Intravenous propofol: unique effectiveness in treating intractable migraine.

OBJECTIVE: To report the unique effectiveness of propofol, an intravenous anesthetic agent, in treating refractory migraines and other headaches in the setting of an outpatient headache center. BACKGROUND: We initially observed the dramatic abolition of ongoing migraine in patients (n=6) being treated with propofol in preparation for epidural and other nerve blocks in the headache and pain clinic. The reduction of headache severity was virtually 100%. We decided to treat an additional cohort of patients with intravenous propofol in the headache clinic; these patients had intractable migraines that were refractory to the usual abortive treatments. Subanesthetic doses of propofol were employed in this study. This is the first known report of the utility of this agent specifically for the treatment of intractable headache. METHODS: Seventy-seven patients were treated for intractable headache in the clinic with intravenous propofol, for both migraine and nonmigrainous headache refractory to the usual methods of abortive treatment. RESULTS: The average reduction in headache intensity was 95.4% after an average of 20 to 30 minutes of intravenous propofol treatment, using a patient-rated visual analog scale of 0 to 10. Sixty-three of 77 patients reported complete abolition of their headache. The average dose of propofol was 110 mg, which is well within the usual range of preanesthetic doses and is clearly subanesthetic. Moreover, only three of the treated patients reported a return of the headache on the day following treatment. The neuropharmacology of propofol and the putative multiple mechanisms of action upon various neurotransmitter systems in the brain, particularly gamma aminobutyric acid A receptor subtypes, are discussed to explain the results in our patients. CONCLUSIONS: The use of intravenous propofol may represent a new, rapid, and highly effective form of abortive headache treatment in the headache clinic or emergency room setting and may offer an alternative to other treatment modalities for acute migraine and other severe intractable headaches. The effectiveness of propofol raises many new questions about the pathophysiology of migraine and other headaches.

Role of the adrenergic nerve terminal in digitalis-induced cardiac toxicity: a study of the effects of pharmacological and surgical denervation.

This study determined whether the protective action of bretylium against ouabain-induced ventricular arrhythmia in the cat is related to an action of bretylium on the adrenergic nerve terminal. Bretylium pretreatment (20 mg/kg, i.v.) administered 2 h prior to ouabain (2 micrograms/kg/min, i.v. until death) increased the dose of ouabain to produce premature ventricular contraction, ventricular tachycardia, and death from 77.2 +/- 5.2 to 107.7 +/- 6.7 micrograms/kg; from 84.9 +/- 5.2 to 113.9 +/- 7.1 micrograms/kg; and from 108.8 +/- 4.0 to 146.7 +/- 5.7 micrograms/kg, respectively (p less than 0.05). Surgical denervation 2 weeks prior to the experiment or 6-hydroxydopamine (6OH dopamine), 20 mg/kg, i.v., administered 3 or 14 days prior to the ouabain infusion did not protect against the arrhythmogenic effects of ouabain. When bretylium was administered to cats pretreated with 6OH dopamine 3 days prior to the ouabain infusion or to surgically denervated cats, the protective action against ouabain-induced arrhythmia did not develop. Since 6OH dopamine and surgical denervation prevented the action of bretylium on ouabain-induced ventricular arrhythmia, it appears that bretylium is acting on the adrenergic nerve terminal. Thus, agents like bretylium that act on the adrenergic nerve terminal, leaving it structurally intact but not functional, are effective against ouabain-induced ventricular arrhythmia while procedures which cause the degeneration of the adrenergic nerve terminal, such as 6OH dopamine and surgical denervation, are not. These observations indicate that for the protective effect of sympathectomy against ouabain-induced arrhythmia to develop, the adrenergic nerve terminal must be present, although not functional as far as adrenergic neurotransmission is concerned. Changes in the heart rate or blood pressure did not appear to be a factor in the protective effect of bretylium.

The action of reserpine, 6-hydroxydopamine, and bretylium on digitalis-induced cardiotoxicity.

This study determined whether the protective effect of reserpine against ouabain-induced ventricular arrhythmias in the cat is due to an action of the drug on the adrenergic nerve terminal. Reserpine (5 mg/kg i.p.) administered 24 h prior to ouabain (2 micrograms/kg per min i.v., until death) increased the dose of ouabain to produce premature ventricular contractions, ventricular tachycardia, and death from 77.3 +/- 5.2 to 105.0 +/- 6.0; 84.9 +/- 5.2 to 132.7 +/- 9.1; and 108.8 +/- 4.0 to 165.7 +/- 10.4 micrograms/kg, respectively (P less than 0.05). When 6-hydroxydopamine (6OHDA; 20 mg/kg i.v.) was given 3 days prior to the experiment, the protective effect of reserpine was not evident. When bretylium (20 mg/kg i.v., 2 h prior to ouabain) was administered to animals previously treated with reserpine, the dose of ouabain which produced premature ventricular contractions, ventricular tachycardia, and death was increased to 109.0 +/- 7.2; 146.1 +/- 12.6; and 165.8 +/- 7.6 micrograms/kg, respectively (P less than 0.05). However, the magnitude of this protective action was similar to that produced by reserpine alone. Lathers et al. (Fed. Proc. 40, 672, 1981) reported that bretylium alone provides protection of a similar order of magnitude as reserpine. Thus, the effects of reserpine and bretylium were not additive; this indicates that the two agents may be acting on the same locus or they may be acting at different sites with the action of one drug masking or blocking the action of the other. Since 6OHDA prevented the action of reserpine on ouabain-induced ventricular arrhythmia and since 6OHDA only produces degeneration of adrenergic nerve terminals, it is probable that the protective effect of both reserpine and bretylium is due to an action at the adrenergic nerve terminal. The heart rate and blood pressure were not involved in the antiarrhythmic effects of reserpine.

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.