To the Editor
I read with interest the 2 case reports and discussion by Drs. Cullen and Kirby of central nervous system (CNS) catastrophes that occurred in patients undergoing shoulder procedures in the beach chair position.1 I noticed that the 2 cases had another common factor that was not discussed in their article; both patients had received labetalol while in the operating room. According to the original article, the first patient was given 50 mg of labetalol to treat high blood pressure readings obtained immediately prior to induction2—while the second patient received 20 mg of labetalol in divided doses as part of a deliberate hypotensive technique. Interestingly, neither patient had a history of hypertension.2
Labetalol is marketed for control of blood pressure in severe hypertension. It combines selective alpha1 blocking action with non-selective beta1 and beta2 blockade. The ratio of alpha to beta blockade is 1:7 when used intravenously.3,4 Relatively weak alpha1 blockade causes vasodilation, while stronger beta1 blocking decreases heart rate and contractility. Beta2 blocking prevents sympathetically mediated vasodilation and bronchodilation. Labetalol itself produces postural hypotension. The package inserts report a 58% incidence of “symptomatic postural hypotension” in awake patients when tilted or placed upright following labetalol injection, presumably referring to complaints of lightheadedness or dizziness. This is a sufficiently concerning effect that the administration guideline reads: “Patients should always be kept in a supine position during the period of intravenous drug administration.”3,4 Manufacturers’ recommendations do not constitute a legal standard of care, and the fact remains that many anesthesiologists do administer labetalol intravenously in patients in beach chair positions without complications. I personally question, however, whether this could be a contributing factor to some instances of CNS infarcts, such as the 2 presented in the Newsletter article.
Despite autoregulation, in the standing position, cerebral blood flow (CBF) in healthy individuals falls by 14-21% of supine values.5 Only with tilts up to 20 degrees does CBF remain constant. There is evidence that in the upright position, CBF is more dependent on the arterial-venous pressure gradient than it is on mean arterial pressure,5 so extra caution might be advisable when using drugs that alter hemodynamics under these circumstances, especially when measuring cuff pressures alone. Labetalol injection has already been shown to act synergistically with at least 2 potent inhalational anesthetics in producing hypotension, reducing cardiac output, and increasing CVP.3,4,6 Since 1996, package inserts for the drug have included the following warning: “Several deaths have occurred when Labetalol HCl injection was used during surgery (including when used in cases to control bleeding).”3,4,7
I first became interested in the clinical pharmacology of labetalol after reviewing a number of anesthesiology malpractice claims in which otherwise healthy patients became bradycardic and arrested within 20 minutes of being given the drug to treat epinephrine-induced hypertension. I was surprised to find that literature regarding the physiologic explanation for this is available,8-11 although it remains a rather underappreciated phenomenon in much of the anesthesia community. In the presence of epinephrine, norepinephrine, or phenylephrine, the weak alpha-adrenergic blockade of labetalol, in addition to strong combined beta-blockade, allows for unopposed adrenergic stimulation. This can result in severe increases in systemic vascular resistance along with declines in cardiac output, and has been associated with cases of pulmonary edema and death—even in healthy adults and children.8 In the current article, while discussing patient safety in the beach chair position, the authors suggest using “vasopressor infusion, as needed during the time of the procedure when the patient is upright and at risk.” I am concerned that the infusion of phenylephrine or epinephrine in a patient who has already received labetalol (or another beta-blocker) might potentially produce the life-threatening complication described above.
Labetalol is not a short-acting drug, and its effects would likely have lasted the duration of both surgeries described in the article—and substantially into the postoperative periods. Its elimination half-life after IV administration is estimated at 5.5 hours. In drug company studies, it took an average of 16 to 18 hours for blood pressure to return to pretreatment values.3,4 Accordingly, the not uncommon practice of using labetalol to treat transient episodes of high blood pressure and tachycardia in otherwise non-hypertensive patients that result from preoperative anxiety, intubation stimuli, or surgical stress, strikes me as odd, considering its pharmacology. There are certainly other means available to treat temporarily high heart rates and vasoconstriction.
While the beach chair position has now become standard of care for shoulder procedures in many orthopedic practices, the addition of labetalol to general anesthesia adds another layer of complexity to physiology in the upright position, with implications that have yet to be fully determined. I agree with the authors that the use of the beach chair position combined with deliberate hypotension will likely compromise cerebral perfusion. But using labetalol for any reason—thereby blocking all of the body’s usual responses to postural change: vasoconstriction, increased heart rate, and increased contractility—might also affect cerebral perfusion in patients who are positioned head-up. I applaud Drs. Cullen and Kirby for spotlighting many of the potential problems with this situation and for advocating caution whenever one is positioning a patient in beach chair. Let us hope we can continue to identify ways of decreasing the anesthesia risk for a patient position that improves surgical technique.
Ann S. Lofsky, MD
Santa Monica, CA
- Cullen DJ, Kirby, RR. Beach chair position may decrease cerebral perfusion; catastrophic outcomes have occurred. APSF Newsletter 2007;22(2):25,27.
- Pohl A, Cullen DJ. Cerebral ischemia during shoulder surgery in the upright position: a case series. J Clin Anesth 2005;17:463-9.
- Bedford Labs labetalol hydrochloride injection package insert. Available at http://www.bedfordlabs.com/products/inserts/LBTL-P02.pdf. Accessed August 13, 2007.
- Mayne Pharma labetalol hydrochloride injection package insert. Available at http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=2227&type=display. Accessed August 13, 2007.
- Moraine JJ, Berre J, Melot C, et al. Is cerebral perfusion pressure a major determinant of cerebral blood flow during head elevation in comatose patients with severe intracranial lesions? J Neurosurg 2000;92:606-14.
- Kalyanaraman M, Carpenter RL, McGlew MJ, et al. Cardiopulmonary compromise after use of topical and submucosal a-agonists: possible added complication by the use of b-blocker therapy. Otolaryngol Head Neck Surg 1997;117:56-61
- FDA drug labeling changes. November, 1996. Available at http://www.fda.gov/medwatch/SAFETY/LABEL/nov96.htm#normod. Accessed August 13, 2007.
- Groudine SB, Hollinger I, Jones J, et al. New York state guidelines on the topical use of phenylephrine in the operating roo
m. Anesthesiology 2000;92:859-64.
- Jay GT, Chow MS. Interaction of epinephrine and beta-blockers. JAMA 1995;274:1830, 1832.
- Centeno R, Yu Y. The propanolol-epinephrine interaction revisited: a serious and potentially catastrophic adverse drug interaction in facial plastic surgery. Plast Reconstr Surg 2003;111:944-5.
- Chung PCH, Li AH, Lin CC, et al. Elevated vascular resistance after labetalol during resection of a pheochromocytoma. Can J Anaesth 2002;49:148-50.