British Journal of Anaesthesia 1992; 68: 85-89
EFFECT OF VERAPAMIL ON THE CARDIOVASCULAR RESPONSES TO TRACHEAL INTUBATION H. YAKU, K. MIKAWA, N. MAEKAWA AND H. OBARA
SUMMARY
KEY WORDS Complications' hypertension Intubation, trachea/ • cardiovascular response, verapamil.
Laryngoscopy and tracheal intubation often provoke a marked sympathetic response, which may result in hypertension, tachycardia and arrhythmias [1]. Such cardiovascular disturbances, although transient, may be dangerous in some patients, particularly those suffering from myocardial or cerebrovascular disease. This stress response may be attenuated by opioids [1], a- or [3-adrenergic blocking agents [1], ganglionic block [2] and vasodilating agents including nitroglycerine [3], sodium nitroprusside [4] and prostaglandin Ej [5]. Recently, calcium antagonists such as nifedipine [6], nicardipine [7] and diltiazem [8], have also been shown to be effective. We undertook the present study, which was conducted in two parts, to examine the time course and magnitude of changes in mean arterial pressure (MAP) after administration of verapamil during anaesthesia, and to assess its value in attenuating the cardiovascular response to laryngoscopy and tracheal intubation. PATIENTS AND METHODS
This randomized, placebo-controlled, double-blind study was approved by the Human Investigation Committee of Kobe University School of Medicine
Part 1 The time course and magnitude of changes in MAP and heart rate (HR) after a single rapid i.v. injection of verapamil (Vasolan, Eisai, Japan) were determined in 20 patients during anaesthesia but in the absence of stimulation produced by tracheal intubation. Premedication comprised diazepam O.lmgkg"1 orally and atropine 0.01 mg kg"1 i.m. Anaesthesia was induced with thiopentone 5 mg kg"1 and the trachea was intubated after administration of vecuronium 0.2 mg kg"1. Anaesthesia was maintained with 1 % enflurane and 50 % nitrous oxide in oxygen and end-tidal carbon dioxide partial pressure (PEco,) was measured using a Datex Capnometer (Datex, Helsinki, Finland). Ventilation of the lungs was controlled to maintain PE'COI at 4.0-5.1 kPa. After MAP and HR had stabilized, the patients were allocated randomly to two groups and given either verapamil 0.05 mg kg"1 (group A) or O.lmgkg" 1 (group B) as a single rapid i.v. injection. MAP, monitored via a radial artery cannula, was recorded before injection of verapamil and then for 6 min after administration of the drug. HR was calculated from a 15-s portion of the electrocardiogram (ECG). All measurements were completed before skin incision. Part 2 Thirty normotensive patients were allocated randomly into three groups of 10. Premedication comprised diazepam 0.1 mg kg"1 orally and atropine 0.01 mg kg"1 i.m. 60 and 30 min, respectively, before induction of anaesthesia. In the operating room, a radial arterial cannula was inserted under local anaesthesia for continuous monitoring of MAP. HR was calculated from 15-s portions of lead II of the ECG. After a 10-min stabilization period, the patients breathed 100% oxygen via a mask for 3 min. Immediately before induction of anaesthesia, MAP and HR were reHIDEAKI YAKU, M.D. ; KATSUYA M K A W A , M.D.; NOBUHIRO MAEKAWA, M.D. ; HIDEFUMI OBARA, M.D. ; Department of Anaes-
thesiology, Kobe University School of Medicine, Kusunoki-cho 7, Chuo-ku, Kobe 650, Japan. Accepted for Publication: June 8, 1991.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
We have studied the efficacy of verapamil in attenuating the cardiovascular responses to trachea/ intubation in three groups of ASA grade I patients given verapamil 0.05 mg kg'1 or 0.1 mg kg~' or saline 45 s before the start of laryngoscopy. Anaesthesia was induced with thiopentone 5 mg kg~' i.v. and trachea/ intubation was facilitated with vecuronium 0.2 mg kg'1. During anaesthesia, ventilation was assisted or controlled with 1 % enflurane and 50% nitrous oxide in oxygen. In patients who received saline, there was a significant increase in mean arterial pressure and rate-pressure product associated with trachea/ intubation. The increases were significantly less in verapamil-treatedpatients compared with those in the control group, although verapamil failed to prevent tachycardia caused by laryngoscopy and intubation.
and informed consent was obtained. All patients were ASA physical status I, undergoing elective gynaecological or orthopaedic surgery. The present study comprised two parts, as did those of Stoelting [4], and Mikawa, Obara and Kusunoki [7].
BRITISH JOURNAL OF ANAESTHESIA
86
1 TABLE I. Patient data (mean (SD) [range]). No significant differences. A = Verapamil 0.05 mg kg' i.v.; B = verapamil 0.1 mg kg'1 i.v.; C = control (saline) group; D = verapamil 0.05 mg kg'1 i.v.; E = verapamil 0.1 mg kg'1 i.v.
Part 2
Part 1
n
Sex (M:F) Age (yr) Weight (kg)
B
C
D
E
10 5:5
10 4:6
10 4:6
10 5:5
43.9 [28.2-51.5] 55.8(10.4) [43.8-69.5]
45.6 [25.4-54.6] 54.2(10.8) [42.2-72.4]
45.2 [24.8-55.2] 56.2 (9.8) [43.6-70.2]
46.1 [25.6-56.1] 57.3(11.0) [44.3-73.5]
10 4:6 47 .4 [23 .3-58.4] 56 .6(11.7) [42 .4-74.5]
110 -i
- 90
100 -
- 80
90 -
70
80 -
- 60
f c
£ E
2
3
4
Time after verapamil (min)
FIG. 1. Mean (SEM) changes in mean arterial pressure (MAP) ( • , O) and heart rate (HR) (A, A) after a single rapid i.v. injection of verapamil 0.05 mg kg"1 ( # , A) or 0.1 mg kg"1 (O> A) without concomitant laryngoscopy for intubation or surgery. P < 0.05: *compared with basal value; -f 0.05 mg kg"1 compared with 0.1 mg kg"1.
corded by an independent observer. Anaesthesia was induced with thiopentone 5 mg kg"1 followed by vecuronium 0.2 mg kg"1 to facilitate tracheal intubation. Direct laryngoscopy was attempted 2 min after induction, and tracheal intubation was completed within 30 s in all patients, with the aid of a standard Macintosh laryngoscope blade. Verapamil 0.05 mg kg"1 (group D), verapamil O.lmgkg" 1 (group E) or saline (group C) was injected 45 s before direct laryngoscopy was commenced (75 s after induction). All tracheal intubations were performed by the first author, who was blinded to the nature of the injection. After induction of anaesthesia, ventilation of the lungs was assisted as required or controlled with 1.0% enflurane and 50% nitrous oxide in oxygen and PE'CO, was maintained at 4.1—4.9 kPa. PE'CO, w a s measured by means of a catheter placed in the nostril until after insertion of the tracheal tube, when sampling took place from a T-piece connected to the tube. Further measurements were taken at 1, 2, 2.5, 2.75, 3, 3.5, 4, 4.5 and 5 min after induction. MAP, HR, and rate—pressure product (RPP) were compared with corresponding measurements among the three
groups (C-E) and with preinduction measurements within the same group. Statistical analysis Data were analysed by analysis of variance followed by multiple t test with Bonferroni correction when indicated using the super ANOVA (Abacus Concepts, Inc., CA, 1989) computer software package. P < 0.05 was deemed significant. RESULTS
The five groups were comparable in age, weight and gender (table I). Part 1 MAP decreased significantly after verapamil in a dose dependent manner 20 s after administration, reached its minimum after 90 s and a return toward control was apparent by 4 min (fig. 1). HR increased slightly but significantly, but there was no difference between the two doses. Confidence intervals (95%) for these haemodynamic variables are summarized in table II.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
~ en
A
VERAPAMIL AND TRACHEAL INTUBATION TABLE II. Confidence intervals (95 %) of means of haemodynamic variables in Part 1. For clanty, only eight points are shown. A = Verapamil 0.05 mgkg'1 i.v.; B = verapamil 0.1 mgkg' i.v. P < 0.05: + group A compared with group B; * compared with basal values withm groups
Time after administration of verapairul (min) 0 (basal) MAP (mm Hg) A B
76-87*f 66-78*+
74-85*+ 64-76*+
75-86*+ 65-77*+
78-86* 72-85*
81-92* 75-88*
82-100* 75-92*
85-100* 80-98*
J
1
2
3
Timp after thinnfintnne- vecnroniiim (mini
FIG. 2. Mean (SEM) changes in mean arterial pressure (MAP) after thiopentone-vecuronium and in response to laryngoscopy and tracheal intubation, after verapamil 0.05 mgkg"1 ( • ) , 0.1 mgkg"1 (O) or saline (control) (Q) administered i.v. 45 s before starting laryngoscopy. Arrow indicates injection of saline or verapamil and the stippled area indicates duration of laryngoscopy and tracheal intubation. P < 0.05: * compared with control; f 0.05 mg kg"1 compared with 0.1 mg kg"1.
Part 2
There was no significant difference in MAP immediately before the start of laryngoscopy or before induction between the three groups (fig. 2). In response to laryngoscopy and tracheal intubation, MAP increased significantly in all groups, but the increase was significantly less in the verapamiltreated groups than in the control group. The larger dose of verapamil was associated with significantly greater attenuation of MAP than the smaller dose. HR increased after induction of anaesthesia and immediately after tracheal intubation in all three groups, and there was no significant difference between the groups (fig. 3). After laryngoscopy and tracheal intubation, RPP was significantly smaller in both verapamil-treated groups than in the control group (fig. 4). Verapamil 0.1 mg kg~l had a greater inhibitory effect than 0.05 mg kg"1 on the increase in RPP after tracheal intubation. Confidence limits (95%) for these haemodynamic variables are summarized in table III.
No patient was sufficiently hypotensive to require pressor drugs. The least MAP was 60 mm Hg (systolic 82 mm Hg, diastolic 49 mm Hg). No abnormal ECG was observed in any patient. DISCUSSION
We have found that verapamil 0.05 mg kg"1 and 0.1 mgkg"1 attenuated the increases in MAP and RPP after tracheal intubation; the inhibitory effect was greater with the larger dose. The maximum mean RPP after tracheal intubation in the group given verapamil 0.1 mgkg"1 was 14892 mm Hg beat min"1. This value compares favourably with those seen in patients given prostaglandin E! [5] and buprenorphine [9]. However, this RPP value is greater than normal and indicates that the use of verapamil before intubation may not have a myocardial oxygen-sparing effect. Since the report by Hass and Hartfelder [10] in which verapamil was shown to be a putative coronary vasodilator with negative inotropic and chronotropic
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
70
92-104 91-103
1.5
BRITISH JOURNAL OF ANAESTHESIA 130 -i
Saline or Verapamil
120 110 E
100 -
a:
90 80 70 J
0
1
2 3 Time after thiopentone-vecuronium (mini
FIG. 3. Mean (SEM) changes in heart rate (HR) after thiopentone-vecuronium and in response to laryngoscopy and tracheal intubation, after verapamil 0.05 mg kg"1 (#), 0.1 mg kg"1 (O) or saline (control) ( • ) . Stippled area denotes duration of laryngoscopy and trachea] intubation. No difference among the three groups at any time. *P < 0.05 compared with basal value within group.
Saline or Verapamil
20000 -
—
18000
c
1 2
16000
E E
14000 -
i
Q_ CC
12000 10000 8000 -1
r
0
2 3 Time after thiopentone-vecuronium (mini
FIG. 4. Mean (SEM) changes in rate-pressure product (RPP) after thiopentone-vecuronium and in response to laryngoscopy and tracheal intubation, after verapamil 0.05 mgkg"1 (#), 0.1 mg kg"1 (O) or saline (control) (D)Stippled area denotes duration of laryngoscopy and tracheal intubation. P < 0 . 0 5 : * compared with control; f0.05 mgkg"1 compared with 0.1 mgkg"1.
effects, it has been used for treatment of supraventricular tachyarrhythmias [11]. Although the principal pharmacological effect of verapamil is on the sinoatrial and atrioventricular nodes, it also possesses vasodilating properties, in particular when administered i.v., making it useful in the treatment of angina pectoris and hypertension [11]. Verapamil dilates coronary [11], renal and hepatic arteries [12] and it is likely that these effects are advantageous. In common with other vasodilators, verapamil failed to prevent tachycardia caused by laryngoscopy
and intubation, despite the direct negative chronotropic effect of the agent which was masked by reflex sympathetic cardiac compensation induced by peripheral vasodilatation. This lack of effect limits its usefulness, because HR is a major determinant of myocardial oxygen supply. The onset and duration of action of verapamil were rapid and transient, similar to the effects of other calcium channel blockers and vasodilators. No patient in the current study had severe hypotension with either of the two doses. The least MAP in our
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
60
VERAPAMIL AND TRACHEAL INTUBATION
89
TABLE III. Confidence intervals (95 %) of means of haemodynamic variables in Pan 2. Laryngoscopy for tracheal intubation lasting 30 s was started 2 min after thiopentone—vecuromum. For clarity, only six points are shown. C= Saline i.v. (control); D = verapamil 0.05 mg kg'1 i.v.; E = verapamil O.I mg kg~' i.v. P < 0.05: * compared with Group C; -{group E compared with group D Time after thiopentone-vecuronium (mm) 0 (basal)
2
MAP (mm Hg) C D E
80-95 82-96 84-98
73-96 71-89 69-88
HR (beat min"1) C D E
68-90 69-87 69-82
83-100 79-96 83-97
92-114 93-112 92-111
9059-11731 8202-11105 8855-10754
15415-17741 13403-15427* 11298-13494*f
RPP (mm Hg beat min"1) C 8082-11287 D 7907-11125 E 8036-11588
2.5 111-131 96-111* 83-100*t
REFERENCES 1. Ng WS. Pathophysiological effects of tracheal intubation. In: Latto IP, Rosen M, cds. Difficulties in Tracheal Intubation Eastbourne: Bailliere Tindall, 1985; 12-35. 2. Saitoh N, Mikawa K, Kitamura S, Maekawa N, Goto R, Yaku H, Yamada M, Obara H. Effects of trimetaphan on the cardiovascular response to tracheal intubation. British Journal of Anaesthesia 1991; 66: 340-344. 3. Fassoulaki A, Kaniaris P. Intranasal administration of nitroglycerine attenuates the pressor response to laryngoscopy and intubation of the trachea. British Journal of Anaesthesia 1983; 55: 49-52.
3
5
116-136 105-122* 95-11l*f
113-134 97-115* 84-101*t
92-106 83-97* 73-89*
103-122 102-119 102-117
100-119 100-113 98-112
87-107 87-100 85-100
18348-20902 16324-18682* 13578-16206*t
17134-19798 15361-17451* 12403-14845*+
12237-14421 10371-12239* 9328-11330*
4. Stoelting RK. Attenuation of blood pressure response to laryngoscopy and trachcal intubation with sodium nitroprusside. Anesthesia and Analgesia 1979; 58: 116-119. 5. Mikawa K, Ikegaki J, Maekawa N, Hoshina H, Tanaka O, Goto R, Obara H. Effects of prostaglandin Ej on the cardiovascular response to trachea] intubation. Journal of Clinical Anesthesia 1990; 2: 420-^124. 6. Puri GD, Batra YK. Effect of nifedipine on cardiovascular responses to laryngoscopy and intubation. British Journal of Anaesthesia 1988; 60: 579-581. 7. Mikawa K, Obara H, Kusunoki M. The effect of nicardipine on the cardiovascular response to tracheal intubation. British Journal of Anaesthesia 1990; 64: 240-242. 8. Mikawa K, Ikegaki J, Maekawa N, Goto R, Kaetsu H, Obara H. The effect of diltiazem on the cardiovascular response to tracheal intubation. Anaesthesia 1990; 45: 289-293. 9. Khan FA, Kamal RS. Effect of buprenorphine on the cardiovascular response to tracheal intubation. Anaesthesia 1989; 44: 394-397. 10. Hass H, Hartfelder G. ot-Isopropyl-a-[(N-methyl-Nhomoveratyl)-Y-aminopropyl]-3,4-dimethoxyphenyl acetonitnl, eine Substance mit coronaryefafierweitemden Eigenschaftcn. Arzneimtttel Forschung 1962; 12: 549-558. 11. Murad F. Drugs used for the treatment of angina: organic nitrates, calcium channel blockers, and p-adrenergic antagonists. In: Gilman AG, Rail TW, Nies AS, Taylor P, eds. Goodman and Gilman1 s The Pharmacological Basis of Therapeutics, 8th Edn. New York: Pcrgamon Press, 1990; 764-783. 12. Meredith PA, Elliott HL, Pasanisi F, Kelman AW, Sumner DJ, Reid JL. Verapamil pharmacokinetics and apparent hepatic and renal blood flow. British Journal of Clinical Pharmacology 1985; 20: 101-106. 13. Khan RM, Khan TZ, Hakim S, Khan S, Haq G, Aslam M. Verapamil as a hypotensive agent under general anaesthesia. Journal of The Indian Medical Association 1990; 88: 251-253. 14. McTavish D, Sorkin EM. Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1989; 38: 19-76. 15. Frishman WH, Weinberg P, Peled HB, Kimmel B, Charlap S, Beer N. Calcium entry blockers for the treatment of severe hypertension and hypertensive crisis. American Journal of Medicine 1984; 77 : 35-45. 16. McAllister RG Jr. Calcium antagonists. In: Wood M, Wood AJJ, eds. Drugs and Anesthesia: Pharmacology for Anesthesiologists, 2nd Edn. Baltimore: Williams & Wilkins, 1990; 509-534.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
study was 60 mm Hg (systolic 82 mm Hg, diastolic 49 mm Hg). The 95 % confidence interval of the mean MAP 1.5 min after the administration of verapamil was 64-76 mm Hg in the group given 0.1 mg kg"1. If the "true" value of the mean MAP was 64 mm Hg, there may have been a few patients with an MAP less than 50 mm Hg, which may be hazardous even for ASA I patients. Khan and colleagues reported that a bolus injection of verapamil 0.05-0.075 mg kg"1 produced dose-dependent reductions in MAP in ASA I patients undergoing general anaesthesia [13]. Thus using verapamil 0.05 mg kg"1 may be safer than O.lmgkg"1. However, in clinical use, because laryngoscopy for tracheal intubation begins before verapamil has attained its maximal hypotensive effect, undue hypotension during induction of anaesthesia can probably be avoided even when using a dose of 0.1 mgkg- 1 . A single i.v. administration of verapamil 5—10 mg has been shown to decrease arterial pressure in hypertensive patients at rest and during exercise [14, 15]. The magnitude of arterial pressure decrease caused by a given dose of verapamil is greater in hypertensive than in normotensive subjects [14, 15] and is enhanced by volatile anaesthetics [16]. It is possible that this technique may be useful in hypertensive patients.
2.75
EFFECT OF VERAPAMIL ON THE CARDIOVASCULAR RESPONSES TO TRACHEAL INTUBATION H. YAKU, K. MIKAWA, N. MAEKAWA AND H. OBARA
SUMMARY
KEY WORDS Complications' hypertension Intubation, trachea/ • cardiovascular response, verapamil.
Laryngoscopy and tracheal intubation often provoke a marked sympathetic response, which may result in hypertension, tachycardia and arrhythmias [1]. Such cardiovascular disturbances, although transient, may be dangerous in some patients, particularly those suffering from myocardial or cerebrovascular disease. This stress response may be attenuated by opioids [1], a- or [3-adrenergic blocking agents [1], ganglionic block [2] and vasodilating agents including nitroglycerine [3], sodium nitroprusside [4] and prostaglandin Ej [5]. Recently, calcium antagonists such as nifedipine [6], nicardipine [7] and diltiazem [8], have also been shown to be effective. We undertook the present study, which was conducted in two parts, to examine the time course and magnitude of changes in mean arterial pressure (MAP) after administration of verapamil during anaesthesia, and to assess its value in attenuating the cardiovascular response to laryngoscopy and tracheal intubation. PATIENTS AND METHODS
This randomized, placebo-controlled, double-blind study was approved by the Human Investigation Committee of Kobe University School of Medicine
Part 1 The time course and magnitude of changes in MAP and heart rate (HR) after a single rapid i.v. injection of verapamil (Vasolan, Eisai, Japan) were determined in 20 patients during anaesthesia but in the absence of stimulation produced by tracheal intubation. Premedication comprised diazepam O.lmgkg"1 orally and atropine 0.01 mg kg"1 i.m. Anaesthesia was induced with thiopentone 5 mg kg"1 and the trachea was intubated after administration of vecuronium 0.2 mg kg"1. Anaesthesia was maintained with 1 % enflurane and 50 % nitrous oxide in oxygen and end-tidal carbon dioxide partial pressure (PEco,) was measured using a Datex Capnometer (Datex, Helsinki, Finland). Ventilation of the lungs was controlled to maintain PE'COI at 4.0-5.1 kPa. After MAP and HR had stabilized, the patients were allocated randomly to two groups and given either verapamil 0.05 mg kg"1 (group A) or O.lmgkg" 1 (group B) as a single rapid i.v. injection. MAP, monitored via a radial artery cannula, was recorded before injection of verapamil and then for 6 min after administration of the drug. HR was calculated from a 15-s portion of the electrocardiogram (ECG). All measurements were completed before skin incision. Part 2 Thirty normotensive patients were allocated randomly into three groups of 10. Premedication comprised diazepam 0.1 mg kg"1 orally and atropine 0.01 mg kg"1 i.m. 60 and 30 min, respectively, before induction of anaesthesia. In the operating room, a radial arterial cannula was inserted under local anaesthesia for continuous monitoring of MAP. HR was calculated from 15-s portions of lead II of the ECG. After a 10-min stabilization period, the patients breathed 100% oxygen via a mask for 3 min. Immediately before induction of anaesthesia, MAP and HR were reHIDEAKI YAKU, M.D. ; KATSUYA M K A W A , M.D.; NOBUHIRO MAEKAWA, M.D. ; HIDEFUMI OBARA, M.D. ; Department of Anaes-
thesiology, Kobe University School of Medicine, Kusunoki-cho 7, Chuo-ku, Kobe 650, Japan. Accepted for Publication: June 8, 1991.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
We have studied the efficacy of verapamil in attenuating the cardiovascular responses to trachea/ intubation in three groups of ASA grade I patients given verapamil 0.05 mg kg'1 or 0.1 mg kg~' or saline 45 s before the start of laryngoscopy. Anaesthesia was induced with thiopentone 5 mg kg~' i.v. and trachea/ intubation was facilitated with vecuronium 0.2 mg kg'1. During anaesthesia, ventilation was assisted or controlled with 1 % enflurane and 50% nitrous oxide in oxygen. In patients who received saline, there was a significant increase in mean arterial pressure and rate-pressure product associated with trachea/ intubation. The increases were significantly less in verapamil-treatedpatients compared with those in the control group, although verapamil failed to prevent tachycardia caused by laryngoscopy and intubation.
and informed consent was obtained. All patients were ASA physical status I, undergoing elective gynaecological or orthopaedic surgery. The present study comprised two parts, as did those of Stoelting [4], and Mikawa, Obara and Kusunoki [7].
BRITISH JOURNAL OF ANAESTHESIA
86
1 TABLE I. Patient data (mean (SD) [range]). No significant differences. A = Verapamil 0.05 mg kg' i.v.; B = verapamil 0.1 mg kg'1 i.v.; C = control (saline) group; D = verapamil 0.05 mg kg'1 i.v.; E = verapamil 0.1 mg kg'1 i.v.
Part 2
Part 1
n
Sex (M:F) Age (yr) Weight (kg)
B
C
D
E
10 5:5
10 4:6
10 4:6
10 5:5
43.9 [28.2-51.5] 55.8(10.4) [43.8-69.5]
45.6 [25.4-54.6] 54.2(10.8) [42.2-72.4]
45.2 [24.8-55.2] 56.2 (9.8) [43.6-70.2]
46.1 [25.6-56.1] 57.3(11.0) [44.3-73.5]
10 4:6 47 .4 [23 .3-58.4] 56 .6(11.7) [42 .4-74.5]
110 -i
- 90
100 -
- 80
90 -
70
80 -
- 60
f c
£ E
2
3
4
Time after verapamil (min)
FIG. 1. Mean (SEM) changes in mean arterial pressure (MAP) ( • , O) and heart rate (HR) (A, A) after a single rapid i.v. injection of verapamil 0.05 mg kg"1 ( # , A) or 0.1 mg kg"1 (O> A) without concomitant laryngoscopy for intubation or surgery. P < 0.05: *compared with basal value; -f 0.05 mg kg"1 compared with 0.1 mg kg"1.
corded by an independent observer. Anaesthesia was induced with thiopentone 5 mg kg"1 followed by vecuronium 0.2 mg kg"1 to facilitate tracheal intubation. Direct laryngoscopy was attempted 2 min after induction, and tracheal intubation was completed within 30 s in all patients, with the aid of a standard Macintosh laryngoscope blade. Verapamil 0.05 mg kg"1 (group D), verapamil O.lmgkg" 1 (group E) or saline (group C) was injected 45 s before direct laryngoscopy was commenced (75 s after induction). All tracheal intubations were performed by the first author, who was blinded to the nature of the injection. After induction of anaesthesia, ventilation of the lungs was assisted as required or controlled with 1.0% enflurane and 50% nitrous oxide in oxygen and PE'CO, was maintained at 4.1—4.9 kPa. PE'CO, w a s measured by means of a catheter placed in the nostril until after insertion of the tracheal tube, when sampling took place from a T-piece connected to the tube. Further measurements were taken at 1, 2, 2.5, 2.75, 3, 3.5, 4, 4.5 and 5 min after induction. MAP, HR, and rate—pressure product (RPP) were compared with corresponding measurements among the three
groups (C-E) and with preinduction measurements within the same group. Statistical analysis Data were analysed by analysis of variance followed by multiple t test with Bonferroni correction when indicated using the super ANOVA (Abacus Concepts, Inc., CA, 1989) computer software package. P < 0.05 was deemed significant. RESULTS
The five groups were comparable in age, weight and gender (table I). Part 1 MAP decreased significantly after verapamil in a dose dependent manner 20 s after administration, reached its minimum after 90 s and a return toward control was apparent by 4 min (fig. 1). HR increased slightly but significantly, but there was no difference between the two doses. Confidence intervals (95%) for these haemodynamic variables are summarized in table II.
Downloaded from http://bja.oxfordjournals.org/ at Michigan State University on June 30, 2015
~ en
A
VERAPAMIL AND TRACHEAL INTUBATION TABLE II. Confidence intervals (95 %) of means of haemodynamic variables in Part 1. For clanty, only eight points are shown. A = Verapamil 0.05 mgkg'1 i.v.; B = verapamil 0.1 mgkg' i.v. P < 0.05: + group A compared with group B; * compared with basal values withm groups
Time after administration of verapairul (min) 0 (basal) MAP (mm Hg) A B
76-87*f 66-78*+
74-85*+ 64-76*+
75-86*+ 65-77*+
78-86* 72-85*
81-92* 75-88*
82-100* 75-92*
85-100* 80-98*
J
1
2
3
Timp after thinnfintnne- vecnroniiim (mini
FIG. 2. Mean (SEM) changes in mean arterial pressure (MAP) after thiopentone-vecuronium and in response to laryngoscopy and tracheal intubation, after verapamil 0.05 mgkg"1 ( • ) , 0.1 mgkg"1 (O) or saline (control) (Q) administered i.v. 45 s before starting laryngoscopy. Arrow indicates injection of saline or verapamil and the stippled area indicates duration of laryngoscopy and tracheal intubation. P < 0.05: * compared with control; f 0.05 mg kg"1 compared with 0.1 mg kg"1.
Part 2
There was no significant difference in MAP immediately before the start of laryngoscopy or before induction between the three groups (fig. 2). In response to laryngoscopy and tracheal intubation, MAP increased significantly in all groups, but the increase was significantly less in the verapamiltreated groups than in the control group. The larger dose of verapamil was associated with significantly greater attenuation of MAP than the smaller dose. HR increased after induction of anaesthesia and immediately after tracheal intubation in all three groups, and there was no significant difference between the groups (fig. 3). After laryngoscopy and tracheal intubation, RPP was significantly smaller in both verapamil-treated groups than in the control group (fig. 4). Verapamil 0.1 mg kg~l had a greater inhibitory effect than 0.05 mg kg"1 on the increase in RPP after tracheal intubation. Confidence limits (95%) for these haemodynamic variables are summarized in table III.
No patient was sufficiently hypotensive to require pressor drugs. The least MAP was 60 mm Hg (systolic 82 mm Hg, diastolic 49 mm Hg). No abnormal ECG was observed in any patient. DISCUSSION
We have found that verapamil 0.05 mg kg"1 and 0.1 mgkg"1 attenuated the increases in MAP and RPP after tracheal intubation; the inhibitory effect was greater with the larger dose. The maximum mean RPP after tracheal intubation in the group given verapamil 0.1 mgkg"1 was 14892 mm Hg beat min"1. This value compares favourably with those seen in patients given prostaglandin E! [5] and buprenorphine [9]. However, this RPP value is greater than normal and indicates that the use of verapamil before intubation may not have a myocardial oxygen-sparing effect. Since the report by Hass and Hartfelder [10] in which verapamil was shown to be a putative coronary vasodilator with negative inotropic and chronotropic
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70
92-104 91-103
1.5
BRITISH JOURNAL OF ANAESTHESIA 130 -i
Saline or Verapamil
120 110 E
100 -
a:
90 80 70 J
0
1
2 3 Time after thiopentone-vecuronium (mini
FIG. 3. Mean (SEM) changes in heart rate (HR) after thiopentone-vecuronium and in response to laryngoscopy and tracheal intubation, after verapamil 0.05 mg kg"1 (#), 0.1 mg kg"1 (O) or saline (control) ( • ) . Stippled area denotes duration of laryngoscopy and trachea] intubation. No difference among the three groups at any time. *P < 0.05 compared with basal value within group.
Saline or Verapamil
20000 -
—
18000
c
1 2
16000
E E
14000 -
i
Q_ CC
12000 10000 8000 -1
r
0
2 3 Time after thiopentone-vecuronium (mini
FIG. 4. Mean (SEM) changes in rate-pressure product (RPP) after thiopentone-vecuronium and in response to laryngoscopy and tracheal intubation, after verapamil 0.05 mgkg"1 (#), 0.1 mg kg"1 (O) or saline (control) (D)Stippled area denotes duration of laryngoscopy and tracheal intubation. P < 0 . 0 5 : * compared with control; f0.05 mgkg"1 compared with 0.1 mgkg"1.
effects, it has been used for treatment of supraventricular tachyarrhythmias [11]. Although the principal pharmacological effect of verapamil is on the sinoatrial and atrioventricular nodes, it also possesses vasodilating properties, in particular when administered i.v., making it useful in the treatment of angina pectoris and hypertension [11]. Verapamil dilates coronary [11], renal and hepatic arteries [12] and it is likely that these effects are advantageous. In common with other vasodilators, verapamil failed to prevent tachycardia caused by laryngoscopy
and intubation, despite the direct negative chronotropic effect of the agent which was masked by reflex sympathetic cardiac compensation induced by peripheral vasodilatation. This lack of effect limits its usefulness, because HR is a major determinant of myocardial oxygen supply. The onset and duration of action of verapamil were rapid and transient, similar to the effects of other calcium channel blockers and vasodilators. No patient in the current study had severe hypotension with either of the two doses. The least MAP in our
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60
VERAPAMIL AND TRACHEAL INTUBATION
89
TABLE III. Confidence intervals (95 %) of means of haemodynamic variables in Pan 2. Laryngoscopy for tracheal intubation lasting 30 s was started 2 min after thiopentone—vecuromum. For clarity, only six points are shown. C= Saline i.v. (control); D = verapamil 0.05 mg kg'1 i.v.; E = verapamil O.I mg kg~' i.v. P < 0.05: * compared with Group C; -{group E compared with group D Time after thiopentone-vecuronium (mm) 0 (basal)
2
MAP (mm Hg) C D E
80-95 82-96 84-98
73-96 71-89 69-88
HR (beat min"1) C D E
68-90 69-87 69-82
83-100 79-96 83-97
92-114 93-112 92-111
9059-11731 8202-11105 8855-10754
15415-17741 13403-15427* 11298-13494*f
RPP (mm Hg beat min"1) C 8082-11287 D 7907-11125 E 8036-11588
2.5 111-131 96-111* 83-100*t
REFERENCES 1. Ng WS. Pathophysiological effects of tracheal intubation. In: Latto IP, Rosen M, cds. Difficulties in Tracheal Intubation Eastbourne: Bailliere Tindall, 1985; 12-35. 2. Saitoh N, Mikawa K, Kitamura S, Maekawa N, Goto R, Yaku H, Yamada M, Obara H. Effects of trimetaphan on the cardiovascular response to tracheal intubation. British Journal of Anaesthesia 1991; 66: 340-344. 3. Fassoulaki A, Kaniaris P. Intranasal administration of nitroglycerine attenuates the pressor response to laryngoscopy and intubation of the trachea. British Journal of Anaesthesia 1983; 55: 49-52.
3
5
116-136 105-122* 95-11l*f
113-134 97-115* 84-101*t
92-106 83-97* 73-89*
103-122 102-119 102-117
100-119 100-113 98-112
87-107 87-100 85-100
18348-20902 16324-18682* 13578-16206*t
17134-19798 15361-17451* 12403-14845*+
12237-14421 10371-12239* 9328-11330*
4. Stoelting RK. Attenuation of blood pressure response to laryngoscopy and trachcal intubation with sodium nitroprusside. Anesthesia and Analgesia 1979; 58: 116-119. 5. Mikawa K, Ikegaki J, Maekawa N, Hoshina H, Tanaka O, Goto R, Obara H. Effects of prostaglandin Ej on the cardiovascular response to trachea] intubation. Journal of Clinical Anesthesia 1990; 2: 420-^124. 6. Puri GD, Batra YK. Effect of nifedipine on cardiovascular responses to laryngoscopy and intubation. British Journal of Anaesthesia 1988; 60: 579-581. 7. Mikawa K, Obara H, Kusunoki M. The effect of nicardipine on the cardiovascular response to tracheal intubation. British Journal of Anaesthesia 1990; 64: 240-242. 8. Mikawa K, Ikegaki J, Maekawa N, Goto R, Kaetsu H, Obara H. The effect of diltiazem on the cardiovascular response to tracheal intubation. Anaesthesia 1990; 45: 289-293. 9. Khan FA, Kamal RS. Effect of buprenorphine on the cardiovascular response to tracheal intubation. Anaesthesia 1989; 44: 394-397. 10. Hass H, Hartfelder G. ot-Isopropyl-a-[(N-methyl-Nhomoveratyl)-Y-aminopropyl]-3,4-dimethoxyphenyl acetonitnl, eine Substance mit coronaryefafierweitemden Eigenschaftcn. Arzneimtttel Forschung 1962; 12: 549-558. 11. Murad F. Drugs used for the treatment of angina: organic nitrates, calcium channel blockers, and p-adrenergic antagonists. In: Gilman AG, Rail TW, Nies AS, Taylor P, eds. Goodman and Gilman1 s The Pharmacological Basis of Therapeutics, 8th Edn. New York: Pcrgamon Press, 1990; 764-783. 12. Meredith PA, Elliott HL, Pasanisi F, Kelman AW, Sumner DJ, Reid JL. Verapamil pharmacokinetics and apparent hepatic and renal blood flow. British Journal of Clinical Pharmacology 1985; 20: 101-106. 13. Khan RM, Khan TZ, Hakim S, Khan S, Haq G, Aslam M. Verapamil as a hypotensive agent under general anaesthesia. Journal of The Indian Medical Association 1990; 88: 251-253. 14. McTavish D, Sorkin EM. Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1989; 38: 19-76. 15. Frishman WH, Weinberg P, Peled HB, Kimmel B, Charlap S, Beer N. Calcium entry blockers for the treatment of severe hypertension and hypertensive crisis. American Journal of Medicine 1984; 77 : 35-45. 16. McAllister RG Jr. Calcium antagonists. In: Wood M, Wood AJJ, eds. Drugs and Anesthesia: Pharmacology for Anesthesiologists, 2nd Edn. Baltimore: Williams & Wilkins, 1990; 509-534.
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study was 60 mm Hg (systolic 82 mm Hg, diastolic 49 mm Hg). The 95 % confidence interval of the mean MAP 1.5 min after the administration of verapamil was 64-76 mm Hg in the group given 0.1 mg kg"1. If the "true" value of the mean MAP was 64 mm Hg, there may have been a few patients with an MAP less than 50 mm Hg, which may be hazardous even for ASA I patients. Khan and colleagues reported that a bolus injection of verapamil 0.05-0.075 mg kg"1 produced dose-dependent reductions in MAP in ASA I patients undergoing general anaesthesia [13]. Thus using verapamil 0.05 mg kg"1 may be safer than O.lmgkg"1. However, in clinical use, because laryngoscopy for tracheal intubation begins before verapamil has attained its maximal hypotensive effect, undue hypotension during induction of anaesthesia can probably be avoided even when using a dose of 0.1 mgkg- 1 . A single i.v. administration of verapamil 5—10 mg has been shown to decrease arterial pressure in hypertensive patients at rest and during exercise [14, 15]. The magnitude of arterial pressure decrease caused by a given dose of verapamil is greater in hypertensive than in normotensive subjects [14, 15] and is enhanced by volatile anaesthetics [16]. It is possible that this technique may be useful in hypertensive patients.
2.75
