Dimenhydrinate for prophylaxis of postoperative nausea and vomiting: a meta-analysis of randomized controlled trials

BACKGROUND: Diphenhydramine and its theoclate salt dimenhydrinate are traditional antiemetics still in use. However, so far the quantitative effect of dimenhydrinate in the prophylaxis of postoperative nausea and vomiting (PONV) has not been evaluated systematically. METHODS: Results from randomized controlled trials investigating the efficacy of dimenhydrinate vs. a control to prevent PONV were included in a meta-analysis. Studies were systematically searched through MEDLINE, EMBASE, the Cochrane-Library, manually screening of reference lists of matching review articles and current issues of locally available peer-reviewed anesthesia journals, up to June 2001. The numbers of patients with complete absence of PONV within 6 h and within 48 h after surgery were extracted as the main end point. Pooled relative benefits (RB) and numbers-needed-to-treat (NNT) with their corresponding 95% confidence intervals (CI) were calculated using a random effects model. This quantitative systematic review was performed following the recommendations of the QUORUM statement. In all, 18 trials with 3045 patients were included in the analysis: 1658 patients received a placebo (control) and 1387 patients received dimenhydrinate. RESULTS: The RB to stay completely free of PONV was 1.2 (95% CI: 1.1-1.4) for the early period (NNT = 8; 95% CI: 5-25) and 1.5 (1.3-1.8) for the overall investigated period (NNT = 5; 95% CI: 3-9). CONCLUSION: Dimenhydrinate is a traditional and inexpensive antiemetic with an efficacy that might be considered as clinically relevant. Although in use for a long time, the dose-response, precise estimation of side-effects, optimal time of administration and the benefit of repetitive doses still remain unclear.     

Impact of an antiemetic protocol on postoperative nausea and vomiting in children

The objective of the study was to demonstrate a decreased incidence of postoperative nausea and vomiting (PONV) in children through the use of an antiemetic protocol. PONV was recorded in children (1.5-15 years) after inpatient surgery under general anaesthesia in a prospective, interview based survey. Group 1 consisted of children having surgery 1 month before the introduction of a formalized antiemetic protocol and group 2, 2 months after its introduction. Data were collected over a 1-month period in each group. Outcome measures of nausea, emesis, antiemetic requirement and patient satisfaction were monitored for the first 24-h postoperative period. There were 272 children enrolled: 138 in group 1 and 134 in group 2. There was a difference between the two groups for gender (P=0.03), type of surgery (P=0.017), perioperative opioid (P=0.003) and perioperative antiemetic use (P=0.024). However, multivariate analysis did not demonstrate an impact on outcome from these factors. The incidence of postoperative nausea (PON) and postoperative vomiting (POV) following the introduction of the protocol was 36% and 34%, respectively. Moderate to severe nausea was decreased after introduction of the protocol (18% versus 9%, P=0.028) but moderate to severe vomiting failed to reach significance (19% versus 11%, P=0.078). The proportion of children who had repeated nausea decreased after the introduction of the protocol (17% versus 8%, P=0.02) but repeated episodes of vomiting remained unchanged (19% versus 14%). This was attributed to a significant increase in antiemetic prescribing by protocol in group 2 (10% versus 59%, P < 0.001). Patient satisfaction was high in both groups (85% versus 90%). The introduction of a postoperative antiemetic protocol improved prescribing frequency. This resulted in a decreased incidence of moderate to severe PON and a reduction in the number of patients with repeated nausea.     

Intravenous dolasetron and ondansetron in prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study

Background: Intravenous dolasetron mesilate has shown efficacy in the prevention of postoperative nausea and vomiting (PONV) when administered as a single dose prior to emergence from anesthesia. This trial compared intravenous dolasetron and ondansetron for the prevention of PONV when administered at induction of anesthesia.
Methods: This double-blind, placebo-controlled, multicenter trial randomized patients to one of four single IV treatments: placebo, 25 or 50 mg dolasetron, or 4 mg ondansetron. Efficacy was measured by complete response (0 emetic episodes and no rescue medication), nausea severity and patient satisfaction as measured on a visual analog scale (VAS), investigator's rating of nausea severity, and total response (complete response with no nausea [≤ mm VAS]).
Results: 514 patients at 24 sites were evaluated for efficacy. The 50 mg dolasetron and 4 mg ondansetron doses were statistically equivalent, and superior to placebo, for all efficacy measures. Complete response rates were 49%, 51%, 71% and 64% for placebo, 25 and 50 mg dolasetron, and ondansetron, respectively. Dolasetron 50 mg was statistically superior to 25 mg dolasetron for complete response, total response, VAS maximum nausea, time to first emetic episode, and patient satisfaction. The majority of adverse events were of mild-to-moderate intensity. Headache was the most frequently reported treatment-related adverse event with a 3%-5% incidence across treatments.
Conclusion: When given at induction of anesthesia, 50 mg intravenous dolasetron is equivalent to 4 mg ondansetron and superior to 25 mg dolasetron and placebo for the prevention of PONV. All treatments were safely administered and well tolerated.     

Olanzapine as an add-on,pre-operative anti-emetic drug for postoperative nausea or vomiting: a randomised controlled trial

Postoperative nausea or vomiting occurs in up to 40% in patients with multiple risk factors, despite prophylaxis. Olanzapine is an antipsychotic drug that is used to prevent nausea and vomiting in palliative care and to treat chemotherapy-induced nausea and vomiting. This study aimed to examine whether pre-operative olanzapine, as a prophylactic anti-emetic added to intra-operative dexamethasone, ondansetron and total intravenous anaesthesia, reduced the incidence of postoperative nausea or vomiting. We performed a multiply-blinded randomised controlled trial in patients aged 18–60 years with cancer at high risk of postoperative nausea or vomiting (three or four risk factors according to the Apfel criteria) plus a previous history of chemotherapy-induced nausea and vomiting. Patients were allocated at random to receive 10 mg olanzapine or placebo orally 1 h before surgery in addition to a two-drug regimen (dexamethasone and ondansetron) and propofol anaesthesia to prevent postoperative nausea or vomiting. The primary outcome was the incidence of postoperative nausea or vomiting in the first 24 h after surgery. In total, 100 patients were enrolled; 47 in the olanzapine group and 49 in the control group completed the study. The baseline characteristics of the groups were similar. The incidence of postoperative nausea or vomiting in the first 24 h after surgery was lower in the olanzapine group (12/47, 26%) than in the control group (31/49, 63%) (p = 0.008, RR 0.40 (95%CI 0.21–0.79)). Adding pre-operative oral olanzapine to intra-operative dexamethasone and ondansetron was highly effective in reducing the risk of postoperative nausea or vomiting in the first 24 hours after surgery in patients with a previous history of chemotherapy-induced nausea and vomiting and at least three Apfel risk factors for postoperative nausea or vomiting.     

A double-blind, parallel-group, placebo-controlled, dose-ranging, multicenter study of intravenous granisetron in the treatment of postoperative nausea and vomiting in patients undergoing surgery with general anesthesia

Study Objective: To compare the effectiveness of granisetron with placebo in the treatment of established postoperative nausea and vomiting (PONV).

Design: Randomized, placebo-controlled study.

Setting: 34 hospitals in Europe, Scandinavia, and South Africa.

Patients: 519 ASA physical status I, II, and III patients who developed PONV within 4 hours of the end of surgery performed with general anesthesia.

Interventions: Patients received a single intravenous dose of granisetron 0.1 mg, 1 mg, or 3 mg, or placebo when symptoms of nausea or vomiting were experienced. Additional rescue medication could be given at the investigator's discretion if nausea and vomiting were not controlled.

Measurements and Main Results: At all doses investigated, granisetron was significantly more effective (p ≤ 0.001) than placebo in controlling vomiting: 38%, 46%, and 49% of patients receiving granisetron, 0.1 mg, 1.0 mg, and 3.0 mg, respectively, experienced no vomiting in the first 24 hours following drug administration, compared with 20% receiving placebo. There was a statistically significant linear relationship between vomiting control and granisetron dose (p < 0.001). Survival distributions of time to resolution of vomiting confirmed the statistically significant difference between patients receiving granisetron and those receiving placebo. Granisetron was well tolerated: the most common adverse experiences were pain, constipation, anemia, and headache, and the incidence of adverse experiences was not statistically significantly higher in any of the granisetron groups than in the placebo group.

Conclusion: Granisetron was significantly more effective than placebo in all groups. Further studies in specific subgroups may be warranted.     

Prophylactic ondansetron for postoperative emesis.Meta-analysis of its effectiveness in patients with previous history of postoperative nausea and vomiting

BACKGROUND: The objective of this study was to compare, by means of meta-analysis, the postoperative antiemetic efficacy of ondansetron in patients with and without antecedents of postoperative nausea and vomiting. METHODS: MEDLINE and EMBASE databases were searched for randomised placebo-controlled trials which evaluated the antiemetic effectiveness of 4 mg and 8 mg intravenous doses of prophylactic ondansetron in adult patients. A further selection was with respect to those studies which noted the patient's previous history of postoperative nausea and vomiting (PH-PONV) and, for the meta-analysis, the patients were divided into two sub-groups: those with (PH-PONV +) and those without a previous history of postoperative nausea and vomiting (PH-PONV -). Absence of vomiting was used as the index of effectiveness. RESULTS: Twenty-one trials involving 3984 patients (2446 in ondansetron groups and 1538 in placebo groups; 1163 PH-PONV(+) patients and 2821 PH-PONV(-) patients) met the selection criteria. The effectiveness of the 4 mg dose of ondansetron was: OR (95% CI)=2.40 (1.77-3.26) vs. 2.71 (2.23-3.30) for the patients of PH-PONV(+) and PH-PONV(-) sub-groups, respectively. For the 8 mg dose, the effectiveness of ondansetron was: PH-PONV(+)=4.21 (2.66-6.66) and PH-PONV(-)=2.61 (1.81-3.59). For neither of the doses evaluated was there any significant statistical difference between the sub-groups. CONCLUSIONS: The effectiveness of ondansetron in the prevention of postoperative vomiting is not affected by the patients' PH-PONV.     

Evaluation of three risk scores to predict postoperative nausea and vomiting

BACKGROUND: So far there are three different scores to predict postoperative vomiting (PV: Apfel et al., 1998) or postoperative nausea and vomiting (PONV: Koivuranta et al., 1997; Palazzo and Evans, 1993). All three scores used logistic regression analysis to identify and create weights for the risk factors for PV or PONV. In short, these were sex, age, history of previous PONV, motion sickness, duration of anaesthesia, and use of postoperative opioids. However, an external evaluation and a comparison of these scores has not been performed so far. METHODS: Patients undergoing a variety of surgical procedures under general anaesthesia were studied prospectively. Preoperatively, they completed a questionnaire concerning potential risk factors for the occurrence of PV or PONV implemented in the three risk scores. Balanced anaesthesia (induction agent, nondepolarising neuromuscular blocker, opioid, and inhalation agent in nitrous oxide/oxygen) was performed. No intravenous anaesthesia or any antiemetic prophylaxis was applied. Postoperatively, the patients were observed in the recovery room for the occurrence of PV and PONV and were visited twice on the ward within the 24-h observation period. Both the patients and the nursing staff were asked whether PV or PONV was present. The severity of PONV was categorised using a standardised scoring algorithm. A total of 1,444 patients was finally included into the analysis. Using information of the predicted risk for the individual patients and the actual occurrence of PV or PONV, Receiver Operator Characteristics (ROC-curves) were drawn. The area under each ROC-curve was calculated as a means of the predictive properties of each score and was compared for statistical differences. RESULTS: For prediction of PONV (any severity) the AUC-values (AUC=area under the curve) and the corresponding 95%-confidence intervals were: Apfel: 0.70 (0.67-0.72); Koivuranta: 0.71 (0.69-0.73); Palazzo: 0.68 (0.65-0.70). For prediction of PV: Apfel: 0.73 (0.71-0.75); Koivuranta: 0.73 (0.70-0.75); Palazzo: 0.68 (0.65-0.70). Thus, all three scores appeared to have a moderate accuracy as measured by the AUC. The score of Koivuranta predicts PONV (P=0.007) and also PV (P=0.002) significantly better than Palazzo's score. Furthermore, for predicting of PV the score of Apfel was also superior to Palazzo's score (P=0.005). All three scores predict PV with the same accuracy as PONV. CONCLUSION: The occurrence of PV and PONV in patients undergoing surgery under balanced anaesthesia can be predicted with moderate but acceptable accuracy using one of the available risk scores, regardless of local surgical or anaesthesiological circumstances. For clinical practice, we recommend the score published by Koivuranta, since its calculation is very simple.     

A comparison of cyclizine,ondansetron and placebo as prophylaxis against postoperative nausea and vomiting in children

Nausea and vomiting is a relevant and common problem with unfavourable sequelae in children undergoing some plastic surgery procedures. There is a lack of anti-emetic trials performed in children, with only a few investigating the roles of the older anti-emetic agents such as cyclizine compared with newer ones such as ondansetron. This randomised, controlled, double-blind study examined the effectiveness of a single dose of ondansetron (0.1 mg x kg-1), cyclizine (20 mg) and placebo (normal saline) in the prevention of postoperative nausea and vomiting in 150 children (mean age 3.6 years) undergoing plastic genitourinary procedures. Rates of previous postoperative nausea and vomiting and motion sickness were comparable across the groups. Postoperative vomiting was significantly reduced with ondansetron prophylaxis (p = 0.006) but there was no detectable anti-emetic effect with cyclizine. Furthermore, cyclizine caused pain on injection (p < 0.001).     

The influence of a dominating centre on a quantitative systematic review of granisetron for preventing postoperative nausea and vomiting

BACKGROUND: We performed a meta-analysis on granisetron in the prevention of postoperative nausea and vomiting (PONV) and further investigated whether total results and the dose-response characteristics may be significantly affected by a single centre. METHODS: Systematically searched randomised controlled trials (RCT) using granisetron for the prevention of PONV after general anaesthesia were included in the analysis. The pooled relative risks (RR) and numbers needed to treat (NNT) with their corresponding 95%-confidence intervals (CI) were calculated. For all centres, one dominating centre and other centres pooled, comparisons were performed according to all doses, low dose (20 microg/kg) granisetron. RESULTS: A total of 27 RCT with 2938 patients were included in the analysis. RR (CI) to suffer from PONV with granisetron when all comparisons were considered was 0.46 (0.39-0.54), 0.7 (0.6-0.81) and 0.34 (0.28-0.41) for all doses, low and high dose, respectively. RR of the dominating centre (1867 patients) were significantly better compared to the remaining centres (1071 patients), with 0.41 (0.34-0.49) and 0.60 (0.49-0.73), respectively. In the dominating centre low dose granisetron was ineffective with a RR of 0.84 (0.68-1.04), while high dose granisetron led to a strong decrease with a RR of 0.30 (0.26-0.36). In contrast, the RR of other centres pooled for low and high dose granisetron were comparable with 0.62 (0.49-0.79) and 0.56 (0.42-0.75), respectively. CONCLUSIONS: Overall results and dose-response characteristics of meta-analyses may be significantly altered by one dominating centre. Further, if data of a dominating centre do not appear to be valid for other centres, it may seem advisable to either exclude them from the analysis or to perform sub-group analyses so that results without the data from the dominating centre are available.     

A small dose of droperidol decreases postoperative nausea and vomiting in adults but cannot improve an already excellent patient satisfaction

BACKGROUND: We evaluated whether or not 1) a routine prophylaxis with 20 microg x kg(-1) body weight of droperidol would efficiently prevent postoperative nausea and vomiting (PONV) after elective surgery in adults and 2) an efficient prophylaxis would improve patient satisfaction. METHODS: With approval of the local ethics committe and after having obtained informed written consent, 1334 patients in a randomised, single-blinded fashion either received droperidol (group 1, n=665) or saline intravenously (group 2, n=669) 20 min before the end of a standard O2/N2O/fentanyl/isoflurane anaesthesia of at least 30 min duration. End points: incidence of PONV during the first 24 h; individual episodes of nausea or vomiting, overall patient satisfaction with the procedure. RESULTS: Compared to saline, intravenous injection of droperidol substantially and significantly reduced the incidence of PONV from 30% to 20% (P<0.0001). Women suffered three times more frequently from PONV (10.5% vs. 30%, P<0.0001). Droperidol significantly reduced the incidence of PONV from 35.4% to 24.4% in women (relative risk reduction: 31%, P=0.0002), but not in men (13.1% vs. 8.2%, relative risk reduction: 37%, P=0.159)--without impact on overall patient satisfaction (98.8% vs. 97.1%, P=0.439). Distribution of surgical procedures, sex, age, height, weight and anaesthetic duration were not different between groups. To prevent one woman from suffering PONV, nine had to be treated prophylactically at an individual drug cost (German prices) of about Euro0.80 per woman. CONCLUSION: Routine PONV prophylaxis with 20 microg x kg(-1) body weight of droperidol is cost-efficient and appropriate in women but not in men.     

5-羟色胺受体拮抗剂与氟哌利多预防术后恶心呕吐效果的Meta分析

目的 采用Meta分析比较5-羟色胺(5-hydroxytryptamine,5-HT3)受体拮抗剂与氟哌利多预防术后恶心呕吐(postoperative nausea and vomiting,PONV)的效果. 方法 检索Cochrane图书馆、Pubmed、EMBASE、中国生物医学文献数据库(CBM)、中国学术期刊全文数据库(CNKI)、重庆维普中文科技期刊全文数据库(VIP)、万方数据库,检索时间从建库至2013年9月.收集所有比较5-HT3受体拮抗剂与氟哌利多用于预防全麻PONV的文献.采用Cochrane协作网系统评价法评价纳入文献的质量,采用RevMan 5.1软件对收集的患者资料进行Meta分析评价. 结果 共纳入17项随机对照试验(randomized controlled trial,RCT),1 823例患者.Meta分析结果显示:与氟哌利多比较,5-HT3受体拮抗剂能降低全麻患者PONV(术后0～24 h)[比值比(RR)=0.49,95％可信区间(CI)=0.39～0.63]与呕吐(RR=0.54,95％CI=0.43～0.67)的发生率.亚组分析结果表明,昂丹司琼预防PONV(RR=0.67,95％CI=0.47～0.96)与呕吐(RR=0.56,95％CI=0.39～0.82)的发生较氟哌利多更好;格拉司琼预防PONV (RR=0.42,95％CI=0.30～0.58)与呕吐(RR=0.58,95％CI=0.42～0.81)的发生较氟哌利多更好.5-HT3受体拮抗剂与氟哌利多预防术后恶心的效果相当(RR=0.89,95％CI=0.77～1.04).昂丹司琼(RR=0.88,95％CI=0.67～1.14)或格拉司琼(RR=0.94,95％CI=0.75～1.17)与氟哌利多预防术后恶心的效果相当.与氟哌利多比较较,5-HT3受体拮抗剂组头痛发生率明显增加(RR=1.44,95％CI=1.12～1.84);5-HT3受体拮抗剂与氟哌利多术后头晕(RR=I.19,95％CI=0.88～1.62)、嗜睡(RR=1.24,95％CI=0.34～4.49)的发生率相同. 结论 与氟哌利多比较,5-HT3拮抗剂预防全麻患者PONV效果较好.     

An increased body mass index is no risk factor for postoperative nausea and vomiting. A systematic review and results of original data

BACKGROUND: An increased Body Mass Index (BMI) is almost always mentioned as a fundamental risk factor for postoperative nausea (PN), vomiting (PV) or both (PONV). However, multivariate analyses were unable to detect any correlation. Therefore, we asked whether an increased BMI is really a risk factor for PONV. METHODS: For the systematic review, a search of electronic databases and a detailed manual search of reviews were carried out. For the analysis of the original data, 587 adult patients from a randomised controlled antiemetic trial (RCT) who underwent general anaesthesia were allocated to four weight groups: Underweight (BMI < 20), Normal Weight (BMI 20-25), Overweight (BMI 25-30) and Obesity (BMI > or = 30). RESULTS: Four publications with original data were found. Two described a positive relationship, although not clearly supported by the data. Despite this, most narrative reviews claimed a positive correlation between obesity and PONV by quoting again narrative reviews or misquoting originals. In the RCT, the calculated underlying risk profile for PONV was comparable between all groups. Incidences (95% confidence intervals) of PONV were 45.8% (34.0; 57.6), 41.7 (36.5; 46.9), 47.8 (38.4; 57.1) and 44.1 (31.0; 57.1), for the groups Underweight, Normal Weight, Overweight and Obesity, respectively (P=0.69). The incidences of PN and PV also did not differ with P=0.76 and P=0.36, respectively. CONCLUSION: Systematic search of the literature provides no evidence for a positive relationship. Furthermore, our data confirm that an increased BMI is not a risk factor for PONV. This negative finding is important as focussing on the relevant risk factors is needed to allow for an objective risk assessment of PONV.     

Dexamethasone versus ondansetron in combination with dexamethasone for the prophylaxis of postoperative vomiting in pediatric outpatients: a double‐blind,randomized, placebo‐controlled clinical trial

Objectives: To determine the frequency of postoperative vomiting (POV) in children submitted to outpatient surgery and to compare the efficacy of antiemetic drugs in preventing this complication. Background: Nausea and vomiting are common in the immediate postoperative period following anesthetic and surgical procedures. Compared to adults, pediatric patients are more likely to develop postoperative nausea and vomiting, the incidence of which ranges from 8.9% to 42%. Methods: This double‐blind, randomized, placebo‐controlled clinical trial included 129 children. The participants were randomized into three prophylactic treatment groups: dexamethasone (n = 43), ondansetron in combination with dexamethasone (n = 44), and placebo (n = 42). The variables studied were the frequency of POV and the incidence of vomiting after the patient had been discharged from hospital, the need for antiemetic rescue therapy in the postanesthesia care unit (PACU), need for hospitalization, and the time the patient remained in the PACU. A significance level of 5% was adopted. Results: Postoperative vomiting occurred in 12.4% of the children, with no statistically significant difference between the groups: 6.8% in the group receiving ondansetron combined with dexamethasone, 14.3% in the placebo group, and 14% in the group that received dexamethasone alone (P = 0.47). Furthermore, no significant difference was found between the groups with respect to the time the children remained in the PACU, and only five patients reported having vomited following discharge from hospital. Conclusions: The prophylactic use of antiemetic drugs failed to reduce the incidence of POV in pediatric outpatient surgery with a low emetic potential; therefore, routine prophylaxis may be unnecessary.