Acta Anaesthesiol Scand 1991 35: 262-266

Comparison of the haemodynamic effects of pipecuronium and pancuronium during fentanyl anaesthesia J. C. STANLEY, I . W. CARSON, F. M. GIBSON, T. J. MCMURRAY, P. ELLIOTT,S. M. LYONS and R . K. MIRAKHUR Departments of Clinical Anaesthesia, Royal Victoria Hospital nnd Queen's University of Belfast, Belfast, N. Ireland, U K

Haemodynamic variables were measured following administration of pipecuronium 70 pg . kg- I and pancuronium 90 pg. kg-' (approximately equivalent to 1.5 x ED,,) in patients anaesthetised with fentanyl 50 pg. kg-' and scheduled to undergo coronary artery bypass grafting. There were significant inrreases in heart rate (22'',:,), mean arterial pressure (lo"/;), cardiac index (l6Y,,), and the rate pressure product (35",) following administration of pancuronium. 'The absolute values of these parameters were, however, within acceptable rlinical limits. Administration of pipecuronium produced minimal and insignificant changes i n these parameters. Other measured or derived indices showed only small changes with both agents and thew were generally insignificant. T h e were no incidences of significant bradyrardia following pipecuronium administration. The results from the present study suggest that pipecuronium would have advantages for use in patients with significant cardiovascular disease. Received 25 June, arcepted,for publication 23 September 1990

Kcy words: Hemodynamirs: heart rate, blood pressure, rardiac output; neuro~nusruIarblocking agents: pipecuronium, pancuronium; surgery: coronary artery bypass grafting

Pancuronium bromide, due to its lack of significant cardiovacular depression, has now been used for many years to provide neuromuscular block during anaesthesia for patients undergoing cardiac surgery (1-3). A recent editorial (4) has, however, challenged this viewpoint following publication of a report on the use of pancuronium in patients with coronary artery disease (5). This report suggested production of myocardial ischaemia with the use of pancuronium in patients with severe coronary artcry disease. Pipecuronium bromide is a nondepolarizing neuromuscular blocking agent currently undergoing evaluation for clinical use. It resembles pancuronium in its chemical structure, but is somewhat more potent ( 6 ) . Animal studies suggest that it does not cause haemodynamic changes related to histamine release or effects on the autonomic nervous system ( 7 ) . A previous study has shown pipecuronium to lie free from serious cardiovascular effects in patients undergoing coronary artery bypass surgery using midazolam and low-dose fentanyl (8). The aim of the present study was to compare the haemodynamic rfkcts of pipecuronium with those of pancuronium following induction of anaesthesia with fentanyl in a high dose in patients scheduled to undergo coronary artery bypass surgery.

PATIENTS AND METHODS Thirty adult patients, divided randomly into two comparable groups of 15 each (Table I ) , and scheduled for coronary artery bypass graft surgery (CABG), were included in the study after obtaining their informed consent and approval from the Regional Ethical Committee. Those patients with a left ventricular ejection fraction of less than 50"b, or suffering from valvular heart disease or hepatic, renal, or neuromuscular disorders were excluded from the study. T h r majority of patients were receiving beta-adrenergic receptor blocking drugs, calcium entry blocking drugs, and nitrates and these were continued until the morning of surgery. All patients werr in sinus rhythm. Premedication consisted of lorazrpam 3-4 rng orally and morphine 10 mg and hyoscinr 0.2 mg intramuscularly. Monitoring of heart rate and rhythm was commenced on arrival in the operating room. Peripheral arterial and venous cannulatioris and insertion of a multi-lumen pulmonary artrry flotation ratheter were carried out under local anarsthesia. Anaesthesia was indured 'Table 1 Physical chararteristics. Pipecuronium n Age (years) Weight (kg) Body surface area (m') Sex - male - female Values are given as mean k s.d.

Pancuronium

15

15

58 ( _+ 7.1) 70.6 ( 8.7)

54 ( f 6.0) 73.3 ( 12.2)

1.80 ( k O . 1 4 ) II 4

1.89 ( 2 0 . 2 7 ) 12

3

263

HAEMODYNAMIC EFFECTS OF RELAXANTS with HII infusion of fentanyl at a rate of 5 pg . kg-'. min-' up to a total dose of 50 pg . kg-'. At the loss ofeyelash reflex, suxamethonium 1.5 mg. kg-' was administered to facilitate tracheal intubation. Ventilation was carried out with a mixture of air and oxygen and adjusted to maintain the end-tidal carbon dioxide concentration between 4.75 and 5.25 vol yo.Haemodynamic stability and recovery from neuromuscular block due to suxamethonium was allowed to take place over the next 15 min. The patients were then randomly allocated to receive either pipecuronium 70 pg. kg-' or pancuronium 90 pg . kg-' as a rapid bolus injection via the central venous catheter. These are approximately 1.5 x ED,, of the two relaxants (6). Measurements of heart rate (HR), systemic and pulmonary artery pressures, pulmonary capillary wedge pressure (PCWP), and central venous pressure (CVP) were recorded using a Hewlett-Packard 78205C monitor prior to induction of anaesthesia, following induction, following haemodynamic stabilisation after induction and intu-

bation, and 1, 3, 5, and 10 min after administration of pipecuronium or pancuronium. Thermodilution cardiac output determination\ were made in triplicate at the same times at the end of expiration using a cardiac output computer (Edwards Laboratories 9520A) and injections of 10 ml of iced 5% dextrose in water. The mean of thr three readings was taken as the cardiac output at each time. Cardim index (CI), stroke volume index (SVI), left ventricular stroke woik index (LVSWI), right ventricular stroke work index (RVSWI), syatemic vascular resistance (SVR), pulmonary vascular resistanrv (PVR), and rate pressure product (RPP) were calculated from thr measured haemodynamic variables using standard formulae. Arterial blood gas measurements were made before induction of anaesthesia. following intubation, and just prior to administration of the stud\ drugs. End-tidal carbon dioxide concentration was monitored continuously using a capnograph (Hewlett-Packard), and arterial oxygen saturation measured using a pulse oximeter (Ohmeda). Neuro-

Tablt 2 Haemdynamic variables ~~~~

~

~

Time (min) Variable HR I beats min-') PiP Pan CVP immHg) PiP Pan PCWP (mmHg) PiP Pan MAP (mmHg) PiP Pan MPAP (mmHg) PiP Pan CI 11, min-'. m-') PiP Pan SVI 1 ml . beat- I .m-') PiP Pan LVSWI (g.rn.beat-'.m-') PiP Pan RVSWI (g.m.beat-'.m-') PiP Pan SVK (dyn.s . cm-') PiP Pan PVR (dyn.s.cm -,) PiP Pan RPP (mmHg. beats.min-l) PiP pan

- 20

0

+1

+3

+ 10

+5

54 f 8.5 54 f 7.0

53 f 7. I 54 f 10.9

53 f 7.8 66 f 12.5*t

52 f 7.7 64f 1 l.7*t

51 f 8.0 65 f 13.4*t

50 f 7.9 63f 11.3*t

6.5 f 2.4 7.9 f 2.8

6.5 f 2.4 9.3 f 4.2t

6.0 f 2.0 7.82 2.2'

6.0 f 1.8 7.5 f 2.4*

6.3 f 1.9 7.3 f 2.6*

6.1 f 2 . 2 7.6 & 2.1.

9.7 f 3.7 11.3 f 3.0 8 4 f 11.7 8 4 + 11.0

9.9 f 4.2 11.7f3.6 78 f 14.0 78 f 17.2

9.8 f 3.9 10.8 f 2.8

80 f 13.9 85 f 17.0*

9.9 f 3.8 10.2 f 2.5 79 f 14.8 85 f 17.3,

9.5 f 3.9 9.7 f 2.5*

9.8 f 3.6 10.5 f 2.5

80 f 13.7 86f 17.4'

79 f 13.4 83 f 15.9*

13.8 f 3.8 15.5 f 4.1

15.0 f 4.1 16.4 f 4.9

15.2 f 3.5 16.5 f 4.0

15.5 f 3.5 16.0 f 3.9

15.6 f 3.8 16.0 f 4.2

15.2 f 3.7 15.5 f 4.2

2.40 f 0.26 2.1 I f 0.49

2.43 f 0.61 2.1 I f 0.57

2.49 f 0.65 2.43 f 0.62.

2.41 f 0.65 2.39 f 0.59*

2.39 f 0.60 2.39 f 0.63'

2.41 0.60 2.44 f 0.55*

45.3 f 5.4 39.0 f 9.2t

45.5 f 6.6 39.5 9.4

*

46.9 f 6.8 37.6 f 9.6t

45.6 f 6.5 38.0 f 9.67

46.5 f 5.7 37.5 f 9.9t

47.6 f 6.3 39.3 f 8.81

45.5 f 7.5 37.7 f 12.31

42.4 f 11.5 36.3 f 12.6

44.9 f 11.5 38.6 f 13.7

43.1 f 11.4 39.0 f 13.7

44.2 f 10.3 38.4 f 13.3

44.8 f 9.9 39.3 f 12.7

8.422.1 8.2 f 2.5

9.5 f 3.6 9.0 f 4.0

9.8 f 3.2 8.6 f 3.4

9.7 f 3.2 8.4 f 3.3

10.0 f 3.4 8.3 f 3.5

9.9 f 3.0 8.3 f 3.3

1455 f 262 1605 f 373

1356f318 I464 f 406

1380 343 1399 f 359

1420f 377 1427 f 345

1407 f 329 1457 f 397

1393 f 343 1361 f 319

82 f 47 89 f 42

91 f 6 0 99 f 40

100 f 60 101 f 32

108 f 55 104f40

112f50 100 f 49

110f56 105 f 47

7 160 f 201 1 6640 f 1038

6375 f 1631

6421 f I647

6379 f 1775

6229 f 1779

6120f 1678

~

Values are expressed as means f s.d.. Abbreviations: time - 20, values prior to induction of anaesthesia; time 0, values immediately prior 10 relaxant administration; pip, pipecuronium; pan, pancuronium; HR, heart rate; CVP, central venous pressure; PCWP, pulmonary capillai) wecjgr pressure; MAP, mean arterial pressure; MPAP, mean pulmonary artery pressure; CI, cardiac index; SVI, stroke volume index, LVSWI, left ventricular stroke work index; RVSWI, right ventricular stroke work index; SVR, systemic vascular resistance, PVR, pulmonan vascular resistance; RPP, rate pressure product. * P i 0 . 0 5 in comparison to time 0 (control); t P