Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 µg/kg (range, 30-232.7 µg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Anthracyclines and the risk of arrhythmias: A systematic review and meta-analysis.

BACKGROUND: There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing evidence of the risk of arrhythmias in patients treated with anthracyclines. METHODS: PubMed, Scopus, and Web of Science databases were searched up to April 2022 using keywords such as "anthracycline" and "arrhythmia." Dichotomous data were presented as relative risk (RR) and confidence interval (CI), while continuous data were presented as mean difference (MD) and CI. Revman software version 5.4 was used for the analysis. RESULTS: Thirteen studies were included with a total of 26891 subjects. Pooled analysis showed that anthracyclines therapy was significantly associated with a higher risk of arrhythmia (RR: 1.58; 95% CI: 1.41-1.76; P < .00001), ST segment and T wave abnormalities (RR: 1.73, 95% CI: 1.18-2.55, P = .005), conduction abnormalities and AV block (RR = 1.86, 95% CI = 1.06-3.25, P = .03), and tachycardia (RR: 1.736, 95% CI: 1.11-2.69, P = .02). Further analyses of the associations between anthracyclines and atrial flutter (RR = 1.30, 95% CI = 0.29-5.89, P = .74), atrial ectopic beats (RR: 1.27, 95% CI: 0.78-2.05, P = .34), and ventricular ectopic beats (RR: 0.93, 95% CI: 0.53-1.65, P = .81) showed no statistically significant results. Higher doses of anthracycline were associated with a higher risk of arrhythmias (RR: 1.49; 95% CI: 1.08-2.05; P = .02) compared to the lower doses (RR: 1.36; 95% CI: 1.00-1.85; P = .05). Newer generations of Anthracycline maintained the arrhythmogenic properties of previous generations, such as Doxorubicin. CONCLUSION: Anthracyclines therapy was significantly associated with an increased risk of arrhythmias. Accordingly, Patients treated with anthracyclines should be screened for ECG abnormalities and these drugs should be avoided in patients susceptible to arrhythmia. The potential benefit of the administration of prophylactic anti-fibrotic and anti-arrhythmic drugs should also be explored.

Clinical and electrocardiographic factors associated with adverse cardiovascular events in bupropion exposures.

INTRODUCTION: Bupropion toxicity can cause cardiogenic shock, ventricular dysrhythmias, and death. Clinical and electrocardiographic factors associated with adverse cardiovascular events in bupropion toxicity have not been well-studied. This study aimed to identify factors associated with adverse cardiovascular events in adult patients with isolated bupropion exposures. METHODS: This retrospective cohort study queried the National Poison Data System from 2019 through 2020. We included patients 20 years or older with acute or acute-on-chronic single-agent bupropion exposures evaluated in a healthcare facility. Exclusion criteria were confirmed non-exposure, withdrawal as a reason for exposure, lack of follow-up, documentation that exposure was probably not responsible for the effects, and missing data. The primary outcome was adverse cardiovascular events, defined as the presence of any of the following: vasopressor use, ventricular dysrhythmia, myocardial injury, or cardiac arrest. Independent variables were age, the intentionality of exposure, seizures, tachycardia, QRS widening, and QTc prolongation. Multivariable logistic regression was performed to test for independent associations between independent variables and adverse cardiovascular events. RESULTS: Of 4,640 patients included in the final analysis (56.7% female, 56.5% suspected suicidal intent), 68 (1.47%) experienced an adverse cardiovascular event. Age (odds ratio 1.03; 95% confidence intervals 1.02-1.05), single seizure (odds ratio 9.18; 95% confidence intervals 4.24-19.9) and complicated seizures (odds ratio 38.9; 95% confidence intervals 19.3-78.1), QRS widening (odds ratio 3.01; 95% confidence intervals 1.62-5.59), and QTc prolongation (odds ratio 1.76; 95% confidence intervals 1.00-3.10) were independently associated with adverse cardiovascular events. No patients with unintentional exposure experienced adverse cardiovascular events, prohibiting intentionality from inclusion in the regression model. In the post hoc subgroup analysis of intentional exposures, age, single and complicated seizures, and QRS widening remained independently associated with adverse cardiovascular events. CONCLUSIONS: Increasing age, seizures, QRS widening, and QTc prolongation were associated with adverse cardiovascular events in bupropion exposures. Adverse cardiovascular events did not occur in unintentional exposures. Further research is needed to develop screening tools and treatments for bupropion cardiotoxicity.

Effectiveness of intraoperative use of dexmedetomidine in reducing the incidence of tachyarrhythmia after congenital cardiac surgery in neonates and infants: a doubly robust method estimation analysis.

OBJECTIVES: The antiarrhythmic effects of dexmedetomidine (DEX) have been suggested, but there are controversial reports on the effectiveness of intraoperative use of DEX to reduce the incidence of postoperative tachyarrhythmia (POT). METHODS: From a local European Congenital Heart Surgery Association database, we included patients operated for congenital heart diseases under cardiopulmonary bypass within a 5-year period (2017-2021), during which intraoperative use of high dose of DEX (1-1.4 µg/kg/h) was implemented. A doubly robust matching estimation of the causal effect of DEX on the incidence of POT was conducted. We combined a multimodal estimation model in patients not exposed to DEX (disease risk score) as well as a regression analysis in a matched cohort for patients exposured to DEX. RESULTS: From a cohort of 593 surgeries (514 patients) occurring during the study period, doubly matched analysis consisted of the analysis of 426 surgeries conducted under DEX or not (213 per group). The probability of developing POT in patients exposed to DEX was 6.6% (95% confidence interval 0.032-0.099) vs 14.5% (95% confidence interval 0.098-0.193) in the group of patients not exposed to DEX. The doubly robust matched estimation method showed a mean reduction of 8.8% (95% confidence interval -0.137 to -0.023) of POT when DEX is used for intraoperative anaesthesia. CONCLUSIONS: The use of high doses of DEX during anaesthesia for congenital heart surgery in neonates and infants is associated with a moderate but significant reduction of POT.

A Case of Wide QRS Tachycardia After the Local Administration of Epinephrine to Reduce Bleeding During General Anesthesia.

We report a case of wide QRS tachycardia or ventricular tachycardia with a pulse after the administration of epinephrine under general anesthesia. After induction and achieving a sufficiently deep plane of general anesthesia, gauze soaked in a 1:100,000 epinephrine solution was applied to the patient's nasal mucosa and 1% lidocaine with 1:100,000 epinephrine was administered via intraoral infiltration. Several minutes after the start of surgery, the patient's blood pressure and heart rate suddenly increased and a wide QRS tachycardia was observed on the electrocardiogram, which then reverted to a normal sinus rhythm. According to the past reports, similar arrhythmias have occurred after administration of epinephrine in the head and neck. These findings suggest that anesthesia providers must be aware of the risks associated with epinephrine and local anesthetic use, particularly in the head and neck region.

Involvement of ß-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists.

A2A and A2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A2A or A2B receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of ß1 - and ß2 -adrenoceptors in mediating the different cardiovascular responses to selective A2A and A2B receptor stimulation. Hemodynamic variables were measured in conscious male Sprague-Dawley rats (350-450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A2A -selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg-1 .min-1 ) or the A2B -selective agonist BAY 60-6583 (4.0, 13.3, 40.0 µg.kg-1 .min-1 ) in the absence or following pre-treatment with the non-selective ß-antagonist propranolol (1.0 mg.kg-1 ), the selective ß1 -antagonist CGP 20712A (200 µg.kg-1 ), or the selective ß2 -antagonist ICI 118,551 (2.0 mg.kg-1 ) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60-6583-mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60-6583-induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac ß1 -adrenoceptors as a mechanism for the A2A - and A2B -induced tachycardia. However, the regionally selective effects of A2B agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia.

Adverse effects associated with bupropion therapeutic errors in adults reported to four United States Poison Centers.

CONTEXT: Bupropion is a frequently used medication. Excessive doses may cause altered mental status, seizures, and dysrhythmias. There is a need for accurate estimate of seizure risk with therapeutic errors and determination if minor symptoms are harbingers of more severe effects. METHODS: A retrospective review of adult, acute, unintentional therapeutic error, single substance bupropion ingestions with known outcome reported to four poison centers from January 1, 2004 to December 31, 2016. Data included age, gender, single error dose, total bupropion dose over 18 h, prior history of seizure, management site, observation time, occurrence of an out-of-hospital adverse event, "jittery"/anxious/agitated, tachycardia/palpitations, seizures, and dysrhythmias. We recorded the total bupropion dose over 18 h if known; otherwise, we used the single error dose. We compared means for parametric data. We used Fisher's exact test and Mann-Whitney for nonparametric data. RESULTS: We identified 754 potential cases, of which 637 met inclusion criteria after case review. Median age was 42 years, and 76.1% were female. Cases were predominantly managed at home (56.2%). Outcomes were no effect (50.1%), minor (45.5%) and moderate (4.4%). The reported dose with no effect/minor outcome was 694 (±297) mg, and for moderate outcome was 1250 (±815) mg (p < 0.0001). Seizures occurred in four patients with median onset time of 7 h [range 2-21.5 h]. The median reported dose in patients who seized was 900 mg [range 600-3000 mg]. Of patients who developed a seizure and/or an out-of-hospital adverse event, 83% were "jittery"/anxious/agitated whereas "jittery"/anxious/agitated was present in 27% of cases that did not (p = 0.008). Tachycardia/palpitations was reported in 12% of cases; more serious dysrhythmias were not reported. CONCLUSIONS: Outcomes from single unintentional ingestions of bupropion in adults are overall mild and appear to be dose related. Home management may be an option with doses up to 900 mg in an appropriate patient population.

Reacciones adversas por salbutamol en pacientes asmáticos: reflexiones acerca del uso en las exacerbaciones / Adverse reactions from salbutamol in asthmatic patients: reflections on its use and exacerbations / Reações adversas ao salbutamol em pacientes asmáticos: reflexões sobre o seu uso e exacerbações

Las afecciones respiratorias agudas son la primera causa de consulta e ingreso hospitalario en los meses de invierno, y entre ellas el asma ocupa un lugar preponderante. El salbutamol es un broncodilatador con eficacia demostrada en las exacerbaciones y se utiliza de primera línea en el tratamiento. El objetivo de la presente comunicación es analizar dos casos clínicos de niños asmáticos que presentaron efectos adversos al salbutamol y requirieron el ingreso en la Unidad de Terapia Intensiva. Se propone revisar los efectos adversos del salbutamol empleado en crisis asmáticas y analizar las alternativas terapéuticas en esta enfermedad. Los síntomas de los efectos secundarios pueden confundirse con los causados por la propia enfermedad, por lo que puede usarse el fármaco de modo excesivo y es importante conocer el perfil posológico y caracterizar los posibles efectos secundarios en los pacientes para usar de manera racional y segura este medicamento.

Acute respiratory conditions are the first cause of consultation and hospital admission in the Winter months, being asthma the most important. Salbutamol is a bronchodilator with proven efficacy in exacerbations used first-line in treatment. The objective of this paper is to analyze two clinical cases of asthmatic children who presented adverse effects to salbutamol and required admission to the Intensive Care Unit. It is proposed to review the adverse effects of salbutamol used in asthmatic crises and to analyze therapeutic alternatives in this disease. Symptoms of side effects can be confused with those caused by the disease itself, determining the excessive use of this drug, thus, it is important to know the dosage profile and characterize the possible side effects to make rational and safe use of this drug.

As doenças respiratórias agudas são a primeira causa de consultas e internações nos meses de inverno e a asma ocupa é a mais importante. O salbutamol é um broncodilatador com eficácia comprovada nas exacerbações e é usado como tratamento de primeira linha. O objetivo desta comunicação é analisar dois casos clínicos de crianças asmáticas que apresentaram efeitos adversos ao salbutamol e necessitaram de internação em Unidade de Terapia Intensiva. Propõe-se revisar os efeitos adversos do salbutamol utilizado na crise asmática e analisar as alternativas terapêuticas nessa doença. Os sintomas de efeitos colaterais podem ser confundidos com os causados pela própria doença, determinando o uso excessivo desse medicamento, sendo importante conhecer o perfil posológico e caracterizar os possíveis efeitos colaterais nos pacientes para fazer um uso racional e seguro desse medicamento.

A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants.

BACKGROUND: The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. METHODS: Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. RESULTS: Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. CONCLUSIONS: Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03346057 .

Occupational exposure to pesticides and health symptoms among family farmers in Brazil.

OBJECTIVE: To explore the association of occupational pesticide exposure with acute and mental health symptoms. METHODS: Cross-sectional survey carried out with 78 Brazilian family farmers, who were pesticide applicators and helpers conveniently selected. Symptoms and exposure data were collected by interviews, and mental health outcomes by the Self-Reporting Questionnaire. Blood samples were analyzed to assess cholinesterase levels. Exposure indicators and symptoms were compared between applicators and helpers, and Poisson regression was performed to estimate prevalence ratios. RESULTS: Farmers reported exposure to multiple pesticides from early ages; they worked without safety training, technical support, and full protective equipment, and they had a high prevalence of acute and mental health symptoms (e.g., headache, mucosal irritation, tachycardia, and depressive signs). Applicators had more cholinesterase changes than helpers, but less symptoms. Helpers used less personal protection and had significantly higher prevalence ratio of headache, dyspnea, wheezing, cough, poor digestion, tiredness, and feeling worthless, after adjustment. CONCLUSIONS: Acute and mental health symptoms were observed, both among farmers and helpers. Thus, surveillance actions must be reinforced in Brazil, technical support and safety training improved, focused on applicators and helpers, who are occupationally and environmentally exposed to pesticides. Agricultural practices of these groups with less pesticide use should receive incentive.

Assessment of Children Exposed to Maras Powder Intoxication.

INTRODUCTION: A smokeless tobacco known as Maras powder (MP) is commonly consumed in the southern region of Turkey. To the extent of our knowledge, no previous study in literature has reported acute MP intoxication in children. AIM: Our aim was to determine the clinical effects and treatment strategies of MP poisoning in children.Materials and methods: We retrospectively reviewed the medical records of children <18 years of age with MP intoxication who were followed up in the Intensive Care Unit between January 2016 and April 2018 in our center. RESULTS: Forty-one patients (M/F= 25/16) were included in this study. The mean age was 13.2±22.4 months (age range: 7 to 30 months). The patients presented with vomiting (n=23, 56%), cough (n=17, 41.5%), loss of consciousness (n=11, 26.8%), respiratory distress (n=6, 14.6%), convulsion (n=7, 17%), cyanosis (n=1, 2.4%), and abdominal pain (n=1, 2.4%) following oral ingestion of the substance. On their physical examination all patients with convulsion were in a comatose state. Thirty-two patients (78%) had tachycardia; 15 patients (36.5%) had pharyngeal hyperemia; and three (7.3%) had hiccups. Although the female patients had a lesser rate of symptoms than male patients, the difference was not statistically significant. CONCLUSIONS: Our aim was to inform the doctors about the clinical picture that develops after taking this substance and contribute to the understanding of the treatment approach.

Uterine Exteriorization Compared With In Situ Repair of Hysterotomy After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of exteriorized with in situ uterine repair on intraoperative nausea and vomiting during elective cesarean delivery under spinal anesthesia using a phenylephrine infusion. METHODS: This study was a randomized double-blinded controlled trial of 180 women undergoing elective cesarean delivery using a standardized anesthetic protocol. Patients were randomized to exteriorization (n=90) or in situ uterine repair (n=90). The spinal anesthetic, phenylephrine infusion, and blood pressure management were all standardized. The primary outcome was postdelivery intraoperative nausea and vomiting using a 4-point scale (0-3). A sample size of 80 patients per group was needed to demonstrate a 50% reduction in intraoperative nausea and vomiting with in situ repair. RESULTS: From November 2015 through July 2018, 180 patients were enrolled. Incidence of postdelivery intraoperative nausea and vomiting was 39% in the exteriorization group compared with 22% in the in situ group (P=.01). Incidence of hypotension (80% vs 50%; P<.001) and tachycardia (33% vs 17%; P=.02) was significantly higher in the exteriorization group, and more phenylephrine boluses were administered to this group (median 4 boluses [first and third quartiles 1.25-7] vs 2 [0-4]; P<.001). The duration of surgery, blood loss, and postoperative hemoglobin decline were similar between groups. CONCLUSION: In situ uterine repair for elective cesarean delivery under spinal anesthesia with a phenylephrine infusion is associated with less postdelivery intraoperative nausea and vomiting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02587013.

Treatments for priapism in boys and men with sickle cell disease.

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed the risk of bias of the trials. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low. AUTHORS' CONCLUSIONS: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

Bupropion associated seizures following acute overdose: who develops late seizures.

Objectives: Bupropion is an antidepressant that is commonly known to cause seizures in overdose. Because of concern for delayed onset of seizures, patients are frequently observed for prolonged periods after overdose. The primary objective is to evaluate the incidence and clinical parameters associated with late seizures following bupropion overdose.Methods: This retrospective study of acute bupropion overdose who presented to 26 different hospitals in California and Arizona during an 8 year time period.Results: 437 patients were identified. Tachycardia and altered mental status were common. A total of 122 (27.9%) patients had seizures following their overdose. Only eight patients (1.8%) had a seizure more than 8 h after hospital arrival. None of these patients were asymptomatic on arrival. Among patients with tachycardia on arrival, the odds of having a seizure was 6.7 (95% CI 3.7-10.9); the odds of a seizure more than 8 h after arrival was 5.24 (95% CI 1.2-23.5). Similarly, altered mental status on arrival was significantly associated with the risk of a seizure; OR 3.93 (95% CI 2.21-7.0).Conclusion: Seizures are relatively common, and are associated with antecedent tachycardia or altered mental status.

Effects of Anticholinesterase Reversal Under General Anesthesia on Postoperative Cardiovascular Complications: A Retrospective Cohort Study.

BACKGROUND: The anticholinesterase neostigmine and the muscarinic inhibitor glycopyrrolate are frequently coadministered for the reversal of neuromuscular blockade. This practice can precipitate severe bradycardia or tachycardia, but whether it affects the incidence of cardiovascular complications remains unclear. We hypothesized that anticholinesterase reversal with neostigmine and glycopyrrolate versus no anticholinesterase reversal increases the risk of postoperative cardiovascular complications among adult patients undergoing noncardiac surgery with general anesthesia. METHODS: We conducted a prespecified retrospective analysis of hospital registry data from a major health care network for patients undergoing surgery with general anesthesia from January 2007 to December 2015. The primary outcome was a composite of cardiac dysrhythmia, acute heart failure, transient ischemic attack, ischemic stroke, and acute myocardial infarction within 30 days after surgery. We performed sensitivity analyses in subgroups and propensity score adjustment and explored the association between exposure and outcome in subgroups of patients with high risk of cardiovascular complications. RESULTS: Of the 98,147 cases receiving neuromuscular blockade, 73,181 (74.6%) received neostigmine and glycopyrrolate, while 24,966 (25.4%) did not. A total of 5612 patients (7.7%) in the anticholinesterase reversal group and 1651 (6.6%) in the control group (P < .001) experienced the primary outcome. After adjustment for clinical covariates, neostigmine and glycopyrrolate exposure was significantly associated in a dose-dependent fashion (P for trend <.001, respectively) with tachycardia (adjusted odds ratio = 2.1 [95% CI, 1.97-2.23]; P < .001) and bradycardia (adjusted odds ratio = 2.84 [95% CI, 2.49-3.24]; P < .001) but not with postoperative cardiovascular complications (adjusted odds ratio = 1.03 [95% CI, 0.97-1.1]; P = .33). We identified a significant effect modification of anticholinesterase reversal by high age, high-risk surgery, and history of atrial fibrillation (P for interaction = .002, .001, and .02, respectively). By using linear combinations of main effect and exposure-risk interaction terms, we detected significant associations between anticholinesterase reversal and cardiovascular complications toward a higher vulnerability in these patient subgroups. CONCLUSIONS: Neuromuscular blockade reversal with neostigmine and glycopyrrolate was associated with an increased incidence of intraoperative tachycardia and bradycardia but not with 30-day postoperative cardiovascular complications. Exploratory analyses suggest that a high postoperative cardiovascular complication risk profile may modify the effects of anticholinesterase reversal toward clinical relevance.

Single-Agent Bupropion Exposures: Clinical Characteristics and an Atypical Cause of Serotonin Toxicity.

INTRODUCTION: Bupropion is the only Food and Drug Administration-approved synthetic cathinone. It increases the release of norepinephrine in the locus coeruleus and dorsal raphe nucleus, causing an increase in the frequency of serotonergic neuron firing. The diagnosis of serotonin toxicity (ST) from bupropion poisoning is controversial due to the lack of direct serotonergic activity. Nonetheless, there is one documented report of ST after single-agent bupropion overdose and multiple reports describing polypharmacy overdoses where bupropion may have contributed to ST. METHODS: This is a retrospective analysis of data collected by the Toxicology Investigators Consortium (ToxIC), a prospective multi-center toxico-surveillance and research network registry, from 2014 to 2017. Cases were identified if ST was a clinical effect and bupropion was the single agent listed. Data is presented descriptively. RESULTS: Of the 266 recorded single bupropion overdoses, the most common symptoms were seizures (47.1%), tachycardia (greater than 140 bpm) (33.9%), agitation (31.7%), toxic psychosis (20.4%), and myoclonus/tremor/hyperreflexia (19%). Benzodiazepines were the most common therapy (69.2%). Thirteen patients (5.9%) were diagnosed with ST by a medical toxicologist. CONCLUSION: Bupropion overdose is primarily associated with seizures, tachycardia, and agitation; bupropion may be an atypical cause of serotonin toxicity.

Pediatric Bupropion Ingestions in Adolescents vs. Younger Children-a Tale of Two Populations.

BACKGROUND: Bupropion is a unique class of antidepressant. In overdose, it is associated with tachycardia, altered mental status, and a dose-dependent risk of seizures, which can be delayed. Despite being a common medication, there is a paucity of data comparing toxicity in younger versus older children with bupropion exposures. The primary purpose of this study is to examine bupropion toxicity in pediatric patients and assess for toxicity differences between younger and older (teenaged) groups. METHODS: This single-center, observational cohort study reviewed pediatric patients presenting to a toxicology service between 2011 and 2018. The primary outcome measures evaluated were the presence of any seizure, delayed seizure (defined as occurring at least 6 hours after hospital arrival), and a composite endpoint of seizure, hypotension, or need for endotracheal intubation. Patients were subdivided into two groups-those 12 years and under, compared with those 13-17 years. RESULTS: A total of 80 unique pediatric cases were identified. Overall, the median (IQR) age was 14 (2.4-16) years. Patients under 13 years accounted for 31 (39%) of cases, whereas the remaining 49 cases were adolescents. Compared with the adolescents, the younger patients were less likely to be female (41.9% vs. 71.4%; p = 0.009) and more likely to have an unintentional ingestion (100% vs. 10.2%; p < 0.001). The younger group was more likely to present to health care earlier after the ingestion (median 61 (IQR 39-103) min vs. 139 (67-399) min; p = 0.002). The older group was more likely to be tachycardic (73.5% vs. 19.4%; p < 0.001), have sustained tachycardia (71.4% vs. 29% p < 0.001), and more likely to have altered mental status on arrival (38.8% vs. 6.5%; p < 0.001). Seizures were also much more likely in the older group (40.8% vs. 3.2%; p < 0.001). Adolescents were much more likely than younger children to reach the pre-defined composite endpoint (42.9% vs. 6.5%; p < 0.001), but this was largely driven by the seizures. CONCLUSION: Bupropion ingestions are relatively common among pediatric patients. However, adolescents are much more likely to present with more severe toxicity. Seizures are uncommon among younger children with exploratory ingestions.

Occupational exposure to pesticides and health symptoms among family farmers in Brazil

ABSTRACT OBJECTIVE: To explore the association of occupational pesticide exposure with acute and mental health symptoms. METHODS: Cross-sectional survey carried out with 78 Brazilian family farmers, who were pesticide applicators and helpers conveniently selected. Symptoms and exposure data were collected by interviews, and mental health outcomes by the Self-Reporting Questionnaire. Blood samples were analyzed to assess cholinesterase levels. Exposure indicators and symptoms were compared between applicators and helpers, and Poisson regression was performed to estimate prevalence ratios. RESULTS: Farmers reported exposure to multiple pesticides from early ages; they worked without safety training, technical support, and full protective equipment, and they had a high prevalence of acute and mental health symptoms (e.g., headache, mucosal irritation, tachycardia, and depressive signs). Applicators had more cholinesterase changes than helpers, but less symptoms. Helpers used less personal protection and had significantly higher prevalence ratio of headache, dyspnea, wheezing, cough, poor digestion, tiredness, and feeling worthless, after adjustment. CONCLUSIONS: Acute and mental health symptoms were observed, both among farmers and helpers. Thus, surveillance actions must be reinforced in Brazil, technical support and safety training improved, focused on applicators and helpers, who are occupationally and environmentally exposed to pesticides. Agricultural practices of these groups with less pesticide use should receive incentive.

Perioperative adverse events attributed to α2-adrenoceptor agonists in patients not at risk of cardiovascular events: systematic review and meta-analysis.

BACKGROUND: Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented. METHODS: We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 µg kg-1 or with continuous administration alone. CONCLUSIONS: Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia. PROTOCOL REGISTRATION: CRD42017071583.

Brainstem cholinergic pathways diminish cardiovascular and neuroinflammatory actions of endotoxemia in rats: Role of NFκB/α7/α4ß2AChRs signaling.

Nicotine improves endotoxic manifestations of hypotension and cardiac autonomic dysfunction in rats. Here, we test the hypothesis that brainstem antiinflammatory pathways of α7/α4ß2 nicotinic acetylcholine receptors (nAChRs) modulate endotoxic cardiovascular derangements. Pharmacologic and molecular studies were performed to determine the influence of nicotine or selective α7/α4ß2-nAChR ligands on cardiovascular derangements and brainstem neuroinflammation caused by endotoxemia in conscious rats. The i.v. administration of nicotine (50 µg/kg) abolished the lipopolysaccharide (LPS, 10 mg/kg i.v.)-evoked: (i) falls in blood pressure and spectral measure of cardiac sympathovagal balance (ratio of the low-frequency to high-frequency power, LF/HF), (ii) elevations in immunohistochemical protein expressions of NFκB and α4ß2-nAChR in medullary neurons of the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), and (iii) decreases in medullary α7-nAChR protein expression. These favorable nicotine influences were replicated in rats treated intracisternally (i.c.) with PHA-543613 (selective α7-nAChR agonist) or 5-iodo-A-85380 (5IA, selective α4ß2-nAChRs agonist). Measurement of arterial baroreflex activity by the vasoactive method revealed that nicotine, PHA, or 5IA reversed the LPS depression of reflex bradycardic, but not tachycardic, activity. Moreover, the counteraction by nicotine of LPS hypotension was mostly inhibited after treatment with i.c. methyllycaconitine (MLA, α7-nAChR antagonist) in contrast to a smaller effect for dihydro-ß-erythroidine (DHßE, α4ß2-nAChR antagonist), whereas the associated increases in LF/HF ratio remained unaltered. The data signifies the importance of brainstem α7, and to a lesser extent α4ß2, receptors in the nicotine counteraction of detrimental cardiovascular and neuroinflammatory consequences of endotoxemia.