Blood concentrations after accidental cyclosporin overdose

Two cases of children are reported with an accidental oral overdose of cyclosporin in whom blood concentrations were monitored. Despite a tenfold oral overdose, the peak blood concentrations of cyclosporin in both patients were only moderately increased above therapeutic levels. Apart from a transient rise in blood pressure in one patient, no toxic effects of cyclosporia were noticed.     

The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: Guideline methodology

Abstract

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1–9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.     

Digital Holter measurement of QT prolongation in ziprasidone overdose

Objective. QT prolongation is an important complication in drug overdose, particularly with some antidepressants and antipsychotics. There are problems with the accurate measurement of the QT interval and determining for what QT interval patients should be monitored, because of the risk of torsades des pointes (TdP). We report a case of ziprasidone overdose with QT prolongation, demonstrating different methods of measuring the QT interval. Case report. A 47-year-old female presented after taking 1.2 g of ziprasidone and 250 mg of diazepam. She was taking propranolol and venlafaxine therapeutically. She developed bradycardia and QT prolongation (540 msec). She was transferred to a telemetry bed and observed for 48 h until her QT interval returned to normal (460 msec). QT intervals were extracted from (1) 12-lead digital Holter recordings (gold standard); (2) automated measurements on standard electrocardiograms (ECGs); and (3) manual measurements on standard ECGs, and compared on a QT versus time plot. An abnormal QT was determined based on the QT nomogram. Manual QT measurements showed a clear temporal association between ziprasidone overdose and a long QT, consistent with accurate QT measurements using continuous 12-lead Holter recordings with automatic QT measurements. However, standard automated measurements did not indicate an abnormal QT. Conclusions. Manual measurement of the QT interval appeared to be similar to the more accurate measurement of the QT by automated digital Holter recordings and better than standard automated measurements. Manual QT measurements would be more appropriate in clinical assessment of patients.     

云南省部分地区注射吸毒者海洛因过量情况及影响因素分析

目的 了解云南省部分地区注射吸毒者(IDU)海洛因过量情况及其影响因素。方法 采用横断面调查的方法,于2015年7-8月对云南省红河州和德宏州的4个美沙酮维持治疗(MMT)门诊和2个州强制戒毒所的IDU进行问卷调查,内容包括社会人口学特征、毒品使用情况、过去1年海洛因过量情况以及最近1次海洛因过量情况等。对过去1年发生过海洛因过量的相关因素进行logistic回归分析。结果 共340名IDU符合入选标准,男性占85.3%(290/340),年龄为(37.7±8.7)岁,汉族占65.6%(223/340),HIV阳性检出率为49.4%(167/338),过去6个月使用过新型毒品占22.6%(77/340)。自吸毒以来,曾有过海洛因过量的比例为41.8%(142/340),海洛因过量次数M=3次。在过去1年中海洛因过量发生率为15.6%(53/340),M=1次。发生海洛因过量的年龄为(36.7±8.4)岁,吸毒年限为(16.5±7.6)年,男性占83.0%(44/53)。发生海洛因过量的主要原因为增加海洛因用量(26.4%,14/53)和多药滥用(28.3%,15/53)。非条件logistic回归模型分析显示:过去1年参加过MMT(OR=0.534,95%CI:0.290~0.980)可降低海洛因过量的风险,而过去6个月共用针具(OR=2.735,95%CI:1.383~5.407)和刚出戒毒所不满1年(OR=2.881,95%CI:1.226~6.767)会增加海洛因过量的风险。结论 云南省IDU过去1年海洛因过量发生率较高。需要持续促进该地IDU参加MMT并加强预防和应对吸毒过量宣传教育,特别是对戒毒所吸毒人员出所前的宣传教育,同时应建立针对吸毒人员的戒毒所与MMT门诊转介机制。     

Treatment of Severe Pediatric Ethylene Glycol Intoxication Without Hemodialysis

Background: There is limited experience treating severe ethylene glycol poisoning in children without hemodialysis. The objective of this study was to describe the clinical course and outcome of severe pediatric ethylene glycol poisoning treated without hemodialysis. Methods: Patient records were identified retrospectively by hospital discharge diagnosis (ICD‐9 code) of ethylene glycol poisoning from 1999 through 2002 at a pediatric medial center. Patients with initial serum ethylene glycol concentrations less than 50 mg/dL or those who received hemodialysis were excluded. Results: Six patients with an age range of 22 months to 14 years were admitted for treatment of ethylene glycol poisoning over a four‐year period. Initial serum ethylene glycol concentrations ranged from 62 to 304 mg/dL (mean 174.0 mg/dL). The lowest‐measured individual serum bicarbonates ranged from 4 to 17 mEq/L. All patients were initially admitted to intensive care. One patient received ethanol only, two patients received fomepizole only, and three patients received a loading dose of ethanol and then were converted to fomepizole therapy. None of the patients received hemodialysis. Treatment was continued until the serum ethylene glycol was less than 10 mg/dL. Metabolic acidosis resolved with intravenous fluid and supplemental bicarbonate within 24h. All patients had a normal creatinine upon presentation and at discharge. The mean length of stay in intensive care was 21h and on the ward was 33.7h. One episode of hypoglycemia occurred in a 22‐month‐old. All patients recovered without evidence of renal insufficiency or other major complications at discharge. Conclusion: Six pediatric patients with severe ethylene glycol intoxication and normal renal function were successfully treated without hemodialysis.     

Application of pharmacokinetic-pharmacodynamic modelling in management of QT abnormalities after citalopram overdose

Objective

To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring.

Design

Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation.

Main measures and results

The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79?bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting >?600?mg; (2) With citalopram overdoses >?1,000?mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13?h post-dose, so the minimum monitoring time for citalopram overdoses >?1,000?mg should be 13?h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation.

Conclusions

Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor.