Levobupivacaine combined with sufentanil and epinephrine for intrathecal labor analgesia: a comparison with racemic bupivacaine

We performed a randomized, double-blinded study to compare levobupivacaine with racemic bupivacaine for labor analgesia. Eighty term parturients received either levobupivacaine 0.125% or racemic bupivacaine 0.125%, to which was added sufentanil 0.75 microg/mL and epinephrine 1.25 microg/mL. As part of a combined spinal-epidural procedure, 2 mL of this mixture was initially injected intrathecally, and the same solutions were subsequently administered epidurally. For both combinations, onset until the first painless contraction was 4 to 5 min. Most patients were pain free during the second contraction. The duration of initial spinal analgesia was 93.5 +/- 20 min and 94.7 +/- 31 min for levobupivacaine and racemic bupivacaine, respectively. The duration of analgesia for the first epidural top-up dose was also similar in the two groups. Total local anesthetic requirements during labor were not different. The only major difference observed was the absence of motor impairment in levobupivacaine-treated parturients as compared with the Racemic Bupivacaine group, in which the incidence of a Bromage-1 motor block was 34%. Other side effects and obstetric or neonatal outcomes were not different between groups. Intrathecal levobupivacaine has a similar clinical profile as racemic bupivacaine, but at equal doses it produced less motor block. IMPLICATIONS: When used intrathecally and epidurally for labor analgesia, levobupivacaine had the same clinical profile as racemic bupivacaine, but at equal doses it produced less motor block.     

Intrathecal labor analgesia with bupivacaine and sufentanil: the effect of adding 2.25 microg epinephrine

BACKGROUND AND OBJECTIVES: Epinephrine, 25 microg and 200 microg, has been found to prolong the duration of intrathecal labor analgesia when added to an opioid. In our hospital we use the standard epidural mixture, prepared by the pharmacist, containing epinephrine 1:800,000; i.e., 1.25 microg/mL for both spinal and epidural labor analgesia. We wanted to evaluate whether such a low dose, depending on its effect on duration or quality of analgesia, should be maintained or deleted in future mixtures. METHODS: Forty-five term parturients were randomly assigned to receive 1.8 mL intrathecally of a mixture containing bupivacaine 0.125% and sufentanil 0.75 microg/mL with or without epinephrine 1.25 microg/mL. The quality and duration of analgesia, side effects, and obstetric/neonatal outcome were compared. RESULTS: For both combinations, the onset until the first painless contraction was between 5 and 6 minutes. Most patients were pain free during the second uterine contraction. The duration of complete analgesia was 93.2 +/- 24.2 minutes in the epinephrine group and 79.3 +/- 18.1 minutes for patients not receiving epinephrine (P = .014). The quality of the block, bupivacaine consumption, side effects, and obstetric/neonatal outcome were not different between groups. CONCLUSIONS: It was concluded that epinephrine in a dose as low as 2.25 microg significantly prolonged the duration of intrathecal analgesia of bupivacaine-sufentanil by 15 minutes. No other differences were noticed. Diluting the commercially available bupivacaine 0.5% with epinephrine 1:200,000 may avoid the need of freshly prepared epinephrine solutions.     

The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia

BACKGROUND: Regional analgesia for labor often is initiated with an intrathecal injection of a local anesthetic and opioid. The purpose of this prospective, randomized, blinded study was to determine the optimal dose of intrathecal sufentanil when combined with 2.5 mg bupivacaine for labor analgesia. METHODS: One hundred seventy parous parturients with cervical dilation between 3-5 cm were randomized to receive intrathecal 0 (control), 2.5, 5.0, 7.5, or 10.0 microg sufentanil combined with 2.5 mg bupivacaine, followed by a lidocaine epidural test dose, for initiation of analgesia (34 patients in each group). Visual analog scores and the presence of nausea, vomiting, and pruritus were determined every 15 min until the patient requested additional analgesia. Fetal heart rate tracings were compared between groups. RESULTS: Groups were similar for age, height, weight, oxytocin dose, duration of labor, and baseline visual analog scores. Duration of action was significantly shorter for control patients (39 +/- 25 min [mean +/- SD]) compared with those administered sufentanil, all doses (93 +/- 32, 93 +/- 47, 94 +/- 33, 97 +/- 39 min), but was not different among groups administered 2.5, 5.0, 7.5, or 10.0 microg sufentanil. More patients who received 10 microg sufentanil reported nausea and vomiting than did control patients. The severity of pruritus increased with administration of 7.5 and 10.0 microg sufentanil. There was no difference in fetal heart rate changes among groups. CONCLUSIONS: Intrathecal bupivacaine (2.5 mg) without sufentanil did not provide satisfactory analgesia for parous patients. However, bupivacaine combined with 2.5 microg sufentanil provided analgesia comparable to higher doses, with a lower incidence of nausea and vomiting and less severe pruritus.     

Hyperbaric bupivacaine 2.5 mg prolongs analgesia compared with plain bupivacaine when added to intrathecal fentanyl 25 microg in advanced labor

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 micro g and plain bupivacaine 2.5 mg (group P; n = 19) or IT fentanyl 25 micro g 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 micro g 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 degrees 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.     

Neostigmine combined with bupivacaine, clonidine, and sufentanil for spinal labor analgesia.

We previously found that spinal clonidine prolongs labor analgesia when combined with spinal bupivacaine and sufentanil. We sought to determine whether the addition of spinal neostigmine to these drugs would further enhance labor analgesia. By use of a combined spinal/epidural technique, 36 patients were randomized to receive a hyperbaric spinal injection of bupivacaine 2.5 mg plus clonidine 50 microg and sufentanil 10 microg with or without neostigmine 10 microg. Pain, maternal hemodynamics, fetal heart rate, nausea, pruritus, sedation, motor block, sensory levels to pinprick, and maternal oxygen saturation were assessed at regularly specified intervals after spinal injection until additional analgesia was requested. The duration of spinal analgesia was similar between groups (215 +/- 60 min in the Control group versus 205 +/- 62 min in the Neostigmine group). Likewise, pain scores, the duration of labor, Apgar scores, and side effects were similar between groups except that patients administered neostigmine experienced significantly more nausea and vomiting (53% vs 7%, P = 0.01). We conclude that spinal neostigmine 10 microg produces severe nausea and does not potentiate the duration of spinal analgesia in laboring women from spinal bupivacaine, clonidine, and sufentanil. IMPLICATIONS: Spinal neostigmine 10 microg as an adjunct to spinal bupivacaine, clonidine, and sufentanil produces severe nausea and fails to potentiate analgesia in laboring women.     

Accidental intrathecal sufentanil overdose during combined spinal-epidural analgesia for labor

A laboring woman was accidentally given 45 μg of sufentanil intrathecally in the course of combined spinal-epidural analgesia. She experienced intense pruritus and transient swallowing difficulty without respiratory depression, but still had incomplete pain relief, with delivery and episiotomy repair requiring additional analgesia. This case highlights the importance of adding local anesthetic to intrathecal opioids to facilitate effective analgesia during the second stage of labor. The contributory systems issues and multiple factors that allowed this error to occur are examined.     

Bupivacaine 2.5 mg/ml versus bupivacaine 0.625 mg/ml and sufentanil l microg/ml with or without epinephrine 1 microg/ml for epidural analgesia in labour

We have compared three different methods of epidural analgesia in labour, bupivacaine 2.5 mg/ml (group B), bupivacaine 0.625 mg/ml + sufentanil 1 microg/ml (group BS) and bupivacaine 0.625 mg/ml + sufentanil 1 microg/ml + epinephrine 1 microg/ml (group BSE). One hundred and forty parturients with a singleton fetus with cephalic presentation were randomly allocated to one of the three groups. Group BSE had significantly less pain than groups B and BS. Group B had a significantly higher degree of motor blockade assessed on the Bromage scale. Significantly, more women in group B required urinary bladder catheterization than in the two other groups and they also had significantly less urge to push during active delivery. The incidence of mild pruritus was 18% in group BS and 36% in group BSE. The frequency of instrumental delivery and caesarean section was low (12% and 6.4%, respectively) with no significant differences between the groups. All women were highly satisfied with the method of analgesia and 97% would prefer the same kind of pain alleviation at the next delivery. We conclude that epidural analgesia with low-dose bupivacaine and sufentanil is as good an analgesic method as high-dose bupivacaine. Addition of low-dose epinephrine improves the analgesia.     

Determination of the full dose-response relation of intrathecal bupivacaine, levobupivacaine, and ropivacaine, combined with sufentanil, for labor analgesia

BACKGROUND: Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose-response studies have not been performed. The current trial describes the dose-response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia. METHODS: Four hundred fifty term parturients in active labor were included in this double-blind, randomized trial. Combined spinal-epidural anesthesia was performed, and ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 microg sufentanil. Patients were considered responders to spinal analgesia if the visual analog scale score for pain was less than 25 mm within 15 min and the visual analog scale score remained less than 25 mm for 45 min. Patient demographics, obstetric data, maternal side effects, and fetal and neonatal well-being were noted. Group-specific dose-response curves were constructed using a probit regression model. RESULTS: The ED95 of bupivacaine was 3.3 mg (95% confidence interval, 2.9-4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95% confidence interval, 4.0-6.7) and 5.0 mg (95% confidence interval, 4.1-7.0), respectively. Racemic bupivacaine was significantly more potent than ropivacaine (P=0.0027) and levobupivacaine (P=0.0006). Ropivacaine and levobupivacaine were of similar potency (P=0.91). CONCLUSIONS: This full dose-response study suggests that ropivacaine and levobupivacaine are of similar potency, whereas bupivacaine is more potent than both other drugs.     

Comparison of intrathecal bupivacaine and ropivacaine with different doses of sufentanil

Background: Spinal bupivacaine produces a complete anaesthetic block of a longer duration than ropivacaine, which leads to a potentially increased risk of failure. A combination of sufentanil to ropivacaine may improve the block's reliability. Methods: Sixty‐four patients, scheduled for varicose vein stripping or the tension‐free vaginal tape procedure, were allocated to receive double‐blindly, spinal bupivacaine 10 mg (Group 1) or ropivacaine 10 mg without (Group 2) or with sufentanil 2.5 mcg (Group 3), 5 mcg (Group 4). Sensory block was tested with pinprick and motor block was evaluated with the Bromage scale until full recovery. The primary endpoint was to compare the duration of sensory block evaluated by regression to S2. Results: In comparison with bupivacaine, ropivacaine produced a shorter duration sensory block (median at 68, 90 and 120 min in groups 2, 3 and 4, respectively, vs. 150 min in Group 1) and motor block (median at 90, 98 and 120 min in groups 2, 3 and 4 vs. 180 min in Group 1). Motor blockade was significantly less important in patients receiving spinal ropivacaine (median values for the Bromage scale at 3 in groups 2, 3 and 4, vs. 1 in Group 1). Pruritus was significantly more frequent in patients receiving spinal sufentanil (Groups 3 and 4 vs. Groups 1 and 2). Conclusion: Plain bupivacaine 10 mg has a longer recovery profile than the same dose of ropivacaine with or without sufentanil.     

Minimum local analgesic doses of ropivacaine, levobupivacaine, and bupivacaine for intrathecal labor analgesia

BACKGROUND: Doses for intrathecal opioid-local anesthetic mixtures have been arbitrarily chosen. The aim of this study was to compare the analgesic efficacies of intrathecal ropivacaine, levobupivacaine, and bupivacaine for labor analgesia and to determine the analgesic potency ratios for these three drugs. For this purpose, the authors used the up-down sequential allocation model, which estimates the minimum local analgesic dose for intrathecal local anesthetic. METHODS: Ninety-seven nulliparous term parturients in spontaneous labor, requesting combined spinal-epidural analgesia, were randomly allocated to one of three groups to receive 0.25% spinal ropivacaine, levobupivacaine, or bupivacaine. The initial dose of the local anesthetic drug was chosen to be 2.5 mg, and the testing interval was set at 0.25 mg. The subsequent doses were determined by the response of the previous parturient. Efficacy was accepted if the visual analog pain score decreased to 10 mm or less on a 100-mm scale within 30 min. The minimum local analgesic dose was calculated using the method of Dixon and Massey. RESULTS: The intrathecal minimum local analgesic dose was 3.64 mg (95% confidence interval, 3.33-3.96 mg) for ropivacaine, 2.94 (2.73-3.16) mg for levobupivacaine, and 2.37 (2.17-2.58) mg for bupivacaine. The relative analgesic potency ratios were 0.65 (0.56-0.76) for ropivacaine:bupivacaine, 0.80 (0.70-0.92) for ropivacaine:levobupivacaine, and 0.81 (0.69-0.94) for levobupivacaine:bupivacaine. There were significant trends (P levobupivacaine > ropivacaine.     

A comparison of intrathecal fentanyl and sufentanil for labor analgesia

BACKGROUND: The use of intrathecal opioids for labor analgesia continues to gain popularity, but there are limited data to guide this use. Previously, the authors established the ED50 for 60 min of labor analgesia from intrathecal sufentanil using an up-down sequential allocation study design. The current study first establishes an ED50 for intrathecal fentanyl using this same study design to establish an intrathecal potency ratio for fentanyl and sufentanil and then uses this ratio to compare the efficacy, duration of analgesia, and side effects from comparable doses of intrathecal fentanyl and sufentanil. METHODS: Seventy-five healthy nulliparous women requesting labor analgesia were enrolled in this two-part study. In phase I, 20 women received varying doses of fentanyl to establish an ED50 for 60 min of labor analgesia. In phase II, 55 women were randomized to receive either 36 microg intrathecal fentanyl or 8 microg sufentanil (2 times the ED50s) via a combined spinal-epidural technique and by double-blinded design. Pain relief, side effects, block height, maternal hemodynamics, and fetal heart rate were assessed throughout the study. The duration of spinal analgesia was considered to be the time from injection of study drug to the time of the patient's first request for additional analgesia. RESULTS: The ED50 of intrathecal fentanyl for 60 min of labor analgesia was found to be 18.2 microg, and therefore, the potency ratio of intrathecal sufentanil to intrathecal fentanyl at the ED50 level is 4.4:1. The duration of spinal analgesia was significantly longer from 8 microg intrathecal sufentanil than from 36 microg intrathecal fentanyl (104 +/- 34 vs. 79 +/- 34 min, P = 0.009). Otherwise, patient demographics, maternal hemodynamics, duration of labor, mode of delivery, motor block, subjective leg weakness, pruritus, nausea, pinprick sensory levels, visual analog scale pain scores, fetal bradycardia, and Apgar scores were similar between groups. CONCLUSION: The relative potency of intrathecal sufentanil to fentanyl for labor analgesia is 4.4:1. When using intrathecal opioids alone for early labor analgesia, 8 microg sufentanil produces labor analgesia lasting approximately 25 min longer than from 36 microg fentanyl, without a statistically significant increase in side effects. However, when making a choice between fentanyl and sufentanil, one must consider other important factors, such as the higher cost of sufentanil and the greater risk of dosing error due to the higher potency of sufentanil compared with fentanyl.     

Two additional cases of excessive extension of sensory blockade after intrathecal sufentanil for labor analgesia

Combined spinal-epidural anesthesia (CSE) is an effective technique with rapid onset of labor analgesia. We describe two cases of excessive cephalad spread of sensory blockade without motor blockade in two parturients in spontaneous labor with CSE. The patients received sufentanil 5 microg intrathecally with 1.25 mg bupivacaine. Spinal injection produced dyspnea and extension of sensory blockade to cervical or facial level without fetal consequences. We conclude that the risk of these side-effects previously described with the 10 microg dose persists for lower sufentanil spinal doses.     

Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia.

This study compared the analgesic efficacy of intermittent injections of intrathecal fentanyl (10 micrograms), meperidine (10 mg), or sufentanil (5 micrograms) administered to 65 parturients during the first stage of labor. The groups did not differ in onset or duration of effective analgesia. The meperidine group, however, had significantly lower pain scores once cervical dilation progressed beyond 6 cm. Side effects included mild pruritus and nausea. After intrathecal drug injection, variable decelerations of the fetal heart rate increased in the fentanyl and meperidine groups. All neonates had a 5-min Apgar score of 7 or more. We conclude that intermittent intrathecal injections of fentanyl, meperidine, or sufentanil can provide adequate first-stage labor analgesia. Meperidine appears to provide more reliable analgesia as the first stage of labor progresses.     

Efficacy and side effect profile of varying doses of intrathecal fentanyl added to bupivacaine for labor analgesia

The purpose of this randomized, double blinded and controlled study was to determine the optimal dose of intrathecal fentanyl when combined with bupivacaine 2.5 mg for initiation of labor analgesia. Parous parturients with cervical dilation between 3 and 5 cm were randomized to receive intrathecal fentanyl 0 (control), 5, 10, 15, 20 or 25 micrograms, combined with bupivacaine 2.5 mg, followed by a lidocaine/epinephrine epidural test dose. Visual analog pain scores (VAPS) and the presence of side effects were determined every 15 min until the parturient requested additional analgesia. Fetal heart rate (FHR) tracings were compared between groups. All parturients who received fentanyl >/= 15 micrograms had VAPS < 20 mm and duration of analgesia > 15 min, but this was not true for all parturients with fentanyl doses < 15 micrograms. Duration of analgesia was shorter for fentanyl groups 0, 5 and 10 micrograms, compared to groups 15, 20 and 25 micrograms, but there was no difference between the 15, 20 and 25 micrograms groups. There was no difference in the incidence of nausea and vomiting, or in FHR tracing changes. The incidence of pruritus was greater in all fentanyl groups compared to control. These data suggest that, when combined with intrathecal bupivacaine 2.5 mg, fentanyl 15 micrograms provides satisfactory analgesia to all parturients. Higher fentanyl doses produced no additional benefit in duration or quality of analgesia.     

Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine

We sought to determine whether spinal clonidine 50 microg prolongs the analgesia from the spinal administration of sufentanil 7.5 microg and bupivacaine 2.5 mg early in the first stage of labor. Thirty patients were randomized to receive a 2-mL spinal injection of sufentanil 7.5 microg + bupivacaine 2.5 mg with or without clonidine 50 microg using a combined spinal-epidural (CSE) technique. Pain, nausea, pruritus, sedation, motor block, blood pressure, and heart rate were assessed until the patient requested additional analgesia. Analgesia was significantly prolonged in patients who received spinal sufentanil + bupivacaine + clonidine (197 +/- 70 vs 132 +/- 39 min; P = 0.004). Pain scores and side effects, including motor block, sedation, and hypotension, were similar between groups. Spinal clonidine significantly prolongs labor analgesia from spinal sufentanil and bupivacaine without producing serious adverse side effects. IMPLICATIONS: We studied the effects of spinal clonidine administered with spinal sufentanil and bupivacaine on labor analgesia using a combined spinal-epidural technique and conclude that spinal clonidine significantly prolongs labor analgesia from spinal sufentanil and bupivacaine without producing serious adverse effects.     

A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia.

A number of recent studies have suggested that the analgesic effects of highly lipid-soluble opioids are similar when these agents are administered either epidurally or intravenously. We sought to test whether the lipid-soluble opioid sufentanil was more effective when administered intrathecally than when administered epidurally or intravenously. Twenty-four women during active labor received sufentanil 10 micrograms either intrathecally (n = 9), epidurally (n = 8), or intravenously (n = 7), using a combined spinal-epidural technique. The sufentanil was administered alone, without concomitant local anesthetics. Analgesia was assessed using the visual analogue score as well as the time elapsed from the administration of study drug to the patient's request for additional analgesia via the epidural catheter (bupivacaine 0.25%). The median duration of analgesia (median, interquartile range) was 84 (70-92) min in the intrathecal group, 30 (23-32) min in the epidural group, and 34 (17-30) min in the intravenous group (P < 0.001). The intrathecal group showed rapid and significant decrease in visual analogue scale scores, whereas visual analogue scale scores in the other two groups did not decrease and remained significantly elevated compared to those of the intrathecal group at all observation points. Side effects were limited to pruritus in 3 patients (2 moderate and 1 severe) in the intrathecal group. No patient developed post-dural puncture headache. We conclude that sufentanil 10 micrograms intrathecally provides rapid and effective analgesia of 1-2-h duration during labor. Epidural and intravenous use of this dose of sufentanil did not provide evidence of satisfactory analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of duration of analgesia of intrathecal 2.5 mg of bupivacaine, ropivacaine, and levobupivacaine in combined spinal epidural analgesia for patients in labor

We assessed the duration of labor analgesia rendered by intrathecal (IT) local anesthetics as the sole drugs. In this randomized, controlled, and double-blinded study, labor analgesia was induced using combined spinal-epidural technique in 60 ASA physical status I nulliparous parturients with IT bupivacaine 2.5 mg (group B), ropivacaine 2.5 mg (group R), or levobupivacaine 2.5 mg (group L). Pain scores (0-100 visual analog scale) and blood pressure were recorded pre-block and for the first 30 min post-block. The degree of motor block and the highest sensory block were also monitored. The duration of analgesia (our primary outcome) was the longest in group B but was similar between groups R and L (mean +/- SE, 76.3 +/- 5.9 min versus 52.6 +/- 4.0 min and 51.5 +/- 3.4 min, respectively, P < 0.05). Group B had the most frequent incidence of lower limb motor block but there was no difference between groups R and L (5 of 20 parturients versus 2 of 20 and 0 of 20, respectively, P < 0.05). The profile of the other side effects was indistinguishable between the groups. With the current regimen, IT bupivacaine produced the longest duration of labor analgesia. IMPLICATIONS: Intrathecal 2.5 mg bupivacaine significantly prolongs the duration of analgesia in laboring patients compared with ropivacaine or levobupivacaine. This suggests that, at clinically relevant doses, bupivacaine may have greater potency.