*Assistant Professor of Anesthesia

i-Associate Professor of Anesthesia

*Visiting Assistant Professor of Anesthesia

Address reprint requests to Dr. From at the Department of Anesthesia, University of Iowa College of Medicine, Iowa City, IA 52242, USA.

Supported in part by CLINFO Grant No. RR59, Clinical Research Centers Branch of NIH.

Received for publication October 2 1, 1988; revised manuscript accepted for publication February 7, 1989.

Q 1989 Butterxrorth Publishers

r Department o1 j kesthesia, University of howa Gollege of Me&&x,

Iowa City, IA.

EJ&X of serum potassium following succinylcholine was compared sn ~~u~gicd patients undeergoing low-dose, long-term beta 1 -adyenoceptor or beta I ,a-ad?pnoceptor blocking therapy and in those receiving neither of these thrrupies. There were no significant differences in serum potassium concentration prior to, and otrer a study period I_$ 2 hours following succin~$choline udm~~~t~ution among the three groups of patients.

~yw~r~~~ Potassium; neuromuscular relaxants; succinylcholine; sympathetic nervous system; beta-receptor blockade; anesthesia.

The sympathoadrenal system, in articular beta 2-adrenoceptoss, lhas im- omeostasis. ~c~amrno~ and ith propranolol that succinyl-

choline leads to an exaggerated and prolonged increase in t concentration with delayed peak levels occurring at 60-W minutes. Gold- hill et al.’ have shown in dogs pretreated with metoproloi and ICI 118551 that succinylcholine alters the attern of K+ release and deiays return to

resuccinylcholine levels. In c aryniak et ul.” demonstrated, in umans receiving beta-adrenoceptor blo ing therapy, no increase in serum

M+ following succinylcholine. Their study3 was confined to 6 minutes following succinylcholine, and they did not examine the ~oss~~~i~~ty t

350 J. Clin. Anesth., 1989, vol. 1, no. 5

Beta blockade, potassium and surcinylcholine: From et al.

beta blockade may delay the increase in serum K+.4 The present study was designed to examine the change in serum K+ concentration following succinylcholine in patients undergoing low-dose, long-term beta- adrenoceptor blocking therapy Uersm patients on no beta-adrenoceptor blocking drugs over a study period of 2 hours following succinylcholine.

Thirty adult patients, ASA physicai status I-III, scheduled to undergo retinal reattachment andlor vit- rectomy during general anesthesia, were studied fol- lowing institutional review board approval and informed consent. A control group (n = 9) received no beta-adrenoceptor blocking therapy. The remain- ing 2 1 patients were divided into two treatment groups.

received nonselective beta 1,2-adrenocep- tor (pI,p) blocking medications, nadolol (40 mg once a day), propranalol (20-40 mg twice a day), pro- pranolol LA (120-140 mg once a day), or ocular ti- ma101 (0.25% or 0.5% in both eyes twice a day) (n = 11, nonselective group ). The other group received cardioselective beta I -adrenoceptor (p J blocking drugs, atenolol (25-50 mg once a day) or metoproiol (25-X mg once or twice a day) (n = 10, cardiose- lective group). Patients had been receiving beta-ad- renoceptor blocking therapy for the preceding month to more than I year. In all three groups, patients were concurrently receiving diuretics (both potassium spar- ing and nonsparing), antihypertensive agents (cloni- dine, methyldopa, and prazosin), and antidiabetic agents. Patients in bath treatment groups received prescribed oral beta-adrenoceptor blocking medica- tion on the morning of surgery. Two patients on ophthalmic beta-blockers had their medication held on the morning of surgery by surgeon request. Di- uretics were held while other antihypertensive or car- diovascular medications were given. Patients suffering from diabetes and on insulin received one-half their usual insulin dose on the morning of surgery; oral antidiabetic medications were continued through the day before surgery.

Patients wer premeditated with 0.1-0.2 mg/kg morphine and .OO2-0.003 mg/kg IM scopolamine 45-60 minutes before induction of anesthesia. In a preinduction holding unit, an 18-G IV cannula was placed in each antecubital fossa, one for administra- tion of fluid and drugs and the other for collection

ies. Normal saline was infused in all patients for maintenance of fluid balance. Patients were then taken. to the operating room. Anesthesia was induced with IV sodium thiopental 4-5 mglkg

and maintained with nitrous oxide (SO-“SO%), oxygen (3&40%), and end-tidal isoflurane concentration of 0.05--1.0%. Ventilation was controlled to maintain end-

al CO, at 40 i- 5 mm maintained above 35.5”C. Five to ten minutes follaw- ing induction of anesthesia, I mgikg succinylcholine was administered intravenously. Heart rate (FIR) and blood pressure (BP) were monitored by electrocar- diogram (EKG) and automatic OX tonometer, re- spectively. In the preinduction h samples were collected and hemadynamic parameters recorded (preinduction). Blood samples were col- lected following induction of anesthesia but prior to administration of succinylcholine (postinduction) and at 3,3,5, 10, 15,30,60,90, and 12Omi succinylcholine. Serum K+ was analyz electrolyte analyzer (Nova iamedical, Newton, MA) using an ion-specific electrode with a day-to-day pre- cision coefficient of variation of less than I.S%.

Two-way (time and grou ) analysis of variance (AXoVA) with repeated measures an the time factor was used to assess relative change in serum K+. Among group preinduction serum K+ concentrations, de- mographic and hemodynamic differences were ana- lyzed using ANOVA and Newman-Keuls test; P < 0.05 was considered significant. Values are expressed as mean + SEM.

Group demographics were not significantly different (Table I). The mean serum K+ concentrations prior ta induction of anesthesia were 3.62 + 0.07, 3.68 t 0.12, and 3.50 t 0.14 mEq/liter in control, nonselec- tive, and cardioselective groups, respectively, which were not significantly different. The increase in serum

- was seen within 3 minutes and peaked at 5 minutes in the control group and at 15 minutes in the non- selective and cardioselective groups. At peak, mean serum K+ values were 3.87 i 0.1 I, 3.83 t 0.16, and 3.87 -+ 0.18 mEq/liter in control, nonselective, and cardioselective groups, respectively, These values were not significantly different from each other. At 3, 5, 10, 15, and 00 minutes, there was a significant relative change in the serum K+ concentration from rein- duction values in all three groups (Figure I).

reinduction HR was significantly greater in the conrrol group (82 t 4 beats/mm) than in the non- selective (65 + 4 beats/mm) or cardi 4 beats/mm) groups. Mean arterial ferent among the three groups (98 +

g for control, nonselective, and car- dioselective groups, respectively).

J. Clin. Anesth., 1989, vol. I, m. 5 351

Original Contributions

T&k I, Demographic Patient Data in Control (Control Group) and Patients Undergoing 8, ,-adrenoceptor (Nonselective Group) and P,-adrenoceptor (Cardioselective Group) Blocking Therapy

Age (yr) 60 t 4 64 i 5 (32-68) (49-78)

Height (cm) 179 ” 3 167 t 3 (162-180) (165-170)

Weight (kg) 79 5 4 86 ? 7 (5 l-97) (56- 107)

Body mass index? 24 2 1 29 r 0 (19-28) (23-29)

67 t 2 NS (53-77)

166 ‘-+ 5 Nvs (152-170)

81 ‘- 4 NS (56-97)

25 2 1 NS (21-27)

Values are mean 2 SEM (range). “ANOVA = analysis of variance. tBody mass index = weight (kg)/height (m2).j

There are no reports in which succinylcholine-induced hyperkalemia has been suspected to cause morbidity or mortality when administered to patients receiving beta-blocking medication, but patients susceptible to change in membrane potential have suffered adverse effects while concurrently undergoing beta blockade and potassium loading.6,7 Clinically, beta-blocking agents are administered in stepwise increments until adequate physiologic levels have been attained, as in- dicated by resting H or BP.8 A wide variation be-

Time (min)

Figure 1. Mean (L SEM) change in serum M+ concentra- tion from preinduction for patients not receiving beta-ad- renoceptor blocking medication (n = 9, control group) and patients receiving nonselective p,,? (n = 11, nonselective group) or cardioselective p, (n = 10, cardioselective group) adrenoceptor blocking drugs following succinylcholine administration. Open symbols denote peak rise.

tween dose and concentration has been reported at maximum therapeutic response.“-” receive topical ocular timolol obtain Limolol levels.i,‘2m14 The precise de ade was not assessed in any patient, but resting was significantly greater in control than in either breat- ment group of patients, suggesting that the treatment group was beta-blocked. We did not a teria to limit concurrent medications. Pati ing from ischemic and/or hypertensive disease often require several concurrent medications.

Maryniak et d3 fou no significant change in serum IX.+ concentration lowing succinylcholine over a study period of 6 minutes, whereas O’Brien el aE. I5 reported delayed return of the serum K+ concentra- tion following succinylcholine in patients receiving se- lective or nonselective beta-adre~oce~~or blocking therapy during a 30-minute study period. Our results agree with those of Maryniak et ai.” and demonstrate no significant increase in serum K+ imme lowing or during a study period of 2 hours after suc- cinylcholine administration in patients receiving either

,-adrenoceptor blocking therapy compared

There are several possible explanations for differ- ences in these results and studies performed in animal preparations. First, it is possible that t

quate beta-adrenergic blockade presen of symptomatic diseases in this grou inadequate blockade eo influence + borneostasis. Second, the sudden small efflux of potassium released after a bolus of succinylcholine may not ‘be sufficient to demonstrate differences between control and treat- ment groups of patients. I6 Third, thiapental and in- halation anesthetics stabilize the ceil membrane and

352 J. Clin. Anesth., 1989, vol. 1, no. 5

attenuate the increase in serum K+ following succi- nylcholine.lE~li oth of these agents were employed for induction of anesthesia prior to use of succinyl- choline and may have influenced the release of K+ Finaily, in animal studies,“,za18 beta-adrenoceptor blockade is induced via IV administration and follow- ing the induction of anesthesia and endotracheal in- tubation. Qatients in the present study were undergoing chronic therapy prior to stress created by the induction of anesthesia and subsequent airway manipulation.

In conclusion, this study demonstrates over a time course of 2 hours that patients on long-term, low-dose beta-adrenoceptor blocking therapy do not appear to be at increased risk for succinylcholine-induced hy- perkalemia. Clinicians should exercise caution in pa- tients suffering from multiple defects (i.e., renal failure, acidosis) in potassium homeostasis or patients on ex- tremely high-dose beta-blockade. The response to succinylcholine in this latter group of patients is yet to be determined.

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Intern MeA 1986;146:1220-1. Flutter AM: Ischemic heart disease: Angina pectoris. In: Rubenstein E, Federman D, eds. Scientific American

Medicine. New York: Scientific-American Illustrated Li- brary, fY&O;i-20. Pine M, Favrot L, Smith S, cDona%d K, Chidsey CA: Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris. Circulation 1975;52:886-93. Chidsey C, Pine M> Favrot L, et al: The use of drug cmcentration measurements in studies of the thera- peutic response to propranolol. Po.sl,qmd Med j” 1976: 52:26-32. Sill JC, Nugent M, Moyer TP, Schaff H, Tinker JH: Plasma levels of beta-blocking drugs prior to coronary artery bypass surgery. Anesthesiolo~ 1985;62:67-70. Fraunfeider FT: Ocular %-blockers and systemic ef- fects. Arch intern &fed 1986: 146: 1073-4. Passo MS, Palmer EA, Van Buskirk EM: Plasma timolof in glaucoma patients. 0phthalmoloRy 1984;91: 1361-3. Alvan G, Calissendorff B, Seideman P, Widmark K, Widmark G: Absorption of ocular timoiol. Clin Phar- macokinet 1980;5:95-100. O’Brien DJ: Moriarty DC, Hope CE: The effect of pre- existing beta blockade on potassium flux in patients receiving succinylcholine [Abstract]. Ca?z Anaesih Sot J 1986;33:S89. Roth ,JL, Nugent M, Gronert GA: Verapamil does not alter succinylcholine-induced increases in serum potas- sium during halothane anesthesia in normal dogs. An&h Analg 1985;64:1202-4.

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