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Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review

Connors, Nicholas J; Alsakha, Ahmed; Larocque, Alexandre; Hoffman, Robert S; Landry, Tara; Gosselin, Sophie
OBJECTIVE:Benzodiazepines are often recommended first-line for management of cocaine and amphetamine toxicity while antipsychotic treatment is discouraged due to the potential for lowering seizure threshold, prolonging the QT interval, and decreasing heat dissipation. We performed a systematic review including animal and human studies to elucidate the efficacy and safety of antipsychotics in managing sympathomimetic toxicity specifically evaluating the effect of treatment on mortality, seizures, hyperthermia, and cardiovascular effects. METHODS:We searched MEDLINE, Embase, BIOSIS Previews, Web of Science, Scopus, CENTRAL and gray literature from inception to 31 May 2017 to answer: Can antipsychotics be used safely and effectively to treat cocaine or amphetamine toxicity? Citations were screened by title and abstract. Additional citations were identified with citation tracking. Data were extracted from full-texts. RESULTS:6539 citations were identified; 250 full-text articles were assessed. Citation tracking identified 2336 citations; 155 full texts were reviewed. Seventy-three papers were included in this review. In 96 subjects with cocaine toxicity treated with an antipsychotic, there were three deaths, two cardiac arrests, two seizures, and one episode of hyperthermia. In 330 subjects with amphetamine toxicity treated with an antipsychotic, there were two episodes of coma and QT prolongation and one episode of each: hypotension, NMS, cardiac arrest, and death. CONCLUSION/CONCLUSIONS:This systematic review represents an exhaustive compilation of the available evidence. There is neither a clear benefit of antipsychotics over benzodiazepines nor a definitive signal of harm noted. We encourage clinicians to adapt treatment based on specific circumstances and characteristics of their individual patients.
PMID: 30639129
ISSN: 1532-8171
CID: 3595152

Toxicokinetics of hydroxychloroquine following a massive overdose

de Olano, Jonathan; Howland, Mary Ann; Su, Mark K; Hoffman, Robert S; Biary, Rana
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.
PMID: 31477360
ISSN: 1532-8171
CID: 4063542

Hemodialysis for lamotrigine poisoning [Letter]

Gosselin, Sophie; Ghannoum, Marc; Hoffman, Robert S
PMID: 31421953
ISSN: 1532-8171
CID: 4046502

Rebound metabolic acidosis following intentional amygdalin supplement overdose

Shively, Rachel M; Harding, Stephen A; Hoffman, Robert S; Hill, Adam D; Astua, Alfredo J; Manini, Alex F
Introduction: Amygdalin, marketed misleadingly as supplement "Vitamin B17," is a cyanogenic glycoside. When swallowed, it is hydrolyzed into cyanide in the small intestine, which causes histotoxic hypoxia via inhibition of cytochrome c oxidase. It remains available for purchase online despite a ban from the US Food and Drug Administration. We report a case of massive intentional amygdalin overdose resulting in recurrent cyanide toxicity after initial successful antidotal therapy. Case summary: A 33-year-old woman intentionally ingested 20 g of "apricot POWER B17 Amygdalin" supplements. She presented five hours post-ingestion with vital signs: P 127 bpm, BP 112/65 mmHg, RR 25/min, temperature 98.1 °F, and SpO2 98% RA. She was in agitated delirium, diaphoretic, and mydriatic. Her VBG was notable for a pH of 7.27 (rr 7.32-7.42) and lactate 14.1 mmol/L (rr 0.5-2.2), with ECG demonstrating QTc 538 ms (normal <440 ms). She was empirically treated with hydroxocobalamin and supportive care, but worsened clinically, requiring intubation and additional hydroxocobalamin and sodium thiosulfate, which resolved her toxicity. Twelve hours later, she developed recurrent hypotension, acidemia, and QTc prolongation that resolved with repeat hydroxocobalamin and sodium thiosulfate dosing. Discussion: Our case demonstrates rebound metabolic acidosis after massive amygdalin overdose. Toxicity was associated with prolonged QTc, which warrants further investigation into clinical significance. Redosing of combination antidotal therapy suggested efficacy without adverse effects.
PMID: 31322009
ISSN: 1556-9519
CID: 3978072

Comment on "the usefulness of non-contrast abdominal computed tomography for detection of residual drugs in the stomach of patients with acute drug overdose"

Francis, Arie; Howland, Mary Ann; Hoffman, Robert S; Su, Mark K
PMID: 31299873
ISSN: 1556-9519
CID: 3976932

Guidelines for reporting case studies and series on drug-induced QT interval prolongation and its complications following acute overdose

Berling, Ingrid; Hatten, Benjamin W; Hoffman, Robert S; Othong, Rittirak; Roberts, Darren M; Mustafa, Reem A; Yates, Christopher; Cormier, Monique; Gosselin, Sophie
BACKGROUND:The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning. METHODS:We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria. RESULTS:Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented. CONCLUSIONS:We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.
PMID: 31018700
ISSN: 1556-9519
CID: 3821672

Extracorporeal Treatments In Poisonings From Four Non-Traditionally Dialyzed Toxins (Acetaminophen, Digoxin, Opioids, and Tricyclic Antidepressants): A Combined Single-Centre and National Study

Campion, Gabriel H; Wang, Josh J; Hoffman, Robert S; Cormier, Monique; Lavergne, Valéry; Mowry, James B; Roberts, Darren M; Ghannoum, Marc; Su, Mark K; Gosselin, Sophie
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.
PMID: 30248244
ISSN: 1742-7843
CID: 3315602

Treatment of Alcohol Withdrawal Syndrome [Letter]

Harmouche, Elie; Steger, Catherine; Mikhaeil, Michael; Hoffman, Robert S
PMID: 30824508
ISSN: 1937-710x
CID: 3700802

Poison control centers and alternative forms of communicating with the public: what's all the chatter about?

Su, Mark K; Howland, Mary Ann; Alam, Mohammad; Ha, Catherine; Guerrero, Kristine; Schwartz, Lauren; Hoffman, Robert S
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.
PMID: 30729826
ISSN: 1556-9519
CID: 3632302

In Response to: "A Prospective Study of Stingray Injury and Envenomation Outcomes" [Letter]

Harmouche, Elie; Mendoza, Megan Ann V; Kiyohara, Nicole; Hoffman, Robert S
PMID: 30472014
ISSN: 0736-4679
CID: 3500962