Alizaprideand ondansetronin the prevention of postoperative nausea and vomiting: a prospective, randomized, double-blind, placebocontrolled

Transcription

1 Alizaprideand ondansetronin the prevention of postoperative nausea and vomiting: a prospective, randomized, double-blind, placebocontrolled trial. M. Smets N. Van Langenhove G. Dewinter Vrijdagochtendkrans22 juni2012

2 Introduction Previous studies/guidelines Methods Results Discussion Conclusion

3 Introduction PONV = a common postoperative problem INCIDENCE: 20-30% after general anesthesia up to 70% in highriskpatients ASSOCIATED MORBIDITY: Decreased patient satisfaction Delayed hospital discharge and/or unexpected hospital admission Wound dehiscence, bleeding etc.

4 Introduction RISK FACTORS: Patient-related: Age Gender Smokers Previous PONV or motion sickness Surgery-related Breast, ophtalmic, gynaecological, laparoscopic, craniotomy, laparatomy Anesthesia-related Premedication Type of anesthesia(ga vs RA, TIVA vs volatile) Intra-operative use of emetogenic drugs Adequate hydration

5 Previous studies Droperidol, alizaprideand metoclopramide in the prevention and treatment of postoperative emetic sequelae. Kauste et al., female patients for elective orthopaedic surgery under GA 100 or 200 mg alizapride, 1.25 mg droperidol, 20 mg metoclopramide or saline placebo Prevention and treatment of PONV Kausteet al. Droperidol, alizaprideand metoclopramide in the prevention and treatment of post-operative emetic sequelae. Eur J Anaesthesiol 1986(3):1-9

6 Previous studies Prevention: saline group: 83% PONV, droperidol35%, alizapride100 mg 46%, alizapride200 mg 53%, metoclopramide 58% most commonly 3-12 h after anaesthesia Therapy: patients in saline and metoclopramide group needed more additional doses of anti-emetic Conclusion: droperidolwas the most effective, and metoclopramide the least effective anti-emetic Kausteet al. Droperidol, alizaprideand metoclopramide in the prevention and treatment of post-operative emetic sequelae. Eur J Anaesthesiol 1986(3):1-9

7 Previous studies Alizapridein prevention of postoperative nausea and vomiting. Booij et al, ASA I or II female out-patients Laparoscopic gynaecologicalprocedures 4 groups: placebo, alizapride50/100/200 mg iv PONV incidence until 4 hours after anaesthesia Booijet al. Alizapridein prevention of postoperative nausea and vomiting. NethJ Surg1988 feb;40(1):6-9

8 Previous studies Lower PONV-incidence with alizapride-treated patients: -50% Dose-dependent effect of alizapride No prolonged recovery Placebo-group: incidence of vomiting x2 + further anti-emetic medication in 20% Booijet al. Alizapridein prevention of postoperative nausea and vomiting. NethJ Surg1988 feb;40(1):6-9

9 Previous studies Alizapridein the prevention of postoperative vomiting. A double-blind comparison. Vanacker et al, women for planned soft tissue surgery 2 groups: alizapride50 mg iv or placebo 20 min before end of operation + 4 and 8 hours after first injection Therapeutic dose alizapride50 mg if retching or emesis occurred VanackerB, Van AkenH. Alizapridein the prevention of postoperative vomiting. A double-blind comparison. Acta Anesthesiol Belg. 1988;39(4):247-50

10 Previous studies Incidence of nausea, retching or emesis during 24 hours after operation Alizapridegroup: less retching or emesis and higher number of patients without symptoms Still 34% postoperative vomiting in alizapride group (placebo 56%) No untoward side-effects VanackerB, Van AkenH. Alizapridein the prevention of postoperative vomiting. A double-blind comparison. Acta Anesthesiol Belg. 1988;39(4):247-50

11 Previous studies Alizapride in the prevention of postthyroidectomy emetic sequelae. Dejonckheere et al, patients for elective thyroidectomy 2 groups: alizapride100 mg iv or placebo 5 min before induction, every 4h thereafter for 20h Observation period: 24 hours Nausea, vomiting; occurrence and severity Dejonckheere et al. Alizapride in the prevention of post-thyroidectomy emetic sequelae. Eur J Anaesthesiol 1990;7:

12 Previous studies Incidence of nausea (63 vs46%) and vomiting (63 vs41%) higher in placebo group No troublesome side-effects of alizapride Alizaprideeffectively reduces the occurrence of PONV after thyroidectomy Dejonckheere et al. Alizapride in the prevention of post-thyroidectomy emetic sequelae. Eur J Anaesthesiol 1990;7:

13 Previous studies Double-blind comparison of alizapride, droperidoland ondansetronin the treatment of post-operative nausea. Stienstra et al, patients, gynaecologicalprocedures, GA PONV in first hour after surgery 3 groups: alizapride100 mg, droperidol1 mg, ondansetron8 mg iv nausea: VAS + vomiting (present/absent, number) Stienstra et al. Double-blind comparison of alizapride, droperidol and ondansetron in the treatment of post-operative nausea. Eur J Anaesthesiol 1997;14(3):

14 Previous studies 15 and 30 min after study drug: decreased VAS in all groups Comparison between groups: no differences Alizapride100 mg, droperidol1 mg and ondansetron8 mg iv equally effective in the treatmentof established PONV after gynaecologicalprocedures Similar side-effects and sedation scores Stienstra et al. Double-blind comparison of alizapride, droperidol and ondansetron in the treatment of post-operative nausea. Eur J Anaesthesiol 1997;14(3):

15 Previousstudies

16 Previousstudies 0-1 risk factor: low risk 2 risk factors: moderate risk 3-4 risk factors: high risk

17 Currentguidelines Gan T J et al. Anesth Analg 2003;97:62-71

18 Currentguidelines

19 Introduction Goal of the trial: demonstrate non-inferiority of alizaprideto ondansetron in the prevention of PONV Approved by the Ethics Committee

20 Methods 520 females randomised in 3 groups 30 minutes before the end of surgery: Alizapride 100 mg Ondansetron4 mg 4 ml saline -Placebo

21 Methods Inclusion-criteria: ASA 1 and 2 elective laparoscopic gynaecological surgery written informed consent cooperative patient 18 yearsold

22 Methods Exclusion-criteria: ASA 3 and 4 not-coöperative patient allergy to alizapride or ondansetron Parkinson disease pregnancy

23 Methods Premedication: alprazolam 0.5mg IV 1h before surgery Induction of anesthesia: sufentanil0.2µg/kg propofol 2mg/kg rocuronium0.5mg/kg Maintenance: sevofluranein 50% air/oxygenmixture sufentanil Trial drug: 30 minutes before end of surgery Postoperative pain paracetamol IV and ketorolac IV perop piritramide 0.25mg/kg IM and titrating per 2mg IV until pain-free

24 Methods PACU: hourly recording of Severity of nausea: VAS-score Presence and frequency of vomiting VAS > 2 or vomiting: 1.25 mg DHBP IV and 5 mg dexamethasoneiv After15 minutes still VAS >2: ondansetron4 mg and alizapride100 mg IV

25 Methods Evaluation VAS/vomiting after leaving PACU Evaluation VAS/vomiting after 24 hours

26 RESULTS: baselinecharacteristics Patient characteristic Placebo (N=123) Ondansetron (N=196) Alizapride (N=196) P-value Age 41,9 ± 13,59 42,2 ± 13,14 42 ± 14,25 0,968 Body length 165,7 ± 7,24 166,2 ± 7,33 165,2 ± 6,3 0,356 Body weight 66,3 ± 12,59 67,8 ± 11,77 ± 67,5 ± 12,52 0,457 BMI 24 ± 4,72 24,4 ± 4,57 24,7 ± 4,40 0,426 Duration anesthesia Duration operation 133,7 ± 116,83 127,4 ± 81,83 117,4 ± 76,47 0,301 91,2 ± 66,48 92,2 ± 72,11 85,8 ± 69,09 0,590 ASA score 1,4 ±0,5 1,4 ±0,5 1,4 ±0,52 0,512

27 RESULTS: baseline characteristics Patient characteristic ASA score Placebo (N=123) Ondansetron (N=196) Alizapride (N=196) P-value 1 56,10 % 60,71 % 63,27 % 0, ,9 % 38,78 % 35,20 % 3 0,0 % 0,51 % 1,53 % Smoking Yes 28,93 % 23,59 % 24,10 % 0,523 No 71,07 % 76,41 % 75,90 % PONV history Yes 18,70 % 21,94 % 18,37 % 0,653 No 81,30 % 78,06 % 81,63 % Risk group Low risk 23,14 % 19,90 % 18,97 % 0,656 High risk 76,86 % 80,10 % 81,03 %

28 RESULTS 600 N = 515 patients No Yes Nausea 30,87% Vomiting 10,09% PONV 31,26%

29 RESULTS -nausea PACU Placebo Ondansetron Alizapride P-value Nausea 34.15% 28.06% 31.36% No nausea 65.85% 71.94% 68.37% Placebo Intervention P-value Nausea 34.15% 29.85% No nausea 65.85% 70.15% 24 h Placebo Ondansetron Alizapride P-value Nausea 38.18% 30.39% 36.05% No nausea 61.82% 69.61% 63.95% Placebo Intervention P-value Nausea 38.18% 33.14% No nausea 61.82% 66.86%

30 RESULTS -vomiting PACU Placebo Ondansetron Alizapride P-value Vomiting 9.76% 7.65% 12.76% No vomiting 90.24% 92.35% 87.24% Placebo Intervention P-value Vomiting 9.76% 10.20% No vomiting 90.24% 89.80% 24 h Placebo Ondansetron Alizapride P-value Vomiting 10.91% 8.24% 14.04% No vomiting 89.09% 91.76% 85.96% Placebo Intervention P-value Vomiting 10.91% 11.11% No vomiting 89.09% 88.89%

31 RESULTS -PONV PACU Placebo Ondansetron Alizapride P-value PONV 34.15% 28.57% 32.14% No PONV 65.85% 71.43% 67.86% Placebo Intervention P-value PONV 34.15% 30.36% No PONV 65.85% 69.64% 24 h Placebo Ondansetron Alizapride P-value PONV 39.25% 31.46% 36.84% No PONV 60.75% 68.54% 63.16% Placebo Intervention P-value PONV 39.25% 34.10% No PONV 60.75% 65.90%

32 RESULTS -remark No observeddifferenceof vomiting, nausea, or PONV between groups No significant effect of profylaxis was observed Is profylaxis useful?

33 RESULTS Non-inferiorityof alizapride? PACU Alizapride Ondansetron Difference 95% CI Relative Risk Nausea 31,36% 28,06% 3,6% -5,5% -> 12,7% 1,127 Vomiting 12,76% 7,65% 5,1% -0,9% -> 11,3% 1,667 PONV 32,14% 28,57% 3,6% -5,6% -> 12,7% 1, h Alizapride Ondansetron Difference 95% CI Relative Risk Nausea 36,05% 30,39% 5,7% -4,2% -> 15,5% 1,186 Vomiting 14,04% 8,24% 5,8% -0,7% -> 12,3% 1,704 PONV 36,84% 31,46% 5,4% -4,6% -> 15,3% 1,171 RR > > inferiority of alizapride to ondansetron is proven

34 RESULTS Subgroupanalyses -LOW risk PACU N = 104 Alizapride Ondansetron Difference 95% CI Relative Risk Nausea 10,81% 25,64% - 14,8% -31,8% -> 2,1% 0,422 Vomiting 5,41% 5,13% 0,3% -9,8% -> 10,3% 1,054 PONV 10,81% 25,64% -14,8% -31,8% -> 2,1% 0,422 24h N = 95 Alizapride Ondansetron Difference 95% CI Relative Risk Nausea 12,12% 25,64% - 13,5% -31,2% -> 4,1% 0,473 Vomiting 6,06% 5,13% 0,9% -9,8% -> 11,6% 1,182 PONV 12,12% 25,64% -13,5% -31,2% -> 4,1% 0,473 RR < > non- inferiority of alizapride proven

35 RESULTS Subgroupanalyses -HIGH risk PACU N = 408 Alizapride Ondansetron Difference 95% CI Relative Risk Nausea 36,08% 28,66% 7,4% -2,9% -> 17,7% 1,259 Vomiting 13,92% 8,28% 5,6% -1,3% -> 12,6% 1,682 PONV 36,71% 29,30% 7,4% -2,9% -> 17,8% 1,253 24h N = 363 Alizapride Ondansetron Difference 95% CI Relative Risk Nausea 41,3% 31,69% 9,6% -1,6% -> 20,8% 1,303 Vomiting 15,28% 9,09% 6,2% -1,3% -> 13,7% 1,681 PONV 42,34% 33,09% 9,2% -2,1% -> 20,6% 1,279 RR > > inferiority of alizapride to ondansetron is proven

36 Conclusion 1/ Alizaprideis as effective as ondansetronin the prevention of PONV in low-risk-patients undergoing gynaecological laparoscopic surgery 2/ If we focus on the high-risk-group we must conclude that alizapride is inferior to ondansetron 3/ No superiority of intervention versus placebo

37 Gan T J et al. Anesth Analg 2003;97:62-71 Conclusion

38 References Kausteet al. Droperidol, alizaprideand metoclopramide in the prevention and treatment of post-operative emetic sequelae. Eur J Anaesthesiol 1986(3):1-9 Booijet al. Alizapridein prevention of postoperative nausea and vomiting. NethJ Surg 1988 feb;40(1):6-9 VanackerB, Van AkenH. Alizapridein the prevention of postoperativevomiting. A double-blind comparison. Acta Anesthesiol Belg. 1988;39(4): Dejonckheere et al. Alizapride in the prevention of post-thyroidectomy emetic sequelae. Eur J Anaesthesiol 1990;7: Stienstra et al. Double-blind comparison of alizapride, droperidol and ondansetron in the treatment of post-operative nausea. Eur J Anaesthesiol 1997;14(3): ApfelCC, LaaraE, KoivurantaM, GreimCA, RoewerN. A simplified risk score for predicting postoperative nausea and vomiting. Anesthesiology 1999;91: GanTJ, Meyer A, ApfelCC, et al. Society for ambulatory anesthesia guidelines for the management of postoperative nausea and vomiting. Anesthesia and analgesia 2003;97:62-71