Comparison of Prophylactic Phenylephrine Infusion Versus Intravenous Ondansetron on Hypotension During Spinal Anesthesia for Cesarean Section

Abstract

Background:

Multiple methods have been proposed to prevent the incidence of hypotension in women undergoing cesarean section under spinal anesthesia. This study was conducted to compare the efficacy of phenylephrine (50 μg.min⁻¹) versus ondansetron (8 mg) in the prevention of such complications.

Patients and Methods:

We included a total of 184 full-term pregnant women who were randomly divided into two groups: Group P included 92 cases who were commenced on phenylephrine infusion (50 μg.min⁻¹ given after puncture) and Group O included the other 92 cases who were administered ondansetron (8 mg given 5 min before puncture).

Results:

Demographic data were not significantly different between the two groups. Maternal hypotension was significantly more encountered in the ondansetron group (51.6% vs. 22%) and ephedrine was used more significantly in that group (19.8% vs. 8.8%). In addition, nausea and skin flushing were more commonly encountered in the same group. The incidence of vomiting and patient discomfort was not significantly different between the two study groups.

Conclusion:

Phenylephrine is markedly superior to ondansetron in the prevention of maternal hypotension and vasopressor need during cesarean section under spinal anesthesia.

INTRODUCTION

Spinal anesthesia is the most commonly used anesthetic technique for elective cesarean section. It had many advantages over other techniques; it is quicker and easier compared to epidural anesthesia, and the fetus is exposed to fewer drugs compared to general anesthesia. In addition, the mother is awake while delivering the baby.[1]

However, spinal anesthesia has multiple drawbacks. It can induce maternal hypotension, which leads to nausea, vomiting, and dizziness. In severe cases, fetal acidosis and bradycardia along with cardiovascular collapse could be encountered.[2]

The decreased vascular resistance caused by spinal anesthesia is enhanced in pregnant women by inferior vena cava compression by the gravid uterus, and this is partially compensated by an increase in both heart rate and stroke volume.[3]

Multiple interventions have been proposed to prevent the incidence of such complications including intravenous fluid infusion, leg compression, and vasopressors (norepinephrine, ephedrine, phenylephrine, angiotensin 2, metaraminol, or mephentermine).[1]

Historically, ephedrine was considered the drug of choice for treating hypotension secondary to spinal anesthesia. Nevertheless, it has been replaced with phenylephrine as it is associated with lower rates of fetal acidosis.[4]

Furthermore, a previous study has reported that ondansetron administration could prevent serotonin-induced bradycardia and prevent the incidence of hypotension.[5]

Till now, there is a great controversy regarding the ideal method used for the prevention of maternal hypotension. Although a new consensus has recommended the administration of vasopressors to prevent that complication,[6] vasopressor administration has its disadvantages like bradycardia.[1]

This study was conducted to compare the effect of phenylephrine (50 μg.min⁻¹) versus ondansetron (8 mg) on the incidence of hypotension in women undergoing elective cesarean section with spinal anesthesia.

PATIENTS AND METHODS

This is a prospective randomized study that was conducted at Mansoura University Hospitals during the period between January 2020 and July 2020. We included a total of 184 full-term pregnant women who were prepared for elective cesarean section during that time period.

On the other hand, pregnant women with the American Society of Anesthesiologist classification <2, whose ages younger than 20 years or older than 45 years, obesity, or known allergy to any of the study medications (ondansetron or phenylephrine) were excluded. Furthermore, women having an indication for emergency cesarean section or having complicated pregnancies were excluded as well.

The included cases were randomly allocated using the closed envelope method into two equal groups; Group P included 92 cases who were commenced on phenylephrine infusion (50 μg.min⁻¹ given after puncture) and Group O included the other 92 cases who were administered ondansetron (8 mg given 5 min before puncture).

All cases were subjected to complete general and obstetric examination by the attending obstetrician. In addition, all cases were evaluated by the anesthesia team before the operation.

Written in formed consent was obtained from all the subjects before participating in the study after a complete explanation of the benefits and drawbacks of the drugs tested and obtained patient's data is used for research and educational purposes. Besides, the study was approved by the Medical Research Ethical Committee, Institutional Review Board of Mansoura University with IRB No. R.21.02.1211, dated: March 07, 2021. The procedure for performing this study was governed by guidelines laid down by the Declaration of Helsinki 2013.

Cases were recommended to fast for 8 h before surgery, and no premedications were administered. On arrival at the operating room, peripheral venous access was secured through an 18-gauge cannula, and routine patient monitoring (including heart rate, pulse oximetry, noninvasive blood pressure, and electrocardiography) was established.

The patient was positioned in the sitting position, and after that, spinal anesthesia was performed at L 3-4 or L 4-5 levels by a 27-gauge Quincke needle. Hyperbaric bupivacaine (0.5%) along with fentanyl (25 μg) was intrathecally administered. Then, the patient was placed in the supine position, and fluid infusion was started. Sensory blockade was tested by an alcohol swab, whereas motor block was evaluated using the Bromage Scale.

Hypotension was defined as systolic blood pressure <75% of the baseline value.[7] If hypotension was encountered, it was managed by intravenous administration of 10 mg ephedrine. Moreover, atropine was also administered if maternal bradycardia was detected (heart rate <45 beats/min).

The following data were collected: age, body mass index (BMI), operative time, mean arterial blood pressure, incidence of hypotension, nausea, vomiting, skin flushing, patient discomfort, and need for ephedrine use.

Statistical analysis

Data collection, tabulation, and analysis were conducted using the Statistical Package of the Social Sciences (SPSS, IBM, Inc., Chicago; USA) software version 26 for Windows. Quantitative data were tested for normality using Kolmogorov–Smirnov test and expressed as mean ± standard deviation. Categorical data were expressed in percentage and frequency. Independent sample t and Mann–Whitney tests were used for inter-group comparison of parametric and nonparametric continuous data, respectively. Chi-square test or Fisher's exact test was used for comparing two or more groups of categorical data. Probability (P < 0.05) was considered to be statistically significant.

RESULTS

The mean age of the included cases was 25.65 and 26.13 years in phenylephrine and ondansetron groups, respectively. BMI had mean values of 27 and 27.71 kg/m² in the two groups, respectively. As regards operative time, it had mean values of 46.26 and 46.21 min in the two groups, respectively. Neither of the previously described variables was significantly different between the two study groups (P > 0.05) as illustrated in Table 1.

Table 1.

Demographic characteristics and operative time in the studied groups

	Phenylephrine group (n=92)	Ondansetron group (n=92)	95% CI	P
Age	25.65±3.510	26.13±5.400	−1.816-0.849	0.475
Weight	75.15±8.069	77.87±11.273	−5.582-0.153	0.063
Height	167.04±6.254	167.70±5.999	−2.452-1.133	0.469
BMI	27.00±3.234	27.71±3.941	−1.761-0.348	0.188
Total operative time	46.26±10.816	46.21±10.147	−3.013-3.123	0.972

CI=Confidence interval, BMI=Body mass index

Regarding mean arterial pressure (MAP), although both groups showed no significant difference at baseline (P = 0.183), the phenylephrine group showed significantly higher MAP values throughout the operation compared to the ondansetron group (P < 0.05), apart from the 15-min reading which was not significantly different between the two groups (P = 0.057) as illustrated in Table 2.

Table 2.

Basal and follow-up values of mean arterial pressure in the studied groups

	Phenylephrine group (n=92)	Ondansetron group (n=92)	95% CI	P
Basal MAP	113.30±9.385	111.46±9.141	−0.875-4.545	0.183
1 min	104.71±10.581	100.01±10.985	1.548-7.858	0.004
3 min	97.19±10.393	93.16±11.387	0.833-7.211	0.014
5 min	91.51±9.110	86.09±10.901	2.479-8.356	<0.001
7 min	90.15±9.125	83.87±11.217	3.295-9.277	<0.001
9 min	91.42±11.005	83.95±12.397	4.043-10.902	<0.001
11 min	94.08±11.708	88.19±13.267	2.230-9.550	0.002
13 min	97.33±11.811	92.21±13.619	1.392-8.850	0.007
15 min	100.43±12.002	96.73±14.029	−0.116-7.522	0.057
20 min	100.29±12.485	95.35±13.323	1.157-8.711	0.011
25 min	100.31±12.624	95.71±13.733	0.735-8.452	0.020
30 min	100.38±11.906	95.66±14.097	0.908-8.542	0.016

MAP=Mean arterial pressure, CI=Confidence interval

Maternal hypotension was significantly more encountered in the ondansetron group (51.6% vs. 22% – P < 0.001). Accordingly, ephedrine was used more significantly in that group (19.8% vs. 8.8% – P = 0.034). In addition, nausea and skin flushing were more commonly encountered in the same group. Nevertheless, the incidence of vomiting and patient discomfort did not significantly differ between the two study groups (P > 0.05). Table 3 illustrates these data.

Table 3.

Maternal hypotension, ephedrine use, and intraoperative complications in the studied groups

	Phenylephrine group (n=92)	Ondansetron group (n=92)	OR	P
Hypotension	22.0% (20)	51.6% (47)	3.79 (1.99-7.22)	<0.001
Ephedrine	8.8% (8)	19.8% (18)	2.56 (1.05-6.23)	0.034
Nausea	5.5% (5)	14.3% (13)	2.87 (0.98-8.41)	0.047
Vomiting	1.1% (1)	0	0.5 (0.43-0.58)	1
Skin flushing	7.7% (7)	18.7% (17)	2.76 (1.08-7.02)	0.028
Discomfort	4.4% (4)	7.7% (7)	1.81 (0.51-6.42)	0.351

OR=Odds ratio

DISCUSSION

This prospective randomized study was conducted to compare the efficacy of phenylephrine (50 μg.min^{− 1}) versus ondansetron (8 mg) in the prevention of maternal hypotension in women undergoing elective cesarean section under spinal anesthesia.

We included a total of 184 cases who were randomly allocated into two equal groups; Group P included 92 cases who were commenced on phenylephrine infusion (50 μg.min⁻¹) and Group O included the other 92 cases who were administered ondansetron (8 mg).

No significant difference was detected between the two groups regarding demographic variables. Another study conducted by Ortiz-Gómez et al. handled the same perspective and reported no difference between the study groups regarding patient demographics.[2]

Our study revealed that phenylephrine was significantly more effective in the prevention of maternal hypotension compared to ondansetron (P < 0.001). Maternal hypotension was encountered in 22% and 51.6% of pregnant women in the phenylephrine and ondansetron groups, respectively. Therefore, the need for ephedrine as a vasopressor was significantly more requested in the ondansetron group (P = 0.034).

Unluckily, there is a paucity of studies comparing phenylephrine and ondansetron in the prevention of such complications in the previous literature. The only study existing in the literature was conducted by Ortiz-Gómez et al. included a total of 265 cases who were divided into four groups; controls (65 cases), ondansetron (65 cases), phenylephrine (67 cases), and combined ondansetron and phenylephrine (68 cases). The incidence of maternal hypotension was in the phenylephrine group (20.9%), while it occurred in 50.8%, 44.6%, and 25% of cases in controls, ondansetron, and combined groups, respectively.[2] This comes in line with our findings.

Phenylephrine infusion has been reported to be an effective method for preventing maternal hypotension, nausea, and vomiting during cesarean section under spinal anesthesia.[8,9] Although some anesthesiologists recommended initial phenylephrine bolus (100–150 μg), we preferred to use an infusion of 50 μg.min⁻¹ as it balances the risk of hypotension versus reactive hypertension.[9,10,11]

Another meta-analysis has reported that phenylephrine was significantly associated with a decreased risk of maternal hypotension (confidence interval = 0.18–0.73).[12]

On the other hand, multiple previous studies have reported that intravenous administration of ondansetron can attenuate the incidence of hypotension either in the general population[13] or in obstetric patients receiving spinal anesthesia.[14]

Ondansetron may have several mechanisms of action to decrease the incidence of that complication; it can enhance cardiac contractility and stabilize systemic vascular resistance through specific vascular or medullary receptors.[15]

A previous study was conducted to evaluate the effect of different doses of ondansetron on the incidence of maternal hypotension during spinal anesthesia. Cases were divided into four groups; placebo, ondansetron 2 mg, ondansetron 4 mg, and ondansetron 8 mg groups. No difference was detected between the four groups regarding the incidence of hypotension (43.8%, 53.1%, 56.3%, and 53.1%, respectively – P = 0.77). The authors concluded that ondansetron has little effect on the incidence of maternal hypotension during cesarean section under spinal anesthesia.[5]

Another study reported that prophylactic ondansetron administration had no effect on the total number of cases with hypotension compared to controls (P = 0.482). However, its administration was associated with decreasing the number of hypotensive episodes (P = 0.011), the number of ephedrine bolus requirements (P = 0.042), and time point percentage with systolic hypotension per patient compared to controls (P = 0.012).[2]

On the contrary, a previous Tunisian study reported that the prophylactic administration of ondansetron significantly decreased the incidence of hypotension in healthy pregnant women undergoing spinal anesthesia for elective cesarean delivery.[15] These authors attributed the heterogenicity of reports regarding that medication to the different anesthetic techniques used in different studies.

Another Egyptian study compared ondansetron to ephedrine in the prevention of hypotension during percutaneous nephrolithotomy under spinal anesthesia. Results showed that both drugs were comparable as hypotension was encountered in 70% and 50% of cases in the ondansetron and ephedrine groups, respectively (P = 0.154).[16]

Regarding other side effects in the current study, the incidence of nausea and skin flushing was significantly higher in the ondansetron group compared to phenylephrine. Conversely, the incidence of vomiting and patient discomfort did not significantly differ between the two groups.

Ortiz-Gómez et al. reported that the incidence of skin flushing was significantly higher in the ondansetron group (18.5%) compared to the phenylephrine group (6%) (P = 0.001), and that supports our study findings. However, the authors could not attribute that side effect to ondansetron as the group that received both ondansetron and phenylephrine had no cases with skin flushing. Furthermore, no significant difference was reported between the study groups regarding the incidence of nausea (P = 0.564), vomiting (P = 0.530), and patient discomfort (P = 0.973).[2]

Our study has some limitations, first of all, it is a single-center study. Furthermore, we did not include the control group in the current study. Therefore, more studies from different centers including controls should be conducted.

CONCLUSION

Based on the current findings, phenylephrine is markedly superior to ondansetron in the prevention of maternal hypotension and vasopressor need during cesarean section under spinal anesthesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.