガバリン中毒に対してECTRを導入したところ，血中プレガバリン濃度は速やかに低下し早期の意識レベル改善，循環動態改善の効果が得られた。昏睡状態や呼吸不全，循環不全を合併する重症プレガバリン中毒に対しては，正常腎機能であっても早期の状態改善にECTRが有効である可能性が示唆された。

Extracorporeal Treatment for Methotrexate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either "strong" or "weak/conditional") were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate-related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

Validation of a nomogram used to predict lithium concentration in overdose

Introduction Extracorporeal Treatment (ECTR) is an essential component in management of severe lithium toxicity. The Extracorporeal Treatments in Poisoning (EXTRIP) group’s suggested indications for ECTR include “if the expected time to obtain a [Li+] < 1.0mEq/L with optimal management is >36h”. Buckley et al. developed a lithium nomogram which could help predict the fall in lithium concentrations for chronic poisoning. Our aim is to externally validate the lithium nomogram in a cohort of cases with chronic accumulation and acute on chronic lithium poisoning. Methods A retrospective analysis of suspected cases of chronic accumulation and acute on chronic lithium poisoning referred to our Toxicology Unit from May 2013 to 2020 was performed. Results Out of 51 cases, 29 cases of chronic accumulation and eight cases of acute on chronic poisoning were analysed after excluding 14 cases who required haemodialysis. In chronic accumulation cases, the nomogram correctly identified 10 out of 14 patients whose [Li+] failed to drop below 1.0 mmol/L by 36 h (sensitivity 71.4% [95% CI 42 − 92%]), and 8 out of 15 patients whose [Li+] dropped below 1.0 mmol/L by 36 h (specificity 53.3% [95% CI 27 − 78%]), resulting in the positive predictive value (PPV) of 58.8%, negative predictive value (NPV) of 66.7% and accuracy of 62.1%. Conclusions Our study shows that the lithium nomogram is moderately sensitive at identifying patients with chronic lithium accumulation who will have a serum lithium concentration >1 mmol/L at 36 h without ECTR.

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n=38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence=C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence=A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).

Comparison of the EXtracorporeal TReatments In Poisoning (EXTRIP) and Paris criteria for neurotoxicity in lithium poisoned patients.

Two guidelines for haemodialysis in lithium poisoning, one from the Extracorporeal TReatments in Poisoning (EXTRIP) workgroup and a single centre retrospective one (Paris) differ. We compared outcomes in lithium poisoning based on these criteria with a primary outcome of worsening neurological symptoms in patients for whom EXTRIP and Paris criteria were discordant. Poison centre data were queried for lithium poisoned patients for whom haemodialysis was either recommended or performed. Patients were categorized according to EXTRIP and Paris criteria and excluded if the peak lithium concentration was <1.2 mmol/L or if neurological follow-up was unavailable. Comparative analyses were only performed when both criteria could be assessed. In total, 219 patients were analysed. Paris criteria were met in 70 and EXTRIP criteria in 178. Forty two patients were excluded because Paris criteria could not be evaluated. When Paris and EXTRIP both supported haemodialysis, 50/57 (88%) of patients who received haemodialysis improved, as did all 3 who did not receive haemodialysis. When Paris and EXTRIP did not support haemodialysis, all nondialysed patients did well. Among the 86 patients for whom EXTRIP supported haemodialysis but Paris did not, 4/19 (21%) patients not dialysed deteriorated (P =.02; odds ratio =8.7, 95% confidence interval =1.5-51.8), 1 of whom died. All 8 patients for whom Paris criteria supported haemodialysis but EXTRIP did not were dialysed and improved. When the EXTRIP and Paris criteria are discordant, EXTRIP criteria outperforms the Paris criteria at identifying potentially ill patients who might benefit from haemodialysis.

Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs. We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. A total of 44 studies (three in vitro studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug. On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.

Haemodialysis for lithium poisoning: Translating EXTRIP recommendations into practical guidelines.

This study aimed to determine the impact on practice of applying the Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup criteria to lithium toxicity. We retrospectively examined the medical records of patients from three hospitals who presented with chronic or acute on chronic lithium poisoning with a lithium concentration ≥1.3 mmol/L (2008-2018). We determined which criteria were met by patients and their subsequent course. We developed and validated a method to predict if lithium concentration would be >1mmol/L at 36 hours. There were 111 acute on chronic and 250 chronic lithium toxic patients. Nine patients (2.5%) were treated with haemodialysis. Six chronic patients had neurological sequelae. The "estimated lithium concentration at 36 hours > 1 mmol/L" criterion required pharmacokinetic calculations. A simple nomogram was developed using Estimated Glomerular Filtration Rate (eGFR) and lithium concentration. For chronic toxicity, the nomogram would have correctly predicted lithium concentration >1.4 mmol/L at 36 hours in all except two patients. If EXTRIP criteria were followed, dialysis would have been instituted for 211 patients (58%). However, only 51 patients with chronic toxicity fulfilled both a concentration and a clinical criterion. Late neurological sequelae were observed in five out of six patients who fulfilled a concentration and a clinical criterion on admission, with the sixth meeting these criteria shortly after admission. The EXTRIP criteria are too broad, but minor modifications allow haemodialysis to be targeted to those most at risk of sequelae. Most acute on chronic poisonings do not need haemodialysis, but it might shorten hospital stay in those with very high concentrations. The nomogram accurately predicts the fall in lithium concentration for chronic poisoning.

Common Toxidromes and the Role of Extracorporeal Detoxification.

Extracorporeal modalities have been used for detoxification for decades, with hemodialysis the preferred and most commonly used modality. Salicylates, lithium, methanol, and ethylene glycol are the most common poisonings treated with dialysis. For each of these common poisonings, a description of the toxidrome including pharmacokinetics, clinical presentation, an overview of treatment, and the role and application of dialysis is outlined. Inhibition of alcohol dehydrogenase to prevent the formation of toxic metabolites in methanol and ethylene glycol is discussed in detail, including the use of fomepizole and ethanol to complement and in some cases prevent the need for hemodialysis. Hemodialysis has been attempted to treat many poisonings, often without success. A description of EXTRIP (Extracorporeal Treatments in Poisoning), a multidisciplinary project examining the evidence for extracorporeal treatments in poisoning, is also described. Recommendations for poisoning with acetaminophen, baclofen, barbiturates, carbamazepine, digoxin, metformin, phenytoin, thallium, theophylline, tricyclic antidepressants, and valproic acid are provided in a comprehensive table.

Assessment of Extracorporeal Treatments in Poisoning criteria for the decision of extracorporeal toxin removal in lithium poisoning.

To assess recommendations provided by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup on extracorporeal toxin removal (ECTR) in lithium poisoning. Retrospective assessment in a 128 lithium-poisoned patient cohort previously used to identify ECTR initiation criteria that could improve outcome (Paris criteria). ECTR requirement using EXTRIP criteria was compared to the actual practice or if Paris criteria were used. The potential impact on outcome if these different criteria were used was investigated. Using the recommended (Rec-EXTRIP) or recommended + suggested (All-EXTRIP) EXTRIP criteria, ECTR would have been indicated in more patients than was actually done (P < .001), or if Paris criteria were used (P < .01). The non-actually ECTR-treated patients fulfilling Rec-EXTRIP or All-EXTRIP criteria had shorter intensive care unit stay (P < .05) and no significant increase in fatalities and neurological impairment on discharge in comparison to the actually ECTR-treated patients. ECTR requirements using EXTRIP vs Paris criteria were not concordant (P < .001). In the non-actually ECTR-treated patients, 31/106 and 55/106 patients fulfilled Rec-EXTRIP or All-EXTRIP but not Paris criteria, respectively. Those patients had longer stay (P < .01) but no worse neurological impairment on discharge than the patients not fulfilling any of these criteria (50/106 and 26/106, respectively). In the non-actually ECTR-treated patients, 7/106 fulfilled Paris but not Rec-EXTRIP criteria. Those patients had longer stay (P < .05) and worse neurological impairment on discharge (P < .01) than the 50/106 patients not fulfilling any of these criteria. In this cohort of lithium poisonings, EXTRIP criteria may lead to more ECTR than actually performed or if the Paris criteria were used, with no demonstrated improvement in outcome.

Antiepileptic Overdose

ABSTRACTAntiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Common signs of toxicity of these drugs are central nervous system manifestations such as altered sensorium, lethargy, ataxia, and nystagmus. Some ingestions can paradoxically precipitate seizures and even status epilepticus. Sodium valproate can cause hyperammonemic encephalopathy and cerebral edema. Carbamazepine is implicated in cardiac arrhythmias and hyponatremia. Phenobarbital causes sedation, respiratory depression, and hypotension. In suspected overdose, apart from the routine laboratory tests, serum levels of the drug should be sent. Serial levels should be measured, as drug toxicity can be prolonged. Treatment of all these overdoses begins with stabilization of airway, breathing, and circulation, and endotracheal intubation being performed to protect the airway in patients with altered mental status. For decontamination, a single dose of activated charcoal should be given. Multidose of activated charcoal may be useful in phenytoin, carbamazepine, and phenobarbital overdose. Naloxone and carnitine are indicated in valproate overdose. Carbamazepine overdose can cause a widened QRS complex and arrhythmias, which can be treated with sodium bicarbonate. Forced alkaline diuresis is no longer advocated for phenobarbital poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup have formulated guidelines for extracorporeal removal of all these drugs. In most cases, hemodialysis is preferred. Other modalities include charcoal hemoperfusion (especially for carbamazepine) or continuous venovenous hemodialysis. Patients who ingest long-acting preparations should be monitored for longer periods.How to cite this articleMurty S. Antiepileptic Overdose. Indian J Crit Care Med 2019;23(Suppl 4):S290–S295.

Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup

Background: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin. Methods: After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations. Results: Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence = B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D). Conclusion: ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.

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

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.

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

Background. 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. Methods. 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. Results. 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. Conclusions. 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

Background. 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. Methods. 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. Results. 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). Conclusion. Theophylline poisoning is amenable to ECTRs. The workgroup recommended extracorporeal removal in the case of severe theophylline poisoning.

Extracorporeal treatment for acetaminophen poisoning: Recommendations from the EXTRIP workgroup

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.

Extracorporeal Treatment for Barbiturate Poisoning: Recommendations From the EXTRIP Workgroup

The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use ofextracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all articles, extracted data, summarized key 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. 617 articles met the search inclusion criteria. Data for 538 patients were abstracted and evaluated. Only case reports, case series, and nonrandomized observational studies were identified, yielding a low quality of evidence for all recommendations. Using established criteria, the workgroup deemed that long-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with multiple-dose activated charcoal. (3) Intermittent hemodialysis is the preferred mode of ECTR, and multiple-dose activated charcoal treatment should be continued during ECTR. (4) Cessation of ECTR isindicated when clinical improvement is apparent. This report provides detailed descriptions of the rationale for all recommendations. In summary, patients with long-acting barbiturate poisoning should be treated with ECTR provided at least one of the specific criteria in the first recommendation is present.