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Understanding the time course of venom exposure in snakebite patients is important for the optimisation of treatment including antivenom dose and timing. We aimed to investigate the pharmacokinetics of red-bellied black snake (RBBS;Timed venom concentration data were obtained from patients with RBBS envenomation recruited to the Australian Snakebite Project (ASP), including demographics and antivenom treatment. Venom concentrations were measured using an enzyme immunoassay. Data were modelled using NONMEM version 7.3. Uncertainty in venom "dose" was accounted for by arbitrarily fixing the average amount to 1 mg and incorporating between-subject variability on relative bioavailability. A scale parameter for venom clearance was implemented to account for the rapid venom clearance following antivenom dosing. A sensitivity analysis was performed to determine the magnitude of venom clearance amplification.There were 457 venom concentrations in 114 patients (median age 41, 2-90 y; 80 male). Antivenom was administered to 54 patients a median of 4.2 h post-bite (0.67 to 32 h). A one-compartment model with first-order absorption and elimination provided the best description of the data. The estimated clearance and volume of distribution were 5.21 L/h and 39.9 L, respectively. The calculated elimination half-life ofThe information on the exposure time of venom in the body following envenomation will help improve treatment and the timing of antivenom.

Acute kidney injury (AKI) is the most serious clinical manifestation of the Sri Lankan hump-nosed pit viper (We conducted a prospective observational study of suspected viper bites and included 103 confirmed cases ofTen patients developed AKI: seven AKI stage 1 and three AKI stage 3. Ten patients (10%) developed thrombocytopaenia while 11 (11%) had MAHA. All three AKI stage 3 had thrombocytopaenia and MAHA fulfilling the criteria for TMA. Two of them presented with oliguria/anuria and all three required haemodialysis. Serum creatinine within 4 h post-bite was the best predictor of AKI with AUC-ROC of 0.83 (95% CI: 0.67-0.99) and was no better within 8 h of the bite.We found that AKI is uncommon in

Context: Inpatient toxicology services undertake remote as well as inpatient management of poisoned patients. The aim of this study is to describe the introduction of a tablet-based electronic data...

High-dose insulin euglycaemia (HIE) is recommended in the management of toxin-induced cardiac toxicity, with increasing insulin doses now being used. We aimed to investigate the safety of HIE in toxin-induced cardiac toxicity.This was a retrospective review of cases from two clinical toxicology units. Demographics, toxin(s) ingested, clinical effects, investigations (serum glucose, electrolytes), treatments (insulin, glucose, electrolyte replacement), length of stay (LOS) and outcomes were extracted from the patients' medical records. Associations between insulin and glucose/electrolyte homeostasis were explored by comparing insulin administration and glucose or electrolyte concentrations and replacement.There were 22 patients (12 females), median age 57 years (15-88 years) treated with HIE. There were 12 beta-blocker, six calcium channel blocker and three combined beta-blocker and calcium channel blocker ingestions. A total of 19 patients had a systolic blood pressure 80mmHg and 18 patients required inotropes in addition to HIE. There were three deaths. Despite glucose and electrolyte replacement, 16 patients (73%) developed hypoglycaemia (Reference range [RR] 3.5 mmol/L or63 mg/dl). In 7 patients, hypoglycaemia was mild (2.5-3.4 mmol/L or 45-62 mg/dl) and in nine was severe (2.5 mmol/L or45 mg/dl). There were no neurological effects from hypoglycaemia. A total of 18 patients (82%) developed hypokalaemia (3.5 mEq/L). In 16 patients, this was mild (2.5-3.4 mEq/L). There were no cardiac arrhythmias associated with this hypokalaemia. There was no apparent association between insulin dosing and severity of hypoglycaemia or hypokalaemia, or in glucose or potassium replacement. Median insulin loading dose was 80U (range 50-125 U) and the median maximum insulin infusion rate was 150 U/h (range 38-1500 U/h). Median glucose infusions rates were 37.5g/h (range 4-75g/h). There was no apparent association between insulin and glucose administration. Glucose was administered for a median of 18h after ceasing insulin. The duration of glucose administration after ceasing insulin increased with the rate and total insulin administered during HIE.Despite the benefits of HIE in toxin-induced cardiac toxicity, it caused significant disruption to glucose and electrolyte homeostasis, although there were no apparent complications from this. There was no association by comparing the amount of insulin administered on adverse effects or glucose administered, suggesting higher doses of insulin are associated with no more adverse effects.

There are limited reports of adult clonidine overdose. We aimed to describe the clinical effects and treatment of clonidine overdose in adults.This was a retrospective review of a prospective cohort of poisoned patients who took clonidine overdoses (200 μg). Demographic information, clinical effects, treatment, complications (central nervous system and cardiovascular effects) and length of stay (LOS) were extracted from a clinical database or medical records.From 133 admissions for clonidine poisoning (1988-2015), no medical record was available in 14 and 11 took staggered ingestions. Of 108 acute clonidine overdoses (median age 27 years; 14-65 years; 68 females), 40 were clonidine alone ingestions and 68 were clonidine with co-ingestants. Median dose taken was 2100 μg (interquartile range [IQR]: 400-15,000 μg). Median LOS was 21h (IQR: 14-35 h) and there were no deaths. Glasgow coma score [GCS]15 occurred in 73/108 (68%), and more patients taking co-ingestants (8/68; 12%) had coma (GCS9) compared to clonidine alone (2/40; 5%). Miosis occurred in 31/108 (29%) cases. Median minimum HR was 48 bpm (IQR: 40-57 bpm), similar between clonidine alone and co-ingestant overdoses. There was a significant association between dose and minimum HR for clonidine alone overdoses (p = 0.02). 82/108 (76%) had bradycardia, median onset 2.5 h post-ingestion (IQR: 1.7-5.5 h) and median duration 20 h (2.5-83 h), similar for clonidine alone and co-ingestant overdoses. There were no arrhythmias. Three patients ingesting 8000-12,000 μg developed early hypertension. Median minimum systolic BP was 96 mmHg (IQR: 90-105 mmHg) and hypotension occurred in 26/108 (24%). 12/108 patients were intubated, but only 2 were clonidine alone cases. Treatments included activated charcoal (24), atropine (8) and naloxone (23). The median total naloxone dose was 2 mg (IQR: 1.2-2.4 mg), but only one patient given naloxone was documented to respond with partial improvement in GCS.Clonidine causes persistent but not life-threatening clinical effects. Most patients develop mild central nervous system depression and bradycardia. Naloxone was not associated with improved outcomes.

Context: Poisoning due to chloroform ingestion is rare. The classic features of acute chloroform toxicity include central nervous system (CNS) and respiratory depression, and delayed hepatotoxicity. Case details: A 30-year-old female ingested 20–30 mL of 99% chloroform solution, which caused rapid loss of consciousness, transient hypotension and severe respiratory depression requiring endotracheal intubation and ventilation. She was alert by 12 h and extubated 16 h post-overdose. At 38-h post-ingestion, her liver function tests started to rise and she was commenced on intravenous acetylcysteine. Her alanine transaminase (1283 U/L), aspartate transaminase (734 U/L) and international normalized ratio (2.3) peaked 67- to 72-h post-ingestion. She also developed severe abdominal pain, vomiting and diarrhoea. An abdominal CT scan was consistent with severe enterocolitis, and an upper gastrointestinal endoscopy showed erosive oesophagitis, severe erosive gastritis and ulceration. She was treated with opioid analgesia, proton pump inhibitors, sucralfate and total parenteral nutrition. Secretions caused a contact dermatitis of her face and back. Nine days post-ingestion she was able to tolerate food. Her liver function tests normalized and the dermatitis resolved. Chloroform was measured using headspace gas chromatograph mass spectrometry, with a peak concentration of 2.00 μg/mL, 4 h 20 min post-ingestion. The concentration-time data fitted a 1-compartment model with elimination half-life 6.5 h. Discussion: In addition to early CNS depression and delayed hepatotoxicity, we report severe gastrointestinal injury and dermatitis with chloroform ingestion. Recovery occurred with good supportive care, acetylcysteine and management of gastrointestinal complications. Refereed/Peer-reviewed

Sir,Dr Wang and his colleagues raise a number of important issues regarding the diagnosis of chronic digoxin poisoning, timing of digoxin sampling to reflect post-distribution concentration and the...

Objective: Acute beta-blocker overdose can cause severe cardiac dysfunction. Chronic toxicity is rare but potentially severe. We report therapeutic dosing of metoprolol resulting in unusual pharmacokinetics and toxicity, given high-dose insulin therapy for treatment. Case details: A 90-year-old female presented with hypotension, tachycardia and severe cardiac dysfunction after commencing a rapidly increasing metoprolol dose of 250 mg split daily. She was admitted to intensive care and given high-dose insulin therapy (10 U/kg/h), noradrenaline, adrenaline and dobutamine for severe cardiac dysfunction (cardiac index, 0.76 L/min/m²). She developed acute renal failure, ischaemic hepatitis and disseminated intravascular coagulopathy. Inotropes and high-dose insulin were weaned over four days with complete recovery. Metoprolol was quantified with liquid chromatography-tandem mass spectrometry and concentration-time data were analysed using MONOLIX® vs 4.3 (www.lixoft.com). Admission metoprolol concentration was 2.39 μg/mL (therapeutic reference range: 0.035–0.5 μg/mL). Data best fitted a one compartmental model with Michaelis–Menten kinetics and zero order elimination at high concentrations. Final parameter estimates were V, 63.4 L, maximum rate [Vm], 9.57 mg h⁻¹, Michaelis constant [Km], 1.97 mg L⁻¹. Predicted elimination half-life decreased from 20 h over time until there was first order elimination with a half-life 9 h. Conclusion: The time course of cardiac dysfunction was longer than acute overdose but consistent with prolonged zero order elimination of metoprolol, suggesting the patient was a poor CYP2D6 metaboliser. High-dose insulin euglycaemia appeared to be effective in combination with vasoconstrictors/inotropes. Refereed/Peer-reviewed

Russell's viper is more medically important than any other Asian snake, due to number of envenoming's and fatalities. Russell's viper populations in South India and Sri Lanka (Daboia russelii) cause unique neuromuscular paralysis not seen in other Russell's vipers.To investigate the time course and severity of neuromuscular dysfunction in definite Russell's viper bites, including antivenom response.We prospectively enrolled all patients (16 years) presenting with Russell's viper bites over 14 months. Cases were confirmed by snake identification and/or enzyme immunoassay. All patients had serial neurological examinations and in some, single fibre electromyography (sfEMG) of the orbicularis oculi was performed.245 definite Russell's viper bite patients (median age: 41 years; 171 males) presented a median 2.5 h (interquartile range: 1.75-4.0 h) post-bite. All but one had local envenoming and 199 (78%) had systemic envenoming: coagulopathy in 166 (68%), neurotoxicity in 130 (53%), and oliguria in 19 (8%). Neurotoxicity was characterised by ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8 h post-bite in all patients. No bulbar, respiratory or limb muscle weakness occurred. Neurotoxicity was associated with bites by larger snakes (p 0.0001) and higher peak serum venom concentrations (p = 0.0025). Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity. sfEMG in 27 patients with neurotoxicity and 23 without had slightly elevated median jitter on day 1 compared to 29 normal subjects but normalised thereafter. Neurological features resolved in 80% of patients by day 3 with ptosis and weak eye movements resolving last. No clinical or neurophysiological abnormality was detected at 6 weeks or 6 months.Sri Lankan Russell's viper envenoming causes mild neuromuscular dysfunction with no long-term effects. Indian polyvalent antivenom effectively binds free venom in blood but does not reverse neurotoxicity.

The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions.We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion.A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4-9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) 1000 U/L or abnormal ALT.654 paracetamol poisonings were treated with the new protocol; median age 29 y (15-98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31-39%): 173 (26.5%; 95% CI: 23-30%) only gastrointestinal, 50 (8%; 95% CI: 6-10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1-1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13-28%; p0.0001). In 200 overdoses10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced12 h post-ingestion.A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.

Funnel-web spider (Atrax and Hadronyche spp.) envenoming is rare but causes severe neuromuscular, autonomic, and cardiac effects. A rabbit-derived IgG antivenom is available, but venom detection in patients has not been reported.To use serial venom and antivenom concentrations to better define envenoming and antivenom effectiveness.Serum was collected from nine patients with suspected funnel-web spider bites and clinical effects were recorded. Venom-specific enzyme immunoassays were developed to measure funnel-web spider venom and antivenom concentrations. Goat anti-rabbit whole serum was coupled to UltraLink resin and added to samples to remove bound venom and measure free venom. Antivenom efficacy was defined as antivenom binding all free venom and antivenom effectiveness as resolution of clinical features.Venom was detectable in samples from six of nine patients. In three patients without venom detected, there were only moderate effects, which did not completely respond to antivenom in all cases and no spider was identified. In five of six cases, a male Atrax spp. (Sydney funnel-web) spider was identified. Three patients had moderate envenoming which responded to antivenom. Three patients had severe envenoming and developed catecholamine-induced myocarditis and acute pulmonary oedema. Although cholinergic and non-specific clinical features appeared to respond to antivenom, myocarditis and pulmonary oedema lasted 2-4 days. Median venom concentration pre-antivenom in five patients with samples was 5.6 ng/ml (3-35 ng/ml), and immediately post-antivenom decreased to a median of 0 ng/ml (0-1.8 ng/ml). Post-antivenom venom concentrations decreased when bound venom was removed; median, 0 ng/ml (0-0.9 ng/ml), indicating that most venom detected post-antivenom was bound. There was recurrence of venom and clinical features in one patient when a pressure bandage was removed.Detection of venom in suspected funnel-web spider bites identified definite cases with characteristic envenoming and a spider was identified. Measurement of venom concentrations pre- and post-antivenom demonstrated that venom was bound by antivenom, but in severe cases cardiac toxicity was not reversed.

Serum sickness is a delayed immune reaction resulting from the injection of foreign protein or serum. Antivenom is known to cause serum sickness but the incidence and characteristics are poorly defined.To investigate the incidence and clinical features of serum sickness following the administration of Australian snake antivenoms.This was a prospective cohort study of patients recruited to the Australian Snakebite Project who received snake antivenom from November 2012 to March 2014. Demographics, clinical information, laboratory tests and antivenom treatment were recorded prospectively. Patients administered antivenom were followed up at 7-10 days and 6 weeks' post-antivenom. The primary outcome was the proportion with serum sickness, pre-defined as three or more of: fever, erythematous rash/urticaria, myalgia/arthralgia, headache, malaise, nausea/vomiting 5-20 days post-antivenom.During the 16-month period, 138 patients received antivenom. 23 were not followed up (unable to contact, tourist, child, bee sting) and 6 died in hospital. Of 109 patients followed up, the commonest reason for antivenom was venom induced consumption coagulopathy in 77 patients. An acute systemic hypersensitivity reaction occurred post-antivenom in 25 (23%) and 8 (7%) were severe with hypotension. Serum sickness occurred in 32/109 (29%) patients, including 15/37 (41%) given tiger snake, 6/15 (40%) given polyvalent and 4/23 (17%) given brown snake antivenom. There was no association between the volume of antivenom and serum sickness, p = 0.18. The commonest effects were lethargy, headache, muscle/joint aches and fever.The incidence of serum sickness after snake antivenom in Australia was higher than earlier investigations which failed to define symptoms or follow-up patients, but similar to more recent studies of antivenoms in the United States.Serum sickness is common with Australian snake antivenom but does not appear to be predictable based on the volume of antivenom administered.

CONTEXT. Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet. Case Details. A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 μg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 μg/ml. Discussion. Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances. Refereed/Peer-reviewed

Tramadol is a commonly used centrally acting analgesic associated with seizures and suspected to cause serotonin toxicity in overdose.This study sought to investigate the effects of tramadol overdose, and included evaluation for serotonin toxicity based on the Hunter Serotonin Toxicity Criteria where the seven clinical features of spontaneous clonus, inducible clonus, ocular clonus, agitation, diaphoresis, tremor and hyperreflexia are examined for in all patients taking serotonergic medications; seizures and central nervous system depression.This was an observational cases series based on a retrospective review of tramadol overdoses (400 mg) admitted to a tertiary toxicology unit from November 2000 to June 2013. Demographic details, information on ingestion (dose and co-ingestants), clinical effects, complications (seizures, serotonin toxicity and cardiovascular effects) and intensive care unit (ICU) admission were extracted from a clinical database.There were 71 cases of tramadol overdose (median age: 41 years, range: 17-69 years; and median ingested dose: 1000 mg, interquartile range [IQR]: 800-2000 mg). Seizures were dose related and occurred in 8 patients, one of them co-ingested a benzodiazepine compared with 16 patients without seizures. There were no cases of serotonin toxicity meeting the Hunter Serotonin Toxicity Criteria. Tachycardia occurred in 27 and mild hypertension occurred in 32. The Glasgow Coma Score was15 in 29 and9 in 5 patients; three co-ingested tricyclic antidepressants and two tramadol alone (3000 mg and 900 mg). Respiratory depression occurred in 13, median dose: 2500 (IQR: 1600-3000) mg which was significantly different (p = 0.003) to patients without respiratory depression, median dose: 1000 (IQR: 750-1475) mg. Eight patients were admitted to ICU, five due to co-ingestant toxicity and three for respiratory depression.Tramadol overdose was associated with a significant risk of seizures and respiratory depression in more severe cases, both which appear to be related to the ingested dose. There were no cases of serotonin toxicity, while opioid-like effects and adrenergic effects were prominent.Tramadol overdose is associated with seizures and respiratory depression, but is unlikely to cause serotonin toxicity.

Objective. There is limited information on mirtazapine overdose, but cases of severe effects (seizures, serotonin toxicity and coma) have been reported. We aimed to investigate the clinical effects and complications of mirtazapine overdose. Methods. This was an observational case series of mirtazapine overdoses (> 120 mg) identified from admissions to a toxicology unit between January 1987 and August 2013. Demographic information, details of ingestion, clinical effects, ECG parameters (HR, QT and QRS), and length of stay were extracted from a clinical database. Results. From 267 mirtazapine overdoses, there were 89 single-agent mirtazapine ingestions and 178 cases where mirtazapine was taken with at least one other drug. The median age of the 89 single-agent mirtazapine ingestions was 36 years [interquartile range (IQR): 26–49 years; Range: 15–81 years]; 45 were female (51%). The median ingested dose was 420 mg (IQR: 270–750 mg; Range: 150–1350 mg) and 41 patients (46%) had a Glasgow coma score (GCS) < 15, but the minimum GCS was 10. There were no seizures, serotonin toxicity or delirium. Tachycardia occurred in 29 patients (33%) and hypertension in 32 patients (36%). The median QRS was 80 ms (Range: 80–120 ms) and there were no cases with QT prolongation. There were no arrhythmias and no deaths. The median length of stay was 14 h (IQR: 8.8–18.2 h; Range:2.2–75 h). No single-agent mirtazapine patient was admitted to intensive care. The 178 patients taking co-ingestants had more severe toxicity depending on the co-ingested drug. Conclusion. Mirtazapine appears to be relatively benign in overdose, associated with tachycardia, mild hypertension and mild CNS depression not requiring intervention.

Limited information exists on the coagulopathy caused by hump-nosed pit viper (Hypnale hypnale) envenoming.This study aimed to characterise the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting times and factor studies.Cases of hump-nosed pit viper envenoming were included from a prospective cohort study of Sri Lankan snake-bite patients. Patient age, sex, snake identification, time of bite and clinical effects were recorded. Patients did not receive anti-venom because no specific anti-venom to hump-nosed vipers exists. All patients received supportive care and serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor (vWF) antigen and D-Dimer concentrations were measured. The median of highest or lowest test result for each patient was reported with interquartile range (IQR). Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR: 26-51 years) and 48 were male. The WBCT20 was positive in one patient. The median highest INR was 1.9 (1.5-2.2; Range: 1.3 to12) and median highest aPTT was 54 s (46-72 s; Range: 35-170 s). There was low fibrinogen [median: 1.3 g/L;1, -1.8 g/L; Range:0.2-2.9], low factor VIII levels [median: 23%; 16-37%] and low factor V levels [median: 43%; 23-74%]. D-Dimer concentrations [median: 3.4 mg/L; 2-7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen concentrations were normal.Hump-nosed pit viper bites result in a mild coagulopathy which is usually not detected by a WBCT20. It is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII which may be consistent with the venom containing a thrombin-like enzyme.

Mulga snakes (Pseudechis australis) are venomous snakes with a wide distribution in Australia. Objective. The objective of this study was to describe mulga snake envenoming and the response of envenoming to antivenom therapy.Definite mulga bites, based on expert identification or venom-specific enzyme immunoassay, were recruited from the Australian Snakebite Project. Demographics, information about the bite, clinical effects, laboratory investigations and antivenom treatment are recorded for all patients. Blood samples are collected to measure the serum venom concentrations pre- and post-antivenom therapy using enzyme immunoassay.There were 17 patients with definite mulga snake bites. The median age was 37 years (6-70 years); 16 were male and six were snake handlers. Thirteen patients had systemic envenoming with non-specific systemic symptoms (11), anticoagulant coagulopathy (10), myotoxicity (7) and haemolysis (6). Antivenom was given to ten patients; the median dose was one vial (range, one-three vials). Three patients had systemic hypersensitivity reactions post-antivenom. Antivenom reversed the coagulopathy in all cases. Antivenom appeared to prevent myotoxicity in three patients with high venom concentrations, given antivenom within 2 h of the bite. Median peak venom concentration in 12 envenomed patients with samples was 29 ng/mL (range, 0.6-624 ng/mL). There was a good correlation between venom concentrations and the area under the curve of the creatine kinase for patients receiving antivenom after 2 h. Higher venom concentrations were also associated with coagulopathy and haemolysis. Venom was not detected after antivenom administration except in one patient who had a venom concentration of 8.3 ng/ml after one vial of antivenom, but immediate reversal of the coagulopathy.Mulga snake envenoming is characterised by myotoxicity, anticoagulant coagulopathy and haemolysis, and has a spectrum of toxicity that is venom dose dependant. This study supports a dose of one vial of antivenom, given as soon as a systemic envenoming is identified, rather than waiting for the development of myotoxicity.

We present a case of intravenous (IV) paracetamol overdose in a nutritionally malnourished child during hospital admission. A ten-fold IV paracetamol dosing error ocurred, with delayed recognition and treatment resulting in transient hepatotoxicity, with a peak alanine transaminase (ALT) of 1378 IU/L in a 3-year-old child. Our case suggests that hepatotoxicity may occur for lower doses of IV paracetamol compared to oral ingestion, especially in the malnourished, and that a dose less than 150 mg/kg of IV paracetamol should be used to define treatment following overdose in a child with potential nutritional deficiencies.

Methanol and ethylene glycol cause significant mortality post-ingestion. Predicting prognosis based on the biomarkers osmolal gap, anion gap and pH is beneficial.To evaluate the relationship between biomarkers, measured post-methanol and ethylene glycol exposure, and clinical outcomes.A review of the literature identified cases where methanol or ethylene glycol had been ingested and clinical outcomes were recorded. Biomarkers were extracted including osmolal gap, anion gap and pH, with clinical outcomes categorised as recovered, recovered with adverse sequelae and death. Biomarkers were analysed using the Mann-Whitney test for two samples; sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curves.In total, 119 cases of methanol and 88 of ethylene glycol poisoning were identified; 21 methanol and 19 ethylene glycol patients died. For methanol ingestion the mean values, for survival compared to death, were 48 (range: 6-138) and 90 (range: 49-159) mOsm/kg water for osmolal gap (p=0.0052), 31 (range: 11-50) and 41 (range: 30-53) mmol/L for anion gap (p=0.0065) and 7.21 (range: 6.60-7.50) and 6.70 (range: 6.34-7.22) for arterial pH (p0.0001). The area under the ROC curve was highest for arterial pH, 0.94 (95% CI: 0.89-0.99). For ethylene glycol, these were 49 (range: 0-189) and 79 (range: 25-184) mOsm/kg water for osmolal gap (p=0.050), 28 (range: 6-48) and 38 (range: 20-66) mmol/L for anion gap (p=0.0037) and 7.08 (range: 6.46-7.39) and 6.98 (range: 6.50-7.16) for pH (p=0.072), for survival compared to death. The area under the ROC curve was highest for anion gap, 0.73 (95% CI: 0.60-0.87).Post-methanol ingestion a large osmolal gap, anion gap and low pH (7.22) were associated with increased mortality; and pH has the highest predictive value. Post-ethylene glycol ingestion, both osmolal gap and anion gap were associated with increased mortality.

Current treatment of paracetamol (acetaminophen) poisoning involves initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma concentration, taken ≥ 4 h post-overdose, to a nomogram. This may result in dosing errors, a delay in treatment, or possibly more adverse effects - due to the use of a high dose rate for the first infusion when treatment is initiated.Our aim was to investigate a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate.We used a published population pharmacokinetic model of NAC to simulate a scenario where a patient presents to the hospital 2 h post-overdose. The conventional regimen is commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is available. We investigated an NAC infusion using a lower dosing rate initiated immediately on presentation. We determined a dosing rate that gave an area under the curve (AUC) of the concentration-time curve that was the same or greater than that from the conventional regimen on 90% of occasions.Lower dosing rates of NAC initiated immediately resulted in a similar exposure to NAC. An infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used.The novel dosing regimen allowed immediate treatment of a patient using a lower dosing rate. This greatly simplifies the current dosing regimen and may reduce NAC adverse effects while ensuring the same amount of NAC is delivered.

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.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.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.