Publications by authors named "Marc Ghannoum"

70 Publications

Letter to the editor concerning the case report "Successful treatment of severe quetiapine intoxication with CytoSorb hemoadsorption".

J Clin Pharm Ther 2022 Aug 2. Epub 2022 Aug 2.

Research Center, CIUSSS du Nord-de-l'ile-de-Montreal, Hopital du Sacre-Coeur de Montreal, University of Montreal, Montreal, Québec, Canada.

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http://dx.doi.org/10.1111/jcpt.13749DOI Listing
August 2022

The serum glycolate concentration: its prognostic value and its correlation to surrogate markers in ethylene glycol exposures.

Clin Toxicol (Phila) 2022 07 24;60(7):798-807. Epub 2022 Mar 24.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, University of Montreal, Montreal, QC, Canada.

Context: Ethylene glycol poisoning manifests as metabolic acidemia, acute kidney injury and death. The diagnosis and treatment depend on history and biochemical tests. Glycolate is a key toxic metabolite that impacts prognosis, but assay results are not widely available in a clinically useful timeframe. We quantitated the impact of serum glycolate concentration for prognostication and evaluated whether more readily available biochemical tests are acceptable surrogates for the glycolate concentration.

Objectives: The objectives of this study are to 1) assess the prognostic value of the initial glycolate concentration on the occurrence of AKI or mortality in patients with ethylene glycol exposure (); 2) identify surrogate markers that correlate best with glycolate concentrations ).

Methods: A systematic review of the literature was performed using Medline/PubMed, EMBASE, Cochrane library, conference proceedings and reference lists. Human studies reporting measured glycolate concentrations were eligible. Glycolate concentrations were related to categorical clinical outcomes (acute kidney injury, mortality), and correlated with continuous surrogate biochemical measurements (anion gap, base excess, bicarbonate concentration and pH). Receiver operating characteristic curves were constructed to calculate the positive predictive values and the negative predictive values of the threshold glycolate concentrations that predict acute kidney injury and mortality. Further, glycolate concentrations corresponding to 100% negative predictive value for mortality and 95% negative predictive value for acute kidney injury were determined.

Results: Of 1,531 articles identified, 655 were potentially eligible and 32 were included, reflecting 137 cases from 133 patients for the prognostic study and 154 cases from 150 patients for the surrogate study. The median glycolate concentration was 11.2 mmol/L (85.1 mg/dL, range 0-38.0 mmol/L, 0-288.8 mg/dL), 93% of patients were treated with antidotes, 80% received extracorporeal treatments, 49% developed acute kidney injury and 13% died. The glycolate concentration best predicting acute kidney injury was 12.9 mmol/L (98.0 mg/dL, sensitivity 78.5%, specificity 88.1%, positive predictive value 86.4%, negative predictive value 80.9%). The glycolate concentration threshold for a 95% negative predictive value for acute kidney injury was 6.6 mmol/L (50.2 mg/dL, sensitivity 96.9%, specificity 62.7%). The glycolate concentration best predicting mortality was 19.6 mmol/L (149.0 mg/dL, sensitivity 61.1%, specificity 81.4%, positive predictive value 33.3%, negative predictive value 93.2%). The glycolate concentration threshold for a 100% negative predictive value for mortality was 8.3 mmol/L (63.1 mg/dL, sensitivity 100.0%, specificity 35.6%). The glycolate concentration correlated best with the anion gap ( = 0.73), followed by bicarbonate ( = 0.57), pH ( = 0.50) and then base excess ( = 0.25), while there was no correlation between the glycolate and ethylene glycol concentration ( = 0.00). These data can assist clinicians in planning treatments such as extracorporeal treatments and prognostication. Potentially, they may also provide some reassurance regarding when extracorporeal treatments can be delayed while awaiting the results of further testing in patients in whom ethylene glycol poisoning is suspected but not yet confirmed.

Conclusions: This systematic review demonstrates that the glycolate concentration predicts mortality (unlikely if <8 mmol/L [61 mg/dL]). The anion gap is a reasonable surrogate measurement for glycolate concentration in the context of ethylene glycol poisoning. The findings are mainly based on published retrospective data which have various limitations. Further prospective validation studies are of interest.
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http://dx.doi.org/10.1080/15563650.2022.2049811DOI Listing
July 2022

Treating ethylene glycol poisoning with alcohol dehydrogenase inhibition, but without extracorporeal treatments: a systematic review.

Clin Toxicol (Phila) 2022 07 21;60(7):784-797. Epub 2022 Mar 21.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, University of Montreal, Montreal, QC, Canada.

Context: Ethylene glycol is metabolized to toxic metabolites that cause acute kidney injury, metabolic acidemia, and death. The treatment of patients with ethylene glycol poisoning includes competitively inhibiting alcohol dehydrogenase with ethanol or fomepizole to prevent the formation of toxic metabolites, and extracorporeal treatments such as hemodialysis to remove ethylene glycol and its metabolites. In the absence of significant metabolic acidemia or kidney injury, it is hypothesized that extracorporeal treatments may be obviated without adverse outcomes to the patient if alcohol dehydrogenase inhibitors are used.

Objectives: The objectives of this study are to: (1) identify indicators predicting ADH inhibitor failure in patients with ethylene glycol poisoning treated with either ethanol or fomepizole for whom extracorporeal treatment was not performed (aside from rescue therapy, see below) (), and (2) validate if the anion gap, shown in a previous study to be the best surrogate for the glycolate concentration, is associated with acute kidney injury and mortality ().

Methods: We conducted a systematic review to identify all reported patients with ethylene glycol poisoning treated without extracorporeal treatments but with either fomepizole () or ethanol (). Analyses were performed using both one case per patient and all cases (if multiple events were reported for a single patient). Data were compiled regarding poisoning, biochemistry, and outcomes. Treatment failure was defined as mortality, worsening of acid-base status, extracorporeal treatments used as rescue, or a worsening of kidney or neurological function after alcohol dehydrogenase inhibition was initiated. Also, we performed an analysis of previously described anion gap thresholds to determine if they were associated with outcomes such as acute kidney injury and mortality.

Results: Of 115 publications identified, 96 contained case-level data. A total of 180 cases were identified with ethanol monotherapy, and 231 with fomepizole monotherapy. Therapy failure was noted mostly when marked acidemia and/or acute kidney injury were present prior to therapy, although there were cases of failed ethanol monotherapy with minimal acidemia (suggesting that ethanol dosing and/or monitoring may not have been optimal). Ethylene glycol dose and ethylene glycol concentration were predictive of monotherapy failure for ethanol, but not for fomepizole. In the anion gap study (207 cases), death and progression of acute kidney injury were almost nonexistent when the anion gap was less than 24 mmol/L and mostly observed when the anion gap was greater than 28 mmol/L.

Conclusion: This review suggests that in patients with minimal metabolic acidemia (anion gap <28 mmol/L), fomepizole monotherapy without extracorporeal treatments is safe and effective regardless of the ethylene glycol concentration. Treatment failures were observed with ethanol monotherapy which may relate to transient subtherapeutic ethanol concentrations or very high ethylene glycol concentrations. The results are limited by the retrospective nature of the case reports and series reviewed in this study and require prospective validation.
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http://dx.doi.org/10.1080/15563650.2022.2049810DOI Listing
July 2022

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

Clin J Am Soc Nephrol 2022 04 2;17(4):602-622. Epub 2022 Mar 2.

Pharmacy Department, Verdun Hospital, CIUSSS du Sud-Ouest-de-l'ïle-de-Montréal, University of Montreal, Montreal, Quebec, Canada.

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/m]: 91 patients; low-dose [≤0.5 g/m]: 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: () suggested against extracorporeal treatments when glucarpidase is not administered; () recommended against extracorporeal treatments when glucarpidase is administered; and () recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: () extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; () extracorporeal treatments remove folinic acid; () in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and () extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.
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http://dx.doi.org/10.2215/CJN.08030621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993465PMC
April 2022

Extracorporeal Treatment for Gabapentin and Pregabalin Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup.

Am J Kidney Dis 2022 01 17;79(1):88-104. Epub 2021 Nov 17.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Quebec, Canada. Electronic address:

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 (>150mL/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).
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http://dx.doi.org/10.1053/j.ajkd.2021.06.027DOI Listing
January 2022

Recommendations from the EXTRIP workgroup on extracorporeal treatment for baclofen poisoning.

Kidney Int 2021 10 4;100(4):720-736. Epub 2021 Aug 4.

Emergency Medicine Department, Centre Intégré de Santé et de Services Sociaux (CISSS) de la Montérégie-Centre, Hôpital Charles-LeMoyne, Greenfield Park, Québec, Canada; Academic Emergency Medicine Department, Faculty of Medicine, McGill University, Montréal, Québec, Canada; Centre Antipoison du Québec, Québec, Québec, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.kint.2021.07.014DOI Listing
October 2021

Effectiveness of CytoSorb in cases of acute amitriptyline intoxication is not proven.

J Clin Pharm Ther 2022 03 7;47(3):420. Epub 2021 Jul 7.

Hôpital Verdun, Nephrology Service, University of Montreal, Verdun, Quebec, Canada.

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http://dx.doi.org/10.1111/jcpt.13483DOI Listing
March 2022

Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup.

Crit Care 2021 06 10;25(1):201. Epub 2021 Jun 10.

Research Center, CIUSSS du Nord-de-L'île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, QC, Canada.

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.
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http://dx.doi.org/10.1186/s13054-021-03585-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194226PMC
June 2021

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

Pharmacotherapy 2021 05 3;41(5):463-478. Epub 2021 Apr 3.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, University of Montreal, Montreal, Quebec, Canada.

Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABA receptor agonists (weak recommendation, very low quality of evidence).
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http://dx.doi.org/10.1002/phar.2519DOI Listing
May 2021

Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup.

Clin Toxicol (Phila) 2021 May 8;59(5):361-375. Epub 2021 Feb 8.

Research Center, CIUSSS du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, QC, Canada.

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 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.
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http://dx.doi.org/10.1080/15563650.2020.1870123DOI Listing
May 2021

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

J Am Soc Nephrol 2020 10 22;31(10):2475-2489. Epub 2020 Sep 22.

Research Center, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Quebec, Canada

Background: Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs.

Methods: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.

Results: A total of 44 studies (three studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug.

Conclusions: On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.
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http://dx.doi.org/10.1681/ASN.2020050564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609009PMC
October 2020

Assessing the effect of extracorporeal treatments for lithium poisoning.

Br J Clin Pharmacol 2021 01 5;87(1):214-215. Epub 2020 Jun 5.

Departments of Clinical Pharmacology, Toxicology and Renal Medicine, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.

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http://dx.doi.org/10.1111/bcp.14367DOI Listing
January 2021

Hemodialysis removal of caffeine.

Am J Emerg Med 2020 06 19;38(6):1273-1274. Epub 2020 Feb 19.

Hôpital Charles-Lemoyne, Emergency Medicine Service, Greenfield Park, Canada; McGill University, Provisional Emergency Department, Montréal, Canada.

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http://dx.doi.org/10.1016/j.ajem.2020.02.033DOI Listing
June 2020

Hemodialysis for lamotrigine poisoning.

Am J Emerg Med 2020 02 4;38(2):403-404. Epub 2019 Aug 4.

Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.ajem.2019.158385DOI Listing
February 2020

Extracorporeal treatment in salicylate poisoning.

Clin Toxicol (Phila) 2019 05 11;57(5):377-378. Epub 2018 Oct 11.

g Centre Antipoison du Québec, Department of Medicine , McGill University , Montreal , Canada.

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http://dx.doi.org/10.1080/15563650.2018.1517882DOI Listing
May 2019

Extracorporeal treatments in poisonings from four non-traditionally dialysed toxins (acetaminophen, digoxin, opioids and tricyclic antidepressants): A combined single-centre and national study.

Basic Clin Pharmacol Toxicol 2019 Mar 31;124(3):341-347. Epub 2018 Oct 31.

McGill University, Montréal, Quebec, Canada.

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialysed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a 2-Phase retrospective analysis evaluating the main indication for ECTRs in patients with poisoning from a NTDT (defined for this study as acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016, and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 restricted to single toxin ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important.
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http://dx.doi.org/10.1111/bcpt.13135DOI Listing
March 2019

Use of extracorporeal treatments in the management of poisonings.

Kidney Int 2018 10 27;94(4):682-688. Epub 2018 Jun 27.

New South Wales Poisons Information Centre, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia.

Historically, the clinical application of extracorporeal treatments (ECTRs), such as hemodialysis or hemoperfusion, was first intended for poisoned patients. With time, ECTRs were used almost indiscriminately to facilitate the elimination of many poisons, albeit with uncertain clinical benefit. To determine the precise role of ECTRs in poisoning situations, multiple variables need to be considered including a careful risk assessment, the poison's characteristics including toxicokinetics, alternative treatments, the patient's clinical status, and intricacies of available ECTRs, all of which are reviewed in this article. Recently, evidence-based and expert opinion-based recommendations from the EXTRIP workgroup were also published to help minimize the knowledge gap in this area.
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http://dx.doi.org/10.1016/j.kint.2018.03.026DOI Listing
October 2018

Toxicokinetics of Metformin During Hemodialysis.

Kidney Int Rep 2017 Jul 7;2(4):759-762. Epub 2017 Mar 7.

Department of Nephrology, Verdun Hospital, University of Montreal, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1016/j.ekir.2017.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720532PMC
July 2017

Formulas for Calculated Osmolarity and Osmolal Gap: A Study of Diagnostic Accuracy.

Am J Kidney Dis 2017 Sep 31;70(3):347-356. Epub 2017 May 31.

Division of Nephrology, Department of Medicine, Hôpital du Sacré-Cœur de Montréal, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada. Electronic address:

Background: The osmolal gap has been used for decades to screen for exposure to toxic alcohols. However, several issues may affect its reliability. We aimed to develop equations to calculate osmolarity with improved performance when used to screen for intoxication to toxic alcohols.

Study Design: Retrospective cohort study.

Setting & Participants: 7,525 patients undergoing simultaneous measurements of osmolality, sodium, potassium, urea, glucose, and ethanol or undergoing similar measurements performed within 30 minutes of a measurement of toxic alcohol levels at a single tertiary-care center from April 2001 to June 2016. Patients with detectable toxic alcohols were excluded.

Index Test: Equations to calculate osmolarity using multiple linear regression.

Outcomes: The performance of new equations compared with published equations developed to calculate osmolarity, and to diagnose toxic alcohol intoxications more accurately.

Results: We obtained 7,525 measurements, including 100 with undetectable toxic alcohols. Among them, 3,875 had undetectable and 3,650 had detectable ethanol levels. In the entire cohort, the best equation to calculate osmolarity was 2.006×Na + 1.228×Urea + 1.387×Glucose + 1.207×Ethanol (values in mmol/L, R=0.96). A simplified equation, 2.0×Na + 1.2×Urea + 1.4×Glucose + 1.2×Ethanol, had a similar R with 95% of osmolal gap values between -10.9 and 13.8. In patients with undetectable ethanol concentrations, the range of 95% of osmolal gap values was narrower than previous published formulas, and in patients with detectable ethanol concentrations, the range was narrower or similar. We performed a subanalysis of 138 cases for which both the toxic alcohol concentration could be measured and the osmolal gap could be calculated. Our simplified equation had superior diagnostic accuracy for toxic alcohol exposure.

Limitations: Single center, no external validation, limited number of cases with detectable toxic alcohols.

Conclusions: In a large cohort, coefficients from regression analyses estimating the contribution of glucose, urea, and ethanol were higher than 1.0. Our simplified formula to precisely calculate osmolarity yielded improved diagnostic accuracy for suspected toxic alcohol exposures than previously published formulas.
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http://dx.doi.org/10.1053/j.ajkd.2017.03.023DOI Listing
September 2017

Prediction and validation of the duration of hemodialysis sessions for the treatment of acute ethylene glycol poisoning.

Kidney Int 2017 08 12;92(2):453-460. Epub 2017 Apr 12.

CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada; Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada. Electronic address:

The duration of hemodialysis (HD) sessions for the treatment of acute ethylene glycol poisoning is dependent on concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. Ethylene glycol assays are not readily available, potentially leading to undue extension or premature termination of HD. We report a prediction model for the duration of high-efficiency HD sessions based retrospectively on a cohort study of 26 cases of acute ethylene glycol poisoning in 24 individuals treated by alcohol dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD for more than 14 days, and two died. In 19 cases, the mean ethylene glycol elimination half-life during high-efficiency HD was 165 minutes (95% confidence interval of 151-180 minutes). In a training set of 12 patients with acute ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model was then validated in a set of seven acute ethylene glycol poisonings. Thus, the HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.
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http://dx.doi.org/10.1016/j.kint.2017.02.018DOI Listing
August 2017

Availability and cost of extracorporeal treatments for poisonings and other emergency indications: a worldwide survey.

Nephrol Dial Transplant 2017 Apr;32(4):699-706

Department of Medicine, Verdun Hospital, University of Montreal, Montreal, Canada.

Background: Extracorporeal treatments (ECTRs) are used for different conditions, including replacement of organ function and poisoning. Current recommendations for ECTRs in various poisonings suggest that intermittent haemodialysis (IHD) is the most efficient technique. However, the practicality of these recommendations is poorly defined in view of limited information on availability and cost worldwide.

Methods: A survey invitation to an Internet-based questionnaire was emailed between January 2014 and March 2015 to members of international societies to determine the availability, time to initiation and cost of ECTRs (including filters, dialysate, catheter, anticoagulant and nursing/physician salary). The median cost ratio of every ECTR compared with IHD performed in the same institution were presented.

Results: The view rate was estimated at 28.1% (2532/9000), the participation rate was 40.1% (1015/2532) and the completion rate was 16.0% (162/1015). Respondents originated from 89 countries, and nearly three-fourths practiced in a tertiary care centre. A total of 162 respondents provided sufficient data for in-depth analysis. IHD was the most available acute ECTR (96.9%), followed by therapeutic plasma exchange (TPE; 68.3%), continuous renal replacement therapy (CRRT; 62.9%), peritoneal dialysis (PD; 44.8%), haemoperfusion (HP; 30.9%) and liver support devices (LSDs; 14.7%). IHD, CRRT and HP were the shortest to initiate (median = 60 min). The median cost ratios of each ECTR compared with IHD were 1.7 for CRRT and HP, 2.8 for TPE, 6.5 for LSDs and 1.4 for PD (P < 0.001 for all). The median cost ratio of a 4-h IHD treatment compared with 1 day in the intensive care unit was 0.6 (P =  0.2).

Conclusions: IHD appears to be the most widely available ECTR worldwide and is at least 30% less expensive than other ECTRs. The superior efficacy of IHD for enhanced elimination, added to its lower cost and wider availability, strengthens its preference as the ECTR of choice in most cases of acute poisoning.

Keywords: costing, CRRT, EXTRIP, hemodialysis, hemoperfusion.
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http://dx.doi.org/10.1093/ndt/gfw456DOI Listing
April 2017

Pneumocystis pneumonia in patients with inflammatory or autoimmune diseases: Usefulness of lymphocyte subtyping.

Int J Infect Dis 2017 Apr 20;57:108-115. Epub 2017 Feb 20.

Medical Microbiology and Infectious Diseases Department, Sacré-Cœur Hospital, University of Montreal, 5400 Boulevard Gouin Ouest, Montreal, QC, H2V 3A5, Canada. Electronic address:

Objectives: No consensus currently exists on the indications for Pneumocystis jirovecii prophylaxis in patients with inflammatory or autoimmune diseases. The main objective was to identify biomarkers associated with P. jirovecii pneumonia (PCP) in this population.

Methods: A retrospective study was carried out at Beijing Union Medical College Hospital (2003-2014). All patients with an inflammatory or autoimmune disease presenting with acute onset of fever and respiratory symptoms were included.

Results: A total of 123 patients were included, of whom 42% had confirmed PCP, 18% had possible PCP, and 40% were negative for PCP. Immunosuppressive conditions consisted mostly of diffuse connective tissue disease (50%) and primary nephropathy (20%). Immunosuppressive therapies consisted of corticosteroids (95%) with concomitant non-steroidal drugs (80%). Independent predictors of PCP were a CD3+ cell count <625×10/l, serum albumin <28g/l, and PaO/FiO <210. Furthermore, 90% of patients with PCP had a CD3+ cell count <750×10/l. Independent predictors of mortality were a CD8+ cell count <160×10/l and a PaO/FiO <160.

Conclusions: In patients with inflammatory and autoimmune conditions receiving immunosuppressive therapy, low CD3+ and CD8+ cell counts were strongly associated with PCP and its mortality. These results suggest that lymphocyte subtyping is a very useful tool to optimize the selection of patients needing prophylaxis.
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http://dx.doi.org/10.1016/j.ijid.2017.02.010DOI Listing
April 2017

Phenytoin overdose treated with hemodialysis using a high cut-off dialyzer.

Hemodial Int 2017 01 6;21(1):E13-E17. Epub 2016 Sep 6.

Verdun Hospital, Université de Montréal, Montréal, Quebec, Canada.

We describe the case of a 52-year-old man who presented after having ingested an unknown quantity of phenytoin. Peak phenytoin concentration was 51.2 mg/L (therapeutic range 10-20 mg/L). Five days after admission, the patient became comatose and was intubated. Because of persistent toxic phenytoin levels and unchanged clinical status for 12 days, hemodialysis (HD) was prescribed to enhance elimination of phenytoin. HD was performed using a Gambro Theralite filter (Baxter International Inc., Deerfield, USA), a high cut-off filter that allows the removal of molecules of up to 45 kDa. Phenytoin concentration readily decreased during the 8-hour HD treatment from 38.9 mg/L to 27.8 mg/L (28.5% decrease); during HD, phenytoin half-life was 18.5h (compared to 1109.8h before HD and 56.3h after HD), phentyoin clearance averaged 80.1 mL/min and a total of 1.1 g of phenytoin was removed. Albumin removal from the Theralite filter was most important at the beginning of HD. The high clearance of phenytoin obtained with this filter was likely due to its high surface area rather than its capacity to remove the albumin-phenytoin complex.
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http://dx.doi.org/10.1111/hdi.12475DOI Listing
January 2017

Why are we Still Dialyzing Overdoses to Tricyclic Antidepressants? A subanalysis of the NPDS database.

Semin Dial 2016 09 4;29(5):403-9. Epub 2016 Aug 4.

Department of Nephrology, Verdun Hospital, University of Montreal, Montreal, Canada.

A recent analysis of the American Association of Poison Control Centers database, showed that poisonings from toxins not usually considered amenable to extracorporeal purification ("non-classic toxins" such as ethanol and tricyclic antidepressants) continue to be reported. This publication investigates factors that may explain these findings. Our results suggest that: 1) the relatively high absolute number of ECTR performed for non-classic toxins may simply reflect the large number of exposures to these toxins, 2) poisoning from another toxin may have been the reason for ECTR initiation in some exposures to non-classic toxins, 3) poisoning from non-classic toxins may receive ECTR for purposes other than toxin removal, and 4) the decisional threshold to initiate ECTR may be lower for non-classic toxins because of heightened toxicity.
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http://dx.doi.org/10.1111/sdi.12520DOI Listing
September 2016

Extracorporeal treatments in a dapsone overdose: a case report.

Clin Toxicol (Phila) 2016 Nov 18;54(9):886-889. Epub 2016 Jul 18.

b Division of Nephrology , Hôpital du Sacré-Cœur de Montréal, Faculty of Medicine, Université de Montréal , Montréal , Canada.

Introduction: Intentional dapsone intoxication can be life-threatening. There is limited data on the clinical effect of extracorporeal treatments (ECTRs) on dapsone elimination. We describe a case of severe dapsone toxicity treated with different ECTRs.

Case Details: A 23-year-old woman was admitted 2.5 h after ingesting 2.2 g of dapsone. She developed methemoglobinemia (39.9%) and showed signs of toxicity (hemodynamic instability and altered mental status) despite multiple-activated charcoal, methylene blue, vasopressors and endotracheal intubation. Continuous venovenous hemofiltration (CVVH) was then initiated for 5 h, followed by intermittent hemodialysis with hemoperfusion (IHD-HP) for 4 h, and CVVH for another 48 h. The platelet count decreased to 32 × 10/L 3 h after IHD-HP. The elimination half-life of dapsone was 2.0 h during IHD-HP, and 14.2 h during CVVH. Mean dapsone clearance with IHD was 62 mL/min versus 22 mL/min with CVVH. IHD removed 95.3 mg, and CVVH removed 67.8 mg over 3.8 h. No rebound occurred following ECTR cessation. The toxicokinetics of dapsone metabolites were also accelerated during ECTR. The patient was extubated after 3.5 days and discharged without sequelae after 7 days.

Discussion: Dapsone clearance was enhanced by ECTR, especially by IHD-HP. However, HP was associated with severe asymptomatic thrombocytopenia.
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http://dx.doi.org/10.1080/15563650.2016.1209769DOI Listing
November 2016

Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics.

Clin Toxicol (Phila) 2016 Jul 27;54(6):519-22. Epub 2016 Apr 27.

b Department of Emergency Medicine, McGill University Health Centre , Montréal , Québec , Canada ;

Context: Early onset acidosis from mitochondrial toxicity can be observed in massive acetaminophen poisoning prior to the development of hepatotoxicity. In this context, the efficacy of acetylcysteine to reverse mitochondrial toxicity remains unclear and hemodialysis may offer prompt correction of acidosis. Unfortunately, toxicokinetics of acetaminophen and acetylcysteine during extracorporeal treatments hemodialysis have seldom been described.

Case Details: An 18-year-old woman presented to the emergency department 60 minutes after ingestion of 100 g of acetaminophen, and unknown amounts of ibuprofen and ethanol. Initial assessment revealed an agitated patient. Her mental status worsened and she required intubation for airway protection. Investigations showed metabolic acidosis with lactate peaking at 8.6 mmol/L. Liver and coagulation profiles remained normal. Acetaminophen concentration peaked at 981 μg/ml (6496 μmol/L). Pending hemodialysis, the patient received 100 g of activated charcoal and an acetylcysteine infusion at 150 mg/kg over 1 hour, followed by 12.5 mg/kg/h for 4 hours. During hemodialysis, the infusion was maintained at 12.5 mg/kg/h to compensate for expected removal before it was decreased to 6.25 mg/kg for 20 hours after hemodialysis. The patient rapidly improved during hemodialysis and was discharged 48 hours post-admission.

Toxicokinetics: The acetaminophen elimination half-life was 5.2 hours prior to hemodialysis, 1.9-hours during hemodialysis and 3.6 hours post hemodialysis. The acetaminophen and acetylcysteine clearances by A-V gradient during hemodialysis were 160.4 ml/min and 190.3 ml/min, respectively. Hemodialysis removed a total of 20.6 g of acetaminophen and 17.9 g of acetylcysteine.

Conclusion: This study confirms the high dialyzability of both acetaminophen and acetylcysteine. Hemodialysis appears to be a beneficial therapeutic option in cases of massive acetaminophen ingestion with coma and lactic acidosis. Additionally, these results suggest that the infusion rate of acetylcysteine must be more than double during hemodialysis to compensate for its ongoing removal and provide similar plasma concentrations to the usual acetylcysteine regimen.
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http://dx.doi.org/10.1080/15563650.2016.1175006DOI Listing
July 2016

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

Clin Toxicol (Phila) 2016 ;54(2):103-14

h Department of Medicine and Emergency Medicine , McGill University Health Centre, McGill University , Montreal , Canada.

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.
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http://dx.doi.org/10.3109/15563650.2015.1118488DOI Listing
June 2016

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

Am J Kidney Dis 2016 Feb 11;67(2):187-97. Epub 2015 Nov 11.

Department of Pharmacy and Therapeutics, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, PA; Renal Electrolyte Division, Department of Medicine, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, PA. Electronic address:

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.
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http://dx.doi.org/10.1053/j.ajkd.2015.08.031DOI Listing
February 2016

Practice Trends in the Use of Extracorporeal Treatments for Poisoning in Four Countries.

Semin Dial 2016 Jan-Feb;29(1):71-80. Epub 2015 Nov 9.

Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York City, New York.

Extracorporeal treatments (ECTRs) such as hemodialysis (HD), enhance the elimination of a small number of toxins. Changes in overdose trends, prescribing practices, antidotes, and dialysis techniques may alter the indications and rates of ECTR use over time. This study analyzed trends in ECTR for poisonings in four countries. A retrospective study of national poison center databases from the United States, Denmark, United Kingdom, and five regional databases within Canada was performed. All cases of patients receiving an ECTR were included. ECTR cases were totalled annually and reported as annual rates per 100,000 exposures with stratification per types of ECTR and toxins. The data collection varied by countries. United States, 1985-2014; United Kingdom, 2011-2013; Denmark, 2005-2014, and regions of Canada as follows: Alberta, 1991-2015; Saskatchewan, 2001-2015; Nova Scotia-PEI, 2006-2015; Quebec, 2008-2014; Ontario-Manitoba, 2009-2015; British Columbia, 2012-2015. During the study period, the total number of ECTRs and rates per 100,000 exposures, respectively, were: United States, 40,258 and 65.7; United Kingdom, 343 and 232.6; Denmark, 616 and 305.5; Canada, 2709 and 177.5; case rates increased over time for the United States, Denmark, and Canada, but decreased in the United Kingdom. Across the United States and Denmark, HD was the preferred modality used. Toxins for which ECTR was most often used were: United States, ethylene glycol; Canada, methanol; United Kingdom, ethylene glycol; Denmark, salicylates. A high number of ECTRs were performed for atypical toxins such as acetaminophen and benzodiazepines. These data demonstrate a growing use of HD for poisoning with significant regional variations in the overall rates and indications.
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http://dx.doi.org/10.1111/sdi.12448DOI Listing
December 2016

The authors reply.

Crit Care Med 2015 Nov;43(11):e534-5

Department of Nephrology, Verdun Hospital, University of Montreal, Verdun, QC, Canada Department of Emergency Medicine, Medical Toxicology Service, Morristown Medical Center, Morristown, NJ Department of Medical Biology, Sacré-Coeur Hospital, University of Montreal, Montreal, QC, Canada Department of Emergency Medicine, Medical Toxicology, Consultation Service, McGill University Health Centre, Montreal, QC, Canada Division of Nephrology, Department of Medicine, University of California, San Francisco, CA Burns, Trauma and Critical Care Research Centre, School of Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

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http://dx.doi.org/10.1097/CCM.0000000000001248DOI Listing
November 2015
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