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

Sylvanus Kampo; Alfred Parker Afful; Shiraj Mohammed; Michael Ntim; Alexis D. B. Buunaaim; Thomas Winsum Anabah

Disclosures

BMC Anesthesiol. 2019;19(177) 

In This Article

Methods

Ethical Statement

This double-blind, randomized control trial was carried out at the Tamale Teaching Hospital from April 2016 to May 2017. The ethical committee of the Tamale Teaching Hospital approved the study protocol (ID No: TTHERC21/04/16/08). The clinical trial registration number is ISRCTN15475205. The study protocol adhered to the CONSORT guidelines. Written informed consent was obtained from individual parturient after providing them with adequate explanations regarding the aims of the study.

Subjects

This study recruited three hundred and sixty (360) parturients. The inclusion criteria were as follows: Parturients with gestational age ≥ 36 weeks who reported at the obstetric unit of the Tamale Teaching Hospital and were scheduled to undergo elective cesarean section under spinal anesthesia with intrathecal injection of morphine, age 20 to 40 years old, American Society of Anesthesiologists Physical Status (ASA-PS) score 1–2. The exclusion criteria were as follows: parturients who did not give consent, or have history of nausea and vomiting before pregnancy, relevant drug allergy, any co-morbidity, motion sickness, abdominal surgery or experienced intraoperative blood loss (EBL) ≥ 500 mL during surgery.

Randomization

Each recruited parturient was randomly assigned to one of three groups using a computer-generated random number table. The group allocation was concealed in a sealed opaque envelope which was opened just before the administration of the drugs 10–15 min before the end of surgery. Propofol group (n = 115) represented those who received intravenous propofol (0.5 mg/kg), Metoclopramide group (n = 115) represented those who received intravenous metoclopramide (10 mg) and, Control group (n = 115) represented those who received intravenous saline (0.9%) as negative control (Figure 1).

Figure 1.

CONSORT recommended description for patient recruitment

Drugs

The sources of drugs were as follows; 1% propofol (10LF2786, South Africa), metoclopramide (171A-080, Imres), 0.5% hyperbaric bupivacaine (F0223–1, AstraZeneca, UK), preservative-free 2% lidocaine (P7445, Layina pharmaceuticals PYT, LTD, India), morphine (P7445, Layina pharmaceuticals PYT, LTD, India), Suppository diclofenac (P7445, Layina pharmaceuticals PYT, LTD, India), Tramadol (P7445, Layina pharmaceuticals PYT, LTD, India).

Anesthesia Induction and Drug Application

All parturients were prospectively assessed and classified according to the America Society of Anesthesiologist (ASA) physical status classification. Basic intraoperative monitoring (ECG, SpO2, Temperature, and non-invasive blood pressure) were applied, and the baseline vital signs checked and recorded. All recruited parturients had no history of nausea or vomiting 72 h before surgery. Before surgery, the individual parturient was advised not to eat any solid food for at least 6–8 h. An independent anesthesiologist, specialized in obstetric anesthesia was assigned to perform the spinal anesthesia and monitor the parturient till discharged from the hospital.

In the sitting position, the skin and interspinous ligaments were infiltrated with 2 ml of preservative-free 2% lidocaine using a 21G hypodermic needle. Lumbar puncture was then performed aseptically using a 26G pencil point spinal needle by the midline approach at the lumbar region (L2-L3 or L3-L4 interspace). Successful insertion of the spinal needle into the subarachnoid space was confirmed by the presence of the free flow of cerebrospinal fluid. The subarachnoid block was then established with 7.5–10 mg preservative-free hyperbaric bupivacaine, and 0.2 mg morphine. The individual parturient was then asked to return to the supine position with their head supported on a pillow and slightly tilted up to avoid any further spread of the spinal agent toward the head. A left lateral tilted for uterine displacement was employed to prevent aortocaval compression. The vital signs (pulse rate, blood pressure, oxygen saturation, and respiratory rate) of the individual parturient was monitored and recorded for every 5 min for the first 30 min and then for every 15 min. Ice cube was used to confirm adequate sensory block up to T6 level. Supplemental oxygen was given at 3 L/minutes through nasal prongs. Intraoperative hypotension was treated with 5–20 mg of intravenous ephedrine. Any estimated fluid deficit or blood lost was replaced accordingly. After the delivery of the baby, 5–10 unit of intravenous oxytocin was given to aid uterine contraction. An independent anesthesiologist who was blinded to drugs administration was asked to administer; saline (0.9%), metoclopramide 10 mg or propofol 0.5 mg/kg, 10–15 min before to the end of surgery.

Measurements

The episodes of PONV were identified by direct scheduled assessments or by a spontaneous complaint by the patients after the surgery. The incidence of PONV was recorded hourly for the first 4 h and then 4 hourly for the next 24 h using a 3 point ordinal scale (0 = none, 1 = nausea, 2 = vomiting). The incidence of PONV was calculated and categorized as early (0–4 h) or delayed (5 – 24 h). Intravenous Kytril 1–2 mg (anti-emetic) was administered if nausea or vomiting ensues or on request. The proportion of parturient and the number of times they required rescue anti-emetic in each group were recorded.

Pain intensity was measured immediately after the surgery on a 100-mm VAS,[15] 0 mm = no pain, and 100 mm = intolerable pain. If rescue analgesia was required, parturient received suppository diclofenac 100 mg or injection tramadol 100 mg or both. The incidence of pruritus was recorded every 4 h for 48 h after surgery on a four-point categorical scale as; 0 = no pruritus, 1 = mild, 2 = moderate, 3 = severe pruritus. Naloxone hydrochloride 2 μg/kg was injected to manage opioid depression, and Cetirizine 10 mg was administered if pruritus ensues or on request. Overall perioperative satisfaction was evaluated on the day of discharged during an interview as; 4 = excellent, 3 = good, 2 = satisfactory, 1 = poor.

Statistical Analysis

Due to the unknow of our population size, the sample size for this study was calculated using the equation;

95% confidence interval (Z-score = 1.96), Standard Diviation (StdDev = 0.5) and margine of error = ± 5 or 6%. Therefore, our sample size adjustment was between 267 and 384 respondents.

All statistical analyses were carried out using the GraphPad Prism v 7.01 (GraphPad Software, La Jolla, CA, US). Statistical analysis was performed for age, weight, BMI, parity, gestational age, degree of hypotension, dose of ephedrine administered, exteriorization of uterus, duration of surgery, incidence and pattern of PONV, request for rescue antiemetic therapy, the incidence and pattern of pruritus, the use of rescue pain relief, and patient satisfaction of anesthesia service, using one-way ANOVA and multiple comparison by Tukey's test. The student's t-test was used for statistical comparisons between two groups. All values are depicted as mean and considered significant if P < 0.05.

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