This article is accompanied by the following Invited Commentary:
Habib AS. Anaesthesia for caesarean delivery of growth-restricted foetuses: a bird in the hand is worth two in the bush. Eur J Anaesthesiol 2013; 30:5–6.
Subarachnoid block (SAB) is considered simpler and safer than other techniques of anaesthesia for caesarean delivery and is, therefore, the technique of choice of most anaesthesiologists. Current evidence suggests that it may not be safer than general or epidural anaesthesia for foetal wellbeing.1–4 Maternal hypotension following SAB may potentially decrease uteroplacental perfusion, leading to foetal acidosis. However, studies have shown that this is not an issue when hypotension is treated promptly with phenylephrine or when it is used prophylactically to prevent hypotension induced by spinal anaesthesia.5,6 Further, as the newborns are generally vigorous, foetal acidosis may not be of concern in healthy, term parturient women; however, in situations of uteroplacental insufficiency with growth-restricted foetuses, the effect of SAB on neonatal outcome may be detrimental.2–4,7
Chronic uteroplacental insufficiency decreases foetal physiological reserve and, therefore, increases the risk of intrapartum asphyxia. Hence, small changes in perfusion for even a short duration may produce significant changes in foetal blood gas values.7 Doppler velocimetry studies demonstrate abnormal flow velocity in the umbilical arteries, suggesting severe placental dysfunction with foetal growth restriction (FGR) and a possible deterioration in foetal acid–base balance.6 In addition, low Apgar scores, foetal distress and prematurity have been reported with FGR.5 Therefore, these pregnancies require intensive antenatal surveillance using foetal biophysical monitoring in order to select the optimal time of caesarean delivery.8,9 Data are limited on the effect of anaesthesia on growth-restricted foetuses delivered by caesarean section.1,5
We designed this study to compare the effects of general anaesthesia and low-dose spinal anaesthesia (LDSA) on umbilical cord base deficit (both arterial and venous) and maternal haemodynamics in women with growth-restricted foetuses and impaired umbilical Doppler flow undergoing elective caesarean delivery. Our hypothesis was that LDSA would maintain haemodynamics and may not result in foetal acidosis when compared with general anaesthesia. The primary aim of our study was to assess the incidence of cord base deficit more than 8 mmol l−1 and pH less than 7.1. The secondary aims were to assess clinical neonatal outcome and maternal haemodynamics in these two groups.
Ethical approval (MS/309/MS/5966 : 2007) was provided by the Ethics Review Committee of the Postgraduate Institute of Medical Education and Research, Chandigarh, India (Chairperson Professor S.K. Jindal) on 29 August 2007. Forty pregnant women with growth-restricted foetuses and abnormal umbilical artery Doppler velocimetry, systolic/diastolic ratio at least 3 or absent diastolic flow, with gestational age more than 30 weeks and scheduled for elective caesarean section were recruited to the study. A single consultant obstetrician (J.K.) performed sonography according to the established protocol of our institution. Written informed consent was taken from all the women before enrolment into the trial. Women whose sonographic details showed reverse diastolic flow as assessed by Doppler or severe preeclampsia with uncontrolled hypertension, antepartum haemorrhage, nonreassuring foetal heart trace, congenital foetal malformation, twin gestation, difficult maternal airway, coagulation abnormalities or any other contraindication to spinal or general anaesthesia were excluded from the study.
The women were allocated randomly into one of two groups each to receive either general anaesthesia (GA) or LDSA, using a computer-generated random number table. The allocation was kept in opaque sealed envelopes which were opened serially just before the start of anaesthesia by an anaesthesiologist (N.B.) who was not involved further in the management of the patients (Fig. 1).
In accordance with Practice Guidelines for Obstetric Anaesthesia, all women were kept fasted for solids for 6 h.10 Ingestion of clear fluids was allowed until 2 h before surgery. Ranitidine 150 mg and metoclopramide 10 mg were given orally 45 min before the scheduled surgery. Maternal age, weight, height, indication for caesarean delivery and three SBP recordings 1 min apart in the left lateral position were recorded prior to transferring the patient to the operating room. The mean of three readings of SBP was considered as the baseline value. In both groups, women received a bolus of isotonic saline 750 ml over 15 min via an 18-gauge intravenous cannula. A multichannel monitor (Datex-Ohmeda Inc., Madison, WI, USA) was used to monitor heart rate (HR), noninvasive blood pressure, continuous ECG, end-tidal carbon dioxide tension (GA group) and oxygen saturation.
SBP and HR measurements were recorded before induction of anaesthesia and at 1-min intervals until delivery of the baby. In both groups, hypotension was defined as a decrease in SBP at least 20% of baseline. If hypotension occurred, intravenous phenylephrine was given as a 30-μg bolus until the blood pressure returned to within 20% of the baseline value. The number of phenylephrine boluses given, the duration of hypotension and the total dose of phenylephrine used before delivery of the baby were recorded. Intervals of induction to skin incision, induction to uterine incision and uterine incision to delivery were also recorded.
In the GA group, after pre-oxygenation for 3 to 4 min with 100% oxygen, anaesthesia was induced with thiopentone 5 mg kg−1 followed by suxamethonium 1.5 mg kg−1 using a rapid sequence technique. Loss of consciousness was defined as loss of eyelash reflex following administration of thiopentone. One minute later, tracheal intubation was performed with an appropriate sized polyvinyl chloride tracheal tube and bilateral equal air entry was confirmed by auscultation. Anaesthesia was maintained with nitrous oxide 50% and isoflurane 0.5 to 1.0% end-tidal concentration in oxygen, atracurium 0.05 mg kg−1 was administered and the lungs were ventilated to a target end-tidal carbon dioxide concentration of 4.0 to 4.7 kPa using a circle system with a fresh gas flow rate of 5 l min−1. The women were given left uterine displacement until delivery. After delivery of the baby, morphine 0.05 mg kg−1 was administered and an infusion of oxytocin was started (25 IU per 500 ml at a rate of 60 to 100 ml h−1). The umbilical cord was triple-clamped and blood samples from the umbilical artery and vein were taken in pre-heparinised syringes for evaluation of foetal acid–base status. After completion of surgery, residual neuromuscular block was reversed using neostigmine 0.05 mg kg−1 and atropine 0.02 mg kg−1.
In the LDSA group, a single-shot SAB was performed at the L2/L3 or L3/L4 interspace using a midline approach with a 26-gauge Quincke needle (B.Braun, Melsungen, Germany) with the patient in the flexed left lateral position. Once free flow of cerebrospinal fluid was obtained, 1.6 ml (8 mg) of heavy bupivacaine 0.5% with fentanyl 20 μg was injected slowly over 20 s. The women were then turned supine with left uterine displacement and supplemental oxygen (40%) was administered using a Ventimask (Intersurgical, Wokingham, Berkshire, UK). The level of sensory block was assessed bilaterally using pinprick every 5 min. A block height of T4–T6 was considered adequate for surgical anaesthesia. Induction of anaesthesia was defined as the time taken from the spinal injection to achievement of the maximum block height. If the block height was T6 or less and the woman complained of pain (as measured by a visual analogue score > 4) at any time during surgery, rescue analgesia was administered (intravenous fentanyl 1 μg kg−1). The total dose of fentanyl was recorded. A block height of T10 or lower was considered as a failure and the patient was excluded from the study. Any complaint of intraoperative nausea or vomiting was recorded and treated using intravenous ondansetron 4 mg. Intramuscular diclofenac was administered for postoperative analgesia in both groups.
Neonatal outcome was assessed by a paediatrician who was unaware of the anaesthetic technique used. This was ensured by separating the neonatal resuscitation area from the operative field by a curtain. The variables recorded were as follows: neonatal weight; umbilical cord arterial blood gases and venous blood gases; and Apgar scores at 1 and 5 min. A base deficit of more than 8 mmol l−1 and a pH value of less than 7.10 was defined as foetal acidosis.1 Apgar scores of 3 and below were regarded as critically ill, 4 to 6 suboptimal and 7 to 10 normal.11 The need for assisted ventilation in the form of facemask ventilation, tracheal intubation and ventilation, or cardiopulmonary resuscitation, was also recorded. The neonates were followed up for the next 24 h for admission to neonatal ICU, any evidence of respiratory distress (using clinical and radiological features) or the need for respiratory support (nasal continuous positive airways pressure or artificial ventilation of the lungs).
Previous studies have reported a normal value for umbilical arterial base deficit after elective caesarean delivery of 5 ± 3 mmol l−1.1 It was hypothesised that a difference of 3 mmol l−1 or more in the base deficit between the two groups would represent a clinically meaningful difference in growth-restricted foetuses. Assuming an SD of 3, a minimum of 17 women were required to detect the above difference with a power of 80% and type I error of 0.05. To account for attrition, it was decided to enrol 20 women in each group.
The data were assessed for normality using the Kolmogorov–Smirnov test. Data are described as mean and SD, with 95% confidence intervals where appropriate. The Apgar scores are presented as median (Interquartile range). The umbilical blood gas values and Apgar scores were compared between the groups using the Mann–Whitney U-test. The association between neonatal outcome variables and mode of anaesthesia was analysed using the χ2-test or Fisher's exact test. HR, SBP, episodes of hypotension and their duration were analysed using an independent Student's t-test. A P value (two-tailed) of less than 0.05 was taken as significant. SPSS version 15 (SPSS Inc., Chicago, IL, USA) was used to conduct all the statistical analyses. The correlation between Apgar score and base deficit was undertaken using Spearman's correlation coefficient.
A total of 40 women with singleton pregnancy and sonographic evidence of intrauterine FGR were recruited randomly to receive either general anaesthesia (n = 20) or LDSA (n = 20) for elective caesarean delivery. Thirty women had systemic disease (preeclampsia with proteinuria, five; pregnancy-induced hypertension, eight; chronic hypertension, four; anaemia, four; hypothyroidism, two; bronchial asthma, one; and others, six). Women in both GA and LDSA groups were similar in respect of age, height, weight, gestational age, S/D ratio, mean baseline SBP and placental weight. An adequate surgical block (T4–T6) was achieved in all women who received LDSA. The time taken for onset of spinal block was 7.3 ± 0.5 min. No patient complained of visceral pain or required fentanyl during surgery or required conversion to general anaesthesia. General anaesthesia was associated with a significantly shorter induction–delivery interval (P = 0.001). The skin incision–delivery and uterine incision–delivery times were similar in the two groups (Table 1).
The neonatal outcome data were found to be normally distributed. The mean neonatal weight was similar in both groups. The primary outcome variables, mean umbilical cord arterial and venous base deficit, were also similar (Table 2). The mean umbilical cord arterial pH was 7.23 ± 0.06 in the LDSA group and 7.27 ± 0.04 in the GA group (P = 0.01). There was no significant difference in the umbilical vein pH. The mean umbilical cord arterial pO2 (P = 0.001) and umbilical cord venous pO2 (P = 0.007) were significantly higher in the GA group. A base deficit of at least 8 mmol l−1 and umbilical cord arterial pH of less than 7.1 occurred in two neonates in the LDSA group with a maternal diagnosis of severe preeclampsia and absent end-diastolic flow. In the GA group, two neonates had a base deficit of at least 8 mmol l−1, but the umbilical cord arterial pH was more than 7.1. There was no associated severe preeclampsia in these women.
The 1 and 5-min Apgar scores were similar in both groups. There was no correlation between Apgar scores and umbilical cord arterial base deficit. In the LDSA group, suboptimal Apgar scores (1-min Apgar score 4 to 6) occurred in four (20%) neonates. Among these, one neonate was acidotic. This baby required tracheal intubation with short-term oxygen therapy and was discharged without any adverse effect. Sixteen neonates (80%) had normal Apgar (≥ 7) scores in this group compared with 13 (65%) in the GA group (P = 0.48). Critically ill newborns as assessed by Apgar score of less than 3 at 5 min were not seen in either group. Seventy percent of the babies in the LDSA group did not require any mode of resuscitation compared with 45% in the GA group (P = 0.51). At 24 h, 80% of the neonates in both groups were able to maintain a normal oxygen saturation while breathing room air (Table 3). The proportions of babies needing admission to the neonatal ICU and respiratory support were similar in the two groups (LDSA group = 4, GA group = 3). One neonatal death occurred in the GA group due to prematurity. Apart from this, there was no incidence of encephalopathy, seizures or any other complication. In both GA and LDSA groups, the need for resuscitation was not significantly associated with acidosis based either on pH or base deficit (P >0.05).
The mean HR and SBP of the mothers until the time of delivery in the two groups are shown in Fig. 1. In the LDSA group, mean HR remained unchanged, whereas in the GA group there was a significant increase in HR until 3 min following induction of anaesthesia (P < 0.05) when compared with baseline values. A significantly higher HR occurred in the GA group compared with the LDSA group up to 7 min after induction of anaesthesia, after which the HR was similar in both groups.
The baseline SBP in both groups was similar. SBP was significantly higher in the GA group at all times of observation after induction of anaesthesia (P < 0.05). Hypotensive episodes [0 (0 to 2)] requiring treatment with a vasopressor occurred in the LDSA group (P = 0.016); six women in this group received treatment for hypotension with phenylephrine. The duration of pre-delivery hypotension in the LDSA group was 0.7 ± 1.1 min (P = 0.019) compared with the GA group. However, there was no correlation between the duration of hypotension and neonatal base deficit. There was no incidence of nausea and vomiting intraoperatively or postoperatively in either group.
In our study, cord base deficit was similar in both groups. Foetal acidaemia (pH < 7.1) was observed in two neonates in the LDSA group with no associated episode of spinal hypotension. LDSA provided adequate surgical block with a short duration of hypotension, whereas there was a trend suggesting a greater need for immediate resuscitation in the GA group, although this was not statistically significant.
FGR, an important cause of perinatal morbidity and mortality, results from chronic placental insufficiency. Most of the studies on the effects of anaesthetic techniques on neonatal outcome have been restricted to term neonates,12–16 with limited knowledge relating to growth restricted fetuses.7 Reynolds et al.2 reported a higher incidence of low umbilical cord arterial and venous pH and a higher base deficit in term neonates as a result of SAB-induced maternal hypotension and frequent requirements for ephedrine. Although foetal acidaemia did not produce any detrimental effects in term infants, the authors questioned the safety of foetal wellbeing in compromised situations.
In a population-based cohort study of very preterm babies (27 to 32 weeks), investigators found a significantly higher risk of mortality in neonates of mothers who received SAB for caesarean delivery compared with general anaesthesia, probably due to inadequate maternal haemodynamic control and undetected placental hypoperfusion.17 Dyer et al. also reported foetal acidosis with SAB in severely preeclamptic parturient women undergoing emergency caesarean delivery. A significantly greater mean arterial base deficit indicating anaerobic metabolism due to metabolic acidosis in the foetus in the SAB group was observed in their study.1
We did not observe a difference in the incidence of cord base deficit between general anaesthesia and LDSA. However, two neonates born to mothers under SAB had low cord pH values (<7.1). One of these infants had a low Apgar score (<6 at 1 min) and required tracheal intubation. Both the mothers suffered from severe preeclampsia with absent end-diastolic flow. Studies have shown that absence or reversal of end-diastolic flow indicates significant elevation in blood flow resistance and loss of an effective foetal–maternal exchange area in the placenta. Baschat et al.9 reported that these Doppler indices reflect serious deterioration in growth-restricted foetuses, with associated low Apgar and cord gas values. In another study, Salafia et al.18 reported a mean pH of 7.15 and 6.94 in cases of absent or reverse end-diastolic flow, respectively. In a recent publication, the authors observed that chronic intrauterine vascular disease may be associated with acidaemia at delivery in neonates with low Apgar scores. They hypothesised that placental vasculopathy may impair the ability of the foetus to withstand the events of labour and delivery.19 In the present study, we selected FGR of mixed causes and severely preeclamptic women with absent end-diastolic flow were inadvertently randomised to the LDSA group only. From our small sample size, it is difficult to draw any conclusion, but it may be important to note that infants born to these mothers may be at a higher risk of acidosis and low Apgar scores. A larger study is required to examine the issue of clinically significant foetal acidosis and the best mode of anaesthesia.
Various authors have reported a higher rate of lower 1 and 5-min Apgar scores in term neonates exposed to general anaesthesia.1,5 In the present study, 1 and 5-min mean Apgar scores were similar in both groups. This may be due to the fact that women in our study were hospitalised and underwent daily clinical monitoring for foetal wellbeing before delivery. In addition, various confounding factors such as foetal distress or reverse diastolic flow, indicating severe intrapartum asphyxia, were excluded. There was a trend suggesting a greater need for immediate resuscitation (although not statistically significant) in the GA group compared with the LDSA group. In a retrospective study of FGR, general anaesthesia was found to be a predictor of poorer neonatal outcome.7 The authors also reported an increased need for resuscitation among growth-restricted neonates in mothers exposed to general anaesthesia. Because we included FGR of mixed causes, it is also possible that general anaesthesia may have been administered to metabolically compromised foetuses based on the randomisation sequence. Indeed, factors other than acidosis such as maternal sedation due to general anaesthesia, lower birth weight or gestational age may have contributed to low Apgar scores. More studies are required before our results can be extrapolated to situations of FGR in which many factors affect neonatal outcome.
Other investigators have shown higher arterial partial pressures and oxygen saturation with general anaesthesia because of delivery of a higher inspired oxygen concentration to this group.14,15 In our study, we attempted to maintain SBP above 80% of baseline by using a lower dose of spinal anaesthetic and administering bolus doses of phenylephrine. Because SAB causes hypotension and may decrease uteroplacental blood flow, effective control of haemodynamics is recommended.5,6 A dose-dependent decrease in the incidence of hypotension has been reported with bupivacaine 5 to 7.5 mg. There is concern that lowering the intrathecal dose would reduce the quality of anaesthesia and increase the incidence of pain during caesarean section. Therefore, the addition of a short-acting opioid and a ‘backup’ epidural catheter are recommended.20 We decided to use bupivacaine 8 mg with fentanyl 20 μg intrathecally because this dose has been shown to provide good surgical anaesthesia without any adverse effects.21 In our study, we did not observe any breakthrough pain, nausea, vomiting or requirement for rescue analgesia as reported in previous studies.21–23 Although we found no instance of breakthrough pain in our study, this can be attributed to the small sample size. Therefore, the use of a low dose of intrathecal drug must be accompanied by a ‘backup’ epidural catheter.
We found that hypotension occurred in a few mothers before delivery of the baby in the LDSA group, but the episodes were of short duration (<2 min). Studies have shown that such short durations of hypotension do not change foetal acid–base values in term healthy neonates.24 This issue has not been specifically investigated previously in compromised foetuses. Tight control of maternal blood pressure by using a prophylactic infusion of phenylephrine gives the best maternal and foetal outcome.5,6 The use of this strategy may have eliminated the few episodes of hypotension observed in our study. Therefore, further studies using a prophylactic infusion of vasopressor in situations of foetal compromise need to be done.
Umbilical cord acid–base status is the most objective determinant of the foetal metabolic condition at birth. We found no difference in umbilical cord arterial base deficit and a small difference in umbilical cord arterial pH, the clinical significance of which is uncertain. However, the Apgar score remains a conventional and commonly used tool for assessing immediate neonatal wellbeing. We found a trend suggesting a greater need for resuscitation in neonates exposed to general anaesthesia compared to LDSA, although this was not statistically significant. Future research should be directed to a larger maternal population investigating the best mode of anaesthesia and its influence on clinically relevant neonatal acidosis in cases of FGR and impaired Doppler flows.
Assistance with the study: none declared.
Financial support and sponsorship: none declared.
Conflicts of interest: none declared.
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