Lack of toxicity from pediatric beta-blocker exposures.

The risk of toxicity in a child who is unintentionally exposed to a beta-blocking drug remains uncertain. The current study further defines this risk, particularly in the common scenario of ingestion of one or two tablets. A prospective cohort of 208 pediatric patients, 6 months to 6 years of age, reported to two regional poison centers serves as the study population. Data were collected with a standardized instrument during the care of each patient and for a minimum of 24 hours after exposure. No instances of serious toxicity typical of beta-blocker intoxication, such as 'shock-like' states, arrhythmias or seizures were observed in this series. Furthermore, there were no reported episodes of hypoglycemia, symptomatic bradycardia or bronchospasm. Nine instances of altered mental status or behavioral changes were reported. All appeared to be minor in nature. The most serious outcome was charcoal aspiration during gastrointestinal decontamination. This study adds to a growing body of evidence suggesting that exposure to one or two beta-blocker tablets places children at very little, if any, risk of toxicity.

Cardiovascular depression resulting from atenolol intoxication.

A case of massive atenolol ingestion leading to hypotension in association with PR and QRS interval prolongation on the electrocardiogram is presented. These clinical findings are identical to those attributed to the membrane-stabilizing activity of propranolol and other lipophilic beta-blockers. It is commonly believed that hydrophilic agents such as atenolol lack this activity. A review of the literature reveals that hydrophilic beta-blockers may have membrane-stabilizing activity, though much higher concentrations are required to produce this action in comparison with lipophilic agents. This case and a review of the literature provides a potential pathophysiological basis for atenolol-induced haemodynamic depression.

Urinary retention resulting from incarceration of a retroverted, gravid uterus.

Urinary retention resulting from urethral obstruction by a retroverted, gravid uterus is an uncommon disorder that is reported only once in the Emergency Medicine literature. Yet these patients may present in extreme distress and precipitate considerable confusion regarding the cause of and solution to this problem. No study evaluating outcome, risk of complications, or therapy exists. We present two cases that clarify diagnostic and therapeutic controversies and provide a better understanding of what is known about the pathophysiology and treatment alternatives.

The effect of sodium bicarbonate on propranolol-induced cardiovascular toxicity in a canine model.

STUDY OBJECTIVE: To evaluate the potential utility of sodium bicarbonate in an established model of acute propranolol toxicity. METHODS: Two minutes after the completion of a propranolol infusion (10 mg/kg), a bolus of 1.5 mEq/kg of sodium bicarbonate solution (1 mEq/mL) followed by an infusion of 1.5 mEq/kg over the next 26 minutes (n = 6) or an equivalent timing and volume of 5% dextrose solution (n = 6) was administered in each dog. Targeted cardiovascular parameters included heart rate, mean arterial pressure, left ventricular dP/dtmax, and QRS interval. RESULTS: Propranolol infusion significantly depressed heart rate (p < 0.0001), mean arterial pressure (p < 0.0001), dP/dtmax (p < 0.0001) and prolonged the QRS interval (p < 0.0001). Sodium bicarbonate failed to significantly improve these targeted parameters when compared to control animals. CONCLUSION: In this canine model of propranolol toxicity, intravenous sodium bicarbonate appears to be an ineffective single therapy. Furthermore, these results may suggest a different mechanism of sodium channel blockade for propanolol than that of type IA antiarrhythmic agents.

Acute beta blocker overdose: factors associated with the development of cardiovascular morbidity.

OBJECTIVE: To identify factors in exposures to beta blockers (beta-adrenergic receptor antagonists) that are associated with the development of cardiovascular morbidity and contribute to disposition decisions from the emergency department. METHODS: Prospective cohort of 280 beta blocker exposures reported to 2 regional poison centers. Multiple logistic regression was used to determine association of various clinical factors and outcome. RESULTS: In this series of beta blocker exposures, 41 (15%) developed cardiovascular morbidity and 4 (1.4%) died. A history of cardioactive coingestant was the only factor significantly associated with the development of cardiovascular morbidity (p < .05). When cases reporting cardioactive coingestants were excluded, a history of ingesting a beta blocker with membrane stabilizing activity was significantly associated with the development of cardiovascular morbidity (p < .05). All those in whom the timing of symptoms could be determined, developed symptoms within 6 hours of ingestion. CONCLUSIONS: The single most important factor associated with the development of cardiovascular morbidity in beta blocker ingestion is a history of a cardioactive coingestant, primarily calcium channel blockers, cyclic antidepressants, and neuroleptics. In the absence of such coingestion, exposure to a beta blocker with membrane stabilizing activity is associated with an increased risk of cardiovascular morbidity. Beta blocker ingestion is unlikely to result in symptoms if the patient remains asymptomatic for 6 hours after the time of ingestion.

Acebutolol overdose resulting in fatalities.

Two fatal cases of Acebutolol intoxication are presented that demonstrate its clinical characteristics and potential lethality. A review of the literature suggests that acebutolol is one of the most toxic beta blockers when taken as an overdose. In addition to demonstrating characteristics of membrane-stabilizing activity, both fatal cases demonstrate significant QTc prolongation and ventricular tachycardia. The latter findings suggest an impact on ventricular repolarization not seen with Propranolol intoxication. Clarification of these findings has important implications regarding identification and treatment of this potentially fatal intoxication.

A potential role for glucagon in the treatment of drug-induced symptomatic bradycardia.

Nine cases of symptomatic bradycardia are presented in which treatment with intravenous glucagon was administered when atropine failed to improve the patient's condition significantly. Although the cause often was not obvious at presentation, all nine subjects took oral medications that could have contributed to the development of symptomatic bradycardia. Eight of nine patients demonstrated clinical improvement 5 to 10 min after glucagon administration, which was consistent with its peak clinical action. Beta-blockers, calcium channel blockers, and digoxin were ultimately thought to have contributed to the majority of these presentations. This report suggests that glucagon may have a role in the treatment of symptomatic bradycardia, particularly in the presence of beta-adrenergic blockade and perhaps calcium channel blockade. Furthermore, the results in these cases suggest that future clinical trials should not be limited to drug-induced symptomatic bradycardia.

The effect of propranolol intoxication on QTc interval in a canine model.

The objective of this study was to evaluate the effects of propranolol intoxication on the QT and QTc intervals in a canine model. Lead II surface electrocardiograms were retrospectively evaluated from a previous study performed in this laboratory. Thirteen pentobarbital-anesthetized and instrumented animals, after a 30-min baseline period, were given 10 mg/kg dl-propranolol i.v. over 10 min. The electrocardiogram was printed continuously. Average heart rate and QT interval were measured and QTc was calculated at baseline and again 1 min after propranolol infusion was complete. Data for hemodynamic parameters have been previously reported demonstrating significant cardiovascular depression in all animals and one death with the administration of propranol. The QT interval was significantly prolonged by propranolol administration from baseline at 0.257 +/- 0.039 to 0.295 +/- 0.035 s. There was no significant difference in the QTc between baseline (0.371 +/- 0.026 s) and postpropranolol (0.366 +/- 0.021 s) measurements. In this canine model of propranolol intoxication, QT interval prolongation appears to be the result of associated bradycardia. Cardiovascular depression does not appear to include a significant direct effect on ventricular repolarization, as judged by the QTc interval.

Characterization of fatal beta blocker ingestion: a review of the American Association of Poison Control Centers data from 1985 to 1995.

OBJECTIVE: To characterize beta blocker-related deaths. METHODS: This is a retrospective review of beta blocker-related exposure data and fatality case abstracts reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System during the 11 year period, 1985 to 1995. Historical and laboratory data were used to determine those fatalities which resulted primarily from beta blocker intoxication. RESULTS: Of 52,156 reported beta blocker exposures, 164 were fatal. In 38 cases, beta blockers were implicated as the primary cause of death. Propranolol was responsible for the greatest number of exposures (44%) and implicated as the cause of death in a disproportionately high percentage of fatalities (71%). Patients were generally young women; 63% were female and 92% were less than 50 years old. The dysrhythmias most often noted in fatal cases were bradycardia and asystole. Cardiopulmonary arrest did not develop until patients were in the care of health care personnel in 59% of cases. Though glucagon was initiated more often than any other intervention in fatal intoxications (83%), optimal dosing and maintenance infusions appear to have been underutilized. CONCLUSIONS: The predominance of fatalities associated with propranolol compared to other beta blockers reflects both its greater frequency of use over the time period studied and its greater toxicity. Since 59% developed. cardiac arrest after reaching health care personnel, further study should focus on identifying medical intervention that can reduce mortality in this group.

Glucagon therapy in the treatment of symptomatic bradycardia.

Symptomatic bradycardia is commonly seen in the emergency department. Effective drug therapy for this clinical scenario is limited. Although glucagon has been used in no clinical trial in this setting, its cardiac activity may prove useful, particularly in the setting of beta-adrenergic blockade. We report a case series comprising three patients taking maintenance beta-blocker therapy who presented to the ED with symptomatic bradycardia and hypotension and in whom glucagon therapy obviated the need for further treatment. Further study is warranted to evaluate and define the role of glucagon in the treatment of symptomatic bradycardia.

Hemodynamic effects of calcium chloride in a canine model of acute propranolol intoxication.

STUDY OBJECTIVE: To evaluate the hemodynamic effects of calcium chloride in a canine model of acute propranolol toxicity. METHODS: Two minutes after the completion of a propranolol infusion (10 mg/kg), a bolus of .125 mL/kg 10% CaCl solution followed by an infusion of .375 mL/kg over the next 30 minutes or a bolus and subsequent infusion of an equivalent volume of normal saline solution was administered to each dog. RESULTS: CaCl yielded significant improvements in propranolol-induced decreases in cardiac index and stroke volume compared with saline solution-treated control animals (overall alpha = .05). Furthermore, CaCl administration resulted in earlier improvement in propranolol-induced alterations in mean arterial pressure, maximal left ventricular pressure change over time, and peripheral vascular resistance compared with saline solution (overall alpha = .05). We observed no difference between treatment groups in response to propranolol-induced bradycardia or QRS-interval prolongation. CONCLUSION: In this model of acute propranolol toxicity, CaCl therapy improved depressed hemodynamic status, mainly by a positive inotropic action.

Subtalar dislocation: evaluation and management in the emergency department.

Subtalar dislocations are sufficiently uncommon to be unfamiliar but require appropriate recognition and management to effect a good outcome. These dislocations benefit from urgent reduction that is essential to limiting sustained disability. Most can be reduced by closed manipulation at the time of presentation. Three cases of subtalar dislocations are presented followed by a discussion of the subject.

Toxic psychosis: an unusual presentation of propranolol intoxication.

Timely diagnosis of acute propranolol intoxication requires a high index of suspicion and a knowledge of the multiple ways in which these patients may present to the emergency department. We report a case of severe propranolol intoxication that presented as an acute psychotic episode preceding cardiovascular decompensation and seizures by several hours. Though acute reversible psychosis has been appreciated after initiating or increasing propranolol dosage therapeutically, this association has not been reported in the literature regarding beta blocker overdose or intoxication. Propranolol psychosis and several other pertinent aspects of this case are discussed.

Beta blocker toxicity after overdose: when do symptoms develop in adults?

Published reports of beta blocker ingestions in adults are retrospectively reviewed to determine at what point postingestion symptoms develop. Thirty-nine symptomatic beta blocker ingestions were found. The patients ranged from 14 to 67 years of age. Thirty-one (80%) of those who demonstrated symptoms did so within 2 h of ingestion. This number rose to thirty-eight (97%) by 4 h postingestion. Only one patient developed symptoms after more than 4 h of asymptomatic observation. The development of bradycardia and first degree atrioventricular block during observation appeared to predict toxicity in this patient who suddenly developed hypotension 6 h postingestion. No patient required treatment for delayed cardiovascular depression if they remained asymptomatic during a 4-h period of observation postingestion and demonstrated a normal electrocardiogram throughout. Whether the risk of delayed onset of toxicity after 6 h of asymptomatic observation is sufficiently low to warrant "medical clearance" requires further investigation.

Beta-blocker toxicity: a clinical diagnosis.

An overdose of the beta-blocking agent metoprolol is presented in which the patient remained asymptomatic despite blood levels that were more than 25 times that reported to be the upper limit of therapeutic. This case emphasizes the need to diagnose beta-blocker toxicity on clinical grounds, not on blood levels that correlate poorly with the severity of symptoms. Furthermore, the question is raised as to whether patients are at any subsequent risk for morbidity, if they have not demonstrated signs or symptoms within 4 hours of ingestion.

Emphysematous cholecystitis in an elderly woman: case report and review of the literature.

Cholecystitis, a frequent diagnosis in emergency departments, has been discussed extensively in the medical literature. We report a case of emphysematous cholecystitis, an unusual form of this disease process, including the classic radiographic findings. We also offer a review of the literature, emphasizing the proposed pathophysiology and the life-threatening nature of this surgical condition. Early recognition and surgical consultation are vital in these patients.

A comparison of combined amrinone and glucagon therapy to glucagon alone for cardiovascular depression associated with propranolol toxicity in a canine model.

Multiple inotropic agents may be required to improve hypotension associated with beta-blocker toxicity. This study compared combined amrinone and glucagon therapy to glucagon alone and saline control for the treatment of propranolol-induced cardiovascular depression in a canine model. Six animals were pretreated with 10 mg/kg of propranolol intravenously (i.v.), which resulted in significant depression in heart rate (HR), cardiac output (CO), mean arterial pressure (MAP), and maximal left ventricular change in pressure over time (dP/dt max) (P < .0001). Each canine received i.v. amrinone (4 mg/kg) plus glucagon (20 micrograms/kg) therapy during a 2-minute period after propranolol infusion was completed. Cardiovascular parameters were monitored at 1, 6, 11, 21, and 31 minutes after treatment was rendered. Results were compared with those of a previous study, consisting of six animals that received glucagon therapy alone (20 mg/kg) and six controls (normal saline only) in an identical protocol. The addition of i.v. amrinone to glucagon therapy did not increase significantly, HR, CO, stroke volume, or dP/dt max compared with glucagon alone. Total systemic peripheral resistance was reduced significantly during 31 minutes of observation after the administration of combined therapy compared with the control; glucagon alone also reduced systemic peripheral resistance at 1 and 6 minutes. At all time periods except 1 minute of observation there was a significant reduction in MAP when comparing combined therapy with that of glucagon therapy alone. In this model, the addition of amrinone to glucagon therapy seems to have a detrimental effect on the ability of glucagon to increase MAP resulting from propranolol toxicity.

Luxation of the globe.

Emergency physicians encounter globe luxation, anterior dislocation of the eyeball beyond retracted lids, in a limited number of clinical circumstances. The authors present a case of spontaneous luxation followed by a general discussion of luxation. An understanding of the pathophysiology of various causes of luxation and the appropriate method and timing of reduction allows appropriate evaluation, treatment, and follow-up, thereby limiting patient discomfort, recurrence, and perhaps long-term visual impairment.

Isolated anterolateral proximal fibular head dislocation.

A 28-year-old woman fell and sustained an isolated anterolateral dislocation of the proximal fibula. This injury generally presents with a characteristic history and associated physical examination and radiographic findings, but the subtle nature of the salient findings contributes to a high degree of misdiagnosis. Emergency physicians should be familiar with this injury because early reduction reduces long-term morbidity.