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.

The effect of beta blockers on cardiac neural discharge associated with coronary occlusion in the cat.

The effect of timolol on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate, and rhythm changes associated with acute coronary occlusion of the left anterior descending artery was examined and compared with the effects of the beta blockers practolol and metoprolol. Timolol (5 mg/kg, IV) was infused 15 minutes prior to coronary occlusion in cats anesthetized with alpha-chloralose. Control heart rate fell from 129 +/- 10 to 106 +/- 2 one minute prior to coronary occlusion and remained at 106 +/- 2 beats/minute in the minute prior to arrhythmia. Control blood pressure fell from 126 +/- 20 to 91 +/- 19 and stabilized at 99 +/- 19 mm Hg one minute prior to coronary occlusion. Mean time to arrhythmia and death was 4.7 +/- 2.3 and 68.0 +/- 51.0 minutes (P greater than .05 vs no drug), respectively. Three cats died and two were sacrificed six hours after coronary occlusion. Blood pressure fell to 86 +/- 20 mm Hg two minutes after coronary occlusion, rose to 95 +/- 23 mm Hg at ten minutes, and remained there for ten minutes. Timolol did not alter postganglionic cardiac sympathetic neural discharge prior to coronary occlusion. Two minutes after coronary occlusion, mean postganglionic cardiac sympathetic neural discharge was 128 +/- 27 and increased to 139 +/- 36 impulses/second (% control) 4 minutes after coronary occlusion. A similar trend was found for the data recorded in 15 nerves (eight cats) in which coronary occlusion was initiated without timolol. The data suggest that a difference exists among beta blockers because prior to coronary occlusion, the cardioselective drugs metoprolol (1, 5, and 10 mg/kg, IV) and practolol (8 mg/kg, IV) depressed postganglionic cardiac sympathetic neural discharge whereas noncardioselective timolol did not. Because all three beta blockers increased the times to arrhythmia and death (although the increase was significant only after metoprolol and practolol), the acute protective mechanism does not appear to be due primarily to a depression of spontaneous sympathetic neural discharge.

The effect of timolol given five minutes after coronary occlusion on plasma catecholamines.

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 effect of chronic timolol in an animal model for myocardial infarction.

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.

The effect of dilevalol on cardiac autonomic neural discharge, plasma catecholamines, and myocardial beta receptor density associated with coronary occlusion.

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.

Suppression of pentylenetetrazol-elicited seizure activity by intraosseous propranolol in pigs.

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.

An investigation of the pathological and physiological effects of intraosseous sodium bicarbonate in pigs.

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.

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.

Regional distribution of myocardial beta-adrenoceptors in the cat.

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 effect of acute and chronic administration of timolol on cardiac sympathetic neural discharge, arrhythmia, and beta adrenergic receptor density associated with coronary occlusion in the cat.

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)

Endogenous and exogenous plasma catecholamine levels in cardiac arrest in swine.

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.

Needle aspiration of breast masses in the emergency department.

The discovery of a breast mass is often the source of great concern for a patient. The mass may, however, be no more than a benign cyst that may be treated in the emergency department. This article describes the technique of needle aspiration--a simple, safe procedure that in many cases is both therapeutic and curative.

Emergency applications of intraosseous infusion.

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.

A clinical evaluation of the QBCII centrifugal hematology analyzer in the emergency department.

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.

Informed consent for clinical research in the emergency department.

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.

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.

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.

Effect of timolol on the sympathetic nervous system in coronary occlusion in cats.

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.

Comparison of deep and shallow endotracheal administration of dionosil in dogs and effect of manual hyperventilation.

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.