Comparison of Palonosetron Versus Palonosetron and Dexamethasone for Prevention of Postoperative Nausea and Vomiting After Middle Ear Surgeries: A Randomized Controlled Study.

Background: Postoperative nausea and vomiting (PONV) are one of the common distressing conditions after anesthesia. The PONV are related to several potential risk factors are patient related, anesthesia related, and surgery related. In surgery-related risk, middle ear surgery is associated with a high incidence of PONV. Aims: This study aimed to compare the efficiency of palonosetron versus palonosetron with dexamethasone in the prevention of PONV in middle ear surgeries. Settings and Design: This was a prospective, randomized, double-blind study. Statistical Analysis: The data were presented as descriptive statistics for continuous variables and percentages for categorical variables and were subjected to Z-test/Chi-square test/Fisher's exact test. The value of P < 0.05 was considered statistically significant.
Results: Demographic parts in comparison to age, duration of surgery, and duration of anesthesia were similar in both the groups. Our study showed that the incidence of PONV during 0-6 h was 38% (n = 19) in Group A and 12% (n = 6) in Group B and the incidence during 6-12 h postoperatively was 14% (n = 7) in Group A and 8% (n = 4) in Group B. During 12-24 h, the incidence was 8% (n = 4) and 6% (n = 3) in Group A and B, respectively. Hence, the difference of total early PONV in Group A was 60% (n = 30) and in Group B, it was 26% (n = 13) which was statistically significant (P < 0.03). Conclusions: The above result proves that palonosetron and dexamethasone group is superior in the prevention of PONV in middle ear surgery. Copyright:

INTRODUCTION

Nausea and vomiting are two of the most unpleasant and distressing events in the postoperative period with an estimated incidence of 30% in general surgical patients and as high as 80% in high-risk groups.[1] Its incidence after middle ear surgery (mastoidectomy with tympanoplasty) is reported as high as 60%–80% without prophylaxis.[2] It interferes with smooth emergence from anesthesia and may lead to dysphoria, dissatisfaction, and an overall poor experience about surgery and anesthesia.[34] Postoperative nausea and vomiting (PONV) are also associated with a significant delay in discharge from the postanesthesia care unit (PACU), unanticipated hospital readmission, and increased health-care costs.[567] Repeated PONV can adversely lead to more serious and undesirable consequences such as dehydration, electrolyte imbalance, increased postoperative pain, and aspiration of gastric contents. Suture dehiscence and esophageal rupture have also been reported.[89]

The 5-HT3 receptor antagonists are commonly used alone or in combination with dexamethasone, and form the cornerstone of antiemetic prophylaxis for surgery. As a second-generation 5-HT3 receptor antagonist, palonosetron has a 40-h half-life, allosteric binding, positive cooperativity, receptor internalization, and 5-HT3/neurokinin 1 receptor inhibition.[1011]

There were few studies published to compare the effect of ondansetron and a combination of ondansetron with dexamethasone for the prevention of PONV in middle ear surgery. Hence, here, we compared the efficiency of palonosetron versus palonosetron with dexamethasone in the prevention of PONV in middle ear surgeries.

METHODS

This prospective randomized double-blind trial (CTRI/2018/05/014063) on 100 American Society of Anesthesiologists (ASA) physical status I and II patients aged between 18 and 55 and scheduled for middle ear surgery under general anesthesia were studied between May 2018 and November 2019 after the institutional ethical committee approval. Written informed consent was obtained from all patients in their language. Patients who had any of the exclusion criteria (history of motion sickness, were pregnant or menstruating, having coexisting gastrointestinal pathology, known smokers, on chronic antiemetic medications, and any history of allergy to palonosetron) were excluded from the study.

Random allocation cards were made using computer-generated random numbers. The random allocated cards were concealed in an opaque, sealed envelope by an independent researcher and were sequentially arranged. Envelop was opened when a particular patient is allotted a group. Participants and assessors were also be blinded from the study group. Sample size calculation was done according to Panda et al.,[12] it was found that the incidence of vomiting with the use of ondansetron and combination of ondansetron and dexamethasone was 28% and 6%, respectively. Considering the same incidence with palonosetron, the sample size was calculated to be 45 patients in each arm taking a power of 80% with a 95% confidence interval and two-tailed alpha errors of 0.05. Considering a dropout rate of 10%, 50 patients were included in each group.

All patients were subjected to 8-h fasting and were premedicated with tablet pantoprazole 40 mg on the morning of the surgery. After obtaining written informed consent, the patients were randomized into either Group A (n = 50) to receive palonosetron 0.075 mg only or Group B (n = 50) to receive palonosetron 0.075 mg and dexamethasone 4 mg before induction of anesthesia. The Palonosetron trade name of Themiset 75 μg (manufactured by THEMIS Medicare Ltd., India) was used as study drugs in all the patients. An independent senior resident, not involved in the study, prepared the study drugs based on randomization as per a sealed envelope. All the drugs were drawn in identical 5 ml syringes and diluted up to 5 ml with normal saline and labeled as “antiemetic.” The study drugs were injected slowly over 30 s just before the induction of anesthesia. Anesthesiologists involved in intraoperative care and the investigator, collecting the data were unaware of the group allocation.

In the operation theater after securing the intravenous line, standard ASA monitoring including E CG, NIBP, pulse oximetry, and end-tidal carbon dioxide (EtCO2) was attached and baseline parameters recorded. General anesthesia was induced with an injection fentanyl 2 μg.kg–1 body weight, injection propofol 2 mg.kg–1 body weight, and injection vecuronium 0.1 mg.kg–1 body weight. Intubation was done with an oral-cuffed endotracheal tube of appropriate size. Anesthesia was maintained with air, oxygen, and isoflurane with muscle relaxant and controlled ventilation. For pain relief, injection diclofenac 75 mg intravenous infusion in 100 ml of normal saline and injection of paracetamol 1 g were given to all patients intraoperatively toward the end of the surgery. Boluses of injection fentanyl 1 mcg.kg–1 intravenously were given if the heart rate and blood pressure increased more than 20% of the preoperative baseline. After completion of the surgery, neuromuscular blockade was reversed with neostigmine 0.04 mg.kg–1 and glycopyrrolate 0.01 mg.kg–1, and tracheal extubation was done when adequate spontaneous ventilation was established.

All patients were sent to the postoperative recovery room where they received oxygen at 5 L.min–1 by mask in the propped-up position. Postoperative analgesia was given with intravenous boluses of 25 μg of injection fentanyl for the period of time the patients were kept in postanesthesia care unit (PACU) for approximately 2 h for all the patients if the visual analog score was more than four. After the duration of PACU stay, the patients were shifted to the wards where they received an injection of paracetamol 1 g intravenously eight hourly and injection of diclofenac 75 mg intravenously 12 hourly. The primary outcome of the study was the incidence of PONV in all patients after surgery. The patients were asked about nausea and vomiting at 0–6 h, 6–12 h, 12–24 h, 24–36 h, and 36–48 h after tracheal extubation by the investigator. PONV was evaluated on a three-point scale:

0 = none

1 = nausea

2 = vomiting.

The secondary outcome of the study was the number of rescue antiemetic medication, if required, was given in the form of metoclopramide 10 mg, and adverse effects if any were recorded in all patients.

The data were presented as descriptive statistics for continuous variables and percentages for categorical variables and were subjected to Z-test/Chi-square test/Fisher's exact test. All the data were analyzed using the SPSS package (version 23.0 SPSS INC, Chicago, IL, USA) software for Windows. In all parameters, the value of P < 0.05 was considered statisticallysignificant.

RESULTS

A randomized double-blind controlled trial was conducted on 50 patients each of Group A (palonosetron Group) and Group B (palonosetron and dexamethasone Group) between the age group of 18–55 years and analyzed various data as given below [Figure 1].

Figure 1

Consort flow diagram

Demographic profile of the patients

Patients under 27 years of age comprised the majority of the study population. The value of P was 0.281. There was no statistically significant difference in the age of the patients between the two study groups [Table 1].

Table 1

Age distribution

Age	Group A		Group B		P
	n	Mean±SD	n	Mean±SD
18–27	30	21.2±3.22	26	21.42±3.32	0.281
28–37	10	31±2.82	12	31.25±2.81
38–47	4	40.75±3.59	8	42.12±2.35
48–55	6	49.33±1.03	4	50.25±1.70
Total (mean±SD)	28.1±10.37		29.4±10.24

SD=Standard deviation

The mean value for the duration of surgery in Group A and Group B was 1.20 min and 1.25 min, respectively. Based on t-test, the value of P was 0.072. There is no statistical difference between the two groups, and hence, they are comparable in terms of the duration of surgery [Table 2].

Table 2

Duration of Surgery

Group	Mean (min)±SD	P
Group A	1.20±0.01	0.072
Group B	1.25±0.02

SD=Standard deviation

Based on t-test for equality of means, the value of P was found to be 0.116. It is no statistically significant difference and the duration of anesthesia was comparable between the two groups [Table 3].

Table 3

Duration of anesthesia

Group	Mean (min)±SD	P
Group A	1.354±0.05	0.116
Group B	1.300±0.04

SD=Standard deviation

The study showed that the incidence of PONV during 0–6 h was 38% (n = 19) in Group A and 12% (n = 6) in Group B and the incidence during 6–12 h postoperatively was 14% (n = 7) in Group A and 8% (n = 4) in Group B. During 12–24 h, the incidence was 8% (n = 4) and 6% (n = 3) in Group A and B, respectively. Hence, the difference of total early PONV in Group A was 60% (n = 30) and in Group B 26% (n = 13) was statistically significant (P < 0.03).

During 24–36 h (late PONV), the incidence of PONV in Group A was 12% (n = 6) and in group B, it was 8% (n = 4). The difference is statistically insignificant (P = 0.08). The incidence of PONV during 36–48 h was 8% (n = 4) with Group A and 0% (n = 0) with Group B. The difference is statistically significant (P = 0.02 and 0.05) [Table 4].

Table 4

Nausea and vomiting in palonosetron group versus palonosetron and dexamethasone group

	Group A (n=50), n (%)	Group B (n=50), n (%)	P
0–6 h
Nausea	16 (32)	5 (10)	0.004
Vomiting	3 (6)	1 (2)	0.3
6–12 h
Nausea	5 (10)	3 (6)	0.4
Vomiting	2 (4)	1 (2)	0.5
12–24 h
Nausea	3 (6)	2 (4)	0.6
Vomiting	1 (2)	1 (2)	1
24–36 h
Nausea	4 (8)	3 (6)	0.03
Vomiting	2 (4)	1 (2)	0.08
36–48 h
Nausea	3 (6)	0	0.02
Vomiting	1 (2)	0	0.05

DISCUSSION

Various etiological factors, including age, sex, obesity, history of motion sickness and/or previous PONV, menstruation, surgical procedures, anesthetic technique, and postoperative pain, are implicated in the incidence of PONV.[13]

Nausea and vomiting in the postoperative period are the second-most common complication after pain following general anesthesia. The incidence of nausea and vomiting in the postoperative period delays the discharge of the patient undergoing day-care surgery. In the demography profile of patients, there was no statistically significant in comparison of age, sex, duration of surgery, and duration of anesthesia.

In this study, we compared the potency, antiemetic effect, and adverse effect profile of intravenous palonosetron versus palonosetron and dexamethasone. The incidence of nausea is 62% in the palonosetron group when compared to 26% in the palonosetron and dexamethasone group. We found that there was a significant difference in the incidence of PONV between the groups in the first 0–6 h, and it is significantly reduced in palonosetron and dexamethasone group when compared to palonosetron group in the 0–48 h. The use of dexamethasone for prophylaxis against PONV is comparable with 5-HT3 receptor antagonists (primarily ondansetron).[14] However, palonosetron, at a dose of 75 μg, claims superiority over dexamethasone 8 mg for overall PONV reduction in the 0–24 interval.[1516]

During mastoidectomy, drilling and suctioning by the surgeon produces low-frequency sound in the mastoid cavity which may provoke postural instability in patients resulting in PONV. Irrigating fluids used during middle ear surgery is as an irritant to the labyrinth in the middle ear and may cause vertigo and emesis. However, the above factors were well balanced between groups in our study, as the procedure of the surgery was the same. Increased middle ear pressure by nitrous oxide is another factor contributing to PONV which was replaced by air before closing the tympanic membrane. Therefore, we can say that any difference in results between the groups is solely attributed to differences in the antiemetic drugs administered.

The study by Sharma et al. compared palonosetron with ondansetron for the prevention of PONV in middle ear surgery. They found that palonosetron was superior to ondansetron in the prevention of PONV.[17]

The 5-HT3 receptor antagonists as alone or in combination with dexamethasone are commonly used antiemetics. In a meta-analysis, it was found that a combination of 5-HT3 receptor antagonists and dexamethasone significantly reduced the risk of PONV and lower rescue antiemetic requirements compared to 5-HT3 receptor antagonists alone.[18]

Bala et al. and Cho et al. found that palonosetron combined with dexamethasone decreased the incidence of PONV significantly while other studies reported no significant difference between the combined effect of palonosetron and dexamethasone as compared to palonosetron alone.[1920]

Srivastava et al. compared 64 patients with palonosetron–dexamethasone and ondansetron–dexamethasone for the prevention of PONV in middle ear surgery. The overall incidence of PONV (0–24 h postoperatively) was 37.5% in Group O and 9.4% in Group P (P = 0.016). Absolute risk reduction with palonosetron–dexamethasone was 28%, the relative risk reduction was 75%, and the number needed to treat was 4. This recent study proves that even the combination of palonosetron–dexamethasone is superior to ondansetron–dexamethasone for the prevention of PONV after middle ear surgeries.[21] Certain limitation of our study was that we had not included the ASA III class of patients and also not included any placebo group because it would in unethical to not give any antiemetic drugs in the higher risk of PONV in the middle ear surgery.

CONCLUSIONS

Palonosetron and dexamethasone group is superior to palonosetron alone in the prevention of PONV in middle ear surgery.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.