Intrathecal sufentanil and epidural bupivacaine for labor analgesia

Dose-response of individual agents and in combination

William Camann, Amr Abouleish, James Eisenach, David Hood, Sanjay Datta

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Backgrounds and Objectives. Combinations of local anesthetics and opioids are frequently used during spinal and epidural analgesia for the relief of labor pain. This combination allows for a dose-sparing effect which may reduce potential side effects or toxicity. The precise nature of the interaction between opioids and local anesthetics in the clinical setting, i.e., additivity versus synergism, has not been established. This trial was designed to utilize a validated technique of analysis of drug interactions, isobolography, to investigate this interaction. Methods. One hundred healthy laboring patients at term receiving a combined spinal and epidural technique were divided into nine groups as follows: intrathecal sufentanil 2, 5, or 10 μg (2 mL volume) and epidural saline (10 mL); epidural bupivacaine 5, 12.5, or 25 mg and intrathecal saline (2 mL volume); or combination of 1, 2.5, and 5 μg intrathecal sufentanil plus 2.5, 6.25, or 12.5 mg epidural bupivacaine, using similar volumes, respectively. All drugs were administered in a randomized, double-blind fashion. Pain relief scores were assessed 20 minutes after drug injection, and isobolographic analysis was utilized to determine the nature of the interaction. Results. The ED50 of intrathecal sufentanil alone was 2.3 μg (95% CI 1.7-3.2), and the ED50 for epidural bupivacaine was 24 mg (95% CI 12-50). The combined sufentanil and bupivacaine fractional dose ED50 (in fractions of the single-dose ED50 values) was found to be approximately one-third and one-tenth of the single drug fractional dose, respectively: sufentanil 0.85 μg (0.36) and bupivacaine 2.2 mg (0.09). The duration of analgesia was nearly equivalent in all sufentanil-alone groups (83, 102, and 99 minutes); a dose-response effect was more apparent in the bupivacaine group (35, 42, and 74 minutes; P = .006) and the combination group (60, 79, 101 minutes; P = .028). Isobolography showed the combination dose to lie well within the area of synergism; however, the 95% confidence limits cross the line of additivity thus a pure additive interaction cannot be excluded. Conclusions. Markedly reduced doses of these drugs in combination can be used to provide adequate analgesia during labor compared with either single drug alone.

Original languageEnglish
Pages (from-to)457-462
Number of pages6
JournalRegional Anesthesia and Pain Medicine
Volume23
Issue number5
StatePublished - Sep 1998
Externally publishedYes

Fingerprint

Sufentanil
Bupivacaine
Analgesia
Local Anesthetics
Pharmaceutical Preparations
Opioid Analgesics
Labor Pain
Epidural Analgesia
Drug Combinations
Drug Interactions
Pain
Injections

Keywords

  • Bupivacaine
  • Isobolography
  • Sufentanil

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Intrathecal sufentanil and epidural bupivacaine for labor analgesia : Dose-response of individual agents and in combination. / Camann, William; Abouleish, Amr; Eisenach, James; Hood, David; Datta, Sanjay.

In: Regional Anesthesia and Pain Medicine, Vol. 23, No. 5, 09.1998, p. 457-462.

Research output: Contribution to journalArticle

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abstract = "Backgrounds and Objectives. Combinations of local anesthetics and opioids are frequently used during spinal and epidural analgesia for the relief of labor pain. This combination allows for a dose-sparing effect which may reduce potential side effects or toxicity. The precise nature of the interaction between opioids and local anesthetics in the clinical setting, i.e., additivity versus synergism, has not been established. This trial was designed to utilize a validated technique of analysis of drug interactions, isobolography, to investigate this interaction. Methods. One hundred healthy laboring patients at term receiving a combined spinal and epidural technique were divided into nine groups as follows: intrathecal sufentanil 2, 5, or 10 μg (2 mL volume) and epidural saline (10 mL); epidural bupivacaine 5, 12.5, or 25 mg and intrathecal saline (2 mL volume); or combination of 1, 2.5, and 5 μg intrathecal sufentanil plus 2.5, 6.25, or 12.5 mg epidural bupivacaine, using similar volumes, respectively. All drugs were administered in a randomized, double-blind fashion. Pain relief scores were assessed 20 minutes after drug injection, and isobolographic analysis was utilized to determine the nature of the interaction. Results. The ED50 of intrathecal sufentanil alone was 2.3 μg (95{\%} CI 1.7-3.2), and the ED50 for epidural bupivacaine was 24 mg (95{\%} CI 12-50). The combined sufentanil and bupivacaine fractional dose ED50 (in fractions of the single-dose ED50 values) was found to be approximately one-third and one-tenth of the single drug fractional dose, respectively: sufentanil 0.85 μg (0.36) and bupivacaine 2.2 mg (0.09). The duration of analgesia was nearly equivalent in all sufentanil-alone groups (83, 102, and 99 minutes); a dose-response effect was more apparent in the bupivacaine group (35, 42, and 74 minutes; P = .006) and the combination group (60, 79, 101 minutes; P = .028). Isobolography showed the combination dose to lie well within the area of synergism; however, the 95{\%} confidence limits cross the line of additivity thus a pure additive interaction cannot be excluded. Conclusions. Markedly reduced doses of these drugs in combination can be used to provide adequate analgesia during labor compared with either single drug alone.",
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