Implications: Amphetamines are powerful, sympathomimetic amines that, when used chronically, can profoundly effect a patient’s cardiovascular stability during anesthesia and surgery. Amphetamines are the third most widely abused class of drugs in the United States. They also have legitimate medical use for attention deficit disorder with hyperactivity, exogenous obesity, and narcolepsy. We report a case of a patient with a 40-yr history of chronic amphetamine use having undergone two general anesthesias without complication.
Department of Anesthesia, Stanford University School of Medicine, Stanford, California
May 22, 2000.
Address correspondence and reprint requests to Stephen P. Fischer, MD, Stanford University Medical Center, Department of Anesthesia, 300 Pasteur Drive, Room H3580, Stanford, CA 94305-5640.
Previous reports have described severe adverse reactions, including death, in patients undergoing general anesthesia who have a history of chronic (1) and acute (2) illicit amphetamine use. Although amphetamines have a high abuse potential, there are many legitimate indications for their use in the treatment of a variety of conditions, including attention deficit disorder (3), obesity (4), and narcolepsy (5). As these patients may require anesthesia in an emergency situation, it may be impossible to discontinue amphetamines before anesthesia administration. We present a case in which a patient with a 40-yr history of amphetamine use for narcolepsy was anesthetized for emergency laparoscopic treatment of a small bowel obstruction.
A 61-yr-old man was admitted from the emergency room with a small bowel obstruction and was scheduled for laparoscopic lysis of adhesions under general anesthesia. The patient had been taking a combination of dextroamphetamine and amphetamine daily for more 40 yr because of severe narcolepsy, with adequate control of somnolence. Medications at the time of surgery included dextroamphetamine, 10 mg daily; amphetamine, 10 mg daily; lisinopril, 10 mg daily; verapamil, 240 mg daily; meclizine; and salbuterol and flunisolide inhalers. All medications were administered on the morning of surgery with the exception of warfarin, which was discontinued two days before his admission. His medical history included coronary artery disease, recent anterior myocardial infarction, peripheral vascular disease, supraventricular tachycardia, chronic obstructive pulmonary disease, and hypertension. His myocardial infarction occurred 4 mo previously and was treated with angioplasty, stenting of the left anterior descending coronary artery, and long-term warfarin anticoagulation. Of considerable interest to us was his abdominal aortic aneurysm repair 2 yr previous. At that time, the patient’s amphetamines had not been discontinued. The general anesthesia and aneurysm surgery were uneventful, except that during surgery, phenylephrine was used shortly after release of aortic clamp. The only complication noted was the development of a postoperative pulmonary embolism requiring acute thrombolysis.
Preoperative vital signs and results of physical examination and laboratory studies before the laparoscopic surgery were unremarkable, with the exception of the International Normalized Ratio, which was 1.9. An epidural anesthetic was not considered secondary to the increased International Normalized Ratio. The electrocardiogram revealed sinus rhythm with poor R wave progression.
The patient was given midazolam (2 mg IV) 30 min before surgery. The usual monitors were used. A right radial arterial catheter was placed for beat-to-beat measurement of blood pressure. Heart rate was 84 bpm. Arterial blood pressure was 130/70 mm Hg. Anesthesia was induced with sufentanil 60 mg, etomidate 20 mg, and succinylcholine 100 mg IV. The trachea was intubated, and anesthesia was maintained with isoflurane, 0.5% in a 30% oxygen/70% nitrous oxide mixture. The patient’s surgery time was 7:30 am to avoid an excessive intravascular volume depletion that could potentially affect blood pressure stability. Heart rate immediately after the induction and before intubation remained <100 bpm, suggesting a normal intravascular volume.
Neuromuscular blockade was maintained with rocuronium. With the exception of a brief hypertensive episode at the time of laryngoscopy and endotracheal intubation (blood pressure = 190/110 mm Hg), arterial blood pressure did not change by more than 10% from baseline during surgery. No direct-acting vasopressors were administered. An additional 20 μg of sufentanil was administered in divided doses intraoperatively, according to the patient’s response to surgical stimulation. After surgery, neuromuscular blockade was reversed with neostigmine and glycopyrrolate. He remained hemodynamically stable during emergence from anesthesia, awakened without discomfort, and was taken to the recovery room in stable condition. His subsequent hospital course and recovery were uneventful. Amphetamine therapy was restarted on the third postoperative day.
Amphetamine, a racemic mixture of β-phenyl-isopropylamine, is an indirect sympathomimetic drug. Amphetamine is a powerful central nervous system (CNS) stimulant with peripheral α and β actions. The CNS mechanism of amphetamine appears dependent on the local release of biogenic amines such as norepinephrine from storage sites in nerve terminals (6). Such chronic, intense stimulation of adrenergic nerve terminals in the CNS, as well as peripherally, depletes CNS catecholamines and the sympathetic response to hypotension (7).
Oral administration of amphetamine results in increased systolic and diastolic blood pressures, as well as reflex bradycardia. CNS effects include stimulation of respiratory centers, increased alertness, diminished fatigue, euphoria, and improved ability to concentrate. Amphetamine has been used in the treatment of obesity. This site of action appears to be in the lateral hypothalamic feeding center, which reduces the desire for food intake. Additionally, there is a small measure of increased metabolism contributing to weight loss.
Our patient was treated for narcolepsy with stable doses of amphetamine and dextroamphetamine for more than 40 years. He was unable to perform even simple tasks without these medications as a result of continual somnolence.
Chronic amphetamine use leads to the development of tolerance, as is seen in long-term cocaine abuse. This may be manifested clinically as depression and fatigue (7). Cross-tolerance to other sympathomimetic drugs is also observed. Intraoperatively, a decrease in a patient’s sympathetic tone is often needed or wanted. Amphetamines, however, act to reduce a patient’s sympathetic reflex integrity with a down regulation of endogenous catecholamine. Refractory hypotension can result, which requires prompt pharmacologic intervention. Postoperatively, there is the potential for unexpected hypotension, as when a patient begins ambulation. Although our patient had no postoperative hypotension, we cannot generalize this observation to all patients using amphetamines.
Of particular concern to anesthesiologists is the diminished pressor response to ephedrine after chronic amphetamine use (8). Tolerance may result from catecholamine depletion in central and peripheral adrenergic neurons; intraneuronal catecholamine levels may not return to normal for days to weeks after cessation of amphetamine use.
A history of either acute or chronic amphetamine use may present a challenge for the anesthesiologist. Acute amphetamine use dramatically increases anesthetic requirement (9,10) and has been implicated in a case of severe intraoperative intracranial hypertension (2) without postoperative sequelae. Chronic amphetamine use results in a markedly diminished anesthetic requirement (8), which is thought to result from catecholamine depletion in the CNS, and has been implicated in a case of cardiac arrest during general anesthesia. In a case report, Samuels et al. (1) speculated that chronic catecholamine depletion led to an inability to respond to the stress of anesthetic induction, specifically, the increase in venous capacitance and the resulting decrease in preload that resulted from the induction dose of thiopental.
In our case, careful titration of anesthetic drugs and avoidance of those likely to cause wide swings in arterial blood pressure likely contributed to our patient’s overall hemodynamic stability. Our choice of etomidate as an induction drug was based on its relative lack of hemodynamic effects, as was our decision to avoid large concentrations of isoflurane and to use relatively large doses of opioid. Our choice of sufentanil over fentanyl was based on its reputation for improved hemodynamic stability.
We recommend that patients with a history of chronic amphetamine use requiring emergency or urgent general anesthesia receive direct intraarterial blood pressure monitoring and an opioid-based anesthetic. Direct-acting vasopressors, including phenylephrine (IV, 50–100 μg) and epinephrine (IV, 50–100 μg), should be immediately available to treat hypotension or bradycardia. However, in this case, the patient had no requirement for these drugs.
In conclusion, we have observed in this case that chronic pharmacological doses of amphetamines need not be discontinued before elective surgery. The absence of any significant cardiovascular events during our case and the patient’s previous surgery and general anesthesia leads us to question if there is physiological cause for concern when general anesthesia is contemplated in a patient receiving chronic amphetamine therapy. This is similar to a common dilemma in anesthetic practice 25 years ago when antihypertensive therapy was discontinued before general anesthesia (10). Although we have not yet successfully anesthetized a series of patients on chronic amphetamine therapy, we believe that the recommendation to withhold amphetamines before elective surgery may prove to be unnecessary.
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