Publications by authors named "Darren M Roberts"

107 Publications

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

Crit Care 2021 Jun 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
June 2021

A case of a markedly elevated dabigatran concentration resistant to the approved dose of idarucizumab.

Intern Med J 2021 Apr;51(4):616-617

Department of Haematology, St Vincent's Hospital, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/imj.15278DOI Listing
April 2021

A cluster of lysergic acid diethylamide (LSD) poisonings following insufflation of a white powder sold as cocaine.

Clin Toxicol (Phila) 2021 Apr 13:1-6. Epub 2021 Apr 13.

NSW Poisons Information Centre, Sydney Children's Hospitals Network, Westmead, Australia.

Objective: Adulteration, substitution or contamination of illicit substances can have clinically significant implications when other illicit substances are included. Such circumstances can present as clusters of poisonings, including severe toxicity and death following exposure to unexpected illicit substances. We report a cluster of laboratory-confirmed lysergic acid diethylamide (LSD) in a powder that was sold as cocaine and used recreationally.

Methods: The Prescription, Recreational and Illicit Substance Evaluation (PRISE) program established by the New South Wales Ministry of Health includes State-based hospital toxicology services, Poisons Information Centre, Forensic & Analytical Science Service and emergency services to identify clusters of severe and unusual toxicity associated with substance use. PRISE criteria include a known cluster (geographically or situationally related) of people with acute severe toxicity, especially when accompanied by a toxidrome that is inconsistent with the history of exposure. A timely comprehensive drug screen and quantification is performed in eligible cases and the results are related to the clinical features. The need for a public health response is then considered. Four individuals inhaled a white powder that was sold as cocaine and developed severe toxicity that was not consistent with cocaine which prompted transfer to hospital for further management.

Results: LSD was confirmed in four subjects, and the concentrations in 3 of the individuals were 0.04-0.06 mg/L which are among the highest reported in the literature. Common clinical features were hallucinations, agitation, vomiting, sedation, hypertension, and mydriasis. One subject required intubation and admission to the intensive care unit, two required overnight admission, and the fourth was discharged following oral diazepam after observation. No subject suffered persistent injury.

Conclusions: A close working relationship between pre-hospital emergency services, hospital-based clinical services, public health authorities, and analytical laboratories appears to be advantageous. Favourable clinical outcomes are observed from LSD poisoning despite high exposures with good supportive care.
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http://dx.doi.org/10.1080/15563650.2021.1904140DOI Listing
April 2021

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

Pharmacotherapy 2021 May 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

Poor relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and level of consciousness following intentional ingestion of eucalyptus oil.

Clin Toxicol (Phila) 2021 Mar 1:1-3. Epub 2021 Mar 1.

Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, Australia.

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http://dx.doi.org/10.1080/15563650.2021.1887884DOI Listing
March 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

Managing hyperuricemia and gout in chronic kidney disease: a clinical conundrum.

Curr Opin Nephrol Hypertens 2021 Mar;30(2):245-251

Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital.

Purpose Of Review: There is controversy regarding the impact of hyperuricemia on the progression of chronic kidney disease (CKD), and gout remains sub optimally managed in this population. We discuss the prescribing of drugs for the treatment of gout in patients with CKD.

Recent Findings: There is a lack of consensus from expert guidelines, and prescribers have concerns regarding the risk of adverse reactions from medicines used to treat gout. These situations appear to contribute to suboptimal management of gout in this cohort. Recent data have challenged the role of urate lowering therapy (ULT) in the management of asymptomatic hyperuricemia in CKD.

Summary: ULT should be commenced in all patients with severe, recurrent disease, tophaceous gout and evidence of joint damage. Most international guidelines recommend a treat-to-target approach for the management of gout. In CKD, ULT should be started at low dose with up titration adjusted to serum urate levels, rather than being based on the creatinine clearance. If patients fail first-line therapy, alternative agents are utilized, the specific agent depending on ease of access, burden of disease and other comorbidities. This approach should be incorporated into routine practice to ensure optimal treatment of gout in CKD. More research is required to investigate whether treatment of asymptomatic hyperuricemia has clinical benefits.
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http://dx.doi.org/10.1097/MNH.0000000000000691DOI Listing
March 2021

Evaluation of a Pilot Vancomycin Precision Dosing Advisory Service on Target Exposure Attainment Using an Interrupted Time Series Analysis.

Clin Pharmacol Ther 2021 01 5;109(1):212-221. Epub 2020 Dec 5.

Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.

This study evaluated the ability of a pilot therapeutic drug monitoring (TDM) Advisory Service to facilitate vancomycin therapeutic target attainment within a real-world clinical setting. The Service provided area under the concentration-time curve (AUC)-guided vancomycin dose recommendations, using Bayesian forecasting software and clinical expertise, to prescribers at an Australian hospital. A retrospective audit of intravenous vancomycin therapy (> 48 hours) in adults (≥ 18 years old) was undertaken over a 54-month period to evaluate attainment of established vancomycin pharmacokinetic/pharmacodynamic targets (AUC over 24 hours / minimum inhibitory concentration: 400-600) before (36-month period) and after (18-month period) Service implementation. Interrupted time series analysis was employed to evaluate monthly measures of the median proportion of therapy spent within the target range. Indices of time to target attainment were also assessed before and after Service implementation. The final cohort comprised 1,142 courses of vancomycin (816 patients); 835 courses (596 patients) and 307 courses (220 patients) administered before and after Service implementation, respectively. Prior to piloting the Service, the median proportion of time in the target range was 40.1% (95% CI, 34.3-46.0%); this increased by 10.4% (95% CI, 1.2-19.6%, P = 0.03) after the Service, and was sustained throughout the post-Service evaluation period. Post-Service target attainment at 48-72 hours after initiation of therapy was increased (7.8%, 95% CI, 1.3-14.3%, P = 0.02). The findings of this study provide evidence that a consultative TDM Service can facilitate attainment of vancomycin therapeutic targets; however, optimization of the Service may further improve the use of vancomycin.
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http://dx.doi.org/10.1002/cpt.2113DOI Listing
January 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

Management of proteinuria: blockade of the renin-angiotensin-aldosterone system.

Aust Prescr 2020 08 3;43(4):121-125. Epub 2020 Aug 3.

Drug Health Services and Clinical Pharmacology and Toxicology, Royal Prince Alfred Hospital, Sydney.

Proteinuria, in particular albuminuria, is a potentially significant modifiable risk factor for cardiovascular disease and the progression of kidney disease. Current treatment guidelines for albuminuria recommend a single renin–angiotensin–aldosterone inhibitor. This can be an ACE inhibitor or an angiotensin receptor antagonist. The routine use of combined renin–angiotensin–aldosterone inhibition for albuminuria is not supported by current evidence. Combination therapy is associated with higher rates of adverse events such as hyperkalaemia and progressive renal impairment.
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http://dx.doi.org/10.18773/austprescr.2020.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450775PMC
August 2020

COVID-19 and the quality use of medicines: evidence, risks and fads.

Aust Prescr 2020 Jun 8;43(3):78-80. Epub 2020 May 8.

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

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http://dx.doi.org/10.18773/austprescr.2020.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358054PMC
June 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

Estimating renal function for patients in wheelchairs.

Aust Prescr 2020 Apr 1;43(2):67. Epub 2020 Apr 1.

Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney.

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http://dx.doi.org/10.18773/austprescr.2020.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186273PMC
April 2020

Antiemetic drugs: what to prescribe and when.

Aust Prescr 2020 04 1;43(2):49-56. Epub 2020 Apr 1.

Drug Health Services and Clinical Pharmacology and Toxicology, Royal Prince Alfred Hospital, Sydney.

Nausea and vomiting are common symptoms with many possible causes, including the adverse effects of drugs. If a drug is indicated, the cause guides the choice of antiemetic drug The main antiemetic classes include antagonists of the serotonin, dopamine, histamine, muscarinic and neurokinin systems, corticosteroids and benzodiazepines. Some antiemetics appear more effective for specific indications Serotonin and neurokinin antagonists, such as ondansetron and aprepitant, are highly effective in treating chemotherapy-induced nausea and vomiting. Metoclopramide and antihistamines are first-line options for nausea and vomiting in pregnancy Serotonin antagonists and some dopamine antagonists, such as metoclopramide, can prolong the QT interval on the ECG. Dopamine antagonists can cause extrapyramidal adverse effects, particularly in children
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http://dx.doi.org/10.18773/austprescr.2020.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186277PMC
April 2020

Incomplete responses to the recommended dose of idarucizumab: a systematic review and pharmacokinetic analysis.

Clin Toxicol (Phila) 2020 Apr 8:1-12. Epub 2020 Apr 8.

Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia.

Dabigatran, a direct thrombin inhibitor, is 80% renally eliminated and demonstrates multi-compartmental pharmacokinetics. Idarucizumab is a monoclonal antibody that reverses dabigatran-induced anticoagulation and displays single compartment pharmacokinetics, with a smaller volume of distribution and shorter elimination half-life than dabigatran. These differences in pharmacokinetics mean that redistribution of dabigatran from peripheral compartments can occur after idarucizumab has been eliminated, resulting in rebound in the dabigatran plasma concentration and treatment failure. Clinical experience notes failure of a single idarucizumab 5 g dose to fully reverse coagulopathy in certain patients. To identify factors predisposing to an incomplete response to the standard idarucizumab 5 g dose. A systematic literature search in PubMed using terms "dabigatran" and "idarucizumab" covering 2015 to October 2019 identified 387 entries. Titles and abstracts were screened initially, followed by full text review and data extraction from 97 eligible articles. Data extracted included clinical information, dabigatran concentrations, coagulation results, idarucizumab dosage and patient outcomes. Pharmacokinetic simulations were conducted using a two-compartment model to predict the likelihood that acute or chronic kidney disease will contribute to an incomplete reversal of dabigatran-induced anticoagulation. Of 240 published cases receiving idarucizumab, 33 reported dabigatran concentration rebound, within a median time of 22 h. From 231 cases reporting idarucizumab dose, 10 received repeated administration due to a rebound in dabigatran concentrations. Baseline dabigatran concentrations >228 ng/mL were more likely to experience a rebound post-idarucizumab to >30 ng/mL (detectable). For baseline dabigatran >488 ng/mL, the concentration rebounded to >75 ng/mL (therapeutic). Idarucizumab is expected to neutralise a maximum plasma dabigatran concentration of 980 ng/mL, but most likely a lesser amount. Pharmacokinetic modelling suggests, for patients taking dabigatran 150 mg twice daily, an incomplete response to 5 g idarucizumab is predicted after approximately 72 h dosing when GFR less than 30 mL/min (25% of normal), and after 36 h with severely impaired renal function (GFR 6 mL/min; GFR 5% of normal). Idarucizumab has neutralised dabigatran following deliberate self-poisoning with dabigatran in a limited number of cases, even in the absence of bleeding. There are insufficient data regarding the use of idarucizumab as part of standard supportive care in this context. The dilute thrombin time can be used to determine the dabigatran concentration, but other more standard coagulation assays are less precise. A normal aPTT largely excludes dabigatran. We suggest performing coagulation assays and dabigatran concentrations every 6 h for a minimum of 36 h after idarucizumab administration to detect a rebound in dabigatran. This is particularly necessary in patients with glomerular filtration rate <30 mL/min or those with a plasma dabigatran concentration exceeding approximately 500 ng/mL. If a rebound in dabigatran is noted, then repeat administration of idarucizumab 5 g can be considered for reversal of recurrent coagulopathy if clinically indicated. The use of idarucizumab for reversal of dabigatran is complex and requires consideration of clinical circumstances and laboratory investigations. Monitoring post-idarucizumab may be required in acute or chronic kidney disease to detect a rebound in dabigatran concentration and the need for additional doses of idarucizumab.
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http://dx.doi.org/10.1080/15563650.2020.1743846DOI Listing
April 2020

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

Clin Infect Dis 2021 04;72(8):1369-1378

Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets.

Methods: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.

Results: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.

Conclusions: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
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http://dx.doi.org/10.1093/cid/ciaa224DOI Listing
April 2021

Consensus statements for clinical practice require rigorous and transparent methods.

Pediatr Nephrol 2020 05 7;35(5):911-912. Epub 2020 Mar 7.

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

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http://dx.doi.org/10.1007/s00467-019-04407-3DOI Listing
May 2020

Transient accelerated idioventricular rhythm after 1,4-butanediol exposure.

Clin Toxicol (Phila) 2020 11 5;58(11):1071-1072. Epub 2020 Mar 5.

Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, Australia.

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http://dx.doi.org/10.1080/15563650.2020.1728296DOI Listing
November 2020

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

Hepatotoxicity in a child following an accidental overdose of liquid paracetamol.

Clin Toxicol (Phila) 2020 11 18;58(11):1063-1066. Epub 2020 Feb 18.

New South Wales Poisons Information Centre, Children's Hospital at Westmead, Westmead, Australia.

Accidental pediatric liquid paracetamol exposure is common. Most children do not require treatment with acetylcysteine and acute liver injury is rare. An otherwise well 3-year-old (15.4 kg) girl with recent vomiting and low-grade fever presented 1 h post-accidental ingestion of up to 150 mL of 24 mg/mL (240 mg/kg) of liquid paracetamol. Paracetamol concentrations 2 and 4 h post-ingestion were 105 and 97 mg/L, respectively, both below the nomogram treatment threshold so acetylcysteine was not administered. The ALT was elevated to 52 U/L 4 h post-ingestion, and then 219 U/L at 17 h, so intravenous acetylcysteine was commenced at 25 h. ALT peaked at 1393 U/L 5d post-ingestion, and INR peaked at 1.5 at 44 h post-ingestion. Acetylcysteine continued for 64 h and she made an uneventful recovery. Paracetamol metabolites were measured including, nontoxic glucuronide and sulphate conjugates and toxic cytochrome P450 (CYP) metabolites (cysteine and mercapturate). The apparent paracetamol half-life was 6.3 h. Her CYP metabolites were higher than usual, 11% of total metabolites. Glucuronide and sulphate conjugates accounted for 71 and 18% of total metabolites, respectively. This uncommon case of hepatotoxicity in a child following accidental liquid paracetamol ingestion may have been due to increased susceptibility from a recent viral illness with decreased oral intake, as evidenced by the higher proportion of CYP metabolites.
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http://dx.doi.org/10.1080/15563650.2020.1722150DOI Listing
November 2020

How to adjust drug doses in chronic kidney disease.

Aust Prescr 2019 10 1;42(5):163-167. Epub 2019 Oct 1.

Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney.

Drugs excreted by the kidney require dose reduction in chronic kidney disease. This adjustment depends on the severity of the disease and what proportion of the drug is eliminated by the kidneys The estimated glomerular filtration rate can generally be used to guide dose adjustment in patients with stable kidney function. However, the formula can be misleading in some patient subsets and other approaches are required At extremes of body mass, the estimated glomerular filtration rate can under- or overestimate kidney function. It may need to be adjusted for body surface area, particularly for drugs with a narrow therapeutic range or requiring a minimum concentration to be effective. Close monitoring of drug effect and toxicity is also needed and can be supported by therapeutic drug monitoring For short courses of drugs with a wide therapeutic index, dose adjustment may not be needed Alternative methods for quantifying kidney function include the Cockcroft-Gault formula (estimates creatinine clearance) or direct measures of glomerular filtration rate using exogenous isotope compounds. These are not commonly required
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http://dx.doi.org/10.18773/austprescr.2019.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787303PMC
October 2019

Consensus statements on the approach to patients in a methanol poisoning outbreak.

Clin Toxicol (Phila) 2019 12 22;57(12):1129-1136. Epub 2019 Jul 22.

The Norwegian CBRNE Centre of Medicine, Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

Methanol poisoning is an important cause of mortality and morbidity worldwide. Although it often occurs as smaller sporadic events, epidemic outbreaks are not uncommon due to the illicit manufacture and sale of alcoholic beverages. We aimed to define methanol poisoning outbreak (MPO), outline an approach to triaging an MPO, and define criteria for prioritizing antidotes, extracorporeal elimination treatments (i.e., dialysis), and indications for transferring patients in the context of an MPO. We convened a group of experts from across the world to explore geographical, socio-cultural and clinical considerations in the management of an MPO. The experts answered specific open-ended questions based on themes aligned to the goals of this project. This project used a modified Delphi process. The discussion continued until there was condensation of themes. We defined MPO as a sudden increase in the number of cases of methanol poisoning during a short period of time above what is normally expected in the population in that specific geographic area. Prompt initiation of an antidote is necessary in MPOs. Scarce hemodialysis resources require triage to identify patients most likely to benefit from this treatment. The sickest patients should not be transferred unless the time for transfer is very short. Transporting extracorporeal treatment equipment and antidotes may be more efficient. We have developed consensus statements on the response to a methanol poisoning outbreak. These can be used in any country and will be most effective when they are discussed by health authorities and clinicians prior to an outbreak.
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http://dx.doi.org/10.1080/15563650.2019.1636992DOI Listing
December 2019

High-dose insulin euglycemic therapy to treat cardiomyopathy associated with massive venlafaxine overdose.

Clin Toxicol (Phila) 2020 04 10;58(4):299-300. Epub 2019 Jul 10.

St. Vincent's Clinical School, University of NSW, Darlinghurst, New South Wales, Australia.

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http://dx.doi.org/10.1080/15563650.2019.1638930DOI Listing
April 2020

1,4-Butanediol overdose mimicking toxic alcohol exposure.

Clin Toxicol (Phila) 2020 03 20;58(3):204-207. Epub 2019 Jun 20.

Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia.

1,4-butanediol (1,4-BD) is a gamma-hydroxybutyrate (GHB) analogue with a similarly narrow therapeutic window that is becoming a more common cause of recreational overdose. Reports of confirmed exposures are limited. A 44 year-old man who had consumed alcohol subsequently became unconscious after ingesting what was thought to be GHB. The presentation was not entirely consistent with GHB poisoning, including a longer duration of unconsciousness and features that mimicked toxic alcohol exposure including a high anion gap metabolic acidosis (HAGMA) and osmol gap. The patient was treated supportively with intubation, haemodiafiltration and intravenous ethanol until the diagnosis was refined using specific laboratory testing. The concentration of 1,4-BD was the highest reported in the literature and the outcome favourable. This case highlights pharmacokinetic issues peculiar to 1,4-BD, including the interaction with ethanol which delays the onset of psychoactive effects from 1,4-BD's metabolite GHB, and dose-dependent pharmacokinetics. In overdose, 1,4-BD can induce a HAGMA and other features of toxic alcohol poisoning. Managing an unconscious patient with these features can prompt certain treatments until the diagnosis is refined, which can require specific laboratory testing to identify the culprit. The actual risk of toxic alcohol and other causes is adjusted on a case-by-case basis from the history of exposure and local epidemiology of substance use and poisoning.
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http://dx.doi.org/10.1080/15563650.2019.1617419DOI Listing
March 2020

Guidelines for reporting case studies and series on drug-induced QT interval prolongation and its complications following acute overdose.

Clin Toxicol (Phila) 2020 01 24;58(1):20-28. Epub 2019 Apr 24.

Department of Emergency Medicine, Hôpital Charles-Lemoyne, Greenfield Park, Canada.

The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning. We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. standards were developed for acceptance or rejection of individual criteria. Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented. We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.
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http://dx.doi.org/10.1080/15563650.2019.1605077DOI Listing
January 2020

A spotlight on the role, use, and availability of codeine and the implications faced.

Expert Rev Clin Pharmacol 2018 Nov 27;11(11):1057-1059. Epub 2018 Oct 27.

c Alcohol and Drug Service and Department of Clinical Pharmacology and Toxicology , St Vincent's Hospital , Darlinghurst , NSW , Australia.

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http://dx.doi.org/10.1080/17512433.2018.1537122DOI Listing
November 2018

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

Complex decisions in the use of extracorporeal treatments in acute metformin overdose: which modality, when and how to measure the effect.

Br J Clin Pharmacol 2018 12 3;84(12):2689-2691. Epub 2018 Oct 3.

Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia.

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http://dx.doi.org/10.1111/bcp.13762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255999PMC
December 2018

Successful Treatment of PD Peritonitis Due to .

Perit Dial Int 2018 Sep-Oct;38(5):379-381

Renal Medicine, The Canberra Hospital, Garran, ACT, Australia

is a rare cause of peritoneal dialysis-associated peritonitis (PD peritonitis). One documented case report described poor outcome despite treatment with appropriate antibiotics. Here, we report the successful treatment of PD peritonitis due to with 21 days of intraperitoneal (IP) antibiotics using the regimen described for , notably IP gentamicin (10 days) followed by IP cefepime and oral ciprofloxacin (11 days). Despite the favorable outcome, measurement of antibiotic concentrations in the PD effluent suggests that the cefepime and possibly ciprofloxacin regimens do not achieve key antibiotic concentration targets that are reported to maximize bacterial kill. The role of routine therapeutic drug monitoring to maximize clinical outcomes from antibiotic therapy for PD peritonitis requires further consideration.
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http://dx.doi.org/10.3747/pdi.2018.00014DOI Listing
February 2019

Communication and ciprofloxacin-associated acute kidney injury.

Aust Prescr 2018 Aug 1;41(4):122. Epub 2018 Aug 1.

Renal Medicine, Canberra Hospital and Community Services.

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http://dx.doi.org/10.18773/austprescr.2018.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091775PMC
August 2018