Severe colchicine poisoning treated successfully with kidney replacement therapy and plasmapheresis: a case report.

Colchicine is commonly prescribed for treatment of inflammatory conditions but has a narrow therapeutic window and dangerous toxicity profile. Here we describe a case of survival after massive unintentional colchicine overdose treated with plasmapheresis and renal replacement therapy. A 37 year old male with history of pericarditis presented to the Emergency Department with a chief complaint of nausea, vomiting, and diarrhea after unintentionally ingesting 36 mg of colchicine 17 h prior to arrival. An initial colchicine concentration resulted at 5.1 ng/mL (30 h post-ingestion) and peaked at 12 ng/mL (40 h post-ingestion). He was treated with continuous kidney replacement therapy (CKRT) beginning on his first day of hospitalization and with plasmapheresis on hospital days two through four. The patient's course was complicated by multiorgan failure including coagulopathy, respiratory failure, neuropathy, renal failure, pancytopenia, and heart failure. He was discharged to inpatient rehabilitation on hospital day 24. On clinical follow up four months after discharge the patient was found to have no significant persistent morbidity related to colchicine overdose.

Traumatic pedestrian and bicyclist injuries associated with intoxication.

BACKGROUND: Drug and alcohol use are risk factors for trauma among operators of motor vehicles and contribute to trauma in pedestrians and bicyclists. We describe the prevalence of drug and alcohol use and clinical consequences in a cohort of pedestrians and bicyclists with trauma. METHODS: We analyzed a 25-month data set of 916 trauma team activations from January 2017-January 2019 at an urban, level I trauma center. Blood ethanol levels and urine toxicology screens were obtained in 94 pedestrian and bicyclist trauma activations. We compared pedestrians or bicyclists with a positive urine or blood screen (n = 69) to those with negative screens (n = 25). We conducted a retrospective chart review to determine mechanism of injury, injury pattern, and disposition from the emergency department (ED). RESULTS: Overall, 38 (55%) of injured patients with positive screen were pedestrians and 31 (45%) were bicyclists. Fentanyl was the most commonly detected drug (n = 38; 40%), followed by opiates (n = 27; 29%), and tetrahydrocannabiol (THC) (n = 23; 25%). Twenty-one patients were positive for ethanol. Pedestrians and bicyclists with positive toxicology screens were significantly more likely to sustain fractures (p < .01), require an operative procedure (p < .05), or intensive care unit admission (p < .05). CONCLUSION: Our study builds on previous literature which suggests that intoxicated bicyclists and pedestrians suffer frequent and more severe injury than their sober counterparts. Public health campaigns should educate bicyclists and pedestrians about the risks of cycling or walking in areas of road traffic while under the influence of alcohol or illicit drugs.

Intentional Hydroxychloroquine Overdose Treated with High-Dose Diazepam: an Increasing Concern in the COVID-19 Pandemic.

INTRODUCTION: Recent attention on the possible use of hydroxychloroquine and chloroquine to treat COVID-19 disease has potentially triggered a number of overdoses from hydroxychloroquine. Toxicity from hydroxychloroquine manifests with cardiac conduction abnormalities, seizure activity, and muscle weakness. Recognizing this toxidrome and unique management of this toxicity is important in the COVID-19 pandemic. CASE REPORT: A 27-year-old man with a history of rheumatoid arthritis presented to the emergency department 7 hours after an intentional overdose of hydroxychloroquine. Initial presentation demonstrated proximal muscle weakness. The patient was found to have a QRS complex of 134 ms and QTc of 710 ms. He was treated with early orotracheal intubation and intravenous diazepam boluses. Due to difficulties formulating continuous diazepam infusions, we opted to utilize an intermitted intravenous bolus strategy that achieved similar effects that a continuous infusion would. The patient recovered without residual side effects. DISCUSSION: Hydroxychloroquine toxicity is rare but projected to increase in frequency given its selection as a potential modality to treat COVID-19 disease. It is important for clinicians to recognize the unique effects of hydroxychloroquine poisoning and initiate appropriate emergency maneuvers to improve the outcomes in these patients.

Chloroquine, hydroxychloroquine and COVID-19.

The media have featured the antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) to treat coronavirus (COVID-19). Political leaders have touted their use and recommended availability to the public. These anti-inflammatory agents have substantial human toxicity with a narrow therapeutic window. CQ and HCQ poisoning cause myocardial depression and profound hypotension due to vasodilation. Bradycardia and ventricular escape rhythms arise from impaired myocardial automaticity and conductivity due to sodium and potassium channel blockade. With cardiotoxicity, ECGs may show widened QRS, atrioventricular heart block and QT interval prolongation. CQ may also cause seizures, often refractory to standard treatment. Of concern is pediatric poisoning, where 1-2 pills of CQ or HCQ can cause serious and potentially fatal toxicity in a toddler. The treatment of CQ/HCQ poisoning includes high-dose intravenous diazepam postulated to have positive ionotropic and antidysrhythmic properties that may antagonize the cardiotoxic effects of CQ. Infusions of epinephrine titrated to treat unstable hypotension, as well as potassium for severe hypokalemia may be required. Current scientific evidence does not support treatment or prophylactic use of these agents for COVID-19 disease. Regulatory and public health authorities recognize that CQ/HCQ may offer little clinical benefit and only add risk requiring further investigation before wider public distribution.

Antibiotic-associated diarrhoea in emergency department observation unit patients.

Clostridium difficile diarrhoea is an urgent threat to patients, but little is known about the role of antibiotic administration that starts in emergency department observation units (EDOUs). We studied risk factors for antibiotic-associated diarrhoea (AAD) and C. difficile infection (CDI) in EDOU patients. This prospective cohort study enrolled adult patients discharged after EDOU antibiotic treatment between January 2013 and 2014. We obtained medical histories, EDOU treatment and occurrence of AAD and CDI over 28 days after discharge. We enrolled and followed 275 patients treated with antibiotics in the EDOU. We found that 52 (18·6%) developed AAD and four (1·5%) had CDI. Patients treated with vancomycin [relative risk (RR) 0·52, 95% confidence interval (CI) 0·3-0·9] were less likely to develop AAD. History of developing diarrhoea with antibiotics (RR 3·11, 95% CI 1·92-5·03) and currently failing antibiotics (RR 1·90, 95% CI 1·14-3·16) were also predictors of AAD. Patients with CDI were likely to be treated with clindamycin. In conclusion, AAD occurred in almost 20% of EDOU patients with risk factors including a previous history of diarrhoea with antibiotics and prior antibiotic therapy, while the risk of AAD was lower in patients receiving treatment regimens utilizing intravenous vancomycin.

Nitrogen isotopes as indicators of NO(x) source contributions to atmospheric nitrate deposition across the midwestern and northeastern United States.

Global inputs of NO(x) are dominated by fossil fuel combustion from both stationary and vehicular sources and far exceed natural NO(x) sources. However, elucidating NO(x) sources to any given location remains a difficult challenge, despite the need for this information to develop sound regulatory and mitigation strategies. We present results from a regional-scale study of nitrogen isotopes (delta15N) in wet nitrate deposition across 33 sites in the midwestern and northeastern U.S. We demonstrate that spatial variations in delta15N are strongly correlated with NO(x) emissions from surrounding stationary sources and additionally that delta15N is more strongly correlated with surrounding stationary source NO(x) emissions than pH, SO4(2-), or NO3- concentrations. Although emission inventories indicate that vehicle emissions are the dominant NO(x) source in the eastern U.S., our results suggest that wet NO3- deposition at sites in this study is strongly associated with NO(x) emissions from stationary sources. This suggests that large areas of the landscape potentially receive atmospheric NO(y) deposition inputs in excess of what one would infer from existing monitoring data alone. Moreover, we determined that spatial patterns in delta15N values are a robust indicator of stationary NO(x) contributions to wet NO3- deposition and hence a valuable complement to existing tools for assessing relationships between NO3- deposition, regional emission inventories, and for evaluating progress toward NO(x) reduction goals.

Altered mental status from olanzapine overdose treated with physostigmine.

BACKGROUND: Olanzapine is commonly prescribed to patients with schizophrenia. One retrospective study demonstrates the efficacy of physostigmine in reversing mental status changes induced by olanzapine. We report two patients with delirium due to confirmed olanzapine overdose treated with physostigmine. One patient's mental status transiently returned to normal. The other patient completely recovered. CASE 1: A 25-year-old man ingested 300 mg of olanzapine. On presentation, he was agitated, delirious, tachycardic, had dry skin and mucous membranes, and dilated pupils (6 mm) minimally reactive to light. Physostigmine, 0.5 mg, was given intravenously (IV) without effect. Additional physostigmine doses of 1.5 mg IV administered 5 minutes later and then 1 mg IV resulted in the patient having a clear sensorium and normal mentation. The patient's mental status continued to remain normal for the duration of his hospital stay. Olanzapine was identified in the urine by high performance liquid chromatography. CASE 2: A 20-year-old female ingested 600 mg of olanzapine. On presentation, she was tachycardic, obtunded, and minimally responsive to painful stimuli, with decreased bowel sounds, dry skin and dry mucous membranes. Physostigmine, 2 mg, was given IV. Shortly thereafter she regained full consciousness and began speaking coherently. She remained in this condition for approximately 30 minutes, and then became obtunded. Her serum olanzapine concentration was 1230 ng/mL. No further doses of physostigmine were administered. On day 3 of admission her mental status returned to normal. CONCLUSION: We report two cases of olanzapine-induced mental status changes treated with physostigmine. The utility of physostigmine as a safe or necessary antidote in the setting of olanzapine overdose remains to be determined.

Childhood methanol ingestion treated with fomepizole and hemodialysis.

Fomepizole (4-methylpyrazole; Antizol) is used increasingly in the treatment of methanol toxicity in adults. Little experience exists with this drug in the pediatric population, however. We present a case of methanol poisoning in a child in whom the use of fomepizole averted intravenous ethanol infusion and the attendant side effects of this therapy.

Severe ethylene glycol ingestion treated without hemodialysis.

Fomepizole (4-methylpyrazole, Antizol) is being increasingly used in the treatment of ethylene glycol toxicity in adults. Little experience exists with this drug, however, in the pediatric population. We present a case of ethylene glycol poisoning in a child where use of fomepizole averted intravenous ethanol infusion and hemodialysis, limited the duration of intensive care monitoring, and decreased the overall cost of treatment.

Cocaine-associated chest pain: how common is myocardial infarction?

OBJECTIVE: Prior studies addressing the incidence of acute myocardial infarction (AMI) in patients with cocaine-associated chest pain have found divergent results. Previous prospective studies, which found approximately a 6% incidence of AMI, have been criticized for selection bias. This study sought to determine the rate of AMI in patients with cocaine-associated chest pain. METHODS: All patients seen in an urban university-affiliated hospital between July 1996 and February 1998 were identified by ICD-9 medical records search for cocaine use and chest pain/ acute coronary syndromes. In this system, all faculty admit all patients with cocaine-associated chest pain for at least 23-hour observation periods. Data collected included demographics, medical and cocaine use history, presenting characteristics, hospital course, cardiovascular complications, and diagnostic tests using a 119-item closed-question data instrument with high interrater reliability. The main outcome measure was AMI according to World Health Organization (WHO) criteria. RESULTS: There were 250 patients identified with a mean age of 33.5 +/- 8.5 years; 77% were male; 84% were African American. Of 196 patients tested, 185 had cocaine or cocaine metabolites in the urine (94%). The incidence of cardiac risk factors were: hypercholesterolemia, 8%; diabetes, 6%; family history, 34%; hypertension, 26%; tobacco use, 77%; prior MI, 6%; and prior chest pain, 40%. Seventy-seven percent admitted to cocaine use in the preceding 24 hours: crack, 85%; IV, 2%; nasal, 6%. Twenty-five patients (10%) had electrocardiographic evidence of ischemia. A total of 15 patients experienced an AMI (6%; 95% CI = 4.1% to 8.9%) using WHO criteria. Complications were infrequent: bradydysrrhythmias, 0.4%; congestive heart failure, 0.4%; supraventricular tachycardia, 1.2%; sustained ventricular tachycardia, 0.8%. CONCLUSION: The incidence of AMI was 6% in patients with cocaine-associated chest pain. This result is identical to that found in prior prospective studies.

Extracellular alkaline amylase from a Bacillus species.

A selective medium was used to isolate a bacterium (Bacillus species NRRL B-3881) that produced extracellular alkaline amylase in an alkaline medium (pH 9.5). Maximal enzyme yield was obtained in an aerated medium after 21 hr at 36 C. The enzyme was purified 18-fold by ultrafiltration and ammonium sulfate precipitation. Three active isoenzymes (one major and two minor) of alkaline amylase were detected by disc electrophoresis in polyacrylamide gel. The enzyme was only 12% inactivated by 20 mm ethylenediaminetetraacetic acid after 1 hr at pH 9.2 and 32 C. The optimal temperature was 50 C at pH 9.2, and the optimal pH was 9.2 at 50 C. The enzyme was stable between pH 7.5 and 10. It had an endomechanism of substrate encounter. The products produced from amylose and amylopectin had the beta-configuration. Cyclomaltoheptaose was hydrolyzed to maltotriose, maltose, and glucose. The main final product produced from amylose and amylopectin was beta-maltose; the other final products were maltotriose and small quantities of glucose and maltotetraose. The predominant product at early stages of hydrolysis was maltotetraose; other products were maltose through maltonanaose.

Extracellular transglucosylase and alpha-amylase of Streptococcus equinus.

Culture filtrates of Streptococcus equinus 1091 contained alpha-amylase and transglucosylase. The effects of calcium carbonate, age of inoculum, concentration of maltose, and duration of the fermentation on alpha-amylase and transglucosylase production were determined. The extracellular alpha-amylase was purified 48-fold and was free of transglucosylase activity. The alpha-amylase (amylose substrate) required Cl(-) for maximum activity; ethylenediaminetetraacetic acid (EDTA) partially inhibited activity, but CaCl(2) prevented EDTA inhibition. The temperature optimum was 38 C at pH 7.0, and the pH optimum was 7.0 at 37 C in the presence of CaCl(2). Predominant final products of amylose hydrolysis, in order of decreasing prevalence, were maltose, maltotriose, maltotetraose, and glucose. The alpha-amylase showed no evidence of multiple attack. The extracellular transglucosylase was purified 27-fold, but a small amount of alpha-amylase remained. Transglucosylase activity (amylose substrate) was not increased in the presence of CaCl(2). The temperature optimum was 37 C at pH 6.5, and the pH optimum was 6.0 at 37 C. Carbohydrates that served as acceptors for the transglucosylase to degrade amylose were, in order of decreasing acceptor efficiency: d-glucose, d-mannose, l-sorbose, maltose, sucrose, and trehalose. The extracellular transglucosylase of S. equinus 1091 synthesized higher maltodextrins in the medium when the cells were grown in the presence of maltose.