A systematic review of phenibut withdrawal focusing on complications, therapeutic approaches, and single substance versus polysubstance withdrawal.

INTRODUCTION: Phenibut is an unregulated supplement that acts primarily as a gamma-aminobutyric acid type B receptor agonist. Use of phenibut can lead to dependence and subsequent withdrawal when use is stopped. Phenibut withdrawal can cause severe symptoms such as delirium, hallucinations, and seizures. The purpose of this systematic review is to characterize the natural history of phenibut withdrawal and summarize treatment strategies published in the literature. METHODS: A systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses checklist. English language peer-reviewed articles or conference abstracts in humans describing phenibut withdrawal after cessation of use were included. Databases (Ovid/MEDLINE, Web of Science, and Science Direct) and references of included articles were searched. Case reports were appraised using the Joanna Briggs Institute critical appraisal checklist for case reports. Patient demographics and key outcomes, including withdrawal characteristics and treatment characteristics, were collected into a predefined data collection sheet by six independent reviewers. RESULTS: Search results yielded 515 articles of which 25 were included. All articles were case reports or published conference abstracts. All of the cases (100 percent) involved male patients and the median age was 30 years, (interquartile range 23.5-34 years, range 4 days-68 years). The median daily phenibut dose prior to experiencing withdrawal was 10 g (interquartile range 4.75-21.5 g, range 1-200 g). The shortest duration of phenibut use (2-3 g daily) prior to withdrawal was one week. Withdrawal symptoms occurred as quickly as two hours after the last phenibut dose. Sixteen patients (64 percent) reported progression of withdrawal severity within the first 24 hours of healthcare contact. Seizures were reported in two patients (8 percent), intubation in six patients (24 percent), and intensive care unit admission in 11 patients (44 percent). Withdrawal patterns and outcomes were similar in those using phenibut alone and those with comorbid polysubstance use. Withdrawal treatment strategies varied widely. Only three cases (12 percent) were managed outpatient and all three utilized a phenibut tapering strategy. All patients undergoing medication-assisted abstinence were admitted inpatient for symptom management and received a drug that acts on gamma-aminobutyric acid receptors. The most commonly used medication was a benzodiazepine, reported in 17 cases (68 percent). Nineteen patients (76 percent) required at least two drug therapies to manage symptoms. Baclofen was used in 15 cases (60 percent), primarily in conjunction with gamma-aminobutyric acid type A agonists (12 of 15 cases) or as monotherapy during a phenibut taper (two of 15 cases). Two patients using baclofen monotherapy outpatient, after initial stabilization with multiple drug classes, reported adverse effects. One patient had a seizure and the other experienced recurrent withdrawal symptoms, returned to using phenibut, and was admitted to a hospital for withdrawal symptom management with benzodiazepines. LIMITATIONS: This review is subject to several limitations. Due to the manual nature of article selection, it is possible relevant articles may not have been included. As the entire data set is comprised of case reports it may suffer from publications bias. Outcomes and meaningful conclusions from specific treatment strategies were rarely available because of the heterogeneous nature of case reports. It is possible those reporting only phenibut use were actually using multiple substances. The doses of phenibut a user believed they were taking may be different from what was present in the unregulated product. CONCLUSIONS: Phenibut withdrawal appears to have a range of severity. It is important to recognize that patients undergoing phenibut abstinence may have progressive symptom worsening during early withdrawal. All published cases of abrupt phenibut abstinence were admitted inpatients for symptom management. Benzodiazepines or barbiturates with adjunctive baclofen appear to be the most commonly used drugs for moderate to severe withdrawal. Outpatient management via slow phenibut tapers with or without adjunctive gamma-aminobutyric acid agonist therapy may be successful. However, there is no standard treatment, and consultation with experts (e.g., toxicologists, addiction specialists) experienced in managing withdrawal syndromes is recommended. Significant study is warranted to develop methods of triaging phenibut withdrawal (e.g., severity scoring, inpatient versus outpatient management) and creating optimal treatment regimens.

Outcomes of pediatric ingestions of alcohol-based hand sanitizers during the COVID-19 pandemic.

INTRODUCTION: In July 2020, an outbreak of methanol-contaminated hand sanitizers in the United States prompted our regional poison center to implement a more conservative triage guideline for hand sanitizer exposures. All pediatric hand sanitizer ingestions of more than a "taste" were referred to a healthcare facility for assessment. We then evaluated the effect of this change on identifying patients with methanol poisoning. METHODS: This was a single-center, retrospective review of pediatric (<19 years) hand sanitizer ingestions reported to our poison center from May 1, 2020 through January 28, 2022. Methanol and ethanol concentrations were collected if available. RESULTS: During the study period, we received 801 calls regarding hand sanitizer exposure, of which 140 children were referred to a healthcare facility for hand sanitizer ingestions. Of those, 88 (63%) had methanol and/or ethanol concentrations measured. No child had a detectable methanol concentration, 78 had ethanol testing, and 12 had a detectable ethanol concentration. CONCLUSIONS: In this sample, no patient tested had a detectable methanol concentration. Children who consumed enough to have a detectable ethanol concentration were symptomatic or had an intentional ingestion. Asymptomatic children with unintentional ingestion of hand sanitizer were at low risk for methanol toxicity.

Incidence of rebound salicylate toxicity following cessation of urine alkalinization.

INTRODUCTION: Management of patients with salicylate toxicity frequently requires urine alkalinization to enhance excretion of salicylate. One strategy for determining when to stop urine alkalinization is to wait for two consecutive serum salicylate concentrations to be less than 300 mg/L (2.17 mmol/L) and declining. When alkalinization of the urine ceases, a rebound in serum salicylate concentration can occur from tissue redistribution or delayed gastrointestinal absorption. Whether this can lead to rebound toxicity is not well understood. METHODS: This was a single-center, retrospective review of cases with a primary ingestion of acetylsalicylic acid reported to the local poison center over a five-year period. Cases were excluded if the product was not listed as the primary ingestion or if there was no serum salicylate concentration documented after discontinuation of intravenous sodium bicarbonate infusion. The primary outcome was the incidence of serum salicylate rebound to a concentration greater than 300 mg/L (2.17 mmol/L) after discontinuation of intravenous sodium bicarbonate infusion. RESULTS: A total of 377 cases were included. Of these, eight (2.1%) had a serum salicylate concentration increase (rebound) after stopping the sodium bicarbonate infusion. All these cases were acute ingestions. Five of the eight cases had rebound serum salicylate concentrations that were greater than 300 mg/L (2.17 mmol/L). Of these five patients, only one reported recurrent symptoms (tinnitus). Prior to stopping urinary alkalinization, the last or the last two serum salicylate concentrations were less than 300 mg/L (2.17 mmol/L) in three and two cases, respectively. CONCLUSIONS: In patients with salicylate toxicity, the incidence of rebound in serum salicylate concentration after cessation of urine alkalinization, is low. Even if serum salicylate rebounds to supratherapeutic concentrations, symptoms are often absent or mild. Routine repeat serum salicylate concentrations after urine alkalinization is stopped may be unnecessary unless symptoms recrudesce.

Seizure Occurring During Baclofen Monotherapy for Phenibut Withdrawal.

OBJECTIVE: Phenibut is a widely available gamma-aminobutyric acid B receptor agonist. When taken chronically, phenibut causes dependence and subsequent withdrawal if stopped. Baclofen, a gamma-aminobutyric acid B receptor agonist structurally related to phenibut, has been used to manage phenibut withdrawal (PW), although baclofen doses for PW are not well defined and may exceed Food and Drug Administration-approved doses. Little data described outcomes from baclofen use. METHODS: This case details a patient who experienced a seizure while on baclofen 10 mg thrice daily as monotherapy for PW and highlights a potential risk of underdosing baclofen as monotherapy in the management of PW. RESULTS: A man in his early 30s with anxiety, depression, and substance use disorder presented to the emergency department by family for lethargy and confusion starting earlier that day. He had been using 25-30 g of phenibut daily for the past 6 months. On arrival, he was hypertensive, tachycardic, tachypneic, and lethargic. The patient received 1 mg of intravenous lorazepam and was admitted to the hospital for presumed PW. His symptoms improved overnight, and he was discharged on 10 mg of baclofen thrice daily. He returned 28 hours later after having a seizure and required intensive care admission in addition to multimodal drug therapy. CONCLUSIONS: Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.

QTc Prolongation in Poison Center Exposures to CredibleMeds List of Substances with "Known Risk of Torsades de Pointes".

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias.

Qualitative description of sexual harassment and discrimination of women in emergency medicine: Giving the numbers a voice.

Introduction: Gender disparities in medicine are well documented; however, little qualitative data exist. This study sought to provide a qualitative assessment of harassment and discrimination experienced by female physicians in emergency medicine (EM) specifically by colleagues or supervisors. Methods: An electronic survey was distributed to female EM physicians on October 18, 2018, asking if they have felt harassed, diminished, uncomfortable, or discriminated against by a male colleague or supervisor at work based on a sexual comment or unwanted advance. Space for descriptive experiences was provided. A data abstraction tool was developed, and experiences were placed into thematic categories. The survey was closed on December 18, 2018, and data were analyzed. Results: There were 1280 responses. Responses that were incomplete, not attributable to women, and outside of EM were excluded leaving 1144 to be analyzed. Respondents were primarily White (81%) and working in nonacademic environments (53.5%). The majority (57.3%) felt harassed, diminished, uncomfortable, or discriminated against by a male colleague or superior at work based on sexual comment or innuendo; 22.3% experienced an unwanted sexual act or advance. There were 482 descriptive experiences reported, most frequently focusing on patronizing behavior (16.5%), pregnancy/maternity leave (15.9%), and physical appearance (12.5%). Conclusions: Women in EM experience sexual harassment and discrimination at work by their peers and supervisors. Exploring the themes of their shared experiences can guide and focus efforts on both prevention and intervention. Further studies are needed to determine if these experiences contribute to disparities in earnings, promotion, and leadership roles of women in medicine.

Hemolysis after subcutaneous deoxycholic acid overdose.

This report describes a case of hemolysis in a patient injecting deoxycholic acid and benzyl alcohol for aesthetic benefit without medical supervision. The concentration and dose injected by the patient resulted in a 10-fold overdose of deoxycholic acid in comparison to the FDA-recommended dosing for the approved indication. Providers should be aware of medically unsupervised use of DCA and other injectables and the potential risks associated with this practice.

Implementation and evaluation of an interprofessional physical assessment skills workshop for Wisconsin pharmacists.

BACKGROUND: Pharmacists have a critical, expanding role in health care delivery. In particular, pharmacists in community pharmacy and ambulatory care settings are important and frequent access points for health care services. OBJECTIVE: We describe the interprofessional development and implementation of an interactive, broadly applicable physical assessment skills-based continuing pharmacy education program to provide an avenue for the attainment of this warranted set of skills for pharmacists who desire to provide advanced patient care services in their respective practices. METHODS: Pharmacists, in collaboration with family medicine and emergency medicine physicians, developed workshop content, design, and flow. The structure of the workshops consisted of didactic training, hands-on practical application, simulated practice, and case-based certification examinations. RESULTS: On a postworkshop survey, all respondents answered "agree" or "strongly agree" when asked if the workshops were useful, advanced their skills, and advanced their confidence. It was also found that more than 50% of the participants used their physical assessment skills monthly and 11% daily. The most common assessment performed was obtaining an accurate manual blood pressure. CONCLUSION: The interprofessional development and implementation of workshops dedicated to physical assessment skills education is feasible and led to the incorporation of these skills into pharmacists' practice, particularly in the community and ambulatory care settings.

Complications from Needle Thoracostomy: Penetration of the Myocardium.

We report a rare but serious complication of needle thoracostomy, penetration of the myocardium. Needle thoracostomy is typically performed in the prehospital setting or upon arrival in the emergency department for suspected tension pneumothorax. Needle decompression is generally taught and done anteriorly, in the 2nd intercostal space on the midclavicular line (MCL). An alternative approach is laterally, along the anterior axillary line (AAL) in the 4th intercostal space. Our case supports prior literature that the anterior MCL location has a low rate of efficacy to decompress the chest, as well as a high rate of complications. We recommend performing needle decompression laterally at the AAL whether in the field or in the emergency department.

Trioxane Ingestion in a Child.

Trioxane is a stable cyclic trimer of formaldehyde. It is an active ingredient in fuel bars for heating prepackaged foods by military and outdoorspeople. Trioxane depolymerizes to formaldehyde in an acidic environment and is further oxidized to formic acid, which causes neurologic and ocular damage. Because it is solid at room temperature, trioxane is a greater potential hazard to children than aqueous formaldehyde. Little information is available regarding the management of ingestion of solid, compressed fuel bars. We present a case of a 19-mo-old male child who ingested an unknown amount of a trioxane fuel bar, with fortunately limited consequences.

Carbon monoxide detector effectiveness in reducing poisoning, Wisconsin 2014-2016.

Introduction: Carbon monoxide (CO) is a colorless, odorless, and nonirritating gas. The most common exposures are from gas powered appliances such as furnaces, water heaters, stoves, and vehicles. To prevent poisoning, CO detectors with audible alarms were developed. This study aims to evaluate the effectiveness of CO detectors in reducing poisoning in Wisconsin.Methods: Records were queried from National Poison Data System for unintentional CO exposures that occurred in residences in Wisconsin during 2014-2016 (N = 703). After applying sample exclusion criteria, notes were abstracted for cases where CO detector use was mentioned (n = 408). Logistic regression analyses were used to assess the association between having a CO detector alarm and CO poisoning. Linear regression analyses were used to assess the relationship between having a CO detector alarm and poisoning severity.Results: In logistic models, odds of CO poisoning were 3.2 times higher (95% CI: 1.5, 6.9) among those who had no CO detector compared to those who had a CO detector that alarmed. In linear models, not having a CO detector was associated with a 0.34 point (95% CI: 0.17, 0.54) change in outcome severity score compared to having a CO detector that alarmed.Discussion: Individuals who were exposed to CO in the absence of a CO detector were more likely to be poisoned and to have more severe medical outcomes than those that had a CO detector that alarmed.

Time to development of metformin-associated lactic acidosis.

Objective: Metformin-associated lactic acidosis (MALA) is a complication of metformin overdose. Recommendations for observation time after an acute ingestion to monitor for MALA vary. The aim of this study was to characterize the time to development of MALA after an acute metformin overdose.Methods: Utilizing Crystal Reports (Version 11.0), all metformin cases reported to the Illinois Poison Center (IPC) with a National Poison Data System (NPDS) clinical effects code of "acidosis" or "anion gap" were retrospectively queried over a 14-year period (2001-2014). Demographic data, time to MALA, co-ingestants, therapeutic modality use, and case outcome were extracted. Interrater reliability was assessed using kappa analysis.Results: A total of 88 cases were identified of which 44 met criteria for MALA; 40 were acute, acute on chronic, or unknown ingestions. The remaining four were chronic ingestions which were excluded. The mean age was 41 years (range 19-79 years). Most were female (55.0%) and over half (62.5%) were acute on chronic ingestions. Hypoglycemia was seen in three ingestions of metformin only. Of the 40 MALA cases, 18 developed MALA less than or equal to 6 h after ingestion, 9 between 6-12 h, 3 after 12 h, and 10 patients had an unknown time to MALA. The only death in the cohort had MALA detected beyond the typical 6-h observation period. Of the exposures when time to MALA was known, 40% (12/30) developed MALA greater than 6 h post ingestion.Conclusion: A 6-h observation period after a single acute ingestion of metformin may be inadequate, as a significant portion of exposures developed MALA beyond this time. We recommend a minimum of 12 h of observation following an acute overdose. Further study defining prospectively the time to development of MALA may improve management of this population.

Pelvic organ prolapse: An unusual cause of small bowel obstruction.

We present the rare case of a small bowel obstruction secondary to pelvic organ prolapse (POP). A 77-year-old female presented with four days of abdominal pain, nausea, and vomiting. She had a history of abdominal hysterectomy with bilateral salpingo-opherectomy and a mildly symptomatic cystocele. She was found to have an enterocele causing small bowel obstruction. The enterocele was manually reduced and subsequently managed non-operatively with a pessary. Prior case reports of small bowel obstructions secondary to POP required emergent surgical intervention. Post-menopausal women should be asked about symptoms or presence of pelvic organ prolapse and in the correct patient population, pelvic examination can be important for diagnosis and treatment of small bowel obstruction. If the enterocele is manually reduced non-operative management can be safe and effective.

Folate as an Adjuvant Therapy in Methanol Poisoning.

Folate and its derivatives have long been used as an adjunctive treatment in methanol poisoning. Methanol is ultimately metabolized to formate, the toxic compound. The accumulation of formate can lead to acidemia, retinal damage, visual impairment, and death. Formate is converted to carbon dioxide and water in a folate-dependent manner, and folate is often given in cases of methanol poisoning. In this paper, the evidence for folate as an adjunctive therapy in methanol poisoning is reviewed.

Exposures to Opioids Among Wisconsin Children and Adolescents, 2002-2016.

BACKGROUND: Opioid overdoses and opioid-related fatalities have increased dramatically in Wisconsin over the past decade. The observed rise in morbidity and mortality parallels increased opioid prescribing and greater use of illicit drugs such as heroin. Increased availability of both prescription and illicit opioids may increase the risk of exposure and overdose among the pediatric population. METHODS: We examined demographics and temporal trends in opioid exposures among children aged 0-19 years using hospital encounter and Wisconsin Poison Control Center (WPC) data. Exposures were categorized by type of opioid. RESULTS: We identified 3,320 WPC calls and 2,725 hospital encounters involving opioids during 2002-2016. Within the hospital encounter data, the rate of opioid-involved exposures increased significantly in children aged 0-5 years and adolescents aged 13-19 years. The majority of opioid-related hospital encounters involved prescription opioids. However, the proportion of hospital encounters involving heroin increased significantly among 13-19 year olds from 2002-2016. Within WPC data, the proportion of calls involving tramadol increased among 0-5 year olds and 13-19 year olds. However, calls about opioid/acetaminophen combinations decreased significantly as a proportion of opioid exposures. DISCUSSION: These findings suggest the need for caregiver education regarding safe storage and disposal of prescription opioids to prevent unintentional or intentional exposure to these substances among young children and adolescents. Overdose rates among teens continue to rise and an increasing proportion are due to heroin; comprehensive treatment and prevention strategies targeting this demographic are needed.

The Beef Jerky Blues: Methemoglobinemia From Home Cured Meat.

Methemoglobinemia can result from ingestion of nitrite- or nitrate-containing foods. Here, we report a case where an adolescent girl and her father developed clinically significant methemoglobinemia after ingestion of "homemade" beef jerky prepared with sodium nitrate salt purchased at a local grocery store. Both had palpitations, dyspnea, and visible mucosal cyanosis. The daughter had a methemoglobin level of 44.2% and the father's methemoglobin level was 34.2%. Prompt recognition of methemoglobinemia is important for initiating antidotal therapy with methylene blue.

The general approach to the poisoned patient.

The poisoned patient can present many challenges to the healthcare practitioner. An organized and thoughtful approach to the poisoned patient is necessary. Understanding the nuances of a toxicological history and physical examination can aid in the management of these patients. Supportive care with attention to the body systems at risk from the poisoning is the mainstay of therapy. Consultation with a medical toxicologist or regional poison control center can positively impact diagnosis, management, and disposition of poisoned patients.