Intranasal Nicotine for Postoperative Pain Treatment: A Comparison of Its Effects in the Context of Isoflurane-induced Anesthesia Versus Propofol Anesthesia

A. Study Proposal and Rational

The purpose of this study is to determine whether intranasal nicotine can decrease the negative side effects of the general anesthetic isoflurane. Isoflurane and other volatile anesthetics are potent antagonists of central nicotinic receptors. Nicotinic receptors are inhibited by isoflurane at the low concentrations that are present on emergence from anesthesia. Evidence from animal experiments suggests that inhibition of nicotinic receptors may cause increased sensitivity to pain and amnesia that occurs at low anesthetic concentrations. These anesthetic concentrations are frequently present on emergence from anesthesia. In these experiments, treatment with nicotine prevented the hyperalgesic state caused by isoflurane.

Intranasal nicotine treatment has been used in smokers as an aid to smoking cessation. As nicotine acts as an agonist at sympathetic ganglia, it can cause increases in heart rate and blood pressure. At the dose to be used in this protocol (3mg intranasally) there was an average increase of 7 mM of mercury in systolic blood pressure and no change in diastolic blood pressure or heart rate in nonsmoking volunteers.

B. Study Design and Statistical Analysis

The study is a randomized prospective controlled trial. Women scheduled to undergo total abdominal hysterectomy or myomectomy will be randomly allocated intranasal nicotine or intranasal saline before emergence from a standard general anesthetic. The patient will be randomized to one of two standard anesthetics regimens that are described below. Both patient and investigator will be blinded to treatment. Nicotine or saline will be placed in a single use nasal spray bottle by the research pharmacy and identified by number. Randomization will be accomplished with a random number table. Patients will be enrolled sequentially.