Life-threatening triclopyr poisoning due to diethylene glycol monoethyl ether solvent.

INTRODUCTION: Triclopyr is a synthetic auxin-like herbicide. It is considered to have low toxicity and there are few reports of poisoning. We report two cases of life-threatening toxicity following ingestions of 250 mL of 50 g/L triclopyr co-formulated with diethylene glycol monoethyl ether (DEGEE). CASE REPORTS: A 79-year-old male with a background of hypertension and atrial fibrillation presented two hours after ingestion with sedation, a severe high anion gap metabolic acidosis, raised osmolar gap and an aspiration pneumonitis. He was ventilated and dialysed for 10 h with resolution of the acidaemia. He was discharged home on day 33. A 66-year-old male with a past history of alcoholism and hypertension presented following a collapse. He had sedation, a severe high anion gap metabolic acidosis with a raised osmolar gap, acute kidney injury and vasodilatory shock. He was ventilated and received dialysis for 43 h. He had poor neurological recovery and died on day 10. DISCUSSION: Ingestion of triclopyr formulations can produce life-threatening toxicity. In large poisonings of triclopyr co-formulated with DEGEE, a high anion gap metabolic acidosis appears to be due to the glycol ether solvent rather than triclopyr itself. Management should focus on good supportive care including dialysis for significant metabolic acidosis.

Antivenom cross neutralisation in a suspected Asian pit viper envenoming causing severe coagulopathy.

There is evidence of cross-neutralisation between common toxin groups in snake venoms and therefore the potential for antivenoms to be effective against species they are not raised against. Here we present a 49 year old female bitten by an unknown pit-viper in Nepal. She developed a venom induced consumption coagulopathy with an unrecordable international normalised ratio and undetectable fibrinogen. On return to Australia 5 days post-bite she was treated successfully with one antivenom raised against Malayan pit viper and green pit viper venoms (Haemato-polvalent antivenom from Thailand) and then subsequently with another antivenom raised against American pit-viper venoms (Antivipmyn). Presumed pit viper venom was detected in patient sera with an enzyme immunoassay against Hypnale hypnale venom. There was increased absorbance before antivenom compared to non-envenomed control samples, which then decreased after the administration of each antivenom. The recurrence of venom detected by enzyme immunoassay between antivenom doses was accompanied by a recurrence of the coagulopathy. Cross reactivity between the unknown venom and both antivenoms was supported by the fact that no venom was detected in the pre-antivenom samples after they were incubated in vitro with both antivenoms. This case and investigation of the venom and antivenoms suggest cross-neutralisation between pit vipers, including pit vipers from different continents.

A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18).

BACKGROUND: Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming. OBJECTIVES: To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation. PATIENTS/METHODS: This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs. no FFP within 4 h of antivenom administration. Patients (> 2 years) recruited to the Australian snakebite project with VICC (International Normalized Ratio [INR] > 3) were eligible. Patients were randomized 2 : 1 to receive FFP or no FFP. The primary outcome was the proportion with an INR of < 2 at 6 h after antivenom administration. Secondary outcomes included time from antivenom administration to discharge, adverse effects, major hemorrhage, and death. RESULTS: Of 70 eligible patients, 65 consented to be randomized: 41 to FFP, and 24 to no FFP. Six hours after antivenom administration, more patients randomized to FFP had an INR of < 2 (30/41 [73%] vs. 6/24 [25%]; absolute difference, 48%; 95% confidence interval 23-73%; P = 0.0002). The median time from antivenom administration to discharge was similar (34 h, range 14-230 h vs. 39 h, range 14-321 h; P = 0.44). Seven patients developed systemic hypersensitivity reactions after antivenom administration - two mild and one severe (FFP arm), and three mild and one severe (no FFP). One serious adverse event (intracranial hemorrhage and death) occurred in an FFP patient with pre-existing hypertension, who was hypertensive on admission, and developed a headache 6 h after FFP administration. Post hoc analysis showed that the median time from bite to FFP administration was significantly shorter for non-responders to FFP than for responders (4.7 h, interquartile range [IQR] 4.2-6.7 h vs. 7.3 h, IQR 6.1-8 h; P = 0.002). CONCLUSIONS: FFP administration after antivenom administration results in more rapid restoration of clotting function in most patients, but no decrease in discharge time. Early FFP administration (< 6-8 h) post-bite is less likely to be effective.

Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal.

OBJECTIVE: The aim of this study was to describe the clinical effects of promethazine in overdose and explore the relationship between delirium and possible predictor variables. METHODS: A case series of promethazine poisonings was identified from a prospective database of poisoning admissions to a regional toxicology service. Data were extracted including demographics, details of ingestion, clinical features including delirium, complications and medical outcomes. In addition to descriptive statistics, a fully Bayesian approach using logistic regression was undertaken to investigate the relationship between predictor variables and delirium. RESULTS: There were 199 patients with 237 presentations, including 57 patients with 78 promethazine alone overdoses. Of these 57 patients who ingested promethazine alone the median age was 22 years [interquartile range (IQR): 17-31] and 42 were female (74%). The median dose ingested was 625 mg (IQR: 350-1250 mg). Median length of stay was 19 h (IQR: 13-27 h), ten were admitted to the intensive care unit (ICU) and four were ventilated. Delirium occurred in 33 patients (42%), tachycardia (HR>100) occurred on 44 occasions (56%) and hypotension only twice. There were no seizures, dysrhythmias or deaths. Multivariate analysis of 215 presentations (in 181 patients) where dose of promethazine ingested was known demonstrated that dose, administration of charcoal within 2 h and co-ingestants predicted whether patients developed delirium. No relationship was shown for sex and age. A plot of probability that a patient will develop delirium vs. dose was constructed which showed the probability of delirium for 250 mg was 31%, 500 mg was 42% and for 1 g was 55% for promethazine alone overdoses. CONCLUSION: The main feature of promethazine toxicity is delirium, the probability of which can be predicted from the dose ingested. The administration of charcoal and the presence of co-ingestants appears to reduce the probability of delirium in a predictable manner.