Anaesthesia, 1992, Volume 47, pages 107-109
Pipecuronium versus high dose vecuronium 11. A comparison of speed of onset and cumulation during propofol anaesthesia
W. HARROP-GRIFFITHS, M. PLATT, N. HIRSCH A N D S. FELDMAN
Summary The onset time and tendency to cumulation of pipecuronium and high-dose vecuronium were compared during nitrous oxide anaesthesia supplemented with a propofol infusion. Pipecuronium 0.06 mg.kg- had a similar duration of action to vecuronium 0.2 rng.kg-’ (49 vs 43). Patients who received vecuronium had a shorter onset time of neuromuscular blockade ( p < 0.01). Neither pipecuronium nor vecuronium showed marked cumulation.
Key words Neuromuscular, relaxants; pipecuronium, vecuronium. Anaesthetics, intravenous; propofol
The introduction of propofol into clinical practice has rekindled interest in general anaesthesia that is supplemented by an intravenous rather than an inhalational agent. The current vdatile agents all potentiate the effects of nondepolarising neuromuscular blocking agents; isoflurane appears to have the greatest effect [I-31. The accompanying paper [4] reports that during an anaesthetic that included the use of isoflurane, doses of pipecuronium and vecuronium that have similar initial durations of action resulted in a more rapid onset of block with vecuronium and cumulation of effect after successive maintenance doses of pipecuronium. The aim of this trial was to study the onset time and tendency to cumulation of pipecuronium and high-dose vecuronium during nitrous oxide anaesthesia supplemented with a propofol infusion. Methods
Institutional ethics approval was obtained. Informed written consent was given by 30 ASA 1 or 2 patients who were scheduled for elective surgery. The surgical procedures comprised craniotomy for clipping of aneurysm (12 patients) or for tumour resection (18 patients). The patients were allocated randomly to one of two groups of 15; one group received pipecuronium and the other vecuronium. No premedication was given. Anaesthesia was induced with a sleep dose of propofol and was maintained with 33%
oxygen in nitrous oxide supplemented with a propofol infusion according to a scheme suggested by Roberts et al. [S]: 10 mg.kg-’ for the first 10 min, then 8 mg.kg-l for the next 10 min and 6 mg.kg-’ thereafter, adjusted as necessary. Fentanyl (0-4 pg.kg-’) was given during anaesthesia to provide analgesia. A Datex Relaxograph was 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 0.2 mg.kg-’. Onset time for 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 (TI) reached less than 5% of control. Intubation was performed at this time. Maintenance doses (one-fifth of the initial dose) were given when T1 returned to 10% of control. Statistical analysis was performed using unpaired Student’s t-tests.
Results Demographic data are presented in Table 1. Mean onset time and duration of the initial dose of neuromuscular blocking agent are shown in Table 2. There was a shorter
A.W. Harrop-Griffiths, MA, MB, BS, FFARCS, Consultant, M.W. Platt, MB, BS, FFARCS, Senior Registrar, Department of Anaesthesia, St Mary’s Hospital, Praed Street, London W2 INY, N.P. Hirsch, MB, BS, FFARCS, Consultant, Department of Anaesthesia, The National Hospital for Neurology and Neurosurgery, Queen Square, London WCI, 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. 0003-2409/92/020107
+ 03 $03.00/0
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
107
108
W. Harrop-Grifiths et al. Table 1. Mean (SD) age and weight.
Pipecuronium
Vecuronium
were no statistically significant differences between the two groups in the durations of the first and subsequent maintenance doses. Neither group showed evidence of marked cumulation.
49.1 (14.1) 71.3 ( 1 1 . 1 )
49.7 (14.6) 70.3 (16.1)
Discussion
Study group
Age; years Weight; kg
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
Vecuronium
(0.06 mg.kg-I)
(0.2 mg.kg-l)
3.97 (0.72)' 48.5 (25.1)
1.69 (0.38) 42.6 (8.5)
* Significant difference beween groups (p < 0.01). Table 3. Number of patients ( n ) from whom data were acquired for Figure I .
Study group Pipecuronium
Vecuronium
n
n
14 13 8 6 3
15 14 10 6 3
Maintenance dose number I 2 3 4 5
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 shown in Table 3. There
-
6
i
I50
-
I25
-
References RUPPSM, MILLER RD. GENCARELLI PJ. Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans. Anesthesiology 1984; 60:
e :
102-5. WIERDA JMKH, RICHARDSON FJ, AGOSTONS. Dose-response relation and time course of action of pipecuronium bromide
100
0 .+ ._
.c 75 v-
8
-
-
in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl. Anesthesia and Analgesia 1989; 68: 208-13.
50-
PITTETJ-F, TASSONYI E, MORELDR, GEMPERLE G, RICHTER M, ROUGE J-C. Pipecuroniuminduced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane and halothane anesthesia in adults and children. Anesthesiology
0
z
250
I 0
The dose of vecuronium used in this study (0.2 mg.kg-'), differs from that used in the previous study (015 mg.kg-') [4]. Isoflurane is known to potentiate the action of vecuronium [I], and the larger dose was used to allow a degree of clinical comparability between the duration of the initial dose of vecuronium in this study (mean 42.6 min) and that in the previous study (mean 48.6 min) [4]. The onset times observed in this study are in broad agreement with those reported previously [6,71. The faster onset time in the vecuronium group is likely to be due to its inherently greater speed of onset and the fact that greater multiples of EDm of vecuronium were given than of pipecuronium. Our previous study [4] showed that the concomitant use of isoflurane gives rise to an increase in the duration of action of successive maintenance doses of pipecuronium, i.e. cumulation. This confirms previous observations of the potentiating effect of isoflurane on pipecuronium [2,3]. The absence of cumulation with pipecuronium in this study can be ascribed to our use of an anaesthetic technique that did not include a halogenated inhalational anaesthetic agent. Foldes et al. [8] reported that pipecuronium, even in the absence of halogenated inhalational agents, shows a tendency towards prolongation of effect. Our results do not support this finding. However, the anaesthetic technique used by Foldes e t al. [8] (fentanyl, droperidol, nitrous oxide) differs from that used in this study (propofol, nitrous oxide). Neither the pipecuronium group nor the vecuronium group showed evidence of marked cumulation under the conditions pertaining in this study. We conclude that both pipecuronium and highdose vecronium are suitable for use in long operations and that neither agent demonstrates significant cumulation with an anaesthetic technique that includes the use of nitrous oxide and a propofol infusion. The use of high-dose vecuronium in this setting may confer the advantage of a shorter onset time.
1
I
I
I
I
I
2
3
4
5
1
Maintenance dose number Fig. 1. Cumulation data: Mean durations of maintenance doses expressed as a percentage of initial dose duration. Bars represent SEM. A,pipecuronium; 0 , vecuronium.
1989; 71: 210-13.
HARROP-GRIFFITHS AW, FAUVELNJ, PLUMLEYMH, S. Pipecuronium versus high dose vecuronium. 1. A FELDMAN comparison of speed of onset and cumulation during isoflurane anaesthesia. Anaesthesia 1992; 47: 105-6. ROBERTSFL, DIXON J. LEWIS GTR, TACKLEYRM, PRYS-ROBERTS C. Induction and maintenance of propolol
Pipecuronium versus high-dose vecuronium anaesthesia. A manual infusion scheme. Anaesthesia 1988; 43 (SUPPI):14-17. [6] FELDMANSA, LIBAN JB. Vecuronium-a variable dose technique. Anaesthesia 1987; 42: 199-201. [7] LAKIJANI GE. BARTKOWSKI RR, AZAII SS, SELTZERJL, WEINBERGER MJ, BEACH CA, GOLDBERGME. Clinical
109
pharmacology of pipecuronium bromide. Anesrhesia and Analgesia 1089; 68: 734-9. [8] FOLDES FF, NAGASHIMA H, NGUYENHD. WEISSR, GOLDINER PL. The human cumulative dose-response of pipecuronium bromide under balanced anesthesia. Anesthesiology 1986; 65: A1 16.
Pipecuronium versus high dose vecuronium 11. A comparison of speed of onset and cumulation during propofol anaesthesia
W. HARROP-GRIFFITHS, M. PLATT, N. HIRSCH A N D S. FELDMAN
Summary The onset time and tendency to cumulation of pipecuronium and high-dose vecuronium were compared during nitrous oxide anaesthesia supplemented with a propofol infusion. Pipecuronium 0.06 mg.kg- had a similar duration of action to vecuronium 0.2 rng.kg-’ (49 vs 43). Patients who received vecuronium had a shorter onset time of neuromuscular blockade ( p < 0.01). Neither pipecuronium nor vecuronium showed marked cumulation.
Key words Neuromuscular, relaxants; pipecuronium, vecuronium. Anaesthetics, intravenous; propofol
The introduction of propofol into clinical practice has rekindled interest in general anaesthesia that is supplemented by an intravenous rather than an inhalational agent. The current vdatile agents all potentiate the effects of nondepolarising neuromuscular blocking agents; isoflurane appears to have the greatest effect [I-31. The accompanying paper [4] reports that during an anaesthetic that included the use of isoflurane, doses of pipecuronium and vecuronium that have similar initial durations of action resulted in a more rapid onset of block with vecuronium and cumulation of effect after successive maintenance doses of pipecuronium. The aim of this trial was to study the onset time and tendency to cumulation of pipecuronium and high-dose vecuronium during nitrous oxide anaesthesia supplemented with a propofol infusion. Methods
Institutional ethics approval was obtained. Informed written consent was given by 30 ASA 1 or 2 patients who were scheduled for elective surgery. The surgical procedures comprised craniotomy for clipping of aneurysm (12 patients) or for tumour resection (18 patients). The patients were allocated randomly to one of two groups of 15; one group received pipecuronium and the other vecuronium. No premedication was given. Anaesthesia was induced with a sleep dose of propofol and was maintained with 33%
oxygen in nitrous oxide supplemented with a propofol infusion according to a scheme suggested by Roberts et al. [S]: 10 mg.kg-’ for the first 10 min, then 8 mg.kg-l for the next 10 min and 6 mg.kg-’ thereafter, adjusted as necessary. Fentanyl (0-4 pg.kg-’) was given during anaesthesia to provide analgesia. A Datex Relaxograph was 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 0.2 mg.kg-’. Onset time for 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 (TI) reached less than 5% of control. Intubation was performed at this time. Maintenance doses (one-fifth of the initial dose) were given when T1 returned to 10% of control. Statistical analysis was performed using unpaired Student’s t-tests.
Results Demographic data are presented in Table 1. Mean onset time and duration of the initial dose of neuromuscular blocking agent are shown in Table 2. There was a shorter
A.W. Harrop-Griffiths, MA, MB, BS, FFARCS, Consultant, M.W. Platt, MB, BS, FFARCS, Senior Registrar, Department of Anaesthesia, St Mary’s Hospital, Praed Street, London W2 INY, N.P. Hirsch, MB, BS, FFARCS, Consultant, Department of Anaesthesia, The National Hospital for Neurology and Neurosurgery, Queen Square, London WCI, 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. 0003-2409/92/020107
+ 03 $03.00/0
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
107
108
W. Harrop-Grifiths et al. Table 1. Mean (SD) age and weight.
Pipecuronium
Vecuronium
were no statistically significant differences between the two groups in the durations of the first and subsequent maintenance doses. Neither group showed evidence of marked cumulation.
49.1 (14.1) 71.3 ( 1 1 . 1 )
49.7 (14.6) 70.3 (16.1)
Discussion
Study group
Age; years Weight; kg
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
Vecuronium
(0.06 mg.kg-I)
(0.2 mg.kg-l)
3.97 (0.72)' 48.5 (25.1)
1.69 (0.38) 42.6 (8.5)
* Significant difference beween groups (p < 0.01). Table 3. Number of patients ( n ) from whom data were acquired for Figure I .
Study group Pipecuronium
Vecuronium
n
n
14 13 8 6 3
15 14 10 6 3
Maintenance dose number I 2 3 4 5
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 shown in Table 3. There
-
6
i
I50
-
I25
-
References RUPPSM, MILLER RD. GENCARELLI PJ. Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans. Anesthesiology 1984; 60:
e :
102-5. WIERDA JMKH, RICHARDSON FJ, AGOSTONS. Dose-response relation and time course of action of pipecuronium bromide
100
0 .+ ._
.c 75 v-
8
-
-
in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl. Anesthesia and Analgesia 1989; 68: 208-13.
50-
PITTETJ-F, TASSONYI E, MORELDR, GEMPERLE G, RICHTER M, ROUGE J-C. Pipecuroniuminduced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane and halothane anesthesia in adults and children. Anesthesiology
0
z
250
I 0
The dose of vecuronium used in this study (0.2 mg.kg-'), differs from that used in the previous study (015 mg.kg-') [4]. Isoflurane is known to potentiate the action of vecuronium [I], and the larger dose was used to allow a degree of clinical comparability between the duration of the initial dose of vecuronium in this study (mean 42.6 min) and that in the previous study (mean 48.6 min) [4]. The onset times observed in this study are in broad agreement with those reported previously [6,71. The faster onset time in the vecuronium group is likely to be due to its inherently greater speed of onset and the fact that greater multiples of EDm of vecuronium were given than of pipecuronium. Our previous study [4] showed that the concomitant use of isoflurane gives rise to an increase in the duration of action of successive maintenance doses of pipecuronium, i.e. cumulation. This confirms previous observations of the potentiating effect of isoflurane on pipecuronium [2,3]. The absence of cumulation with pipecuronium in this study can be ascribed to our use of an anaesthetic technique that did not include a halogenated inhalational anaesthetic agent. Foldes et al. [8] reported that pipecuronium, even in the absence of halogenated inhalational agents, shows a tendency towards prolongation of effect. Our results do not support this finding. However, the anaesthetic technique used by Foldes e t al. [8] (fentanyl, droperidol, nitrous oxide) differs from that used in this study (propofol, nitrous oxide). Neither the pipecuronium group nor the vecuronium group showed evidence of marked cumulation under the conditions pertaining in this study. We conclude that both pipecuronium and highdose vecronium are suitable for use in long operations and that neither agent demonstrates significant cumulation with an anaesthetic technique that includes the use of nitrous oxide and a propofol infusion. The use of high-dose vecuronium in this setting may confer the advantage of a shorter onset time.
1
I
I
I
I
I
2
3
4
5
1
Maintenance dose number Fig. 1. Cumulation data: Mean durations of maintenance doses expressed as a percentage of initial dose duration. Bars represent SEM. A,pipecuronium; 0 , vecuronium.
1989; 71: 210-13.
HARROP-GRIFFITHS AW, FAUVELNJ, PLUMLEYMH, S. Pipecuronium versus high dose vecuronium. 1. A FELDMAN comparison of speed of onset and cumulation during isoflurane anaesthesia. Anaesthesia 1992; 47: 105-6. ROBERTSFL, DIXON J. LEWIS GTR, TACKLEYRM, PRYS-ROBERTS C. Induction and maintenance of propolol
Pipecuronium versus high-dose vecuronium anaesthesia. A manual infusion scheme. Anaesthesia 1988; 43 (SUPPI):14-17. [6] FELDMANSA, LIBAN JB. Vecuronium-a variable dose technique. Anaesthesia 1987; 42: 199-201. [7] LAKIJANI GE. BARTKOWSKI RR, AZAII SS, SELTZERJL, WEINBERGER MJ, BEACH CA, GOLDBERGME. Clinical
109
pharmacology of pipecuronium bromide. Anesrhesia and Analgesia 1089; 68: 734-9. [8] FOLDES FF, NAGASHIMA H, NGUYENHD. WEISSR, GOLDINER PL. The human cumulative dose-response of pipecuronium bromide under balanced anesthesia. Anesthesiology 1986; 65: A1 16.
