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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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

The use of epinephrine in cardiac arrest remains an area of continuing controversy. This study was undertaken to characterize the effect of endogenous and exogenous epinephrine on plasma epinephrine levels, and the relationship between plasma epinephrine and norepinephrine and mean arterial pressure and diastolic arterial pressure. Nineteen young swine were anesthetized with ketamine and alpha-chloralose and instrumented with arterial and central venous lines. Ventricular fibrillation was induced by pacemaker. At 5 min post arrest cardiopulmonary resuscitation (CPR) was begun with a mechanical resuscitator. Animals were randomized to receive either saline placebo (n = 9), 0.01 mg/kg epinephrine (n = 5) or 0.1 mg/kg epinephrine (n = 5) via the central venous line. Plasma was drawn for high pressure liquid chromatographic analysis of catecholamines every 2 min. The resuscitation was carried on for 30 min after the arrest. Plasma epinephrine levels differed significantly between treated subjects and controls, as did mean arterial pressure and diastolic arterial pressure. There was a correlation between both mean arterial pressure and diastolic arterial pressure with plasma epinephrine and log epinephrine, but no correlation with plasma norepinephrine. The two doses of epinephrine did not differ in the degree to which they elevated the mean arterial pressure and diastolic pressure. We conclude that the endogenous catecholamine response to cardiac arrest while producing norepinephrine and epinephrine levels many times greater than those in the resting animal, is not sufficient to maintain blood pressure. There is a strong correlation between blood pressure and the log of the plasma epinephrine concentration, but epinephrine concentration alone does not solely account for changes in blood pressure during arrest.

Cats anesthetized with alpha chloralose received saline or dilevalol (1 mg/kg, IV) during a 10-minute infusion. Fifteen minutes later, the left anterior descending coronary artery was subjected to coronary occlusion 2 mm below its origin. Regional differences in the beta receptor densities were found for the atria and ventricles and for the areas within the left ventricle in cats with no coronary occlusion and dilevalol or saline. The variation in beta receptor density distribution may be related to functional differences. Coronary occlusion and saline or dilevalol did not modify the myocardial beta receptor density regional distribution. Mean times to arrhythmia and death in five saline cats were 5.8 +/- 3.6 (N = 3) and 5.4 (N = 2) minutes; three cats were killed 6 hours after coronary occlusion. In five dilevalol cats the times to arrhythmia and death were 2.2 +/- 0.8 (N = 5) and 75.9 +/- 70.7 (N = 4); 1 cat was killed. Dilevalol induced a significant decrease in blood pressure and heart rate prior to coronary occlusion. Coronary occlusion decreased blood pressure and heart rate in both groups. Twenty-five minutes after dilevalol but prior to coronary occlusion, postganglionic cardiac sympathetic neural discharge decreased to 81%. In the minutes prior to arrhythmia, postganglionic cardiac sympathetic neural discharge was 95% and was significantly increased to 121% 3 minutes after coronary occlusion. The postganglionic cardiac sympathetic neural discharge values after coronary occlusion were similar to those in the saline cats. Dilevalol depressed postganglionic cardiac sympathetic neural discharge prior to coronary occlusion but did not prevent the nonuniform (i.e., increases, decreases, or no change) discharge in the postganglionic cardiac sympathetic neural discharge associated with coronary occlusion-induced arrhythmia. Norepinephrine and epinephrine values in saline cats increased the first 5 minutes after coronary occlusion; this increase was associated with arrhythmia. Norepinephrine and epinephrine values from minute 15 to minute 360 did not differ from control. Dilevalol prevented the increase in norepinephrine and epinephrine levels associated with arrhythmia and death.

Our clinical observations suggested that vigorous fluid therapy in children often resulted in hypokalemia. A retrospective review was conducted of four years of admissions to a pediatric intensive care unit. A total of 29 patients were identified who received at least 20 ml/kg of intravenous fluid in their first hour of care and had a pretreatment and posthydration serum K obtained. The potassium levels dropped from a mean pretreatment value of 4.6 +/- 1.0 mEq/L to a mean of 3.3 +/- 0.8 mEq/L (P less than 0.005). Coincidental arterial pH measurements were available in 16 cases. A separate analysis of potassium change in this group revealed that pH change alone could not account for the drop in serum K. Significant hypokalemia may occur after aggressive rehydration of critically ill pediatric patients.

The endotracheal route has been used as a second route of choice for administration of emergency drugs for several years; however, the optimal technique for administration of drugs by this route has not been clearly defined. One important aspect of technique involves the question of how distribution to the distal-most endobronchial tree is influenced by initial depth of endotracheally administered drug instillation and use of forced manual hyperventilation. This study demonstrates that depth of instillation of drugs administered by the endotracheal route may not be an important factor in the delivery of medications to absorptive sites in the lung. It appears, however, that forced manual hyperventilation is essential to assure bilateral and optimal distal delivery of endotracheally administered medications.

IV magnesium sulfate was administered to a 72-year-old man with acute respiratory failure secondary to a severe asthma attack. The patient had clinically deteriorated despite aggressive standard treatment and evidenced acidosis and hypercarbia by arterial blood gas determination. An IV dose of 1 g MgSO4 produced rapid clinical and arterial blood gas improvement and enabled management of the patient without endotracheal intubation and mechanical ventilation. This is the first reported case of the use of IV MgSO4 to prevent intubation and assisted ventilation in a patient with acute respiratory failure complicating asthma.

The intraosseous (IO) route provides a rapid and effective alternative venous access in the pediatric population when the conventional intravenous (IV) route cannot be easily obtained. DL-propranolol, a beta-adrenoceptor antagonist, exhibits antiepileptic activity in various animal seizure models. This study assessed the efficacy of IO propranolol in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, ECG and electrocortical activity. Seizure activity was induced by pentylenetetrazol (PTZ; 100 mg/kg; IV). Sixty seconds after the onset of seizure activity, the animals either received no drug (control) or propranolol (IV or IO via an 18-gauge spinal needle placed in the right proximal tibia). A transient increase (16.3-50.0%) in the mean arterial blood pressure (MAP) was observed following PTZ administration. Both IO and IV propranolol significantly suppressed the seizure duration (SD) (sec/min interval) at 1 min following drug administration; SD control, 36.3 +/- 4.8; IV propranolol, 12.3 +/- 5.1; IO propranolol, 18.3 +/- 6.0. In addition, both IV and IO propranolol produced a maximal decrease of 32-38% in the basal heart rate; and reduced the transient increase in MAP elicited by PTZ, with no significant effect on the basal MAP. The data demonstrate that 1) propranolol possesses anticonvulsant activity against PTZ-induced seizure in the pig, and 2) the intraosseous route is a rapid and effective alternative venous access for propranolol administration in swine.

Intravenous access for the administration of antiepileptic drugs can be both time-consuming and difficult in an actively seizing infant. We conducted a study to examine the intraosseous route as an alternate means of vascular access for the administration of diazepam in a pentylenetetrazol-seizure model in pigs. Epileptogenic activity was induced with pentylenetetrazol 100 mg/kg in 15 domestic swine that had undergone craniotomies for electrocortical recording. Diazepam (0.1 mg/kg) was administered IV (n = 5) or intraosseously (n = 5); control animals received no drug (n = 5). Epileptogenic activity was suppressed below control levels within one minute in the IV group and within two minutes in the intraosseous group. A two-way analysis of variance did not show a significant difference between the IV and intraosseous routes; however, both were significantly different when compared to the control. There also was no significant difference in plasma diazepam levels between the two groups at one, two, five, ten, 15, and 20 minutes. Our study demonstrated that the intraosseous route is a rapid and effective alternative for diazepam administration.

The reported study determined whether timolol would afford a protective effect by preventing the coronary occlusion-induced arrhythmias associated with the increase in plasma norepinephrine (NE) and epinephrine (E). Ten anesthetized cats received saline or timolol (5 mg/kg, IV) five minutes after coronary occlusion of the left anterior descending coronary artery 10 to 14 mm below its origin. Coronary occlusion produced arrhythmia in three of the cats that received saline and in four of the cats that received timolol. Three of the saline-treated cats died in cardiogenic shock; two were sacrificed six hours postocclusion. Four of the timolol-treated cats died in congestive heart failure postcoronary occlusion. There was a gradual increase in NE (P greater than .05) and E (P less than .05) in both groups after coronary occlusion. Death produced a significant increase in NE and E levels. Timolol did not modify the occurrence of arrhythmias and the associated increase in plasma NE and E that developed after coronary occlusion and at death.

The drug of choice for local anesthesia in most emergency departments is lidocaine. However, it wears off shortly after suturing is complete and patients may experience pain after closure of the wound. We conducted a study to determine the degree of anesthesia obtained during and after repair of lacerations using lidocaine 1% versus bupivacaine 0.25%, a long-acting local anesthetic. Lidocaine and bupivacaine were administered in a double-blind, randomized fashion to 104 patients. Each patient was asked to rate his pain on a 0 to 10 scale (0, no pain; 10, severe pain) prior to administration of the anesthetic. They then rated pain on an identical scale at 30 minutes, and one, two, three, four, five, six, 12, 18, and 24 hours after completion of suturing. The mean baseline pain was 2.96 for the lidocaine group and 3.07 for the bupivacaine group. This decreased to less than 1.0 in both groups 30 minutes after infiltration. It remained low for the bupivacaine group for the next five hours, but increased almost to preanesthesia levels by two hours in the lidocaine group. A three-way analysis of variance revealed a significant difference (P less than .001) between the pain response of the two groups. There was no statistical difference (P greater than .05) between the age of the patients, size of laceration, and amount of drug used. The study shows that patients do experience pain after a wound is sutured and the anesthetic has worn off. It also demonstrates that bupivacaine significantly reduces the pain a patient may experience after repair of a wound.

The case of a 3-month-old male infant who was found unresponsive and cyanotic in a crib at home is presented. On arrival in the emergency department the child was receiving basic cardiopulmonary resuscitation (CPR) by a rescue squad and was without vital signs in asystole. The patient achieved a stable rhythm and blood pressure before intravenous access was obtained. Epinephrine and atropine were given via the endotracheal route and sodium bicarbonate through intraosseous infusion.

Intravenous (i.v.) access for administration of antiepileptic drugs can be time-consuming and difficult in an infant during a seizure. This study examined the intraosseous (i.o.) route as an alternative means of vascular access for drug administration in an animal-seizure model. Domestic swine (13-20 kg) were anesthetized with ketamine (20 mg/kg i.m.) and alpha-chloralose (80 mg/kg i.v.) and given gallamine (4 mg/kg i.v.) to prevent muscle fasciculations. Tracheosotomies were performed and the animals were ventilated with a Harvard respirator. The left femoral vein was cannulated and pentylenetetrazol (PTZ) (100 mg/kg) was given to elicit epileptogenic activity. Sixty seconds after onset of epileptogenic activity, the animals received saline or diazepam (DZP) (0.1 mg/kg) or propranolol (2.5 mg/kg) i.v. or via the i.o. route (18-gauge spinal needle placed in the right proximal tibia). Both DZP and propranolol were effective in suppressing epileptogenic activity via the i.v. or i.o. routes. Thus, the i.o. route is a rapid and effective alternative route for the administration of antiepileptic drugs when an i.v. route cannot be readily established.

Vascular access is an important step in the care of the critically ill child but can be very difficult and time consuming. Recently, intraosseous infusion has experienced a resurgence as a rapid alternative to venous cannulation. Several cases illustrate the usefulness of this technique in the emergency department. Included are the first reports of the use of intraosseous diazepam and succinylcholine.

Use of the intraosseous (i.o.) route as an alternative venous access for drug administration has increased. This study examined the efficacy of i.o. lorazepam (LZP) in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, EEG, and electrocortical activity. Seizure activity was induced by PTZ (100 mg/kg i.v.). Sixty seconds after onset of seizure activity, animals either received no drug (control) or LZP (1.0 mg/kg) administered i.v. or i.o. via an 18- or 13-gauge spinal needle inserted in the right proximal tibia. Both i.o. and i.v. LZP significantly suppressed the duration of seizure activity (DSA) (s/min interval) within 1 min following drug administration: DSA control, 46.2 +/- 3.6; i.v. LZP, 25.0 +/- 5.1; i.o. (18-gauge) LZP, 27.6 +/- 6.0; i.o. (13-gauge) LZP, 24.0 +/- 2.4. Seizure activity was essentially abolished at 1 min following LZP infusion. In addition, both i.v. and i.o. LZP did not have significant effects on the basal heart rate and mean arterial blood pressure. The data demonstrate that in swine (1) the i.o. route is an effective alternative venous access for LZP administration, and (2) the size of spinal needles does not affect the antiepileptic efficacy of i.o. infusion of LZP.

Obtaining venous access continues to be one of the most difficult problems faced by a physician caring for the pediatric patient in cardiac arrest. Our study examined the use of the intraosseous route (through the bone) to obtain venous access for sodium bicarbonate administration in a cardiac arrest model. Ventricular fibrillation was induced in 23 domestic swine. Cardiopulmonary resuscitation was performed for five minutes and sodium bicarbonate (1 mEq/kg) was administered through a peripheral IV line (n = 6), a central IV line (n = 5), or intraosseously (n = 6). Controls (n = 6) did not receive bicarbonate. Blood pH was sampled every two minutes for 30 minutes from the right ventricle, left ventricle, and femoral artery. An analysis of variance revealed that the central and intraosseous routes were significantly different (P less than .05) from the peripheral group, and that all three groups were significantly different (P less than .05) from the control. Pathology studies revealed only minor damage to bone when sodium bicarbonate was administered intraosseously. These data demonstrate that the intraosseous route is a rapid and effective alternative for venous access in a cardiac arrest model.

As part of an effort to reduce patient waiting time for laboratory results, the QBCII desktop CBC analyzer was evaluated in an emergency department. CBCs were performed by the emergency department staff (multiple observers) on 498 patients and by a single observer on 250 patients. Time required by the emergency department staff to obtain a CBC was 10.1 minutes compared with 47.8 minutes for the hospital laboratory. Correlation coefficients between hospital laboratory and QBCII were WBC 0.94, hematocrit 0.92, platelets 0.88, lymphocytes/monocytes 0.92, and granulocytes 0.90.

The effect of no drug or timolol (5 mg/kg, PO, for 1, 2, or 8 weeks on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate and beta-receptor density after acute coronary occlusion of the left anterior descending artery was compared. Beta-receptor density, determined by binding of 3H-dihydroalprenolol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal and LV2 = distal left anterior descending artery distribution, LV3 = posterior left ventricle, S = septum, and RV = right ventricle). In control cats (no coronary occlusion or timolol) beta-receptor density of LV2 and LV3 was greater (P less than .05) than LA, RA, LV1, and RV. LV3 was greater (P less than .05) than S and RA, and LA was less than S. Longer treatment with timolol increased beta-receptor density. When compared with no timolol, beta-receptor density was greater in RA after 8 weeks and in LV1 after 2 weeks and not different in LV2 and S. Beta-receptor density and LV3 and RV were greater after 8 weeks than after 1 week or no timolol. Spearman rank correlation coefficients between dose and beta-receptor density revealed an increase (P less than .05) for all heart areas. Heart rate did not vary before timolol and was decreased after all doses of timolol. Timolol increased the mean times to coronary occlusion-induced death although the increase was not statistically significant. Timolol did not prevent postganglionic cardiac sympathetic neural discharge associated with arrhythmia. Timolol may increase beta-receptor density and decrease synaptic norepinephrine, causing a decreased release per cardiac sympathetic nerve impulse. Alternatively, molecules of timolol may accumulate in nerve endings and be released in greater concentrations at the receptors. This could explain the protection against coronary occlusion-induced arrhythmia and death.

We conducted a study to evaluate the absorption of endotracheally administered diazepam and the pulmonary pathologic changes induced by its administration. Six cats received diazepam and five cats received saline endotracheally. Serial blood gases and serum diazepam levels were drawn at intervals for 90 minutes after the administration of diazepam. The cats were sacrificed after two days and their lungs were examined by a pathologist. Mean diazepam levels reached a peak two minutes after the administration of diazepam and remained elevated above therapeutic levels for 90 minutes. There was no significant change in pH, PO2, or PCO2 for either group. Histologic examination of the lungs showed a significantly increased incidence of pneumonitis in the diazepam group as compared to the saline group. This study demonstrates that although diazepam is well absorbed when administered endotracheally, it has adverse effects on the lungs that may preclude endotracheal use in the currently available commercial form.

Clinical studies have shown that treatment with chronic timolol after a myocardial infarction decreases the incidence of reinfarction and mortality. It also limits the size of infarction when it is given IV during the acute phase of an infarction and followed by chronic oral dosing. It has been postulated that beta blockers work not only by a direct mechanism on the heart, but by altering neural discharge to the heart and depressing the sympathetic overactivity seen in 35% of patients immediately after an infarction. Our study examined the effect of timolol on sympathetic cardiac neural discharge, blood pressure, heart rate, and rhythm during acute coronary occlusion produced by ligation of the left anterior descending artery 10 to 14 mm below its origin in alpha-chloralose-anesthetized cats. Timolol or normal saline 5 mg/kg IV was given five minutes post coronary occlusion. The infusion of timolol significantly decreased the mean arterial blood pressure and heart rate. Sympathetic cardiac neural discharge in the group treated with timolol five minutes post coronary occlusion did not differ from that in the saline group. Thus there was a nonuniform (an increase, a decrease, or no change) sympathetic cardiac neural discharge associated with the production of occlusion-induced arrhythmia. These data suggest that the action of timolol on the sympathetic cardiac neural discharge is not its major mode of protection.

The purpose of this study was to delineate the distribution of beta-adrenoceptor density in the cat heart, with an emphasis on areas within the left ventricle. beta-Adrenoceptor densities, determined for hearts obtained from five cats, were not significantly different in the left and rights atria, i.e. 47.6 +/- 7.2 and 32.8 +/- 7.5 fmol/mg protein, respectively. beta-Adrenoceptor densities for the septum and right ventricle were 105.4 +/- 15.0 and 65.0 +/- 14.0 fmol/mg protein, respectively. The beta-adrenoceptor density for the proximal distribution of the left anterior descending artery LV1, distal distribution of the left anterior descending artery LV2 and posterior wall of the left ventricle LV3 were: 81.3 +/- 11.5, 145.1 +/- 20.8 and 165.4 +/- 35.8 fmol/mg protein, respectively. Thus, the distribution of the beta-adrenoceptor densities was greatest in the apex of the left ventricle. The data suggest that there are regional differences in the beta-adrenoceptor densities among the areas of the heart and within the left ventricle. These differences may be related to functional differences.

The technique of intraosseous infusion has attracted increasing interest in recent years, and has proven valuable for drug administration. This study was undertaken to determine whether it was also a potential route for fluid resuscitation. Thirteen- or eighteen-gauge tibial intraosseous needles were placed in eight "large" (mean weight, 14.4 kg) and eight "small" (mean weight, 5.8 kg) swine and the flow rate of blood and saline measured under gravity and 300 mm Hg. Flow was significantly greater using 13-gauge needles in the "large" swine, significantly greater for saline than for blood, and for pressure infusion versus gravity in all animals. A fluid bolus of 20 ml/kg could be given to all animals in less than 10 minutes using pressure infusion. These data suggest that intraosseous infusion is a reasonable initial step in fluid resuscitation of pediatric subjects until more conventional vascular access has been established.

Conventional nebulized beta-agonist therapy has met with disappointing results in an increasing number of moderate to severe asthmatics who may be characterized as "poor responders." Thirty-eight patients suffering from acute exacerbations of moderate to severe asthma were treated in an emergency department with an intravenous infusion of saline placebo or 1.2 g of magnesium sulfate after conventional beta-agonist therapy failed to produce significant improvement in peak expiratory flow rate. Nineteen patients were randomized into each of two groups in a placebo-controlled, double-blind clinical trial. The treatment group demonstrated an increase in peak expiratory flow rate from 225 to 297 L/min as compared with 208 to 216 L/min seen in the placebo group. In addition, the number admitted vs discharged was significantly better for the treatment group (7 vs 12) than the placebo group (15 vs 4). Intravenous magnesium sulfate may represent a beneficial adjunct therapy in patients with moderate to severe asthma who show little improvement with beta-agonists.

Recent interest in the intraosseous (IO) route as an alternative venous access for drug and fluid administration has increased. This study examined the physiological and skeletal pathological effects of IO NaHCO3 in pigs. In the pathological studies, swine (8-10 kg) received NaHCO3 (1 mEq/kg) in one tibia and saline (1 ml/kg) in the other tibia via an 18-gauge spinal needle inserted into the anteromedial surface of the bone. The animals were then observed for one month, sacrificed, and the tibias were isolated, sectioned, and stained for pathological examinations. The physiological effects of IO NaHCO3 infusion were studied and compared with that of intravenous (IV) administration using a cardiac arrest model as previously described. The results demonstrated that NaHCO3 had no effect on the mean arterial blood pressure and plasma catecholamine levels, but increased arterial pH values within two minutes of administration. Similar effects were found with IV NaHCO3. Pathological data indicated signs of minimal local increase in skeletal turnover associated with IO NaHCO3 infusion. It is concluded that the IO route is a safe alternative venous access for NaHCO3 administration in swine.

Informed consent serves as the basis for a partnership between patients and physicians as they attempt to find better methods of diagnosis and treatment. Despite the importance of informed consent, this is an area of research that is frequently overlooked. In fact, an improperly designed consent form is the most common reason research protocols are rejected or approval is delayed. The essential elements of informed consent and problems obtaining informed consent from patients is an emergency department are reviewed.

The effect of timolol (5 mg/kg, p.o., b.i.d. 7 or 14 days) on cardiac beta adrenergic receptor density, the times to arrhythmia (AR) and death (D), heart rate, mean arterial blood pressure, and postganglionic cardiac sympathetic neural discharge after acute coronary occlusion in cats was examined. In the control animals, receptor densities in the left and right atria did not differ, but were lower than the right ventricle. Left ventricle and septum receptor densities were higher, with the left ventricle the highest. The importance of the gradation of beta receptors with increasing density from base to apex appears to be its relation to cardiac contractile function. Occlusion in cats not treated with timolol did not alter the cardiac beta receptor densities. After timolol for 7 or 14 days, no occlusion, receptor density increased in left ventricle and septum although the increase was only significant after 14 days. A comparison of the beta adrenergic receptor densities in cats pretreated with timolol for 7 or 14 days with or without occlusion revealed that, in general, a decrease (p greater than 0.05) occurred for the occlusion group. Timolol decreased heart rate and blood pressure prior to occlusion. The mean times to AR and D were not significantly increased by either dosing regimen of timolol, although the trend was for an increase in the time to D after 7 days of timolol and an increase in the time to AR and D after 14 days of timolol. When compared with data obtained in saline cats, chronic timolol produced minimal changes in postganglionic cardiac sympathetic neural discharge. Timolol given chronically (p.o.) or acutely (5 mg/kg, i.v. given 15 min prior to occlusion) also did not prevent the cardiac sympathetic discharge associated with the development of AR. The time to AR and D in the acutely treated cats was increased but not significantly. Since cardiac sympathetic neural discharge increased as blood pressure fell in the control period but did not increase after occlusion in the timolol treated animals, the combination of timolol and occlusion may have modified neural discharge via an action on the baroreceptor mechanism. That chronic administration of timolol produces an effect not present in cats in which only occlusion was done is supported by the observation that chronic treatment produced an occlusion-induced decrease in beta adrenergic receptor density.(ABSTRACT TRUNCATED AT 400 WORDS)