A low dose of spinal morphine is probably the most common form of postoperative analgesia after caesarean section. Its main advantages are its low cost and simplicity and the fact that a single spinal dose usually provides high-quality postoperative analgesia for a full 24 h. However, dose-related side-effects, such as pruritus, nausea and vomiting, may occur. Nausea and vomiting may be extremely unpleasant after caesarean section and may reduce the patients’ satisfaction, not only impairing the quality of postoperative care but also jeopardising the new mothers’ ability to take care of her baby.
Several strategies have been used to reduce the incidence of nausea and vomiting after caesarean section under regional anaesthesia combined with opioids. Research has focused on various antiemetic agents, used either alone or in combination with other drugs in varying regimens. A single dose of dexamethasone administered immediately before surgery has been shown to reduce the incidence of nausea and vomiting in patients undergoing caesarean section under both epidural and spinal anaesthesia with 3 mg and 200 μg of morphine.1–4 Our current protocol uses a much smaller dose of spinal morphine (60 μg) in combination with systemic NSAIDs as part of a multimodal approach for analgesia after caesarean section. Reducing the morphine dose may contribute to a reduced incidence of nausea and vomiting in the postoperative period.
The purpose of the study was to evaluate whether a single dose of dexamethasone given immediately before surgery prevented nausea and vomiting in patients undergoing caesarean under spinal anaesthesia utilising a small dose of morphine.
This interventional, double-blinded and randomised, placebo-controlled study protocol was approved by the local Hospital Ethics Committee (Comite de Ética em Pesquisa of Irmandade Santa Casa de São Paulo, Sao Paulo, Sao Paulo, Brazil; Ethical Committee number: 269/07; Chairperson: Professor Dr Nelson Keiske Ono, date of meeting: 11 July 2007). Full-term pregnant patients (ASA physical status 1 or 2) undergoing elective caesarean section under spinal anaesthesia were recruited and written informed consent was obtained from all participants. Patients were invited to participate during their admission to a pre-partum room. Patients were excluded if they had any contraindication to receiving regional anaesthesia; were allergic to dexamethasone, to opioids or local anaesthetics; presented with pregnancy-induced hypertension or diabetes; or had received any antiemetic drug in the 24 h prior to the scheduled caesarean section.
Patients were randomly allocated into two groups using a computer-generated table and received a single dose of dexamethasone 10 mg in 100 ml 0.9% saline immediately prior to surgery or placebo (100 ml 0.9% saline).
Spinal anaesthesia was administered with 15 mg of hyperbaric bupivacaine and 60 μg of morphine. Patients received 10 ml kg−1 of lactated Ringer's solution. Blood pressure was measured every 3 min until delivery and hypotension was treated with a 0.2 mg bolus of metaraminol. Hypotension was defined as any decrease in the SBP from the control value defined as the mean of three measurements obtained immediately before the administration of spinal anaesthesia. After their infants were delivered, patients received ketoprofen 100 mg, dipyrone 2 g and oxytocin 15 IU intravenously. Starting 6 h after delivery, patients received diclofenac 75 mg orally every 8 h and dipyrone 2 g every 6 h.
The study was double-blinded and the anaesthesiologist who was responsible for the postoperative evaluations was not present during surgery. The evaluations were performed every hour for the first 3 h and then at 6, 12 and 24 h following the administration of spinal morphine. The primary endpoint was the incidence of nausea and vomiting in the first 24 h after surgery. Patients who had a nausea score more than 1 (0 = no nausea; 1 = mild; 2 = moderate; and 3 = severe nausea) or who had two or more episodes of vomiting were treated with dimenhydrinate 50 mg and pyridoxine 10 mg. Pain was evaluated using a visual analogue scale (VAS) (0 = no pain and 10 = worst pain possible) at rest and on movement. To evaluate pain with movement, patients were asked to cough while in the recovery room and asked to sit in bed while in the ward. Breakthrough pain (>3 on the VAS or when indicated as such by the patient) was treated with tramadol 100 mg infused over 20 min.
Fisher's exact test was used to compare the incidence of nausea, vomiting, pain at rest and pain with movement at multiple time points. The time to event analysis was performed using Kaplan–Meier curves and the log-rank test, considering nausea or vomiting as a unique event and pain at any time within the first 24 h of treatment as an event. The sample size was determined prospectively; with 33 patients per group. A reduction in the incidence of nausea and vomiting from 35% to 10% at any time within the first 24 h of treatment could be determined with a statistical power of 85% (β=0.85), assuming statistical significance at 0.05 (α=0.05).
Seventy full-term pregnant patients were studied (Fig. 1) from 1 January to 30 June 2008. Only patients who were scheduled as the first procedure of the day were included. The groups comprised 35 patients each and patient characteristics were similar in the two groups (Table 1).
The incidence of nausea and vomiting was similar between the two groups during the periods of observation. At 6 h pain at rest was lower in the group who received dexamethasone. Pain with movement was lower among patients who received dexamethasone at 1, 6, 12 and 24 h (Table 2). The cumulative incidence of nausea and vomiting for the period in the post-anaesthesia care unit (up to 3 h after surgery) and in the ward (between 3 and 24 h after surgery) was lower in the patients who received dexamethasone (Table 3).
Our results indicate a lower cumulative incidence of nausea and vomiting with dexamethasone, although the incidence was not lower at all time points. Dexamethasone also reduced pain scores at rest and with movement during the first postoperative day.
Wu et al.1 and Nortcliffe et al.2 found that a single dose of dexamethasone administered to full-term pregnant patients who underwent caesarean section under spinal anaesthesia, including spinal morphine, did not prevent nausea and vomiting during the postoperative period. Wu et al.1 observed a benefit when dexamethasone was used in combination with droperidol, and Nortcliffe et al.2 found that 50 mg of intravenous cyclizine alone was better than dexamethasone. Both of the studies used a much higher dose of morphine than we use in our current practice (200 vs. 60 μg) which may explain the difference in the incidence of nausea and vomiting between their studies and ours (33 vs. 10%, respectively).
Jokela et al.5 reported similar findings with regard to improved postoperative pain control; they found that dexamethasone 10 mg administered intravenously immediately before induction of anaesthesia in patients undergoing laparoscopic hysterectomy reduced oxycodone consumption during the first two postoperative hours. However, it should be emphasised that the study population, the anaesthetic technique and the surgical procedure were different from those in our study. These differences may explain why they observed a major benefit only during the first 2 h, whereas in our study dexamethasone was advantageous during the first 24 h. It is known that pregnancy may significantly modify the pain modulation process after a surgical procedure. The outcome measures also varied between the two studies: Jokela et al. used a reduction in the oxycodone consumption of patients who were using patient-controlled analgesia pumps, whereas we evaluated pain using VAS pain scores at rest and on movement. Other studies have also demonstrated the potential benefits of steroids for improving the quality of postoperative analgesia, both at rest and with movement, which is of special interest in the obstetric population, as mothers generally want to take care of their babies. Wu et al. also demonstrated that the VAS scores during rest or with movement between 6 and 24 h postoperatively were lower in patients who received dexamethasone.1 The analgesic effects of steroids are mainly provided through peripheral inhibition of phospholipase enzymes which decreases the products of the cyclooxygenase and lipoxygenase pathways in the inflammatory response.6 These characteristics make dexamethasone a suitable drug for the treatment of pain, both at rest and on movement.7
The potential side-effects of steroids used during the postoperative period remain a concern. One of the major problems is impaired wound healing during the acute postoperative period. However, meta-analyses indicate that a single dose of dexamethasone does not increase infection or other complications.8,9 Another concern is respiratory depression after the use of intrathecal morphine as constituent of a spinal anaesthesia. Although there was no specific protocol to address this side-effect, the dose used was considered to be small enough to carry a low risk of respiratory depression.10,11
Our study included only a small number of participants when the total number in our hospital is considered. The service is in a tertiary referral hospital and the majority of patients admitted had pregnancy-related problems or were hospitalised for some time prior to their due date. In addition, although patients may have declared an understanding of the protocol, some were not included because they were considered illiterate by the investigator who interviewed them (M.M.C.S.). Thus, there was a risk of a type II error because the study did not have sufficient power to detect a statistically significant difference between the groups.
In conclusion, although we observed a trend towards a lower incidence of postoperative nausea and vomiting in the dexamethasone group, this effect was significant only when considering the cumulative incidence. It was also associated with reduced pain scores during the first postoperative day.
Assistance with the study: the authors would like to thank Dr Joaquim Vieira for his assistance with the study.
Financial support and sponsorship: this work was supported by the Department of Anaesthesiology, Santa Casa de Misericordia, São Paulo, Brazil.
Conflicts of interest: none declared.
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