Cookie monster of a pediatric ingestion of zinc phosphide.

BACKGROUND: Zinc phosphide is a highly toxic rodenticide that reacts with hydrochloric acid in the stomach to form phosphine gas. Ingestion of zinc phosphide can result in consequential toxicity even when ingested in small quantities. Clear guidelines are lacking on appropriate personal protective equipment for providers to avoid additional exposure. CASE PRESENTATION: We present the case of a four-year-old boy who suffered mild gastrointestinal symptoms after an unintentional ingestion of zinc phosphide. After discussion with the regional Poison Control Center, providers wore powered air-purifying respirators in a negative pressure room and experienced no symptoms of phosphine exposure. The patient was discharged the next day after a complete recovery. CONCLUSIONS: Clinicians should be aware of the potential clinical ramifications to patients who ingest zinc phosphide and the potential risks of caring for such patients. To prevent additional exposure, providers should don appropriate personal protective equipment and contact HAZMAT (or local health department) to safely remove additional zinc phosphide.

Do Patients Die with or from Metformin-Associated Lactic Acidosis (MALA)? Systematic Review and Meta-analysis of pH and Lactate as Predictors of Mortality in MALA.

OBJECTIVES: Metformin-associated lactic acidosis (MALA) may occur after acute metformin overdose, or from therapeutic use in patients with renal compromise. The mortality is high, historically 50% and more recently 25%. In many disease states, lactate concentration is strongly associated with mortality. The aim of this systematic review and meta-analysis is to investigate the utility of pH and lactate concentration in predicting mortality in patients with MALA. METHODS: We searched PubMed, EMBASE, and Web of Science from their inception to April 2019 for case reports, case series, prospective, and retrospective studies investigating mortality in patients with MALA. Cases and studies were reviewed by all authors and included if they reported data on pH, lactate, and outcome. Where necessary, authors of studies were contacted for patient-level data. Receiver operating characteristic (ROC) curves were generated for pH and lactate for predicting mortality in patients with MALA. RESULTS: Forty-four studies were included encompassing 170 cases of MALA with median age of 68.5 years old. Median pH and lactate were 7.02 mmol/L and 14.45 mmol/L, respectively. Overall mortality was 36.2% (95% CI 29.6-43.94). Neither lactate nor pH was a good predictor of mortality among patients with MALA. The area under the ROC curve for lactate and pH were 0.59 (0.51-0.68) and 0.43 (0.34-0.52), respectively. CONCLUSION: Our review found higher mortality from MALA than seen in recent studies. This may be due to variation in standard medical practice both geographically and across the study interval, sample size, misidentification of MALA for another disease process and vice versa, confounding by selection and reporting biases, and treatment intensity (e.g., hemodialysis) influenced by degree of pH and lactate derangement. The ROC curves showed poor predictive power of either lactate or pH for mortality in MALA. With the exception of patients with acute metformin overdose, patients with MALA usually have coexisting precipitating illnesses such as sepsis or renal failure, though lactate from MALA is generally higher than would be considered survivable for those disease states on their own. It is possible that mortality is more related to that coexisting illness than MALA itself, and many patients die with MALA rather than from MALA. Additional work looking solely at MALA in healthy patients with acute metformin overdose may show a closer relationship between lactate, pH, and mortality.

Correction to: Utility of 2-Pyridine Aldoxime Methyl Chloride (2-PAM) for Acute Organophosphate Poisoning: A Systematic Review and Meta-Analysis.

The names of coauthors Roshanak Benabbas and and Ian S. deSouza were given incorrectly (as "Roshnak Benabbas" and "Ian de Souza", respectively) in this article as originally published.

Utility of 2-Pyridine Aldoxime Methyl Chloride (2-PAM) for Acute Organophosphate Poisoning: A Systematic Review and Meta-Analysis.

Organophosphates (OP) account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries. The therapeutic role of atropine is well-established for patients with acute OP poisoning. The benefit of adding 2-pyridine aldoxime methyl chloride (2-PAM), however, is controversial. We performed a systematic review and meta-analysis of available randomized controlled trials (RCT) to compare 2-PAM plus atropine in comparison to atropine alone for acute OP poisoning. We searched PubMed, EMBASE, and SCOPUS up to March 2017. The Cochrane review handbook was used to assess the risk of bias. Data were abstracted and risk ratios (RR) were calculated for mortality, rate of intubation, duration of intubation, intermediate syndrome, and complications such as hospital-acquired infections, dysrhythmias, and pulmonary edema. We found five studies comprising 586 patients with varying risks of bias. The risk of death (RR = 1.5, 95% CI 0.9-2.5); intubation (RR = 1.3, 95% CI 1.0-1.6); intermediate syndrome (RR = 1.6, 95% CI 1.0-2.6); complications (RR = 1.2, 95% CI 0.8-1.8); and the duration of intubation (mean difference 0.0, 95% CI - 1.6-1.6) were not significantly different between the atropine plus 2-PAM and atropine alone. Based on our meta-analysis of the available RCTs, 2-PAM was not shown to improve outcomes in patients with acute OP poisoning.

The evolving clinical management of cerebral metastases.

Concepts in the management of brain metastases are evolving. Until recently, brain metastases have been considered as a homogenous condition, managed with whole brain radiotherapy, surgical resection for large lesions and stereotactic radiosurgery for smaller lesions. Increasingly, specific systemic medical therapies are being used to treat brain metastases based on the primary site of disease. This disease specific management is causing a change in perspective about brain metastases and has led to improved survival for patients with primary disease subtypes amenable to tailored medical therapies. We review the recent literature to present evidence for the use of subtype specific medical therapies, advances in surgical resection techniques and stereotactic radiosurgery as the primary treatment modalities. The decline in use of whole brain radiotherapy as first line treatment is also discussed. Based on the recent literature, we propose a new management algorithm to reflect the progress in available options for tailoring disease specific treatments and support the change in paradigm to consider brain metastases as separate disease states based on the primary site of cancer rather than as a homogenous entity.

Toxicologic acid-base disorders.

Acid-base disorders may complicate the presentation of patients with poisoning. This article summarizes an approach to acid-base disorders from a toxicologic perspective. It aims to assist the reader in identifying underlying acid-base processes, generating a differential diagnosis for each, and approaching that differential diagnosis in a systematic fashion. Understanding these processes will help to guide management and interventional strategies.

Systematic review evaluating cardiovascular events of the 5-alpha reductase inhibitor - Dutasteride.

WHAT IS KNOWN AND OBJECTIVES: A recently published large, long-term randomized controlled trial (RCT) brought into question the safety of dutasteride after a significantly increased risk of 'cardiac failure' was noted in the dutasteride arm of the trial compared with placebo. Our objective was to perform a meta-analysis to assess the risk of cardiovascular adverse events with the use of dutasteride for the prevention or treatment of prostatic disease. METHODS: We searched MEDLINE and EMBASE, unpublished articles identified through FDA/EMEA websites, study registers of pharmaceutical companies and reference lists of articles. Parallel-group, randomized controlled trials where men received dutasteride for the prevention of prostate cancer or treatment of prostatic hyperplasia against any comparator intervention were included. Heart failure was the primary outcome of interest but we also looked at myocardial infarction and stroke. Fixed-effect meta-analysis of pooled relative risk (RR) ratios of adverse effect outcomes was conducted. RESULTS AND DISCUSSION: In all, 12 RCTs were included in the meta-analysis after detailed screening of 564 citations. The total number of participants was 18,802, and study duration ranged from 6 to 208 weeks. Only two trials provided details on adequate allocation concealment, whereas all the trials stated they were double blind in nature. Dutasteride was not associated with a statistically significant increased risk of heart failure (RR 1·05; 95% confidence interval [CI], 0·71-1·57, I(2) = 20%), myocardial infarction (RR 1·00; 95% CI 0·77-1·30, I(2) = 0%) and stroke (RR, 1·20; 95% CI 0·88-1·64, I(2) = 0%) as compared to controls. WHAT IS NEW AND CONCLUSION: We did not find consistent evidence of a significant association between dutasteride therapy and the risk of cardiovascular adverse events.

Ethanol elimination kinetics following massive ingestion in an ethanol naive child.

OBJECTIVE: At low-to-moderate concentrations, ethanol elimination follows zero-order kinetics. It is unknown whether renal, pulmonary or other first-order processes become significant in patients with very high serum ethanol concentrations. Additionally, it is unclear whether ethanol naive subjects induce their metabolism during acute intoxication. We present the toxicokinetic analysis in a child with a massive ingestion of ethanol. CASE REPORT: A 15-year-old girl without significant medical history presented to the Emergency Department after drinking 24 ounces of tequila. She was found unresponsive at home with a Glasgow Coma Score of 3. Her presenting vitals were as follows: 118/69 mmHg blood pressure; pulse rate was 88 beats per minute; respiratory rate of 20 breaths per minute; pulse-oximetry is 96% on room air. Other than obtundation, her physical examination was normal. She was intubated for airway protection and admitted to the ICU. Her initial serum ethanol concentration was 543 mg/dL. A repeat level 3 h later was 722 mg/dL. Post-absorptive ethanol concentrations decreased from 693 mg/dL to 291 mg/dL over the following 15.5 h. The patient had spontaneous eye opening 24 h after presentation. Her projected serum ethanol concentration at that time was 215 mg/dL. She was extubated 2 h later and had an uneventful recovery. RESULTS: The elimination of ethanol in the post-absorptive phase remained zero-order at a rate of 26.3 mg/dL/h (5.7 mmol/L/h) with a Pearson's correlation coefficient (R (2)) of 0.9968 (p < 0.01). There was no evidence of acute induction in metabolism although pharmacodynamic tolerance likely occurred. CONCLUSION: Even at very high ethanol concentrations in ethanol naive subjects, elimination of ethanol follows a zero-order toxicokinetic model.

Ethylene glycol toxicity presenting with non-anion gap metabolic acidosis.

Ethylene glycol classically produces an elevated anion gap metabolic acidosis. We report a series of patients with ethylene glycol toxicity with a component of non-anion gap metabolic acidosis without known associated confounding factors. A retrospective review of Poison Control Center records were searched more than 8 years (2000-2007) for ethylene glycol and antifreeze. Cases were reviewed and excluded for miscoding, information calls, animal exposures, or non-ingestion exposures. The bicarbonate gap, or delta ratio (DR), was calculated using the formula: DR = (AG - 12)/[24 - measured serum where anion gap (AG) = [Na(+)] - [Cl(-)] - , all in mEq/l. Non-anion gap metabolic acidosis was considered present when the DR < 1. Of 254 cases, 175 were excluded. Of the remaining 79 cases, 14 had a component of non-anion gap metabolic acidosis at presentation. Their calculated anion gap was 14-28, and measured serum ranged from 2-20 mEq/l. A normal anion gap was present in two patients who presented with non-anion gap metabolic acidosis. The DR ranged from 0.28-0.95. Seven out of 14 patients with non-anion gap metabolic acidosis had elevated serum [Cl(-)]. In the other cases, no explanation for the non-anion gap metabolic acidosis could be determined. The absence of a significant anion gap elevation in the setting of metabolic acidosis after ethylene glycol ingestion without other confounding factors (such as ethanol, lithium carbonate or bromide) has not previously been recognized. Clinicians should be aware of the potential for non-anion gap metabolic acidosis in patients with ethylene glycol toxicity, and should not exclude the diagnosis in patients who present with a non-anion gap metabolic acidosis. Further study is needed to determine the mechanisms by which this occurs.

Trends in clinical toxicology: advances that may change your practice.

Recent studies have had a significant impact on the practice of Medical Toxicology. We review selected articles that have advanced our thinking about consequential issues such as gastrointestinal decontamination, paracetamol poisoning, ethanol withdrawal, cocaine-associated chest pain, carbon monoxide poisoning and over-anticoagulation.

Nerve agents: a comprehensive review.

Nerve agents are perhaps the most feared of potential agents of chemical attack. The authors review the history, physical characteristics, pharmacology, clinical effects, and treatment of these agents.

Efficacy of Crotalidae polyvalent antivenin for the treatment of hognosed viper (Porthidium nasutum) envenomation.

Envenomation from pit vipers native to North America can be treated successfully with either of the 2 commercially available antivenoms licensed in the United States. However, envenomations from imported snakes held in zoos or private collections often pose unique challenges to management because of the lack of specific antivenom and the unclear efficacy of the available licensed products. We report the case of a 37-year-old man who was envenomated on his left hand by his pet hognosed viper (Porthidium nasutum ). He had swelling at the wound site that progressively worsened over 3 to 4 hours. His symptom progression included the structural motor impairment of his fingers and a sensory deficit. Treatment with 8 vials of Antivenin (Crotalidae) polyvalent was associated with a halt of extremity swelling and restoration of neurologic and motor function of his hand. Limited experimental evidence provides support for antigenic cross-reactivity between Antivenin (Crotalidae) polyvalent and P nasutum venom.