Background:
To observe the effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting (PONV) in gynaecological day surgery under remimazolam-based general anesthesia.
Methods:
A total of 120 patients, aged from 18 to 65 years old, American Society of Anesthesiologists grade I or II, were scheduled to undergo hysteroscopy under total intravenous anesthesia. The patients were divided into 3 groups (n = 40 each): dexamethasone plus saline group (DC group), dexamethasone plus droperidol group (DD group) and dexamethasone plus propofol group (DP group). Dexamethasone 5 mg and flurbiprofen axetil 50 mg were given intravenously before induction of general anesthesia. Anesthesia induction: remimazolam 6 mg/kg/hours was continuously pumped until sleep and slow intravenous injection of alfentanil 20 ug/kg and mivacurium chloride 0.2 mg/kg was given. Anesthesia maintenance: remimazolam 1 mg/kg/hour and alfentanil 40 ug/kg/hours were continuously pumped. After the start of surgery, DC group was given 2 mL saline, DD group was given droperidol 1 mg, and DP group was given propofol 20 mg. Primary outcome: incidence of PONV in the postanesthesia care unit (PACU). Secondary outcome: incidence of PONV in patients within 24 hours after surgery, as well as general patient data, duration of anesthesia, the recovery time of patients, dose of remimazolam and alfentanil, etc.
Results:
In PACU, patients of group DD and DP showed less PONV than those in group DC (P < .05). Within 24 hours after operation, there was no significant difference in the incidence of PONV among the 3 groups (P > .05), but the incidence of vomiting in DD group and DP group was significantly lower than that in DC group (P < .05). There was no significant difference in general data, anesthesia time, the recovery time of patients and dosage of remimazolam and alfentanil among the 3 groups (P > .05).
Conclusion:
The effect of low-dose propofol combined with dexamethasone to prevent PONV under remimazolam-based general anesthesia was similar to that of droperidol combined with dexamethasone, both of which significantly reduced the incidence of PONV in the PACU compared to dexamethasone alone. However, low-dose propofol combined with dexamethasone had little effect on the incidence of PONV within 24 hours compared to dexamethasone alone and only reduced the incidence of postoperative vomiting in patients.
Keywords: alfentanil, dexamethasone, droperidol, postoperative of nausea and vomiting, propofol, remimazolam
1. Introduction
Postoperative nausea and vomiting (PONV) is one of the common adverse effects after general anesthesia. PONV prolongs postoperative feeding time and length of hospital stay, reducing patient satisfaction.[1] Day surgery patients have high mobility, and most of them are discharged on the day of surgery. Therefore, it is important to prevent PONV for day surgery patients.[2]
Remimazolam is a new sedative-hypnotic drug used for the induction and maintenance of general anesthesia.[3] It has been reported that the incidence of hypotension, bradycardia and injection pain of remimazolam is lower than that of propofol in general anesthesia, but it is inferior to propofol in preventing PONV.[4,5]
Antiemetics such as dexamethasone, droperidol and tropisetron are commonly used, but each has its own side effects and increases the medical burden on the patient.[6,7] Hvarfner et al[8] found that small doses of propofol also had an anti-nausea and vomiting effect. However, there is no relevant research on whether low-dose propofol can effectively prevent PONV after remimazolam-based general anesthesia, and it is worth exploring whether low-dose propofol can have the same antiemetic effect as the classic antiemetic droperidol.
This study investigates the effect of low-dose propofol combined with dexamethasone on the prevention of PONV in gynaecological day surgery under remimazolam combined with alfentanil anesthesia. To provide clinical reference for the prevention of nausea and vomiting after remimazolam-based general anesthesia.
2. Methods
2.1. Patients and study protocol
The study was approved by the Ethics Committee of Weifang People’s Hospital and registered at http://www.chictr.org.cn (Chinese Clinical Trial Registry, ChiCTR2200057803). The study protocol followed the CONSORT guidelines. The study protocol was performed in the relevant guidelines. Informed consent was signed by the patients and their families who participated in the study.
Patients proposed for hysteroscopy day surgery under total intravenous anesthesia, aged 18 to 65 years, American Society of Anesthesiologists (ASA) grade I or II were selected. Exclusion criteria were breastfeeding, a history of chronic pain, a history of sedative and analgesic administration or allergy to any of the study drugs, severe hypertension, and diabetes mellitus. Reject criteria were a procedure time of more than 1 hour, discharged the next day, missing follow-up with the electronic questionnaire pushed 24 hours after the procedure. The included patients were randomized into 3 groups: dexamethasone plus saline group (DC group), dexamethasone plus droperidol group (DD group) and dexamethasone plus propofol group (DP group). The DC group was used as the control group and the remaining 2 groups as the intervention group. Random allocation of included patients by an independent researcher using Excel 2016 (Microsoft) with a 1:1:1 allocation. The participating patients, the outcome assessment fellows, were unaware of the group allocation, only the doctor administering the anesthetic was aware of the grouping of patients and all patients were anesthetized by the same anesthetist.
Patients were routinely fasted and no pre operative medication was administered. After the patient entered the operating room, the intravenous channel was established, and the patient’s ECG, SPO2, NIBP, and BIS were monitored. Patients in each group were given dexamethasone 5 mg for anti-inflammatory and antiemetic prophylaxis before induction, and flurbiprofen axetil 50 mg for preemptive analgesia. Induction of anesthesia: remimazolam 6 mg/kg/hours was continuously infused until sleep, and then mivacurium 0.2 mg/kg and alfentanil 20 ug/kg were slowly injected, after 3 minutes of mask ventilation, the laryngeal mask was placed by the anesthesiologist and mechanical ventilation was performed. Anesthesia maintenance: alfentanil 40 ug/kg/hours and remimazolam 1 mg/kg/hour continuous infusion, stop infusion at the end of the operation. BIS value was maintained between 40 and 60, and 0.1 mg/kg of mivacurium was injected intermittently when necessary. After the start of surgery DC group was given 2ml saline, DD group was given droperidol 1 mg, and DP group was given propofol 20 mg. After awakening and extubation, the patient was taken to the postanesthesia care unit (PACU) and assessed for nausea and vomiting. Patients were discharged after meeting discharge criteria as assessed by the Post-anesthetic Discharge Scoring System (PADSS) criteria. An electronic follow-up questionnaire was pushed 24 hours after the operation. Basic information about the patient’s medical history and surgery was obtained through pre operative anesthesia clinic assessment, intraoperative anesthesia monitoring, in the inpatient electronic medical record, and observation notes in the PACU.
2.2. outcomes
Primary outcome: Observe the incidence of PONV in the PACU. Secondary outcome: Observe the incidence of PONV within 24 hours after surgery; General data such as age, weight, body mass index, ASA classification, and Apfel score were collected; Record the operation time, recovery time and dosage of remimazolam and alfentanil. Postoperative nausea is when the patient only has a feeling of nausea but no contractile movements of the diaphragm or abdominal muscles. Postoperative vomiting occurs when the patient experiences contraction of the diaphragm or abdominal muscles with or without vomiting of stomach contents, or when both nausea and vomiting are present.[1] Appel designed a PONV risk score[9] based on 4 major risk factors for adult PONV: female, nonsmoking, history of PONV and/ or motion sickness, and postoperative use of opioids. The risk of PONV was 10 %, 20 %, 40 %, 60 % and 80 % for each factor scored 0, 1, 2, 3, and 4, respectively.
2.3. Sample size and statistical analysis
Sample size was calculated by PASS 15.0 software (https://www.ncss.com/online-store/). According to the preliminary test results, the incidence of nausea in the PACU in the DC group, DD group and DP group was 49 %, 12 % and 13 %, respectively. The required sample size was calculated at 36 patients per group with α = 0.05, and power of 80%. Considering the possible 10 % loss of follow-up rate, 120 patients were finally included, 40 in each group.
Data were analyzed statistically using SPSS 25.0 software (IBM Corporation, New Orchard Road, Armonk, NY; https://www.ibm.com/products/spss-statistics). All measurement data were tested for normality and homogeneity of variance. Data that conformed to a normal distribution were expressed as mean ± standard deviation (x̄ ± S). One-way analysis of variance was used for comparison between groups. Data that did not conform to the normal distribution were expressed as interquartile range [M (Q1–Q3)], and rank sum test was used for comparison between groups. Count data were expressed as percentage, and chi-square (χ2) test was used for comparison between groups. P < .05 was considered statistically significant.
3. Results
The study initially included 120 patients and excluded 7 patients who were lost to follow up, resulting in 113 patients included in the analysis: 37 in the DC group, 39 in the DD group and 37 in the DP (Figure 1.)
Figure 1.
CONSORT diagram describing patient progress through each stage of the randomized trial. Methods: (A) total number of 120 patients were randomized into 3 groups (n = 40). The study excluded 7 patients who were lost to follow up after discharge, resulting in 113 patients included in the analysis: 37 in the DC group, 39 in the DD group and 37 in the DP. DD group = dexamethasone plus droperidol group, DC group = dexamethasone plus saline group.
There was no significant differences in age, weight, body mass index, ASA grade and Apfel score, anesthesia time, the recovery time of patients and the dosage of remifentanil and alfentanil among the 3 groups (Table 1). Patients were assessed for risk of PONV using the simplified Apfel score[9] prior to anesthesia and all 3 groups were scored as 2 to 3, being at medium to high risk of PONV.
Table 1.
Characteristics of patients.
| DC group (n = 37) | DD group (n = 39) | DP group (n = 37) | P value | |
|---|---|---|---|---|
| Age (yr) | 42.32 ± 1.44 | 42.24 ± 1.71 | 41.56 ± 1.67 | .348 |
| Weight (kg) | 59.61 ± 1.17 | 60.53 ± 1.33 | 62.80 ± 1.13 | .169 |
| BMI (kg/m2) | 23.06 ± 0.45 | 23.02 ± 0.46 | 23.70 ± 0.39 | .482 |
| ASA grade | .946 | |||
| I | 6 (16.2%) | 6 (15.4%) | 5 (13.5%) | |
| II | 31 (83.8%) | 33 (84.6%) | 32 (86.2%) | |
| Apfel Score | .741 | |||
| 2 | 24 (64.9%) | 22 (56.4%) | 23 (62.2%) | |
| 3 | 13 (35.1%) | 17 (43.6%) | 14 (37.8%) | |
| Anesthesia time (min) | 24.50 (17.25–29.50) | 22.00 (17.00–30.00) | 20.00 (17.00–26.00) | .272 |
| Recovery time (min) | 6.00 (5.00–10.00) | 8.00 (6.00–10.00) | 7.00 (5.50–11.00) | .353 |
| Remimazolam dosage (mg) | 32.36 (24.72–41.61) | 31.33 (24.68–39.14) | 31.12 (24.59–38.77) | .798 |
| Alfentanil dosage (mg) | 1.54 (1.40–2.08) | 1.56 (1.36–1.77) | 1.66 (1.40–2.91) | .286 |
Data are mean ± SD, number of patients (%), or median (interquartile range).
ASA = American Society of Anesthesiologists, BMI = body mass index, DD group = dexamethasone plus droperidol group, DC group = dexamethasone plus saline group, DP group = dexamethasone plus propofol group.
In the PACU, the incidence of nausea and vomiting in DS group was higher than the other 2 groups, and the difference was statistically significant (P < .05). Within 24 hours after operation, the incidence of nausea was 54.1%, 43.6% and 51.4% in the 3 groups respectively, with no significant difference (P > .05), but the incidence of vomiting was lower in the DD and DP groups than in the DC, with a significant difference (P < .05) (Table 2).
Table 2.
Incidence of nausea and vomiting after surgery.
| DC group (n = 37) | DD group (n = 39) | DP group (n = 37) | P value | |
|---|---|---|---|---|
| PACU | ||||
| Nausea | 19 (51.4%) | 5 (12.8%)* | 4 (10.8%)* | .000 |
| Vomiting | 14 (37.8%) | 3 (7.7%)* | 4 (10.8%)* | .001 |
| 0–24 h | ||||
| Nausea | 20 (54.1%) | 17 (43.6%) | 19 (51.4%) | .637 |
| Vomiting | 14 (37.8%) | 5 (12.8%)* | 5 (13.5%)* | .011 |
Comparison with DC group.
DD group = dexamethasone plus droperidol group, DC group = dexamethasone plus saline group, DP group = dexamethasone plus propofol group, PACU = postanesthesia care unit.
P < .05; Data are presented as the numbers of patients and the percentage in the parentheses.
4. Discussion
The incidence of postoperative nausea and vomiting in gynaecological surgery patients can be as high as 60% to 83% in the absence of prophylactic antiemetic.[10] The occurrence of PONV is related to the patient himself, the anesthetic and the procedure. Patients in this study had a 40% to 60% risk of developing PONV by Apfel score.[9] In this study, Remimazolam combined with alfentanil was used for total intravenous anesthesia. Remimazolam is a new type of water-soluble ultra-short-acting sedative. By acting on γ-aminobutyrate A receptor (GABA), it causes chloride influx, inhibits neuronal electrical activity, and reduces neuronal excitability, resulting in sedation.[11] The safety and efficacy of remimazolam are not inferior to propofol in total intravenous anesthesia.[5] Alfentanil is a short-acting opioid with mild respiratory depression, low incidence of PONV and cough.[12,13] Langevin et al[14] found in a randomized controlled study that alfentanil caused less postoperative nausea and vomiting in outpatients compared to the same dose of fentanyl or sufentanil. It is recommended to combine sedatives for pain caused by short surgery.[15] A high incidence of nausea and vomiting after remimazolam combined with alfentanil anesthesia was found in a previous study and antiemetics needs to be given prophylactically to reduce the adverse experience of patients caused by PONV.[16] This study proposes to use low-dose propofol combined with dexamethasone as an antiemetic to observe its effectiveness in preventing PONV in gynaecological day surgery under remimazolam combined with alfentanil anesthesia.
The results of the study showed that in the postoperative PACU, low-dose propofol and droperidol combined with dexamethasone respectively significantly reduced the incidence of PONV in remimazolam combined with alfentanil anesthesia compared to dexamethasone alone, and the antiemetic effects of droperidol and low-dose propofol were comparable. Within 24 hours after surgery, the incidence of nausea was similar among the 3 groups, but the incidence of vomiting was lower in patients using low-dose propofol or droperidol than in those using dexamethasone alone.
In this study, dexamethasone 5 mg was given prophylactically to stop vomiting in each group before induction of anesthesia. Dexamethasone, a cortisol hormone with a slow onset and long duration of action, is a first-line option for the prevention and treatment of postoperative nausea and vomiting, either alone or in combination with other antiemetics.[17,18] Droperidol is a commonly used antiemetic drug in clinic. Low-dose droperidol (1 mg) can reduce the incidence of postoperative nausea and vomiting.[19] It exerts antiemetic effects mainly by inhibiting dopamine stimulation of the vomiting center, but there are side effects such as prolonged Q to T interval and extrapyramidal reactions.[19,20] In this study, droperidol 1 mg was used to prevent PONV without obvious adverse drug reactions. In addition, due to the sedative effect of droperidol, it may enhance the central role of hypnotics and analgesics, resulting in prolonged recovery time of patients. In this study, compared with the other 2 groups, the droperidol group did not significantly increase the recovery time of patients, which may be related to the small dose of droperidol. Propofol is an intravenous anesthetic commonly used for induction and maintenance of general anesthesia. Related studies have found that low-dose propofol also has the effect of preventing nausea and vomiting,[8,10,21] but its mechanism is not clear. A multicenter controlled clinical study found that propofol reduced the risk of postoperative nausea and vomiting by 19%.[22] Remimazolam-based anesthesia as a new way of total intravenous anesthesia, how to prevent its related postoperative nausea and vomiting deserves people’s attention. In this study, propofol or droperidol combined with dexamethasone respectively has the same effect in preventing PONV under remimazolam-based general anesthesia. Therefore, the safest and cheapest propofol is first recommended as an antiemetic to reduce the adverse reactions and economic burden caused by other antiemetic drugs.
There were some limitations to this study. Since most of the included patients left the hospital on the day of surgery, this study only studied the incidence of postoperative nausea and vomiting in gynecological patients, without classifying the degree of nausea and vomiting in detail. At the same time, due to ethical issues, each group of patients were given dexamethasone prophylactically. It cannot be determined whether dexamethasone alone can prevent nausea and vomiting after remimazolam-based general anesthesia, and further large sample and multicenter observation is needed.
In conclusion, the effect of low-dose propofol combined with dexamethasone to prevent PONV under remimazolam-based general anesthesia was similar to that of droperidol combined with dexamethasone, both of which significantly reduced the incidence of PONV in the PACU compared to dexamethasone alone. However, low-dose propofol combined with dexamethasone had little effect on the incidence of PONV within 24 hours compared to dexamethasone alone and only reduced the incidence of postoperative vomiting in patients.
Acknowledgments
All authors acknowledged Huan Zhang, Min Fu, Fangli Yue, who provided trial monitor in PACU.
Author contributions
Conceptualization: Hongyi Xiao, Fanceng Ji.
Formal analysis: Mingming Liu, Yan Man.
Investigation: Yan Man, Yaxin Wei.
Methodology: Hongyi Xiao.
Supervision: Fanceng Ji.
Writing – original draft: Hongyi Xiao, Yan Man, Yaxin Wei.
Writing – review & editing: Hongyi Xiao, Mingming Liu, Fanceng Ji.
Abbreviations:
- ASA
- American Society of Anesthesiologists
- DD group
- dexamethasone plus droperidol group
- DC group
- dexamethasone plus saline group
- DP group
- dexamethasone plus propofol group
- PACU
- postanesthesia care unit
- PONV
- postoperative nausea and vomiting
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Xiao H, Liu M, Man Y, Wei Y, Ji F. Effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting in gynaecological day surgery under remimazolam-based general anesthesia. Medicine 2023;102:10(e33249).
Contributor Information
Hongyi Xiao, Email: 1185549168@qq.com.
Mingming Liu, Email: liuriyue123@163.com.
Yan Man, Email: 1243734079@qq.com.
Yaxin Wei, Email: 2485692214@qq.com.
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