Toxicity and Adverse Effects in Clozapine-Related Presentations to a Medical Toxicology Service in Western Sydney.

BACKGROUND: Clozapine is an anti-psychotic agent, reserved for treatment-resistant schizophrenia, with demonstrated efficacy in an otherwise therapeutically challenging patient population. We aimed to review the full spectrum casemix of clozapine presentations to our tertiary toxicology service. METHODS: In this retrospective study, we reviewed consecutive clozapine related toxicity presentations to a tertiary medical toxicology inpatient and consultation service-including deliberate self-poisoning (DSP), adverse drug reaction (ADR), recreational use, and therapeutic misadventure over a 10-year period from 2011 to 2021. Data were extracted for demographics, ingested dose, exposure characteristics, and patient outcome. RESULTS: We identified 83 patients with clozapine-related presentations over the 10-year period. Twenty-two patients were excluded. Of the remaining 61 patients, 28 patients presented with DSP, 20 patients with accidental overdose, and 13 patients with an ADR; no patients presented with recreational use. It was noted that ADRs were largely idiosyncratic reactions and not always related to dose adjustments. In the context of therapeutic misadventure and DSP, we noted that a lower mean dose achieved a higher poison severity score (PSS) in clozapine-naive patients when compared to those patients on regular clozapine. CONCLUSIONS: The presentation of clozapine-related toxicity differs depending on the modality of ingestion, whether DSP, accidental, or as a result of ADR. Patients naive to clozapine therapy tend to experience higher PSS with lower doses ingested either in a deliberate self-poisoning or accidental ingestion context. This is likely due to tolerance to the sedative properties of clozapine. No patients manifested clinical toxicity greater than 8 hours after ingestion, with an observation period of 6 hours accurately identifying toxicity in most patients.

Out of hospital cardiac arrest in Western Sydney-an analysis of outcomes and estimation of future eCPR eligibility.

BACKGROUND: Refractory out of hospital cardiac arrest (OHCA) is associated with extremely poor outcomes. However, in selected patients extracorporeal cardiopulmonary resuscitation (eCPR) may be an effective rescue therapy, allowing time treat reversible causes. The primary goal was to estimate the potential future caseload of eCPR at historically 'low-volume' extracorporeal membrane oxygenation (ECMO) centres. METHODS: A 3-year observational study of OHCA presenting to the Emergency Department (ED of an urban referral centre without historical protocolised use of eCPR. Demographics and standard Utstein outcomes are reported. Further, an a priori analysis of each case for potential eCPR eligibility was conducted. A current eCPR selection criteria (from the 2-CHEER study) was used to determine eligibly. RESULTS: In the study window 248 eligible cardiac arrest cases were included in the OHCA registry. 30-day survival was 23.4% (n = 58). The mean age of survivors was 55.4 years. 17 (6.8%) cases were deemed true refractory arrests and fulfilled the 2-CHEER eligibility criteria. The majority of these cases presented within "office hours" and no case obtained a return of spontaneous circulation standard advanced life support. CONCLUSIONS: In this contemporary OHCA registry a significant number of refractory cases were deemed potential eCPR candidates reflecting a need for future interdisciplinary work to support delivery of this therapy.

Fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose.

OBJECTIVE: Acetylcysteine (NAC), an effective antidote for paracetamol poisoning, is commonly associated with adverse reactions. This has been postulated to be related to the rapid initial infusion rate (150 mg/kg over 1 h) of the traditional three-bag protocol. We hypothesized that a slower rate would result in fewer adverse reactions. Our institution in Western Sydney moved to a modified two-bag protocol in February 2015 - first bag: 200 mg/kg over 4 h (50 mg/kg/h) and second bag: (100 mg/kg over 16 h). METHODS: Data was extracted from our database on paracetamol overdoses treated with NAC from August 2010 to September 2016. We compared adverse reactions in patients receiving the modified two-bag protocol with a historical control (traditional three-bag regimen with initial bolus of 150 mg/kg/h). RESULTS: Over the study period 1011 paracetamol poisonings presented to our toxicology service, of which 476 required NAC (three-bag = 313, two-bag = 163). Demographic characteristics of the two groups were similar. Fewer anaphylactoid reactions (itch, rash, and swelling) occurred using the two-bag regimen (14% versus 5%, p = .002), a relative reduction of 66%. Similarly, there were fewer prescriptions of anti-allergy medications in the two-bag group (11% versus 4%, p = .01). There was no difference in incidence of hepatotoxicity. CONCLUSIONS: Adverse reactions to NAC were less common with the two-bag regimen. These results add to the accumulating evidence that reducing the initial NAC infusion rate reduces the risk of adverse reactions.