British Journal of Anaesthesia 1991; 67: 296-301
EFFECTS OF LABETALOL ON PERIOPERATIVE STRESS MARKERS AND ISOFLURANE REQUIREMENTS! D. AMAR, H. SHAMOON, W. H. FRISHMAN, E. J. LAZAR AND M. D. SALAMA SUMMARY
KEY WORDS Anaesthesia: general. Anaesthetics, volatile: isoflurane. Hormones: stress response to surgery. Sympathetic nervous system: catecholamines. sympathotytics: labetalol.
DAVID AMAR, M.D.*, MAMDOUH D . SALAMA, M.D. (Department of Anesthesiology); HARRY SHAMOON, M.D., WILLIAM H. FRISHMAN, M.D., ELIOT J. LAZAR, M.D. (Department of Medi-
cine); Montefiorc Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, U.S.A. Accepted for Publication: February 22, 1991. *Present address, for correspondence: Department of Anesthesiology and Critical Care Medicine, Memorial SloanKettering Cancer Center, 1275 York Avenue, New York, NY 10021, U.S.A. tPresented in part at the Annual Meeting of the American Society of Anesthesiologists, October 14-18, 1989, New Orleans, LA.
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
We have studied the effect of labetalol on anaesthetic requirements, cardiac and humoral responses in 16 healthy women during elective abdominal surgery. The experimental group (n = 8) received increments of i.v. labetalol 0.15-0.3mg kg-1 to reduce mean arterial pressure (MAP) by 15% from values obtained before anaesthesia. All patients received thiopentone 6 mg kg'1 and anaesthesia was maintained with isoflurane and nitrous oxide. In the placebo group, trachea/ intubation provoked a 33% increase in heart rate (HR) and a 52% increase in MAP (P < 0.001 vs baseline for both). In contrast, pretreatment with labetalol resulted in a 7.3% increase in HR and a 21.3% increase in MAP (P < 0.05 vs baseline for MAP). Two patients treated with labetalol had a reduction in MAP to 50-60 mm Hg during surgery. After trachea/ extubation, the labetalol group had a significantly slower HR than the placebo group (P < 0.05). The cardiovascular response to trachea/ intubation was associated with an increase in plasma noradrenaline concentration in both groups. Labetalol did not affect isoflurane requirements, plasma concentrations of adrenaline, cortisol and aldosterone or arterial Po2, but prevented the decrease in plasma concentration of potassium which occurred in placebo treated patients (P < 0.05) in early recovery. We conclude that preanaesthetic administration of labetalol attenuated the perioperative hypertensive and tachycardic responses, but was accompanied by intraoperative hypotension when given in doses > 0.5 mg kg-', despite an increase in plasma noradrenaline concentrations.
It is assumed generally that the cardiovascular changes following laryngoscopy and tracheal intubation represent an adrenergic response [1-5]. Thus it has been proposed that an abrupt increase in circulating plasma concentrations of catecholamines may be associated with potentially severe hypertension and tachycardia which, in turn, may cause cardiac arrhythmias, myocardial ischaemia, left ventricular dysfunction and rupture of cerebral aneurysms [6, 7] in susceptible individuals [8, 9]. Several agents and regimens have been devised to control these transient haemodynamic responses to tracheal intubation. Labetalol, a nonselective P- and 0.5 mg kg"1 before induction of anaesthesia. We observed a small but significant increase in plasma concentrations of noradrenaline in response to intubation in both groups. This and other [2, 23-25] studies suggest that noradrenaline is the primary neurotransmitter responsible for
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
The plasma concentrations of adrenaline and noradrenaline for both groups are shown in figure 2. Before induction, labetalol caused a 62.3% increase in plasma concentration of noradrenaline compared with placebo (P < 0.003). Further increases during tracheal intubation and surgery were similar in both groups (figure 2). Neither induction of anaesthesia nor tracheal intubation caused significant changes in plasma concentration of adrenaline in both groups. Surgical stimulation caused a substantial increase in plasma concentration of adrenaline (P < 0.001) in both groups, to approximately 50-fold greater than baseline, which persisted into the early recovery period. Plasma concentrations of cortisol and aldosterone (fig. 2, table II) exhibited similar patterns. Plasma renin activity was decreased (normal range 0.56-2.1 ng litre"1 s) throughout the study (table II). Plasma concentration of potassium was unchanged in both groups until the postoperative period. The control group had a lesser (P < 0.05) plasma concentration of potassium in the recovery room (3.4 (0.1) mmol litre"1 vs 3.8(0.1)mmol litre"1). Arterial Po2 values were similar in both groups. Plasma concentrations of labetalol (fig. 3) were compatible with the known rapid distribution of labetalol into the proposed two-compartment model [22].
300
BRITISH JOURNAL OF ANAESTHESIA TABLE II. Mean (SEM) plasma concentrations of renin and aldosurone Plasma renin activity (ng litre"1 s)
Baseline Post-incision 1 min 30 min Recovery room
Placebo
Labetalol
Placebo
Labetalol
0.31(0.06)
0.33(0.09)
1415 (333)
888 (200)
0.25(0.06) 0.47(0.11) 0.41(0.11)
0.41(0.17) 0.50(0.22) 0.36(0.11)
1207(269) 3956(1101) 9043(2721)
816(247) 1800(585) 5348(1612)
1000-
E 800O)
600-
~o bet
CO
400200-
ACKNOWLEDGEMENTS
PT
PI
1 5 Pint.
15 30 PCut
RR
FIG. 3. Mean (SD) plasma concentrations of labetalol after titration of labetalol and throughout the study. (For explanation of time points, see legend to figure 1.)
the haemodynamic changes, and combined a- and P-adrenergic block is a logical treatment. The dissociation seen in the control group between the increased plasma catecholamine concentrations in early recovery and the absence of tachycardia and hypertension, has been described previously [2], and may represent the occurrence of down-regulation of the R-adrenergic receptors [23, 26]. Although the use of small doses of fentanyl and droperidol at the time of peritoneal closure may have affected plasma concentrations of catecholamines, it would seem unlikely given the appreciable hormonal response seen during that time. Plasma concentration of potassium was significantly less in the placebo group in early recovery, presumably because of R-adrenergic activity [27]. Rapid decreases may occur in die perioperative period [28] and may precipitate arrhythmias [29]. No patient receiving labetalol developed an arrhythmia during tracheal intubation, compared with two patients in the control group. This may
This research was supported in part by Clinical Research Center Grant No. M01-RR-50 and an educational grant by Key Pharmaceuticals. H.S. was supported by grants DK 36617 and DK 40501 from the National Institute of Health.
REFERENCES 1. Forbes AM, Dally FG. Acute hypertension during induction of anaesthesia and endotracheal intubation in the normotensive man. British Journal of Anaesthesia 1970; 42: 618-624. 2. Derbyshire DR, Smith G. Sympathoadrenal responses to anaesthesia and surgery. British Journal of Anaesthesia 1984; 56: 725-739. 3. Derbyshire DR, Chmiclewski A, Fell D, Vater M, Achola K, Smith G. Plasma catecholamine responses to trachea! intubation. British Journal of Anaethesia 1983; 55: 855-859. 4. Russell WJ, Morris RG, Frewin DB, Drew SE. Changes in plasma catecholamine concentrations during endotracheal intubation. British Journal of Anaesthesia 1981; 53: 837-839. 5. Tomori Z, Widdicombe JG. Muscular bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract. Journal of Physiology {London) 1969; 200: 25-^9. 6. Fox EJ, Sklar GS, Hill CH, Villaneuva R, King BD. Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977; 47: 524-525. 7. Prys-Roberts C, Greene LT, Meloche R, Fo6x P. Studies of anaesthesia in relation to hypertension. II. Haemodynamic consequences of induction and endotracheal intubation. British Journal of Anaesthesia 1971; 43: 531-547.
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
be a result of a protective effect of labetalol on the myocardium or its Class I antiarrhythmic effect [30]. In conclusion, labetalol, in a dose sufficient to reduce MAP by 15 %, abolished the HR response to tracheal intubation and significantly attenuated the pressor response. Greater doses of labetalol may cause significant hypotension.
1200-,
c
Plasma aldosterone concn (pmol litre"1)
LABETALOL AND PERIOPERATIVE STRESS
301
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
hypoglyccmia. Journal of Clinical Endocrinology and 8. Low JM, Harvey JT, Prys-Roberts C, Dagnino J. Studies Metabolism 1989; 68: 9-16. of anaesthesia in relation to hypertension. British Journal 19. Foster LB, Dunn RT. Single antibody technique for of Anaesthesia 1986; 58: 471-477. radioimmunoassay of cortisol in unextracted serum or 9. Bedford RF, Feinstein B. Hospital admission blood plasma. Clinical Chemistry 1974; 20: 365-368. pressure: A predictor for hypertension following endotracheal intubation. Anesthesia and Analgesia 1980; 20. Alton KB, Leitz F, Bariletto S, Jaworsky L, Desriviers D, Patrick J. High performance liquid chromatography assay 59: 367-370. for labetalol in human plasma using a PRP-1 column and 10. Roelofse JA, Shipton EA, Joubert JJ DeV, Grotepass fluorometric detection. Journal of Chromatography 1984; FW. A comparison of labetalol, acebutolol and lidocaine 305: 222-227. for controlling the cardiovascular responses to cndotracheael intubation for oral surgical procedures. 21. Bock D. Multivariate Statistical Methods in Behavioral Research. New York: McGraw HU1, NYC, 1975. Journal of Oral Maxillofadal Surgery 1987; 45: 835-840. 11. Leslie JB, Kalayjian RW, McLoughlin TM, Plachetka 22. Kanto J, Allonen H, Kleimola T, Mantyla R. Pharmacokinetics of labetalol in healthy volunteers. JR. Attenuation of the hemodynamic responses to International Journal of Clinical Pharmacology 1981; 19: endotracheal intubation with preinduction intravenous 41^4. labetalol. Journal of Clinical Anesthesia 1989; 1: 194-200. 12. Inada E, Cullen DJ, Nemeskal AR, Tcplick R. Effect of 23. Cryer PE. Physiology and pathophysiology of the human sympathoadrenal ncuroendocrine system. New England labetalol or lidocaine on the hemodynamic responses to Journal of Medicine 1980; 303: 436-444. intubation: A controlled randomized double-blind study. 24. Hamberger B, Jarnberg PO. Plasma catecholamincs Journal of Clinical Anesthesia 1989; 1: 207-213. during surgical stress: Differences between neurolept and 13. Bernstein JS, Ebert TJ, Stowe DF, Schmeling WT, enflurane anesthesia. Acta Anaesthesiologica ScanaHnavica Nelson MA. Partial attenuation of hemodynamic 1983; 27: 307-310. responses to rapid sequence induction and intubation with_ 25. Udelsman R, Norton JA, Jclenich SA, Goldstein DS, labetalol. Journal of Clinical Anesthesia 1989; 1: 444Linchan WM, Loriaux DL, Chrousos GP. Responses of 451. the hypothalamic-pituitary-adrenal and rcnin—angiotensin 14. Fischlcr M, Dubois C, Brodaty D, Schlumberger S, aces and the sympathetic system during controlled surgical Melchior JC, Guilmet D, Vourc'h G. Circulatory and anesthetic stress. Journal of Clinical Endocrinology responses to thiopentonc and tracheal intubation in Metabolism 1987; 64: 986-994. patients with coronary artery disease: effects of 26. Marty J, Nimier M, Rocchioccioli C, Mantz J, Luscombe pretreatment with labetalol. British Journal of Anaesthesia F, Hcnzel D, Loiseau A, Desmonts JM. P-Adrenergic 1985; 57: 493-^96. receptor function is acutely altered in surgical patients. 15. Ramanathan J, Sibai B, Mabie WC, Chauhan D, Ruiz Anesthesia and Analgesia 1990; 71: 1-8. AG. The use of labetalol for attenuation of the hy- 27. Brown MJ, Brown DC, Murphy MB. Hypokalcmia from pertensive response to endotrachcal intubation in beta-2 receptor stimulation by circulating epinephrine. prceclampsia. American Journal of Obstetrics and New England Journal of Medicine 1983; 309: 1414-1419. Gynecology 1988; 159: 650-654. 28. Kharasch ED, Bodle TA. Prevention of preinduction 16. Richards DA, Maconochie JG, Bland RE, Hopkins R, hypokalemia by beta-2 blockade. Anesthesia and Analgesia Woodinas EP. Relationship between plasma 1990; 70: S202. concentrations and pharmacological effects of labetalol. 29. McGovem B. Hypokalemia and cardiac arrhythmias. European Journal of Clinical Pharmacology 1977; 11: Anesthesiology 1985; 63: 127-129. 85-90. 30. Frishman WH, MacCarthy EP, Kimmel B, Lazar E, 17. Passon PG, Peuler JD. A simplified radiometric assay for Michelson EL, Bloomfield SS. Labetalol: A new bctaplasma norepinephrine and epinephrine. Annals of Bioadrenergic blocker vasodilator. In: Frishman WH, ed. Clinical Pharmacology of the Beta-Adrenergic Blocking chemistry 1973; 51: 618-631. Drugs. Norwalk: Appleton-Century Crofts, 1984; 18. Sotsky MJ, Shilo S, Shamoon H. Regulation of counter 219-220. regulatory hormone secretion in man during exercise and
EFFECTS OF LABETALOL ON PERIOPERATIVE STRESS MARKERS AND ISOFLURANE REQUIREMENTS! D. AMAR, H. SHAMOON, W. H. FRISHMAN, E. J. LAZAR AND M. D. SALAMA SUMMARY
KEY WORDS Anaesthesia: general. Anaesthetics, volatile: isoflurane. Hormones: stress response to surgery. Sympathetic nervous system: catecholamines. sympathotytics: labetalol.
DAVID AMAR, M.D.*, MAMDOUH D . SALAMA, M.D. (Department of Anesthesiology); HARRY SHAMOON, M.D., WILLIAM H. FRISHMAN, M.D., ELIOT J. LAZAR, M.D. (Department of Medi-
cine); Montefiorc Medical Center/Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, U.S.A. Accepted for Publication: February 22, 1991. *Present address, for correspondence: Department of Anesthesiology and Critical Care Medicine, Memorial SloanKettering Cancer Center, 1275 York Avenue, New York, NY 10021, U.S.A. tPresented in part at the Annual Meeting of the American Society of Anesthesiologists, October 14-18, 1989, New Orleans, LA.
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
We have studied the effect of labetalol on anaesthetic requirements, cardiac and humoral responses in 16 healthy women during elective abdominal surgery. The experimental group (n = 8) received increments of i.v. labetalol 0.15-0.3mg kg-1 to reduce mean arterial pressure (MAP) by 15% from values obtained before anaesthesia. All patients received thiopentone 6 mg kg'1 and anaesthesia was maintained with isoflurane and nitrous oxide. In the placebo group, trachea/ intubation provoked a 33% increase in heart rate (HR) and a 52% increase in MAP (P < 0.001 vs baseline for both). In contrast, pretreatment with labetalol resulted in a 7.3% increase in HR and a 21.3% increase in MAP (P < 0.05 vs baseline for MAP). Two patients treated with labetalol had a reduction in MAP to 50-60 mm Hg during surgery. After trachea/ extubation, the labetalol group had a significantly slower HR than the placebo group (P < 0.05). The cardiovascular response to trachea/ intubation was associated with an increase in plasma noradrenaline concentration in both groups. Labetalol did not affect isoflurane requirements, plasma concentrations of adrenaline, cortisol and aldosterone or arterial Po2, but prevented the decrease in plasma concentration of potassium which occurred in placebo treated patients (P < 0.05) in early recovery. We conclude that preanaesthetic administration of labetalol attenuated the perioperative hypertensive and tachycardic responses, but was accompanied by intraoperative hypotension when given in doses > 0.5 mg kg-', despite an increase in plasma noradrenaline concentrations.
It is assumed generally that the cardiovascular changes following laryngoscopy and tracheal intubation represent an adrenergic response [1-5]. Thus it has been proposed that an abrupt increase in circulating plasma concentrations of catecholamines may be associated with potentially severe hypertension and tachycardia which, in turn, may cause cardiac arrhythmias, myocardial ischaemia, left ventricular dysfunction and rupture of cerebral aneurysms [6, 7] in susceptible individuals [8, 9]. Several agents and regimens have been devised to control these transient haemodynamic responses to tracheal intubation. Labetalol, a nonselective P- and 0.5 mg kg"1 before induction of anaesthesia. We observed a small but significant increase in plasma concentrations of noradrenaline in response to intubation in both groups. This and other [2, 23-25] studies suggest that noradrenaline is the primary neurotransmitter responsible for
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
The plasma concentrations of adrenaline and noradrenaline for both groups are shown in figure 2. Before induction, labetalol caused a 62.3% increase in plasma concentration of noradrenaline compared with placebo (P < 0.003). Further increases during tracheal intubation and surgery were similar in both groups (figure 2). Neither induction of anaesthesia nor tracheal intubation caused significant changes in plasma concentration of adrenaline in both groups. Surgical stimulation caused a substantial increase in plasma concentration of adrenaline (P < 0.001) in both groups, to approximately 50-fold greater than baseline, which persisted into the early recovery period. Plasma concentrations of cortisol and aldosterone (fig. 2, table II) exhibited similar patterns. Plasma renin activity was decreased (normal range 0.56-2.1 ng litre"1 s) throughout the study (table II). Plasma concentration of potassium was unchanged in both groups until the postoperative period. The control group had a lesser (P < 0.05) plasma concentration of potassium in the recovery room (3.4 (0.1) mmol litre"1 vs 3.8(0.1)mmol litre"1). Arterial Po2 values were similar in both groups. Plasma concentrations of labetalol (fig. 3) were compatible with the known rapid distribution of labetalol into the proposed two-compartment model [22].
300
BRITISH JOURNAL OF ANAESTHESIA TABLE II. Mean (SEM) plasma concentrations of renin and aldosurone Plasma renin activity (ng litre"1 s)
Baseline Post-incision 1 min 30 min Recovery room
Placebo
Labetalol
Placebo
Labetalol
0.31(0.06)
0.33(0.09)
1415 (333)
888 (200)
0.25(0.06) 0.47(0.11) 0.41(0.11)
0.41(0.17) 0.50(0.22) 0.36(0.11)
1207(269) 3956(1101) 9043(2721)
816(247) 1800(585) 5348(1612)
1000-
E 800O)
600-
~o bet
CO
400200-
ACKNOWLEDGEMENTS
PT
PI
1 5 Pint.
15 30 PCut
RR
FIG. 3. Mean (SD) plasma concentrations of labetalol after titration of labetalol and throughout the study. (For explanation of time points, see legend to figure 1.)
the haemodynamic changes, and combined a- and P-adrenergic block is a logical treatment. The dissociation seen in the control group between the increased plasma catecholamine concentrations in early recovery and the absence of tachycardia and hypertension, has been described previously [2], and may represent the occurrence of down-regulation of the R-adrenergic receptors [23, 26]. Although the use of small doses of fentanyl and droperidol at the time of peritoneal closure may have affected plasma concentrations of catecholamines, it would seem unlikely given the appreciable hormonal response seen during that time. Plasma concentration of potassium was significantly less in the placebo group in early recovery, presumably because of R-adrenergic activity [27]. Rapid decreases may occur in die perioperative period [28] and may precipitate arrhythmias [29]. No patient receiving labetalol developed an arrhythmia during tracheal intubation, compared with two patients in the control group. This may
This research was supported in part by Clinical Research Center Grant No. M01-RR-50 and an educational grant by Key Pharmaceuticals. H.S. was supported by grants DK 36617 and DK 40501 from the National Institute of Health.
REFERENCES 1. Forbes AM, Dally FG. Acute hypertension during induction of anaesthesia and endotracheal intubation in the normotensive man. British Journal of Anaesthesia 1970; 42: 618-624. 2. Derbyshire DR, Smith G. Sympathoadrenal responses to anaesthesia and surgery. British Journal of Anaesthesia 1984; 56: 725-739. 3. Derbyshire DR, Chmiclewski A, Fell D, Vater M, Achola K, Smith G. Plasma catecholamine responses to trachea! intubation. British Journal of Anaethesia 1983; 55: 855-859. 4. Russell WJ, Morris RG, Frewin DB, Drew SE. Changes in plasma catecholamine concentrations during endotracheal intubation. British Journal of Anaesthesia 1981; 53: 837-839. 5. Tomori Z, Widdicombe JG. Muscular bronchomotor and cardiovascular reflexes elicited by mechanical stimulation of the respiratory tract. Journal of Physiology {London) 1969; 200: 25-^9. 6. Fox EJ, Sklar GS, Hill CH, Villaneuva R, King BD. Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977; 47: 524-525. 7. Prys-Roberts C, Greene LT, Meloche R, Fo6x P. Studies of anaesthesia in relation to hypertension. II. Haemodynamic consequences of induction and endotracheal intubation. British Journal of Anaesthesia 1971; 43: 531-547.
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
be a result of a protective effect of labetalol on the myocardium or its Class I antiarrhythmic effect [30]. In conclusion, labetalol, in a dose sufficient to reduce MAP by 15 %, abolished the HR response to tracheal intubation and significantly attenuated the pressor response. Greater doses of labetalol may cause significant hypotension.
1200-,
c
Plasma aldosterone concn (pmol litre"1)
LABETALOL AND PERIOPERATIVE STRESS
301
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on July 26, 2015
hypoglyccmia. Journal of Clinical Endocrinology and 8. Low JM, Harvey JT, Prys-Roberts C, Dagnino J. Studies Metabolism 1989; 68: 9-16. of anaesthesia in relation to hypertension. British Journal 19. Foster LB, Dunn RT. Single antibody technique for of Anaesthesia 1986; 58: 471-477. radioimmunoassay of cortisol in unextracted serum or 9. Bedford RF, Feinstein B. Hospital admission blood plasma. Clinical Chemistry 1974; 20: 365-368. pressure: A predictor for hypertension following endotracheal intubation. Anesthesia and Analgesia 1980; 20. Alton KB, Leitz F, Bariletto S, Jaworsky L, Desriviers D, Patrick J. High performance liquid chromatography assay 59: 367-370. for labetalol in human plasma using a PRP-1 column and 10. Roelofse JA, Shipton EA, Joubert JJ DeV, Grotepass fluorometric detection. Journal of Chromatography 1984; FW. A comparison of labetalol, acebutolol and lidocaine 305: 222-227. for controlling the cardiovascular responses to cndotracheael intubation for oral surgical procedures. 21. Bock D. Multivariate Statistical Methods in Behavioral Research. New York: McGraw HU1, NYC, 1975. Journal of Oral Maxillofadal Surgery 1987; 45: 835-840. 11. Leslie JB, Kalayjian RW, McLoughlin TM, Plachetka 22. Kanto J, Allonen H, Kleimola T, Mantyla R. Pharmacokinetics of labetalol in healthy volunteers. JR. Attenuation of the hemodynamic responses to International Journal of Clinical Pharmacology 1981; 19: endotracheal intubation with preinduction intravenous 41^4. labetalol. Journal of Clinical Anesthesia 1989; 1: 194-200. 12. Inada E, Cullen DJ, Nemeskal AR, Tcplick R. Effect of 23. Cryer PE. Physiology and pathophysiology of the human sympathoadrenal ncuroendocrine system. New England labetalol or lidocaine on the hemodynamic responses to Journal of Medicine 1980; 303: 436-444. intubation: A controlled randomized double-blind study. 24. Hamberger B, Jarnberg PO. Plasma catecholamincs Journal of Clinical Anesthesia 1989; 1: 207-213. during surgical stress: Differences between neurolept and 13. Bernstein JS, Ebert TJ, Stowe DF, Schmeling WT, enflurane anesthesia. Acta Anaesthesiologica ScanaHnavica Nelson MA. Partial attenuation of hemodynamic 1983; 27: 307-310. responses to rapid sequence induction and intubation with_ 25. Udelsman R, Norton JA, Jclenich SA, Goldstein DS, labetalol. Journal of Clinical Anesthesia 1989; 1: 444Linchan WM, Loriaux DL, Chrousos GP. Responses of 451. the hypothalamic-pituitary-adrenal and rcnin—angiotensin 14. Fischlcr M, Dubois C, Brodaty D, Schlumberger S, aces and the sympathetic system during controlled surgical Melchior JC, Guilmet D, Vourc'h G. Circulatory and anesthetic stress. Journal of Clinical Endocrinology responses to thiopentonc and tracheal intubation in Metabolism 1987; 64: 986-994. patients with coronary artery disease: effects of 26. Marty J, Nimier M, Rocchioccioli C, Mantz J, Luscombe pretreatment with labetalol. British Journal of Anaesthesia F, Hcnzel D, Loiseau A, Desmonts JM. P-Adrenergic 1985; 57: 493-^96. receptor function is acutely altered in surgical patients. 15. Ramanathan J, Sibai B, Mabie WC, Chauhan D, Ruiz Anesthesia and Analgesia 1990; 71: 1-8. AG. The use of labetalol for attenuation of the hy- 27. Brown MJ, Brown DC, Murphy MB. Hypokalcmia from pertensive response to endotrachcal intubation in beta-2 receptor stimulation by circulating epinephrine. prceclampsia. American Journal of Obstetrics and New England Journal of Medicine 1983; 309: 1414-1419. Gynecology 1988; 159: 650-654. 28. Kharasch ED, Bodle TA. Prevention of preinduction 16. Richards DA, Maconochie JG, Bland RE, Hopkins R, hypokalemia by beta-2 blockade. Anesthesia and Analgesia Woodinas EP. Relationship between plasma 1990; 70: S202. concentrations and pharmacological effects of labetalol. 29. McGovem B. Hypokalemia and cardiac arrhythmias. European Journal of Clinical Pharmacology 1977; 11: Anesthesiology 1985; 63: 127-129. 85-90. 30. Frishman WH, MacCarthy EP, Kimmel B, Lazar E, 17. Passon PG, Peuler JD. A simplified radiometric assay for Michelson EL, Bloomfield SS. Labetalol: A new bctaplasma norepinephrine and epinephrine. Annals of Bioadrenergic blocker vasodilator. In: Frishman WH, ed. Clinical Pharmacology of the Beta-Adrenergic Blocking chemistry 1973; 51: 618-631. Drugs. Norwalk: Appleton-Century Crofts, 1984; 18. Sotsky MJ, Shilo S, Shamoon H. Regulation of counter 219-220. regulatory hormone secretion in man during exercise and
