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OBSTETRIC ANESTHESIA

Intrathecal Versus Intravenous Fentanyl for Supplementation of Subarachnoid Block During Cesarean Delivery

Department of Anesthesiology, American University of Beirut, Medical Center, Beirut, Lebanon

Address correspondence and reprint requests to Anis Baraka, MD, FRCA, Department of Anesthesiology, American University of Beirut, PO Box 11-0236, Beirut, Lebanon. Address e-mail to abaraka{at}aub.edu.lb

	Abstract

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Forty-eight healthy parturients scheduled for elective cesarean delivery were randomly allocated to receive intrathecally either 12 mg of hyperbaric bupivacaine plus 12.5 µg of fentanyl (n = 23) or bupivacaine alone (n = 25). In the latter group, IV 12.5 µg of fentanyl was administered immediately after spinal anesthesia. We compared the amount of IV fentanyl required for supplementation of the spinal anesthesia during surgery, the intraoperative visual analog scale, the time to the first request for postoperative analgesia, and the incidence of adverse effects. Additional IV fentanyl supplementation amounting to a mean of 32 ± 35 µg was required in the IV Fentanyl group, whereas no supple- mentation was required in the Intrathecal Fentanyl group (P = 0.009). The time to the first request for postoperative analgesia was significantly longer in the Intrathecal Fentanyl group than in the IV Fentanyl group (159 ± 39 min versus 119 ± 44 min; P = 0.003). The incidence of systolic blood pressure <90 mm Hg and the ephedrine requirements were significantly higher in the IV Fentanyl group as compared with the Intrathecal Fentanyl group (P = 0.01). Also, intraoperative nausea and vomiting occurred less frequently in the Intrathecal Fentanyl group compared with the IV Fentanyl group (8 of 23 vs 17 of 25; P = 0.02).

IMPLICATIONS: Supplementation of spinal bupivacaine anesthesia for cesarean delivery with intrathecal fentanyl provides a better quality of anesthesia and is associated with a decreased incidence of side effects as compared with supplementation with the same dose of IV fentanyl.

	Introduction

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Spinal anesthesia is often used for elective cesarean delivery (1). However, intrathecal (IT) bupivacaine alone may be insufficient to provide complete analgesia, despite the high sensory block; one article states that 13% of the patients undergoing cesarean delivery had visceral pain after the IT administration of 15 mg of bupivacaine (2). Furthermore, such large doses of IT bupivacaine were associated with severe hypotension and delayed recovery of motor block (3).¹ Therefore, smaller doses of bupivacaine supplemented by IT opioids have been recommended for spinal anesthesia in parturients undergoing cesarean delivery (4–8).

Although IT opioids supplement spinal anesthesia, that fact alone does not prove that the drug site of analgesic action resides in the spinal cord (9). An experimental study showed that a significant amount of an IT administered lipophilic opioid, such as fentanyl, is lost by diffusion into the epidural space and subsequently into the plasma (10), suggesting that IT-administered fentanyl may induce analgesia by a systemic rather than by a spinal action.

Our hypothesis was that, if IT fentanyl induces analgesia predominantly through absorption into the bloodstream rather than by a spinal action, it will produce at best the same effect as the same dose injected IV. No previous clinical study has compared IT fentanyl with the same dose of IV fentanyl for supplementation of spinal anesthesia for cesarean delivery. This study compares the effect of IT fentanyl versus the same dose of IV fentanyl on the amount of intraoperative analgesic supplementation in women undergoing elective cesarean delivery. Also, the onset, duration, and quality of bupivacaine-induced spinal block, the incidence of adverse effects, and the time to the first request for postoperative analgesics were compared between the two groups.

	Methods

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After obtaining approval from our IRB and consent from the patients, a randomized, double-blinded, prospective study was performed in 48 parturients scheduled for elective cesarean delivery. Patients were all classified as ASA physical status I or II and had no contraindication to spinal anesthesia. Complicated pregnancies, such as multiple pregnancy, pregnancy-induced hypertension, and morbidly obese patients, were excluded. Patients received no preoperative medications.

The 48 subjects were allocated into 2 groups by using a sealed-envelope technique. The IT Fentanyl group received 12 mg of hyperbaric bupivacaine 0.75% (Abbott Laboratories, North Chicago, IL) and 12.5 µg of IT fentanyl (23 patients). The IV Fentanyl group received 12 mg of hyperbaric bupivacaine 0.75% alone (25 patients).

After arriving in the operating room, all parturients were given a rapid IV infusion of 500 mL of polygeline (Hemaccel®) (Hoechst Marion Roussel, Frankfurt, Germany). Electrocardiogram, pulse oximetry, and noninvasive blood pressure were monitored. Lumbar puncture was performed in the sitting position at the L2-3 or L3-4 interspace with a 25-gauge Whitacre needle with the aperture directed cephalad. In the IT Fentanyl group, IT bupivacaine and fentanyl were used, whereas in the IV Fentanyl group, bupivacaine was mixed with cerebrospinal fluid to achieve the same final volume as in the IT bupivacaine-fentanyl mixture. Immediately after IT administration of the local anesthetic mixture, 12.5 µg of fentanyl (0.25 mL) was administered IV in the IV Fentanyl group, whereas 0.25 mL of IV saline was injected in the IT Fentanyl group. Immediately after the block, each parturient was placed supine with 15° to 20° of left uterine displacement. Oxygen 5 L/min was given via a face mask during the surgery. The investigators who observed and evaluated the patients during and after surgery were not involved in performing the spinal anesthesia or the first IV fentanyl or placebo administration and were blinded to patient group.

Intraoperative blood pressure was measured by a noninvasive blood pressure monitor every minute until delivery of the baby and at 3-min intervals until the end of the surgery. Whenever systolic blood pressure (SBP) was less than 100 mm Hg or 20% below the preinduction level (defined as hypotension), ephedrine 5 mg was administered IV. Severe hypotension was defined as SBP <90 mm Hg. The number of hypotensive episodes and the total dose of ephedrine used for each patient were recorded. Sensory block level was measured by pinprick at the midclavicular line every minute until the block reached the T6 dermatome. Thereafter, the level was checked every 2 min until the maximum sensory block level was confirmed. The degree of motor block was assessed with the Bromage scale (BS): 0, full flexion of knee and feet; 1, just able to move knees; 2, able to move feet only; 3, unable to move feet and knees.

The surgical technique was uniform in all patients and included exteriorization of the uterus. Pain was evaluated with a 10-cm linear visual analog scale (VAS), with 0 corresponding to no pain and 10 to the worst pain imaginable. The use of the VAS had been explained to each patient before surgery. Patients were asked to rate the VAS before delivery (VAS_pre), when the uterus was exteriorized, after replacement of the uterus into the abdominal cavity, and whenever the patient complained of discomfort or pain during surgery. Each time VAS exceeded 3, 25-µg increments of fentanyl IV were administered every 5 min until the VAS became <3.

Intraoperative nausea, vomiting, pruritus, and shivering were recorded. Also, the level of maternal sedation was noted by using a graded score, with 0 = no sedation, 1 = mild sedation, 2 = moderate sedation, and 3 = severe sedation with difficulty to arouse. After delivery, the Apgar scores were assessed at 1 and 5 min.

On arrival in the postanesthesia care unit (PACU), sensory level was assessed by pinprick; the times required from the spinal injection until sensory recovery to T12 and until motor recovery to BS 0 were recorded. The time to the first request for postoperative analgesics was recorded in the PACU.

Group size was determined by power analysis with = 0.05 and ß = 0.1 (i.e., power = 90%) to detect a 30% reduction in the intraoperative analgesic supplementation between the two groups (11). It was estimated that a minimum of 20 subjects would be necessary in each group.

Data were analyzed by using the unpaired Student’s t-test, Fisher’s exact test, ² tests, or the Mann-Whitney U-test, as required. P < 0.05 was considered statistically significant. Data are presented as mean values ± SD, median (range), and n (%).

	Results

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There were no significant differences between the IT Fentanyl group and the IV Fentanyl group with respect to age, height, weight, parity, or gestational age (Table 1). IT injection to delivery time and duration of surgery did not differ between the two groups. Also, the level of analgesia to pinprick, the onset of sensory block, the sensory level upon arrival at the PACU, and the time to T12 regression were similar in both groups. The degree of motor block in all patients reached a BS of 3; also, the duration of motor block was not statistically significant between the two groups (Table 2).

The incidence of severe hypotension, defined as SBP <90 mm Hg, and ephedrine requirements was significantly more frequent in the IV Fentanyl group as compared with the IT Fentanyl group (P = 0.01). Also, intraoperative nausea and vomiting occurred less frequently in the IT Fentanyl group (8 of 23), as compared with the IV Fentanyl group (17 of 25) (P = 0.02). All cases of nausea or vomiting were related to hypotension and could be relieved by ephedrine administration alone; no other medication was required to treat nausea and vomiting. There was a trend toward more pruritus in the IT Fentanyl group as compared with the IV Fentanyl group (P = 0.09), and there was a trend toward more shivering in the IV Fentanyl group as compared with the IT Fentanyl group (P = 0.08) (Table 3). However, no patient required treatment.

	Discussion

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This clinical investigation in patients undergoing elective cesarean delivery compared the quality of analgesia when spinal bupivacaine was supplemented with IT fentanyl versus the same dose of IV fentanyl. We found that intraoperative supplementation of bupivacaine spinal anesthesia with IT fentanyl resulted in a better quality of spinal anesthesia, as evidenced by the lack of need for additional intraoperative analgesics, as well as a lower intraoperative VAS before delivery. In addition, the time to the first postoperative analgesic requirement was longer in the IT Fen-tanyl group as compared with the IV Fentanyl group. These results suggest that IT fentanyl, a lipophilic opioid, may have a spinal cord site of action as opposed to systemic uptake. It is probable that IT fentanyl, despite its high volume of distribution and very low integral exposure within the spinal cord (10), diffuses partially through the substance of the spinal cord and thus has access to opioid receptors.

Many of the side effects after IT opiates, such as delayed respiratory depression, nausea, and vomiting, are associated with morphine, which is hydrophilic (12). In contrast, spinal administration of fentanyl, a lipophilic drug, may potentiate spinal anesthesia and be associated with a decreased incidence of side effects. This article shows that the IT Fentanyl group had a less frequent incidence of intraoperative side effects such as severe hypotension, nausea, and vomiting.

The mechanism by which IT fentanyl decreases severe hypotension is unclear but, as suggested by a previous article (6), might be related to a decrease in visceral pain or to a decrease in the intraoperative need for supplementation by IV opioids. The decreased incidence of nausea and vomiting after supplementation of spinal anesthesia with IT fentanyl in this study has also been reported by other investigators (5,13–16). The increased incidence of nausea and vomiting in the IV Fentanyl group may be secondary to the increased incidence of severe hypotension, because it was relieved when the blood pressure was increased after the administration of ephedrine; it might also be related to the larger dose of IV fentanyl required to block visceral pain in the IV Fentanyl group. Thus, as previously reported, it appears that the addition of IT fentanyl to bupivacaine spinal anesthesia potentiates analgesia for somatic and visceral pain without increased sympathetic block (17).

IT fentanyl-induced pruritus is very common, with the incidence varying from 40% to 73% in a dose-dependent fashion (18). In our study, the incidence of pruritus was 26% in the IT Fentanyl group compared with 8% in the IV Fentanyl group. Despite a clear trend toward more pruritus in the IT Fentanyl group, this result did not reach statistical significance (P = 0.09). The addition of IT bupivacaine to IT fentanyl reduces the incidence of pruritus, but the mechanism remains unclear (18). It may involve neuronal blockade or direct modulation of the opioid receptor (19). This side effect is well tolerated and may be underreported; usually it does not require treatment. In addition, our report showed a trend toward more shivering in the IV Fentanyl group than in the IT Fentanyl group (P = 0.08). This may suggest that IT fentanyl exerts a protective effect against shivering (20). However, a larger number of patients are required to confirm this finding.

Of note, the sample size and power calculation are merely valid for the primary end point, which in this study was the significant reduction of IV fentanyl requirements in the IT Fentanyl group. VAS and side effects such as nausea, vomiting, hypotension, pruritus, and shivering are secondary end points for which the power calculation may not be valid.

In conclusion, supplementation of bupivacaine-spinal block during cesarean delivery with IT fentanyl produces a better quality of spinal anesthesia than supplementation with the same dose of IV fentanyl. This was evidenced by a lack of need for additional intraoperative analgesia, a lower VAS before delivery, and a longer time to first request for analgesia. In addition, the IT Fentanyl group had a less frequent incidence of side effects, such as severe hypotension, nausea, and vomiting.

	Footnotes

 
¹ Swami A, McHale S, Abbot P, Morgan B. Low dose spinal anesthesia for cesarean section using combined spinal-epidural (CSE) technique [abstract]. Anesth Analg 1993;76:S423.

	References

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