Pharmacokinetic analysis of a phenobarbital overdose treated with urinary alkalinization alone.

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was preliminary positive for barbiturates and confirmed to be phenobarbital only. The initial serum phenobarbital concentration, drawn nine hours post-ingestion, was 97.4 mcg/ml (normal range 15-40 mcg/ml). Urinary alkalinization with sodium bicarbonate was started approximately 12 h post-ingestion and stopped at 72 h post-ingestion; clinical toxicity resolved by hospital day 5. The infusion was titrated to a urinary pH of greater than 7.5. Serial serum and urine phenobarbital measurements were obtained to determine elimination half-life and urinary excretion. The elimination half-life while undergoing urinary alkalinization was 81.3 h. Prior to initiation of urinary alkalinization, the urine phenobarbital concentration was 37 mcg/ml. Approximately 8.75 h after initiation, it was greater than 200 mcg/ml at a urine pH of 8.5. Urinary alkalinization appeared to augment urinary phenobarbital excretion, though with no discernible effect on elimination half-life and unclear clinical benefit. Further research is needed to better characterize the clinical effects of urinary alkalinization for phenobarbital overdose.

Identification and management of low-risk isolated traumatic brain injury patients initially treated at a rural level IV trauma center.

STUDY OBJECTIVE: Our goal was to determine if low-risk, isolated mild traumatic brain injury (TBI) patients who were initially treated at a rural emergency department may have been safely managed without transfer to the tertiary referral trauma center. METHODS: This was a retrospective observational analysis of isolated mild TBI patients who were transferred from a rural Level IV Trauma Center to a regional Level I Trauma Center between 2018 and 2022. Patients were risk-stratified according to the modified Brain Injury Guidelines (mBIG). Data abstracted from the electronic medical record included patient presentation, management, and outcomes. RESULTS: 250 patients with isolated mild TBI were transferred out to the Level I Trauma Center. Fall was the most common mechanism of injury (69.2%). 28 patients (11.2%) were categorized as low-risk (mBIG1). No mBIG1 patients suffered a progression of neurological injury, had worsening of intracranial hemorrhage on repeat head CT, or required neurosurgical intervention. 12/28 (42.9%) of mBIG1 patients had a hospital length of stay of 2 days or less, typically for observation. Those with longer lengths of stay were due to medical complications, such as sepsis, or difficulty in arranging disposition. CONCLUSION: We propose that patients who meet mBIG1 criteria may be safely observed without transfer to a referral Level I Trauma Center. This would be of considerable benefit to patients, who would not need to leave their community, and would improve resource utilization in the region.

Pediatric Rattlesnake Envenomations Treated With Crotalidae Equine Immune F(Ab') 2 Antivenom : A 3-Year Retrospective Observational Analysis.

OBJECTIVES: Rattlesnake envenomations are uncommon, and the majority occur in adults. Although Crotalidae equine immune F(ab') 2 antivenom (F(ab') 2 AV; trade name ANAVIP) was introduced in 2018, no pediatric specific studies of F(ab') 2 AV have been reported to date. The objective of this study was to evaluate the clinical performance and adverse effects of F(ab') 2 AV in children. METHODS: A single-center, retrospective chart review was performed on patients with rattlesnake envenomation presenting to a children's hospital between October 2018 and August 2022. Inclusion criteria were age younger than 18 years and F(ab') 2 AV use. Exclusion criteria were other antivenom use at any time and presentation beyond 24 hours postenvenomation.Demographic characteristics, hemoglobin, platelet count, fibrinogen, international normalized ratio, number of F(ab') 2 AV vials used, infusion-related complications, and clinical outcomes were collected. RESULTS: Twenty-six patients, 19 males and 7 females, with a mean age of 7.7 years (0.67 to 16 years) met inclusion criteria. Fourteen (54%) were treated with only the initial 10 vial F(ab') 2 AV doses. Twelve patients were given additional doses with a median additional vials of 10 (4-34 vials; interquartile range, 8.75-12 vials). The median total vials given for all patients was 10 (10-44 vials; interquartile range, 10-20 vials).Two patients developed acute infusion reactions. Both were treated by slowing the infusion rate and with medications (diphenhydramine, corticosteroids). No delayed reactions were noted. No patients required blood products or surgical interventions.After discharge, no complications, recurrent symptoms, return visits, or readmissions were reported. Follow-up by chart review or phone was obtained for 18 patients, and no postdischarge complications were noted. Seven patients had postdischarge hematologic laboratory evaluations and all were normal. CONCLUSIONS: Although limited by small sample size and postdischarge follow-up, F(ab') 2 AV was well tolerated in our series of pediatric patients, consistent with prior studies of all age groups.

Symptomatic Diethylene Glycol Ingestion Successfully Treated with Fomepizole Monotherapy.

BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.

Interobserver agreement between emergency clinicians and nurses for Clinical Opiate Withdrawal Scale.

OBJECTIVES: The Clinical Opiate Withdrawal Scale (COWS) is a validated, commonly used tool to objectively quantify withdrawal symptoms, often in anticipation of treatment with buprenorphine. Our primary aim was to determine the agreement between emergency department (ED) nurses compared with emergency physicians in determining this score in ED patients who presented for opioid withdrawal treatment. Secondarily, we wanted to investigate the safety of buprenorphine induction in the ED setting. METHODS: Scoring for opioid withdrawal using the COWS was performed by ED clinicians and ED nurses independently on 120 patients. In addition to overall concordance, agreement (weighted kappa) was calculated between the 2 scores by various cutoffs: overall severity, COWS ≥ 5, and the 11 different individual measures. Patient documents also were reviewed for complications that could be possibly linked to buprenorphine induction. RESULTS: Our study sample of 120 subjects was 77% Hispanic and 78.3% male. The clinicians assigned a median interquartile range overall COWS score of 6 (2-12), which categorizes as mild withdrawal. Seventy-eight (65%) subjects met the criteria of withdrawal (≥ 5 COWS) and 69 (58%) received an induction dose of buprenorphine (range 2 mg-24 mg) during the ED visit. No adverse effects or worsening withdrawal were reported. The overall observed concordance, based on severity withdrawal categorization, for all clinician pairs, was 67.5% (81/120) (95% confidence interval [CI], 58.7-75.2%). The weighted kappa for that concordance was 0.55 (95% CI, 0.43-0.67), giving a moderate strength of agreement. When data are dichotomized by COWS score ≥5, concordance was 82.5% (99/120) (95% CI, 74.7%-88.3%) and the weighted kappa was 0.65 (95% CI, 0.51-0.78), indicating substantial agreement. The breakdown by the 11 factors that constitute COWS showed only substantial agreement for pulse measurement. CONCLUSION: The agreement between ED clinicians and nurses for the overall COWS scoring in patients presenting for opioid withdrawal treatment was substantial. COWS scoring by ED nurses may help expedite treatment with buprenorphine on presentation.

Prevalence of Acute Hypersensitivity Reactions in Pediatric Patients Receiving Crotalidae Polyvalent Immune Fab.

INTRODUCTION: Studies of acute hypersensitivity reactions in pediatric populations receiving Crotalidae Polyvalent Immune Fab (CPIF) are complicated by small size, wide age ranges, and diverse definitions of such reactions. METHODS: This is a retrospective chart review of patients aged 13 years or younger treated with CPIF for Crotalid envenomation from November 2006 to 2016. The primary outcome was the presence of an acute hypersensitivity reaction to CPIF and was defined as the development of any of the following symptoms within 3 hours of initiation of CPIF infusion: urticaria, wheezing or respiratory distress, angioedema, hypotension, nausea, and/or vomiting. Demographics, CPIF dose to control and total dose, bite location, level of care, and length of stay were also recorded. RESULTS: Thirty-four patients were ultimately treated with CPIF. Ages ranged from 10 months to 13 years. Twenty-one patients (60%) were male, 24 (70.6%) were admitted to the ICU, and the median length of stay was 2 days with a range of 1-11 days. Zero patients developed an acute hypersensitivity reaction to CPIF. CONCLUSION: Acute hypersensitivity reactions to CPIF did not occur in this cohort. Such reactions are rare with the use of CPIF in pediatric patients.

Trifluoroacetic acid: Three times the fluoride, three times the toxicity?

Trifluoroacetic acid (TFAA) is a carboxylic acid, similar to acetic acid, used industrially and in laboratories. There is a paucity of data regarding exposure and the concern is that toxicity may mimic that of hydrofluoric acid (HF), causing electrolyte abnormalities, dysrhythmia, and cardiac arrest. We report a case of a 27-year-old male that presents with a dermal exposure to TFAA. His exam was remarkable for a 4% body surface area partial thickness burn to the right forearm. There were no initial electrolyte abnormalities or dysrhythmias and the patient was admitted to telemetry monitoring overnight. Serial laboratories were normal, dysrhythmias did not occur, and patient was ultimately discharged with routine burn care of the wound. Previously reported TFAA exposures are uncommon and tend to be very small body surface area chemical burns without clear systemic toxicity. HF as well as sodium and ammonium bifluorides have been shown to cause clinically significant electrolyte disturbances that can lead to dysrhythmias and fatalities. While TFAA may be structurally similar, it does not appear to have similar toxicity. This is an important difference in presentation and treatment that emergency physicians should be aware of as occupational exposures are likely to present to the emergency department.

North American Snake Envenomation.

Native US snakes that produce clinically significant envenomation can be divided into 2 groups, crotalids and elapids. The crotalids include rattlesnakes, cottonmouths, and copperheads. Crotalid envenomation can result in significant local tissue damage as well as thrombocytopenia and coagulopathy. Rarely are bites fatal. Native US elapids are all coral snakes that possess neurotoxic venom that can cause weakness, respiratory paralysis, and rarely death. Treatment of both types of envenomation revolves around general supportive care and antivenom administration when indicated. Previously advocated treatments, such as tourniquets, venom extraction, and bite site excision are not recommended.

Loperamide Trends in Abuse and Misuse Over 13 Years: 2002-2015.

STUDY OBJECTIVE: With the increasing amount of information available on the Internet describing techniques for using loperamide either for self-treatment of opioid withdrawal syndromes or for recreational use (so-called legal highs), the objective was to describe a statewide poison control system's experience with loperamide misuse and abuse, with specific interest in cases of cardiotoxicity, and to determine if reported loperamide misuse or abuse cases have recently increased. DESIGN: Retrospective review. DATA SOURCE: Statewide poison control system electronic database. PATIENTS: A total of 224 adults who presented or were referred to a health care facility between January 1, 2002, and November 10, 2015, for intentional ingestions of loperamide, and whose cases were reported to the poison control system by either physicians or nurses at the bedside. MEASUREMENTS AND MAIN RESULTS: Between 2002 and 2013, the number of yearly calls to the poison control system regarding loperamide cases ranged from 12-19 (mean 16.4, median 17.5 calls). In 2014, a sharp increase to 41 calls was noted. On completion of the study (November 10, 2015), 27 calls had been recorded. Medical outcomes of loperamide exposure for each patient were classified in accordance with the American Association of Poison Control Center's classification system as minor, moderate, or severe. For those patients with known outcomes, 3 resulted in death, 9 had major effects, 49 had moderate effects, and 36 had minor effects. We identified nine reports of patients who developed cardiotoxicity, with eight of them occurring between 2012 and 2015. A spike in the number of cases of loperamide toxicity reported in 2014 and 2015 coincided with an abundance of online instructions on how to abuse this drug. Almost all cases of recorded cardiotoxicity occurred over the last 3 years. Cardiotoxicity from loperamide abuse has only recently been recognized as a potential complication during the last few years, so earlier cases of cardiotoxicity resulting from loperamide abuse were likely missed. CONCLUSION: Our data suggest that loperamide may be increasing in popularity as a drug of abuse and for treatment of opioid withdrawal symptoms. Given the potential for significant toxicity with loperamide exposure, including life-threatening cardiac dysrhythmias, clinicians should consider obtaining a screening electrocardiogram for patients presenting after acute or chronic high-dose ingestions of loperamide. In addition, increased control over the availability of loperamide may be warranted.

Inadvertent Methylergonovine Administration to a Neonate.

BACKGROUND Methylergonovine is an ergot alkaloid used to treat post-partum hemorrhage secondary to uterine atony. Mistaking methylergonovine for vitamin K with accidental administration to the neonate is a rare iatrogenic illness occurring almost exclusively in the delivery room setting. Complications of ergot alkaloids in neonates include respiratory depression, seizures, and death. CASE REPORT A term infant was inadvertently given 0.1 mg of methylergonovine intramuscularly in the right thigh. The error was only noted when the vial of medication was scanned, after administration, identifying it as methylergonovine rather than vitamin K. The local poison center was notified, and the infant was transferred to the neonatal intensive care unit for observation. Two hours after transfer, the infant was noted to have oxygen desaturations and required oxygen via nasal cannula. Supplemental oxygen was continued for 4 hours until the neonate was able to maintain normal oxygen saturations in room air. Feeding was started by 10 hours of life, and the infant was discharged home in good condition after a 72-hour stay without further complications. CONCLUSIONS Because of the potential for serious adverse events, vigilance is required to prevent accidental administration of methylergonovine to the neonate as a result of possible confusion with vitamin K in the early post-partum period.

A Case of Acute Pericarditis Following Intravenous Injection of Crushed Morphine Tablets.

A 37-year-old male presented with sharp, severe chest pain following seven days of intravenous injection of crushed morphine tablets. The chest pain was positional and pleuritic in nature and resolved with leaning forward. Work-up was notable for an ECG with inferior and anterolateral PR depressions as well as a CT chest with diffuse centrilobular nodules. Per radiology, the CT findings along with the patient's history were concerning for pulmonary granulomatosis from deposition of talc or some other foreign body. Cardiology was consulted and diagnosed the patient with acute pericarditis, given his typical symptoms and ECG changes. On review of the literature, pulmonary granulomatosis following intravenous injection of foreign bodies is well documented. There are numerous studies documenting foreign body deposition and granulomatosis in organs other than the lungs on post-mortem analyses of individuals with a history of IV injection of crushed tablets. We are suggesting that intravenous injection of crushed morphine tablets can cause pericardial irritation and a syndrome of acuter pericarditis. To our knowledge, there has not been a previous report of acute pericarditis secondary to intravenous injection of crushed tablets.

Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): randomized, controlled trial of ibuprofen versus placebo for prevention of altitude illness.

OBJECTIVE: To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH). METHODS: Double-blind, randomized, placebo-controlled trial. RESULTS: Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P = .01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P = .01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P = .035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P = .129 for AMS incidence, 9.6% vs 8.2%; P = .74 for AMS severity, 54.8% vs 42.7%; P = .11 for HAH incidence, and 8.2% vs 3.6%; P = .18 for HAH severity). CONCLUSIONS: Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS.