Source: Cohen et al. Anesth Analg 2002; 94: 674-9

Reviewer:  R. Prasad, MD

Conclusion:

• Pts receiving IV (vs. epid) fent reqd higher infusion rates and larger total doses of fentanyl, had more pain, and greater incidences of nausea, vomiting, and excessive sedation.
• Total required dose of epidural (but not IV) fentanyl is reduced by very small epidural bupiv + epinephrine

• Appears to be a nicely designed, executed study
• Forgot to include detailed power analysis info?
• Epid bupiv groups received very low bupiv doses (0.015%, 12ml/hr = 1.8 mg/hr) with epi (1.2 mcg/hr)
• data consistent with synergism between one/both of these and epidural fentanyl
• extends other studies showing local anesthetic-fentanyl synergism (in non-OB pts)
• Nice discussion section on why older studies failed to demonstrate spinal effect of epidural vs IV fent - may be due to
• use of lower infusion rates (with less spread, which is vital for epid efficacy)
• high fentanyl concentrations (resulting in higher systemic absorption, producing analgesia through supraspinal mech)
• In this study their gtt rate was only 2ml/hr! However, it would have been delivered along with the "carrier" epidural infusion (either saline or dilute bupiv), running at 12ml/hr for a final volume of 14ml/hr, plus 0-6ml/hr from PCA boluses.

• 100 ASA I-II women s/p c-sect under epidural anes, studied for 48h
• power analysis to detect 30% diff in total fentanyl, epid vs IV groups
• alpha, beta, gamma, delta?
• LR 1.5-2L, then epid dosed to T4-6 level (lido 2% with fent and epi) for surgery
• Randomly assigned (in PACU), double-blinded study. 4 groups:
• I-BeFe: Bupiv epid, Fent epid
• II-BeFi: Bupiv epid, Fent IV
• III-SeFi: Saline epid, Fent IV
• IV-SeFe: Saline epid, Fent epid
• I, II: bupiv 0.015% with epi 1 mcg/ml at 12ml/hr x 48hrs
• III, IV: epid NS at 12ml/hr
• all: Fent by PCA (20 mcg/ml; 2 ml/h + 1ml q10min PCA) hooked up to epid and IV by hidden 3-way stopcock turned to appropriate route
• if no PCA demand in 4h, investigator offered to reduce infusion rate
• no other analgesics given
• Serum fent measured at 0, 24, and 48h
• Colostrum at 24, 48h (not enough samples collected for reliable info)

• Groups similar age, parity
• SeFi weight "slightly less" than BeFe (specifics not given)
• 5pts dropped out of study (2 in BeFi, 2 in SeFi, 1 in SeFe)
• mean fent gtt rate, total fent (48h): BeFe < SeFe < BeFi or SeFi
• PCA demands: SeFi > BeFi, SeFi (howerver, actual doses delivered did not differ)
• mean pain scores (VAS 0-10): BeFi, SeFi > BeFe, SeFe
• pruritus (requests for tx): BeFi < others
• sedation (VAS [0-10] > 3): BeFe, SeFe < BeFi, SeFi
• nausea, vomiting: BeFi, SeFi > BeFe, SeFe
• uterine cramping: BeFe < SeFe
• time to resume liquid diet: BeFi, SeFi > BeFe, SeFe
• time to flatus: SeFi > BeFe, SeFe
• combined analysis, fent given epid vs IV:

• fent plasma concentration at 24h and 48h: BeFi, SeFi > BeFe, SeFe