|Year : 2017 | Volume
| Issue : 1 | Page : 230-236
Intrathecal hyperbaric bupivacaine with fentanyl for labor pain control: a comparative study with continuous epidural analgesia with bupivacaine
Mokhtar Younes1, Khaled Gamil2, Ahmed M. Elgarhy1
1 Department of Anaesthesia and Intensive Care, Faculty of Medicine, Al Azhar University, Egypt
2 Department of Anesthesiology, ICU, and Pain Relief, National Cancer Institute, Cairo University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Ahmed M. Elgarhy
14 Aboelfeda Street, Alharam, Giza
Source of Support: None, Conflict of Interest: None
Objective The aim of the study was to assess single-dose intrathecal bupivacaine in combination with fentanyl as a safe and effective alternative to epidural for labor analgesia.
Patients and methods Sixty women aged 20–30 years, of American Society of Anesthesiology I–II, and with a single uncomplicated pregnancy were included in this study. Patients were randomly allocated to two equal groups: the spinal group received hyperbaric bupivacaine 0.5% at a dose of 1 ml plus 25 μg fentanyl (0.5 ml), whereas the epidural group received bupivacaine 0.25% at a 14 ml bolus dose with a background epidural infusion of bupivacaine 0.125% at 10 ml/h. Pain intensity was recorded on a visual analogue scale. The quality of pain relief was also related to patient satisfaction after delivery. Side effects such as hypotension, motor block, pruritus, sedation, and nausea were noted. Obstetric parameters and Apgar score were noted, and all results were compared.
Results Onset of sensory block was earlier (5.6 ± 1.27 vs. 8.8 ± 1.62 min, P < 0.001) and visual analogue scale at 5, 60, 90, 120, and 150 min was lower in the spinal group compared with the epidural group. All these results were statistically signifi cant. Ninety percent of the parturients in the spinal group versus 62% in the epidural group scored the analgesic quality as excellent. No significant hemodynamic changes were recorded in either group. There were no significant differences between the two groups in motor block, sedation, and nausea. No cesarean section or instrumental delivery was performed. Oxytocin augmentation was needed in 33.3 versus 50% of the parturients in the spinal and epidural groups, respectively. Fetal heart rate disturbances were seen in 10% in the epidural group versus 6.6% in the spinal group. Apgar scores were high and no neonate had Apgar score less than 7 in either group. The overall cost was lower in the spinal group compared with the epidural group.
Single-dose intrathecal local anesthetic with narcotics is shown to relieve pain safely in most laboring women, with rapid onset and prolonged duration of labor analgesia comparable to that of epidural analgesia while being more easily performed, less time-consuming, and less expensive, and providing similarly excellent analgesia.
Keywords: bupivacaine, fentanyl, labor analgesia
|How to cite this article:|
Younes M, Gamil K, Elgarhy AM. Intrathecal hyperbaric bupivacaine with fentanyl for labor pain control: a comparative study with continuous epidural analgesia with bupivacaine. Ain-Shams J Anaesthesiol 2017;10:230-6
|How to cite this URL:|
Younes M, Gamil K, Elgarhy AM. Intrathecal hyperbaric bupivacaine with fentanyl for labor pain control: a comparative study with continuous epidural analgesia with bupivacaine. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2020 Feb 21];10:230-6. Available from: http://www.asja.eg.net/text.asp?2017/10/1/230/238463
| Introduction|| |
Labor pain is so agonizing that it can lead to severe physical and psychological stress in both the mother and the fetus. Labor pain and painful uterine contractions cause hyperventilation and high catecholamine levels resulting in maternal and fetal hypoxemia .
Epidural analgesia (EA) has been extensively used to provide pain relief in labor. Epidural bupivacaine is still the most widely used local anesthetic in obstetric analgesia . Its hyperbaric form is prepared by the addition of dextrose. It controls pain at the nerve level by interfering with the nerve membrane potential. It physically blocks the sodium channel by reversibly binding to receptors on the intracellular side of the membrane, while the sodium channel is inactive. An action potential cannot form and nerve impulse conduction cannot occur across the nerve membrane and up to the brain. The result of this is loss of sensation or numbness in the area where the drug is given .
However, its potential for motor blockade and central nervous system and cardiac toxicity by accidental intravenous injection of a high dose is clinically undesirable, especially for obstetric patients . In addition, to minimize unwanted motor block, use of lower concentrations of local anesthetics combined with opioids has been followed in many clinical trials with good results ,,.
Fentanyl has been widely used as an analgesic adjuvant to EA and it acts on substantia gelatinosa in the dorsal horn of the spinal cord by blocking fibers carrying nociceptive impulses both presynaptically and postsynaptically . However, the addition of opioids to local anesthetics has the disadvantages of causing pruritus and respiratory depression, which are difficult to be prevented by prophylactic medications .
This prospective, randomized, double-blind comparative study is designed to assess the usage of single-dose intrathecal hyperbaric bupivacaine in combination with fentanyl as an alternative to epidural for labor analgesia.
| Patients and methods|| |
A prospective comparative study was conducted in the Department of Obstetrics and Gynecology, Fakhry Hospital, from September 2014 to March 2015. Following the local Ethics Committee approval, written consent was taken from the patients. Healthy parturients in the first stage of labor with a cervical dilatation greater than 4 cm were taken to the operating room and randomly allocated – using a computer-generated random sequence – into two groups (30 patients each): the spinal group and the epidural group. Patients with systemic diseases such as diabetes, hypertension, and ischemic heart disease, or with obstetric complications such as multiple pregnancy, premature labor, abnormal presentation, or preeclampsia, or with contraindications to regional analgesia were excluded from this study.
Upon patient request for labor analgesia during active labor with cervical dilation between 4 and 5 cm and normal fetal heart rate (FHR), and under completely aseptic conditions, blocks were performed with the patient in the sitting position. Patients in the spinal group received spinal block with a 25-G standard needle (IDA Business and Technology Park, Athlone, Ireland) that was inserted and directed to the middle line to reach the intrathecal space between L3 and L4 or the L4 and L5 intervertebral space after a successful dural puncture with acceptable cerebrospinal fluid flow using 1 ml (5 mg) of hyperbaric bupivacaine 0.5% [heavy bupivacaine is available as a 5 ml vial 0.5% (5 mg/ml); its trade name is MARCA, Giza, Egypt)] plus 25 μg fentanyl (0.5 ml).
Intheepiduralgroup, EAwasinducedwithan18-GTuohy epidural needle (Tuohy catheter, prefix set for continuous epidural anesthesia; B-Braun Medical Inc., D 34209, Melsungen, Germany) using loss-of-resistance-to-air technique. Upon feeling good loss of resistance, an epidural catheter was introduced cranially through the needle for 2–4 cm in the L3–L4 or L4–L5 epidural space. After negative aspiration for blood or spinal fluid a test dose of 3 ml lidocaine was given through the inserted catheter, with the patient in the same position. A bolus dose of 14-ml bupivacaine (0.25%) with background epidural infusion of bupivacaine (0.125%) at 10 ml/h was started. Bupivacaine was available as a 20 ml vial 0.5% (Bucain; Astra Zeneca, Sweden).
After the administration of the anesthetic solution, each patient was evaluated every 5 min for the first 15 min. Further assessment was done every 15 min until additional analgesia was requested. Patient assessment included vital signs such as blood pressure, heart rate (HR), and respiratory rate.
Fetal heart rate and uterine activity monitoring
FHR was continuously monitored during labor. Normal FHR tracing was identified as baseline rate between 110 and 160 beats per minute (bpm), moderate variability (6–25bpm), presenceofaccelerations, andnodecelerations. Uterine activity was also monitored simultaneously: contraction frequency, duration, amplitude, and relaxation time must also be normal. Abnormal baseline HR above 160 bpm for 10 min or more is termed tachy cardia and that below 110 bpm as bradycardia.
Patients pain was assessed with a 10-cm linear visual analogue scale (VAS), where 0 represented no pain and 10 represented most severe pain. Pain scores were determined just before epidural placement and 5, 20, 40, 60, 90, 120, and 150 min after epidural injection. When VAS was greater than and equal to 4, a second dose of the local anesthetic was given; those patients for whom the second dose of the local anesthetic had to be given within 150 min of the study protocol were excluded from the study.
Assessment of the onset and level of sensory block (time from IT replaced by intrathecal or epidural injection until sensory loss) was made by pin prick. Grading of motor block was done as per the modified Bromage scale , which is as follows: grade 0, no motor block; grade 1, inability to raise the extended leg, able to move knees and feet; grade 2, inability to raise the extended leg and move the knee, but able to move the feet; grade 3, complete motor block of the lower limbs. Patients were monitored for the presence of other side effects such as pruritus, sedation, nausea, and vomiting.
All parturients in the two groups received oxytocin infusion at a dose of 5 U in 500 ml glucose 5% when the cervix reach 8 cm according to guidelines set by the obstetrical management team. Also the decision to proceed to operative delivery was made by the team according to maternal or fetal indications. The number of parturients who needed instrumental delivery or cesarean section was recorded. The fetus was assessed 1 and 5 min after delivery by Apgar score.
Postdelivery ambulation was assessed by the ability of the parturient to stand and walk alone without support.
Sample size calculation was based on previous studies. We calculated that a sample of 30 patients in each group was sufficient to give α = 0.05 with confidence interval 95% and actual power 90% and β = 0.10, when onset of sensory block and analgesia were compared between the two groups using computer software (G∗Power, version 22.214.171.124).
Data were analyzed using IBM SPSS advanced statistics (version 20.0; SPSS Inc., Chicago, Illinois, USA). Numerical data were expressed as mean ± SD or as median and range as appropriate. Qualitative data were expressed as frequency and percentage. The χ2 test (Fisher's exact test) was used to examine the relationship between qualitative variables. For quantitative data, comparison between the two groups was made using the unpaired Student t-test. Nonparametric variables were compared using the Kruskall–Wallis and Mann–Whitney tests. A P value less than 0.05 was considered significant.
| Results|| |
The present study is a randomized, double-blind, comparative study between intrathecal combination of hyperbaric bupivacaine with fentanyl and epidural for labor analgesia. The distribution of patients according to mean age, height, weight, and gestational age with SD was determined. The two groups were matched in terms of age, height, and weight. There was no significant difference between the two groups as regards patient demographics and gestational age. There was no significant difference between the two groups as regards cervical dilatation. The duration of the first and second stages of labor in the spinal group was shorter than that in the epidural group. Ninety percent of parturients in the spinal group versus 60% in the epidural group were satisfied by the analgesic quality ([Table 1]).
The mean onset of analgesic effect was significantly earlier in the spinal group (5.6 ± 1.27 min) compared with the epidural group (8.8 ± 1.62 min) (P < 0.01), whereas there was no significant difference between the two groups in sensory level. Maximum modified Bromage scores were comparable in the two groups. No cases showed Bromage scores more than 2 in either group ([Table 2]).
The incidences of nausea and vomiting were highest in the epidural group than in the spinal group with no significant difference between them, whereas pruritus was significantly higher in the spinal group compared with the epidural group (P < 0.05). Incidence of respiratory depression was nil in both groups. Oxytocin augmentation was needed in 33.3 versus 50% of the parturients in the spinal and epidural groups, respectively. Nonsignificant difference was seen in FHR (>160 or <100/min) and Apgar score between the two groups. Fetal distress that occurred (two and three cases in the spinal and epidural groups, respectively) did not need emergency interference as FHR became reassuring within a short period of time (<1 min). Apgar scores were high and no neonate had Apgar score less than 7 in either group ([Table 3]).
The mean VAS score was comparable in the two groups at baseline (T0), T20, and T40 (P > 0.05). At T5 and from T60 to T150 there was a significant decrease in mean arterial pressure in the spinal group compared with the epidural group (P < 0.05) ([Figure 1] and [Table 4]).
|Figure 1 Visual analogue scale (VAS) pain scores over the study period in the two studied groups. Data are presented as median. ∗P < 0.05, statistically significant.|
Click here to view
Mean arterial pressure and HR showed a nonsignificant decrease in the spinal group compared with the epidural group ([Figure 2] and [Figure 3]).
|Figure 3 Maternal mean arterial pressure (MAP) during the study period in the two studied groups.|
Click here to view
| Discussion|| |
Labor EA is a technique for pain relief in a parturient that is being increasingly used widely. EA was acknowledged as the most effective pain management technique as compared with inhaled analgesia, systemic opioid and nonopioid analgesics, and nonpharmacologic interventions . It enables us to achieve high maternal satisfaction rates with regard to pain management, sense of control in labor, and overall childbirth experience .
A small dose of hyperbaric bupivacaine produces a short-lasting spinal anesthesia, which may be clinically useful in ambulatory surgical procedures. It also reduces the risk for transient neurologic symptoms .
In our study we used single-dose spinal analgesia as a safe and effective alternative to EA for labor pain. The results of the current study indicated good patient satisfaction and early postdelivery ambulation by using a single-dose intrathecal local anesthetic with narcotics.
Leighton et al.  studied the effect of intrathecal fentanyl and morphine in labor analgesia. All of the participating nulliparous women said that they were satisfied with their analgesia and would like to receive intrathecal analgesia during future labor.
The findings of Herpolsheimer and Schretenthaler  in their study on multiparous patients support ours, as the parturients preferred intrathecal narcotic (ITN) analgesia to the epidural anesthesia they had received during previous labors. Other studies conducted by Zapp and Thorne  reported a high level of patient satisfaction with ITN.
However, in the study by Wong et al.  conducted to investigate the efficacy of analgesia and maternal side effects on the basis of the dose response of intrathecal sufentanil added to bupivacaine for labor analgesia, 170 parous women with cervical dilation between 3 and 5 cm were randomized to receive intrathecal 0 (control), 2.5, 5, 7.5, or 10 μg sufentanil combined with 2.5 mg bupivacaine, followed by a lidocaine epidural test dose, for initiation of analgesia (34 patients in each group). Visual analogue scores and the presence of nausea, vomiting, and pruritus were determined every 15 min until the patient requested additional analgesia. FHR tracings were compared between groups: Intrathecal bupivacaine (2.5 mg) without sufentanil did not provide satisfactory analgesia in parous patients. However, bupivacaine combined with 2.5 μg sufentanil provided analgesia comparable to that of higher doses, with a lower incidence of nausea and vomiting and less severe pruritus.
In contrast to the current study, 82 women with uncomplicated full-term pregnancies were enrolled upon analgesia request during spontaneous labor with cervical dilation 3 to 7 cm. Sixty-three chose ITNs (morphine and fentanyl), and 19 chose EA. ITNs provided excellent analgesia for a subgroup of women who delivered within 2–3 h of receiving them. Although women in both groups were satisfied with their pain management, women receiving ITNs had statistically lower overall satisfaction scores .
The results of this study found that the VAS changes across all measuring intervals were always significant in the spinal group compared with the epidural group. Bucklin et al.  investigated the efficacy of analgesia and obstetric outcome using single-injection intrathecal opioids versus that using epidural local anesthetics. Combined test results indicated comparable analgesic efficacy 15–20 min after injection when using single-injection intrathecal opioid.
In another study, ITNs were associated with significantly higher pain scores compared with EA during the first and second stages of labor and on an overall postpartum rating .
As regards the sensory level and onset of sensory block (time from intrathecal or epidural injection until sensory block) there was no significant difference between the spinal and epidural group. But the onset of sensory block was significantly earlier in the spinal group compared with the epidural group.
Buvanendran et al.  investigated the efficacy of intrathecal bupivacaine in reducing pruritus and prolonging the duration of fentanyl analgesia during labor. This combination resulted in rapid onset and prolonged duration of labor analgesia compared with either drug alone.
Palmer et al.  proved that early-onset and beneficial analgesic effects and a lack of significant maternal and neonatal side effects occurred with addition of 2.5 mg isobaric bupivacaine to 25 μg fentanyl for intrathecal labor analgesia compared with plain intrathecal fentanyl.
As regards the maternal side effects in the current study, there was no significant difference between the two groups as regards nausea, vomiting, and sedation. The occurrence of pruritus in parturients who received intrathecal local anesthetics with narcotics can be explainedbytheeffectof ITNs. Bucklin et al. proved that intrathecal opioid injections were associated with a greater incidence of pruritus using single-injection intrathecal opioids versus epidural local anesthetics in labor analgesia.
Also Buvanendran et al.  investigated the efficacy of intrathecal bupivacaine to reduce pruritus and prolong the duration of fentanyl analgesia during labor: in a study conducted on 65 laboring parturients, it was proven that bupivacaine 2.5 mg when administered intrathecally with fentanyl 25 μg in laboring parturients attenuates the frequency of pruritus on all parts of the body except the face.
Leighton and Halpern  proved that there was no difference in the incidence of nausea, vomiting, and sedation between epidural and intrathecal analgesia. Also in agreement with the current study, Bucklin et al.  proved that there was no difference in the incidence of nausea, vomiting, and sedation between epidural and intrathecal modalities in labor analgesia.
Bucklin et al.  in their study comparing single-injection intrathecal opioids with epidural local anesthetics found no significant difference in the method of delivery between the two.
The current study demonstrated that there were no significant FHR changes between intrathecal and epidural groups.
Palmer et al.  proved that there were no significant FHR changes reported with the addition of 2.5 mg isobaric bupivacaine to 25 μg fentanyl for intrathecal labor analgesia compared with plain intrathecal fentanyl.
Also, Capogna  proved that EA in the absence of maternal hypotension or uterine hypertonus causes minimal change in FHR and described these changes as transient and not necessarily resulting in maternal or fetal morbidity.
The results of this study did not show any hemodynamic changes between the two groups. This finding agrees with the study done by El-Kerdawy and Farouk , who proved that both, parturients receiving EA alone and parturients receiving remifentanil intravenous patient-controlled analgesia alone, were comparable with respect to maternal hemodynamics in terms of systolic blood pressure and HR.
Palmer et al.  demonstrated no change in maternal blood pressure with the addition of 2.5 mg isobaric bupivacaine to 25 μg fentanyl for intrathecal labor analgesia compared with plain intrathecal fentanyl.
In contrast to the current study, van der Vyver et al.  demonstrated that maternal hypotension occurred in less than 3% of cases in their study comparing epidural bupivacaine patient-controlled analgesia with epidural bupivacaine continuous infusion for labor analgesia.
The current study demonstrated that newborns in the two groups had normal Apgar score at 1 and 5 min. This finding agrees with that of El-Kerdawy and Farouk , who proved that neither EA nor remifentanil had an effect on the Apgar score of newborns.
In agreement with the current study Reynolds et al. proved that EA is associated with improved neonatal acid base status suggesting that placental exchange is well preserved and maternal hypotension should be avoided.
| Conclusion|| |
On the basis of the results of our study we concluded that single-dose intrathecal local anesthetic with narcotics relieves pain safely in most laboring women, who report being highly satisfied with this method of pain control. This combination also results in a rapid onset and prolonged duration of labor analgesia. Spinal anesthesia compared with epidural is easier to perform, less time-consuming, and less expensive, and provides better analgesia.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dilesh PK, 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. [Full text]
Selim MF, Elnabtity AM, Hasan AM. Comparative evaluation of epidural bupivacaine–dexmedetomidine and bupivacaine -fentanyl on Doppler velocimetry of uterine and umbilical arteries during labor. J Prenat Med 2012; 6:47–54.
Makwana JC, Shivraj TN, Khade A, Bansal S, Mandal N, Goswami S, et al.
Comparison between hyperbaric bupivacaine and hyperbaric bupivacaine plus fentanyl intrathecally in major gynecological surgeries. Int J Med Sci Public Health 2014; 3:319–323.
Wang LZ, Chang XY, Liu X, Hu XX, Tang BL. Comparison of bupivacaine, ropivacaine and levobupivacaine with sufentanil for patient-controlled epidural analgesia during labor: a randomized clinical trial. Chin Med J (Engl) 2010; 123:178–183.
Fischer C, Blanié P, Jaouën E, Vayssière C, Kaloul I, Coltat JC. Ropivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison. Anesthesiology 2000; 92:1588–1593.
Owen MD, Thomas JA, Smith T, Harris LC, D’Angelo R. Ropivacaine 0.075% and bupivacaine 0.075% with fentanyl 2 microg/mL are equivalent for labor epidural analgesia. Anesth Analg 2002; 94:179–183, table of contents.
Fernández-Guisasola J, Serrano ML, Cobo B, Muñoz L, Plaza A, Trigo C, Del Valle SG A comparison of 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with fentanyl for continuous epidural labor analgesia. Anesth Analg 2001; 92:1261–1265.
El-Feky EM, Abd El Aziz AA. Fentanyl, dexmedetomidine, dexamethasone as adjuvant to local anesthetics in caudal analgesia in pediatrics: a comparative study. Egypt J Anaesth 2014; 30:1–6.
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; 27:339–343.
Graham AC, McClure JH. Quantitative assessment of motor block in labouring women receiving epidural analgesia. Anaesthesia 2001; 56:470–476.
Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al
. Pain management for women in labour: an overview of systematic reviews. Cochrane Database Syst Rev 2012; 14:CD009234.
Rimaitis K, Klimenko O, Rimaitis M, Morkūnaitė A, Macas A. Labor epidural analgesia and the incidence of instrumental assisted delivery. Medicina (Kaunas) 2015; 51:76–80
Keld DB, Hein L, Dalgaard M, Krogh L, Rodt SA. The incidence of transient neurologic symptoms (TNS) after spinal anaesthesia in patients undergoing surgery in the supine position: hyperbaric lidocaine 5% versus hyperbaric bupivacaine 05%. Acta Anaesthesiol Scand 2000; 44:285–290.
Leighton BL, DeSimone CA, Norris MC, Ben-David B. Intrathecal narcotics for labor revisited: the combination of fentanyl and morphine intrathecally provides rapid onset of profound, prolonged analgesia. Anesth Analg 1989; 69:122–125.
Herpolsheimer A, Schretenthaler J. The use of intrapartum intrathecal narcotic analgesia in a community-based hospital. Obstet Gynecol 1994; 84:931–936.
Zapp J, Thorne T. Comfortable labor with intrathecal narcotics. Mil Med 1995; 160:217–219.
Wong CA, Scavone BM, Loffredi M, Wang WY, Peaceman AM, Ganchiff JN. The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia. Anesthesiology 2000; 92:1553–1558.
Fontaine P, Adam P, Svendsen KH. Should intrathecal narcotics be used as a sole labor analgesic? A prospective comparison of spinal opioids and epidural bupivacaine. J Fam Pract. 2002; 51:630–635.
Bucklin BA, Chestnut DH, Hawkins JL. Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis. Reg Anesth Pain Med 2002; 2723–30.
Buvanendran A, Newman LM, McCarthy RJ, Ivankovich AD, Tuman KJ. Intrathecal bupivacaine reduces purities and prolongs duration of fentanyl analgesia during labor: a prospective randomized controlled trial anesthesia and analgesia. Anesth Analg 1998; 87:1309–1315.
Palmer CM, van Maren G, Nogami WM, Alves D. Bupivacaine augments intrathecal fentanyl for labor analgesia. Anesthesiology 1999; 91:84–89.
Leighton BL, Halpern SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: a systematic review. Am J Obstet Gynecol 2002; 186 (5 Suppl Nature):S69–S77.
Capogna G. Effect of epidural analgesia on fetal heart rate. Eur J Obstet Gynecol Reprod Biol 2001; 98:160–164.
El-Kerdawy H, Farouk A. Labor analgesia in preeclampsia: remifentanil patient controlled intravenous analgesia versus epidural analgesia. Middle East J Anaesthesiol 2010; 20539–545.
Van der Vyver M, Halpern S, Joseph G. Patient-controlled epidural analgesia versus continuous infusion for labour analgesia: a meta-analysis. Br J Anaesth 2002; 89:459–465.
Reynolds F, Sharma KS, Paul TS. Analgesia in labor and fetal acid-base balance: a meta analysis comparing epidural with systemic opioid analgesia. BJOG 2002; 109:1344–1353.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]