Analgesics administered intraoperatively as part of the anaesthetic technique are expected to decrease the postoperative analgesic requirements or to be associated with less postoperative pain. For example preoperative or intraoperative ketorolac has been shown to decrease postoperative morphine requirements .
Opioids are routinely given intraoperatively and postoperatively to control pain. Their efficacy to provide analgesia after surgery depends largely on their physical properties and pharmacokinetic profile. It has been shown that postoperative analgesia after abdominal surgery is better after intraoperative target-controlled infusion with sufentanil than after intraoperative target-controlled infusion with remifentanil and bolus administration of morphine .
In the postanaesthesia care unit (PACU), acute pain is usually treated with intravenous (i.v.) morphine as intermittent doses and subsequently with patient-controlled analgesia (PCA) morphine or subcutaneous morphine. As the dose of analgesics between surgical patients varies for several reasons and some patients may need fewer analgesics than others , administration of analgesics intraoperatively may or may not affect the postoperative analgesic requirements. In fact, it has been shown that higher doses of sufentanil administered during surgery were associated with more intense postoperative pain in the PACU, thus including the high sufentanil dose among the independent predictive factors of severe postoperative pain .
Our hypothesis is that morphine administered intraoperatively after caesarean delivery will decrease the postoperative requirements of PCA morphine. Thus, the aim of the study was to investigate the effect of morphine given intraoperatively on the postoperative morphine consumption and postoperative pain during the first 24 h after caesarean section under subarachnoid anaesthesia.
After obtaining approval from the Hospital Ethics Committee, 62 full-term gravida 1 parturients, scheduled for elective caesarean section under subarachnoid anaesthesia from 12 October 2006 until 30 September 2008, were recruited for the study. During the preoperative visit, women were informed about the study, the PCA pump and how to use it, and the visual analogue scale (VAS) for scoring pain and gave their written informed consent to participate. Exclusion criteria were diabetes mellitus, hypertension, preeclampsia, hydramnios, recent intake of analgesic medication, more than 20 kg weight gain during pregnancy, extremes of height (>175 cm, <155 cm), and inadequate knowledge of Greek language.
Parturients were randomly allocated to two groups: the morphine group to receive 0.15 mg kg−1 of morphine after delivery of the baby and the control group to receive an equal volume of normal saline solution. Randomization was done by means of sealed envelopes containing odd or even numbers representing the morphine or the control group, respectively. An independent anaesthesiologist not participating in the study and not aware of the study protocol was responsible for patient randomization and solution preparation according to the group assignment.
In the operating room, standard monitor was applied, including five-lead electrocardiogram, noninvasive measurement of blood pressure, and pulse oximetry (S/5 Anaesthesia Monitor, Datex-Ohmeda Division, Helsinki, Finland). Two 16G catheters were inserted in peripheral veins via which we administered slowly 10 mg of metoclopramide and 50 mg of raniditine. All women received 500 ml of 6% hetastarch before the subarachnoid injection.
The L3–L4 interspace was identified and the skin was infiltrated with 2% lidocaine. Subsequently, 2 ml of 0.75% ropivacaine and 10 μg of fentanyl were injected in the subarachnoid space using a 25 G pencil point needle. If hypotension occurred, incremental doses of 2.5 mg of ephedrine were given i.v. as needed until systolic blood pressure was restored to 100 mmHg or higher. After delivery of the baby, 0.15 mg kg−1 of morphine with droperidol 50 μg mg−1 of morphine in 100 ml normal saline or 100 ml isotonic saline alone were prepared by the independent anaesthesiologist and given i.v. within 15 min in the morphine or the control group, respectively.
Postoperative analgesia and pain assessment
When surgery was completed, patients were transferred to the PACU. Postoperative analgesia was assured by means of a 60 ml PCA pump (Freedom 5, Vygon, Ecouen, France) filled with morphine 1 mg ml−1 and droperidol 50 μg ml−1 and a lock out interval of 7 min for i.v. morphine administration. Patients stayed in the PACU as long as residual motor block was present.
PCA morphine consumption and postoperative pain at rest and after cough were recorded 2, 4, 8, and 24 h postoperatively. Pain was assessed with the VAS.
The primary endpoint of the study was the analgesic consumption within the first 24 h postoperatively, and the secondary outcome measures were the VAS scores at rest and after cough.
Initial sample size estimation (10 patients in each group) showed that 27 patients should be included in each group to have a power of 0.95 for detecting a difference of 10 mg (20%) in cumulative 24-h morphine consumption between the two groups. The error was assumed to be 0.05.
Levene's test was used to compare equality of variances. The Kolmogorov–Smirnov test was used to compare normality of distributions. Patient characteristics between the groups were compared with independent samples t-test and duration of surgical procedure with the Mann–Whitney test. PCA cumulative morphine consumption and VAS scores 2, 4, 8, and 24 h postoperatively were compared with analysis of variance (ANOVA) repeated measures. Wherever appropriate, intragroup comparisons at each time point were analysed with t-test. A P value of 0.05 was considered statistically significant.
Patients' characteristics were similar regarding age and body weight (33 ± 3.9 versus 31.50 ± 3.9 years and 78 ± 11.7 versus 77 ± 11.2 kg in the morphine and the control groups, respectively). A statistically significant difference was found between the two groups regarding the height (163 ± 4.3 versus 167 ± 4.9 cm in the morphine and the control groups, respectively, P = 0.006, DF = 59, t = −2.861). Duration of surgery was similar in the two groups (56 ± 15.7 versus 58 ± 15.4 min, respectively).
Cumulative morphine consumed by the patients using the PCA pump 2, 4, 8, and 24 h postoperatively was 6 ± 4.8, 14 ± 6.6, 22 ± 9.6, and 42 ± 15.7 mg in the morphine group. For the same time points, the control group consumed 8 ± 5.1, 18 ± 7.7, 28 ± 9.4, and 43 ± 17.4 mg of morphine (F = 2.70, DF = 1, and P = 0.105 for intergroup comparisons; Fig. 1). When taking into account the morphine given intraoperatively, the overall morphine consumption was increased in women treated with morphine compared with the morphine consumed by the parturients treated with placebo (F = 13.99, DF = 1, P = 0.0005).
At rest, the VAS scores 2, 4, 8, and 24 h postoperatively were 28 ± 22.3, 40 ± 21.4, 28 ± 18.5, and 28 ± 22.2 mm in the morphine group. The pain scores in the control group were 28 ± 21.5, 43 ± 23.5, 29 ± 24.2, and 19 ± 24.8 (F = 0.37, DF = 1, P = 0.848, for intergroup comparisons; Fig. 2). After cough, VAS scores for the same time points were 35 ± 20.6, 51 ± 22.5, 42 ± 18.2, and 46 ± 23.6 mm in the morphine group. We found similar VAS values in the control group, thus 40 ± 22.1, 54 ± 28.9, 47 ± 26.5, and 38 ± 26.9 mm (F = 0.50, DF = 1, P = 0.825 for intergroup comparisons; Fig. 3).
Our results show that i.v. morphine administered during caesarean delivery does not improve postoperative pain and does not decrease the amount of morphine consumed by the parturients postoperatively.
In previous studies, including a meta-analysis of eight trials, it has been shown that preemptive administration of opioids has no effect on postoperative pain or analgesic requirements in patients undergoing abdominal hysterectomy [5–7]. However, these studies with opioids concern patients receiving general anaesthesia and the same analgesic before or during the painful stimulus. In the present study, it is surprising that a loading dose of morphine, when compared with the placebo, has no effect on postoperative pain and analgesic requirements.
In the present study, an i.v. dose of morphine intraoperatively did not attenuate the postoperative pain or the analgesic requirements. These results are partly consistent with those of Aubrun et al. who reported that immediately before the end of surgery, 0.15 mg kg−1 of morphine did not alter morphine requirements during the first 24 h postoperatively. The authors studied patients undergoing major orthopaedic surgery under general anaesthesia. These investigators found lower visual analogue pain scores in the morphine versus the placebo group in the PACU and during the first 24 h postoperatively.
However, our patients were submitted to a different type of surgery, caesarean delivery versus orthopaedic. Opioid analgesics may exhibit different efficacy in the orthopaedic versus low abdominal surgery such as caesarean section. Also, the anaesthetic technique was different. Our patients did not need titration of the opioid as they were fully awake and they used the PCA morphine along with the regression of the sensory subarachnoid block. Despite these differences and disregarding the inconsistency in the VAS pain scores between the two studies, the additional morphine 0.15 mg kg−1 administered intraoperatively did not influence the postoperative opioid consumption.
Though intraoperative opiates are expected to ameliorate postoperative pain, this may not be the case in subarachnoid anaesthesia for caesarean delivery. More studies are required to investigate the impact of systemic opiates given during surgery under a single shot subarachnoid anaesthesia on the postoperative analgesic requirements and pain.
The overall higher consumption we found in the morphine group can be explained by the fact that within this group some patients received morphine, though they did not need it. McQuay et al. have shown that 23 of the 410 patients undergoing orthopaedic limb surgery did not need analgesia at all during their hospital stay. Thus, by administering opioids routinely intraoperatively, some patients will be unnecessarily treated. Also, a number of patients will require a smaller dose of analgesics than other patients. Single shot subarachnoid anaesthesia may be more beneficial for postoperative pain control compared with general anaesthesia. Despite the clinical regression of the motor and sensory block, a subclinical analgesic effect of the local anaesthetic may remain longer.
Another explanation of our results is the possibility of acute opioid tolerance development. Exposure to morphine intraoperatively may affect opioid receptors causing desensitization and downregulation, and diminishing the efficacy of the drug [9,10]. Opioid tolerance development has a negative influence on pain management.
The difference in height between the two groups might be considered as a flow of our study. However, in the term parturient, it has been shown that the level of sensory block obtained after subarachnoid anaesthesia does not correlate with the patient's height or body weight, whereas regarding the vertebral length, the results are debatable [11–13]. The pain intensities we recorded within the first 24 h postoperatively did not differ between the two groups subjected to different interventions, and this finding is consistent with a study design of higher validity .
In conclusion, i.v. morphine given during caesarean delivery under subarachnoid anaesthesia and under the study experimental design does not offer any advantages regarding postoperative analgesic requirements or postoperative pain.
The support for the study was provided solely from institutional sources and no conflict of interest is involved.
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