Faculty Bibliography

OBJECTIVE: In contrast to patients with acute digoxin overdose, the prognostic utility of the serum potassium concentration for patients with chronic digoxin toxicity is unclear. In such patients, we aimed to evaluate the relationship between pre-treatment serum potassium and survival. METHODS: This was a case-control study at an urban Poison Control Center affiliated with a large urban medical center. We compared the serum potassium concentration between patients with chronic digoxin toxicity resulting in fatality (cases) over a 7-year period (2000-2006) versus survivors (controls) over a 1-year period (2007-2008). RESULTS: During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab). There were no statistically significant differences between cases and controls with respect to serum digoxin concentration, creatinine, age, or sex. Serum potassium elevation pre-Fab was significantly associated with fatality both in mean difference (p < 0.03) and using a dichotomous cutoff of 5.0 mEq/L (p < 0.001), which performed with 92% sensitivity (95% CI 67, 99). In 86% of deaths despite appropriate Fab administration, the clinical presentation included the combination of bradycardia plus hyperkalemia. CONCLUSION: In these patients with chronic digoxin toxicity, elevated serum potassium was associated with fatality. The combination of bradycardia and hyperkalemia strongly predicted fatality even in cases with appropriate Fab administration

Objective. To report a case of seizures and supraventricular tachycardia (SVT) following confirmed synthetic cannabinoid ingestion. Background. Despite widespread use of legal synthetic cannabinoids, reports of serious toxicity following confirmed use of synthetic cannabinoids are rare. We report severe toxicity including seizures following intentional ingestion of the synthetic cannabinoid JWH-018 and detail confirmation by laboratory analysis. Case Report. A healthy 48 year old man had a generalized seizure within thirty minutes of ingesting an ethanol mixture containing a white powder he purchased from the Internet in an attempt to get high. Seizures recurred and abated with lorazepam. Initial vital signs were: pulse, 106/min; BP, 140/88 mmHg; respirations, 22/min; temperature, 37.7 degrees C. A noncontrast computed tomography of the brain and EEG were negative, and serum chemistry values were normal. The blood ethanol concentration was 3.8 mg/dL and the CPK 2,649 U/L. Urine drug screening by EMIT was negative for common drugs of abuse, including tetrahydrocannabinol. On hospital day 1, he developed medically refractory SVT. The patient had no further complications and was discharged in his normal state of health 10 days after admission. The original powder was confirmed by gas chromatography mass spectrometry to be JWH-018, and a primary JWH-018 metabolite was detected in the patient's urine (200 nM) using liquid chromatography tandem mass spectrometry. Discussion. Synthetic cannabinoids are legal in many parts of the world and easily obtained over the Internet. Data on human toxicity are limited and real-time confirmatory testing is unavailable to clinicians. The potential for toxicity exists for users mistakenly associating the dose and side effect profiles of synthetic cannabinoids to those of marijuana. Conclusion. Ingestion of JWH-018 can produce seizures and tachyarrhythmias. Clinicians, lawmakers, and the general public need to be aware of the potential for toxicity associated with synthetic cannabinoid use

Background: In a previous study we derived high-risk ECG features associated with adverse cardiovascular events (ACVEs) in emergency department (ED) patients with acute drug overdose. Objectives: We aimed to externally validate that ischemia, non- sinus rhythm, and ectopy are associated with ACVE in this population. Methods: This prospective cohort study evaluated consecutive ED patients with acute drug overdose over 5 months at two urban teaching hospitals uninvolved in the original derivation cohort. Data included demographics, history, vital signs, and elements of the initial ECG (rhythm, intervals, ischemia, infarction), interpreted by a masked cardiologist. ECG evidence of ischemia and infarction were defined according to AHA criteria. In-hospital ACVE was defined by composite outcome: shock (vasopressors), myocardial injury (troponin I > 0.09ng/mL), severe dysrhythmia (VT/VF), or cardiac arrest (loss of pulse). Results: of 238 initially screened, 81 were excluded (30 age <18, 41 no ECG, 2 alternate diagnosis, 8 insufficient data), leaving 157 for analysis (48% female, mean age 40.8, 14% prior coronary disease). Most common drug classes ingested were acetamino- phen-containing (24%), sympathomimetics (20%), and opioids (19%). Included patients had mean pulse=84/minute (range 32-156), mean QRS=90 msec (range 68-174), mean QTc=433 msec (range 296-704), while 17% had ischemia, 9% infarction, and 4% ectopy. In-hospital ACVE occurred in 11 patients (7%), of whom 18% had prior coronary disease (p=NS). There were 9 myocardial injury, 3 shock, 2 dysrhythmia, and 3 cardiac arrests. Ischemia (OR 15.2, p<0.001), non-sinus rhythm (OR 8.6, p<0.01), and ectopy (OR 7.4, p<0.05) were highly associated with ACVE, while QRS, QTc, and infarction were not significantly predictive. Conclusion: This study validates the predictive utility of high- risk ECG features for ED patients with acute drug overdose. A screening ECG may be an important tool to evaluate in-hospital prognosis for acute drug overdose

Poisoning is a significant public health threat as the second leading cause of injury-related death in the US. Disagreements on cause of death determination may have widespread implications across several realms of public health including policy and prevention efforts, interpretation of the poisoning literature, epidemiologic data analysis, medical-legal case outcomes, and individualized autopsy interpretation. We aimed to test agreement between the cause of death determined by the medical examiner (ME) and a medical toxicologist (MT) adjudication panel (MTAP) in cases of poisoning. This retrospective 7-year study evaluated all deaths attributed to poisoning in one large urban catchment area. Cross-matched data were obtained from Department of Vital Statistics and the Poison Control Center (PCC). Out of >380,000 deaths in the catchment area over the study period, there were 7050 poisonings in the Vital Statistics database and 414 deaths reported to PCC. Cross-matching yielded 321 cases for analysis. The ME and MTAP concurred on cause of death in 66%, which was only fair agreement (kappa 0.25, CI 0.14-0.38). Factors associated with the likelihood of agreement were peri-mortem fire exposures, prehospital cardiac arrest, and timing of drug toxicity (chronic versus acute). In conclusion, agreement for poisoning cause of death between specialties was much lower than expected. We recommend an improved formal process of information sharing and consultation between specialties to assure that all existing information is analyzed thoroughly to enhance cause of death certainty

Experience with toxicity relating to intravenous (IV) paracetamol is discussed in the context of international experience. Issues in management and recent international strategies to minimise hazard are highlighted

Amlodipine is a potent vasodilator with a long half-life and delayed onset of action that is particularly concerning after an overdose. Vasodilation occurs through stimulation of nitric oxide release with increased cyclic guanosine monophosphate (cGMP) production. Methylene blue inhibits guanylate cyclase. This enzyme is responsible for the production of cGMP. Methylene blue also has the ability to scavenge nitric oxide, as well as inhibit nitric oxide synthase. We report the use of methylene blue for refractory shock in a patient with amlodipine toxicity

Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from some lipophilic drugs. We present a 51-year-old woman with severe bupropion toxicity whose haemodynamic status transiently improved after IFE. Serum analysis demonstrated an increase in serum concentration of hydroxybupropion, an active metabolite of bupropion, after IFE administration, lending support to one of the proposed mechanisms of IFE. A 51-year-old woman presented to the emergency department with generalised tonic-clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high-dose norepinephrine. IFE was administered with haemodynamic improvement over the course of 30 min., followed by a significant decrease in norepinephrine requirement. The patient had an episode of ventricular tachycardia 24 hr after presentation, and received a second infusion of IFE. Analysis of serum for a panel of myocardial sodium channel blocking drugs revealed that significant bupropion ingestion had occurred. Bupropion poisoning may produce life-threatening clinical effects, and IFE may be considered in cases of severe haemodynamic instability. Further studies would be instrumental in determining the optimal clinical situations for utilisation of IFE