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Intrathecal Sufentanil for Labor Analgesia: Do Sensory Changes Predict Better Analgesia and Greater Hypotension?

Riley, Edward T. MD; Ratner, Emily F. MD; Cohen, Sheila E. MB, ChB

Obstetric Anesthesia
Free
SDC

Sensory changes and hypotension occur after intrathecal sufentanil (ITS) is given during labor.The goal of this study was to determine whether sensory changes are predictive of hemodynamic changes or duration of pain relief. We also examined whether sensory and hemodynamic changes relate to the concentration of ITS administered. Forty-five ASA physical status I and II women in active labor were randomly assigned to receive 10 micro g ITS diluted in either 1, 2, or 3 mL of normal saline (15 in each group). An observer blinded to treatment recorded verbal pain scores, blood pressure, and sensory changes to light touch, pinprick, and cold at frequent intervals. Excellent analgesia was obtained in 42 of 45 patients. There were no differences among the groups with respect to the number of patients with sensory changes, the duration of analgesia or sensory changes, the quality of analgesia, or the severity of hypotension. The groups were therefore combined for further analyses. Among this combined group, the duration of analgesia was 99 +/- 7 min (mean +/- SE). Cold, pinprick, and light touch sensation were decreased in 66%, 50%, and 33% of patients, respectively. Motor block was absent in all patients. The duration and quality of analgesia were similar in subjects with and without sensory changes. Systolic blood pressure decreased 23 +/- 2 mm Hg (P < 0.05) during the first 30 min after ITS, and six patients were given ephedrine. The magnitude of blood pressure change was not affected by the diluent volume or the presence of sensory changes. Because sensory changes were not predictive of the duration or quality of analgesia or the degree of hemodynamic change, we conclude that analgesia with ITS is predominantly mediated via spinal cord opioid receptors rather than by a local anesthetic-type conduction blockade.

(Anesth Analg 1997;84:346-51)

Department of Anesthesia, Stanford University School of Medicine, Stanford, California.

This study was partially presented at the October 1994 meeting of the American Society of Anesthesiologists in San Francisco, CA.

Accepted for publication October 21, 1996.

Address correspondence to Edward T. Riley, MD, Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305. e-mail: edriley@Leland.Stanford.edu.

The lipid soluble opioids sufentanil and fentanyl are frequently given intrathecally during labor as they provide rapid, effective analgesia with no clinically significant motor blockade [1-4]. We [5] and others [6-9] have found that intrathecal sufentanil (ITS) used in this circumstance can cause sensory changes and hypotension. These findings suggest that sufentanil, like meperidine [10,11], may act as a weak local anesthetic. Our hypothesis was that if a local anesthetic action of ITS contributed significantly to the resulting analgesia, then patients with sensory changes would experience better analgesia and exhibit greater decreases in blood pressure after ITS than those without such changes. In order to examine the relationships between sensory changes and both blood pressure and analgesia, we studied these variables in laboring women given ITS for pain relief.

An additional goal was to test whether the diluent volume of the ITS affects analgesia, sensory changes, or hypotension. Other investigators have reported analgesia after ITS with little or no sensory changes or hypotension [2,3]. In contrast, we frequently observe such changes [5]. As the only apparent difference between techniques was the amount [3] or concentration [2] of sufentanil administered, we studied the effect of diluent volume on these outcomes.

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Methods

With institutional review board approval and patients' informed consent, 49 ASA physical status I and II women in the first stage of labor were enrolled in the study. Exclusion criteria included administration of intravenous opioids prior to the study, pregnancy-induced hypertension, and diabetes. Four of the original 49 patients were excluded from analysis because there was no return of cerebrospinal fluid (CSF) from the spinal needle. Subjects were randomized to receive 10 micro g ITS in either 1, 2, or 3 mL of normal saline (15 in each group) through a 24-gauge Sprotte[TM] needle introduced via an 18-gauge Tuohy needle. All blocks were performed with the woman in the sitting position, using the L2-3 or L3-4 interspace; the distal opening of the Sprotte[TM] needle was directed caudad when the sufentanil was injected. An epidural catheter was then placed but not tested or dosed during the study period. The patient labored in a lateral, semirecumbent position. A blind observer recorded verbal pain scores (VPS) on a scale of 0-10 (0 = no pain and 10 = the worst imaginable pain), blood pressure (measured with an automated blood pressure device), and sensory changes to light touch, pinprick, and cold 2.5, 5, 7.5, 10, 15, 20, 25, 30, 45, and 60 min after injection of ITS. Cold sensation was tested with an alcohol pad, pinprick sensation with a 25-gauge needle, and light touch with a cotton swab. Further measurements were made every 30 min until patients requested additional analgesia. The study ended when additional analgesia was requested. The day after delivery, mothers were asked whether they recalled any adverse effects (e.g., itching, nausea, sedation, etc.) and rated their satisfaction with analgesia during the first stage of labor on a scale of 0-10 (0 = completely unsatisfied; 10-completely satisfied). Neonatal outcome was assessed by Apgar scores at 1 and 5 min. Statistical analyses included Student's t-tests, one-way and two-way analyses of variance, linear regression, and chi squared with Yates' correction. Unless otherwise noted, values are reported as mean +/- SE with P < 0.05 considered significant.

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Results

The three groups designated by volume of diluent were similar demographically (Table 1). Mean VPS decreased markedly in all groups after ITS administration, with no differences among the groups (Figure 1). All but three subjects (one from each group) developed excellent analgesia, achieving pain scores <or=to2 within 15 min of ITS injection. Systolic blood pressure (SBP) also decreased after ITS (Figure 1), again with no differences among the groups. Of all subjects, 66% lost sensation to cold, 50% lost sensation to pinprick, and 33% developed changed sensation to light touch (Figure 2). There was never a complete loss of light touch sensation, only a change in its perception. The proportions of patients who developed these sensory changes were similar among the three groups. When sensory changes were present, the median upper levels of the blocks were T5 for cold and T8 for pinprick and light touch. The blocks extended caudally to at least S3 (S3 was the lowest dermatome tested). There were no differences in the number of dermatomes blocked among the three groups. Sensory changes were relatively short lived compared with the average duration of analgesia (Figure 3).

Table 1

Table 1

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

As there were no differences among the diluent volume groups with respect to the onset, quality, or duration of analgesia, the presence or extent of sensory changes, or the magnitude of blood pressure changes, the data were pooled. Subjects were then divided into two groups: those who did and those who did not have blocks to cold and pinprick. Figure 4 shows the VPS and SBP changes in subjects with and without a block to cold. In both groups, there were rapid decreases in VPS and SBP; however, there were no differences between the groups. Results were the same for patients with and without a pinprick block. Similarly, the duration and extent of sensory changes did not correlate with the duration of analgesia (Figure 5).

Figure 4

Figure 4

Figure 5

Figure 5

The maximum change in systolic blood pressure in women with and without sensory blocks also did not differ, as determined by a t-test, with both groups experiencing an average decrease in SBP of 23 +/- 2 mm Hg. Decreases in blood pressure did not result in any emergent cesarean sections or low Apgar scores. In six cases, ephedrine was given based on the clinical judgment of the anesthesiologist. In all cases, the treated SBP was less than 100 mm Hg, and it was at least 30% less than the baseline SBP. There was one fetal bradycardia, unrelated to hypotension (SBP was always greater than 110 mm Hg), which resolved without intervention. Despite these events, maternal and neonatal outcomes were excellent in all groups (Table 1). Spontaneous vaginal delivery occurred in 37 women (84%) with four cesarean deliveries and four instrumented vaginal deliveries. No subject delivered or entered Stage 2 of labor before receiving local anesthetics via the catheter. Postdelivery interviews revealed a high degree of satisfaction with the analgesia during the first stage of labor; 85% of patients rated their satisfaction as 8 or greater on a scale of 0-10.

Pruritus occurred in 55% of patients and was the most significant side effect mentioned the day after delivery. However, only four women required treatment for itching during labor; two patients received diphenhydramine, one received nalbuphine, and one received both drugs. Eight patients received metoclopramide for nausea and vomiting, although only four mentioned this the following day as an adverse effect. One postdural puncture headache occurred, but the patient did not require an epidural blood patch.

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Discussion

ITS generally provided excellent analgesia. Failure to obtain adequate analgesia because of lack of CSF flow in the spinal needle (four cases), or lack of response to ITS (three cases) was a problem in 14% of patients. Some of these failures may be due to improper placement of the epidural needle or to the spinal needle being too short relative to the epidural needle [12].

As in a previous report [5], we found a high incidence of sensory changes and decreased blood pressure after ITS administration. These findings suggest that ITS may have some local anesthetic effect on nerve conduction. In support of this hypothesis, Power et al. [10] and Gissen et al. [11] have shown that fentanyl and sufentanil decreased conduction in isolated nerve fibers in vitro. However, in both of these studies, high opioid concentrations (50 and 100 micro g/mL) were needed to significantly depress nerve conduction. In the current study, administered sufentanil concentrations were only 3 to 10 micro g/mL, with further dilution occurring in the CSF. Despite the increased sensitivity to opioids found in pregnancy [14] based on the results from animal studies, these concentrations are probably too low for sufentanil to function clinically as a local anesthetic.

Findings from the current study that demonstrate the separation of sensory changes and analgesia are inconsistent with a clinically important local anesthetic mechanism of ITS analgesia. With ITS, neither the presence nor the extent of sensory changes were predictive of the quality or duration of analgesia or of the degree of blood pressure changes. If ITS does not have a clinically significant local anesthetic action on the spinal cord or nerve root, why does it cause decreased blood pressure and sensory changes? We believe that the sensory changes may be caused by the direct effect of sufentanil on micro receptors in the spinal cord. Alfentanil, another lipophilic opioid, has been shown by Wang et al. [14] to depress A partial and C-fiber afferent pathways to the spinal cord when given intrathecally to dogs. This effect was naloxone reversible. Altered sensation, therefore, may be an expected finding after intrathecal administration of opioids.

Reduction of afferent input to the spinal cord does not however, explain the decreases in blood pressure that follow ITS administration. In Wang et al.'s study [14], clinical doses of alfentanil depressed C-fiber-mediated responses in dogs but did not affect blood pressure. Thus, there does not appear to be a direct micro-receptor-mediated sympatholytic effect. This hypothesis is supported by studies in humans. Moses et al. [15] found no decrease in blood pressure when nonlaboring women having elective cesarean sections were prehydrated and then given intrathecal fentanyl 25 micro g. Similarly, in another study in which we gave male volunteers ITS, there was no significant change in blood pressure [16]. Perhaps the relief of preexisting pain during labor leads to the observed decreases in blood pressure. In the current study, all the subjects were experiencing severe labor pain. Intrathecal administration of sufentanil probably blocked the C-fiber-mediated pain stimuli to the spinal cord and either inhibited the sympathetic reflex arc and/or decreased circulating catecholamines that had been causing relative hypertension. In support of this explanation, Nagasaka and Yaksh [17] recently demonstrated that intrathecal administration of micro-agonists to unstimulated halothane-anesthetized rats had no effect on blood pressure or heart rate. In contrast, pretreatment with the same micro-agonists produced dose-dependent inhibition of pain-induced blood pressure and heart rate increases resulting from a painful stimulus applied to the tail. In addition, Cascio et al. [18] found that serum epinephrine levels decreased after administration of intrathecal fentanyl to laboring women. A preliminary report by Newman et al. [19] confirms our results. They found that blood pressure decreased when laboring women received ITS when, as in the current study, the baseline blood pressure was measured immediately before the block. However, when the baseline blood pressure was the last blood pressure recorded in the prenatal chart, blood pressure was actually higher after ITS. This suggests that laboring women are relatively hypertensive during painful labor compared with the prenatal period prior to labor.

Although the sensory changes and blood pressure decreases are probably not mediated by a local anesthetic or sympatholytic mechanism, they still may be clinically important. For example, high levels of sensory blockade involving the cranial nerves have been reported after ITS administration in labor and can be quite distressing to the patient [20]. In the current study, several patients required ephedrine for treatment of hypotension, with systolic blood pressures as low as 80 mm Hg in some instances.

Another area of concern with ITS use during labor is its possible effect on the fetus. A recent report [21] documents several cases of severe fetal bradycardia after the administration of intrathecal fentanyl and suggests that this may result from increased uterine tone after removal of sympathetic inhibition as maternal catecholamines decrease with the onset of analgesia. One case of fetal bradycardia occurred in the current study. In a previous study in which 73 fetal heart rate tracings were examined after maternal administration of ITS, Cohen et al. [5] found a 15% incidence of fetal heart rate changes, including one bradycardia. As in the current study, fetal heart rate changes were not correlated with maternal hypotension. An effect of ITS on the spinal cord, nerve roots, or the sympathetic nervous system or the rapid onset of analgesia with a sudden decrease in circulating catecholamines could affect uterine blood flow or uterine tone with resultant slowing of the fetal heart rate. Alternatively, such fetal bradycardias may merely be coincidental with ITS administration. Women often request analgesia as the intensity of their pain increases. This may be a sign that labor is progressing into an accelerated phase. Fetal bradycardia from head or cord compression may occur at this point in labor even when women have not received regional analgesia.

We also found that diluent volume did not affect analgesia or the incidence of sensory changes or hypotension. Considering the relatively large volume of CSF compared with injectate volume and the narrow range of diluent volumes tested, these findings are not surprising. In support of our results, Van Zundert et al. [22] found that diluent volume did not affect the duration or the intensity of lidocaine spinal anesthesia.

In summary, ITS provides rapid onset of intense analgesia to laboring women. It produces sensory and blood pressure changes in some patients, which are most consistent with opioid-mediated spinal cord effects. Within the ranges tested, the volume of diluent was unimportant with respect to analgesia or side effects.

We acknowledge Beemeth T. Robles, MD, and Jayshree B. Desai, MD, for helping to collect the data.

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REFERENCES

1. Leighton BL, DeSimone CA, Norris MC, Ben-David B. Intrathecal narcotics for labor revisted: the combination of fentanyl and morphine intrathecally provides rapid onset of profound, prolonged analgesia. Anesth Analg 1989;69:122-5.
2. Camann WR, Denney RA, Holby ED, Datta S. A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia. Anesthesiology 1992;77:884-7.
3. Honet JE, Arkoosh VA, Norris MC, et al. Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia. Anesth Analg 1993;75:734-9.
4. Collis RE, Baxandall ML, Srikantharajah ID, et al. Combined spinal epidural (CSE) analgesia: technique, management, and outcome of 300 mothers. Int J Obstet Anesth 1994;3:75-81.
5. Cohen SE, Cherry CM, Holbrook RH, et al. Intrathecal sufentanil for labor analgesia-sensory changes, side effects, and fetal heart rate changes. Anesth Analg 1993;77:1155-60.
6. Mandell G, Jamnback L, Ramanathan S, et al. Spinal anesthesia for labor analgesia [abstract]. Anesthesiology 1994;81:A1152.
7. Stein SA, Kinsella SM, Norris MC. Hemodynamic changes associated with intrathecal sufentanil analgesia during early labor [abstract]. Anesthesiology 1994;81:A1143.
8. D'Angelo R, Anderson MT, Philip J, Eisenach JC. Intrathecal sufentanil compared to epidural bupivacaine for labor analgesia. Anesthesiology 1994;80:1209-15.
9. Chronister T, Carter BL, Van Decar T, Knape KG. Dose effect of intrathecal narcotics on maternal blood pressure [abstract]. Anesthesiology 1993;79:A1001.
10. Power I, Brown DT, Wildsmith JAW. The effect of fentanyl, meperidine, and diamorphine on nerve conduction in vitro. Reg Anesth 1991;16:204-8.
11. Gissen AJ, Gugino LD, Datta S, et al. Effects of fentanyl and sufentanil on peripheral mammalian nerves. Anesth Analg 1991;66:1272-6.
12. Hamilton CL, Riley ET, Ratner EF, Cohen SE. Failure rates with the 24 G Sprotte[TM] and Gertie Marx[TM] spinal needles for combined spinal epidural analgesia [abstract]. Anesthesiology 1995;83:A979.
13. Jayaram A, Carp H. Progesterone-mediated potentiation of spinal sufentanil in rats. Anesth Analg 1993;76:745-50.
14. Wang C, Chakrabarti MK, Whitwam JG. Effect of low and high concentrations of alfentanil administered intrathecally on A partial and C fibre mediated somatosympathetic reflexs. Br J Anaesth 1992;68:503-7.
15. Moses M, Cascio M, Zakowski MI, Grant GJ. Hemodynamic effects of intrathecal fentanyl in term parturients [abstract]. Anesthesiology 1994;81:A1150.
16. Hamilton C, Riley E, Cohen S. Intrathecal sufentanil produces sensory changes without hypotension in male volunteers [abstract]. Anesthesiology 1995;83:A940.
17. Nagasaka H, Yaksh TL. Effects of intrathecal micro, partial, and kappa agonists on thermally evoked cardiovascular and nociceptive reflexes in halothane-anesthetized rats. Anesth Analg 1995;80:437-43.
18. Cascio M, Pygon B, Bernett C, Ramanathan S. Effects of intrathecal fentanyl on plasma catecholamine levels in term laboring parturients [abstract]. Anesthesiology 1995;83:A493.
19. Newman LM, Wlodarski JC, Tanck EN, Ivankovich AD. Neither intrathecal sufentanil nor intrathecal sufentanil plus nalbuphine cause hypotension in laboring patients [abstract]. Anesthesiology 1994;81:A1153.
20. Hamilton CL, Cohen SE. High sensory block after intrathecal sufentanil for labor analgesia. Anesthesiology 1995;83:1118-21.
21. Clarke VT, Smiley RM, Finster M. Uterine hyperactivity after intrathecal injection of fentanyl for analgesia during labor: a cause of fetal bradycardia [abstract]. Anesthesiology 1994;81:1083.
22. Van Zundert AAJ, Grouls RJE, Korsten HHM, Lambert DH. Spinal anesthesia. Volume or concentration-what matters? Reg Anesth 1996;21:112-8.
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