|Year : 2014 | Volume
| Issue : 2 | Page : 69-74
A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia
PK Dilesh, S Eapen, S Kiran, Vivek Chopra
Department of Anaesthesiology and Critical Care, Command Hospital (EC), Kolkata - 700027, West Bengal, India
|Date of Web Publication||1-Nov-2014|
1681, Brahmaputra Apartments, Sector 29, Noida - 201 303, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Context: Combined spinal epidural (CSE) analgesia technique is effective for labor analgesia and various concentrations of bupivacaine and lipophilic opioids like fentanyl have been studied. Dexmedetomidine is a highly selective alpha 2 adrenoreceptor agonist with analgesic properties and has been used intrathecally with bupivacaine for prolonged postoperative analgesia. Recent reviews have shown that it is highly lipophilic and does not cross placenta significantly.
Aim: The aim of this study is to compare the duration and quality of analgesia, maternal and neonatal outcomes after CSE labor analgesia with intrathecal dexmedetomidine and intrathecal fentanyl followed by epidural bupivacaine.
Settings and Design: A randomized observational study with 112 parturients in a tertiary care hospital.
Materials and Methods: 112 parturients were randomly divided to two groups. Group D (n = 58) received dexmedetomidine 10 μg and group F (n = 54) received fentanyl 20 μg intrathecally for labor analgesia. The time of onset, time to maximum analgesia, duration and quality of analgesia were noted. Maternal parameters of heart rate, noninvasive blood pressure, motor block and side-effects of pruritus, nausea and vomiting were recorded. Neonatal outcome in terms of mode of delivery, neonatal APGAR score, time to first cry, need for resuscitation, umbilical cord blood pH, initiation of breast feeding, Neurologic and Adaptive Capacity Score at 24 h and exclusivity of breast feeding at 6 weeks were recorded.
Results: Duration of analgesia was 160.54 ± 52.4 min with dexmedetomidine and 124.1 ± 46.93 min with fentanyl (P < 0.001). Visual analog score (VAS) recorded at maximal analgesia was significantly lesser in the fentanyl group compared to dexmedetomidine group, denoting a significantly deeper level of analgesia with fentanyl. However, all the mothers in the dexmedetomidine group achieved a VAS <3 and were satisfied with the quality of analgesia. About 74% patients in the fentanyl group experienced pruritus after intrathecal injection whereas none of the mothers in dexmedetomidine group experienced pruritus (P < 0.001). There were no significant differences in neonatal outcome between the two groups.
Conclusion: 10 μg dexmedetomidine intrathecally provides a longer duration of analgesia with lesser incidence of pruritus compared to 20 μg fentanyl intrathecally for CSE labor analgesia with comparable neonatal side-effects.
Keywords: Combined spinal epidural labor analgesia, dexmedetomidine, fentanyl
|How to cite this article:|
Dilesh P K, Eapen S, Kiran S, Chopra V. A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia
. J Obstet Anaesth Crit Care 2014;4:69-74
|How to cite this URL:|
Dilesh P K, Eapen S, Kiran S, Chopra V. A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia
. J Obstet Anaesth Crit Care [serial online] 2014 [cited 2018 Dec 19];4:69-74. Available from: http://www.joacc.com/text.asp?2014/4/2/69/143875
| Introduction|| |
Labor pain is excruciating and leads to a spectrum of adverse physical and psychological stress to mother and fetus. Painful uterine contractions cause hyperventilation and high catecholamine levels resulting in maternal and fetal hypoxemia. Combined spinal epidural (CSE) analgesia is widely an accepted technique to alleviate labor pain with minimal side-effects to mother and fetus.  CSE analgesia combines the advantages of the epidural analgesia along with the rapid onset and consistency of spinal anesthesia.
Fentanyl has been used along with bupivacaine for labor analgesia extensively to decrease motor block, however the addition of opioids to local anesthetics has disadvantages of pruritus and respiratory depression.  Dexmedetomidine, a highly selective and potent alpha 2 adrenergic agonist has intrinsic analgesic properties and has been used with spinal bupivacaine to prolong postoperative analgesia.  Recent reviews of use of dexmedetomidine in pregnancy have shown that it does not cross the placenta significantly due to its high placental retention.  Several studies have used dexmedetomidine intravenously and epidurally in labor without any adverse effects on mother or fetus. ,, However, in pregnancy, dexmedetomidine intrathecally or intravenously, still remains an off label use.
The aim of this observational study was to compare the clinical efficacy of intrathecal dexmedetomidine versus the well-established intrathecal fentanyl as the initial step of CSE technique and to study their efficacy, motor block and maternal and fetal side-effects.
| Materials and mehtods|| |
A comparative prospective observational study was carried out in our tertiary care hospital on 112 parturients over a period of 1-year. Permission of the Hospital Ethical Committee was obtained before conducting the study. The expectant mothers were explained about procedure of labor analgesia and its benefits. Obstetrician concurrence was obtained for inclusion of any patient in the study. Written and informed consent after explaining the effects of drugs being used for labor analgesia was obtained from the patient for their participation in the observational study.
The patients who consented for CSE labor analgesia were divided into two groups by allocating them a random number by a computer generated table. Group 'D' received intrathecal dexmedetomidine 10 μg (in 1 ml) and the second group 'F' received intrathecal fentanyl 20 μg (in 1 ml). Maternal data was analyzed after 50 cases were completed in each group. The study continued for 6 weeks thereafter to ensure follow-up of at least 50 newborns at 6 weeks, by which time 112 cases were totally conducted. All the 112 cases were followed up for a further 6 weeks and were included for analyses of neonatal outcomes. Of the 112 newborns for neonatal analyses, 58 were in the dexmedetomidine group and 54 were in the fentanyl group.
Inclusion criteria were booked antenatal cases at term, American Society of Anesthesiologists (ASA) I and II grade parturient, uncomplicated pregnancy scheduled for normal vaginal delivery, vertex presentation not in fetal distress, singleton fetus and parturients aged between 18 and 35 years. Exclusion criteria were patient refusal, local infection, altered coagulation profile, maternal valvular heart disease, previous caesarean section, preexisting neurological disease and severe deformity of spine.
All patients included in the study received 15 ml/kg Ringer lactate solution intravenously. Baseline hemodynamic parameters heart rate, noninvasive blood pressure, pulse oximetry, respiratory rate and temperature was recorded. Stage of labor, cervical dilatation and fetal heart rate were noted. Intrathecal analgesia was administered when the patient was in active labor, having pain with uterine contractions and cervical dilatation of 3 cm to 4 cm as confirmed by the obstetrician. The baseline visual analog score (VAS) for pain recorded was between 6 and 9 for all the patients in which 0 represented no pain and 10 represented worst possible pain. After taking proper aseptic precautions, with patient in sitting position an intrathecal injection of study drug was administered using a CSE set at L3-L4 intervertebral space. The patients received either 10 μg dexmedetomidine in 01 ml normal saline or 20 μg fentanyl in 01 ml normal saline. The time of the intrathecal injection was noted and the monitoring of clinical parameters, VAS for pain and side-effects was initiated. An epidural catheter was inserted 05 cm into the epidural space using the CSE set and secured for future administration of 0.125% bupivacaine as and when required. The top-ups with 10 ml of 0.125% bupivacaine were initiated when the VAS for pain was recorded above 3. This was repeated as and when the VAS for pain was recorded above 3 till delivery of the baby.
Onset of analgesia was defined as time from intrathecal injection to time of recording a VAS less than 3 during active uterine contraction. Time to reach maximum analgesia was defined as time from intrathecal injection to time of recording the lowest VAS of either 0, 1 or 2 during active uterine contraction. VAS was recorded thereafter at every active uterine contraction. Duration of analgesia was defined as the time from intrathecal injection to the time when VAS, which had reached its lowest level, was again recorded more than 3. The first top-up of 10 ml of 0.125% bupivacaine was administered at this point of time. Repeat top-ups of the same dosage were administered as and when necessary to keep VAS less than 3 till delivery.
Maternal hemodynamic parameters of heart rate and noninvasive blood pressure were recorded every 3 min following the intrathecal injection. Parturient was examined every 3 min for any motor block and the same was recorded as per modified Bromage score. Occurrence of maternal hypotension which was defined as a fall in blood pressure more than 20% from baseline and maternal bradycardia defined as heart rate less than 60 were immediately treated with intravenous fluids, mephentermine or atropine. Fetal bradycardia was monitored by cardiotocograph and was initially treated by giving oxygen to mother and ensuring lateral position to avoid aortocaval compression. Other common maternal side effects such as pruritus, paresthesia, nausea and vomiting were noted.
Neonatal outcome in terms of mode of delivery, neonatal APGAR score, time to first cry, need for resuscitation, umbilical cord blood pH in neonates needing resuscitation were recorded. Establishment of initiation of breast feeding, Neurologic and Adaptive Capacity Score (NACS) at 24 h and exclusivity of breast feeding at 6 weeks were recorded by the pediatrician.
Data were analyzed using IBM SPSS software version 16 and Chi-square tests were applied for categorical variables and continuous variables were compared using one-way ANOVA test. Data are expressed in terms of mean ± standard deviation. P value was reported at the 95% confidence interval and P < 0.05 was considered as significant. Sample size was calculated based on literature search for variation in studied data. To calculate the sample size, a power analysis of α = 0.05 and β = 0.90, showed that 26 patients per study group were needed to detect an increase of 30 min difference in the duration of analgesia between the groups. With 50 patients in each group the power of study was 92%.
| Results|| |
There was no significant difference between the two groups with respect to maternal patient characteristics such as age, weight, parity, ASA grades, baseline VAS for pain and cervical dilatation at initiation of labor analgesia [Table 1].
Onset of analgesia was 50.4 ± 16.81 s in dexmedetomidine group and 71.7 ± 27.6 s in fentanyl group (P < 0.001). Time to reach maximum analgesia was 246.6 ± 77.45 s for dexmedetomidine and 160.8 ± 56.45 s with fentanyl (P < 0.001). Duration of analgesia was 160.54 ± 52.4 min with dexmedetomidine and 124.1 ± 46.93 min with fentanyl (P < 0.001) [Table 2]. 22 parturients out of 50 in dexmedetomidine group delivered without need for subsequent analgesia compared with 15 out of 50 in the fentanyl group.
|Table 2: Onset, time to reach maximum analgesia and duration of analgesia|
Click here to view
To assess the depth of analgesia, lowest VAS score achieved during contractions after administration of intrathecal drug were compared in both groups. In fentanyl group, VAS of 0 was achieved for 29 out of 50 patients and they were pain-free during contractions at the point of maximal analgesia. In the dexmedetomidine group, only 8 out of 50 parturients recorded a VAS of 0. VAS recorded at maximal analgesia was significantly lesser in the fentanyl group compared to dexmedetomidine group, denoting a significantly deeper level of analgesia with fentanyl compared to dexmedetomidine [Table 3].
On comparing the maternal side-effects, hypotension was noted in two patients of dexmedetomidine group and one patient of fentanyl group, which was treated with mephentermine and intravenous fluids. Bradycardia occurred in one parturient each in both groups. This difference in incidence of hypotension and bradycardia were comparable and not statistically significant (P = 0.558). All patients maintained oxygen saturations above 96% and there were no cases of respiratory depression in either group. None of the patients in the study had motor blockade in either group and a modified Bromage score of 0 was recorded in all patients till delivery. One patient in the fentanyl group experienced paresthesia compared to none in the dexmedetomidine group (P = 0.315). 37 patients out of 50 in the fentanyl group experienced pruritus after 10 min of intrathecal injection whereas none of the mothers in dexmedetomidine group experienced pruritus (P < 0.001) [Table 4]. The other side effects like shivering, nausea, vomiting, transient neurological symptoms, postdural puncture headache were not noticed in either group.
When the mode of delivery was compared among the two groups, the number of babies born by normal delivery was 51.7% in dexmedetomidine group compared to 59.3% in the fentanyl group. 3.7% babies required vacuum extraction in the fentanyl group compared to 13.8% in the dexmedetomidine group. Forceps assisted vaginal delivery was 1.7% in the dexmedetomidine group and 1.9% in the fentanyl group. Incidence of emergency lower segment caesarean section (LSCS) was 32.8% the dexmedetomidine group and 35.2% in the fentanyl group. Overall comparison of incidence of normal vaginal delivery between the two groups was comparable (P = 0.317) [Table 5].
APGAR score of the newborns were recorded at 1 min and 5 min. The mean APGAR score at 1 min was 6.97 ± 0.82 in dexmedetomidine group and 7.37 ± 0.92 in the fentanyl group. This difference was statistically significant with better APGAR scores in the fentanyl group (P = 0.046). The mean APGAR score at 5 min was 8.69 ± 0.63 in dexmedetomidine group and 8.83 ± 0.67 in the fentanyl group. This difference was not statistically significant (P = 0.480). Cord blood pH was recorded in all newborns needing any form of resuscitation. The cord blood pH was 7.3 ± 0.07 in dexmedetomidine group and 7.26 ± 0.06 in the fentanyl group, this difference was not statistically significant (P = 0.429) [Table 6].
Comparison of neonatal outcomes were performed on the two groups for need for resuscitation, time to first cry, initiation of breast feeding, NACS at 24 h and exclusivity of breast feeding at 6 weeks. 13.8% newborns needed resuscitation in the dexmedetomidine group compared with 13% in the fentanyl group. 25.9% newborns had a delayed cry in the dexmedetomidine group compared to 27.8% in the fentanyl group. There was no statistical difference between the dexmedetomidine and fentanyl groups on comparison of "time to first cry". The newborns with delayed cry did not require any active intervention and were found to be otherwise normal till they were discharged. Breast feeding could be established within first 24 h in 84.5% of newborns in the dexmedetomidine group compared to 81.5% in the fentanyl group. NACS which has been used extensively to evaluate the neurobehavior of neonates after fetal exposure to a variety of medications used in labor was recorded at 24 h. Newborns were classified as vigorous and nonvigorous based on adaptive capacity and neurologic assessment. 27.6% newborns were non-vigorous on NACS in the dexmedetomidine group compared to 35.2% in the fentanyl group. 84.5% newborns were exclusively breast fed at 6 weeks in the dexmedetomidine group compared to 83.3% in the fentanyl group. All these neonatal outcomes that were compared did not reveal any statistically significant difference between the two groups [Table 7].
| Discussion|| |
Labor analgesia has been evolved over the years to minimize motor blockade, enable walking epidurals and avoid prolongation of labor. Lipophilic opioids like fentanyl have been used extensively intrathecally and epidurally for labor analgesia along with local anesthetics. Dexmedetomidine, a selective alpha 2 adrenoreceptor agonist has been used in spinal and epidural anesthesia as an adjuvant and has several advantages of increased duration of analgesia compared to local anesthetics alone with no adverse neurological effects. , A recent meta-analysis also has shown that intrathecal dexmedetomidine prolonged the duration of spinal anesthesia and improved postoperative analgesia and did not increase the incidence of hypotension and adverse events.  Our study used a preservative free dexmedetomidine intrathecally in labor and no adverse effects of intrathecal administration on the mother or newborn were noted.
Recent review of literature has shown that dexmedetomidine has been used very sparingly for labor analgesia but however has potential uses. Most of the case reports and studies that described the use of dexmedetomidine in parturients have mentioned that babies delivered were with normal APGAR scores which proves that even if there is any uteroplacental transfer, it doesn't affect the fetal well-being. ,,, Dexmedetomidine has a high placental retention (0.77 maternal/foetal index) and does not cross placenta significantly. Being highly lipophilic like fentanyl it is retained in placental tissue.  Studies show that dexmedetomidine has high placental retention and increases the frequency and amplitude of uterine contractions directly and in a dose-dependent fashion suggesting advantages for use as an analgesic adjunct during labor. , Excellent analgesia along with absence of motor block was expected on intrathecal administration of dexmedetomidine, thus making it a suitable drug for labor analgesia. However its intrathecal use in labor remains an off label use. The dose of 10 μg used in this study was lesser than intravenous doses previously used in pregnancy and no adverse effects on the newborn were anticipated. Dexmedetomidine acts on the receptors of the substantia gelatinosa of the dorsal horn of the spinal cord which inhibit the firing of nociceptive neurons stimulated by peripheral Aδ and C fibers. It also inhibits the release of the nociceptive neurotransmitter substance P. This spinal mechanism of dexmedetomidine makes it a viable stand-alone analgesic agent when administered intrathecally. Hence we used intrathecal dexmedetomidine without bupivacaine for the initiation of labor analgesia with the CSE technique.
Doses of dexmedetomidine of 10 μg and 15 μg have been used intrathecally in studies and have shown prolongation of analgesic effects of spinal hyperbaric bupivacaine in a dose-dependent manner.  A pilot study with 5 μg and 10 μg dexmedetomidine in 1 ml normal saline administered intrathecally which was carried out at our center showed 10 μg dexemdetomidine to have satisfactory analgesia for labor. Hence a dose of 10 μg dexmedetomidine versus fentanyl 20 μg intrathecally was compared along with epidural bupivacaine for labor analgesia in this study.
The onset of analgesia with dexmedetomidine was faster than fentanyl even though the time to reach maximum analgesia was shorter for fentanyl. Depth of analgesia was better with 20 μg fentanyl compared to 10 μg dexmedetomidine with more mothers achieving a VAS of 0. However all mothers achieved a VAS <3 with dexmedetomidine and were satisfied with the quality of analgesia provided by dexmeditomidine for labor. The duration of analgesia with dexmedetomidine was significantly longer than fentanyl and more parturients did not require epidural top-ups due to the prolonged action. The results are similar to the study reported by Fyneface-Ogan et al. which compared 2.5 μg dexmedetomidine intrathecally along with 2.5 mg hyperbaric bupivacaine versus bupivacaine and fentanyl intrathecally in labor and has shown that dexmedetomidine alongwith bupivacaine intrathecally significantly prolonged sensory block in laboring women.  Pruritus was the only notable side effect with fentanyl which was absent with dexmedetomidine. The incidence of maternal bradycardia and hypotension was comparable in both groups showing that 10 μg dexmedetomidine provides good hemodynamic stability.
There was no significant difference in the rates of emergency LSCS between the two groups in our study. Nonprogress of labor was the most common cause for emergency LSCS in both groups. The emergency LSCS was performed under epidural anesthesia through the epidural catheter for all the patients.
APGAR scores were higher in the fentanyl group at 1 min but was not significantly different from dexmedetomidine group at 5 min. 5 min mean APGAR scores are more credible and have been mainly used in other studies assessing the neonatal outcomes.  Though the "need for resuscitation" was not statistically significant in both the groups, the 'time to first cry' was noticed to be longer in both the groups. A large number of the newborns in both groups had a delay in the time to first cry, defined by a time of more than 30 s without any features of birth asphyxia. There was no statistical difference between the dexmedetomidine and fentanyl groups on comparison of "time to first cry". These newborns however did not require any active intervention and were found to be otherwise normal till they were discharged. NACS was also noted at 24 h and newborns were classified as vigorous and non-vigorous. The results suggested that there was no statistically significant difference between the groups. The figures were similar to the other studies comparing NACS at 24 h in patients receiving epidural analgesia.  Successful breast feeding initiation within 24 h after birth along with early maternal infant bonding was similar in the two groups and breast feeding exclusivity at 6 weeks when analyzed showed a comparable performance in both groups suggesting that the analgesic methods used in labor did not have any effect on lactation success. 
| Conclusion|| |
10 μg dexmedetomidine is an attractive alternative to 20 μg fentanyl as an intrathecal agent for CSE labor analgesia. It provides acceptable quality of labor analgesia with increased duration of analgesia compared to fentanyl. It maintains hemodynamic stability with no adverse effects on mother and the newborn.
| Acknowledgments|| |
Department of Obstetrics and Gynecology, Command Hospital (EC), Kolkata, Department of Pediatrics, Command Hospital (EC), Kolkata.
| References|| |
Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet 1995;345:1413-6.
Gupta R, Verma R, Bogra J, Kohli M, Raman R, Kushwaha JK. A Comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to Bupivacaine. J Anaesthesiol Clin Pharmacol 2011;27:339-43.
Nair AS, Sriprakash K. Dexmedetomidine in pregnancy: Review of literature and possible use. J Obstet Anaesth Crit Care 2013;3:3-6.
Abu-Halaweh SA, Al Oweidi AK, Abu-Malooh H, Zabalawi M, Alkazaleh F, Abu-Ali H, et al.
Intravenous dexmedetomidine infusion for labour analgesia in patient with preeclampsia. Eur J Anaesthesiol 2009;26:86-7.
Palanisamy A, Klickovich RJ, Ramsay M, Ouyang DW, Tsen LC. Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet Anesth 2009;18:258-61.
Hanoura SE, Hassanin R, Singh R. Intraoperative conditions and quality of postoperative analgesia after adding dexmedetomidine to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anesthesia. Anesth Essays Res 2013;7:168-72.
Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol 2011;27:297-302.
Mahendru V, Tewari A, Katyal S, Grewal A, Singh MR, Katyal R. A comparison of intrathecal dexmedetomidine, clonidine, and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: A double blind controlled study. J Anaesthesiol Clin Pharmacol 2013;29:496-502.
Niu XY, Ding XB, Guo T, Chen MH, Fu SK, Li Q. Effects of intravenous and intrathecal dexmedetomidine in spinal anesthesia: A meta-analysis. CNS Neurosci Ther 2013;19:897-904.
Karaman S, Evren V, Firat V, Cankayali I. The effects of dexmedetomidine on spontaneous contractions of isolated gravid rat myometrium. Adv Ther 2006;23:238-43.
Sia AT, Kwek K, Yeo GS. The in vitro
effects of clonidine and dexmedetomidine on human myometrium. Int J Obstet Anesth 2005;14:104-7.
Candiotti KA, Bergese SD, Bokesch PM, Feldman MA, Wisemandle W, Bekker AY, et al.
Monitored anesthesia care with dexmedetomidine: A prospective, randomized, double-blind, multicenter trial. Anesth Analg 2010;110:47-56.
Eid HE, Shafie MA, Youssef H. Dose-related prolongation of hyperbaric bupivacaine spinal anesthesia by dexmedetomidine. Ain Shams J Anesthesiol 2011;4:83-95.
Fyneface-Ogan S, Job OG, Enyindah CE. Comparative effects of single shot intrathecal bupivacaine with dexmedetomidine and bupivacaine with fentanyl on labor outcome. ISRN Anesthesiol 2012:2012. Available from: http://www.dx.doi.org/10.5402/2012/816984.
Halpern SH, Leighton BL, Ohlsson A, Barrett JF, Rice A. Effect of epidural vs parenteral opioid analgesia on the progress of labor: A meta-analysis. JAMA 1998;280:2105-10.
Leighton BL, Halpern SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: A systematic review. Am J Obstet Gynecol 2002;186:S69-77.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]