Adding Ondansetron in Morphine Intravenous Analgesia Pump for Prevention of Postoperative Nausea and Vomiting in Women

BAI Bing, PEI Lijian, ZHANG Yuelun, SANG Nuoer, ZHANG Xiuhua, HUANG Yuguang

Acta Academiae Medicinae Sinicae ›› 2018, Vol. 40 ›› Issue (3) : 373-377.

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Abbreviation (ISO4): Acta Academiae Medicinae Sinicae      Editor in chief: Xuetao CAO

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Acta Academiae Medicinae Sinicae ›› 2018, Vol. 40 ›› Issue (3) : 373-377. DOI: 10.3881/j.issn.1000-503X.2018.03.013
Original Articles

Adding Ondansetron in Morphine Intravenous Analgesia Pump for Prevention of Postoperative Nausea and Vomiting in Women

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Abstract

Objective To evaluate the application of adding ondansetron in morphine intravenous analgesia pump for prevention of postoperative nausea and vomiting(PONV)in women.Methods Data of surgical female inpatients who received general anesthesia and postoperative intravenous analgesia with morphine in our center from January 1st,2013 to December 31st,2014 were retrospectively analyzed. Based on whether ondansetron was added,patients were divided into the observation group(n=834) and the control group(n=856). Outcome variables including morphine consumption,visual analogue scale(VAS) score,nausea score,and total times of vomiting within 48 hours after surgery were collected and compared.Results Age(t=0.432,P=0.665),morphine consumption during the first post-operative day(t=0.599,P=0.548) and during the second post-operative day(t=0.236,P=0.813),maximum VAS score of postoperative pain during movement during the first post-operative day [3(2,4) vs. 3(2,5);Z=1.850,P=0.064] and at rest during the second post-operative day [0(0,1) vs. 0(0,1);Z=1.511,P=0.131] were not significantly different between two groups. While the maximum VAS score of postoperative pain at rest during the first post-operative day [0(0,2) vs.0(0,2);Z=2.435,P=0.015] and during movement during the second post-operative day [3(1,3)vs.3(2,4);Z=3.445,P=0.001] were significantly different between two groups. The maximum score of postoperative nausea(χ 2=9.810,P=0.020) and cumulative frequency of postoperative vomiting(Z=3.726,P=0.002)in the observation group were significantly lower than those in the control group during the first post-operative day;however,there was no significant difference during the second post-operative day(χ 2=5.017,P=0.170;Z=0.000,P=1.000). Logistic regression analysis showed that adding ondansetron in morphine intravenous analgesia pump was an independent influencing factor of reduced postoperative nausea. The probability of nausea during the first post-operative day was 0.781 time(P=0.015)of that in the control group and 0.736 time(P=0.030)during the second post-operative day.Conclusion Adding ondansetron in morphine intravenous analgesia pump may reduce PONV in women.

Key words

postoperative nausea and vomiting / ondansetron / intravenous patient-control analgesia

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BAI Bing , PEI Lijian , ZHANG Yuelun , et al . Adding Ondansetron in Morphine Intravenous Analgesia Pump for Prevention of Postoperative Nausea and Vomiting in Women[J]. Acta Academiae Medicinae Sinicae. 2018, 40(3): 373-377 https://doi.org/10.3881/j.issn.1000-503X.2018.03.013

References

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Kim MS, Park JH, Choi YS , et al. Efficacy of palonosetron vs. ramosetron for the prevention of postoperative nausea and vomiting:a meta-analysis of randomized controlled trials[J]. Yonsei Med J, 2017,58(4):848-858. DOI: 10.3349/ymj.2017. 58.4.848.
This study was designed as a meta-analysis of randomized controlled trials (RCTs) that included the comparison of palonosetron and ramosetron for postoperative nausea and vomiting (PONV) prophylaxis. A systematic search was conducted for the PubMed, EMBASE, Web of Science, CENTRAL, KoreaMed, and Google Scholar databases (PROSPERO protocol number CRD42015026009). Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) during the first 48 hrs after surgery. The total 48-hr period was further analyzed in time epochs of 0–6 hrs (early), 6–24 hrs (late), and 24–48 hrs (delayed). Subgroup analyses according to number of risk factors, sex, and type of surgery were also performed. Eleven studies including 1373 patients were analyzed. There was no difference in PON or POV between the two drugs for the total 48-hr period after surgery. However, palonosetron was more effective in preventing POV during the delayed period overall [relative risk (RR), 0.59; 95% confidence interval (CI), 0.39 to 0.89;p=0.013], as well as after subgroup analyses for females and laparoscopies (RR, 0.56; 95% CI, 0.36 to 0.86;p=0.009 and RR, 0.46; 95% CI, 0.23 to 0.94;p=0.033). Subgroup analysis for spine surgery showed that ramosetron was more effective in reducing POV during the total 48-hr (RR, 3.34; 95% CI, 1.46 to 7.63;p=0.004) and early periods (RR, 8.47; 95% CI, 1.57 to 45.72;p=0.013). This meta-analysis discovered no definite difference in PONV prevention between the two drugs. The significant findings that were seen in different time epochs and subgroup analyses should be confirmed in future RCTs.
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Yazbeck-Karam VG, Siddik-Sayyid SM, Barakat HB , et al. Haloperidol versus ondansetron for treatment of established nausea and vomiting following general anesthesia:a randomized clinical trial[J]. Anesth Analg, 2017,124(2):438-444. DOI: 10.1213/ANE.0000000000001723.
Haloperidol is an antipsychotic. At low doses, it is a useful agent for the prophylaxis of postoperative nausea and vomiting (PONV). However, its use for treating established PONV has not been well studied.This randomized double-blinded trial tested whether haloperidol is noninferior to ondansetron for the early treatment of established PONV in adult patients undergoing general anesthesia. The primary outcome is whether patients were PONV free during the first 4 hours. The noninferiority margin was set at 15%. One hundred twenty patients with PONV received either haloperidol 1 mg intravenously (n = 60) or ondansetron 4 mg intravenously (n = 60).Data from 112 patients (59 in the haloperidol group and 53 in the ondansetron group) were analyzed. Thirty-five patients (52%) in the haloperidol group received 1 or 2 prophylactic antiemetics compared with 42 (79%) in the ondansetron group. Haloperidol was noninferior to ondansetron for the end point of complete response to treatment (defined as the rate of PONV-free patients) for the early (0–4 hour) and the 0- to 24-hour postoperative periods by both the per-protocol and intention-to-treat analyses. In the per-protocol analysis, complete responses in the early period were noted in 35 of 59 patients (59%) and 29 of 53 patients (55%) for the haloperidol and ondansetron groups, respectively (difference 5%; 95% confidence interval [CI]: 6113% to 22 %), and in the 0- to 24-hour period in 31 of 59 patients (53%) and 26 of 53 patients (49%) for the haloperidol and ondansetron groups, respectively (difference 4%; 95% CI of the difference: 6115% to 21%). In the intention-to-treat analysis, complete responses in the early period were noted in 35 of 60 patients (58%) and 29 of 60 patients (48%) for the haloperidol and ondansetron groups, respectively (difference 10%; 95% CI of difference: 618% to 27%) and in the 0- to 24-hour period in 31 of 60 patients (52%) and 26 of 60 patients (43%) for the haloperidol and ondansetron groups, respectively (difference 8%; 95% CI of the difference: 619% to 25%). All other PONV secondary outcomes were comparable. Twenty-five percent of patients in the haloperidol group were sedated versus 2% in the ondansetron group (P < .001; difference 23%; 95% CI of the difference: 11%–36%). Pain, satisfaction scores, need for analgesics, and changes in QTc intervals were not different between the 2 groups.Haloperidol is at worst 13% and 8% less effective than ondansetron by per-protocol analysis and by intention-to-treat analysis, respectively. Thus, it is noninferior to ondansetron for the early treatment of established PONV, but is associated with sedation.
[3]
裴丽坚, 桑诺尔, 高鲜丽 , 等. 女性术后吗啡静脉镇痛泵中加入昂丹司琼不能减少术后恶心呕吐[J]. 基础医学与临床, 2014,34(4):519-522.
目的 评价术后吗啡静脉镇痛泵中加入昂丹司琼预防术后恶心呕吐的有效性。方法 对2012-01-01-2012-06-30北京协和医院女性全麻+术后吗啡静脉镇痛患者进行单因素回顾性分析。结果 578例女性患者纳入最终分析,其中术后吗啡静脉镇痛泵中未加入昂丹司琼55例,加入昂丹司琼523例(昂丹司琼0.2mg~0.5mg/h,持续泵入48h)。两组间术后静息疼痛视觉模拟评分(VAS)最大值、活动后疼痛视觉模拟评分最大值以及术后镇静评分均无差异。术后恶心评分最大值以及术后48h内累计呕吐次数无差异。结论 女性术后吗啡静脉镇痛泵中加入昂丹司琼并不能减少术后恶心呕吐的发生。
[4]
Gao C, Li B, Xu L , et al. Efficacy and safety of ramosetron versus ondansetron for postoperative nausea and vomiting after general anesthesia:a meta-analysis of randomized clinical trials[J]. Drug Des Devel Ther, 2015,9:2343-2350. DOI: 10.2147/DDDT.S80407.
Abstract BACKGROUND: Postoperative nausea and vomiting is a common side effect of general anesthesia. In this study, we performed a meta-analysis on the efficacy and safety of ramosetron versus ondansetron in the prevention of postoperative nausea and vomiting using the most recently published randomized controlled clinical studies. METHODS: PubMed and EMBASE were searched for randomized controlled clinical trials comparing the efficacy and safety of ramosetron and ondansetron. The meta-analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK). Dichotomous outcomes are presented as the relative risk (RR) with a 95% confidence interval (CI). RESULTS: A total of 898 patients from nine selected studies were treated with antiemetics after surgery, including 450 patients who received ondansetron 4 mg and 448 patients who received ramosetron 0.3 mg. The meta-analysis showed no statistically significant difference between the two groups with regard to prevention of postoperative nausea (PON) during different time periods in the 48 hours after surgery. When comparing the efficacy of ramosetron and ondansetron in the prevention of postoperative vomiting (POV), at various time intervals in the 24 hours after surgery, ramosetron was significantly more efficient than ondansetron: 0-6 hours (RR 0.46, 95% CI 0.24-0.92; P=0.03), 0-24 hours (RR 0.72, 95% CI 0.52-1.00; P=0.05), and 6-24 hours (RR 0.51, 95% CI 0.31-0.84; P=0.008). At other time periods between 24 and 48 hours after surgery, ramosetron did not show better efficacy than ondansetron. When comparing the safety profiles of ramosetron and ondansetron, fewer side effects were recorded in the ramosetron group (RR 0.65, 95% CI 0.47-0.91; P=0.01). CONCLUSION: Our meta-analysis demonstrates that ramosetron was more effective than ondansetron in the prevention of early POV (0-24 hours) with fewer recorded side effects. However, our study did not reveal any statistically significant differences in efficacy between ramosetron and ondansetron in the prevention of PON or late POV (at 24-48 hours).
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Munro FJ, Fisher S, Dickson U , et al. The addition of antiemetics to the morphine solution in patient controlled analgesia syringes used by children after an appendicectomy does not reduce the incidence of postoperative nausea and vomiting[J]. Paediatr Anaesth, 2002,12(7):600-603. DOI: 10.1046/j.1460-9592.2002.00900.x.
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Cao X, White PF, Ma H . An update on the management of postoperative nausea and vomiting[J]. J Anesth, 2017,31(4):617-626. DOI: 10.1007/s00540-017-2363-x.
Abstract Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. PONV and PDNV can delay discharge and recovery and increase medical costs. The high incidence of PONV has persisted in part because of the tremendous growth in ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major operations. Pharmacological management of PONV should be tailored to the patients' risk level using the PONV and PDNV scoring systems to minimize the potential for these adverse side effects in the postoperative period. A combination of prophylactic antiemetic drugs should be administered to patients with moderate-to-high risk of developing PONV in order to facilitate the recovery process. Optimal management of perioperative pain using opioid-sparing multimodal analgesic techniques and preventing PONV using prophylactic antiemetics are key elements for achieving an enhanced recovery after surgery. Strategies that include reductions of the baseline risk (e.g., adequate hydration, use of opioid-sparing analgesic techniques) as well as a multimodal antiemetic regimen will improve the likelihood of preventing both PONV and PDNV.
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Ondansetron is widely used in general practice for nausea and vomiting due to any cause. We report a rare side effect, life-threatening hypokalaemia following intravenous Ondansetron injection. It may be judicious to restrict the use of Odansetron to patients with severe vomiting due to chemotherapy or in post- operative state. Life-threatening hypokalemia can occur without any warning and may be difficult to manage in a primary set up.
[9]
Boonmak P, Boonmak S, Bunsaengjaroen P , et al. Antiemetic effect of ondansetron 0.2 mg ml-1 in PCA morphine solution[J]. Eur J Anaesthesiol, 2007,24(8):664-667. DOI: 10.1017/S0265021507000208.
Abstract BACKGROUND AND OBJECTIVES: To study the effect of 0.2 mg mL-1 of ondansetron added to morphine patient-controlled analgesia solution after a 4 mg loading dose on the incidence and severity of postoperative nausea and vomiting. METHODS: One hundred and sixty patients scheduled for elective surgery, between 18 and 65 yr old, were studied. Patients who smoked, received antiemetics and hormonal therapy, had a history of motion sickness or gastrointestinal disease, a body mass index >35 or menstruation at the time of the study were excluded. Patients were assigned to the ondansetron and control groups by block randomization. At the end of anaesthesia, all patients received 4 mg of ondansetron intravenously and the same patient-controlled analgesia regimen of morphine. The ondansetron group (n = 80) received 0.2 mg of ondansetron per 1 mg of morphine. The nausea score, vomiting score and the requested ondansetron dose were evaluated at 1, 2, 6, 12 and 24 h. Patient-satisfaction for nausea/vomiting was recorded at the end of the study. RESULTS: Patient characteristics and cumulative morphine consumption were similar but ondansetron group had higher pain scores (P = 0.006). The ondansetron group had a lower nausea and vomiting scores, and more patients were free from nausea and vomiting than the control group (41 vs. 26, respectively, P = 0.025). The ondansetron group had fewer cumulative ondansetron doses than the control group and better patient satisfaction than the control group (P < 0.05). CONCLUSION(S): Ondansetron 4 mg plus 0.2 mg mL-1 given with PCA morphine can reduce nausea and vomiting thus improving patient satisfaction.
[10]
Jellish WS, Owen K, Fluder E , et al. Patient-controlled analgesia combined with either ondansetron or ondansetron plus prochlorperazine for control of pain and nausea and vomiting in patients undergoing abdominal surgery[J]. J Clin Anesth, 2008,20(8):594-600.DOI: 10.1016/j.jclinane.2008.06.008.
To compare ondansetron with ondansetron plus prochlorperazine, added to a patient-controlled analgesia (PCA) solution for control of postoperative nausea and vomiting (PONV). Prospective, randomized, double-blinded study. University hospital. 150 ASA physical status I, II, and III patients undergoing abdominal surgery. Patients were given a PCA morphine solution containing either 30 mg of ondansetron (Group O), 30 mg of ondansetron plus 20 mg of prochlorperazine (Group OP), or no antiemetic (Group C; control group). Demographic data were recorded, along with anesthetic and surgical time, total fluid intake, frequency of Postanesthesia Care Unit (PACU) PONV, discharge time and length of stay, frequency of PONV while on the hospital floor, highest nausea scores, total PCA morphine use, and PCA utilization times. Demographic and intraoperative variables were similar in all groups. In the first 24 hours after surgery, nausea was higher in Group C than Group OP. Emesis in Group C was twice that of either Group O or Group OP. No differences were noted between groups in PACU PONV. Patients receiving ondansetron plus prochlorperazine when on the hospital floor had a lower frequency of nausea, while patients receiving ondansetron alone had a lower frequency of vomiting than did the control group. The adjusted odds of vomiting doubled for every 12 hours for Group C patients when receiving PCA. Combination antiemetics added to PCA reduced emetic symptoms after abdominal surgery.

Footnotes

The authors have declared that no competing interests exist.

作者已声明无竞争性利益关系。

感谢北京协和医院手术室任丽英老师和曾在我科进行一阶段规范化培训的基地住院医高鲜丽、贺文丽、黄秀丽、杨建、苏宁在数据收集和整理工作中的大力帮助

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