Anaesthesia, 1992, Volume 47, pages 105-106
Pipecuronium versus high dose vecuronium I. A comparison of speed of onset and cumulation during isoflurane anaesthesia W. HARROP-GRIFFITHS, N . FAUVEL, M . P L U M L E Y
AND
S. F E L D M A N
Summary The onset time and tendency to cumulation of pipecuronium and high-dose vecuronium were studied during nitrous oxide anaesthesia supplemented with isojurane. Pipecuronium 0.06 mg.kg - had a similar duration of action to vecuronium 0.015 mg.kg-’ (42 vs 49 min). Patients who received vecuronium had a shorter onset time of neuromuscular blockade ( p < 0.01). The use of pipecuronium was associated with marked cumulation.
’
Key words Neuromuscular relaxants; pipecuronium, vecuronium. Anaesthetics, volatile; isoflurane.
It has been suggested [ I ] that pipecuronium may be an ideal neuromuscular blocking agent for long operations in patients with cardiovascular disease, as it possesses a duration of action and potency similar to pancuronium [2] and a greater degree of haemodynamic stability [3]. Vecuronium has a shorter duration of action than pipecuronium when given in doses equipotent for the degree of neuromuscular block (i.e. similar multiples of ED,, or ED,,), but can be given safely in doses of up to 0.4 mg.kg-’ in order to prolong its duration of action [4-61. The purpose of this study was to determine whether doses of pipecuronium and vecuronium that have similar initial durations of action show differences in onset time and tendency to cumulation.
used to monitor neuromuscular function, recording the response of the adductor pollicis muscle to supramaximal stimulation of the ulnar nerve. The Relaxograph was attached before induction, after which baseline values were established. After a period of stabilisation, patients were given either pipecuronium 0.06 mg.kg-’ or vecuronium 0.15 mg.kg-I; these doses were estimated to have a similar initial duration of action. Onset time of neuromuscular blockade was taken as the time between the administration of the neuromuscular blocking agent and the time when the first ‘twitch’ of the train-of-four (Tl) reached less than 5% of control. Tracheal intubation was performed a t this time. Maintenance doses (one fifth of the initial dose) were given when TI returned to 10% of control. Statistical analysis was performed using unpaired Student’s t-tests.
Methods Institutional ethics approval was obtained for the study. Thirty ASA physical status 1 or 2 patients scheduled for elective surgery gave informed written consent, and were admitted to the study. The surgical procedures comprised major abdominal surgery ( 1 1 patients) or joint replacement surgery (19 patients). The patients were allocated randomly into one of two groups, and received either pipecuronium or vecuronium. After premedication with papaveretum and hyoscine, anaesthesia was induced with a sleep dose of thiopentone and maintained with 33% oxygen in nitrous oxide supplemented with an inspired concentration of between 0.5 and 1% isoflurane. A Datex Relaxograph was
Results Demographic data are presented in Table I . Mean onset time and duration of the initial dose of neuromuscular Table 1. Mean (SD) age and weight. Study group
Age; years Weight; kg
Pipecuronium
Vecuronium
53.5 (13.1) 64.5 (13.5)
47.0 (16.5) 62.8 (8.9)
A.W. Harrop-Griffiths, MA, MB, BS, FFARCS, Consultant, Department of Anaesthesia, St Mary’s Hospital, Praed Street, London W2 INY, N.J. Fauvel, MB, BS, FFARCS, SIMS Research Fellow, M.H. Plumley, MB, BS, FFARCS, Senior Registrar, S. Feldman, BSc, MB, BS, FFARCS, Professor of Anaesthesia, Magill Department of Anaesthesia, Westminster Hospital, Page Street Wing, Page Street, London S W l P 2AP. Accepted 8 June 1991. 0003-2409/92/020105 +02 rS03.00/0
0 1992 The Association of Anaesthetists of G t Britain and Ireland
105
I06
W . Harrop-Grifiths et a1
r
Table 3. Number of patients (n) from whom data were acquired for Figure I .
150
*
i
C
0
+
e
T
Study group ~~
-P U
t
c
%
Pipecuronium
Vecuronium
n
n
9 8 8 6 -
9 4 4 3 3
Maintenance dose number
ag C
1
0 +
5 25t I 0
I
I
I
I
I
I
2
3
4
5
I
2 3 4 5
Maintenance dose number
Fig. 1. Cumulation data: Mean durations of maintenance doses expressed as a percentage of duration of initial dose. Bars
represent SEM. A,pipecuronium; 0 , vecuronium ; *, significant difference between groups, p < 0.05.
blocking agent are shown in Table 2. There was a shorter mean onset time after vecuronium than after pipecuronium (p < 0.01). There was no statistically significant difference in mean duration of the initial dose between the pipecuronium and vecuronium groups. Figure 1 illustrates cumulation data. The durations of the first and subsequent maintenance doses for each patient were expressed as percentages of the duration of the initial dose. The numbers of patients from whom data were acquired for each data point in Figure 1 are given in Table 3. The mean percentage duration of the first and subsequent maintenance doses in the pipecuronium group were greater than those in the vecuronium group (p < 0.05). The pipecuronium group showed evidence of marked cumulation.
Discussion Vecuronium has a more rapid onset than pipecuronium [1,4] when given in equipotent doses (i.e. similar multiples of ED, dose). This, combined with our use of a 2 x ED, dose of pipecuronium and 4 x ED, dose of vecuronium in order to produce a similar duration of block, is likely to explain the markedly shorter onset time seen in the vecuronium group. The mean durations of the initial dose of pipecuronium and vecuronium were similar (42 and 49 min respectively). This would suggest that both Table 2. Mean (SD) onset time and duration of action of initial dose of neuromuscular blocking agent.
Study group
Onset time; min Duration; min
Pipecuronium (0.06 mg.kg-l)
Vecuronium (0.15 mg.kg-l)
3.28 (0.78)* 42.1 (12.2)
1.57 (0.50) 48.6 (10.8
* Significant difference beween groups (p < 0.01).
agents, in the doses given, would prove suitable for providing surgical relaxation for a period of around 50 to 60 min. Isoflurane is known to potentiate the neuromuscular blocking effects of both vecuronium [7] and pipecuronium [8,9]. We conclude that both agents are suitable for providing muscle relaxation for long operations but that high-dose vecuronium may have advantages over pipecuronium in terms of a shorter onset time and a lesser tendency to cumulation if isoflurane is used as part of the anaesthetic technique.
References [I] AGOSTONS,
RICHARDSONFJ. Pipecuronium bromide (Arduan)-a new long-acting non-depolarizing neuromuscular blocking drug. Clinics in Anesthesiology 1985; 3: 361-9. [2] CALDWELL JE, CASTAGNOLI KP, CANFELL PC, FAHEYMR, LYNAM DP, FISHERDM, MILLERRD. Pipecuronium and pancuronium: comparison of pharmacokinetics and duration of action. British Journal of Anaesthesia 1988; 61: 693-7. E, NEIDHART P, PITTET J-F, MORELDR, GEMPERLE [3] TASSONYI M. Cardiovascular effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting. Anesthesiology 1988; 6 9 793-6. SA, LIBANJB. Vecuronium-a variable dose [4] FELDMAN technique. Anaesthesia 1987; 42: 199-201. [5] GINSBERG B, GLASSPS, QUILLT, SHAFRON D, OSEY KD. Onset and duration of neuromuscular blockade following high-dose vecuronium administration. Anesthesiology 1989; 71: 201-5. [6] R0RVIK K, HUSBY P, GRAMSTADL, VAMNES JS,
BITSCH-LARSEN L, KOLLER M-E. Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade. British Journal of Anaesthesia 1988; 61: 180-5. [7] RUPPSM, MILLER ED, GENCARELLI PJ. Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans. Anesthesiology 1984; 60: 102-5. [8] WIERDA JMKH, RICHARDSON FJ, AGOSTON S. Dose-response relation and time course of action of pipecuronium bromide
in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl. Anesrhesiu and Analgesia 1989; 68: 208-13. J-F, TASSONYI E, MORELDR, GEMPERLE G, RICHTER [9] PITTET
M, ROUGE J-C. Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane and halothane anesthesia in adults and children. Anesfhesiology 1989; 71: 210-13.
Pipecuronium versus high dose vecuronium I. A comparison of speed of onset and cumulation during isoflurane anaesthesia W. HARROP-GRIFFITHS, N . FAUVEL, M . P L U M L E Y
AND
S. F E L D M A N
Summary The onset time and tendency to cumulation of pipecuronium and high-dose vecuronium were studied during nitrous oxide anaesthesia supplemented with isojurane. Pipecuronium 0.06 mg.kg - had a similar duration of action to vecuronium 0.015 mg.kg-’ (42 vs 49 min). Patients who received vecuronium had a shorter onset time of neuromuscular blockade ( p < 0.01). The use of pipecuronium was associated with marked cumulation.
’
Key words Neuromuscular relaxants; pipecuronium, vecuronium. Anaesthetics, volatile; isoflurane.
It has been suggested [ I ] that pipecuronium may be an ideal neuromuscular blocking agent for long operations in patients with cardiovascular disease, as it possesses a duration of action and potency similar to pancuronium [2] and a greater degree of haemodynamic stability [3]. Vecuronium has a shorter duration of action than pipecuronium when given in doses equipotent for the degree of neuromuscular block (i.e. similar multiples of ED,, or ED,,), but can be given safely in doses of up to 0.4 mg.kg-’ in order to prolong its duration of action [4-61. The purpose of this study was to determine whether doses of pipecuronium and vecuronium that have similar initial durations of action show differences in onset time and tendency to cumulation.
used to monitor neuromuscular function, recording the response of the adductor pollicis muscle to supramaximal stimulation of the ulnar nerve. The Relaxograph was attached before induction, after which baseline values were established. After a period of stabilisation, patients were given either pipecuronium 0.06 mg.kg-’ or vecuronium 0.15 mg.kg-I; these doses were estimated to have a similar initial duration of action. Onset time of neuromuscular blockade was taken as the time between the administration of the neuromuscular blocking agent and the time when the first ‘twitch’ of the train-of-four (Tl) reached less than 5% of control. Tracheal intubation was performed a t this time. Maintenance doses (one fifth of the initial dose) were given when TI returned to 10% of control. Statistical analysis was performed using unpaired Student’s t-tests.
Methods Institutional ethics approval was obtained for the study. Thirty ASA physical status 1 or 2 patients scheduled for elective surgery gave informed written consent, and were admitted to the study. The surgical procedures comprised major abdominal surgery ( 1 1 patients) or joint replacement surgery (19 patients). The patients were allocated randomly into one of two groups, and received either pipecuronium or vecuronium. After premedication with papaveretum and hyoscine, anaesthesia was induced with a sleep dose of thiopentone and maintained with 33% oxygen in nitrous oxide supplemented with an inspired concentration of between 0.5 and 1% isoflurane. A Datex Relaxograph was
Results Demographic data are presented in Table I . Mean onset time and duration of the initial dose of neuromuscular Table 1. Mean (SD) age and weight. Study group
Age; years Weight; kg
Pipecuronium
Vecuronium
53.5 (13.1) 64.5 (13.5)
47.0 (16.5) 62.8 (8.9)
A.W. Harrop-Griffiths, MA, MB, BS, FFARCS, Consultant, Department of Anaesthesia, St Mary’s Hospital, Praed Street, London W2 INY, N.J. Fauvel, MB, BS, FFARCS, SIMS Research Fellow, M.H. Plumley, MB, BS, FFARCS, Senior Registrar, S. Feldman, BSc, MB, BS, FFARCS, Professor of Anaesthesia, Magill Department of Anaesthesia, Westminster Hospital, Page Street Wing, Page Street, London S W l P 2AP. Accepted 8 June 1991. 0003-2409/92/020105 +02 rS03.00/0
0 1992 The Association of Anaesthetists of G t Britain and Ireland
105
I06
W . Harrop-Grifiths et a1
r
Table 3. Number of patients (n) from whom data were acquired for Figure I .
150
*
i
C
0
+
e
T
Study group ~~
-P U
t
c
%
Pipecuronium
Vecuronium
n
n
9 8 8 6 -
9 4 4 3 3
Maintenance dose number
ag C
1
0 +
5 25t I 0
I
I
I
I
I
I
2
3
4
5
I
2 3 4 5
Maintenance dose number
Fig. 1. Cumulation data: Mean durations of maintenance doses expressed as a percentage of duration of initial dose. Bars
represent SEM. A,pipecuronium; 0 , vecuronium ; *, significant difference between groups, p < 0.05.
blocking agent are shown in Table 2. There was a shorter mean onset time after vecuronium than after pipecuronium (p < 0.01). There was no statistically significant difference in mean duration of the initial dose between the pipecuronium and vecuronium groups. Figure 1 illustrates cumulation data. The durations of the first and subsequent maintenance doses for each patient were expressed as percentages of the duration of the initial dose. The numbers of patients from whom data were acquired for each data point in Figure 1 are given in Table 3. The mean percentage duration of the first and subsequent maintenance doses in the pipecuronium group were greater than those in the vecuronium group (p < 0.05). The pipecuronium group showed evidence of marked cumulation.
Discussion Vecuronium has a more rapid onset than pipecuronium [1,4] when given in equipotent doses (i.e. similar multiples of ED, dose). This, combined with our use of a 2 x ED, dose of pipecuronium and 4 x ED, dose of vecuronium in order to produce a similar duration of block, is likely to explain the markedly shorter onset time seen in the vecuronium group. The mean durations of the initial dose of pipecuronium and vecuronium were similar (42 and 49 min respectively). This would suggest that both Table 2. Mean (SD) onset time and duration of action of initial dose of neuromuscular blocking agent.
Study group
Onset time; min Duration; min
Pipecuronium (0.06 mg.kg-l)
Vecuronium (0.15 mg.kg-l)
3.28 (0.78)* 42.1 (12.2)
1.57 (0.50) 48.6 (10.8
* Significant difference beween groups (p < 0.01).
agents, in the doses given, would prove suitable for providing surgical relaxation for a period of around 50 to 60 min. Isoflurane is known to potentiate the neuromuscular blocking effects of both vecuronium [7] and pipecuronium [8,9]. We conclude that both agents are suitable for providing muscle relaxation for long operations but that high-dose vecuronium may have advantages over pipecuronium in terms of a shorter onset time and a lesser tendency to cumulation if isoflurane is used as part of the anaesthetic technique.
References [I] AGOSTONS,
RICHARDSONFJ. Pipecuronium bromide (Arduan)-a new long-acting non-depolarizing neuromuscular blocking drug. Clinics in Anesthesiology 1985; 3: 361-9. [2] CALDWELL JE, CASTAGNOLI KP, CANFELL PC, FAHEYMR, LYNAM DP, FISHERDM, MILLERRD. Pipecuronium and pancuronium: comparison of pharmacokinetics and duration of action. British Journal of Anaesthesia 1988; 61: 693-7. E, NEIDHART P, PITTET J-F, MORELDR, GEMPERLE [3] TASSONYI M. Cardiovascular effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting. Anesthesiology 1988; 6 9 793-6. SA, LIBANJB. Vecuronium-a variable dose [4] FELDMAN technique. Anaesthesia 1987; 42: 199-201. [5] GINSBERG B, GLASSPS, QUILLT, SHAFRON D, OSEY KD. Onset and duration of neuromuscular blockade following high-dose vecuronium administration. Anesthesiology 1989; 71: 201-5. [6] R0RVIK K, HUSBY P, GRAMSTADL, VAMNES JS,
BITSCH-LARSEN L, KOLLER M-E. Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade. British Journal of Anaesthesia 1988; 61: 180-5. [7] RUPPSM, MILLER ED, GENCARELLI PJ. Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans. Anesthesiology 1984; 60: 102-5. [8] WIERDA JMKH, RICHARDSON FJ, AGOSTON S. Dose-response relation and time course of action of pipecuronium bromide
in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl. Anesrhesiu and Analgesia 1989; 68: 208-13. J-F, TASSONYI E, MORELDR, GEMPERLE G, RICHTER [9] PITTET
M, ROUGE J-C. Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane and halothane anesthesia in adults and children. Anesfhesiology 1989; 71: 210-13.
