James R. Roberts

Blood Levels Following Intravenous and Endotracheal Epinephrine Administration

The blood levels of epinephrine and its metabolites which were obtained when the drug was given by both the intravenous (IV) and endotracheal (ET) routes were compared. Anesthetized dogs were subjected to radioactive epinephrine in doses of 0.005, 0.03, 0.06, and 0.09 mg/kg administered both intravenously and endotracheally. Blood levels were obtained at 0.25, 0.75, 1.5, 3, 5, 10 and 30 minutes following injection and analyzed by thin layer chromatography. The maximum measured concentration following IV injection was observed at 15 seconds. Epinephrine was rapidly metabolized with 20% of the original concentration detected at 5 minutes following IV injection. When the drug was given by the ET route, the maximum measured concentration was similarly observed at 15 seconds. Following ET installation, initial blood concentrations are sustained over a much longer period of time and 80% of the initial concentration was detected at 5 minutes. Maximum concentrations are approximately one-tenth of those achieved with an equal IV dosage. It is concluded that endotracheally and intravenously administered epinephrine rapidly reach maximum blood levels although there are differences in kinetics between the two routes.

Comparison of the pharmacological effects of epinephrine administered by the intravenous and endotracheal routes

Epinephrine in various dosages was administered to anesthetized dogs by intravenous and endotracheal routes. Both methods produced measurable effects on heart rate, blood pressure, and respiration. Tachycardia occurred more rapidly after endotracheal administration than after intravenous administration. Respiration appeared to be supported more advantageously with the larger endotracheal dosages. The maximum blood pressure rise was delayed only 60 seconds by the endotracheal route. With an endotracheally administered dose of ten times the intravenous dose, equal responses in blood pressure were obtained. However, when equal doses are compared, there is only a two to three fold increase with the intravenous route. The endotracheal route may be less toxic at higher doses, affording greater safety when large amounts of epinephrine are used. It is concluded that endotracheally administered epinephrine produces significant pharmacologic effects in anesthetized dogs.

The Use of Glucagon in a Case of Calcium Channel Blocker Overdose

The hypotension and myocardial depression that result from calcium channel blocker ingestion often are refractory to standard therapeutic modalities. Anecdotal reports on the use of glucagon have failed to show significant hemodynamic improvement. We report the first case of calcium channel blocker overdose that responded to glucagon. We conclude that glucagon is safe and effective in the management of hemodynamic instability associated with calcium channel blocker poisonings.

Endotracheal epinephrine in cardiorespiratory collapse

The endotracheal route for the administration of epinephrine has been studied extensively in dogs. There has been little in the medical literature to document the successful use of this technique in humans. The successful use of endotracheally administered epinephrine in two patients with cardiorespiratory collapse is reported. Specific points concerning endotracheal drugs are discussed and a set of guidelines for clinical use is offered.

Clinical characteristics of angiotensinconverting enzyme inhibitor-induced angioedema

We present the cases of two patients with angiotensin-converting enzyme (ACE) inhibitor-induced angioedema that required intubation for life-threatening airway compromise. This side effect has been previously reported with all ACE inhibitors, but its incidence and potential for a fatal outcome may not be fully appreciated. A review of the literature reveals 227 reports of this reaction with an overall incidence of approximately 0.1% to 0.2%. The etiology is nonimmunogenic and thought to be related to accentuated bradykinin activity. There is no clinical profile that identifies patients at increased risk for this side effect. There are unique clinical characteristics to this idiosyncratic reaction: angioedema may suddenly occur even though the drug has been well tolerated for months or years; symptoms may regress spontaneously while the patient continues the medication, erroneously prompting an alternative diagnosis; the pathology has a special predilection for the tongue, a circumstance that renders orotracheal and nasotracheal intubation difficult; symptoms may progress rapidly despite aggressive medical therapy, necessitating emergency airway procedures; and a rebound phenomenon following successful medical therapy has been described. We recommend intensive medical treatment before angioedema is severe enough to thwart standard methods to ensure a protected airway. Once even minor angioedema is attributed to an ACE inhibitor, an alternative class of antihypertensive medication should be chosen. Individuals with a history of idiopathic angioedema probably should not be given ACE inhibitors.

Endotracheal naloxone reversal of morphine-induced respiratory depression in rabbits

In an emergency, intravenous access may be difficult to obtain rapidly. Alternate routes of administration for drugs are, therefore, desirable. Our study was performed to determine if naloxone could be efficacious in reversing morphine-induced respiratory depression in rabbits when administered using the endotracheal route. Our results indicate that naloxone administered in this fashion is effective in reversing morphine-induced respiratory depression in the rabbit. Mean minute ventilation was depressed to greater than half of resting baseline levels using morphine sulfate. Endotracheally administered naloxone reversed this respiratory depression and resulted in a greater than five-fold increase in mean minute ventilation above baseline levels. We concluded that endotracheal naloxone is efficacious in reversing morphine-induced respiratory depression in the rabbit. The endotracheal route may be an effective alternative for naloxone administration in man when rapid intravenous access is not obtainable.

Multiple Cranial Nerve Deficits After Ethylene Glycol Poisoning

We report the cases of two patients who developed cranial nerve palsies after drinking ethylene glycol. A 33-year-old man developed multiple cranial nerve deficits nine days after the ingestion of ethylene glycol in a suicide attempt. Clinical findings included profound bilateral cranial nerve VII palsies and severe dysfunction of cranial nerves IX and X. The neuropathy occurred despite treatment with hemodialysis. The dysphagia completely cleared within two weeks, but at six months a severe bilateral cranial nerve VII dysfunction persisted. A 22-year-old man undergoing hemodialysis for ethylene glycol-induced renal failure developed bilateral cranial nerve VII dysfunction 14 days after ingestion. At a three-month follow-up, the patient demonstrated only moderate functional recovery. The etiology of the cranial nerve deficits is unknown but may be related to oxalate crystal deposition of ethylene glycol-induced pyridoxine dysfunction.

Endotracheal epinephrine in a canine anaphylactic shock model.

This study was undertaken to determine if epinephrine administered endotracheally is as effective in treating anaphylactic shock as is intravenously administered epinephrine. An animal model of anaphylactic shock was produced in anesthetized dogs by the intravenous administration of histamine phosphate. Both the endotracheal and intravenous routes of epinephrine administration resulted in efficient and effective reversal of histamine-induced hypotension. At the doses employed, the intravenous administration of epinephrine resulted in the production of significantly (p less than 0.05) greater numbers of ventricular cardiac arrhythmias than did the endotracheal route of administration.

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.

Intravenous regional anesthesia

A series of 33 patients who underwent intravenous regional anesthesia for treatment of orthopedic and surgical procedures is reported. Intravenous regional anethesia is a safe and reliable alternative to general or other regional anesthesia techniques for use in the emergency department. The technique is easily mastered and requires minimal special equipment. The agent of choice is lidocaine in a dosage of 3 mg/kg administered as a 0.5% solution. Complications are few and are usually related to rapid systemic absorption of the anesthetic agent or minor mistakes in technique.