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Anesth Analg 2003;97:873-877 © 2003 International Anesthesia Research Society
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Abstract |
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We investigated the effect of sequential administration of intrathecal (IT) hyperbaric bupivacaine (after the initial administration of IT hypobaric fentanyl) on the duration of spinal analgesia. Thirty-seven nulliparous parturients with a cervical dilation
5 cm were randomized to receive either IT fentanyl 25 µg and plain bupivacaine 2.5 mg (group P; n = 19) or IT fentanyl 25 µg and hyperbaric (with 8% glucose) bupivacaine 2.5 mg (group H; n = 18). The two components of the IT injectate were administered sequentially (fentanyl 25 µg diluted in 2 mL of normal saline, immediately followed by 0.5 mL of 0.5% bupivacaine). Patients were then positioned with their torso elevated at 30° for 30 min. Pain scores using 0–100 visual analog scales were collected before combined spinal/epidural analgesia and at 5, 15, and 30 min after the block. Patients in Group H had a longer median duration of analgesia (122 min; range, 80–210 min) than Group P (95 min; range, 75–125 min) (P < 0.01). Group H also had a more limited dermatomal spread (median highest sensory level of T8 versus T4 in group P; P < 0.05). The side-effect profile was similar. Under these circumstances, hyperbaric bupivacaine conferred an increased duration of IT analgesia compared with plain bupivacaine. IMPLICATIONS: For late labor pain, the effect of intraspinal injection of bupivacaine with a higher density than cerebral spinal fluid lasts longer than a similar dose of bupivacaine with a lower density. There were no additional side effects with this technique.
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Introduction |
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The use of intrathecal (IT) fentanyl and plain bupivacaine is well established as the initial component of the combined spinal/epidural (CSE) modality for labor analgesia (1,2). Various IT combinations have been attempted in pursuit of the optimal intrapartum analgesia. The small-dose, multimodal approach appears to be in vogue, as witnessed by the shrinking dose of IT lipophilic opioids plus local anesthetic combination over the years (3–5), juxtaposed against the backdrop of adding IT epinephrine (6), clonidine (7), and even neostigmine (8) in an attempt to prolong the duration of analgesia.
Pain in the early first stage of labor is primarily mediated by visceral afferent nerves. As labor progresses and the cervix dilates further, perineal pain becomes prominent because of the pressure asserted by the descending fetus. In this study, we evaluated the viability of accomplishing "dissociative" spinal analgesia by a sequential subarachnoid block (induced with the parturients in the upright position) with two drugs of different baricities, namely, IT fentanyl 25 µg diluted in normal saline (therefore, hypobaric to the cerebral spinal fluid) (9) to achieve a suprasacral analgesia to address the visceral component of labor pain, followed by IT hyperbaric bupivacaine 2.5 mg to obtain a sacral block. We hypothesized that with CSE performed with our novel sequential technique on parturients sitting upright, hyperbaric bupivacaine would pool to the dependent area and achieve maximal analgesic effects on the sacral nerve roots, thus prolonging the duration of effective spinal analgesia.
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Methods |
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We conducted a prospective, randomized, double-blinded, controlled study (with hospital ethics committee approval) comprising 40 ASA physical status I and II nulliparous parturients in labor with a cervical dilation
5 cm who had given written, informed consent for CSE analgesia. Exclusion criteria were cervical dilation 
4 cm, chronological age >45 yr, medical conditions such as bleeding dyscrasias, the presence of any obstetric complications (such as pregnancy-induced hypertension, multiple pregnancy, preterm labor, or abnormal lie), and the administration of intramuscular meperidine <2 h before CSE. On request for labor analgesia, parturients were randomized by sealed envelope assignment into two groups: group P (control group) and group H (study group). Those in group P received IT fentanyl 25 µg (David Bull Lab, Australia) and plain bupivacaine 2.5 mg (0.5 mL of 0.5%) (AstraZeneca, Sweden), whereas parturients in group H received IT fentanyl 25 µg and hyperbaric bupivacaine 2.5 mg (0.5 mL of 0.5% bupivacaine with 8% glucose; AstraZeneca).
IV access was established, and each parturient was prehydrated with 1000 mL of IV Hartman’s solution. The parturients were then placed with the their torsos resting comfortably on the top half (head) of the bed, which had been elevated 30° over the horizontal lower half. The following baseline variables were then obtained: preblock pain scores (on a 100-point visual analog scale (VAS): 0 = no pain and 100 = worst pain imaginable pain), blood pressure (measured with a right brachial noninvasive cuff: Dinamap; Critikon, Tampa, FL), and baseline fetal heart tracing. The concurrent use of oxytocin was also noted.
CSE was performed by the principal investigator (WHLT) with parturients in the sitting position at the L3-4 level with a 17-gauge Weiss epidural needle. The epidural space was identified by using the loss of resistance to air technique, followed by dural puncture with a 120-mm 27-gauge Whitacre spinal needle (Durasafe; BD). The epidural needle served as the introducer for the spinal needle. Correct placement of the tip in the subarachnoid space was confirmed with free flow of cerebrospinal fluid.
Parturients then received IT fentanyl 25 µg (diluted into 2 mL with normal saline in a 3-mL luerslip syringe; BD) over 20 s, followed immediately by 0.5 mL of 0.5% plain or hyperbaric bupivacaine (injected over 5 s in a 1-mL luerslip syringe), depending on the study group to which they had been assigned. Both drugs were administered sequentially with the orifices of the spinal needles facing cephalad. The solutions were prepared by the other investigator, who was not involved in the assessment of the parturient after CSE had been instituted.
After the administration of the IT component, the epidural catheter was inserted 3–4 cm into the epidural space. After a negative aspiration test for blood, the epidural catheter was flushed with 1 mL of isotonic sodium chloride solution. No test dose was given epidurally. The patient was then placed with her torso elevated at 30° for 30 min after the subarachnoid administration to minimize cephalad spread of hyperbaric bupivacaine.
During the first 30 min after CSE, the parturients were assessed on the following variables at Time 0 (time at the start of IT injection) and at 5, 15, and 30 min:
- Blood pressure.
- Pain scores.
- Highest sensory block to cold (ice pack).
- Maximal degree of motor block in the lower limbs, based on the modified Bromage scale (0 = no impairment; 1 = unable to raise the extended leg but able to move knees and feet; 2 = unable to raise extended leg or flex knees, but able to move foot; 3 = not able to flex ankle, feet, or knees; complete block). A Bromage score of 0 was ensured before CSE.
- Shivering, pruritus, nausea, and vomiting. These were noted as either present or absent.
Hypotension (defined as a reduction of systolic blood pressure >20% of baseline) was promptly treated with boluses of ephedrine 6 mg IV. Nausea and vomiting were treated with metoclopramide 10 mg IV only on patient request.
The duration from the time of injection to the time when the parturient began to experience the onset of pain again, as determined by the request for further analgesia, was noted. This indicated the end point of the study. The epidural catheter was then used for further analgesia.
Fetal heart rate was monitored continuously. All the fetal cardiotocograms were confirmed to be normal (reactive) by the on-call obstetrician (who was not involved in the study) before labor analgesia was instituted. Abnormal cardiotocograms were treated with the appropriate obstetric intervention. The following data were also collected for each group: the mode of delivery and the number of parturients who delivered before requiring any supplemental analgesia.
The number of subjects in each group (n = 20) was determined by prospective power analysis based on our earlier study (4) to detect a clinically significant difference of 30 min in the duration of analgesia between the two study groups (ß = 0.2; 
= 0.05). The following tests were used to compare the data between the two groups: Student’s t-test for demographic data and baseline blood pressures; Wilcoxon’s ranked sum test (Mann-Whitney U-test) for cervical dilation before CSE administration, pain scores, extent of sensory block, and time to request of first top-up analgesia; Fisher’s exact test for the incidence of hypotension, nausea, vomiting, shivering, pruritus, and sedation, Bromage scores, and other categorical data; the Kaplan-Meier technique and log-rank test for analysis of the duration of analgesia, taking parturients who delivered before requiring any top-up analgesia into account; and repeated-measures analysis of variance for changes in pain scores.
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Results |
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Thirty-seven patients completed the study (18 in group H and 19 in group P). Three parturients were excluded because of breach of protocol: 1) failure to place one patient in the 30° head-up position for the first 30 min (the catheter had to be resited because of inadvertent venous puncture), 2) incomplete data collection (this was also complicated by an accidental venous catheterization), and 3) refusal to cooperate with data collection (one patient opted instead for solitude and rest after attaining rapid pain relief).
Patient demographics were comparable in terms of age, weight, and height. No significant difference was noted in the baseline values of systolic blood pressure, pain scores, or cervical dilation (Table 1). More patients in the plain bupivacaine group (9 of 19 versus 2 of 18 in the other group; P < 0.05) were receiving an oxytocin infusion at the point of CSE induction. All fetal heart rates were normal/reactive before CSE was instituted. Two patients in group H and four patients in group P delivered before loss of spinal analgesia (P = 0.66).
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Parturients in group H who received IT hyperbaric bupivacaine had a significantly longer duration of effective spinal analgesia (122.5 min; range, 80–210 min) versus group P (95.0 min; range, 75–125 min; P < 0.01) (Fig. 1). The duration of analgesia is defined as the duration from the IT injection to the time when the parturient first complained of pain due to the loss of spinal analgesia. This excluded the two patients in group H and the four patients in group P who had delivered. Application of survival analysis, which included data from patients who delivered before loss of spinal analgesia (hence removing the potential bias of excluding parturients who had delivered before the loss of analgesia), again confirmed that group H parturients had a significantly longer duration to first analgesia request after CSE (P < 0.05).
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There was a more limited dermatomal spread in group H (Fig. 2). There was no significant difference in the incidence of side effects between the two groups (Table 2). Pruritus occurred in most patients in both groups but was self-limiting and required no intervention. Only one patient in Group H had weakness in leg raising 5 min after CSE was administered, but this resolved within 30 min. No one experienced respiratory depression, defined as a respiratory rate <8 breaths/min or observation of shallow, irregular respiration (or both).
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The reduction in VAS pain scores over 30 min after the administration of CSE was not significantly different between the two groups (Fig. 3). At the time of first request for analgesia, there appeared to be a trend toward group H patients experiencing less pain (median pain score, 60 versus 80 in Group P; P = 0.05). Although technically not statistically significant, this could be indicative of a less precipitous perception of breakthrough pain in Group H.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Our study showed that in comparison with plain (marginally hypobaric) bupivacaine (9), the use of the hyperbaric preparation with parturients in a head-up position in late labor confers the advantage of prolonging the duration of analgesia despite the same mass of local anesthetic used. We used a dose of hyperbaric bupivacaine (2.5 mg) in combination with IT fentanyl 25 µg in this study because our earlier investigation showed that at a dose of 1.25 mg, hyperbaric bupivacaine failed to confer an advantage in prolonging the analgesia rendered by IT fentanyl (10).
In an attempt to preserve the effects due to the different baricities of the two drugs, we devised this technique to administer the two spinal injectates sequentially so as not to hinder the cephalad spread of fentanyl. An earlier study demonstrated the relative ineffectiveness of a hyperbaric opioid solution (11). Because the IT fentanyl in our study was hypobaric, it could be argued that with parturients remaining in a 30° head-up position, the effect of IT fentanyl providing suprasacral (thoracolumbar) analgesia and the "pooling" of the local anesthetic in the dependent area providing sacral analgesia had a desirable effect on the duration of pain relief.
The effect of hyperbaricity of IT administered local anesthetic in prolonging the duration of analgesia was similarly demonstrated in postoperative orthopedic patients by Kooger Infante et al. (12). They showed that for an identical mass of IT bupivacaine, a greater spread of the block resulted in a more expeditious elimination of the local anesthetic secondary to its increased exposure to the meninges and blood vessels. Therefore, with a greater cephalad spread, the duration of analgesia was shortened. Our study also demonstrates that a more limited dermatomal spread in the hyperbaric bupivacaine group corresponded to a prolonged spinal analgesia. The role of our current regimen in early labor or in parturients who do not remain in a 30° head-up position needs further investigation.
In our study, more patients who received IT plain bupivacaine were receiving oxytocin at the point of the induction of CSE. It may be argued that the need to augment contractions in these parturients already signifies dysfunctional and possibly more painful labor. However, the management of labor was not standardized and was left to the attending obstetrician. The similarity of the baseline pain scores before the induction of analgesia indicated that the use of oxytocin did not influence preblock pain. Similarly, there was no difference in the mode of delivery between the two study groups, despite the disparity in the use of oxytocin at the start of the study. Further analysis of our data also revealed that irrespective of the IT local anesthetic used, parturients who had received preblock oxytocin did not have a shorter duration of analgesia (mean, 101 minutes; SD, 24 minutes) than those who had had oxytocin (mean, 120 minutes; SD, 33 minutes; P = 0.1). Admittedly, our sample size was small, and more research needs to be done in this regard.
We conclude that under the circumstances of the study, IT hyperbaric bupivacaine 2.5 mg after fentanyl 25 µg resulted in a block with a lesser degree of dermatomal spread compared with plain bupivacaine. Under these circumstances, hyperbaric bupivacaine may confer an increased duration of analgesia compared with plain bupivacaine.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Palmer C, Cork RC, Hays R, et al. The dose-response relation of intrathecal fentanyl for labor analgesia. Anesthesiology 1998; 88: 355–61.[Web of Science][Medline]
- Collis RE, Davies DWL, Aveling W. Randomized comparison of combined spinal-epidural and standard epidural analgesia in labor. Lancet 1995; 345: 1413–6.[Web of Science][Medline]
- Campbell DC, Camann WR, Datta S. The addition of bupivacaine to intrathecal sufentanil for labor analgesia. Anesth Analg 1995; 81: 305–9.[Abstract]
- Sia AT, Chong JL, Chiu JW. Combination of intrathecal sufentanil 10 µg plus bupivacaine 2.5 mg for labor analgesia: is half the dose enough? Anesth Analg 1999; 88: 362–6.
[Abstract/Free Full Text] - Mardirosoff C, Dumont L. Two doses of intrathecal sufentanil (2.5 and 5 µg) combined with bupivacaine and epinephrine for labor analgesia. Anesth Analg 1999; 89: 1263–6.
[Abstract/Free Full Text] - Campbell DC, Banner R, Crone LA, et al. Addition of epinephrine to intrathecal bupivacaine and sufentanil for ambulatory labor analgesia. Anesthesiology 1997; 86: 525–31.[Web of Science][Medline]
- Sia AT. Optimal dose of intrathecal clonidine added to sufentanil plus bupivacaine for labor analgesia. Can J Anaesth 2000; 47: 875–80.[Web of Science][Medline]
- Nelson KE, D’Angelo R, Foss ML, et al. Intrathecal neostigmine and sufentanil for early labor analgesia. Anesthesiology 1999; 91: 1293–8.[Web of Science][Medline]
- Richardson MG, Wissler RN. Densities of dextrose-free intrathecal local anesthetics, opioids, and combinations measured at 37°C. Anesth Analg 1997; 84: 95–9.[Abstract]
- Lim EHL, Sia ATH, Wong K, Tan HM. Addition of bupivacaine 1.25 mg to fentanyl confers no advantage over fentanyl alone for intrathecal analgesia in early labor. Can J Anaesth 2002; 49: 57–61.[Medline]
- Gage JC, D’Angelo R, Miller R, Eisenach JC. Does dextrose affect analgesia or the side effects of intrathecal sufentanil? Anesth Analg 1997; 85: 826–30.[Abstract]
- Kooger Infante NE, Van Gessel E, Forster A, Gamulin Z. Extent of hyperbaric spinal anesthesia influences the duration of spinal block. Anesthesiology 2000; 92: 1319–23.[Web of Science][Medline]
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