Sub-hypnotic dose of propofol as antiemetic prophylaxis attenuates intrathecal morphine-induced postoperative nausea and vomiting, and pruritus in parturient undergoing cesarean section — a randomized control trial

Cesarean section is among the most commonly performed surgeries in women, and it is associated with a more intense postoperative pain compared to the post-vaginal delivery pain [1]. Excellent postoperative analgesia is very crucial in providing maternal comfort, improving breastfeeding, improving mother-child bonding, early ambulation, early discharge, and enhancing patient satisfaction [2]. The use of spinal anesthesia for cesarean section provides an avenue for rendering better postoperative analgesia with neuraxial opioids [1]. Intrathecal morphine provides excellent postoperative analgesia. The current practice of using spinal anesthesia with morphine for parturient presenting for elective cesarean delivery in some hospitals has received mixed reactions from both parturient and staff. Although the addition of intrathecal morphine to bupivacaine offers excellent postoperative analgesia which covers for about 12 to 24 h, some fraction of parturients commonly experiences dose-dependent PONV and pruritus [3].

PONV is an unpleasant condition, often underestimated side effect of anesthesia and surgery [4]. Despite the increasing fear of pain after surgery, patients still consider PONV to be a significant concern or complication of anesthesia [5]. When questioned about issues of concern, 22% of 800 patients in a study gave PONV the highest level of concern compared with 34% for postoperative pain and 24% for waking up during surgery [6]. Gan et al. [7] reported that most patients associated value to the avoidance of PONV and were willing to pay between the US $56 and the US $100 for a completely effective antiemetic. Due to its medical, surgical, patient and anesthetic etiological factors, its incidence is estimated to be 40 to 60% of all surgical interventions and patient population of which, 0.18% is resistant to PONV [8]. The intense efforts accompanying PONV increases the risk of aspiration pneumonitis, wound dehiscence, bleeding, hypertension, and increased intracranial pressure [9]. It also leads to higher consumption of calories, requires additional postoperative monitoring, and delayed discharge leading to a higher cost of care [10]. Other morbidities synonymous with PONV also includes; dehydration, electrolyte disturbance, interference with nutrition and, more rarely, esophageal rupture [11].

Prophylaxis with antiemetic has been shown to reduce the incidence of PONV in surgical procedures by 15–30% (absolute risk reduction) [12]. Numerous antiemetic has been studied for the prevention of PONV with varying degrees of success [13]. The efficacy of metoclopramide as an antiemetic is undoubted. Propofol anesthesia is known to have a low emetic score, and its antiemetic properties have been investigated. While it was found to be effective by some studies, the contrary was reported in some other studies [8]. Series of clinical trials have also reported that, at a sub-hypnotic dose, propofol is equally effective in reducing the incidence of not only PONV but also pruritus following intrathecal morphine [14]. Although routine PONV prophylaxis seems appropriate, the choice of antiemetic agents is wide, whereas some are too expensive in our setting for regular use. This study, therefore, aimed to ascertain the antiemetic effect, as well as reducing pruritus by a sub-hypnotic dose of propofol and compare its effect with metoclopramide among parturients receiving neuraxial morphine for cesarean section.

Of the 360 parturients that were recruited for this study, data for 15 parturients were excluded from the analysis (10 parturients experienced spontaneous labor and received an emergency cesarean operation and 5 parturients estimated intraoperative blood loss (EBL) was greater than 500 mL). Therefore, data for 345 parturients comprising 115 each for control, propofol, and metoclopramide groups were included in the analysis (Fig. 1).

The data showed that there was no significant difference among parturients from the control group, propofol group, and the metoclopramide group regarding age, weight, BMI, primip parity, multiparity, grand multiparity and gestational age (P value = 0.73; P value = 0.92; P value = 0.78; P value = 0.91; P value = 0.49; P value = 0.91; and P value = 0.61 respectively) (Table 1).

The degree of hypotension experienced during the intraoperative period after the subarachnoid blockade indicated that 84 (73.0%) parturients from the control group, 76 (66.1%) from the propofol group, and 89 (77.4%) from the metoclopramide group experienced no degree of hypotension compared with baseline blood pressure. While 19 (16.5%) parturients from the control group, 27 (23.5%) from the propofol group, and 15 (13.0%) from the metoclopramide group experienced 10–20% decreased in blood pressure compared with the baseline blood pressure (Table 2). 8 (7.0%) parturients from the control group, 9 (7.8%) from the propofol group, and 10 (8.7%) from the metoclopramide group experienced 21–31% decreased in blood pressure compared with the baseline blood pressure. Also, 4 (3.5%) parturients from the control group, 3 (2.6%) from the propofol group, and 1(0.9%) from the metoclopramide group experienced 31–40% decreased in blood pressure when compared with the baseline blood pressure (Table 2). The results indicated that there was no significant difference among parturients from the propofol group, metoclopramide and the control group regarding 0%, 10–20%, and 31–40% decreased in blood pressure (P <  0.01; P <  0.01; P <  0.05 respectively). However, the 21–31% decreased in blood pressure showed no significant difference between the groups (Table 2). Hypotension caused by the subarachnoid block in individual parturient responded to ephedrine (5–20 mg) treatment. The doses of ephedrine administered indicated significant difference between the groups (P <  0.01; P <  0.01; P <  0.02) (Table 2). The duration of surgery ranged from 25 to 90 min and showed significant difference between the groups (P <  0.01; P <  0.01; P <  0.01) (Table 2). No episode of intraoperative emetic was noted for the individual groups.

Obstetrics and gynecological surgeries, including cesarean section, are associated with the incidence of PONV as high as 60–83% most especially when no prophylactic antiemetic is provided [16]. This may be due to multiple complex factors such as; stimulation of uterus, broad ligament, vagina, and cervix, which may induce vomiting through afferents signals to the spinal cord along hypogastric and pelvic plexus. Surgical pain increases the circulating catecholamines, which cause PONV by stimulating area poster. Other nonanesthetic causes include surgical bleeding, medications, such as antibiotics and early motion at the end of surgery or history of motion sickness. Few anesthetic causes of PONV include hypotension, increased vagal activity, administration of neuraxial or parenteral opioids, and the addition of phenylephrine or epinephrine to local anesthetics. Also, peak block height ≥ T₅, use of procaine, baseline heart rate ≥ 60 beats/min.

This study was designed to test the hypothesis that propofol use as antiemetic prophylaxis prevents intrathecal morphine-induced postoperative nausea and vomiting, as well as pruritus in parturients undergoing a cesarean section. The following principal observation emerged: First, the data indicated that sub-hypnotic dose of propofol was equally effective as metoclopramide in the prevention of PONV in parturients undergoing cesarean section under spinal anesthesia with intrathecal morphine. Second, the data showed that sub-hypnotic dose of propofol significantly reduced the incidence of postoperative pruritus following intrathecal morphine used. Some variables in this current study were kept constant for all study groups; the type of surgery, anesthesia technique, anesthetic drugs, and the level of the spinal block was all standardized, including postoperative analgesics. Duration of anesthesia and surgery were comparably the same, and there was no significant difference between age, weight, and BMI of patients from individual study groups. These, therefore, suggested that the significant difference in incidence and severity of PONV between study groups were solely attributed to the drugs tested.

Factors noted to induce emesis during cesarean delivery under spinal anesthesia includes; peritoneal traction, exteriorization of the uterus, fundal pressure during delivery of the baby and hypoxia associated with hypotension following spinal anesthesia. Pusch et al. [17] noted that emetic symptoms were reduced in patients who developed post-spinal hypotension after being given 100% oxygen, thus, implicating hypoxemia at the emetic center as a probable causative factor. This study recorded no significant changes between the groups concerning maternal blood pressure, pulse rate, respiratory rate, and oxygen saturation. The amount of ephedrine used for the treatment of hypotension was also similar between the groups. No intraoperative emesis was recorded from the study groups.

Metoclopramide is an inexpensive generic drug. As a benzamide, it acts on Dopamine 2 receptor to prevent the stimulation of the vomiting center. Its effectiveness as prophylaxis has also been confirmed [18]. Propofol is well known for its role in decreasing the incidence of PONV when used at a sub-hypnotic dose. However, the exact mechanism by which propofol prevents emesis is unknown. It has been postulated to be an antagonist at the 5HT3 receptor. Other reports suggest that the antiemetic effect of propofol is due to modulation of the subcortical pathways [19]. Patients who received propofol experienced a significant reduction in nausea and vomiting compared with patients treated with placebo. A survey demonstrated that 86% of patients who received a sub-hypnotic dose of propofol recorded no symptoms of emetic after surgery [20]. Emerging evidence also indicates that propofol, given at sub-hypnotic dose significantly decreases the incidence of emetic episodes in patients undergoing cesarean delivery with spinal anesthesia. In a study by Song et al. [16] it was demonstrated that propofol given after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy significantly decreased the incidence of PONV compared with control. Similarly, reports suggest that low-dose of propofol (0.5 or 1 mg/kg) administration at the end of surgery effectively reduce the incidence of PONV within 2 h postoperatively in highly susceptible women undergoing a laparoscopy-assisted vaginal hysterectomy and receiving opioid-based PCA [21]. In this present study, it was realized that 105 (91.30%) from the propofol group experienced no incidence of PONV compared with 7 (6.09%) parturient from the control group, a similar observation Chatterjee et al. [22], Apfel et al. [23] and Warltier et al. [24] have also earlier submitted. Comparing the episodes and severity of PONV, the data from this study suggested that parturient who received metoclopramide (10 mg) experienced less incidence of PONV than those who received sub-hypnotic dose of propofol (0.5 mg/kg). However, the used of rescue antiemetic was higher in the metoclopramide group compared with the propofol group.

Pruritus is one of the most common adverse effects of intrathecal morphine. It is most challenging to treat and respond poorly to conventional antihistamine treatment [25]. Therefore, it remains a significant challenge for the anesthesiologist. Existing reports indicate that a low dose of propofol could alleviate morphine-induced pruritus without disrupting intrathecal morphine analgesia [26‐28]. In this study, it was noted that sub-hypnotic dose of propofol decreased the incidence of pruritus compared with metoclopramide, an observation Liu et al. [29] has earlier reported. This emerging evidence, therefore, suggested that a low dose of propofol as antiemetic prophylaxis attenuate not only PONV but also, morphine-induced pruritus.

In conclusion, this study findings suggested that a sub-hypnotic dose of propofol could be as effective as metoclopramide in the prevention of PONV in parturient undergoing cesarean section under spinal anesthesia with intrathecal morphine. Also, a single sub-hypnotic dose of propofol may result in a low incident of opioid-induced pruritus. Therefore, propofol may be a better choice of antiemetic prophylaxis for opioid-induced PONV and pruritus in cesarean section.