The effect of the menstrual cycle on asthma presentations in the emergency department.

BACKGROUND: Seventy-five percent of all adult hospital admissions for asthma are women. OBJECTIVE: To determine whether a relationship exists between phases of the menstrual cycle and asthma exacerbations in adult females. METHODS: Data were analyzed from 182 nonpregnant, adult females with asthma aged 13 years to menopause. Date of presentation, patient age, duration of asthma attack, date of last menstrual period, regular interval between menses, presenting peak expiratory flow rate, and admission and discharge decision were recorded prospectively. Treatment interventions abstracted retrospectively from patient charts included use of oxygen, xanthines, beta-adrenergic agonists, corticosteroids, and magnesium sulfate. The menstrual cycle was divided into 4 phases based on fluctuations in serum estradiol levels. The 4 intervals were preovulatory (days 5-11), periovulatory (days 12-18), postovulatory (days 19-25), and perimenstrual (days 26-4). RESULTS: Data were analyzed with a goodness-of-fit chi 2. Between June 1991 and May 1992, 182 females (mean +/- SD age, 28.5 +/- 8.0 years) were surveyed. No significant differences were noted for use of oxygen, beta-adrenergic agonists, xanthines, or magnesium among members of the 4 menstrual groups. Intervention with corticosteroids was least in the postovulatory interval (y:n) 0.5:1 and greatest in the preovulatory interval 3.0:1 (alpha = .03) Presentations by menstrual interval were as follows: preovulatory, 36 (20%); periovulatory, 43 (24%); postovulatory, 18 (10%); and perimenstrual, 85 (46%) (alpha < .01). CONCLUSIONS: Asthma presentations are least frequent when serum estradiol levels are at a sustained peak. We observed a 4-fold variation in asthma presentations during the perimenstrual interval, when serum estradiol levels decrease sharply after that prolonged peak. These findings suggest that monthly variations in serum estradiol levels may influence the severity of asthma in adult females.

A retrospective analysis of institutional review board and informed consent practices in EMS research.

STUDY OBJECTIVE: To assess the frequency of institutional review board (IRB) review and informed consent in emergency medical services (EMS) research. DESIGN: Two-year, retrospective review of published EMS research. MEASUREMENTS AND MAIN RESULTS: One hundred two studies were analyzed. Seventy-one (70%) were exempt from IRB review; 31 (30%) were not exempt. Seventeen nonexempt studies (55%) did not obtain IRB review. Eight of these did not specify a consent method; one used implied consent and eight used volunteers. Volunteers gave informed consent in one study. Of the 14 nonexempt studies with IRB approval, seven did not specify a consent method. Two used informed consent, one received an informed consent waiver, one used verbal consent, and three involved volunteers. Written parent permission was used once when volunteers were minors. CONCLUSION: IRB review is often omitted by EMS investigators. This raises ethical concerns about EMS research. Investigators should document their consent method or approval to use an informed consent waiver in their manuscripts. A consent method should be specified for volunteers.

A clinical trial of escalating doses of flumazenil for reversal of suspected benzodiazepine overdose in the emergency department.

STUDY OBJECTIVE: To determine if flumazenil, when used in doses higher than those currently recommended, could reverse the effects of a benzodiazepine (BDZ) overdose in patients who might not otherwise respond and whether the higher dose was associated with increased adverse effects. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, balanced, with parallel groups. Open-label flumazenil administration was available if a patient failed to respond or became resedated. SETTING: Sixteen emergency departments in the United States. POPULATION: Patients presenting to the ED with clinically significant signs and symptoms of a known or suspected BDZ overdose. INTERVENTIONS: Patients were randomized to receive 10 mL/min of placebo or flumazenil (1 mg/10 mL) each minute for ten minutes. If there was no response, up to 3 mg of open-label flumazenil could be administered. MEASUREMENTS AND MAIN RESULTS: Of 170 patients enrolled, 87 received flumazenil and 83 received placebo. The demographic characteristics of both groups were comparable. Ten minutes after the beginning of study drug infusion, patients were evaluated using the Clinical Global Impression Scale (CGIS), Glasgow Coma Scale (GSC), and Neurobehavioral Assessment Scale (NAS). The mean +/- SD CGIS score at ten minutes for BDZ-positive patients was 1.41 +/- 0.72 for patients who received flumazenil and 3.41 +/- 0.91 for the placebo group (P < .01). There was no difference in the mean CGIS score between the flumazenil (3.25 +/- 1.15) and placebo (3.75 +/- 0.69) groups in BDZ-negative patients. The GCS and NAS were also significantly better in patients who were BDZ-positive and received flumazenil. The mean +/- SD dose of flumazenil administered during the double-blind phase was 71.3 +/- 34.2 mL (7.13 mg) compared with 95.06 +/- 16.03 mL of placebo. Of the 39 patients who had BDZ-positive drug screens and received flumazenil, 29 (74%) responded to 3 mg or less. Six additional patients responded to 4 or 5 mg, and one patient responded to 8 mg. The most common adverse effects in patients who received flumazenil were injection site pain (10.3%), agitation (8%), vomiting (3.4%), dizziness (3.4%), headache (3.4%), tachycardia (3.4%), and crying (3.4%). Three patients developed seizures. Two were associated with significant tricyclic antidepressant overdoses and one with propoxyphene ingestion. Two patients had positive drug screens for BDZ. CONCLUSION: Flumazenil rapidly and effectively reverses the clinical signs and symptoms of a BDZ overdose. Most patients will respond to 3 mg or less, but a small number may require a higher dose for reversal of clinical symptoms. Patients with concomitant tricyclic antidepressant overdose may be at risk for developing seizures.

Comparison of intermittent and continuously nebulized albuterol for treatment of asthma in an urban emergency department.

STUDY OBJECTIVE: To compare continuously nebulized albuterol with intermittent bolus nebulization of albuterol. DESIGN: Consecutive block enrollment in groups of ten to continuous or intermittent therapy. SETTING: Urban emergency department. TYPE OF PARTICIPANTS: Patients who presented to the ED with moderate to severe asthma and did not improve after one treatment with nebulized albuterol. INTERVENTIONS: All patients received an initial nebulized treatment with 2.5 mg albuterol followed by 125 mg solumedrol. Patients in the intermittent group received 2.5 mg nebulized albuterol at 30, 60, 90, and 120 minutes after the initial treatment. Patients in the continuous group received 10 mg albuterol nebulized in 70 mL over two hours. RESULTS: There was no difference between groups in age, sex, or initial peak expiratory flow rate (PEFR). Ninety-nine patients were included in the study (47 continuous and 52 intermittent). There was no statistically significant difference in PEFRs or admission rate between groups over the two-hour study period. One subgroup analysis was performed on patients with PEFRs on presentation to the ED of 200 L/min or less. Mean +/- SD baseline PEFR at presentation to the ED was 135 +/- 35 in the 35 patients in the continuous group and 137 +/- 45 in the 34 patients in the intermittent group). At 120 minutes, PEFR was 296 +/- 98 in the continuous group and 244 +/- 81 in the intermittent group (P = .01). Admission: discharge ratios for this subgroup analysis were 11:24 in the continuous group and 19:14 in the intermittent group (P = .03). Mean +/- SD heart rate in the subgroup analysis was 102 +/- 21 at baseline for the continuous group and 109 +/- 22 at baseline in the intermittent group. At 120 minutes, heart rate was 90 +/- 18 in the continuous group and 104 +/- 16 in the intermittent group (P = .002). CONCLUSIONS: Continuous nebulization offers no benefit over intermittent therapy in patients with an initial PEFR of more than 200 L/min. In PEFRs of 200 or less, continuous nebulization may decrease admission rate and improve PEFRs when compared with standard therapy.

Death notification in the emergency department: a survey of residents and attending physicians.

STUDY OBJECTIVE: To delineate the topics discussed with families during the death notification process and to identify which of these topics are stressful to the physician. Also, the survey served as a needs assessment in designing an educational program for emergency medicine residents in death notification. DESIGN AND PARTICIPANTS: Forty-five residents and 20 attendings physicians in emergency medicine at the Medical College of Pennsylvania were given an anonymous, self-administered, 47-item questionnaire seeking demographic information and assessing topics discussed during notification, perceived importance to the family of these topics, and the stressfulness of these topics. RESULTS: One hundred percent of the participants responded to the survey. Hospital care, prehospital care, and cause of death were most often discussed with the family, although no topic was discussed 100% of the time by all physicians. Those items that may be perceived as emotionally charged, such as organ donation and autopsy, were rated as more stressful and were less frequently addressed during notification. CONCLUSION: Factual information is discussed most often, and emotional issues are considered most stressful. Therefore, a program in death notification must address those issues that must be handled during a notification and provide mechanisms for residents to feel comfortable with emotional responses from the family.

Magnesium sulfate for the treatment of bronchospasm complicating acute bronchitis in a four-months'-pregnant woman.

A four-months'-pregnant woman without a prior history of asthma presented to the emergency department with acute bronchitis compounded by bronchospasm. The patient failed to respond adequately to aggressive treatment with conventional therapy. Prior to hospital admission, a bolus of 3 g IV magnesium sulfate was infused with complete abatement of her bronchospasm, significantly increasing peak expiratory flow rate without any significant side effects. The patient was discharged home and remained asymptomatic thereafter.

The influence of age and sex on asthma admissions.

OBJECTIVE: To describe demographic data from a large population of asthmatic patients to define the role of age and sex as risk factors for asthma admission. DESIGN: A retrospective review of all asthma admissions as defined by International Classification of Diseases, Ninth Revision, code 493.0. SOURCE: All medical-surgical admissions from 67 hospitals in five counties of southeastern Pennsylvania from 1986 through 1989. RESULTS: Patients admitted for asthma treatment (33,269) were reviewed. In the 0- to 5-year-old and 6- to 10-year-old age groups, males were admitted nearly twice as often as age-identical females. In the 11- to 20-year-old age group, admissions for males and females were nearly identical. Between 20 and 50 years of age, the female-to-male ratio was nearly 3:1. Thereafter, females were admitted for asthma at a rate of about 2.5:1 when compared with their age-equivalent male counterparts. Length of stay increased proportionally as the patient age increased. After 30 years of age, the length of stay was slightly greater for females than males. CONCLUSIONS: There is a much higher rate of admission for prepubertal males than females. However, there is a higher incidence of asthma admissions for adult females than adult male asthmatic patients, and female asthmatic patients experience longer hospital stays per admission as well. These data indicate that adult females are more severely affected by asthma and raise the possibility that hormonal or biochemical differences related to sex may play a role in the pathophysiology of asthma.

Flumazenil and seizures: analysis of 43 cases.

Flumazenil is a new drug indicated for the reversal of the sedative effects of benzodiazepines mediated at the benzodiazepine-receptor site. Worldwide sources to date have disclosed 43 cases of seizures related, at least temporally, to the intravenous administration of flumazenil. There was no apparent relationship between the dose of flumazenil and the development of seizures, which occurred at doses ranging from 0.2 to 10.0 mg. The seizures were not considered to be a toxic effect of flumazenil, but many of them probably were due to an unmasking of the anticonvulsant effect of the previously used benzodiazepine or to a severe benzodiazepine-withdrawal syndrome. Eighteen (42%) of the patients had ingested overdoses of cyclic antidepressants, which were considered responsible for the seizures. In addition to patients with concurrent cyclic antidepressant poisoning, high-risk populations include patients who have been treated with benzodiazepines for a seizure disorder or an acute convulsive episode, patients with concurrent major sedative-hypnotic drug withdrawal, patients who have recently been treated with repeated doses of parenteral benzodiazepines, and overdose patients with myoclonic jerking or seizure activity before flumazenil administration. To minimize the likelihood of a seizure, it is recommended that flumazenil not be administered to patients who have used benzodiazepines for the treatment of seizure disorders or to patients who have ingested drugs (eg, cyclic antidepressants, cocaine, lithium, methylxanthines, isoniazid, propoxyphene, monoamine oxidase inhibitors, buproprion HCl, and cyclosporine) that place them at risk for the development of seizures.

Plasma catecholamine levels after intraosseous epinephrine administration in a cardiac arrest model.

STUDY OBJECTIVE: To measure plasma catecholamine levels and the cardiovascular response after administering epinephrine by the intraosseous (IO) route in an animal cardiac arrest model. MODEL: Eighteen anesthetized swine (weight, 12 to 15 kg) subjected to five minutes of electrically induced ventricular fibrillation followed by 25 minutes of chest compression and ventilation. INTERVENTIONS: Animals were anesthetized with 30 mg/kg IM ketamine and 75 mg/kg IV a-chloralose, intubated, placed on a respirator, and surgically instrumented. Ventricular fibrillation was induced. After five minutes of cardiac arrest, mechanical chest compressions were initiated and continued until the end of the experiment. Animals received 0.01 mg/kg IO epinephrine (five) or 0.1 mg/kg IO epinephrine (five) at ten and 20 minutes. The eight controls did not receive epinephrine. MEASUREMENTS AND MAIN RESULTS: Plasma epinephrine levels increased from 1.0 to approximately 40 to 85 ng/mL with the initiation of CPR. Epinephrine (0.01 mg/kg) increased plasma epinephrine levels to 222 +/- 72 ng/mL at 12 minutes after arrest but did not increase diastolic or mean blood pressure. Epinephrine (0.1 mg/kg) increased plasma epinephrine levels to 1,103 +/- 157 ng/mL at 12 minutes after arrest and increased diastolic and mean arterial blood pressures. CONCLUSION: IO epinephrine is rapidly transported to the central circulation but requires larger than currently recommended doses to produce a significant change in blood pressure.

Effects of calcium channel blocker overdose-induced toxicity in the conscious dog.

STUDY OBJECTIVE: To evaluate the effects of nifedipine, diltiazem, and verapamil overdose on systemic hemodynamics and blood flows to the coronary, superior mesenteric, renal, and iliac arteries in the unanesthetized dog. DESIGN: Nonblinded, controlled animal study. SETTING: Research laboratory of a large pharmaceutical company. TYPE OF PARTICIPANTS: Nineteen healthy mongrel dogs obtained from a commercial supplier. INTERVENTIONS: Under general anesthesia, flow probes were placed about the ascending aorta, circumflex coronary, superior mesenteric, renal, and iliac arteries; a micromanometer was implanted into the tip of the left ventricle; and a catheter was inserted into the descending aorta. Experiments were performed after a recovery period of at least two weeks. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, heart rate, cardiac output, left ventricular pressure, and regional blood flows were measured prior to drug administration, and after 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg IV administration of the study drugs. Dogs receiving diltiazem or verapamil also received a dose of 10.0 mg/kg. When the blood pressure had been reduced from baseline by 30%, 1.43 mg/kg nifedipine IV (six dogs) decreased total peripheral resistance by 51%, increased cardiac output by 35%, and increased heart rate by 132%. Coronary blood flow and iliac blood flow increased 93% and 45%, respectively, but mesenteric blood flow and renal blood flow were not significantly altered. Diltiazem (eight) and verapamil (seven) at equivasodepressor doses (1.43 to 4.43 mg/kg) caused less peripheral vasodilation and reflex tachycardia. At severely toxic levels when arterial blood pressure fell by 50%, all three drugs decreased cardiac output. Nifedipine still increased heart rate. Diltiazem and verapamil caused high-grade atrioventricular block, resulting in bradycardia. All three drugs caused a redistribution of cardiac output favoring the coronary bed over the other beds. CONCLUSIONS: In the conscious dog, calcium channel blocker-induced hypotension at the moderate level is associated with disparate effects on systemic hemodynamics, probably resulting from differential reflex sympathetic activation. However, at a more severe level, their toxic effects are similar and manifested predominantly by their actions on the slow calcium channel.

Comparison of two doses of endotracheal epinephrine in a cardiac arrest model.

STUDY OBJECTIVE: The objective of this study was to measure plasma catecholamine levels and the cardiovascular response before and after endotracheal administration of epinephrine in a swine cardiac arrest model. DESIGN: Prospective, controlled laboratory investigation. TYPE OF PARTICIPANTS: Twenty-one swine weighing 10 to 12 kg, anesthetized with ketamine and alpha-chloralose and ventilated with room air. INTERVENTIONS: Ventricular fibrillation was induced with 90 V of 60 Hz current delivered to the right ventricle by transvenous pacemaker. Blood samples for epinephrine were drawn before arrest and every two minutes thereafter. At five minutes, external mechanical cardiac compressions were initiated. Nine animals received no further therapy and served as controls. Two groups of six animals received either 0.01 mg/kg or 0.1 mg/kg of epinephrine through the endotracheal tube at ten and 20 minutes. Blood samples were assayed for epinephrine. MEASUREMENTS: Arterial blood pressure, lead II ECG, and plasma epinephrine. MAIN RESULTS: Swine receiving epinephrine 0.01 mg/kg had an increase in epinephrine levels after drug administration, but these were not significantly different from control levels. The 0.1-mg/kg dose group had a significant increase in plasma epinephrine levels compared with controls and the 0.01-mg/kg dose group after receiving epinephrine at ten and 20 minutes. These increases were from 14 +/- 3 to 215 +/- 40 ng/mL (+/- SEM) at 12 minutes after arrest and from 151 +/- 56 to 402 +/- 80 ng/mL at 22 minutes after arrest. CONCLUSION: These data suggest that standard dosing of epinephrine through the endotracheal tube during arrest does not produce significant increases in plasma catecholamines or blood pressure. Epinephrine 0.1 mg/kg produces a significant increase in plasma epinephrine levels, but it is not sufficient to produce a significant change in blood pressure.

Neurologic complications of cocaine abuse.

The neurologic complications of cocaine toxicity are responsible for a major portion of the morbidity and mortality associated with cocaine. Most of the complications appear to be related to the hyperadrenergic state induced by cocaine and may be treated symptomatically. Diazepam is the most effective drug for cocaine-induced seizures.

Effect of magnesium chloride on rabbit bronchial smooth muscle.

STUDY OBJECTIVE: The objective of this study was to determine the extent to which magnesium relaxes bronchial smooth muscle during induced contraction. DESIGN: An in-vitro model using bronchial rings from New Zealand White rabbits stimulated to contract by electrical stimulation, histamine, or bethanechol. INTERVENTIONS: Magnesium chloride 1, 6, 16, 36, and 86 mM was added to each tissue bath and resting tension was measured. Electrical stimulation 100 V/100 ms, histamine 10 mM, or bethanechol 6.25 mM was added to washed tissues to induce contraction. This was followed with magnesium chloride 5, 10, and 50 mM, and the response of bronchial smooth muscle was measured. MEASUREMENTS AND MAIN RESULTS: Magnesium chloride 1, 6, 16, 36, and 86 mM decreased the mean +/- SEM resting tension of bronchial rings by 40 +/- 16, 100 +/- 11, 110 +/- 10, 170 +/- 9, and 275 +/- 22 mg, respectively. Electrical stimulation (4) of 100 V/100 ms increased the mean +/- SEM resting tension by 168 +/- 52 mg. Magnesium chloride 5, 15, and 50 mM added to the tissue bath decreased the response to 100 V/100 ms to 65 +/- 27, 40 +/- 23, and 1 +/- 0 mg, respectively. Histamine 10 mM (4) increased mean +/- SEM resting tension by 490 +/- 121 mg. Magnesium chloride 5, 15, and 50 mM decreased the histamine response by 80 +/- 56, 250 +/- 74, and 475 +/- 131 mg, respectively. Bethanechol 6.25 mM (14) increased the mean +/- SEM resting tension by 495 +/- 74 mg. Magnesium chloride (5, 15, 50 mM) decreased bethanechol-induced tension by 52 +/- 18, 184 +/- 26, and 506 +/- 64 mg, respectively. CONCLUSION: Magnesium chloride produced dose-dependent relaxation of bronchial smooth muscle at rest and when stimulated by histamine, bethanechol, or electrical impulse. Calcium chloride was unable to significantly reverse magnesium-induced relaxation. These data support the hypothesis that magnesium relaxes smooth muscle and dilates bronchial rings.