Hunter Criteria Research Articles

Is the combination of domperidone and metoclopramide increasing the risk of developing serotonin syndrome?: a case report

Metoclopramide and domperidone are dopamine antagonists that can cause an acute dystonic reaction. Metoclopramide is a rare but major contributor to serotonin syndrome, particularly when used with other serotonergic agents. Serotonin syndrome is a rare, potentially life-threatening adverse reaction characterized by a triad of altered mental status, autonomic dysfunction, and neuromuscular hyperactivity that typically results from exposure to serotonergic agents. Herein, we report a previously healthy 9-year-old girl who was brought to the emergency department with an alteration in the level of conscious and involuntary repetitive movements after approximately 24 hours of receiving a therapeutic dose of metoclopramide and domperidone. Physical examination showed tachycardia, hyperthermia, and a Glasgow Coma Scale score of 11, as well as mydriasis and hyperreflexia. In addition to resolving the symptoms after administering midazolam and diphenhydramine, the diagnosis of serotonin syndrome was made based on the classical symptoms and signs, which met the Hunter criteria. This case indicates the need for clinical awareness of the life-threatening syndrome and caution with medications having potential interactions with metoclopramide.

Cyproheptadine in serotonin syndrome: A retrospective study.

Serotonin syndrome (SS) is an iatrogenic life-threatening condition caused by serotonergic agents. The treatment for SS involves the administration of a serotonin antagonist (cyproheptadine). However, the dosing schedule for cyproheptadine is not uniform in the literature. We retrospectively evaluated 23 adult patients (>18 years) admitted to the Neurology Department and met the Hunter criteria for SS. The mean age was 35.2 years, and 52% were female. Ten patients were managed in the intensive care unit (ICU), whereas thirteen patients were admitted to the ward. Hyperreflexia was the most common clinical feature (100%), followed by clonus (91%), tachycardia (83%), and tremor (83%). Other common clinical features were rigidity (65%), increased bowel sound (61%), diaphoresis (48%), fever (43%), hypertension (39%), and myoclonus (30%). All but one patient received two or more serotonergic drugs. Tramadol was the most common serotonergic agent (39%), followed by sodium valproate (21%), and amitriptyline (21%). Cyproheptadine was administered to all patients. All patients admitted in the ICU received a loading dose of 12 mg followed by 2 mg every 2 h for at least 24 h. All patients admitted to the ward were given 4 mg of cyproheptadine three times each day. Every patient showed at least some response to cyproheptadine within 24 h. The total doses of cyproheptadine and the length of treatment differed between patients. Any response to cyproheptadine at a therapeutic dose within 24 h, even a partial one, could be a diagnostic indicator of the existence of SS.

P524 Etrasimod shows low risk of adverse events following concomitant use with opioids or antidepressants in patients with ulcerative colitis

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the other S1P receptor modulator approved for UC, etrasimod and its metabolites do not have a molecular structure to inhibit monoamine oxidase (MAO).1 Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs), including hypertension.2 This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials. Methods Safety data pooled from both trials were analysed in patients receiving etrasimod 2 mg QD (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥1 concurrent AE potentially related to serotonin syndrome, consisting of one standardised MedDRA Query, one query based on the Hunter Criteria and supplemental preferred terms (pyrexia, tachycardia and hypertension-related AEs).3 Results Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) patients were taking concomitant opioids or antidepressants, respectively. Most patients on concomitant opioids or antidepressants were White (80.0–88.3%); male (50.6–51.4%); their median age was 35.0 (18.0–70.0) and 41.0 (19.0–74.0) years, respectively. More patients with vs without concomitant opioids or antidepressants, respectively, consumed alcohol (40.3% vs 24.7% and 48.6% vs 25.4%) and used tobacco (40.3% vs 20.9% and 34.3% vs 23.0%). The incidence of other AEs potentially related to serotonin syndrome was low and generally comparable in all subgroups; reported rates of pyrexia and tachycardia were similar in patients with/without concomitant opioids or antidepressants (Table). Hypertension-related AEs were infrequent and generally balanced. No AEs per the Hunter Criteria were reported in patients on concomitant opioids or antidepressants (Table). No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications. Conclusion The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis supports the low likelihood of clinically relevant drug–drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants.

Serotonin syndrome in the acute treatment landscape of migraine: the lasmiditan experience.

Serotonin syndrome (SS) symptoms overlap with adverse events associated with lasmiditan, a 5-HT (serotonin)1F receptor agonist for acute treatment of migraine. Because SS symptoms are heterogeneous, diagnosis can be challenging, and potential cases observed with lasmiditan treatment led to questions about SS pathophysiology. Here, we provide an overview of the potential risk of SS based on experience with lasmiditan. Results of eight phase 2 and phase 3 lasmiditan trials (n = 5,916) and a controlled intravenous trial of lasmiditan (n = 88) were analyzed for symptomatology consistent with SS. Post-marketing surveillance data from lasmiditan's US launch date (January 2020) until data cut-off (April 2021) were also examined. Established Sternbach and Hunter diagnostic criteria were used for formal determination of SS. Of 6,004 lasmiditan-treated clinical trial patients, 15 reported ≥1 treatment-emergent adverse event consistent with signs and symptom(s) of SS. After review, one case met Sternbach and Hunter criteria, two cases potentially met Sternbach criteria, and three cases reported as SS had limited/no information to determine if either criterion was met. During post-marketing surveillance (approximately 13,400 lasmiditan prescriptions), 17 cases with symptom complexes consistent with SS were reported; 3/17 cases had adequate case descriptions to apply predefined criteria. Of these, two met Sternbach and Hunter criteria, and one met Sternbach criteria. Awareness of clinical symptomatology and diagnostic criteria of SS can help clinicians with recognition of rare instances of SS that may occur with lasmiditan. NCT03670810, NCT00384774, NCT00883051, NCT02565186.

Real-world evaluation of linezolid-associated serotonin toxicity with and without concurrent serotonergic agents

The risk of linezolid-associated serotonin toxicity remains unclear. This study sought to evaluate the incidence of serotonin toxicity among hospitalized patients who received linezolid with or without concurrent serotonergic agents (SAs). Secondary outcomes were to assess the dose, agent selection and number of SAs. A single-centre, retrospective cohort study of hospitalized patients aged ≥18 years who received at least one dose of linezolid with or without SAs between 1 January 2014 and 30 June 2021 was performed. Patients were excluded if they were aged <18 years, had linezolid ordered but not administered, were pregnant or were incarcerated. Up to five concurrent SAs were assessed, and dose category was classed as low, moderate or high (dose <33%, 33-66% or >66% of maximum daily dose, respectively). Serotonin toxicity was identified by searching patients' electronic medical records. If identified, the Sternbach criteria and Hunter criteria were applied. Of 2022 patients screened, 1743 were included in this study. Mean age, weight and linezolid duration were 58.5 years, 90.7 kg and 3.8 days, respectively. Approximately 67% (1168/1743) of patients received linezolid with at least one SA, and several patients received multiple SAs. Most patients (53.8%; 616/1144) received moderate- and/or high-dose SAs. Only two patients (0.11%) were identified as possible cases of serotonin toxicity based on the electronic medical record search. However, the incidence of serotonin toxicity was 0.06% (1/1743) based on the Sternbach criteria and 0% (0/1743) based on the Hunter criteria. Serotonin toxicity among hospitalized patients who received linezolid with or without SAs was exceedingly rare, even among those who received multiple and high-dose SAs.

Risk Factors and Clinical Correlates of Pediatric Serotonin Syndrome in Hospitalized Suicide Attempters

To evaluate the risk factors and clinical correlates of pediatric serotonin syndrome (SS) given that research on SS in adults exists, there is a dearth of literature on pediatric SS. We conducted a retrospective chart review of 183 pediatric patients who were medically hospitalized after a suicide attempt. We investigated associations between SS and several of its risk factors and clinical correlates. We also assessed the sensitivity/specificity of Hunter's criteria and criterion symptoms in predicting SS. SS occurred in 21.7% of patients with a serotonergic overdose. Recent marijuana use and overdose on a selective serotonin reuptake inhibitor were significantly associated with SS. Individuals with SS required a greater number of days to be medically stabilized and had a greater likelihood of being placed on a ventilator during treatment. Hunter's criteria had 66.7% sensitivity and 92.3% specificity in diagnosing SS. Our study reveals both novel risk factors associated with SS (eg, recent marijuana use) and clinical correlates for patients with pediatric SS. In children, Hunter's criteria appeared to have good specificity but poor sensitivity in identifying SS. Our results set the stage for future work aimed at enhancing clinicians' ability to more rapidly identify and treat pediatric SS.

741. Evaluation of Serotonin Syndrome with Linezolid and Serotonergic Agents at an Academic Medical Center

Abstract Background The risk of linezolid-associated serotonin syndrome based on the potency and number of serotonergic agents is unclear. Thus, the primary outcome was to evaluate the incidence of serotonin syndrome among hospitalized patients who are concurrently receiving linezolid with or without serotonergic agents. Secondary outcomes were to assess the potency, agent selection, and number of serotonergic agents. Methods This was a single-center, retrospective cohort study of hospitalized patients &amp;gt;18 years of age who received &amp;gt;1 dose of linezolid with or without a concurrent serotonergic agent between 1/1/14–6/30/2021. Patients were excluded if &amp;lt; 18 years of age, had linezolid ordered but not administered, were pregnant, or incarcerated. Up to five concurrent serotonergic agents were recorded and potency was divided into low, moderate, and high potency based on if the drug strength was &amp;lt; 33%, 33–66%, and &amp;gt;66% of the maximum daily dose, respectively. Serotonin syndrome was identified by searching patients’ electronic medical record for ‘serotonin syndrome’ or ‘serotonin toxicity’. If either term was identified, Hunter and Sternbach criteria were applied. Descriptive statistics including number (percentages) and mean (standard deviation) were used. Results Of 2022 patients screened, 1743 were included. Mean age, weight, and linezolid duration were 58.5 years, 90.7 kg, and 4.1 days, respectively. Of patients included who received linezolid, 43.2%, 16.2%, 5.7%, 1.4%, and 0.5% received at least one, two, three, four, and five concurrent serotonergic agents, respectively. Most patients received either a moderate and/or high potency (53.8%) compared to a low potency serotonergic agent (46.2%). Only 2 patients (0.11%) were identified with ‘serotonin syndrome’ or ‘serotonin toxicity’. Patient 1 received escitalopram moderate potency and trazodone low potency but did not meet either Hunter or Sternbach criteria. Patient 2 received duloxetine moderate potency, vilazodone moderate potency, and metoclopramide low potency but only met Sternbach criteria. Conclusion Serotonin syndrome among hospitalized patients receiving linezolid with other serotonergic agents was exceedingly rare, even among those who received multiple and more potent serotonergic agents. Disclosures Wesley D. Kufel, Pharm.D., BCPS, BCIDP, AAHIVP, Melinta: Grant/Research Support|Merck: Grant/Research Support|Theratechnologies, Inc.: Advisor/Consultant.

Risk of serotonin syndrome in acutely ill patients receiving linezolid and opioids concomitantly: a retrospective cohort study

IntroductionLinezolid is an oxazolidinone antibiotic with a reversible, non-selective, monoamine oxidase inhibitory effect. Combining linezolid with serotonergic agents may increase serotonin syndrome (SS) risk.Linezolid is recommended in patients with suspected or confirmed resistant Gram-positive bacterial infections, especially if vancomycin cannot be used. However, it is unclear whether co-administration of linezolid with opioids increases the risk of serotonin syndrome. Research objectiveTo establish whether combining linezolid with opioids will increase the incidence of SS in acutely ill patients. MethodsThis was a retrospective observational study. All adult patients who were admitted and received linezolid between March and September 2020 were included in the study. The primary outcome was the prevalence of SS, as defined by Hunter's criteria. ResultsThe study included 106 patients, most whom were males (91.5%). More than half of the cohort (56.6%) received a concomitant opioid agent. Morphine and fentanyl were the most prescribed opioids (37.7% and 34%, respectively). Among patients who received opioids, only one patient (1.6%) had spontaneous clonus. However, this patient developed spontaneous clonus post cardiac arrest, which made an association with the linezolid–opioids combination less likely. ConclusionIn this study, the incidence of SS was low in acutely ill patients who received concomitant linezolid and opioids. However, larger prospective studies are required to confirm this finding.

Serotonin syndrome as a complication of opioid withdrawal therapy (clinical case)

Serotonin syndrome is a dangerous, potentially fatal condition resulting from increased intrasynaptic serotonin levels, leading to activation of serotonin 5‑HT2A receptors in the central nervous system (CNS). The most common iatrogenic cause of this syndrome is the prescription of serotomimetic agents (selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic and tetracyclic antidepressants, etc.). Excess serotonin in the CNS manifests itself as neuromuscular hyperactivity, autonomic dysfunction, and changes in mental status. Symptoms occur suddenly and progress rapidly: in 60 % of cases they appear within 6 hours of administration, and after 24 hours, clinical manifestations are observed in &gt; 85 % of patients. Due to the lack of specific laboratory criteria, Hunter criteria and Sternbach criteria have been adopted for diagnosing this syndrome. The purpose of the work: to analyze pharmacotherapy of a patient with opioid withdrawal syndrome to assess its rationality and possible complications.

A Cross-sectional Analysis of Linezolid in Combination with Methadone or Buprenorphine as a Cause of Serotonin Toxicity.

BackgroundSerotonin toxicity (also referred to as serotonin syndrome) results from medications that affect the neurotransmitter serotonin. The antibiotic linezolid and the opioids methadone and buprenorphine are all reported to cause serotonin toxicity, but the degree of risk with use of linezolid in combination with methadone or buprenorphine is unknown.MethodsWe conducted a retrospective cross-sectional analysis of adult patients hospitalized from November 2015 to October 2019 who were administered linezolid in combination with methadone and/or buprenorphine within 24 hours and a subgroup that received the combination for ≥3 days. Cases of serotonin toxicity were identified from the clinical notes in the electronic medical record and were classified as possible or definite based on the clinical record. The Hunter diagnostic criteria were retrospectively applied.ResultsThere were 494 encounters in which linezolid was administered concurrently with methadone and buprenorphine. The mean patient age was 42.5 years, and 52.4% of encounters were of female patients. The mean duration of concurrent administration was 1.9 days. There were 106 encounters with a duration of concurrent administration ≥3 days (mean, 5.4 days). Two cases of possible serotonin toxicity and 0 cases of definite serotonin toxicity occurred; neither possible case met the Hunter criteria from the available information. Possible cases occurred in 0.40% of all encounters and 1.89% of encounters with ≥3 days of overlap (upper 1-sided 95% CI, 0.87% and 4.06%).ConclusionsSerotonin toxicity occurring during the administration of linezolid in combination with methadone and/or buprenorphine occurred rarely among 494 hospital encounters, including 106 encounters with ≥3 days of overlap. Limitations include potential missed diagnoses of serotonin toxicity and short durations of overlap. Further study evaluating the short-term risk of this combination is needed.

EVALUATION OF RESULTS OF NON OPERATIVE TREATMENT OF FRACTURE SHAFT OF THE HUMERUS WITH A FUNCTIONAL BRACE

Introduction: Fractures of the humeral shaft account for roughly 3% of all fractures due to fall on the outstretched hand, motor vehicle accidents and direct loads to the arm. The brace effectively compresses the bulky biceps and triceps muscle allowing early shoulder, elbow, wrist and hand motion with nonunion and radial nerve palsy in a signicant percentage of humeral shaft fractures. This study intends to assess the results of non-operative treatment of fracture shaft of the humerus with a functional brace. Materials and Methods: Prospective observational study was conducted in NMCTH, Birgunj among 50 patients from 16 years onwards of age who presented with fracture of humerus shaft. The patients with open fracture, oating elbow, bilateral humeral fracture, polytrauma, pathological fracture, additional injury of the extremities and patients with neurologic and psychiatric disorders were excluded from the study. The patients were treated with close reduction and immobilization in functional humeral cast brace and were followed up in outpatient department basis once a week for the rst four weeks and every four weeks subsequently till fracture united. After removal of brace functional evaluation of results of upper limb was done according to Hunter's criteria. RESULTS: Six patients out of 50 lost to follow up and was removed from nal analysis . Out of 44 cases, mean age of patient was 34.77 year. Most of them 28(64%) were male. RTA was most common mode of injury 24(54%). Most of the patient 26(59%) had rd fracture on non dominant side. Majority of the fractures 24(55%) were in the middle 1/3 . Thirty two cases (72%) attended the hospital within 24 hours of injury. Union was achieved in 41(93%) patients within a mean time of 11.48 weeks. One transverse and two comminuted fractures in middle and distal third of diaphysis did not unite and were treated surgically. According to Hunter's criteria of evaluation of results, 31(75.6%) of united fractures had excellent (G5) and 10(24.4%) had good (G4) results. Restriction of few degrees of terminal range of movements of shoulder abduction and external rotation present initially improved subsequently after physiotherapy. Mean varus angulation in 39 patients at the time of removal of brace was 7.05° and mean valgus angulation in four patients was 6.00°. Mean anterior angulation of 6.85° was present in 21 patients and mean posterior angulation of 7.11° was present in 20 patients at the time of removal of brace. Mean shortening of 6.5 mm was present in 36 patients. The various angulation deformities and shortening at the end of union did not cause functional and cosmetic effect. Conclusion: Fracture shaft of humerus treated by close reduction and functional bracing has good functional outcomes.

Drug interaction between a selective serotonin reuptake inhibitor and a triptan leading to serotonin toxicity: a case report and review of the literature

BackgroundSerotonin toxicity is a known side effect of selective serotonin reuptake inhibitors and has previously also been described as a possible side effect of 5-hydroxytryptamine receptor agonist (triptan) medications. However, the literature is conflicted about the risk of developing serotonin toxicity as a result of drug interaction between selective serotonin reuptake inhibitors and triptans.Case presentationA 30-year-old Caucasian woman with a history of depression on regular fluvoxamine presented to the emergency department with right-sided facial and lower limb twitching. The patient had recently been prescribed sumatriptan for migraines and had taken her first ever dose shortly prior to the onset of symptoms. She was tachycardic, diaphoretic, and hypertonic on initial assessment with bilateral lower limb and ocular clonus. Electrocardiogram showed sinus tachycardia with QT interval under the treatment interval, and pathology and imaging findings were unremarkable. Her symptoms improved with supportive management and cyproheptadine.ConclusionsThis patient’s presentation fulfilled both Sternbach and Hunter criteria for serotonin toxicity, illustrating a potential case of serotonin toxicity as a result of drug interaction between a selective serotonin reuptake inhibitor and a triptan.

Chronic serotonin syndrome: A retrospective study.

BACKGROUNDSerotonin syndrome (SS) is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin. Very limited information is available about chronic SS.AIMTo evaluate the epidemiological, clinical, and other aspects of the insidious onset SS.METHODSWe retrospectively evaluated 14 consecutive adult patients (> 18 years) who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS.RESULTSThe mean age was 41.1 years (range: 21-61 years), with a male preponderance (64%). Although tremors were observed in all patients, this was a presenting complaint in only 43% of patients. Generalized body pain, insomnia, and restlessness were common presenting features (50% each). Other common clinical features were stiffness of the limbs (43%), diaphoresis (43%), gait disturbances (36%), bowel disturbances (36%), dizziness (29%), sexual dysfunctions (21%), incoordination (14%), and fatigue (14%) The mean duration of symptoms before the diagnosis of SS was 13.5 ± 5.8 wk (range: 6-24 wk). Amitriptyline was the most common drug (n = 6, 43%), followed by tramadol (n = 5, 36%) and sodium valproate (n = 5, 36%). All patients received cyproheptadine, a 5- hydroxytryptamine2A antagonist, as treatment and noted an excellent response over the course of 4-14 d.CONCLUSIONThis study represents the largest study on chronic SS. We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.

Neuroleptic Malignant Syndrome and Serotonin Syndrome

Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are iatrogenic life-threatening conditions with similar clinical symptoms. Altered mental status, rigidity, and autonomic instability are common in both serotonin overload and toxic dopamine antagonism. It is paramount that providers understand the key differences between these two pathologies, as pharmacologic treatments can exacerbate the condition if SS is mistaken for NMS or vice versa. Hyperreflexia, clonus, diarrhea, and vomiting suggest the excessive activity of serotonin circuits in SS, whereas prominent rigidity and hyporeflexia suggest the underactivity of dopamine circuits in NMS. Supportive care and discontinuing the offending agent(s) are keys to treating both syndromes, but serotonin antagonists (eg, cyproheptadine) could be helpful in SS, whereas NMS may sometimes benefit from muscle relaxants (eg, dantrolene) and dopamine agonists (eg, bromocriptine). Following recovery, decisions about further use of an inciting agent (or similar agents) require reconsideration of risks, benefits, and alternatives, based on newly realized hazards. It is usually important to wait at least 2 weeks before rechallenge with any drugs resembling the inciting agents. This review contains 1 figure, 8 tables, and 32 references. Key Words: bromocriptine, cyproheptadine, dantrolene, Hunter criteria, neuroleptic malignant syndrome, parkinsonism, serotonin syndrome

The prevalence of serotonin syndrome in an intensive care unit: A prospective observational study.

In spite of life-threatening nature of serotonin syndrome (SS), it remains an under-diagnosed condition. The availability of epidemiological data about SS, especially in the ICU setting, may help physicians make early diagnoses and interventions. This was a 6-month prospective study in a medical ICU of a tertiary hospital to find out the prevalence of SS. All consecutive adult patients admitted to the medical ICU were evaluated to see if they fulfilled the Hunter criteria of SS. Patients who met the Hunter criteria were evaluated further for other details. Overall, 309 patients were identified of which 24 (7.8%) met the Hunter criteria. The mean age was 52.4years, and 75% were male. Most patients received two or more serotonergic drugs. Ondansetron was the most common serotonergic drug (58%), followed by tramadol (38%), and cough syrup (dextromethorphan or chlorpheniramine, 21%). None of the patients received a diagnosis of SS by the treating physicians. Chronic obstructive pulmonary disease exacerbation with respiratory failure and metabolic encephalopathy were the two most common admission diagnoses (17% each). Twenty-two patients received cyproheptadine. There were no fatalities. SS is not uncommon in the ICU setting. There is a need to increase awareness among physicians.

A DANGEROUS DRUG AND HERBAL MIXTURE

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Serotonin syndrome (SS) is a life threatening disorder characterized by autonomic dysfunction, altered mental status and neuromuscular excitation (1). Muscle rigidity and hyperthermia can cause cellular damage and enzyme dysfunction leading to rhabdomyolysis, myoglobinuria, metabolic acidosis and multi-organ failure (1). SS is associated with drugs that decrease serotonin breakdown, reuptake or increase its release (1). CASE PRESENTATION: A 20-year-old male with depression, anxiety and substance abuse, presented with dyspnea for two weeks accompanied by non-productive cough and palpitations. For the past two days he reported insomnia and anorexia. His symptoms began after taking phenylethylamine (40 mg daily) and most recently Katrom (Mitragyna speciosa) for his mood. In addition, he takes perphenazine 2 mg-amitriptyline 10 mg per day prescribed by his psychiatrist for anxiety. Bupropion and sertraline were recently discontinued due to lack of symptomatic improvement. He was hemodynamically stable and afebrile, but he was tachycardic, tachypneic without hypoxemia. His neurological examination was significant for bilateral jerk nystagmus, clonus, tremor and hyperreflexia in all four extremities. Patient met Hunter criteria for serotonin syndrome and was admitted to the intensive care unit. EKG showed sinus tachycardia with normal QT interval. Laboratory showed rhabdomyolysis (creatinine phosphokinase (CK) 5068 U/L), mild transaminitis (ALT 50 U/L, AST 97 U/L) and anion gap metabolic acidosis with a bicarbonate of 8 mmol/L. Renal function was normal without electrolyte disturbances. Serum acetaminophen, alcohol, salicylate and lactic acid levels were normal. Urine drug screen was negative. However, urine organic acid panel was significant for elevated ketones and phenylacetate levels. Patient was placed on an intravenous bicarbonate infusion and benzodiazepines with resolution of neurological symptoms within 2 days. The psychotropic agents were discontinued as well. Acid-base balance and CK levels normalized. DISCUSSION: Multiple medications including herbal supplements increase the risk of SS. Phenylethylamine is an "endogenous amphetamine" metabolized by monoamine oxidase to phenylacetate (2). Additionally, Kratom is an understudied psychoactive plant, with stimulant and opiate effects (3). However, it is unclear how much this drug contributed to the development of symptoms. Literature on the acute toxicity of Kratom is confounded by the concomitant use of other drugs (3). CONCLUSIONS: Early recognition of SS is essential to initiate supportive treatment and stop all potential substances responsible for serotonin mediated toxicity. It is important to recognize herbal medications as a potential cause of SS. Reference #1: Wang RZ, Vashistha V, Kaur S et al. Serotonin Syndrome: Preventing, recognizing, and treating it. Cleveland Clinic Journal of Medicine. 2016; 83 (11): 810-817. Reference #2: Irsfeld M, Spadafore M and PruB B. β-phenylethylamine, a small molecule with a large impact. Webmedcentral. 2014; 4(9): 1-15. Reference #3: Swogger MT and Walsh Z. Kratom use and mental health: A systematic review. Drug and Alcohol Dependence. 2018; 183: 134-140. DISCLOSURES: No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Ximena Solis, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response

Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial.

Cryptococcal antigen (CrAg) screening in HIV-infected persons with CD4<100 cells/µl can reduce meningitis and death, yet preemptive fluconazole therapy fails in ∼25%. Sertraline has in vitro and in vivo activity against Cryptococcus and is synergistic with fluconazole in mice. We evaluated the efficacy and safety of sertraline in asymptomatic cryptococcal antigenemia. We conducted a randomized trial of asymptomatic CrAg-positive Ugandans from November 2017 to February 2018. All subjects received WHO standard therapy of fluconazole 800mg for 2 weeks, then 400mg for 10 weeks, then 200mg through 24 weeks. Participants were randomized to receive adjunctive sertraline or placebo, given in once-weekly escalating 100mg/day doses up to 400mg/day, which was then given for 8 weeks, then tapered. The primary endpoint was meningitis-free 6-month survival. The data and safety monitoring board halted the trial after 21 subjects were enrolled due to safety concerns. Meningitis-free 6-month survival occurred in 9 of 11 of placebo participants and 10 of 10 of sertraline participants. However, seven serious adverse events (SAEs) occurred (n=4 sertraline group; n=3 placebo group). Three SAEs in the sertraline group presented with psychosis and aggressive behavioral changes with one meeting Hunter's criteria for serotonin syndrome while receiving 200mg/day sertraline. Two transient psychoses were associated with antecedent fluconazole and sertraline interruption. The serotonin syndrome resolved within 1 day, but psychosis persisted for 4 months after sertraline discontinuation. Sertraline was associated with excess SAEs of psychosis. Due to early stopping, we were unable to determine any efficacy for cryptococcal antigenemia.

Serotonin syndrome: a clinical review of current controversies.

Serotonin syndrome is a state of increased central and peripheral serotonin (5-hydroxytryptamine) activity. Unless recognized and treated early, serotonin syndrome can lead to seizures, shock and death. Both substances with direct and indirect serotonergic activity can precipitate the syndrome. Serotonin syndrome can occur not only in psychiatric but also in non-psychiatric settings. Yet, clinicians may not be familiar with the condition. We explore some of the current controversies regarding serotonin syndrome. Specifically, we tested the following assumptions: (i) Despite being rare, serotonin syndrome is still clinically relevant; (ii) The Hunter criteria are the gold standard for diagnosing serotonin syndrome; (iii) Hyperthermia is common in cases of serotonin syndrome; (iv) Serotonin syndrome usually develops fast; (v) Severe serotonin syndrome usually or almost exclusively involves monoamine oxidase inhibitors. We found that (i) despite being rare, serotonin syndrome was clinically relevant, (ii) the Hunter criteria could not be regarded as the gold standard for the diagnosis of serotonin syndrome since they missed more cases than the other two diagnostic criteria systems (Sternbach and Radomski criteria), (iii) Serotonin syndrome could occur in the absence of an elevated temperature, (iv) fast onset could not be regarded as a reliable clinical sign of serotonin syndrome, and (v) absence of monoamine oxidase inhibitors treatment did not exclude a diagnosis of serotonin syndrome. Clinicians should bear in mind that in the context of relevant drug history, serotonin syndrome may still be possible in these circumstances.

Triptan and ergotamine overdoses in the United States: Analysis of the National Poison Data System.

To examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS). This was a 5-year retrospective cross-sectional study (2014-2018) using the NPDS. Demographics, exposure characteristics, and outcomes were described. Univariate logistic regression was used to estimate the odds ratio (OR) for major effect or death. A multivariable logistic regression model with inclusion criteria of p < 0.1 in univariate analysis was implemented with backwards selection. In this population (n = 1,489), multiple exposure was most common (n = 1,145). The mean age was 31.2 years and 1,197 (80.4%) participants were female. Major effects from a single exposure were seen in <1% with no recorded deaths. Triptan ingestion (n = 328) resulted in hypertension (14%), tachycardia (10.7%), drowsiness (11%), nausea (6.4%), vomiting (4.6%), vertigo (4%), chest pain (3.7%), and diaphoresis (2.4%). Ergotamine ingestion (n = 16) resulted in abdominal pain (16%), vomiting (12.5%), numbness (12.5%), nausea (6.3%), diarrhea (6.3%), and vertigo (6.3%). No clinical effect was seen in 90 (26.2%). No cases met Hunter criteria for serotonin syndrome. There is risk of major event or death due to age (OR 1.02; 95% confidence interval [CI] 1.01-1.04; p = 0.004), multiple product exposure (OR 9.50; 95% CI 2.29-39.48; p = 0.002), and concomitant overdose with benzodiazepines (OR 1.71; 95% CI 1.05-2.78; p = 0.032) or tricyclic antidepressants (OR 3.16; 95% CI 1.88-5.31; p < 0.001). The risk of major effect or death was low and predicted by age, multiple product exposure, and concomitant benzodiazepine or tricyclic antidepressant. The triptan toxidrome consists of hypertension, tachycardia, and drowsiness. The toxic effects of ergotamine are acute gastrointestinal syndrome with vertigo and numbness. No cases of serotonin syndrome were seen.

Severe complications of tramadol overdose in Iran.

OBJECTIVESSevere complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran.METHODSPatients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose.RESULTSIn total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score <15, having taken a tramadol dose of >1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose.CONCLUSIONSAlthough seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.