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MATERNAL AND NEONATAL RESPONSES TO ALFENTANIL ADMINISTERED BEFORE INDUCTION OF GENERAL ANAESTHESIA FOR CAESAREAN SECTION
Br.J. Anaesth. (1987), 59, 1392-1396
MATERNAL AND NEONATAL RESPONSES TO ALFENTANIL ADMINISTERED BEFORE INDUCTION OF GENERAL ANAESTHESIA FOR CAESAREAN SECTION W. L. DANN, A. HUTCHINSON AND D. P. CARTWRIGHT
SUMMARY The cardiovascular response to tracheal intubation was compared in two groups of patients undergoing elective Caesarean section. Both groups received a standard technique of general anaesthesia. One of the groups received alfentanil 10 ng kg'1 1 min before induction of anaesthesia, the other acted as a control group. In the alfentanil group there was a significant modification of the cardiovascular response to intubation as compared with the control group (? < 0.01). No adverse effect on the neonate was seen. However, a significant increase in the incidence of postoperative nausea occurred in mothers in the alfentanil group (P < 0.05).
explanation of the study and its aims. We stressed that there was a small risk of awareness with this anaesthetic technique, but that it was a technique which was, until recently, considered the standard method of anaesthesia for Caesarean section. Patients about to undergo Caesarean section under general anaesthesia between 36 and 42 weeks gestation, taking no medication other than iron and folate supplements, and who suffered PATIENTS AND METHODS from neither hypertension nor any other intercurThe design of the study was approved by the rent disease were entered to the trial. These hospital ethics committee and informed consent patients in every way fitted the description of was obtained from all patients after a full "clinically acceptable ideal cases" (Crawford, Burton and Davies, 1972). The patients were then allocated to either control or alfentanil groups by use of a random number table. W . L . DANN, M.B., CH.B., F.F.A.R.C.S.; D . P. CAHTWHIGHT, The anaesthetic technique was similar in both M.B., CH.B., F.F.A.R.C.S. ; Derby City Hospital, Unoxeter Road, Derby, DE3 3NE. A. HUTCHINSON, M.B., B.S., F.F.A.R.C.S., groups. Premedication was ranitidine 150 mg and University Department of Anaesthesia, Qaeen's Medical 0.03-molar sodium citrate 30 ml by mouth; no Centre, University Hospital and Medical School, Clifton Boulevard, Nottingham, NG7 2UH. Accepted for publica- sedative was given. All patients were placed supine with a wedge under the right buttock and tion: March 27, 1987. Correspondence to W . L . D . were pre-oxygenated for 5 min. After preoxygena-
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
An increase in arterial pressure and tachycardia commonly follows laryngoscopy and tracheal intubation under general anaesthesia (King et al., 1951; Millar-Forbes and Dally, 1970; Black, Kay and Healy, 1984). This response is probably of little concern in the majority of patients; however, in those with cardiovascular or intracranial disease, complications may occur (Prys-Roberts et al., 1971; Fox etal., 1977). Patients with eclampsia and pre-eclampsia also fall in this category, and may be at risk if the anaesthetic provokes a further increase in arterial pressure. Narcotics have been shown to be effective in reducing the cardiovascular response to intubation (Dahlgren and Messeter, 1981; Martin et al., 1982), but concern about neonatal respiratory depression has prevented their use during Caesarean section. The cardiovascular response to intubation is decreased by alfentanil 15ugkg -1 (Black, Kay and Healy, 1984). The pharmacological profile of alfentanil (short duration of action, high protein binding and low lipid solubility) may offer advantages over the older opioids, as it suggests that neonatal depression will be minimal when it is used in an appropriate dose.
ALFENTANIL AT CAESAREAN SECTION
1393
200 190 a 180 I |
170 160
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140
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treatment Group
* * # • * * * # *
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#
3 4 5 6 7 Recording number
8
-^Baseline
!
I
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Alfentanil Induction Intubation
9
FIG. 1. Changes (± 1 SD) in systolic arterial pressure before and after the induction of anaesthesia, in the control group (bold bars) and treatment group (narrow bars). Shaded area represents the time from administration of alfentanil to administration of thiopentone and therefore is of significance only for the treatment group. By t test: *P < 0.05; ** P < 0.01; others not significant.
tion, patients in the treatment group received alfentanil lOugkg"1 by i.v. bolus injection. One minute later patients in both groups received thiopentone 3.5mgkg"'. Cricoid pressure was applied as consciousness was lost, and suxamethonium 1 mg kg"1 given. Laryngoscopy and intubation were performed 1 min after induction, and the cricoid pressure released after confirmation of the correct placement of the tracheal tube. Anaesthesia was maintained with 50% nitrous oxide in oxygen given by IPPV. End-tidal carbon dioxide was monitored and ventilation adjusted to maintain normocarbia. Neuromuscular blockade was maintained with alcuronium 15 mg. At delivery Syntocinon 10 i.u. was given i.v. and anaesthesia supplemented with papaveretum 15 mg i.v. At the end of the procedure residual neuromuscular block was antagonized by neostigmine 2.5 mg given with atropine 1.2 mg. Maternal heart rate and arterial pressure were measured throughout using a Dinamap 1846 (Critikon Ltd) and a standard cuff (Cat. no. 8306); a linked printer provided a permanent record. Following a period of 10 min to allow the cardiovascular system to stabilize, recordings were taken at 30-s intervals from the preoxygenation period until 5 min following intubation, and at 1-min intervals thereafter.
The neonates were assessed by a paediatrician who was unaware to which group the mother belonged. Apgar scores were awarded at 1 and 10 min. Further routine examinations were carried out 24 h after delivery. On the first day after operation the mothers were questioned about awareness, dreams and postoperative nausea and vomiting. Data were analysed by the use of paired and unpaired t tests, Chi-square tests and analysis of variance. The Mann-Whitney U test was used where appropriate. A probability value of P < 0.05 was considered significant.
RESULTS
Thirty-seven patients entered the trial; 21 received alfentanil and 16 acted as the control group. The groups were comparable in age, weight, obstetric history and duration of gestation. Maternal results There was no significant difference in arterial pressure or heart rate between the groups before the induction of anaesthesia (figs 1, 2 and 3). Neither the administration of alfentanil nor the
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
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BRITISH JOURNAL OF ANAESTHESIA
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* * * * Treatment f Baseline . G r o u P T T Ot 1 I ' ' Alfentanil Induction Intubation
* * * * * * * * * * * * 2 3 4 5 6 Recording number
7
8
9
FIG. 2. Changes ( ± 1 S D ) in diastolic arterial pressure before and after induction of anaesthesia. Explanation as for figure 1.
140 1
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Alfentanil Induction Intubation FIG. 3. Changes in heart rate before and after induction of anaesthesia. Explanation as for figure 1.
induction of anaesthesia produced any significant change. Following intubation there was a significant increase in systolic arterial pressure in the control group (mean systolic AP 166, SD 15 mm Hg, P < 0.01) which was not seen in the alfentanil group. The difference between the two groups was significant (P < 0.01). In the control group, diastolic arterial pressure increased following intubation (mean diastolic AP 105.5, SD 15 mm Hg, P < 0.01). The increase was not seen in the
alfentanil group, and again the difference between the groups was significant (P < 0.01). As anaesthesia progressed, both systolic and diastolic arterial pressures in the control group returned towards the baseline values and towards those in the alfentanil group. No significant change in AP was found after either skin incision or the administration of alcuronium. There was no significant change in heart rate until after intubation. Following intubation, heart
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
Q 40
ALFENTANIL AT CAESAREAN SECTION TABLE I. Maternal 24-h assessment. *P<0.05 (Chi-square test with Yatef correction for small numbers')
n
Awareness Dreaming Vomiting Nausea
Control
Alfentanil
16 2 4 3 3
21 2 6 3 12*
delivery (control median 9, alfentanil median 10, P > 0.1) were similar in the two groups. No neonate in either group required intubation of the trachea or the administration of naloxone. One neonate in the control group had slight respiratory distress and was observed in the special care baby unit for 24 h. Two of the alfentanil group had prolonged uterine-incision delivery times as a result of obstetric difficulties and were observed in the special care baby unit. No special management was required in any of these subjects. DISCUSSION
It is difficult to assess the importance of hypertension provoked by tracheal intubation in eclamptic and pre-eclamptic patients. Transient hypertensive episodes of this type often pass unnoticed and morbidity resulting from these episodes is often unreported. The Confidential Inquiry into Maternal Mortality in England and Wales gives little detailed information concerning individual patients. There is little doubt that the hypertension following intubation is important in other disease states in which cerebral oedema is present (Fitch and McDowall, 1969; Shapiro, Galindo and Wyte, 1972). Even though hypertension on Neonatal results intubation is short-lived, complications may All the neonates were between 36 and 42 weeks follow (Shapiro, Galindo and Wyte, 1972; Fitch gestation. Induction to delivery times were similar and McDowall, 1969; Fox et al., 1979). All our in the control (10.4 min±2.6) and the alfentanil patients were previously normotensive but, even so, two of the control group developed systolic (11.8 min±2.5) groups (table II). arterial pressures greater than 240 mm Hg followApgar scores at 1 min (control median 9, alfentanil median 9, P > 0.1) and at 10 min after ing intubation of the trachea (the maximum recorded by the Dinamap). In the previously hypertensive patient the arterial pressure may well increase even more (Prys-Roberts etal., 1971; TABLE II. Neonatal results Fox et al., 1977). To the authors' knowledge, there is no information available on this subject in Alfentanil Control obstetric patients. 21 n 16 It is known that automated oscillometers can be Induction-delivery 10.4±2.6 11.8±2.5 inaccurate, particularly when recording rapidly interval (min) (Hutton, Dye and Prys-Roberts, 1984). These (mean±SD) inaccuracies are, however, small when compared Weight (g) (mean±SD) 3280 ±690 3240 ±600 with the changes in arterial pressure which we 0 Intubated 0 0 0 Naloxone observed. Also, at high pressures these devices 1 2 Admitted to Special Baby tend to underestimate and it is, therefore, possible Unit that some of the arterial pressures attained in the Apgar 1 min control group were even greater than we recorded. 9 9 Median We did not consider it ethically acceptable to Range 4-10 5-10 Apgar 10 min perform arterial puncture in these healthy par10 10 Median turients in order to obtain recordings of i.a. Range (all 10) 9-10 pressure.
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
rate in the control group increased by a mean of 40 beat min"1 {P < 0.05). In the alfentanil group the initial increase in heart rate did not reach statistical significance, but the increase continued and became significant 2 min after intubation. Two patients in each group were aware at some time during the operation (table I), but none of these patients experienced any pain or was particularly distressed by this experience. Dreaming also occurred in 10 patients (four control, six alfentanil). None of the dreams was recalled as unpleasant. The patients had been informed of this possibility at the preoperative visit. The alfentanil group experienced more postoperative nausea (12/21) than the control group (3/16).
1395
1396
In conclusion, our original hypothesis was confirmed. Alfentanil 10 ug kg"1 given before induction of anaesthesia reduced significantly the cardiovascular response to tracheal intubation, without producing any detectable neonatal depression. Hoewever, the incidence of awareness and postoperative nausea suggest that modifications may be necessary to make this technique more acceptable for use in obstetric anaesthesia. Further investigations are, therefore, indicated. The simplicity and effectiveness of alfentanil administration used to control pressor responses may prove beneficial in the anaesthetic management of the parturient. Black, T. E., Kay, B., and Healy, T. E. J. (1984). Reducing the haemodynamic responses to largyngoscopy and intubation. A comparison of alfentanil with fentanyl. Anaesthesia, 39, 883. Crawford, J. S., Burton, M., and Davies, P. (1972). Time and lateral tilt at Caesarean section. Br. J. Anaesth., 44, 477. Lewis, M., and Davies, P. (1985). Maternal and neonatal responses related to the volatile agent used to maintain anaesthesia at Caesarean section. Br. J. Anaesth., 57, 482. Dahlgren, N., and Messeter, K. (1981). Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesia, 36, 1022. Famon, D., and Curran, J. (1981). Beta-receptor blockade and tracheal intubation. Anaesthesia, 36, 803. Fitch, W., and McDowall, D. G. (1969). Hazards of anaesthesia in patients with intra-cranial space-occupying lesions. Inurnall Ancsthesiol. Clin., 7, 639. Fox, E. J., Sklar, G. S., Hill, C. H., Villanueva, R., and King, B. D. (1977). Complications related to the pressor response of cndotracheal intubation. Anestheswlogy, 47, 524. Helmers, J. H., Van Leeuwen, L., Adam, A. A., Giezen, J., and Deen, L. (1982). Double-blind comparison of the postoperative respiratory depressant effects of alfentanil and fentanyl. Ada Anaesthesiol. Belg., 31, 13. Hutton, P., Dye J., and Prys-Roberts, C. (1984). An assessment of the Dinamap 845. Anaesthesia, 39, 261. King, B. D., Harris, L. C , Greifenstein, F. E., Elder, J. D., and Dripps, R. D. (1951). Reflex circulatory responses to direct laryngoscopy and tracheal intubation performed during general anesthesia. Anesthesiology, 12, 556. McLeskey, C. H., Cullen, B. F., Kennedy, R. D., and Galindo, A. (1974). Control of cerebral perfusion pressure during induction of anesthesia in high-risk neurosurgical patients. Anesth. Analg., 53, 985. Martin, D. E., Rosenberg, H., Aukburg, S. J., Bartowski, R. R., Edwards, M. W., Greenhow, D. E., and Klineberg, P. L. (1982). Low dose fentanyl blunts circulatory responses to tracheal intubation. Anesth. Analg., 61, 680. Millar-Forbes, A., and Dally, F. G. (1970). Acute hypertension during induction of anaesthesia and endotracheal intubation in normotensivc man. Br. J. Anaesth., 42, 618. Prys-Roberts, C , Greene, L. T., Meloche, R., and Foe*, P. (1971). Studies of anaesthesia in relation to hypertension II: Haemodynamic consequences of induction and endotracheal intubation. Br. J. Anaesth., 43, 531. Shapiro, H. M., Galindo, A., and Wyte, S. R. (1972). Acute intracranial hypertension during anesthetic induction. Europ. Neurol., 82, 118.
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
Several methods have been described which reduce the pressor response to intubation (PrysRoberts et al., 1971; McLeskey et al., 1974; Martin et al., 1982). Some of these are complicated or time consuming and so may be inappropriate in an emergency situation. Complications have been ascribed to some of these techniques (Farnon and Curran, 1981). Opioids are commonly used in anaesthesia to promote cardiovascular stability. Fears of neonatal respiratory depression have, however, restricted their application at Caesarean section. Alfentanil is rapid in onset and has the shortest duration of action of the currently available opioids, and as such it is most appropriate for the anaesthetic management of brief periods of intense stimulation. Black, Kay and Healy (1984) showed 15 ngkg"1 to be effective in blocking the pressor response to intubation, and our own experience in non-pregnant patients suggested that 10 (ig kg"1 was effective. From our results it can be seen that this dose of alfentanil was effective in obtunding the increase in arterial pressure on intubation in the parturient. In common with the other opioids, alfentanil crosses the placenta, resulting in a maternal: neonatal plasma ratio of approximately 3:1 (H. Waldron, Janssen Pharmaceuticals Ltd, personal communication). Even so, the rapid decline in the maternal plasma concentration with time would be expected to be reflected by a similar decrease in the neonatal plasma concentration. Thus any effects on the neonate would be expected to be brief. This may not be the case with the other opioids. As the average induction to delivery time in our hospital is 11 min, it was reasonable to assume, using the 10-ug kg"1 dose, that the neonatal plasma concentration at delivery would be low. Alfentanil is readily antagonized by naloxone (Helmers et al., 1982). Thus respiratory depression in the neonate, arising from residual narcotic, would be reversed rapidly by naloxone. In the event no evidence of residual narcosis of the neonate was observed in our study, Apgar scores being very similar in the control and alfentanil groups. We were concerned about the possible additive effects of alfentanil and a volatile agent on the baby, and for this reason volatile agents were not used in this study. Two cases of awareness were observed in each of our groups. Although the numbers are small, this incidence of awareness is comparable to that in other reported series (Crawford, Lewis and Davies, 1985).
BRITISH JOURNAL OF ANAESTHESIA
MATERNAL AND NEONATAL RESPONSES TO ALFENTANIL ADMINISTERED BEFORE INDUCTION OF GENERAL ANAESTHESIA FOR CAESAREAN SECTION W. L. DANN, A. HUTCHINSON AND D. P. CARTWRIGHT
SUMMARY The cardiovascular response to tracheal intubation was compared in two groups of patients undergoing elective Caesarean section. Both groups received a standard technique of general anaesthesia. One of the groups received alfentanil 10 ng kg'1 1 min before induction of anaesthesia, the other acted as a control group. In the alfentanil group there was a significant modification of the cardiovascular response to intubation as compared with the control group (? < 0.01). No adverse effect on the neonate was seen. However, a significant increase in the incidence of postoperative nausea occurred in mothers in the alfentanil group (P < 0.05).
explanation of the study and its aims. We stressed that there was a small risk of awareness with this anaesthetic technique, but that it was a technique which was, until recently, considered the standard method of anaesthesia for Caesarean section. Patients about to undergo Caesarean section under general anaesthesia between 36 and 42 weeks gestation, taking no medication other than iron and folate supplements, and who suffered PATIENTS AND METHODS from neither hypertension nor any other intercurThe design of the study was approved by the rent disease were entered to the trial. These hospital ethics committee and informed consent patients in every way fitted the description of was obtained from all patients after a full "clinically acceptable ideal cases" (Crawford, Burton and Davies, 1972). The patients were then allocated to either control or alfentanil groups by use of a random number table. W . L . DANN, M.B., CH.B., F.F.A.R.C.S.; D . P. CAHTWHIGHT, The anaesthetic technique was similar in both M.B., CH.B., F.F.A.R.C.S. ; Derby City Hospital, Unoxeter Road, Derby, DE3 3NE. A. HUTCHINSON, M.B., B.S., F.F.A.R.C.S., groups. Premedication was ranitidine 150 mg and University Department of Anaesthesia, Qaeen's Medical 0.03-molar sodium citrate 30 ml by mouth; no Centre, University Hospital and Medical School, Clifton Boulevard, Nottingham, NG7 2UH. Accepted for publica- sedative was given. All patients were placed supine with a wedge under the right buttock and tion: March 27, 1987. Correspondence to W . L . D . were pre-oxygenated for 5 min. After preoxygena-
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
An increase in arterial pressure and tachycardia commonly follows laryngoscopy and tracheal intubation under general anaesthesia (King et al., 1951; Millar-Forbes and Dally, 1970; Black, Kay and Healy, 1984). This response is probably of little concern in the majority of patients; however, in those with cardiovascular or intracranial disease, complications may occur (Prys-Roberts et al., 1971; Fox etal., 1977). Patients with eclampsia and pre-eclampsia also fall in this category, and may be at risk if the anaesthetic provokes a further increase in arterial pressure. Narcotics have been shown to be effective in reducing the cardiovascular response to intubation (Dahlgren and Messeter, 1981; Martin et al., 1982), but concern about neonatal respiratory depression has prevented their use during Caesarean section. The cardiovascular response to intubation is decreased by alfentanil 15ugkg -1 (Black, Kay and Healy, 1984). The pharmacological profile of alfentanil (short duration of action, high protein binding and low lipid solubility) may offer advantages over the older opioids, as it suggests that neonatal depression will be minimal when it is used in an appropriate dose.
ALFENTANIL AT CAESAREAN SECTION
1393
200 190 a 180 I |
170 160
^
140
m
'« 130 to
o 120
100
90
treatment Group
* * # • * * * # *
****
#
3 4 5 6 7 Recording number
8
-^Baseline
!
I
Of
1 2
Alfentanil Induction Intubation
9
FIG. 1. Changes (± 1 SD) in systolic arterial pressure before and after the induction of anaesthesia, in the control group (bold bars) and treatment group (narrow bars). Shaded area represents the time from administration of alfentanil to administration of thiopentone and therefore is of significance only for the treatment group. By t test: *P < 0.05; ** P < 0.01; others not significant.
tion, patients in the treatment group received alfentanil lOugkg"1 by i.v. bolus injection. One minute later patients in both groups received thiopentone 3.5mgkg"'. Cricoid pressure was applied as consciousness was lost, and suxamethonium 1 mg kg"1 given. Laryngoscopy and intubation were performed 1 min after induction, and the cricoid pressure released after confirmation of the correct placement of the tracheal tube. Anaesthesia was maintained with 50% nitrous oxide in oxygen given by IPPV. End-tidal carbon dioxide was monitored and ventilation adjusted to maintain normocarbia. Neuromuscular blockade was maintained with alcuronium 15 mg. At delivery Syntocinon 10 i.u. was given i.v. and anaesthesia supplemented with papaveretum 15 mg i.v. At the end of the procedure residual neuromuscular block was antagonized by neostigmine 2.5 mg given with atropine 1.2 mg. Maternal heart rate and arterial pressure were measured throughout using a Dinamap 1846 (Critikon Ltd) and a standard cuff (Cat. no. 8306); a linked printer provided a permanent record. Following a period of 10 min to allow the cardiovascular system to stabilize, recordings were taken at 30-s intervals from the preoxygenation period until 5 min following intubation, and at 1-min intervals thereafter.
The neonates were assessed by a paediatrician who was unaware to which group the mother belonged. Apgar scores were awarded at 1 and 10 min. Further routine examinations were carried out 24 h after delivery. On the first day after operation the mothers were questioned about awareness, dreams and postoperative nausea and vomiting. Data were analysed by the use of paired and unpaired t tests, Chi-square tests and analysis of variance. The Mann-Whitney U test was used where appropriate. A probability value of P < 0.05 was considered significant.
RESULTS
Thirty-seven patients entered the trial; 21 received alfentanil and 16 acted as the control group. The groups were comparable in age, weight, obstetric history and duration of gestation. Maternal results There was no significant difference in arterial pressure or heart rate between the groups before the induction of anaesthesia (figs 1, 2 and 3). Neither the administration of alfentanil nor the
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
% 11°
•o
BRITISH JOURNAL OF ANAESTHESIA
1394 120 110
_
E 100 pressi
90 80 -
art
70 -
-T- } +]
-1-
—
-
J.
60
u
50
30 -
* * * * Treatment f Baseline . G r o u P T T Ot 1 I ' ' Alfentanil Induction Intubation
* * * * * * * * * * * * 2 3 4 5 6 Recording number
7
8
9
FIG. 2. Changes ( ± 1 S D ) in diastolic arterial pressure before and after induction of anaesthesia. Explanation as for figure 1.
140 1
130 120
1 i
:
110
-
T
-
•
j -• i
1
-
i
.1 Baseline
1
-
-
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•
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rl
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^
•
Treatment Group
I
t
Ot
1
2
3
4
5
6
7
8
9
Alfentanil Induction Intubation FIG. 3. Changes in heart rate before and after induction of anaesthesia. Explanation as for figure 1.
induction of anaesthesia produced any significant change. Following intubation there was a significant increase in systolic arterial pressure in the control group (mean systolic AP 166, SD 15 mm Hg, P < 0.01) which was not seen in the alfentanil group. The difference between the two groups was significant (P < 0.01). In the control group, diastolic arterial pressure increased following intubation (mean diastolic AP 105.5, SD 15 mm Hg, P < 0.01). The increase was not seen in the
alfentanil group, and again the difference between the groups was significant (P < 0.01). As anaesthesia progressed, both systolic and diastolic arterial pressures in the control group returned towards the baseline values and towards those in the alfentanil group. No significant change in AP was found after either skin incision or the administration of alcuronium. There was no significant change in heart rate until after intubation. Following intubation, heart
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
Q 40
ALFENTANIL AT CAESAREAN SECTION TABLE I. Maternal 24-h assessment. *P<0.05 (Chi-square test with Yatef correction for small numbers')
n
Awareness Dreaming Vomiting Nausea
Control
Alfentanil
16 2 4 3 3
21 2 6 3 12*
delivery (control median 9, alfentanil median 10, P > 0.1) were similar in the two groups. No neonate in either group required intubation of the trachea or the administration of naloxone. One neonate in the control group had slight respiratory distress and was observed in the special care baby unit for 24 h. Two of the alfentanil group had prolonged uterine-incision delivery times as a result of obstetric difficulties and were observed in the special care baby unit. No special management was required in any of these subjects. DISCUSSION
It is difficult to assess the importance of hypertension provoked by tracheal intubation in eclamptic and pre-eclamptic patients. Transient hypertensive episodes of this type often pass unnoticed and morbidity resulting from these episodes is often unreported. The Confidential Inquiry into Maternal Mortality in England and Wales gives little detailed information concerning individual patients. There is little doubt that the hypertension following intubation is important in other disease states in which cerebral oedema is present (Fitch and McDowall, 1969; Shapiro, Galindo and Wyte, 1972). Even though hypertension on Neonatal results intubation is short-lived, complications may All the neonates were between 36 and 42 weeks follow (Shapiro, Galindo and Wyte, 1972; Fitch gestation. Induction to delivery times were similar and McDowall, 1969; Fox et al., 1979). All our in the control (10.4 min±2.6) and the alfentanil patients were previously normotensive but, even so, two of the control group developed systolic (11.8 min±2.5) groups (table II). arterial pressures greater than 240 mm Hg followApgar scores at 1 min (control median 9, alfentanil median 9, P > 0.1) and at 10 min after ing intubation of the trachea (the maximum recorded by the Dinamap). In the previously hypertensive patient the arterial pressure may well increase even more (Prys-Roberts etal., 1971; TABLE II. Neonatal results Fox et al., 1977). To the authors' knowledge, there is no information available on this subject in Alfentanil Control obstetric patients. 21 n 16 It is known that automated oscillometers can be Induction-delivery 10.4±2.6 11.8±2.5 inaccurate, particularly when recording rapidly interval (min) (Hutton, Dye and Prys-Roberts, 1984). These (mean±SD) inaccuracies are, however, small when compared Weight (g) (mean±SD) 3280 ±690 3240 ±600 with the changes in arterial pressure which we 0 Intubated 0 0 0 Naloxone observed. Also, at high pressures these devices 1 2 Admitted to Special Baby tend to underestimate and it is, therefore, possible Unit that some of the arterial pressures attained in the Apgar 1 min control group were even greater than we recorded. 9 9 Median We did not consider it ethically acceptable to Range 4-10 5-10 Apgar 10 min perform arterial puncture in these healthy par10 10 Median turients in order to obtain recordings of i.a. Range (all 10) 9-10 pressure.
Downloaded from http://bja.oxfordjournals.org/ at New York University on July 12, 2015
rate in the control group increased by a mean of 40 beat min"1 {P < 0.05). In the alfentanil group the initial increase in heart rate did not reach statistical significance, but the increase continued and became significant 2 min after intubation. Two patients in each group were aware at some time during the operation (table I), but none of these patients experienced any pain or was particularly distressed by this experience. Dreaming also occurred in 10 patients (four control, six alfentanil). None of the dreams was recalled as unpleasant. The patients had been informed of this possibility at the preoperative visit. The alfentanil group experienced more postoperative nausea (12/21) than the control group (3/16).
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In conclusion, our original hypothesis was confirmed. Alfentanil 10 ug kg"1 given before induction of anaesthesia reduced significantly the cardiovascular response to tracheal intubation, without producing any detectable neonatal depression. Hoewever, the incidence of awareness and postoperative nausea suggest that modifications may be necessary to make this technique more acceptable for use in obstetric anaesthesia. Further investigations are, therefore, indicated. The simplicity and effectiveness of alfentanil administration used to control pressor responses may prove beneficial in the anaesthetic management of the parturient. Black, T. E., Kay, B., and Healy, T. E. J. (1984). Reducing the haemodynamic responses to largyngoscopy and intubation. A comparison of alfentanil with fentanyl. Anaesthesia, 39, 883. Crawford, J. S., Burton, M., and Davies, P. (1972). Time and lateral tilt at Caesarean section. Br. J. Anaesth., 44, 477. Lewis, M., and Davies, P. (1985). Maternal and neonatal responses related to the volatile agent used to maintain anaesthesia at Caesarean section. Br. J. Anaesth., 57, 482. Dahlgren, N., and Messeter, K. (1981). Treatment of stress response to laryngoscopy and intubation with fentanyl. Anaesthesia, 36, 1022. Famon, D., and Curran, J. (1981). Beta-receptor blockade and tracheal intubation. Anaesthesia, 36, 803. Fitch, W., and McDowall, D. G. (1969). Hazards of anaesthesia in patients with intra-cranial space-occupying lesions. Inurnall Ancsthesiol. Clin., 7, 639. Fox, E. J., Sklar, G. S., Hill, C. H., Villanueva, R., and King, B. D. (1977). Complications related to the pressor response of cndotracheal intubation. Anestheswlogy, 47, 524. Helmers, J. H., Van Leeuwen, L., Adam, A. A., Giezen, J., and Deen, L. (1982). Double-blind comparison of the postoperative respiratory depressant effects of alfentanil and fentanyl. Ada Anaesthesiol. Belg., 31, 13. Hutton, P., Dye J., and Prys-Roberts, C. (1984). An assessment of the Dinamap 845. Anaesthesia, 39, 261. King, B. D., Harris, L. C , Greifenstein, F. E., Elder, J. D., and Dripps, R. D. (1951). Reflex circulatory responses to direct laryngoscopy and tracheal intubation performed during general anesthesia. Anesthesiology, 12, 556. McLeskey, C. H., Cullen, B. F., Kennedy, R. D., and Galindo, A. (1974). Control of cerebral perfusion pressure during induction of anesthesia in high-risk neurosurgical patients. Anesth. Analg., 53, 985. Martin, D. E., Rosenberg, H., Aukburg, S. J., Bartowski, R. R., Edwards, M. W., Greenhow, D. E., and Klineberg, P. L. (1982). Low dose fentanyl blunts circulatory responses to tracheal intubation. Anesth. Analg., 61, 680. Millar-Forbes, A., and Dally, F. G. (1970). Acute hypertension during induction of anaesthesia and endotracheal intubation in normotensivc man. Br. J. Anaesth., 42, 618. Prys-Roberts, C , Greene, L. T., Meloche, R., and Foe*, P. (1971). Studies of anaesthesia in relation to hypertension II: Haemodynamic consequences of induction and endotracheal intubation. Br. J. Anaesth., 43, 531. Shapiro, H. M., Galindo, A., and Wyte, S. R. (1972). Acute intracranial hypertension during anesthetic induction. Europ. Neurol., 82, 118.
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Several methods have been described which reduce the pressor response to intubation (PrysRoberts et al., 1971; McLeskey et al., 1974; Martin et al., 1982). Some of these are complicated or time consuming and so may be inappropriate in an emergency situation. Complications have been ascribed to some of these techniques (Farnon and Curran, 1981). Opioids are commonly used in anaesthesia to promote cardiovascular stability. Fears of neonatal respiratory depression have, however, restricted their application at Caesarean section. Alfentanil is rapid in onset and has the shortest duration of action of the currently available opioids, and as such it is most appropriate for the anaesthetic management of brief periods of intense stimulation. Black, Kay and Healy (1984) showed 15 ngkg"1 to be effective in blocking the pressor response to intubation, and our own experience in non-pregnant patients suggested that 10 (ig kg"1 was effective. From our results it can be seen that this dose of alfentanil was effective in obtunding the increase in arterial pressure on intubation in the parturient. In common with the other opioids, alfentanil crosses the placenta, resulting in a maternal: neonatal plasma ratio of approximately 3:1 (H. Waldron, Janssen Pharmaceuticals Ltd, personal communication). Even so, the rapid decline in the maternal plasma concentration with time would be expected to be reflected by a similar decrease in the neonatal plasma concentration. Thus any effects on the neonate would be expected to be brief. This may not be the case with the other opioids. As the average induction to delivery time in our hospital is 11 min, it was reasonable to assume, using the 10-ug kg"1 dose, that the neonatal plasma concentration at delivery would be low. Alfentanil is readily antagonized by naloxone (Helmers et al., 1982). Thus respiratory depression in the neonate, arising from residual narcotic, would be reversed rapidly by naloxone. In the event no evidence of residual narcosis of the neonate was observed in our study, Apgar scores being very similar in the control and alfentanil groups. We were concerned about the possible additive effects of alfentanil and a volatile agent on the baby, and for this reason volatile agents were not used in this study. Two cases of awareness were observed in each of our groups. Although the numbers are small, this incidence of awareness is comparable to that in other reported series (Crawford, Lewis and Davies, 1985).
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