Diane Alves

Dose-Response Relationship of Intrathecal Morphine for Postcesarean Analgesia

BACKGROUND This series investigated the quality of analgesia and the incidence and severity of side effects of intrathecal morphine for post-cesarean analgesia administered over a dose range of 0.0-0.5 mg. METHODS ONE hundred eight term parturients undergoing cesarean delivery at term and given spinal anesthesia were randomized to receive a single dose of intrathecal morphine (0.0, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.4, or 0.5 mg). A patient-controlled analgesia (PCA) device provided free access to additional analgesics. PCA morphine use, incidence and severity of side effects, and need for treatment interventions were recorded for 24 h. Data were analyzed with analysis of variance and linear regression analysis for trends among groups. RESULTS Patient-controlled analgesia use differed significantly between groups; PCA use was higher in the control group than in groups receiving 0.075, 0.1, 0.3, 0.4, or 0.5 mg. Twenty-four-hour PCA morphine use was 45.7 mg lower (95% CI, 4.8-86.6 mg lower) in the 0.075-mg group than the control group. There was no difference in PCA morphine use between the 0.075- and 0.5-mg groups (95% CI, 36.8 mg lower to 45.0 mg higher); despite a fivefold increase in intrathecal morphine dose, PCA morphine use remained constant. There was no difference between control and treatment groups or among treatment groups with respect to nausea and vomiting. Pruritus and the need for treatment interventions increased in direct proportion to the dose of intrathecal morphine (linear regression, P = 0.001 and P = 0.0002, respectively). CONCLUSIONS These data indicate there is little justification for use of more than 0.1 mg for post-cesarean analgesia. For optimal analgesia, augmentation [corrected] of intrathecal morphine with systemic opioids may be necessary.

The dose-response relation of intrathecal fentanyl for labor analgesia.

Background This study determined the dose‐response relation of intrathecal fentanyl for labor analgesia and described the onset, duration, and quality of analgesia when used as the sole analgesic. Methods Eighty‐four parturients in active labor who requested analgesia were randomized to one of seven treatment groups. They received 5–45 micro gram intrathecal fentanyl as part of a combined spinal‐epidural technique. Visual analog pain scores were recorded before and at intervals after injection patients requested additional analgesia. The occurrence and severity of pruritus, nausea, and vomiting were also recorded. Maternal blood pressure was recorded before injection and at intervals after injection. Fetal heart rate was recorded before and 30 min after injection. Results By 5 min after injection, pain scores were significantly different among groups (P < 0.001). Mean duration of analgesia increased to 89 min as the dose increased to 25 micro gram. Maternal diastolic blood pressure was significantly lower 10 and 30 min after injection. There was no difference among groups in the incidence of pruritus; nausea and vomiting were uncommon. Fetal heart rates did not change after injection. A dose‐response curve indicates that the median effective dose of intrathecal fentanyl for labor analgesia is 14 micro gram (95% confidence interval, 13–15 micro gram). Conclusions Intrathecal fentanyl produces rapid, profound labor analgesia with minimal side effects. These data indicate that there is little benefit to increasing the dose beyond 25 micro gram when it is used as the sole agent for intrathecal labor analgesia.

Postcesarean epidural morphine: a dose-response study.

The purpose of this study was to describe the dose-response relationship of epidural morphine for postcesarean analgesia for quality of analgesia and relation to the side effects of pruritus, nausea, and vomiting. Sixty term parturients undergoing nonurgent cesarean delivery were enrolled and randomized to receive a single dose of epidural morphine after delivery (0,1.25, 2.5, 3.75, or 5 mg). A patient-controlled analgesia (PCA) device provided free access to additional analgesics. PCA morphine use and the incidence and severity of side effects were recorded for 24 h. Data were analyzed with analysis of variance, Student’s t-tests, and &khgr;2 analysis. Nonlinear regression was used to describe a dose-response curve. PCA use differed significantly among groups (P < 0.001); PCA use was significantly greater in Group 0 mg than Groups 2.5, 3.75, and 5 mg (P < 0.05). PCA use was also significantly greater in Group 1.25 mg than Groups 3.75 and 5 mg (P < 0.05). Pruritus scores were significantly higher in all groups given epidural morphine than the control group (0 mg) (P < 0.05), but did not differ among the treatment groups (1.25–5 mg), although pruritus scores were significantly higher in treatment groups than in the control (P < 0.05). No relation was found between epidural morphine dose and incidence or severity of nausea and vomiting. We concluded that, for optimal analgesia, augmentation of epidural morphine with systemic analgesics or other epidural medications may be necessary. Implications: Quality of analgesia increases as the dose of epidural morphine increases to at least 3.75 mg; increasing the dose further to 5 mg did not improve analgesia. Side effects were not dose related. For optimal analgesia, augmentation of epidural morphine with systemic analgesics or other epidural medications may be necessary.