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OBSTETRIC ANESTHESIA

The Effect of a Lidocaine Test Dose on Analgesia and Mobility After an Epidural Combination of Neostigmine and Sufentanil in Early Labor

From the Department of Anesthesiology, Université Catholique de Louvain, St. Luc Hospital, Brussels, Belgium.

Address correspondence and reprint requests to P. Lavand’homme, MD, Department of Anesthesiology, St. Luc Hospital, Av Hippocrate 10-1821, 1200 Brussels, Belgium. Address e-mail to lavandhomme{at}anes.ucl.ac.be.

	Abstract

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We previously demonstrated the effectiveness of epidural sufentanil and the cholinesterase inhibitor, neostigmine, to initiate selective labor analgesia. Because the traditional lidocaine plus epinephrine test dose (TD) may alter the effect of subsequent epidural drugs, we undertook this investigation to evaluate the impact of a lidocaine TD on analgesia from a combination of epidural neostigmine plus sufentanil administered in early labor. Eighty healthy parturients were randomly allocated to two groups to receive a 3 mL-TD, either lidocaine 2%–epinephrine (1:200,000) or saline–epinephrine (1:200,000), followed 3 min later by epidural neostigmine 500 µg plus sufentanil 10 µg. Pain scores were recorded for 30 min after injection, as was the time elapsed from initial bolus until request for supplemental analgesia. Thirty minutes after injection, adequacy of motor function was evaluated by the parturient’s ability to sit, stand up, bend her knees, and walk. Lidocaine TD hastened the onset (5 min vs 15 min) and increased duration (122 ± 53 min vs 98 ± 54 min; P = 0.02) of analgesia from epidural neostigmine plus sufentanil bolus. In contrast, the TD did not significantly impair the ability to sit, stand up, or bend the knees. The ability to ambulate, however, was reduced (57% vs 82%; P = 0.04). In conclusion, a traditional lidocaine TD significantly enhances the analgesic effect from the epidural neostigmine plus sufentanil combination, but affects ambulation in early labor.

	Introduction

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Selective analgesia, i.e., pain relief without motor or sympathetic block, especially during the first stage of labor, is currently a goal when providing analgesia in laboring women (1). Although large randomized studies have not shown a benefit of ambulation on obstetric outcome, parturients, labor nurses, and obstetricians are now requesting neuraxial techniques that do not affect ambulation and do not interfere with the normal mechanisms of labor (2). Further, maintaining mobility and avoiding bladder catheterization strongly enhances patient satisfaction. Different techniques using small doses of local anesthetic in association with lipophilic opioids have been advocated to achieve these goals (2,3).

We (4) have assessed and reported on the efficacy of an epidural combination devoid of local anesthetic (i.e., neostigmine 500 µg and sufentanil 10 µg) to induce a labor analgesia. However, in that study, administration was preceded by a traditional lidocaine plus epinephrine test dose (TD). The TD, however, may have an impact on the analgesic effect of subsequent epidural analgesics (5) and has also been reported to affect motor function when preceding epidural injection of local anesthetic in parturients (6). Further, in our earlier study, motor function was evaluated by the use of a modified Bromage scale that may not correlate with the ability to perform other motor tests such as standing up, bending the knees, and walking (7).

The present study, therefore, aimed to specifically evaluate the impact of a traditional lidocaine plus epinephrine TD on both analgesia and mobility resulting from an epidural injection of neostigmine 500 µg combined with sufentanil 10 µg used to initiate labor analgesia.

	METHODS

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After approval by the Clinical Research Practices Committee and obtaining informed consent, 80 ASA physical status I and II healthy parturients (n = 40 per group), whose gestational age was more than 36 wk and requesting epidural analgesia during labor were enrolled in the study. A lumbar epidural was performed with an 18-gauge Tuohy needle, and an epidural catheter (multiport) was inserted 4 cm at the L3-4 level in all parturients. Exclusion criteria included parturients with obstetric complications (multiple pregnancy, premature labor, or non-vertex presentation) and contraindications to regional analgesia. Accidental dural puncture during the placement of the epidural also excluded patients from the study. All parturients were in established labor when the epidural technique was initiated and all received an oxytocin infusion during the course of labor.

Pain was assessed with a 100-mm visual analog scale (VAS 0–100). When the VAS score reached the level of 30, the parturients were randomly allocated to one of the two study groups to receive through the epidural catheter a 3 mL TD of either lidocaine 2% with epinephrine 1:200,000 (Group TD+S10N500) or saline with epinephrine 1:200,000 (Group S10N500). In all parturients, the TD was administered 3 min before an epidural combination of sufentanil 10 µg and neostigmine 500 µg. Careful aspiration of the catheter was performed before every epidural injection. Further, to avoid any intravascular injection of the drug (especially in the case of neostigmine, which may be associated with bradycardia and enhancement of gastrointestinal and bladder motility if injected intravascularly), we chose to add epinephrine to the saline TD. Neostigmine was provided from the commercial solution of neostigmine methylsulfate (Prostigmine®, 0.5 mg/mL; Roche, Summerville, NJ) for which safety assessment has been reported after spinal use (8). The dose of epidural neostigmine used in the present study, 500 µg (i.e., 6–7 µg/kg), was chosen on the basis of the results from earlier clinical trials showing that smaller doses (4 µg/kg) were ineffective for initiating labor analgesia (4,9). All the parturients received this first epidural bolus in a total volume of 12 mL (4). The data were collected by an anesthesiologist, who was blinded to the patient group and to the epidural drugs.

Maternal noninvasive arterial blood pressure, heart rate, and oxygen saturation were monitored. Fetal heart rate was also continuously recorded on a cardiotocograph. Pain scores (VAS) were recorded 3, 5, 10, 15, 20, and 30 min after the epidural injection. Level of sensory block (ether swab), and lower limb motor block by using a modified Bromage score (1 = complete motor blockade; 2 = almost complete motor blockade [only able to move feet]; 3 = partial motor blockade [able to bend knees]; 4 = detectable weakness of hip flexion [able to raise leg, but unable to keep it raised]; 5 = no detectable weakness of hip flexion [able to keep leg raised for more than 10 s]; 6 = no weakness at all) were recorded 15 and 30 min after the epidural injection in addition to maternal and fetal variables. Further, the adequacy of motor function allowing mobility for the parturient, either sitting or ambulating, was assessed 30 min after the administration of the different analgesic solutions. The patients were asked to perform a straight leg raise, to sit on the edge of the bed, to stand up and then to do a deep knee bend, and finally to walk three steps unassisted. Maternal heart rate and arterial blood pressure were also monitored in relation to the different postural changes of the parturient: lying in the bed, after 3 min sitting on the edge of the bed, and finally after 3 min standing up. Finally, the ability to void spontaneously during the course of labor was evaluated.

The duration of analgesia of the first epidural bolus dose was considered as the time elapsed until the patient’s first request for further analgesia. At that time, a second epidural injection was administered followed by continuous infusion with ropivacaine 0.1% (10 mL/h) and rescue doses of ropivacaine as needed for the maintenance of analgesia.

The total duration of labor from the time of the first epidural injection until delivery, the mode of delivery (cesarean, vaginal instrumental, or spontaneous), as well as cervical dilation at the time of second epidural injection were recorded.

Maternal adverse events (nausea and vomiting, pruritus, sedation) and fetal side effects (bradycardia during labor and low Apgar score at 5 and 10 min) were also evaluated.

Results were expressed as mean ± sd, 95% confidence interval, or median (interquartile range), as indicated. Demographic data and continuous variables were compared between the groups by one-way analysis of variance and repeated measures, followed, if appropriate, by post hoc Scheffé test (Statistica, StatSoft, Tulsa, OK). A comparison of ordinal categorical data between groups was performed using the Mann–Whitney test. The incidence of adverse effects, impact of the solutions on mobility, and installation of satisfactory analgesia were compared between the two groups by ² analysis. A P < 0.05 was considered significant.

A power analysis (SigmaStat, SPSS Science Software, UK) was based on preliminary data regarding the duration of analgesia resulting from a first epidural bolus of sufentanil 10 µg and neostigmine 500 µg with and without a lidocaine TD. A prospective sample size calculation indicated that 40 subjects were required in each group to have 80% power to detect a 25% difference at an -level of 0.05 in the duration of analgesic effect.

	RESULTS

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Eighty patients (40 per group) completed the study. No parturient had to be excluded for either intrathecal or intravascular catheter placement. Variables, including age, weight, and parity, were similar between the groups, as well as cervical dilation at the first injection and when a second epidural injection was required (Table 1). Maternal hemodynamic variables (arterial blood pressure, heart rate, and oxygen saturation) were not modified by the first epidural injection, regardless of TD used.

Epidural Analgesia
The administration of a lidocaine TD speeded the onset of epidural analgesia and allowed a significantly greater reduction of the initial pain score from 3 to 30 min after injection of sufentanil 10 µg with neostigmine 500 µg (Fig. 1). To better evaluate the effect of the lidocaine plus epinephrine TD, we recorded the percentage of parturients presenting with satisfactory analgesia (defined as a VAS <30/100) at different times after injection (Fig. 2). Further, the lidocaine TD significantly improved the effectiveness of epidural analgesia from 3 to 30 min before injection. After 15 and 30 min, 79.4% and 94.4% of the parturients in the lidocaine TD group were comfortable when compared with 54.3% and 72% in the saline–epinephrine group. The use of a TD slightly, but significantly enhanced the duration of epidural analgesia and reduced the subsequent requirements for local anesthetic, i.e., ropivacaine consumption during labor (Table 2), although labor duration did not differ between the groups (Table 1).

View larger version (26K): [in this window] [in a new window]   Figure 1. Evolution of pain scores: before (T0) and from 3 to 30 min (T3–T30) after first epidural injection in the different groups of parturients. Legend for the groups: epidural test dose lidocaine–epinephrine followed by sufentanil 10 µg and neostigmine 500 µg (TD+S10N500), and saline– epinephrine followed by sufentanil 10 µg and neostigmine 500 µg (S10N500). *P < 0.05 with visual analog scale (VAS 0–100) score at T0 before epidural injection; +P < 0.05 with the Group S10N500 at similar time point after epidural injection.

View larger version (14K): [in this window] [in a new window]   Figure 2. Efficacy of epidural injection based on the percentage of parturients experiencing a satisfactory level of analgesia (defined as a score strictly <30/100 on visual analog scale) at different times after injection of the two analgesic solutions. Legend for the different groups: epidural test dose lidocaine–epinephrine followed by sufentanil 10 µg and neostigmine 500 µg (TD+S10N500), and saline–epinephrine followed by sufentanil 10 µg and neostigmine 500 µg (S10N500). *P < 0.05 and **P < 0.01 with the Group TD+S10N500.

A difference in sensory level between groups was observed at 15 and 30 min after epidural injection. Without a lidocaine TD, no difference in sensory level was observed in 32% and 22.5% of the parturients at 15 and 30 min after epidural injection of sufentanil 10 µg with neostigmine 500 µg.

Evaluation of Motor Function
With the parturient lying in bed, the degree of motor block assessed by modified Bromage score did not differ between the two groups and did not show motor impairment.

In contrast, in the other tests evaluating motor function, the presence of a lidocaine TD affected parturient’s mobility, specifically when ambulation was required: 82% were able to walk three steps unassisted in the group without TD versus 57% in the group with TD (Table 3).

Side Effects Recorded During the Protocol and the Course of Labor
In both groups, maternal hemodynamic variables, heart rate, and arterial blood pressure, remained unaffected by the different postural changes performed 30 min after the first epidural bolus (unshown data). Maternal side effects were very few, i.e., nausea and vomiting did not occur (0/40 in both groups), while the incidence of pruritus was 0/40 in TD group versus 4/40 in the group without TD.

Finally, epidural administration of a lidocaine TD did not modify the total duration of labor, nor did it impact the mode of delivery (Table 1). No harmful side effects, e.g., bradycardia, were noted in fetuses during labor, and Apgar scores did not differ between the groups.

	DISCUSSION

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Although its routine use has been controversial (10), the traditional 3-mL lidocaine TD (1.5% or 2%) with epinephrine still remains widely used by anesthesiologists to exclude unintentional spinal or vascular catheter placement. As previously demonstrated in clinical trials (5,6,11,12), however, each component of the TD i.e., lidocaine and epinephrine may interact with subsequently administered epidural medications.

Epinephrine by itself, is an adrenergic agonist, produces analgesia through spinal 2-adrenergic receptor binding, and a dose as low as 30 µg has been shown to both hasten onset and prolong duration of epidural local anesthetic in parturients (5). The combination of lidocaine and epinephrine, the "traditional" TD, enhances analgesia, both onset and duration that results from injection of small-dose epidural local anesthetic during labor (6). Effective pain relief (score lower than 3 on VAS scale 0–10) was obtained more quickly when administration of 10 mL bupivacaine 0.125% combined with sufentanil 10 µg was preceded by a TD of 45 mg lidocaine. Similarly, in an earlier study, the TD prolonged the duration of analgesia of 20 µg epidural sufentanil alone from 93 (SD 38) (11) to 138 min (SD 50) (12). In our study, we observed that the lidocaine plus epinephrine TD has a significant impact on analgesia resulting from the epidural injection of neostigmine 500 µg and sufentanil 10 µg: it reduces the onset (5 min vs 15 min), enhances the effectiveness and increases the duration (from 98 to 122 min). In addition, the spinal analgesic effect of neostigmine also might have been enhanced by neuraxial administration of lidocaine (13) and epinephrine (14).

Apart from its own analgesic effect, it is worth noting that a major concern regarding the use of a local anesthetic TD remains linked to its potential impact on motor function, which has been considered to be a barrier to the realization of a "walking epidural" technique (6,7).

The aim of this study was not to promote ambulation during labor, but, rather to examine the benefit of using epidural neostigmine to obtain a selective analgesia (i.e., efficacy with minimal motor and sympathetic block) in parturients. In this context, neostigmine offers some advantage (i.e., absence of motor and sympathetic block) over the use of a local anesthetic. However, although devoid of sympatholytic effect, spinal injection may provoke muscle weakness. In volunteers (8,14,15), lumbar intrathecal injection of neostigmine decreased motor strength and deep tendon reflexes in the lower limbs in a dose-dependent manner. This effect probably results from a direct inhibitory action on motor neuron activity by enhancement of local concentrations of acetylcholine. On the basis of the hydrophylic nature of neostigmine, we can suppose, as did Lauretti et al. (13), that an epidural dose of 500 µg might correspond to an intrathecal dose of 50 µg, a dose which, in volunteers, produced only subjective legs weakness (8,14,15). This weakness was unaffected by concomitant use of epidural clonidine (14), but dose-dependently enhanced by IV opioid administration in volunteers (15). Combined with a local anesthetic and at doses up to 10 µg/kg, epidural neostigmine has not been reported to provoke motor impairment when administered for postoperative analgesia (13,16).

The present study, involving parturients at term, only allowed us to assess the effect of epidural neostigmine on motor function by comparison with other mobile techniques used in labor. To compare the results of the different studies on ambulatory analgesia is not easy. First, different drugs, doses, and techniques have been used via the combined spinal epidural or epidural route. Second, the best test to assess motor function before ambulation has not been determined, and the tests differ among the different trials. Finally, several factors are involved in the success of the technique: the presence of a correct postural stability, being aware that pregnancy itself affects balance, absence of orthostatic hypotension, and the parturient opinion on her ability to mobilize or ambulate (17). For example, Collis et al. (18) have observed that, although the spinal injection they administered did not induce a motor block in 97% of the parturients, only 52% of them chose to stand, walk, or sit during labor.

When not preceded by a TD, the effect of our epidural combination on mobility does not differ from those of the studies in which the TD was omitted before spinal or epidural injection of a small dose of local anesthetic and µ-opioid agonist. Effectively, 100% of our parturients were able to sit, 86% to stand up, and 82% to walk unassisted. Calimaran et al. (7) reported 70% of parturients able to stand and to sit, and 70% able to walk, 30 min after 2.5 mg spinal bupivacaine. Cohen et al. (6) found 53%–86% of their patients able to walk unassisted 30 min after an epidural injection of 9–19 mg bupivacaine. In contrast, the administration of a TD with lidocaine 60 mg before neostigmine and sufentanil slightly impaired motor function and decreased the ability to stand and to walk to 73% (P = 0.24) and 57% (P = 0.04), respectively. Using a smaller TD than we did, i.e., lidocaine 30 mg, before epidural analgesia provided by µ-opioid agonist fentanyl alone, Breen et al. (3) reported a 70% rate of ambulation. However, when labor analgesia was induced by spinal or epidural administration of a local anesthetic, even at a small dose, the lidocaine TD reduced the percentage of parturients who are able to ambulate to 40% (7) and 36%–60%, respectively (6).

Although the role of epidural analgesia in bladder hypotonia and urinary retention in the obstetric patient is controversial, neuraxial administration of local anesthetics and µ-opioid agonist may predispose women to difficulty with micturition (19,20). Because intermittent repeated bladder catheterizations are unpleasant and carry a risk of infection, the capacity to void spontaneously during labor should be considered, particularly in the context of mobile analgesia, as an advantage provided by the technique. In our study, approximately 70% of the parturients were able to void spontaneously during the course of labor, a result unaffected by the use of a TD and consistent with the observations made by Cohen et al. (6) after the use of small dose epidural bupivacaine. The role played by epidural neostigmine on spinal control of micturition is unclear, but should be minimal at the doses we used. In volunteers, both urinary retention and sense of urinary urgency occurred after intrathecal injection, but only when neostigmine doses were higher than 150 µg (8).

In conclusion, beyond safety concerns in the obstetric patient i.e., to prevent intravascular and intrathecal administration of analgesics, the traditional lidocaine plus epinephrine TD demonstrates its usefulness when an epidural combination of neostigmine and sufentanil is used to induce selective labor analgesia. Effectively, the lidocaine TD significantly enhances the analgesic effect of the epidural combination. However, as demonstrated in earlier clinical trials assessing ambulatory techniques in obstetric analgesia, the lidocaine TD also reduces the parturient’s ability to ambulate.

	Footnotes

 
Accepted for publication August 25, 2006.

Supported by Department of Anesthesiology of the University of Louvain, St Luc Hospital, 1200 Brussels, Belgium.

	REFERENCES

Top Abstract Introduction METHODS RESULTS DISCUSSION REFERENCES

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Roelants, F. Articles by Lavand’homme, P. M. Search for Related Content PubMed PubMed Citation Articles by Roelants, F. Articles by Lavand’homme, P. M. Related Collections Obstetrics Regional Anesthesia Pharmacology