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Blood Purification in Toxicology: Nephrology's Ugly Duckling
Abstract
Contrary to popular opinion, application of extracorporeal therapies for poisonings predates their use for ESRD. Despite this observation, the science of blood purification in toxicology remains desperately stagnant today. In fact, much of our current knowledge is derived from George Schreiner's 1958 review. Original publications are almost exclusively composed of case reports and case series, from which good inference is impossible. Until randomized controlled trials become available, the medical community would be well served by a group mandated to systematically review available literature, extract relevant information, provide recommendations based on current evidence, and propose research initiatives. The EXtracorporeal TReatments In Poisoning workgroup, formed by several international experts in different medical fields and represented by over 20 societies, now has this mission.
... The intervention of a nephrologist or intensivist is often necessary, to correct electrolyte or acid-base disturbances, manage kidney or other organ dysfunctions and evaluate the need for extracorporeal treatment (ECTR). 2 Currently there is a lack of randomized control trials comparing extracorporeal versus support treatment, due to the relative rarity of poisonings treated with extracorporeal treatment, the low mortality from most poisons, the heterogeneity of poisoned patients and the ethical obstacles when measuring ECTR versus placebo. [3][4][5] However since 2010, a multidisciplinary group named EXtracorporeal TReatments In Poisoning (EXTRIP), has been reviewing and publishing evidence-based recommendations, grading the available evidence and establishing guidelines to standardize the use of extracorporeal detoxification in poisoned patients. 3,5 The aim of this narrative review is to describe the available extracorporeal modalities that can be used for poisoned patients, reflecting on their main indications and limitations and provide a practical view on the management of the most common poisons found in clinical practice. ...
... [3][4][5] However since 2010, a multidisciplinary group named EXtracorporeal TReatments In Poisoning (EXTRIP), has been reviewing and publishing evidence-based recommendations, grading the available evidence and establishing guidelines to standardize the use of extracorporeal detoxification in poisoned patients. 3,5 The aim of this narrative review is to describe the available extracorporeal modalities that can be used for poisoned patients, reflecting on their main indications and limitations and provide a practical view on the management of the most common poisons found in clinical practice. n METHODS A non-systematic search of the PubMed database for English-language articles using the keywords "extracorporeal treatment", "hemodialysis" and "poisoning" was performed to construct this narrative review. ...
Accidental or intentional poisoning and drug overdose are a significant source of morbidity, mortality and health care expenditure worldwide. Extracorporeal removal treatments have been used to treat poisoning for decades and different modalities are available, including
hemodialysis, hemofiltration, hemoperfusion, continuous renal replacement therapy and therapeutic plasma exchange. A comprehensive
understanding of their purpose is key to choose the right modality for each clinical scenario.
Lithium, salicylates, metformin and toxic alcohols are amongst the most common poisons treated with extracorporeal removal. Unfortunately, due to poison characteristics and specific modality limitations, extracorporeal treatments are useful to treat only a small number of
poisons. Nevertheless, they have been increasingly used for supportive care in poisoning caused by substances not amenable for removal.
Evidence regarding extracorporeal treatment in poisoning is modest. However, its use has been systematically reviewed in several poisons
within the last decade by the Extracorporeal Treatment in Poisoning workgroup. The preferred treatment for extracorporeal removal of poisons
is intermittent hemodialysis, according to the most recent guidelines and case reports available, as it effectively removes most of the common
substances involved in poisoning and corrects electrolytes and acid base imbalances.
This narrative review gives an overview of the available extracorporeal modalities used for poisoned patients, reflecting on their main
indications and limitations as well as a practical view on the management of the most common poisons found in clinical practice.
... As the prognosis of most toxic exposures remains excellent with supportive measures alone, only a small minority of poisonings benefit from active elimination enhancement; for example, MDAC, urine alkalinization, and hemodialysis were only used in 0.06 %, 0.5 %, and 0.1 %, respectively, of patients reported to the US poison control centers [2]. Although the large proportion of the literature reviewing the efficacy of elimination enhancement techniques is derived from human case reports, evidencebased and consensus-based recommendations are now available for extracorporeal treatments [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. ...
... The EXTRIP (EXtracorporeal Treatment In Poisoning, http://www.extrip-workgroup.org/) workgroup [3,4] have published guidelines for the use of blood purification for 16 key poisons [5-10, 12, 15, 47, 48]. For poisons not covered by these clinical recommendations, a comprehensive risk assessment that includes weighing the costbenefit ratio for ECTR is required, which can be summarized in Fig. 3. ...
Along with active supportive care, judicious gastrointestinal decontamination, and antidotal therapy, elimination enhancement techniques should be considered in the comprehensive management of any poisoned patient. Elimination enhancement techniques are defined as any procedure that accelerates the endogenous clearance of poison already absorbed and located either in the blood or tissue compartment. Corporal techniques provide their effects inside the body and include multiple-dose activated charcoal (MDAC), resins, and urine pH manipulation, as discussed elsewhere. Extracorporeal treatments (ECTRs) occur in a circuit outside the body (with the exception of peritoneal dialysis) and include hemodialysis, hemoperfusion, hemofiltration, and plasma exchange [1]. As the prognosis of most toxic exposures remains excellent with supportive measures alone, only a small minority of poisonings benefit from active elimination enhancement; for example, MDAC, urine alkalinization, and hemodialysis were only used in 0.06%, 0.5%, and 0.1%, respectively, of patients reported to the US poison control centers. Although the large proportion of the literature reviewing the efficacy of elimination enhancement techniques is derived from human case reports, evidence-based and consensus-based recommendations are now available for extracorporeal treatments [2–15].
... The use of activated charcoal filters (coated and non-coated) as an adjunct to the extracorporeal treatment (ECT) of AT intoxications is not widely applied, and only few cases are reported with varying degree of effect [9,15,16]. Likewise, we find the indication for initiating treatment involving ECT including coated activated charcoal filters (CAC-HP) vague and the evidence low [17]. Accordingly, a literature search in PubMed and EMBASE has not been able to identify any controlled clinical toxicological studies concerning CAC-HP. ...
... For several decades, ECT modalities have been used in various settings [17,26]. The pioneer in the field of extracorporeal clearance was the US-born biochemist, John Jacob Abel, who in the seeking of a way to detoxify salicylate-poisoned patients made the first artificial kidney [27]. ...
Coated activated charcoal hemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomised clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared to standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes following AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control group were found when analysing for differences in AT levels in plasma at any time point. Furthermore, significant differences between the control and intervention group in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared to standard treatment alone. We hypothesize that the effect of modern CAC-HP as a treatment modality in AT poisoned human patients may be inadequate. This article is protected by copyright. All rights reserved.
... Moreover, this selection bias is complicated by the phenomenon of confounding-by-indication, where dogs exposed to higher toxic doses were more likely to be treated with either ILE or TPE, because of a greater clinical concern for morbidity and mortality. 33 As a retrospective study, the data acquired are inherently limited by their availability and accuracy within the medical record. Time to presentation and maximal exposure dose were provided as estimates and were associated with a margin of error. ...
Background:
Traditional management of non-steroidal anti-inflammatory drug (NSAID) intoxication includes gastrointestinal decontamination, intravenous administration of fluids (IVF), and gastroprotection. Intravenous administration of lipid emulsion (ILE) and therapeutic plasma exchange (TPE) are popular novel therapeutic strategies.
Hypothesis:
Compare outcomes of dogs treated with IVF, ILE, and TPE for NSAID intoxications and evaluate outcome predictors for drug subgroups.
Animals:
Four hundred thirty-four dogs with NSAID intoxications (2015-2020).
Methods:
Multicenter retrospective study of ibuprofen, carprofen, and naproxen intoxication. An ordinal outcome was defined as mild gastrointestinal, moderate kidney, or signs of severe central nervous system disease.
Results:
Signs of neurological disease were overrepresented and acute kidney injury underrepresented in the TPE group among dogs exposed to kidney- or CNS-toxic doses (P = .05), though all TPE dogs with signs of neurological disease had evidence of neurotoxicity at presentation. Dogs treated with IVF had a higher maximal creatinine concentration (median, 1.1 mg/dL; range, 0.4-8.44 mg/dL) compared with IVF + ILE (median, 0.9 mg/dL; range, 0.4-6.2 mg/dL; P = .01). Increased maximum time to presentation (P < .001), higher baseline creatinine (P < .001) and PCV (P = .007), and absence of induced emesis (P < .001) were associated with greater clinical severity. Ibuprofen toxicosis was associated with more severe clinical signs compared with carprofen (P = .03). Overall survival rate was 99%.
Conclusions and clinical importance:
NSAID toxicosis generally carries an excellent prognosis in dogs. Despite similar outcomes of lower incidence of AKI in the TPE group, and slightly lower maximal creatinine concentration in dogs treated with ILE vs IVF alone, ILE and TPE should be considered in the management of severe NSAID toxicosis.
... Its mission is to provide recommendations on the use of ECTRs in poisoning. [4][5][6][7][8] The objective of this article is to present EXTRIP's systematic review of the literature and recommendations for the use of ECTR in patients poisoned from gabapentin or pregabalin. ...
... org). 10,11 We present EXTRIP's comprehensive review and recommendations for the use of ECTR in patients with baclofen poisoning. ...
Baclofen toxicity results from intentional self-poisoning ("acute baclofen poisoning") or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies. (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation.
... extrip-workg roup. org) [2][3][4][5]. We present EXTRIP's systematic review and recommendations for the use of ECTR in patients with BAA poisoning. ...
Background
β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.
Methods
We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.
Results
A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.
Conclusions
BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.
... 37 However, because the goal in the treatment of intoxications and overdoses is the rapid clearance of the offending agent, IHD is generally preferred over CRRT in this setting, even in patients who are hemodynamically unstable. 38,39 The role of RRT in the management of hyperammonemia is uncertain. Based on molecular weight, ammonia is readily cleared by both diffusion and convection. ...
Continuous renal replacement therapy (CRRT) is commonly employed to provide renal support for critically ill patients with acute kidney injury (AKI); particularly patients who are hemodynamically unstable. A variety of techniques that vary in their mode of solute clearance may be used, including continuous venovenous hemofiltration (CVVH) with predominantly convective solute clearance, continuous venovenous hemodialysis (CVVHD) with predominantly diffusive solute clearance and continuous venovenous hemodiafiltration (CVVHDF), which combines both dialysis and hemofiltration. Herein we compare CRRT with other modalities of renal support and review indications for initiation of renal replacement therapy, and dosing and technical aspects in the management of CRRT.
... The science of blood purification in toxicology has remained rather stagnant for a long period of time [8] and is still based on case reports and small case series. Over the last decade, several of those reports have shown that high-flux hemodialysis represents an excellent treatment method even for compounds that are predominantly proteinbound [9,10]. ...
Hemodialysis is the extracorporeal treatment of choice for various life-threatening intoxications, with the exception of highly protein-bound substances, which are preferably removed by charcoal hemoperfusion. This technique, however, is limited by its availability and its significant side effects. We present a potentially life-threatening diphenhydramine (DPH) overdose in a stuporous female patient in which high cut-off hemodialysis was used. Timely detoxification resulted in rapid gain of consciousness, allowing the patient to state the existence and location of another poison victim.
... Rationale, background, objectives, complete methodology, and many toxin-specific recommendations are already published. [1][2][3][4][5][6][7][8][9][10][11][12][13] The following presents the workgroup's systematic review and clinical recommendations regarding the use of ECTR in patients with digoxin poisoning. ...
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.
... The rationale, background, objectives, methodology, and its initial recommendations have been published previously. [1][2][3][4][5][6][7][8][9][10][11][12][13] In this Special Report, we present a systematic literature review and evidence-based recommendations for the use of ECTR in phenytoin poisoning. ...
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.
... The rationale, background, objectives, methodology, and other recommendations have been published previously. [23][24][25][26][27][28][29][30][31][32] Predetermined methodology, incorporating guidelines from the Appraisal of Guidelines for Research and Evaluation 33 and Grades of Recommendation Assessment, Development and Evaluation, 34 is described in detail elsewhere. 25 The primary literature search was conducted on July 10, 2012, in MEDLINE, EMBASE, and the Cochrane Library (Reviews and Central). ...
Study objective Salicylate poisoning is a challenging clinical entity associated with substantial morbidity and mortality. The indications for extracorporeal treatments such as hemodialysis are poorly defined. We present a systematic review of the literature along with evidence-and consensus-based recommendations on the use of extracorporeal treatment in salicylate poisoning. Methods The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup is a multidisciplinary group with international representation whose aim is to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. We conducted a systematic literature review followed by data extraction and summarized findings, following a predetermined format. The entire work group voted by a 2-round modified Delphi method to reach 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 Eighty-four articles met inclusion criteria, including 1 controlled clinical trial, 3 animal studies, and 80 case reports or case series, yielding an overall very low quality of evidence for all recommendations. Clinical data on 143 patients (130 sets of which could be analyzed for patient-level entry data), including 14 fatalities, were reviewed. Toxicokinetic data on 87 patients were also included. After the second round of voting, the workgroup concluded that salicylates are dialyzable by hemodialysis and hemoperfusion (level of evidence=B) and recommended extracorporeal treatment in patients with severe salicylate poisoning (1D), including any patient with altered mental status (1D), with acute respiratory distress syndrome requiring supplemental oxygen (1D), and for those in whom standard therapy is deemed to be failing (1D) regardless of the salicylate concentration. High salicylate concentrations warrant extracorporeal treatment regardless of signs and symptoms (>7.2 mmol/L [100 mg/dL] [1D]; and >6.5 mmol/L [90 mg/dL] [2D]), with lower thresholds applied for patients with impaired kidney function (>6.5 mmol/L [90 mg/dL] [1D]; >5.8 mmol/L [80 mg/dL] [2D]). Extracorporeal treatment is also suggested for patients with severe acidemia (pH ≤7.20 in the absence of other indications) (2D). Intermittent hemodialysis is the preferred modality (1D), although hemoperfusion (1D) and continuous renal replacement therapies (3D) are acceptable alternatives if hemodialysis is unavailable, as is exchange transfusion in neonates (1D). Conclusion Salicylates are readily removed by extracorporeal treatment, with intermittent hemodialysis being the preferred modality. The signs and symptoms of salicylate toxicity listed warrant extracorporeal treatment, as do high concentrations regardless of clinical status.
... The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup consists of an international panel of experts whose primary mission is to develop evidence-based recommendations for the use of extracorporeal treatments (ECTRs) for poisonings (1)(2)(3)(4)(5)(6)(7). Members of the EXTRIP Workgroup provide expertise from a broad range of medical specialties and represent diverse professional societies (Table 1). ...
Metformin toxicity, a challenging clinical entity, is associated with a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is poorly defined at present. Here, the Extracorporeal Treatments In Poisoning workgroup, comprising international experts representing diverse professions, presents its systematic review and clinical recommendations for extracorporeal treatment in metformin poisoning.
A systematic literature search was performed, data extracted, findings summarized, and structured voting statements developed. A two-round modified Delphi method was used to achieve consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Anonymized votes and opinions were compiled and discussed. A second vote determined the final recommendations.
One hundred seventy-five articles were identified, including 63 deaths: one observational study, 160 case reports or series, 11 studies of descriptive cohorts, and three pharmacokinetic studies in end-stage renal disease, yielding a very low quality of evidence for all recommendations. The workgroup concluded that metformin is moderately dialyzable (level of evidence C) and made the following recommendations: extracorporeal treatment is recommended in severe metformin poisoning (1D). Indications for extracorporeal treatment include lactate concentration greater than 20 mmol/L (1D), pH less than or equal to 7.0 (1D), shock (1D), failure of standard supportive measures (1D), and decreased level of consciousness (2D). Extracorporeal treatment should be continued until the lactate concentration is less than 3 mmol/L (1D) and pH greater than 7.35 (1D), at which time close monitoring is warranted to determine the need for additional courses of extracorporeal treatment. Intermittent hemodialysis is preferred initially (1D), but continuous renal replacement therapies may be considered if hemodialysis is unavailable (2D). Repeat extracorporeal treatment sessions may use hemodialysis (1D) or continuous renal replacement therapy (1D).
Metformin poisoning with lactic acidosis appears to be amenable to extracorporeal treatments. Despite clinical evidence comprised mostly of case reports and suboptimal toxicokinetic data, the workgroup recommended extracorporeal removal in the case of severe metformin poisoning.
... The science of blood purification in toxicology has remained rather stagnant for a long period of time [8] and is still based on case reports and small case series. Over the last decade, several of those reports have shown that high-flux hemodialysis represents an excellent treatment method even for compounds that are predominantly proteinbound [9,10]. ...
Hemodialysis is the extracorporeal treatment of choice for various life-threatening intoxications, with the exception of highly protein-bound substances, which are preferably removed by charcoal hemoperfusion. This technique, however, is limited by its availability and its significant side effects. We present a potentially lifethreatening diphenhydramine (DPH) overdose in a stuporous female patient in which high cut-off hemodialysis was used. Timely detoxification resulted in rapid gain of consciousness, allowing the patient to state the existence and location of another poison victim.
... extrip-workgroup.org) (13). The predetermined methodology incorporated guidelines from Appraisal of Guidelines for Research and Evaluation and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and it is described in detail elsewhere (14). ...
Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning.
Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus.
Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH ≤7.15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/osmolar gap may be informative; or, in the context of impaired kidney function. Intermittent hemodialysis is the modality of choice and continuous modalities are acceptable alternatives. Extracorporeal treatment can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed. Extracorporeal Treatments in Poisoning inhibitors and folic/folinic acid should be continued during extracorporeal treatment. General considerations: Antidotes and extracorporeal treatment should be initiated urgently in the context of severe poisoning. The duration of extracorporeal treatment extracorporeal treatment depends on the type of extracorporeal treatment used and the methanol exposure. Indications for extracorporeal treatment are based on risk factors for poor outcomes. The relative importance of individual indications for the triaging of patients for extracorporeal treatment, in the context of an epidemic when need exceeds resources, is unknown. In the absence of severe poisoning but if the methanol concentration is elevated and there is adequate alcohol dehydrogenase blockade, extracorporeal treatment is not immediately required. Systemic anticoagulation should be avoided during extracorporeal treatment because it may increase the development or severity of intracerebral hemorrhage.
Extracorporeal treatment has a valuable role in the treatment of patients with methanol poisoning. A range of clinical indications for extracorporeal treatment is provided and duration of therapy can be guided through the careful monitoring of biomarkers of exposure and toxicity. In the absence of severe poisoning, the decision to use extracorporeal treatment is determined by balancing the cost and complications of extracorporeal treatment to that of fomepizole or ethanol. Given regional differences in cost and availability of fomepizole and extracorporeal treatment, these decisions must be made at a local level.
... Finally, when data supporting ECTR in a specific poisoning become sufficiently convincing and controversy is limited, new reports decline as they are not sufficiently novel or informative for publication. This is the case for salicylate poisoning, where most nephrologists would agree that ECTR may be life saving (15). ...
There are currently limited data on the trends in case reporting of poisoned patients undergoing enhanced elimination with an extracorporeal treatment (ECTR). The present manuscript specifically reviews the longitudinal trends of reports according to technique, poison, and country of publication. To identify case reports of ECTR use in the management of poisoning, multiple databases were searched. There were no limitations on language and year of publication. All case reports describing individual patients undergoing ECTR with the intent of enhancing the elimination of a poison were included in the analysis. Since 1913, 2908 reports were identified. There were an increasing number of published reports with time except for a slight decrease during the 1990s. Hemodialysis was by far the most commonly used ECTR in poisoning, followed by hemoperfusion. The number of reported peritoneal dialyses decreased steadily since 1980s. Methanol, ethylene glycol, lithium, and salicylates remained among the most commonly reported poisons in every decade. The large majority of publications originated from either Europe or North America, and more specifically from the United States, Germany, the United Kingdom, and China. Despite the emerging apparition of new techniques, hemodialysis remains to this day the favoured ECTR in the treatment of poisoned patients.
... Rationale, background, objectives, complete methodology, and the first poison recommendation have been previously published (1)(2)(3). The following text reviews the results and recommendations for tricyclic antidepressants (TCAs). ...
The Extracorporeal Treatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, the workgroup presents its results for tricyclic antidepressants (TCAs). After an extensive literature search, using a predefined methodology, the subgroup responsible for this poison reviewed the articles, extracted the data, summarized 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 RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed in person at a meeting. A second vote determined the final recommendations. Seventy-seven articles met inclusion criteria. Only case reports, case series, and one poor-quality observational study were identified yielding a very low quality of evidence for all recommendations. Data on 108 patients, including 12 fatalities, were abstracted. The workgroup concluded that TCAs are not dialyzable and made the following recommendation: ECTR is not recommended in severe TCA poisoning (1D). The workgroup considers that poisoned patients with TCAs are not likely to have a clinical benefit from extracorporeal removal and recommends it NOT to be used in TCA poisoning.
... Differences in physician preferences for enhanced elimination in lithium poisoning are noted within a single institution, and physicians often choose not to follow recommendations by clinical toxicologists (2,3). This suggests that the management of lithium poisoning is uncertain among physicians and this is illustrated by a lack of concordance between existing recommendations and practice. ...
Three patterns of lithium poisoning are recognized: acute, acute-on-chronic, and chronic. Intravenous fluids with or without an extracorporeal treatment are the mainstay of treatment; their respective roles may differ depending on the mode of poisoning being treated. Recommendations for treatment selection are available but these are based on a small number of observational studies and their uptake by clinicians is not known. Clinician decision-making in the treatment of four cases of lithium poisoning was assessed at a recent clinical toxicology meeting using an audience response system. Variability in treatment decisions was evident in addition to discordance with published recommendations. Participants did not consistently indicate that hemodialysis was the first-line treatment, instead opting for a conservative approach, and continuous modalities were viewed favorably; this is in contrast to recommendations in some references. The development of multidisciplinary consensus guidelines may improve the management of patients with lithium poisoning but prospective randomized controlled trials are required to more clearly define the role of extracorporeal treatments.
... It was assembled to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning (www.extrip-workgroup.org). Rationale, background, objectives, and complete methods of this endeavor, supported by the Acute Dialysis Quality Initiative, were reported previously (1,2). ...
The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl).
After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized 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 RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations.
Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D).
Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.
... The science of blood purification in toxicology has been remaining rather stagnant for a long period of time [6] and is still based on case reports and small case series. Several of those reports over the last decade have shown that high-flux hemodialysis represents an excellent treatment method even for compounds that a largely protein bound [7,8]. ...
High-flux hemodialysis is the extracorporeal treatment of choice for various life threatening intoxications. Most published reports support the use of hemoperfusion in the context of severe theophylline poisoning, but the technique is limited by its significant side-effects. We present a potentially life threatening theophylline overdose treated with hemodialysis in a pregnant patient. For the first time the amount of theophylline removed was measured in the total collected spent dialysate, after a 3.75 hour hemodialysis and an 8 hour extended dialysis.
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid–base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong (“we recommend”) or weak/conditional (“we suggest”), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8–12 mmol/L or anion gap 23–27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
Poisoning and toxic ingestions cause significant morbidity and mortality worldwide. Extracorporeal therapies such as dialysis, haemoperfusion and plasma exchange are selectively applied to patients with severe intoxications unresponsive to standard interventions and can be lifesaving. Extracorporeal therapies are a complex but fundamental aspect of the practice of nephrology. Without high‐quality evidence to guide implementation, an understanding of toxicokinetics and the physiochemical principles of the enhanced elimination techniques is especially important. This review provides a comphrensive, user‐friendly outline of the application of extracorporeal therapy in the poisoned patient.
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.
Objective
To investigate the clinical outcome and complications associated with extracorporeal blood purification (EBP) using either hemodialysis (HD), hemodialysis and hemoperfusion (HD + HP), or therapeutic plasma exchange (TPE) for the management of acute toxin ingestion in small animals.
Design
Retrospective, multicenter study from January 2011 to July 2018.
Setting
One university teaching hospital and one private specialty hospital.
Animals
Fifty-one dogs and 3 cats with a history of acute toxin exposure that could lead to severe morbidity and mortality, managed with different EBP techniques.
Main Results
Nonsteroidal anti-inflammatory drugs (38/54, 52%), baclofen (8/54, 15%), and ethylene glycol (7/54, 13%) were the most common toxicities treated with EBP. Membrane-based TPE was used most commonly (22/54, 40.7%), followed by HD (17/54, 31.5%) and then HD + HP (15/54, 27.8%). There was an 83.3% (45/54) overall survival, with 88.9% (8/9) of nonsurvivors having clinical signs prior to therapy. One third (18/54) of the patients never developed clinical signs of toxicity. Treatment complications occurred in 44.4% (24/54) of the animals, although only 18.5% (10/54) of these complications, such as mild hypotension, thrombocytopenia secondary to the HP cartridge, facial swelling after plasma transfusion for TPE, bleeding from catheter size secondary to heparinization, or clotting of the system, could be attributed to the EBP treatment. None of the nonsurvivors died because of EBP complications.
Conclusions
Early initiation of EBP therapy might be considered as an alternative route of decontamination in severe acute toxicities with high potential for significant morbidity and mortality. The survival rate in small animals undergoing EBP is high despite exposure to potential lethal doses of toxins, and survival appears to be more likely if clinical signs of toxicity are not present at the time of EBP. Continued research is warranted with randomized controlled clinical trials to further evaluate the clinical efficacy and benefit of EBP.
Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150 mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as “dialyzable” for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).
Drug overdose and poisoning(s) continue to remain a significant cause of morbidity and mortality. Extracorporeal treatments are instinctively and sometimes indiscriminately used under the assumption that removal of poison from the body will reverse the toxic effects and improve survival. In actuality, the maximum benefit from extracorporeal treatments is seen only when they are used prudently for a select group of patients with drug overdose/poisoning, as vast majority of the cases can be managed by supportive therapy alone or in combination with a specific antidote if available. For judicious utilization of extracorporeal therapy, one ought to be familiar with the toxicokinetic properties of the poison as well as the intricacies of different extracorporeal therapies. With that goal, this chapter provides an in-depth review of clinically important pharmacokinetic principles that determine extracorporeal removal of drugs (toxins) and highlights unique features of different extracorporeal therapies. Understanding of these basic principles can help clinician make a sound management decision even in situations where no previous experience exists for a particular toxin. Finally, the chapter concludes with summary of practical recommendations for the management of some of the most commonly encountered poisonings.
Background:
Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although 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.
Objectives:
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.
Methods:
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.
Results:
Forty-three studies (two animal studies, 34 patient reports or patient series, and 7 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 extracorporeal removal of pyridoxine.
Conclusions:
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 modulators (weak recommendation, very low quality of evidence).
Background:
Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning.
Methods:
We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods.
Results:
A total of 83 publications (6 in vitro and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR.
Conclusions:
Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning.
Accidental death was the fourth leading cause of mortality in the United States in 2014. Within causes of accidental deaths, unintentional poisoning has been at the top since 2011 [1]. This does not include deaths from intentional self-poisoning and thus underestimates the total number of deaths related to poisoning. This information underscores the importance of developing adequate treatment strategies for the poisoned patient.
This article examines, using an organ-systems based approach, rapid diagnosis, resuscitation, and critical care management of the crashing poisoned patient in the emergency department. The topics discussed in this article include seizures and status epilepticus, respiratory failure, cardiovascular collapse and mechanical circulatory support, antidotes and drug-specific therapies, acute liver failure, and extracorporeal toxin removal.
Introduction
Paraquat (PQ) is a widely used herbicide which is inexpensive and easily accessible for people in rural areas. A small amount of PQ ingestion could be lethal, yet currently, the optimal treatment is still controversial. Extracorporeal therapies (ECTR) have been practised in PQ poisoning management, though limited evidence could be obtained to suggest its superiority over conservative therapy. Haemodialysis (HD) and haemoperfusion (HP) are most commonly used, while some institutions also choose HP–HD concurrent therapy. The object of the present trial is to investigate whether haemopurification therapy can reduce mortality compared with conservative therapy.
Methods and analysis
This is a planned single-centre, non-blinded, randomised controlled trial. Acute PQ poisoned adults who have orally ingested PQ within 24 hours would be recruited. A total of 360 patients would be recruited and randomly assigned to four groups, that is, HP, HD, concurrent HP–HD and control, at a 1:1:1:1 ratio. Subjects would be also stratified by their urine dithionite test results. Primary outcome is 28-day all-cause mortality. Secondary outcomes include survival time, all-cause mortality at the 3rd, 7th and 60th day, rate of major complications, Acute Physiologic and Chronic Health Evaluation score and Poisoning Severity Score, etc.
Ethics and dissemination
The protocol and informed consent documents have been approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University in September 2017 (approval number: 2017-KY-10). The result of this trial would be submitted to peer-reviewed journal.
Trial registration number
NCT03314909; Pre-results.
Along with active supportive care, judicious gastrointestinal decontamination, and antidotal therapy, elimination enhancement techniques should be considered in the comprehensive management of any poisoned patient. Elimination enhancement techniques are defined as any procedure that accelerates the endogenous clearance of poison already absorbed and located either in the blood or tissue compartment. Corporal techniques provide their effects inside the body and include multiple-dose activated charcoal (MDAC), resins, and urine pH manipulation, as discussed elsewhere. Extracorporeal treatments (ECTRs) occur in a circuit outside the body (with the exception of peritoneal dialysis) and include hemodialysis, hemoperfusion, hemofiltration, and plasma exchange [1]. As the prognosis of most toxic exposures remains excellent with supportive measures alone, only a small minority of poisonings benefit from active elimination enhancement; for example, MDAC, urine alkalinization, and hemodialysis were only used in 0.06 %, 0.5 %, and 0.1 %, respectively, of patients reported to the US poison control centers. Although the large proportion of the literature reviewing the efficacy of elimination enhancement techniques is derived from human case reports, evidence-based and consensus-based recommendations are now available for extracorporeal treatments [2–15].
Cette revue est centrée sur les méthodes d’épuration extrarénale des toxiques par circuit extracorporel au sens récemment défini par le groupe EXTRIP. Les méthodes sont nombreuses et les techniques et/ou matériaux en constante évolution. Il s’agit principalement de l’hémodialyse, l’hémoperfusion, l’hémofiltration, la dialyse à l’albumine et l’exsanguinotransfusion. Nous envisagerons successivement les critères d’efficacité à prendre en compte, et les paramètres qui conditionnent potentiellement l’efficacité des principales épurations extracorporelles (EEC) disponibles, en tenant compte des caractéristiques des toxiques concernés. Les indications de la mise en oeuvre d’une EEC seront ensuite discutées sur la base d’une part, des caractéristiques physicochimiques et toxicocinétiques des produits et d’autre part, des principes sur lesquels sont fondées les différentes méthodes.
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 mumol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 mumol/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 mumol/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.
A 26-year-old female walked into our emergency department complaining of persistent nausea and feeling unwell after ingesting about 100 mL laundry detergent in a suicide attempt. The laundry detergent contained 17% of anionic and non-ionic surfactants. She had airway and breathing problems on arrival. We intubated her and performed gastric lavage, before administering activated charcoal and a laxative. We continued the infusion, but her blood lactate level kept rising, and progressive circulatory failure was observed. She fell into a state of shock, and we needed to use noradrenaline. We decided to perform direct hemoperfusion (DHP) using an activated charcoal column. After the initiation of the DHP, the patient’s blood lactate level fell immediately, and we were able to end the noradrenaline treatment. She was extubated on the 3rd hospital day and transferred to another hospital for specialized psychiatric treatment on the 17th hospital day. Although blood purification therapy for acute intoxication is controversial, we herein report a case of surfactant poisoning in which DHP was considered to have contributed to the improvement of circulatory failure.
The modern use of extracorporeal therapies to treat poisoning and drug overdoses dates back to the early 20th century and has evolved along with their use as treatment for acute kidney injury or as maintenance therapy in advanced kidney disease. As our understanding of drug pharmacokinetics and membrane materials has increased, the technologies of extracorporeal therapy and their applications have become more sophisticated. Despite that, there is little robust evidence to guide clinicians on the optimal use of extracorporeal therapy in treating poisoning beyond case reports and series. New efforts are underway to remedy that: the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) is an international effort on the part of nephrologists, pharmacists and toxicologists to review the available data and formulate evidence-based guidelines on how to use extracorporeal techniques to treat poisoning and improve patient outcomes. Meanwhile, new techniques and membranes are under development. This review will summarize those key scientific and technologic developments, the efforts to optimize their use and new directions in research.
Copyright © 2015. Published by Elsevier B.V.
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.
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.
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.
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 of extracorporeal 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 is indicated 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.
Thousands of paraquat (PQ)-poisoned patients continue to die. Plasma perfusion (PP) has recently been incorporated as a method of clinical detoxification. The purpose of this study was to estimate the PQ clearance of PP and observe the effect of PP on PQ concentration in the blood of patients with acute PQ poisoning.
Twenty one PQ-poisoned patients admitted to our poisoning center within 24 hours after the ingestion were prospectively enrolled. Continuous plasma perfusion was performed. Urinary PQ and plasma PQ concentration level at inlet/outlet of the cartridge were obtained right before and 1.5 hours after the start of each perfusion session for the calculation of renal and plasma PQ excretion.
In all 8 rounds (108 sessions) of PP on the 21 patients, PQ clearance rate (mL/min) by PP was always found to be higher than the renal value: (1st 11.14 ± 6.13 versus 6.53 ± 1.46; 2nd 18.36 ± 11.32 versus 6.23 ± 1.51; 3rd 16.13 ± 10.05 versus 4.01 ± 0.93; 4th 12.86 [6.72, 17.47] versus 2.42 [0.65, 4.20]; 5th 14.12 [10.48, 35.20] versus 1.77 [0.63, 2.91]; 6th 16.47 [11.82; 20.69] versus 1.70 [0.23, 3.18]; 7th 13.33 [9.71, 18.75] versus 1.10 [0.14, 2.99]; 8th 11.27 [9.21, 16.02] versus 1.10 [0.09, 2.79], P < 0.05). The survivors showed a higher plasma PQ reduction rate (mg L hour) than the nonsurvivors (0.57 ± 0.03 vs. 0.47 ± 0.06, P < 0.05).
Our data show that PP therapies help in the clearance of PQ and may prove a promising therapeutic tool in patients with acute PQ intoxication.
The use of an extracorporeal treatment (ECTR) in a poisoned patient may be life-saving in a limited number of scenarios. The decision-processes surrounding the use of ECTR in poisoning is complex: most nephrologists are not trained to assess a poisoned patient while clinical toxicologists rarely prescribe ECTRs. Deciding on which ECTR is most appropriate for a poison requires a good understanding of the poison's physicochemical and pharmacokinetic properties. Further, a detailed understanding of the capabilities and limitations of the different ECTRs can be useful to select the most appropriate ECTR for a given clinical situation. This manuscript provides a stepwise approach to assess the usefulness of ECTRs in poisoning.
Sustained low-efficiency dialysis (SLED) is a 'hybrid' form of continuous renal replacement therapy; however, there is very limited information on drug disposition during this procedure. Individuals requiring SLED are often critically ill and require antibiotics. The study aim was to evaluate antibiotic orders for patients requiring SLED compared to literature-based recommendations. We also evaluated whether doses were administered as prescribed and assessed clinical and microbiologic cure.
A retrospective review was performed over a 2-year period for patients who received concurrent SLED and antibiotic therapy. Demographic data, prescribed antibiotic dosing regimens and doses delivered as prescribed were determined for 10 antibiotics: cefepime (C), daptomycin (Da), doripenem (D), gentamicin (G), imipenem-cilastatin (I), linezolid (L), meropenem (M), piperacillin-tazobactam (P), tobramycin (T) and vancomycin (V). Dosing regimens were compared to recommendations from the literature where available. The incidence of clinical and microbiologic cure was also evaluated.
A total of 87 patients met inclusion criteria: mean age 54 ± 14 years, 60% male, 58% white. Prescribed doses were evidence-based for 37% of Da, 97% of L, 15% of M and 7% of V orders. The majority of discrepancies were due to under-dosing. There were 129 (11%) antibiotic doses missed. Of the 13 patients who met criteria for assessment of clinical and microbiologic cure, 10 achieved a microbiologic cure and none reached clinical cure.
Prescribed antibiotic dosing regimens varied substantially and under-dosing was common. There is a need to further define appropriate dosing regimens for antibiotics administered during SLED and determine how pharmacists may help to ensure appropriate therapy.
Nephrologists and critical care physicians are commonly involved in the treatment of severely poisoned patients. Various techniques exist presently to enhance the elimination of poisons. Corporeal treatments occur inside of the body and include multiple-dose activated charcoal, resin binding, forced diuresis, and urinary pH alteration. Extracorporeal treatments include hemodialysis, hemoperfusion, peritoneal dialysis, continuous renal replacement therapy, exchange transfusion, and plasmapheresis. This review illustrates the potential indications and limitations in the application of these modalities as well as the pharmacological characteristics of poisons amenable to enhanced elimination.
Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.
This is the 26th Annual Report of the American Association of Poison Control Centers (AAPCC; http://www. aapcc.org ) National Poison Data System (NPDS). During 2008, 60 of the nation's 61 US poison centers uploaded case data automatically. The median upload time was 24 [7.2, 112] (median [25%, 75%]) minutes creating a real-time national exposure and information database and surveillance system.
We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 28 medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to determine Relative Contribution to Fatality (RCF) from the exposure to the death.
In 2008, 4,333,012 calls were captured by NPDS: 2,491,049 closed human exposure cases, 130,495 animal exposures, 1,703,762 information calls, 7,336 human confirmed nonexposures, and 370 animal confirmed nonexposures. The top five substances most frequently involved in all human exposures were analgesics (13.3%), cosmetics/personal care products (9.0%), household cleaning substances (8.6%), sedatives/hypnotics/antipsychotics (6.6%), and foreign bodies/toys/miscellaneous (5.2%). The top five most common exposures in children age 5 or less were cosmetics/personal care products (13.5%), analgesics (9.7%), household cleaning substances (9.7%), foreign bodies/toys/miscellaneous (7.5%), and topical preparations (6.9%). Drug identification requests comprised 66.8% of all information calls. NPDS documented 1,756 human exposures resulting in death with 1,315 human fatalities deemed related with an RCF of at least contributory (1, 2, or 3).
Poisoning continues to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national resource to collect and monitor US poisoning exposure cases and information calls. NPDS continues its mission as one of the few real-time national surveillance systems in existence, providing a model public health surveillance system for all types of exposures, public health event identification, resilience response and situational awareness tracking.
Extracorporeal removal techniques such as hemodialysis, charcoal hemoperfusion, and peritoneal dialysis have been used to remove toxins from the body. To define trends in the use of these techniques for toxin removal, we analyzed the 19,351 cases requiring extracorporeal removal reported to U.S. poison centers from 1985-2005. The number of such patients who received hemodialysis, excluding those with other medical indications, (normalized per million calls) increased from 231 to 707 whereas hemoperfusion decreased from 53 to 12 in the years 1985-2005. Peritoneal dialysis decreased from 2.2 in 1985 to 1.6 in 1991. The most common toxins removed by hemodialysis were lithium and ethylene glycol. There were more dialysis treatments for poisonings with valproate and acetaminophen in 2001-2005 than for methanol and theophylline, although hemodialysis for acetaminophen removal is generally not recommended. Theophylline was the most common toxin removed by hemoperfusion from 1985-2000, but carbamazepine became the most frequent toxin for removal during 2001-2005. Our study shows that the profile of toxins and the type of extracorporeal technique used to remove the toxins have changed over the years.
Two children underwent acute hemodialysis using high-efficiency dialysis membranes for vancomycin intoxication (plasma levels 238 µg/ml and 182 µg/ml). During a 3-h treatment, plasma vancomycin removal was on average 60%, with a calculated vancomycin half-life (t
1/2) of 2 h. This is in contrast to a recent report using charcoal hemoperfusion for vancomycin intoxication (plasma level of 137 µg/ml), which resulted in a 40% relative plasma clearance and a calculated vancomycin t
1/2 of 12.5 h for a 4-h treatment. The choice of optimal modality for clearing a toxin should take into account the availability of equipment, protein or lipid binding of the toxin, and inherent risks of charcoal hemofiltration (large extracorporeal circuit, reversible hypocalcemia, heat loss, reversible coagulation defects) versus risks of high-efficiency hemodialysis (large extracorporeal circuit).
Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations. Systematic and explicit methods of making judgments can reduce errors and improve communication. We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts. In this article we present a summary of our approach from the perspective of a guideline user. Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk. It is also important to consider costs (resource utilisation) before making a recommendation. Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments. Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues.
Background:
Ethylene glycol (EG) and methanol are responsible for accidental, suicidal, and epidemic poisonings, resulting in death or permanent sequelae. Toxicity is due to the metabolic products of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. Conventional management of these intoxications consists of ethanol and hemodialysis. Fomepizole, a potent ADH inhibitor, has largely replaced antidotal ethanol use in France and two recent prospective U.S. trials definitively established its efficacy. Fomepizole appears safer than ethanol and while no comparative study of efficacy exists, fomepizole is recommended as the first-line antidote.
Focus:
Fomepizole, administered early in EG intoxication, prevents renal injury. In the absence of renal failure, EG clearance is rapid, avoiding the need for prolonged fomepizole administration. The long elimination half-life of methanol poisonings, with absent hemodialysis, necessitates prolonged administration of fomepizole. In the U.S. trials, patients were dialyzed when plasma EG or methanol concentrations were >/=0.5 g/l. However, EG-poisoned patients treated with fomepizole prior to the onset of significant acidosis may not require hemodialysis. Indeed, fomepizole may also obviate the need for hemodialysis in selected methanol-poisoned patients, in the absence of neurological and ocular impairment or severe acidosis. When dialysis is indicated, 1 mg.kg.h continuous infusion of fomepizole should be provided to compensate for its elimination.
Conclusions:
Fomepizole is an effective and safe first-line recommended antidote for EG and methanol intoxication. In selected patients, fomepizole may obviate the need for hemodialysis.
Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge. Design Systematic review of randomised controlled trials. Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists. Study selection: Studies showing the effects of using a parachute during free fall. Main outcome measure Death or major trauma, defined as an injury severity score > 15. Results We were unable to identify any randomiscd controlled trials of parachute intervention. Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
Although there have been descriptive, uncontrolled clinical reports of removal of tablet debris by gastric lavage, there have been no clinical studies that have demonstrated that this has any impact on outcome in patients with tricyclic antidepressant (TCA) poisoning. There is also the possibility that lavage may increase drug absorption by pushing tablets into the small intestine. Furthermore, gastric lavage in patients with TCA poisoning may induce hypoxia and a tachycardia potentially increasing the risk of severe complications such as arrhythmias and convulsions. In view of the paucity of evidence that gastric lavage removes a significant amount of drug and the risk of complications associated with the procedure, the routine use of gastric lavage in the management of patients with TCA poisoning is not appropriate.
Volunteer studies have shown generally that activated charcoal is more likely to reduce drug absorption if it is administered within 1 hour of drug ingestion. In the one volunteer study that looked at later administration of activated charcoal, there was a 37% decrease in plasma concentration associated with administration of activated charcoal at 2 hours post-ingestion. There have been no clinical studies that enable an estimate of the effect of activated charcoal administration on outcome in the management of patients with TCA poisoning.
Volunteer studies have shown that multiple-dose activated charcoal increases the elimination of therapeutic doses of amitriptyline and nortriptyline, but not of doxepin or imipramine; however, these studies cannot be directly extrapolated to the management of patients with TCA poisoning. There have been no well designed controlled studies that have assessed the impact of multiple-dose activated charcoal in the management of patients with TCA poisoning. Because of the large volume of distribution of TCAs, it would not be expected that their elimination would be significantly increased by multiple-dose activated charcoal.
Haemoperfusion, haemodialysis and the combination of these procedures do not result in significant removal of TCAs and are not recommended in the management of patients with TCA poisoning.
Objectives:
To determine whether parachutes are effective in preventing major trauma related to gravitational challenge.
Design:
Systematic review of randomised controlled trials.
Data sources:
Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists.
Study selection:
Studies showing the effects of using a parachute during free fall.
Main outcome measure:
Death or major trauma, defined as an injury severity score > 15.
Results:
We were unable to identify any randomised controlled trials of parachute intervention.
Conclusions:
As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
In this review the efficacy of haemoperfusion in the treatment of paraquat poisoning is addressed. 42 reports containing sufficient information of paraquat-poisoned patients were evaluated. These reports, from 35 patients reported in the literature and 7 new cases, were chosen for the following reasons: the timed plasma paraquat concentrations were known, patient outcome was known, and details of haemoperfusion were available. In some cases, haemodialysis was also performed. The plasma paraquat concentrations and the specific times post-ingestion were plotted on a contour graph that predicts the probability of survival. Comparison of the predicted probability of survival versus the actual outcome showed that haemoperfusion, single or repeated, did not affect patient survival. None of the patients whose initial plasma concentrations were greater than 3 mg/L paraquat survived, regardless of the time after ingestion that the concentrations were measured, and despite haemoperfusion. Therefore, such patients might not be considered for haemoperfusion because of their uniformly bad prognosis, despite the procedure being used, and because of the morbidity, discomfort and costs associated with it. Clearly, the need for better techniques to remove paraquat and to prevent the consequences of the metabolic effects of the compound are required urgently before the treatment of the paraquat-poisoned patient will be successful.
We report two cases of severe lactic acidosis due to massive metformin ingestion. The first case was a 37-year-old man who was discovered several hours after ingesting 45 g of metformin. He had severe lactic acidosis (blood pH 6.81bicarbonate 4 mEq/Llactate 25.7 mEq/L). Despite intravenous bicarbonate therapyhe decompensated and was placed on a combination of hemodialysis and charcoal hemoperfusion for a continuous time of 25 hours. His hospital course was complicated by acute renal failure requiring a period of intermittent hemodialysis. He has since made a complete recovery. The second case was a 53-year-old man who ingested 50 g of metformin. He also presented with severe lactic acidosis (blood pH 6.85bicarbonate 3 mEq/L and lactate 28.4 mEq/L) and deteriorated despite intravenous bicarbonate therapy. He was placed on hemodialysis as a continuous therapy for 21 hours. His hospital course was complicated by acute renal failure requiring a period of intermittent hemodialysis. He has subsequently made a complete recovery. Metformin-associated lactic acidosis carries a high mortality rate. Prolonged hemodialysis should be considered as an early treatment option in these cases.
A description is given of 1 case of chloramine poisoning and 1 case of aniline poisoning, both in children whose lives were apparently saved by treatment with exchange transfusion.
Sten Axteup: Deux cas d'empoisonnement traités par exsanguino-transfusion.
On rapporte un cas d'empoisonnement par la chloramine et un cas par l'aniline, l'un et l'autre chez dos enfants ramenés apparemment à la vie par une exsanguino-transfusion.
Sten Axtrup: Vergiftungsfälle behandelt mit Austausch-Transfusion.
Es werden je 1 Fall von Chloramin- und Anilinvergiftung beschrieben. Das Leben beider Kinder wurde augenscheinlich gerettet durch die Behandlung mit Austausch-Transfusion.
Sten Axtrup: Dos casos de envenenamiento tratados con ex-sanguino-transfusión.
Se demuestra un caso de envenenamiento con cloramina, y otro con anilina, ambos en niños que, al parecer, se han salvado por medio de la ex-sanguinotransfusión.
Guest Editor's Introduction: The effective adsorption of substances by activated charcoal is depressed when such substances are bound to plasma proteins. To remove plasma-bound substances from blood, synthetic resins were evaluated. This paper is the first report regarding the uncharged resin adsorbent and describes effectiveness in the removal of protein-bound substances. Encouraged by the report, more effective anion resins have been developed by Asahi Medical Co. and Kuraray Co. and used for the treatment of fulminant hepatitis and postoperative hepatitis. This paper was printed in Trans Am Soc Artif Intern Organs. vol 16, page 134–140 (1970) and reprinted here with permission.
Uremia resulting from acute renal damage is frequently fatal, because the renal lesion requires more time for healing than the lethal effects of the uremia will permit. Such potentially reversible renal lesions include those resulting from incompatible transfusions, sulfonamide toxicity, massive trauma, suppression of kidney function following surgical trauma to the urinary tract, toxemia of pregnancy, mercury poisoning and certain forms of acute glomerulonephritis.Available methods do not provide for sufficient excretion of retained substances by extrarenal pathways. Clearance of the circulating blood through an artificial dialyzing membrane is one of the recent methods advocated. But the technical difficulties involved, the need of adequate heparinization and the additional vascular load such a method imposes a're serious handicaps to the acceptance of this method.The use of the peritoneum as a dialyzing membrane for extrarenal excretion is not new. Efforts to utilize this structure to treat uremia have been made in
We describe the case of a 42-year-old female who presented to our care 1 hour after ingesting 3.6 g of phenytoin. She was stuporous 48 hours after admission despite supportive therapy. She was treated with hemodialysis (HD) for nearly 6 hours in order to remove phenytoin. Her level of consciousness improved markedly during the procedure. During HD, phenytoin levels decreased by 47% and measured half-life was 6.8 hours as compared to 116 hours when not on HD. Finally, we were able to remove 547 mg of phenytoin (directly measured from the dialysate), representing approximately a third of estimated body stores. The use of extracorporeal therapy in phenytoin overdose is reviewed here. We believe that in severe cases of phenytoin intoxication, hemodialysis can be used to accelerate total body burden of the drug, even if protein binding is significant.
Fluid withdrawal in over-hydrated patients resistant to diuretics was obtained by means of a capillary haemofilter, using the arterio-venous pressure gradient for blood perfusion at a rate of 100 ml/min. The ultrafiltration rate was 200-600 ml/h and could be maintained as long as 48 h without changing the haemofilter. This method, which needs no technical investment, is easy and simple to handle for the physician, bears only a very low risk for the patient, and ensures a negative fluid balance even at a mean blood pressure of only 60 mm Hg.
Elimination of three different cardiac glycosides by hemofiltration was investigated using the flat bed RP-6 (Rhône-Poulenc, Paris). At a filtration rate of 59 +/- 9 ml/min the mean clearance of 3-H-g-strophanthin was 54.9 +/- 10.4, that of a 3-H-digoxin and unlabelled digoxin 36.7 +/- 6.6 and that of digitoxin 4.6 +/- 2.8 ml/min. It is concluded from these results that hemofiltration is able to eliminate more than 50% of the amount excreted during the same period of time by normal kidneys. Elimination of cardiac glycosides by continuous hemofiltration is high enough to justify its use in digitalis intoxication, particularly because of the excellent control of electrolyte balance with this new method of detoxification.
In this review the efficacy of haemoperfusion in the treatment of paraquat poisoning is addressed. 42 reports containing sufficient information of paraquat-poisoned patients were evaluated. These reports, from 35 patients reported in the literature and 7 new cases, were chosen for the following reasons: the timed plasma paraquat concentrations were known, patient outcome was known, and details of haemoperfusion were available. In some cases, haemodialysis was also performed. The plasma paraquat concentrations and the specific times post-ingestion were plotted on a contour graph that predicts the probability of survival. Comparison of the predicted probability of survival versus the actual outcome showed that haemoperfusion, single or repeated, did not affect patient survival. None of the patients whose initial plasma concentrations were greater than 3 mg/L paraquat survived, regardless of the time after ingestion that the concentrations were measured, and despite haemoperfusion. Therefore, such patients might not be considered for haemoperfusion because of their uniformly bad prognosis, despite the procedure being used, and because of the morbidity, discomfort and cost associated with it. Clearly, the need for better techniques to remove paraquat and to prevent the consequences of the metabolic effects of the compound are required urgently before the treatment of the paraquat-poisoned patient will be successful.
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
To compare patients for whom hemodialysis was done for lithium poisoning and those for whom it was recommended by the poison control centre (PCC) but not done and to evaluate the effect of withholding hemodialysis on outcomes.
All lithium overdoses brought to the attention of the PCC were prospectively followed from January 1 to December 31, 1996. Patients for whom hemodialysis was done were compared with those for whom it was recommended but not done in terms of clinical presentation, lithium elimination half-life, need for transfer to another centre for hemodialysis, and outcome (death, or sequel or recovery).
A total of 205 cases of lithium overdoses were collected including 110 with levels higher than 1.5 mmol/l. There were 12 acute lithium overdoses; no patients required hemodialysis and there were no sequel or deaths. There were 174 acute on chronic overdoses; hemodialysis was recommended in 9 patients but only 6 underwent hemodialysis; one patient died during hemodialysis but no other had sequel. There were 19 chronic poisonings; hemodialysis was recommended in 9 patients but only 2 had hemodialysis, a third patient underwent hemodialysis despite it not being recommended; one patient died without hemodialysis and one other had sequel after hemodialysis. No difference were observed between the groups for age, sex, type of poisoning (acute on chronic/chronic), levels (initial/peak/6 hours/extrapolated at 30 hours), time of presentation post-ingestion, presence of co-ingestants, symptoms and signs, Hansen and Amdisen grade, initial creatinine, time of recommendation to perform hemodialysis (daytime or nighttime), need to transfer patients to another centre to perform hemodialysis, and outcome. Patients with acute on chronic poisoning that were not hemodialyzed had longer elimination half-life than those for whom hemodialysis was done even before hemodialysis was performed: 50.1 +/- 13.6 h (n = 3) versus 12.9 +/-12.1 (n = 3) (p = 0.007), respectively.
No difference was observed between patients for whom hemodialysis was done and those for whom it was recommended by PCC but not done. Despite the death of one patient clearly associated with voluntary withholding hemodialysis, sequel was not seen in that group. The indications for hemodialysis in lithium poisoning should be reconsidered to include only the more severe cases.
Paraquat poisoning is characterized by multiorgan failure and pulmonary fibrosis with respiratory failure. Multiorgan failure with circulatory collapse is a major cause of early death within 3 days of paraquat ingestion. Recent studies suggested that continuous venovenous hemofiltration (CVVH) had a role in the treatment of multiorgan failure by promoting hemodynamic stability. We therefore evaluated the effect of prophylactic CVVH in 80 patients with paraquat poisoning (August 1996 to February 1999). The amount ingested was 2.1 +/- 1.0 mouthfuls (as 20% concentrate). All patients were treated with hemoperfusion (HP; duration, 6.4 +/- 3.0 hours) within 24 hours of ingestion and then randomly assigned to the HP-alone or HP-CVVH group. Forty-four patients underwent HP only, and 36 patients underwent CVVH (duration, 57.4 +/- 31.3 hours; ultrafiltration volume, 40.2 +/- 4.8 L/d) after HP. Although time to death after ingestion was significantly longer in the HP-CVVH than HP group (5.0 +/- 5.0 versus 2.5 +/- 2.1 days; P < 0.05), there was no difference in mortality rates between the two groups (66.7% versus 63.6%; P = 0.82). In the HP group, early circulatory collapse was a major cause of death compared with the HP-CVVH group, in which late respiratory failure was a major cause of death. In conclusion, prophylactic CVVH after HP prevented early death caused by circulatory collapse and prolonged survival time. However, it could not prevent late death caused by respiratory failure and did not provide a survival benefit in acute paraquat poisoning.
Tricyclic overdose can be a medical emergency, and therapy with intravenous bicarbonate is not always successful in preventing cardiac toxicity or coma. Mortality in patients developing these complications is from 1% to 15%. Extracorporeal detoxification with sorbents has been used in treatment of patients with very high drug levels and declining clinical condition. Ten patients with serious drug overdose caused by tricyclics failed to respond quickly to standard therapy and were in stage 3-4 encephalopathy. Nine of these patients were on respirator support, 5 had hypotension, and 6 had QRS widening. Average level was 1,423 microg/L at presentation. Enteral activated charcoal and intravenous (IV) bicarbonate were initiated in the emergency room. The patients were treated for 3 to 4 hours with the Liver Dialysis Unit, a hemodiabsorption device using a cellulosic plate dialyzer and sorbent suspension as dialysate. Inflow and outflow blood levels indicated that the hemodetoxifier removed modest amounts of the tricyclics, metabolites, and other consumed drugs. The clinical improvement of the patients was dramatic, with patients reaching stage 0 or 1 encephalopathy during the treatment. Ventilator support was removed at the end of treatment for 3 patients who had not already developed pneumonia, and for others was prolonged up to 48 hours because of pneumonia, rather than mental status. Average length of stay in the intensive care unit (ICU) was 4.8 days (range 1 to 7 days). None of the patients died despite their high risk for ventricular arrhythmias, seizures, and death. Clinical improvement may have been attributable to removal of free drug from the blood or to removal of drug metabolites.
To develop a flowchart to be used as a tool to guide clinicians step by step through the management of salicylate poisoning.
A comprehensive literature search was carried out.
The evidence base was used to develop a management flowchart that guides the clinician through the three main steps in caring for the patient with salicylate poisoning: preventing further absorption, assessing the severity of poisoning and, where appropriate, increasing elimination.
Salicylate poisoning can result in severe morbidity and mortality and this flowchart provides an evidence based guideline that will guide clinicians through the management of patients presenting to the emergency department with salicylate poisoning.
The role of the artificial kidney in acute human poisoning may be considered in two distinct categories: (1) dialyzable poisons, wherein the rate of removal is critical to the welfare of the patient, and (2) nephrotoxic poisons, which produce damage to the kidneys and are not qualitatively different from other causes of acute renal insufficiency. In some instances, general toxicity may be produced from the poison itself, while in others it is a product of the uremic syndrome. It is the purpose of the present study to review eight years of experience with clinical dialyses in acute poisonings and to summarize related studies, with particular emphasis on the role of the artificial kidney in dialyzable poisons.Dialyzable Poisons
The effective use of hemodialysis in any acute poisoning is based on the following assumptions:That the poison molecule can diffuse through cellophane from plasma water and has a reasonable removal rate
Although there have been descriptive, uncontrolled clinical reports of removal of tablet debris by gastric lavage, there have been no clinical studies that have demonstrated that this has any impact on outcome in patients with tricyclic antidepressant (TCA) poisoning. There is also the possibility that lavage may increase drug absorption by pushing tablets into the small intestine. Furthermore, gastric lavage in patients with TCA poisoning may induce hypoxia and a tachycardia potentially increasing the risk of severe complications such as arrhythmias and convulsions. In view of the paucity of evidence that gastric lavage removes a significant amount of drug and the risk of complications associated with the procedure, the routine use of gastric lavage in the management of patients with TCA poisoning is not appropriate. Volunteer studies have shown generally that activated charcoal is more likely to reduce drug absorption if it is administered within 1 hour of drug ingestion. In the one volunteer study that looked at later administration of activated charcoal, there was a 37% decrease in plasma concentration associated with administration of activated charcoal at 2 hours post-ingestion. There have been no clinical studies that enable an estimate of the effect of activated charcoal administration on outcome in the management of patients with TCA poisoning. Volunteer studies have shown that multiple-dose activated charcoal increases the elimination of therapeutic doses of amitriptyline and nortriptyline, but not of doxepin or imipramine; however, these studies cannot be directly extrapolated to the management of patients with TCA poisoning. There have been no well designed controlled studies that have assessed the impact of multiple-dose activated charcoal in the management of patients with TCA poisoning. Because of the large volume of distribution of TCAs, it would not be expected that their elimination would be significantly increased by multiple-dose activated charcoal.Haemoperfusion, haemodialysis and the combination of these procedures do not result in significant removal of TCAs and are not recommended in the management of patients with TCA poisoning.
To determine whether parachutes are effective in preventing major trauma related to gravitational challenge. Design Systematic review of randomised controlled trials.
Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists.
Studies showing the effects of using a parachute during free fall.
Death or major trauma, defined as an injury severity score > 15.
We were unable to identify any randomised controlled trials of parachute intervention.
As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.