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TUBOCURARINE AND THE NEONATE
Br.J. Anaesth. (1976), 48, 687
TUBOCURARINE AND THE NEONATE E. J. BENNETT, A. IGNACIO, K. PATEL, E. M. GRUNDY AND M. R. SALEM SUMMARY
As the newborn appears to be sensitive to tubocurarine (Stead, 1955; Walts and Dillon, 1969), it has been recommended that this drug be given with caution to babies in this age group, and a titration regimen has been recommended (Bush and Stead, 1962). Investigation of pancuronium (Bennett et al., 1975) has shown that the newborn is sensitive to pancuronium also, but that this drug may be given as a bolus. It appeared also that the potency ratio of pancuronium compared with tubocurarine may be altered in these patients. Many newborn patients may present for surgery with few i.v. routes remaining, and many anaesthetists prefer to establish i.v. cannulation after anaesthesia has commenced. Because of this we have re-examined the possibility of administering tubocurarine as a single bolus.
relaxation of the abdominal muscles or control of respiration. A peripheral nerve stimulator was not used as the newborn responds in a "myasthenic" manner (Churchill-Davidson and Wise, 1963), and the painful stimulus would have necessitated a deeper level of anaesthesia. The total dose required was considered the "curarizing" dose. Incremental doses throughout the procedure were one-fifth or one-sixth of this dose. At the end of the surgical procedure the neuromuscular block was antagonized with a mixture of atropine 0.018 mg/kg and neostigmine 0.08 mg/kg given i.v. During the procedure, the patients received dextrose 5% in lactated Ringer's solution (4-8 ml/kg/h). Dose selection
From our previous study (Bennett et al., 1975), it was suggested that the potency of pancuronium PATIENTS AND METHODS compared with tubocurarine was: Fifty neonates (age range 1-28 days) undergoing 0-7 days 9: 1 surgery of the thorax or abdomen were studied. 8: 1 8-14 days Atropine 0.1 mg was given i.m. 1 h before operation. 7: 1 15-21 days The operating room was heated to 26 °C and each 6: 1 22-28 days baby was placed upon a warm water mattress to and that the appropriate dose of pancuronium for the maintain normothermia. Endotracheal intubation was neonatal period given as a single bolus in the mature performed with the child awake, and a 50% mixture of nitrous oxide in oxygen was administered using a healthy neonate was: Rees variation of the T-piece. A dose of tubocurarine 0-1 week 30 i^g/kg was selected and given into a suitable vein on the 1-2 weeks 60 (xg/kg volar aspect of the wrist using a 25-gauge needle. 2-4 weeks According to the response, one-half, one-quarter or This amount of pancuronium could be expected to less of this dose was repeated until the desired result provide 75+15 min of relaxation and was readily was obtained. The end-point was either adequate reversible. The amount of drug should be reduced according to the degree of prematurity, in the presence E. J. BENNETT, F.F.A.R.C.S.; A. IGNACIO, JR, M.D.; K. PATEL, of hypothermia, acidosis or following the adminisM.D.; E. M. GRUNDY, F.F.A.R.C.S.; University of Illinois, tration of antibiotics which may affect the neuroChicago, Illinois 60612, U.S.A. M. R. SALEM, M.D., muscular transmission. Loyola University, Chicago, Illinois 60153, U.S.A.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 21, 2015
Tubocurarine, given as a single bolus, may be used safely for neuromuscular blockade in the neonate. The recommended dose is 250 (ig/kg at birth, increasing to 500 ng/kg at 28 days of age. This dose should be reduced in the event of prematurity, acidosis or hypothermia, or when certain antibiotics or inhalation anaesthetic agents are present in the tissues. A single dose as described has a duration of approximately 1 h and it is only after this time that satisfactory antagonism can be obtained. The potency of pancuronium when compared with tubocurarine in the study is 6 : 1, from birth to 28 days.
688
BRITISH JOURNAL OF ANAESTHESIA
Accordingly, the dose of tubocurarine was selected as: 0-7 days 270 8-14 days 420 15-28 days 540 [xg/kg with similar reductions according to the condition of the patient. In figure 1 the circled points had at least three of these factors present when tubocurarine was given. *
700600.
'
*
>
^
500400-
•
300 J
* >
200-
' '•
V
; 1——i—r—i—i—i—i—\
4
250 ^g/kg 400 jxg/kg 500 [ig/kg
and to give incremental doses as necessary of one-fifth or one-sixth the original dose. This initial dose is reduced in prematurity, acidosis, hypothermia and in the presence of antibiotics or potent anaesthetic agents.
100-
o- -;
0-1 week 1-2 weeks 2-4 weeks
1—i—i
6 8 10 12 14 16 18 20 22 24 26 28 AGE (days)
FIG. 1. Dose of tubocurarine giving optimal "curarization" in neonates of different age. Correlation coefficient r = +0.772. RESULTS
The patients' weight ranged from 520 to 4200 g. Of these, 27 neonates were considered to have a low birth weight (premature) (average 1600 g). The figure shows the results obtained for optimal "curarization"; the correlation coefficient was + 0.772. Antagonism was judged to be satisfactory in all cases. The mean duration of activity was 55 min + SD 25. DISCUSSION
Tubocurarine appears to be satisfactory for use as a neuromuscular blocking drug for neonatal anaesthesia, when used as a single dose. Titration is not always required. Compared with our previous study of pancuronium (Bennett et al., 1975), the regression lines were: 37.40+1.96* Pancuronium: Tubocurarine: 215.77+11.68* Thus the potency ratio for the neonatal period is 6 : 1 . This value is different from the result of the
CONCLUSION
Tubocurarine may be used as the relaxant in the neonate when given in a single bolus. The dose is 250 jxg/kg at birth, ranging to 500 fxg/kg at 28 days of age. This should be reduced when prematurity, acidosis, hypothermia, antibiotics or potent anaesthetic agents are active. This dose has a duration of approximately 1 h before proper reversal can be obtained. REFERENCES
Bennett, E. J., Raj, P. P., and Dalai, F. Y. (1972). Pancuronium bromide: Anticholinesterase effect. M.E.J. Anaesth., 3, 425. Ramamurthy, S., Dalai, F. Y., and Salem, M. R. (1975). Pancuronium and the neonate. Br. J. Anaesth., 47, 75. Bush, G. H., and Stead, A. L. (1962). The use of d-tubocurarine in neonatal anaesthesia. Br.J. Anaesth., 34, 721. Churchill-Davidson, H. C , and Wise, R. P. (1963). Neuromuscular transmission in the newborn infant. Anesthesiology, 24, 271.
Feldman, S. A. (1973). Muscle Relaxants, p. 152. London: W. B. Saunders. Stead, A. L. (1955). The response of the newborn infant to muscle relaxants. Br.J. Anaesth., 27, 124. Walts, L. F., and Dillon, J. B. (1969). The response of newborns to succinylcholine and d-tubocurare. Anesthesiology, 3 1 , 35.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 21, 2015
DUU
previous study. Some possible explanations are: (a) this series with tubocurarine included more small babies (27 v. seven with pancuronium), (b) the modifying factors may be more active with tubocurarine, (c) the anticholinesterase action of pancuronium may affect the "myasthenic" response of the neonate (Bennett, Raj and Dalai, 1972), and (d) small incremental doses (titration) may result in a larger total dose (Feldman, 1973). The comparison of potencies used Bush and Stead's method with titration of drug (Bennett et al., 1975). It is now our practice to administer tubocurarine, in conjunction with nitrous oxide anaesthesia, to the neonate in a single dose of:
TUBOCURARINE AND THE NEONATE LA TUBOCURARINE ET LE NOUVEAU-NE RESUME
TUBOCURARIN UND DAS NEUGEBORENE ZUSAMMENFASSUNG
Tubocurarin, als Einzeldosis verabreicht, kann gefahrlos zur neuromuskularen Blockierung an Neugeborene verabreicht werden. Die empfohlene Dosis betragt bei der Geburt 250 [xg/kg, ansteigend auf 500 (xg/kg bei einem
Alter von 28 Tagen. Bei Fruhgeburten, Azidose oder Hypothermie sollte diese Dosis verringert werden, sowie auch dann, wenn gewisse Antibiotika oder eingeatmete Narkosemittel im Gewebe vorhanden sind. Die beschriebene Einzeldosis hat eine Dauer von etwa 1 h, und erst danach kann ein befriedigender Antagonismus erzielt werden. Die Wirkungsstarke von Pancuronium im Vergleich mit Tubocurarin in dieser Untersuchung ist 6 : 1, von der Geburt bis zum Alter von 28 Tagen. TUBOCURARINA Y EL NEONATO SUMARIO
La tubocurarina, administrada en bolo unico, puede usarse con seguridad para el bloqueo neuromuscular en el neonato. La dosis recomendada es de 250 jxg/kg al nacer, aumentando a 500 fig/kg a los 28 dias de edad. Esta dosis debera reducirse en los casos de premadurez, acidosis o hipotermia, o cuando se hallen en los tejidos ciertos antibioticos o anestesicos de inhalation. Una dosis unica como las descritas tiene una duration de 1 h aprox., y solamente tras este tiempo puede obtenerse un antagonismo satisfactorio. La potencia del pancuronio, cuando se compara con tubocurarina, es de 6 : 1, desde el nacimiento a los 28 dias.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 21, 2015
La tubocurarine, administree en un seul bol, peut etre utilisee en toute securite pour les blocages neuromusculaires chez les nouveaux-nes. La dose recommandee est de 250 (xg/kg a la naissance, augmentant a 500 (ig/kg a l'age de 28 jours. II y aura lieu de diminuer cette dose en cas de naissance prematuree, d'acidose ou d'hypothermie ou encore, lorsque certains antibiotiques ou agents anesthesiants administres par inhalation sont presents dans les tissus. Une seule dose administree suivant les prescriptions ci-dessus a une duree approximative d'une heure et ce n'est qu'apres ce laps de temps que Ton peut obtenir un antagonisme satisfaisant. L'efficacite du pancuronium par rapport a la tubocurarine faisant l'objet de cette etude est de 6 : 1, de la naissance a 28 jours.
689
TUBOCURARINE AND THE NEONATE E. J. BENNETT, A. IGNACIO, K. PATEL, E. M. GRUNDY AND M. R. SALEM SUMMARY
As the newborn appears to be sensitive to tubocurarine (Stead, 1955; Walts and Dillon, 1969), it has been recommended that this drug be given with caution to babies in this age group, and a titration regimen has been recommended (Bush and Stead, 1962). Investigation of pancuronium (Bennett et al., 1975) has shown that the newborn is sensitive to pancuronium also, but that this drug may be given as a bolus. It appeared also that the potency ratio of pancuronium compared with tubocurarine may be altered in these patients. Many newborn patients may present for surgery with few i.v. routes remaining, and many anaesthetists prefer to establish i.v. cannulation after anaesthesia has commenced. Because of this we have re-examined the possibility of administering tubocurarine as a single bolus.
relaxation of the abdominal muscles or control of respiration. A peripheral nerve stimulator was not used as the newborn responds in a "myasthenic" manner (Churchill-Davidson and Wise, 1963), and the painful stimulus would have necessitated a deeper level of anaesthesia. The total dose required was considered the "curarizing" dose. Incremental doses throughout the procedure were one-fifth or one-sixth of this dose. At the end of the surgical procedure the neuromuscular block was antagonized with a mixture of atropine 0.018 mg/kg and neostigmine 0.08 mg/kg given i.v. During the procedure, the patients received dextrose 5% in lactated Ringer's solution (4-8 ml/kg/h). Dose selection
From our previous study (Bennett et al., 1975), it was suggested that the potency of pancuronium PATIENTS AND METHODS compared with tubocurarine was: Fifty neonates (age range 1-28 days) undergoing 0-7 days 9: 1 surgery of the thorax or abdomen were studied. 8: 1 8-14 days Atropine 0.1 mg was given i.m. 1 h before operation. 7: 1 15-21 days The operating room was heated to 26 °C and each 6: 1 22-28 days baby was placed upon a warm water mattress to and that the appropriate dose of pancuronium for the maintain normothermia. Endotracheal intubation was neonatal period given as a single bolus in the mature performed with the child awake, and a 50% mixture of nitrous oxide in oxygen was administered using a healthy neonate was: Rees variation of the T-piece. A dose of tubocurarine 0-1 week 30 i^g/kg was selected and given into a suitable vein on the 1-2 weeks 60 (xg/kg volar aspect of the wrist using a 25-gauge needle. 2-4 weeks According to the response, one-half, one-quarter or This amount of pancuronium could be expected to less of this dose was repeated until the desired result provide 75+15 min of relaxation and was readily was obtained. The end-point was either adequate reversible. The amount of drug should be reduced according to the degree of prematurity, in the presence E. J. BENNETT, F.F.A.R.C.S.; A. IGNACIO, JR, M.D.; K. PATEL, of hypothermia, acidosis or following the adminisM.D.; E. M. GRUNDY, F.F.A.R.C.S.; University of Illinois, tration of antibiotics which may affect the neuroChicago, Illinois 60612, U.S.A. M. R. SALEM, M.D., muscular transmission. Loyola University, Chicago, Illinois 60153, U.S.A.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 21, 2015
Tubocurarine, given as a single bolus, may be used safely for neuromuscular blockade in the neonate. The recommended dose is 250 (ig/kg at birth, increasing to 500 ng/kg at 28 days of age. This dose should be reduced in the event of prematurity, acidosis or hypothermia, or when certain antibiotics or inhalation anaesthetic agents are present in the tissues. A single dose as described has a duration of approximately 1 h and it is only after this time that satisfactory antagonism can be obtained. The potency of pancuronium when compared with tubocurarine in the study is 6 : 1, from birth to 28 days.
688
BRITISH JOURNAL OF ANAESTHESIA
Accordingly, the dose of tubocurarine was selected as: 0-7 days 270 8-14 days 420 15-28 days 540 [xg/kg with similar reductions according to the condition of the patient. In figure 1 the circled points had at least three of these factors present when tubocurarine was given. *
700600.
'
*
>
^
500400-
•
300 J
* >
200-
' '•
V
; 1——i—r—i—i—i—i—\
4
250 ^g/kg 400 jxg/kg 500 [ig/kg
and to give incremental doses as necessary of one-fifth or one-sixth the original dose. This initial dose is reduced in prematurity, acidosis, hypothermia and in the presence of antibiotics or potent anaesthetic agents.
100-
o- -;
0-1 week 1-2 weeks 2-4 weeks
1—i—i
6 8 10 12 14 16 18 20 22 24 26 28 AGE (days)
FIG. 1. Dose of tubocurarine giving optimal "curarization" in neonates of different age. Correlation coefficient r = +0.772. RESULTS
The patients' weight ranged from 520 to 4200 g. Of these, 27 neonates were considered to have a low birth weight (premature) (average 1600 g). The figure shows the results obtained for optimal "curarization"; the correlation coefficient was + 0.772. Antagonism was judged to be satisfactory in all cases. The mean duration of activity was 55 min + SD 25. DISCUSSION
Tubocurarine appears to be satisfactory for use as a neuromuscular blocking drug for neonatal anaesthesia, when used as a single dose. Titration is not always required. Compared with our previous study of pancuronium (Bennett et al., 1975), the regression lines were: 37.40+1.96* Pancuronium: Tubocurarine: 215.77+11.68* Thus the potency ratio for the neonatal period is 6 : 1 . This value is different from the result of the
CONCLUSION
Tubocurarine may be used as the relaxant in the neonate when given in a single bolus. The dose is 250 jxg/kg at birth, ranging to 500 fxg/kg at 28 days of age. This should be reduced when prematurity, acidosis, hypothermia, antibiotics or potent anaesthetic agents are active. This dose has a duration of approximately 1 h before proper reversal can be obtained. REFERENCES
Bennett, E. J., Raj, P. P., and Dalai, F. Y. (1972). Pancuronium bromide: Anticholinesterase effect. M.E.J. Anaesth., 3, 425. Ramamurthy, S., Dalai, F. Y., and Salem, M. R. (1975). Pancuronium and the neonate. Br. J. Anaesth., 47, 75. Bush, G. H., and Stead, A. L. (1962). The use of d-tubocurarine in neonatal anaesthesia. Br.J. Anaesth., 34, 721. Churchill-Davidson, H. C , and Wise, R. P. (1963). Neuromuscular transmission in the newborn infant. Anesthesiology, 24, 271.
Feldman, S. A. (1973). Muscle Relaxants, p. 152. London: W. B. Saunders. Stead, A. L. (1955). The response of the newborn infant to muscle relaxants. Br.J. Anaesth., 27, 124. Walts, L. F., and Dillon, J. B. (1969). The response of newborns to succinylcholine and d-tubocurare. Anesthesiology, 3 1 , 35.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 21, 2015
DUU
previous study. Some possible explanations are: (a) this series with tubocurarine included more small babies (27 v. seven with pancuronium), (b) the modifying factors may be more active with tubocurarine, (c) the anticholinesterase action of pancuronium may affect the "myasthenic" response of the neonate (Bennett, Raj and Dalai, 1972), and (d) small incremental doses (titration) may result in a larger total dose (Feldman, 1973). The comparison of potencies used Bush and Stead's method with titration of drug (Bennett et al., 1975). It is now our practice to administer tubocurarine, in conjunction with nitrous oxide anaesthesia, to the neonate in a single dose of:
TUBOCURARINE AND THE NEONATE LA TUBOCURARINE ET LE NOUVEAU-NE RESUME
TUBOCURARIN UND DAS NEUGEBORENE ZUSAMMENFASSUNG
Tubocurarin, als Einzeldosis verabreicht, kann gefahrlos zur neuromuskularen Blockierung an Neugeborene verabreicht werden. Die empfohlene Dosis betragt bei der Geburt 250 [xg/kg, ansteigend auf 500 (xg/kg bei einem
Alter von 28 Tagen. Bei Fruhgeburten, Azidose oder Hypothermie sollte diese Dosis verringert werden, sowie auch dann, wenn gewisse Antibiotika oder eingeatmete Narkosemittel im Gewebe vorhanden sind. Die beschriebene Einzeldosis hat eine Dauer von etwa 1 h, und erst danach kann ein befriedigender Antagonismus erzielt werden. Die Wirkungsstarke von Pancuronium im Vergleich mit Tubocurarin in dieser Untersuchung ist 6 : 1, von der Geburt bis zum Alter von 28 Tagen. TUBOCURARINA Y EL NEONATO SUMARIO
La tubocurarina, administrada en bolo unico, puede usarse con seguridad para el bloqueo neuromuscular en el neonato. La dosis recomendada es de 250 jxg/kg al nacer, aumentando a 500 fig/kg a los 28 dias de edad. Esta dosis debera reducirse en los casos de premadurez, acidosis o hipotermia, o cuando se hallen en los tejidos ciertos antibioticos o anestesicos de inhalation. Una dosis unica como las descritas tiene una duration de 1 h aprox., y solamente tras este tiempo puede obtenerse un antagonismo satisfactorio. La potencia del pancuronio, cuando se compara con tubocurarina, es de 6 : 1, desde el nacimiento a los 28 dias.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 21, 2015
La tubocurarine, administree en un seul bol, peut etre utilisee en toute securite pour les blocages neuromusculaires chez les nouveaux-nes. La dose recommandee est de 250 (xg/kg a la naissance, augmentant a 500 (ig/kg a l'age de 28 jours. II y aura lieu de diminuer cette dose en cas de naissance prematuree, d'acidose ou d'hypothermie ou encore, lorsque certains antibiotiques ou agents anesthesiants administres par inhalation sont presents dans les tissus. Une seule dose administree suivant les prescriptions ci-dessus a une duree approximative d'une heure et ce n'est qu'apres ce laps de temps que Ton peut obtenir un antagonisme satisfaisant. L'efficacite du pancuronium par rapport a la tubocurarine faisant l'objet de cette etude est de 6 : 1, de la naissance a 28 jours.
689