The technique of combined spinal epidural (CSE) for labour analgesia is popular for its rapid and excellent pain control with little motor block [1,2]. This is true especially when maternal pain is high . Other significant advantages of this technique may include faster cervical dilatation  and a decrease in duration of the first stage of labour , although some authors have disputed these affirmations [6-10]. Intrathecal narcotics are commonly used with CSE analgesia, but appear to increase the risk of worrisome decreases in fetal heart rate (FHR) even in the absence of maternal hypotension. Although Vercautereen and colleagues  first described this phenomenon, it was later challenged in a retrospective study by Palmer and colleagues  who did not find a significant difference in the incidence of fetal bradycardia between intrathecal fentanyl and epidural analgesia for labour (12% vs. 6%, respectively). A more recent meta-analysis by Mardirosoff and colleagues  found a relative risk of 1.81 of having FHR abnormalities when spinal opioids were used. Furthermore, Van de Velde  showed evidence that this relationship could be dose dependent with a greater occurrence of worrisome FHR with higher doses of opioids. The exact mechanism responsible for this occurrence remains elusive. Even though fetal bradycardia post CSE analgesia does not result in an increase in surgical deliveries , some anesthesiologists may refrain from using this technique to avoid fetal distress especially in remote areas lacking neonatal intensive care units. We postulated that factors unrelated to the neuraxial technique might play a role in this phenomenon. For example, high maternal pain at the time of neuraxial blockade may increase the risk for fetal bradycardia from the sudden fall in plasma catecholamines that are tocolytic during labour , and the resulting unopposed uterine contraction [16,17]. Other factors such as exogenous infusion of oxytocin, the level of cervical dilatation at the time of neuraxial blockade, maternal age, parity or ethnicity could be implicated. The identification of factors implicated in the decrease in FHR post CSE analgesia might help anesthesiologists in their decision to use the technique weighing in advantages and disadvantages for the patients. Nevertheless, since these decreases in FHR do not usually result in emergency Caesarean section, knowing which patients are at risk can help the anesthesiologist to contravene these changes and to educate the patients and attending personnel on the risk factors. To our knowledge, no prospective study has looked to identify such factors. The purpose of the present study was therefore to reproduce the common decision-making process that anaesthesiologists go through for the choice of an epidural or a CSE for labour analgesia, to compare the relative risk of worrisome decreases in FHR following epidural and CSE analgesia, and to identify independent predictors for this phenomenon.
Institutional Ethics Committee approval was obtained for this study. The data from 223 consecutive eligible patients who requested a neuraxial technique for labour analgesia was collected for analysis. All patients gave written informed consent for the neuraxial technique. The decision to use epidural or CSE analgesia was left to the anaesthesiologist in charge and the patients were blinded to the technique used for labour analgesia. Exclusion criteria included, patients less than 18 yr of age, significant FHR decelerations prior to regional analgesia, contraindications for neuraxial techniques, and the inability to speak French or English.
The group of patients who received CSE analgesia (123) were given 1.25 mg of bupivacaine and 25 μg of fentanyl intrathecally, followed by a continuous epidural infusion containing bupivacaine 0.0625% and fentanyl 2 μg mL−1 at 12 mL h−1. Patients receiving an epidural (100) were given 20 mg of bupivacaine 0.125% in divided doses, and 50 μg of fentanyl through the epidural catheter, followed by the infusion described for the CSE group. All spinals and epidurals were performed with the patient in the sitting position and with sterile technique at the level of L3-L4. For spinal analgesia, a 27-G Whiteacre needle was used with clear cerebrospinal fluid confirming the position of the needle. Epidural analgesia was performed with a 16-G Tuohy needle and loss of resistance to saline technique for both groups. Monitoring of the patients during and after neuraxial analgesia conformed to institutional guidelines and recommendations.
We collected data on the patient's pain level at the time neuraxial analgesia was requested. Pain was assessed on a verbal analogue scale between 0 and 10 (0 = no pain, 10 = worst pain imaginable).
A clinically significant decrease in FHR was defined as a 30% drop from baseline HR or a FHR below 100 beats min−1 lasting for at least 60 s within the first 20 min after initiation of the neuraxial block. When decreases in FHR occurred, interventions to correct the condition included one or more of the following: administration of supplemental oxygen, a change in lateral decubitus position, crystalloid bolus (250 mL), discontinuation of exogenous oxytocin, sublingual nitroglycerine and cervical stimulation. If the fetal bradycardia continued, the anaesthesiologists were allowed to give ephedrine (5 mg) as a bolus in an attempt to increase maternal blood pressure (BP) and increase uterine blood flow. The patients were monitored with the anaesthesiologist present in the room for the duration of the observation period.
Maternal BP was measured before and at 5, 10 and 15 min post neuraxial blockade. A decrease in BP of more than 20% from baseline or a systolic BP < 90 mmHg was considered clinically significant.
Cervical dilation prior to neuraxial analgesia, parity, gestational age, maternal age and ethnicity were also recorded as well as the rate of administration of exogenous oxytocin.
Sample size was based on an expected 12% rate of decrease in FHR in the CSE analgesia group and the assumption that about half the patients would undergo CSE analgesia and half epidural analgesia. A sample size of 220 patients gives more than 80% power to detect an absolute difference of 10% between the rate of fetal bradycardia under CSE and the rate of fetal bradycardia under epidural with a two-sided 0.05 significance level.
Data are presented as mean ± SD, unless otherwise specified. Continuous variables were compared across groups (CSE vs. epidural) with t-tests or Wilcoxon signed rank sum tests according to the distribution of the variables. The χ2-tests were used for categorical variables. The occurrence of a decrease in FHR was compared between groups using a χ2-test. Univariate analyses (t-tests or Wilcoxon signed rank sum tests and χ2-tests) were performed to identify variables associated with worrisome decreases in FHR. Variables with a P value < 0.20 in univariate analyses were considered as potential predictors of the outcome in a multivariate stepwise logistic regression model. This logistic model was used to compare CSE and epidural analgesia in terms of worrisome decreases in FHR when controlling for important variables.
Analyses were performed using SAS version 8.2 and a P value < 0.05 was considered statistically significant.
The baseline characteristics of the women who received CSE and epidural analgesia are presented in Table 1. There were no differences in baseline characteristics between the groups except for the level of cervical dilatation and the pain scores that were greater in the CSE than in the epidural analgesia group (P = 0.0014 and P < 0.001, respectively). Of the 223 patients, 154 were Caucasian, 18 Black, 17 Asian, 11 Hispanic, 8 East-Indian, 8 North-African, 6 from the Middle-East and 1 Amerindian, there was no statistical difference in the distribution of Caucasian and non-Caucasian women between groups (Table 1).
Significant decreases in FHR occurred in 14 of the 223 patients (6.3%); more often with CSE analgesia (12) than with epidural analgesia (2), P = 0.0176, unadjusted OR = 5.3. In these 14 patients, FHR decreased on average from 135 ± 10 to 83 ± 12 beats min−1 (−38.5%, P < 0.0001). Manoeuvres to correct the FHR were always effective. None of the patients necessitated an emergency Caesarean section. All worrisome FHR occurred within the first 20 min post neuraxial analgesia.
Univariate analyses revealed a clear association between the analgesia techniques, maternal pain scores, maternal age and a decrease in FHR post neuraxial analgesia (Table 2). Other parameters were not significant (Table 2).
Oxytocin was not significantly associated with an increased risk of decrease in FHR post neuraxial analgesia (P = 0.3495, Table 2).
Because of the significant difference between the groups in the pain level and in the cervical dilatation, a multivariate analysis was done. This multivariate analysis identified pain scores and maternal age as independent predictors of a decrease in FHR. When considering these two variables in a logistic regression model, the difference between CSE and epidural analgesia for a decrease in FHR disappeared (P = 0.2264, adjusted OR = 2.7, Table 3).
There were no episodes of maternal hypotension in either the CSE or the epidural analgesia group (data not shown).
The present study uncovered that the level of maternal pain at the time when labour analgesia is requested, and maternal age are independent predictors of decreases in FHR post neuraxial blockade. Some important clinical implications can be extracted from these observations of the present study. The incidence of worrisome FHR post neuraxial analgesia was 6.3%, which compares favourably with literature values ranging from 5% to 17% regardless of the technique used [12,13,18,19]. Different baseline characteristics of patient populations might be the cause of this wide range. Our definition of a significant clinical decrease in FHR is not equivalent to FHR deceleration due to changes in baseline FHR variability, but includes all patients for whom an intervention for fetal bradycardia post neuraxial blockade was required, and all patients in which the decrease in FHR occurred shortly after neuraxial blockade. The fact that none of the decreases in FHR resulted in an emergency Caesarean section differentiates these events from fetal distress due to common causes of fetal hypoxaemia that almost always result in baseline change in heart rate variability and Caesarean section.
A recent study by Van de Velde and colleagues  has shown the incidence of FHR abnormalities to be as high as 11% with epidural analgesia. In the same study, high dose intrathecal opioids (7.5 μg of sufentanil) had a 24% incidence of FHR abnormalities while lower doses of (1.5 μg of sufentanil) had an equivalent rate of FHR abnormalities as epidural analgesia (12%). These results confirm that FHR abnormalities occur with both techniques but leads to the conclusion that a higher dose of intrathecal opioids is the only cause for a greater incidence of FHR abnormalities. Our study brings out other possible causes of FHR abnormalities not usually considered following neuraxial blockade for labour pain. The rate of decreases in FHR with CSE in our study was 9.76%, a value closer to the incidence of FHR abnormality associated with the lower dose of spinal opioids in other studies. The single dose of 25 μg of fentanyl in our study was kept constant to avoid the influence of opioid dosage on the incidence of FHR decreases.
One limitation of the present study is that randomization of the patients was not performed for the allocation of the epidural or the CSE for labour pain. The main reason for allowing the anaesthesiologists to choose which patient would get an epidural or a CSE for labour is that this choice may be one of the reasons why fetal bradycardia is seen post CSE for labour. The technique of CSE for labour is often selected for patients with a high level of pain or who are at a later stage in labour. The results of the present study confirm this and using this study design allowed to reflect common clinical practice and to obtain, from multivariate analysis, factors associated with fetal bradycardia that have not been documented previously.
Maternal pain levels and maternal age have not been associated with decreases in FHR post neuraxial blockade previously. By using a multivariate analysis, we were able to circumvent the initial differences in pain score and cervical dilatation between the two groups to obtain independent predictors of the decrease in FHR following neuraxial blockade for labour analgesia. The interaction between pain levels and the decrease in FHR following neuraxial blockade can theoretically be explained by high levels of plasma catecholamines in patients who have more pain and/or are at a higher degree of cervical dilation. This could predispose to fetal bradycardia through the rapid withdrawal of the sympathetic drive with pain relief using CSE analgesia. The present study, however, was not designed to elucidate the causes of FHR deceleration post neuraxial blockade, but rather, to find out what factors are associated with this phenomenon. Elevated maternal pain scores and increased incidence of fetal bradycardia post neuraxial blockade have not been linked in this context previously.
The association between maternal age and fetal bradycardia post neuraxial analgesia is interesting. We first hypothesized that older parturient might experience more pain than younger women but the multivariate analysis showed maternal age to be an independent predictor, regardless of the pain level. One postulate might be that sympathetic tone during labour is higher in older women. Unfortunately, there is no evidence in the literature at the present time to corroborate this hypothesis and further studies are needed to clarify this point.
Knowledge of risk factors such as the level of pain and maternal age can assist the anaesthesiologists in their preparation for this technique and to educate the nurses and patients on the reversibility of this phenomenon and on the very low incidence of Caesarean sections associated with these temporary decreases in FHR. Furthermore, assuming that further studies can confirm the increase in the rate of cervical dilation with CSE analgesia, if we combine this evidence with our finding of an increased risk of fetal bradycardia with high pain levels, one could argue in favour of using CSE analgesia earlier, than using it later during labour.
In summary, a multivariate analysis of the data reveals that maternal pain scores at the time of neuraxial blockade is associated with an increased incidence of fetal bradycardia independent of whether epidural or CSE analgesia was used. This analysis has also revealed that maternal age is associated with an increase in the incidence of fetal bradycardia post neuraxial blockade independent of maternal pain scores. This is, to our knowledge, the first time maternal pain scores or maternal age has been directly associated decreases in FHR post neuraxial blockade for labour analgesia. Further studies are needed to elucidate the reasons for these associations.
Supported by a grant from the Fédération de la Recherche en Santé du Québec, the Canadian Anesthesia Society, the Association des Anesthésiologistes du Québec, and the Research Institute of the McGill University Health Centre.
Presented in part at the Society of Obstetrics Anesthesia and Perinatology meeting, Florida, 2005.
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