Faculty Bibliography

Objective: We present a patient who developed prolonged coma following treatment of ethanol withdrawal with large doses of diazepam and demonstrated prolonged elimination toxicokinetics. Case report: A 68-year-old man who drank 5-6 alcoholic beverages/day was admitted for an elective transcatheter aortic valve replacement. Two days post-procedure, he developed agitation and was presumptively treated for ethanol withdrawal with diazepam (470 mg IV over 24 hours). He remained comatose for four days prompting a toxicology consult. On day 7 of persistent coma from presumed benzodiazepine excess, flumazenil (0.5 mg) was administered; he opened his eyes for the first time, began speaking, and answering simple questions, but 30 minutes later was comatose again. Flumazenil infusion 0.25mg/h was trialed with unclear effect. His hospitalization was complicated by gastrointestinal bleeding and mild ischemic stroke deemed noncontributory to his clinical status. The flumazenil infusion was discontinued 1 week later. His evaluation was extensive (brain magnetic resonance imaging and computerised tomography, lumbar puncture, and blood cultures) and unremarkable. On hospital week 4, he became only gradually more awake, and was eventually discharged to a rehabilitation facility on hospital week 6, awake, conversive but still confused. Six weeks later, he was discharged home fully recovered. He remains amnestic to his hospitalization. Serum diazepam and nordiazepam concentrations were determined via liquid-chromatography mass-spectrometry. Concentrations obtained four days after the last dose were: diazepam 963 mug/L (therapeutic: 200-1000 mug/L) and nordiazepam 240 mug/L (therapeutic: 100-1500 mug/L). Elimination kinetics were calculated with apparent half-lives of 294 hours and 797 hours for diazepam and nordiazepam, respectively. Genotyping of CYP3A4 and CYP2C19, the two primary metabolizers of diazepam, demonstrated no abnormalities.
Conclusion(s): Diazepam demonstrated extremely atypical elimination kinetics despite normal renal and hepatic function. Acute tolerance which is expected after prolonged benzodiazepine exposure was not clearly demonstrated. The relationship between his serum concentration and clinical status is unclear at this time

Objective: Hyperthermia is a life-threatening complication of agitated delirium, and a potential consequence of sympathomimetic, anticholinergic, or oxidative phosphorylation uncoupling xenobiotics. Failure to promptly cool a hyperthermic patient leads to morbid sequelae, including rhabdomyolysis, acute kidney injury, ischemic hepatitis (shock liver), disseminated intravascular coagulation, and possibly death. The primary objective of this study is to assess one Poison Control Center's (PCC) experience with hyperthermic patients, specifically as it relates to the use of ice or water bath treatment. Secondary objectives include characterizing mortality rate, ambient temperatures at the time of presentation, and initial laboratory abnormalities.
Method(s): This is a retrospective analysis of data from a single PCC from 2014 to 2019. A structured query language search (SQL) of Toxicall

Background: The "Pollyanna Phenomenon," an optimism for useful interventions appearing as efficacious as useless ones, was first described in 1992[1]. An editorial written in 1997 highlighted this phenomenon regarding passive data collection from Poison Control Centers (PCCs) and its limitations related to minimally symptomatic or asymptomatic patients[2]. PCCs continue to collect data passively with an immense data pool. Despite these "big data," limitations to PCC research persist. The term toxicovigilance was borne from this editorial and suggestions were made to improve PCC data fidelity and to overcome the "Pollyanna Phenomenon." We investigated PCC research over the past 40+ years to determine the impact of this editorial on toxicovigilance[2].
Method(s): We searched PubMed and EMBASE for PCC research from 1978 to 2020 using these search terms: "Poison Center", "Poison Control Center", "Poison Centre", "Poison Control Centre." Research articles before 1997 established a baseline for research quality[2]. Research articles from 1997 to April 2020, served as the intervention group assessing for changes in the quality of research and were examined for evidence of toxicovigilance. Articles were included in this study based on the following criteria: written in English; classified as original research; performed in a PCC setting, and the study objective was focused on an identifiable xenobiotic or xenobiotics. Each article was assessed for toxicovigilance based on the following criteria: confirmation of said xenobiotic(s) either qualitatively or quantitatively, study methodology (retrospective or prospective), and clinical recommendations made "beyond the scope of study methodology." If a study did not confirm xenobiotics' presence analytically, the study was considered to make recommendations beyond the scope of the study methodology.
Result(s): Our search initially identified 1614 articles. A random sample of 400 articles was chosen for review. From 1978-1997, 88 articles were initially identified. Twenty-five studies met inclusion criteria. Fifteen were retrospective and ten were prospective. Two studies confirmed exposure confirmation analytically in each group. Ten retrospective studies made clinical recommendations based on their conclusions, none of which confirmed the analytical presence of xenobiotic(s). Ten prospective studies made clinical recommendations with only two analytically confirming the presence of the xenobiotic. From 1998-2020, 138 research studies met inclusion criteria of which 117 were retrospective and 19 were prospective. Of these two groups, 19 and 7 had analytically confirmed xenobiotic presence in the retrospective and prospective studies, respectively. Sixty-eight retrospective studies and ten prospective studies made clinical recommendations without analytically confirming xenobiotic exposures. Comparing the baseline and intervention groups, we observed an increase in the frequency of retrospective studies with a similar proportion making clinical recommendations while lacking confirmation of exposures. There was an increase in rates of xenobiotic confirmation by 2% in the intervention period.
Conclusion(s): Toxicovigilance appears to be lacking in many PCC studies. Despite vast advancements in analytical techniques and the ability to gather and record data, the "Pollyanna Phenomenon" remains vibrant in PCC research. Efforts towards improving the frequency of analytical testing and confirmation of xenobiotic exposure are essential to improve PCC data collection and research and must be considered prerequisites for journal publication. (Table Presented)

BACKGROUND:We report a patient with a massive hydroxychloroquine overdose manifested by profound hypokalemia and ventricular dysrhythmias and describe hydroxychloroquine toxicokinetics. CASE REPORT/METHODS:A 20-year-old woman (60 kg) presented 1 h after ingesting 36 g of hydroxychloroquine. Vital signs were: BP, 66 mmHg/palpation; heart rate, 115/min; respirations 18/min; oxygen saturation, 100% on room air. She was immediately given intravenous fluids and intubated. Infusions of diazepam and epinephrine were started. Activated charcoal was administered. Her initial serum potassium of 5.3 mEq/L decreased to 2.1 mEq/L 1 h later. The presenting electrocardiogram (ECG) showed sinus tachycardia at 119 beats/min with a QRS duration of 146 ms, and a QT interval of 400 ms (Bazett's QTc 563 ms). She had four episodes of ventricular tachydysrhythmias requiring cardioversion, electrolyte repletion, and lidocaine infusion. Her blood hydroxychloroquine concentration peaked at 28,000 ng/mL (therapeutic range 500-2000 ng/mL). Serial concentrations demonstrated apparent first-order elimination with a half-life of 11.6 h. She was extubated on hospital day three and had a full recovery. CONCLUSION/CONCLUSIONS:We present a massive hydroxychloroquine overdose treated with early intubation, activated charcoal, epinephrine, high dose diazepam, aggressive electrolyte repletion, and lidocaine. The apparent 11.6 hour half-life of hydroxychloroquine was shorter than previously described.

The use of extracorporeal treatments (ECTRs) for poisonings with four non-traditionally dialyzed toxins (NTDTs) is increasing in the United States. This study evaluated whether ECTRs are prescribed for toxin removal or the treatment of other medical illnesses or complications. We performed a Phase 2 retrospective analysis evaluating the main indication for ECTRs in patients with: poisoning with a NTDT (defined for this study as: acetaminophen, opioids, tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed all cases from a single site (New York City Poison Control Center) between the years 2000 and 2016 and the second phase surveyed all United States Poison Control Centers (PCCs). In Phase 1, demographics, toxin ingested, and main indication for ECTR were extracted. In Phase 2, a query to the National Poison Data System using the a pragmatic subset of inclusion criteria from Phase 1 that was restricted to single substance ingestions over a narrower time frame (2014-2016) provided the cases for study. A structured online questionnaire was sent to all United States PCCs to request their database review regarding the indication for ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2, 519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%) and Phase 2 411/425 (96.7%) extracorporeal treatments were used to treat underlying medical conditions or poisoning-related complications rather than accelerate toxin removal. The increasing number of ECTRs reported in patients who ingested one of the four NTDTs thus appears to be for medical indications rather than attempts at toxin removal, a distinction that is important to report.

CONTEXT/BACKGROUND:Short messaging service (SMS or text messaging) allows for the exchange of electronic text messages. Online chatting refers to Internet-based transmission of messages for real-time conversation. Poison Control Centers (PCCs) in the United States communicate with the public primarily via telephone. However, people increasingly prefer the convenience of SMS and chatting. Our objective is to describe the use of SMS and chatting by PCCs in the United States. METHODS:An electronic survey questionnaire was distributed to all 55 US poison control center members of the American Association of Poison Control Centers. The survey assessed protocols for SMS and chatting, inquiry volume, and staff satisfaction. Centers reporting use of SMS or chatting services were administered follow-up questions, which further documented SMS and chatting interfaces and startup and maintenance costs. Descriptive statistics were used to describe the data. No statistical analysis was performed. RESULTS:Of the 55 PCCs, 51 (93%) responded to the survey, 6 (12%) of which currently use or formerly used SMS and/or chatting. Inquiry volume ranged from 0 to 1 per day for SMS and 0 to 20 per day for chats. Startup costs ranged from $0 to $25,000. The most beneficial aspect, reported by 4 of the 6 PCCs (66.6%), was providing an alternative contact for inquiries. Most SMS and chatting interactions were completed within 10 and 30 min, respectively. All six centers completed telephone interactions within 10 min. The most disadvantageous aspects, reported by 2 of the 6 PCCs (33.3%), were staff apprehension and interaction length. Technology, such as syncing with existing call queuing software and databases, presented the greatest barrier to implementation. CONCLUSIONS:A minority of PCCs in the United States use SMS and chatting. Further research may investigate the economic feasibility of these systems, if SMS and chatting effectively expands public access, and patient comfort in contacting PCCs.