Very Low Dose Intrathecal Morphine Provides Effective Analgesia and Minimizes Side Effects After CABG Surgery

Abstract

Introduction: Several authors have reported the use of intrathecal morphine (ITM) to provide analgesia after adult cardiac surgery. However, side effects (SE), including sedation, nausea (N), pruritus (P) and respiratory depression may prevent some anesthesiologists from incorporating ITM into their practice. The goal of this study was to determine if very low dose ITM would provide effective analgesia and minimize side effects. Materials and Methods: After informed consent 21 adult patients (pts) undergoing CABG surgery were prospectively randomized in a double blind fashion to receive intrathecal saline (ITS) (Grp1), 4.25 ucg/kg ITM (Grp 2) or 7 ucg/kg ITM (Grp 3). The volume of all injections was increased to 1 ml with preservative free saline. The anesthetic was standardized. Postoperatively pts received IV PCA morphine (MS) as follows; no baseline infusion, MS dose 1 mg, lockout time 8 minutes, 30 mg maximum in 4 hours. If patients were uncomfortable the pain service was permitted to increase the bolus dose of MS and decrease the lockout. Physicians and/or nurses were permitted to administer a rescue bolus dose of IV MS if the pt was in severe pain. A visual analogue scale (0-10) was used to evaluate: chest pain (CP), leg pain (LP), N, and P every 4 hrs for 48 hrs postop. Respiratory rate/min (RR) was measured at the same time intervals. For each variable, the average of measurements at all data collection times was determined. Means were compared between the groups. The groups were also compared for MS (ucg/kg) required via PCA for 48 hrs postop (MS48). To determine whether ITM influenced time until pts were ready for extubation and to control for different surgeons' preferences regarding time of extubation, we measured the number of hrs postop until pts performed 3 extubation criteria (ExtubCrit): negative inspiratory pressure = - 30 cmH2O, vital capacity 12 cc/kg, and 5 second head lift. Values are presented as means +/- SD. Statistical significance was determined with Wilcoxon Rank Sum Test for all variables except the number of rescue doses of MS for which Fisher's exact test was used. p <0.05 was considered significant. Results: To date, there are insufficient subjects to include Grp 3 in the data analysis: (Grp 1, n=10), (Grp 2, n=8), (Grp 3, n=3). CP was significantly less with ITM (0.7 +/- 0.6) vs. control (2.6 +/- 1.5) (p=0.004), as was LP, ITM (0.06 +/- 0.1) vs. control (1.4 +/- 2.1) (p=0.002). ITM did not increase N (0.06 +/- 0.1) vs control (1.4 +/- 2) (p = 0.8) or P: ITM (0.2 +/- 0.4) vs control (0.2 +/- 0.5) (p=0.6). ITM pts required less MS 48 (ucg/kg) (0.27 +/- 0.2) vs control (0.6 +/- 0.4) (p=0.04). There were no differences between the Grps for the number of rescue doses of MS: ITM (38%) vs control (30%) (p=1.0). ITM did not prolong time (hrs) to ExtubCrit (4.1 +/- 2.7) vs control (5.2 +/- 2.4) (p=0.4), and did not slow RR: ITM (17.6 +/- 1.8) vs control (18.4 +/- 1.2) (p=0.2). Discussion: This study determined that very low dose ITM, 4.25 ucg/kg, provided effective analgesia with no increased side effects as compared to placebo. There were inadequate subjects to compare the 4.25 ucg/kg ITM dose to 7 ucg/kg ITM. However, the fact that 4.25 ucg/kg resulted in mean scores for CP and LP of (0.7 +/- 0.6) and (0.06 +/- 0.1) respectively, and the low requirement in the 4.25 ucg/kg ITM Grp for MS 48 (ucg/kg) (0.27 +/- 0.2), provides evidence that this very low dose, 4.25 ucg/kg ITM, does in fact provide effective postop analgesia after CABG. Prior reports of excessive sedation, N, P, and prolonged controlled ventilation, may be due to excessive dosing. Completion of this study will determine whether 7 ucg/kg ITM provides improved analgesia as compared to 4.25 ucg/kg ITM and if this higher dose worsens side effects.