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Anesth Analg 2003;97:1504-1508 © 2003 International Anesthesia Research Society
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Abstract |
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On the basis of our previous clinical experience, we hypothesized in this study that the duration and/or quality of labor analgesia produced by intrathecal sufentanil was less in cocaine-abusing parturients compared with nonabusing parturients. Ten µg of sufentanil was given intrathecally as part of a combined spinal-epidural (CSE) technique to two groups of laboring parturients: 1) those whose urine tested positive for cocaine (cocaine group), and 2) those whose urine tested negative for cocaine (control group). The epidural catheter was not injected with local anesthetic until the patient requested additional pain relief. The time from injection of intrathecal sufentanil until patient request for additional pain relief was defined as duration of analgesia. Baseline visual analog pain score (VAPS) and cervical dilation were measured before the CSE was performed. After injection of intrathecal sufentanil, VAPS was recorded at specific intervals. Cervical dilation was again documented when the patient requested additional analgesia. We found that both groups reported high baseline VAPS and a marked decrease in VAPS after injection of sufentanil that did not differ between groups. Geometric mean duration of pain relief with adjustment for cervical dilation was 87 min in the cocaine group compared with 139 min in the control group (P = 0.019). All patients experienced itching. We conclude that intrathecal sufentanil produces a similar quality but shorter duration of analgesia in cocaine-abusing parturients compared with nonabusing parturients.
IMPLICATIONS: Intrathecal sufentanil administered as part of a combined spinal-epidural technique produces similar quality but reduced duration of labor analgesia in cocaine-abusing parturients compared with nonabusing parturients.
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Introduction |
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Cocaine abuse has become prevalent in our society, reaching epidemic proportions in the last decade. Although the reported incidence varies and geographic differences in incidence occur, increasing numbers of parturients are presenting to labor and delivery suites intoxicated with cocaine (1–3). The fetal effects of maternal cocaine abuse include an increased incidence of uteroplacental insufficiency, small birth weight infants, intrauterine growth retardation, preterm deliveries, abruptio placentae, and congenital abnormalities (1,2).
In our clinical experience, it has seemed more difficult to achieve successful epidural labor analgesia in many cocaine-abusing patients compared with nonabusers. Over the past decade the combined spinal-epidural (CSE) technique has been an effective technique for labor analgesia, and intrathecal sufentanil has been used successfully during parturition with few side effects (4–10). However, the effectiveness of this method of labor analgesia has not been well studied in a cocaine-abusing population, and we decided to undertake a study that compared the quality and duration of intrathecal sufentanil analgesia in cocaine-abusing and nonabusing parturients. We hypothesized that intrathecal sufentanil produces an equivalent duration and quality of labor analgesia in cocaine-abusing and nonabusing parturients.
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Methods |
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Our institution’s Committee on the Conduct of Human Research approved the study. Written informed consent was obtained from all participants. Thirty-one ASA physical status I or II parturients, a singleton pregnancy in the vertex presentation with a cervical dilation of 4 cm or less who requested labor analgesia and consented to the CSE technique were selected for the study. The patients were enrolled based on their preoperative history of positive or negative cocaine use. Patients with a positive cocaine history were assigned to the cocaine-positive group (n = 15) and those with a negative cocaine history were assigned to the cocaine-negative group (n = 16). Urine toxicology testing (benzodiazepines, opiates, amphetamines, barbiturates, phencyclidine, and salicylates) was done on all patients, and the toxicology results confirmed and agreed with histories given by all patients. Three patients giving a positive history of cocaine use also tested positive for opioids and were dropped from the study, leaving 12 in the cocaine-positive group. The toxicology results were not available before placement of the CSE and performance of the study. Staff members were not blinded as to the history of the patients for clinical reasons, but actual toxicology results were not available until each patient’s study was concluded.
Urine drug screens were performed on all patients and were conducted by the hospital pathology laboratory. Urine specimens were analyzed on the Syva-30R Biochemical System, using Emit® II Drug of Abuse Reagents (Syva Company, Dade Behring, Cupertio, CA).
All patients consented to and received CSE labor analgesia. Before placement of the CSE, all patients were prehydrated with 1000 mL of lactated Ringer’s solution, and baseline vital signs, cervical dilation (baseline T0), and Visual Analog Pain Scores (VAPS) were obtained. Epidural needle (17-gauge Tuohy) placement was performed in the sitting position at the L2-3 or L3-4 intervertebral space using a loss of resistance technique. A 25-gauge Sprotte needle was then inserted through the epidural needle and advanced until flow of cerebral spinal fluid was noted. A 10-µg dose of sufentanil in a 1 mL solution (diluted with preservative-free 0.9% NaCl) was injected intrathecally. The Sprotte needle was withdrawn, and the epidural catheter was inserted and secured. Patients were then placed in left lateral position.
Pain was assessed by using a 10-cm VAPS. Vital signs, VAPS, sensory level, and side effects such as pruritus and nausea and vomiting were recorded immediately after sufentanil injection, then every 5 min for 30 min, and then every 30 min until the patient requested additional pain relief. To reduce potential clinician bias, nurses and physicians were instructed to allow patients to initiate a request for additional pain relief without giving any input that might have been influenced by expectations resulting from a patient’s group assignment. The elapsed time from sufentanil injection until request for additional pain medication was defined as the duration of intrathecal analgesia. Once the patient requested additional pain relief, a cervical examination (at first request for additional analgesia, T1) was performed, and the epidural catheter was injected with local anesthetic to achieve patient comfort. The study was then concluded.
Fetal heart rate and uterine activity were monitored by either external tocodynamometer or intrauterine pressure catheter continuously throughout labor as clinical assessment.
The duration of labor, mode of delivery, infant birth weight, Apgar scores, and fetal head position were also recorded. All patients were questioned on release from anesthesia care regarding itching, nausea, and vomiting. Patients were asked to rate their labor analgesia as excellent, good, average, or unsatisfactory.
Demographic data were compared for group differences using the two-sample Student’s t-test except as otherwise noted. Apgar scores at 1 and 5 min and cervical dilation and change were compared using Wilcoxon’s ranked-sum test. The mode of delivery and the side effects—hypotension requiring medication, fetal bradycardia, respiratory depression, and nausea and vomiting—were compared for group difference using the exact 
2 test. Cervical dilation and VAPS were compared using repeated-measures analysis of variance. Duration of sufentanil analgesia was compared on the log scale using the analysis for covariance with a covariate adjustment for baseline cervical dilation and adjustments for unequal group variance. Because sufentanil analgesia durations were compared on the log-scale, their group means were reported as geometric means with their 95% confidence limits. All analyses were performed using SAS software (SAS Institute, Cary, NC).
Because we believed the duration of analgesia was the most clinically significant variable we were studying, we performed a power analysis during the design phase of the protocol before initiation of the study to determine the sample size needed to detect a 30-min difference in duration of sufentanil analgesia between the control and cocaine groups, assuming a within-group standard deviation of 25 min. The power calculations, based on a 2-sample Student’s t-test, determined that a sample size of 12 per group would be needed to find the 30-min difference that was significant with 80% power.
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Results |
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The mean duration of analgesia from intrathecal sufentanil was significantly shorter for the cocaine group. Patients in the cocaine group achieved a mean of 87 min of analgesia after intrathecal sufentanil injection compared with a mean of 139 min for the control group (Table 1). Ethnicity, parity, and age were unrelated to duration of analgesia. The quality of analgesia achieved was similar between the groups with no significant difference in lowest VAPS or percent reduction in VAPS found (Table 1). In addition, all patients reported good to excellent analgesia. Although cocaine abusers requested additional analgesia sooner than nonabusers, the mean cervical dilation at request for additional pain relief was the same for both groups. When we checked for cervical dilation the cocaine abusers seemed to progress to 5 cm 45 min sooner than nonabusers. The median change of dilation was 2 cm for abusers and 1 for nonabusers, which was not significant (Table 1).
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Demographic variables, including age, height, and weight, were similar between the groups. The two groups were also comparable for infant gestational age, birth weight, and 1- and 5-min Apgar scores (Table 2). Two patients in the cocaine group and 1 patient in the control group developed hypotension that required treatment with ephedrine. Neither fetal bradycardia (fetal heart rate <120 bpm for more than 15 s) nor maternal respiratory depression (defined as <10 breaths/min) occurred in any patient. All patients experienced some pruritus but none severe enough to require treatment. No patients in the cocaine group and 4 patients in the control group experienced nausea and vomiting. However, the incidence of nausea and vomiting was not significantly different between the groups. Mode of delivery for patients in each group is described in Table 3. There were no significant differences between the groups. Active phase arrest, experienced by 2 patients, was the indication for cesarean delivery.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
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This study demonstrated that 10 µg of intrathecal sufentanil produces similar quality but significantly shorter duration of labor analgesia in cocaine-abusing parturients (87 minutes) compared with nonabusing parturients (139 minutes). It is interesting to note that the duration of analgesia in our nonabusing parturients is similar to the duration of analgesia reported in other studies of intrathecal sufentanil for labor analgesia (4,7–10).
Previous studies have shown that intrathecal opioids can provide labor analgesia, but they are generally less effective during late first stage of labor (7–9 cm cervical dilation) (4). Viscomi et al. (8) have also shown that intrathecal opioids produce a shorter duration of analgesia when administered in late labor as compared with early labor and cervical dilation. Furthermore, they concluded that the stage of labor significantly impacts the effective duration of intrathecal analgesia. In our study, the durations of analgesia were compared with an adjustment for baseline cervical dilation so that this was not a factor in the difference. We used analysis of covariance to eliminate the covariate effect of cervical dilation. We still found a significantly shorter duration of analgesia in the cocaine-abusing group versus the non-cocaine-abusing group.
There is evidence that cocaine exposure increases contractile activity in the myometrium of both pregnant and nonpregnant rats. Increases in both the force and duration of contractions over time were found (11). More importantly, in vitro studies of human pregnant myometrium have shown that cocaine increases both spontaneous and oxytocin-induced myometrial contractility (12). Cocaine increases systemic circulating catecholamines and selectively blocks beta-receptor sites in the pregnant myometrium, producing excess alpha stimulation and an increase in uterine contractility (13,14). Nonadrenergic mechanisms also seem to play a role in the increased contractility produced by cocaine. This has been demonstrated by an increased response to oxytocin produced by cocaine that could not be blocked by an alpha-adrenergic antagonist (prazosin) (15). These factors involved in contractility may increase the pain intensity of contractions in the cocaine-abusing parturient.
Another study found that patients using opiates and cocaine have decreased pain tolerance (16). The authors suggested that the decreased pain tolerance may be associated with neurophysical changes in the midbrain because the descending inhibitory pain pathways may be less effective in the presence of drugs that provide euphoria. This may lead the cocaine abusers to have an altered perception of pain. Furthermore, differences in catecholamines and endorphin levels in these patients may also contribute to a difference in their pain perception. The differences in pain perception between cocaine abusers and nonabusers might partly explain the shorter duration of labor analgesia that we found in cocaine-abusing patients.
Another study has shown that cocaine may potentiate opioid receptors by an upregulation of mu and kappa receptors in the brain (17). Cocaine inhibits dopamine reuptake, and this increased dopaminergic activity may play a role in the regulation of mu and kappa opioids receptors (18). This would cause one to expect an increase in duration of analgesia in these parturients. Therefore, the mechanism for our reduced duration needs further investigation.
This study was not blinded because of clinical concerns. The patients knew the group to which they belonged. They understood the purpose of the study and could have responded in such a manner. To reduce the potential biases of an unblinded study, clinicians, both nurses and physicians, were instructed to allow the patients to initiate any request for pain relief without prompting and to avoid providing subtle clues about any personal expectations of outcome.
The profile of side effects was similar in the two groups. All 28 patients experienced pruritus, which has been reported in other studies using intrathecal sufentanil (5,6,10). Three patients, 2 in the cocaine group and 1 in the control group, experienced hypotension severe enough to require treatment with ephedrine. All responded satisfactorily to this treatment, and phenylephrine was not required. None of the patients experienced fetal bradycardia or maternal respiratory depression. No patients in the cocaine group and 4 patients in the control group experienced nausea and vomiting, which are other reported side effects of intrathecal sufentanil (5,6).
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Conclusion |
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TopAbstractIntroductionMethodsResultsDiscussionConclusionReferences |
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This study has shown that the duration of labor analgesia from intrathecal sufentanil is significantly decreased in cocaine-abusing parturients compared with nonabusing parturients. Two factors might contribute to the differences found. They include an increased intensity of uterine contractions in cocaine-abusing patients and possible altered perception of pain between abusers and nonabusers. Further studies into the mechanism of this decreased duration are warranted.
Regardless of the decreased duration compared with nonabusers, the CSE technique with intrathecal sufentanil did provide very good labor analgesia for cocaine-abusing parturients with very few side effects. Although the effects of adding local anesthetic to the intrathecal sufentanil were not studied here, a previous study has found that the addition of local anesthetic to intrathecal sufentanil prolongs the duration of labor analgesia (19). When choosing the CSE technique for a cocaine-abusing parturient, one should expect a shorter duration of spinal analgesia. The addition of local anesthetic to the intrathecal opioid or the immediate initiation of an epidural infusion after completion of the CSE procedure should be considered because it might prolong the analgesic effects.
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References |
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- Datta S. Anesthetic and obstetric management of high-risk pregnancy. 2nd ed. St. Louis: Mosby-Year Book, 1996: 514–20.
- Kain ZN, Rimar S, Barash PG. Cocaine abuse in the parturient and effects on the fetus and neonate. Anesth Analg 1993; 77: 835–45.
[Free Full Text] - Kain ZN, Mayes LC, Ferris CA, et al. Cocaine-abusing parturients undergoing cesarean section. Anesthesiology 1996; 85: 1028–35.[Web of Science][Medline]
- Honet JE, Arkoosh VA, Norris MC, et al. Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia. Anesth Analg 1992; 75: 734–9.
[Abstract/Free Full Text] - Cohen SE, Cherry CM, Holbrook RH Jr, et al. Intrathecal sufentanil for labor analgesia: sensory changes, side effects, and fetal heart rate changes. Anesth Analg 1993; 77: 1155–60.
[Abstract/Free Full Text] - Norris MC, Grieco WM, Borkowski M, et al. Complications of labor analgesia: epidural versus combined spinal epidural techniques. Anesth Analg 1994; 79: 529–37.
[Abstract/Free Full Text] - D’Angelo R, Anderson MT, Philip J, Eisenach JC. Intrathecal sufentanil compared to epidural bupivacaine for labor analgesia. Anesthesiology 1994; 80: 1209–15.[Web of Science][Medline]
- Viscomi CM, Rathmell JP, Pace NL. Duration of intrathecal labor analgesia: early versus advanced labor. Anesth Analg 1997; 84: 1108–12.[Abstract]
- Riley ET, Walker D, Hamilton CL, Cohen SE. Intrathecal sufentanil for labor analgesia does not cause a sympathectomy. Anesthesiology 1997; 87: 874–8.[Web of Science][Medline]
- Wehbeh H, Matthews RP, McCalla S, et al. The effect of recent cocaine use on the progress of labor. Am J Obstet Gynecol 1995; 172: 1014–8.[Web of Science][Medline]
- Monga M, Weisbrodt NW, Andres RL, Sanborn BM. Cocaine acutely increases rat myometrial contractile activity by mechanisms other than potentiation of adrenergic pathways. Am J Obstet Gynecol 1993; 169: 1502–6.[Web of Science][Medline]
- Daniel EE, Wolowyk M. The contractile response of the uterus to cocaine. Can J Physiol Pharmacol 1966; 44: 721–30.[Web of Science][Medline]
- Hurd WW, Gauvin JM, Dombrowski MP, Hayashi RH. Cocaine selectively inhibits beta-adrenergic receptor binding in pregnant human myometrium. Am J Obstet Gynecol 1993; 169: 644–9.[Web of Science][Medline]
- Wang FL, Dombrowski MP, Hurd WW. Cocaine and beta-adrenergic receptor function in pregnant myometrium. Am J Obstet Gynecol 1996; 175: 1651–3.[Web of Science][Medline]
- Hurd WW, Betz AL, Dombrowski MP, Fomin VP. Cocaine augments contractility of the pregnant human uterus by both adrenergic and nonadrenergic mechanisms. Am J Obstet Gynecol 1998; 178: 1077–81.[Web of Science][Medline]
- Compton MA. Cold-pressor pain tolerance in opiate and cocaine abusers: correlates of drug type and use status. J Pain Symptom Manage 1994; 9: 462–73.[Web of Science][Medline]
- Sierra V, Duttaroy A, Lutfy K, et al. Potentiation of opioid analgesia by cocaine: the role of spinal and supraspinal receptors. Life Sci 1992; 50: 591–7.[Web of Science][Medline]
- Unterwald EM. Regulation of opioid receptors by cocaine. Ann N Y Acad Sci 2001; 937: 74–92.[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]
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