1 / 55

Journal Club

Journal Club. Lei Zhang PGY 3 7/16/09. Case. 55 y.o. F, PMH HTN, DM, TIA, and diverticulosis Had multitple diverticulitis, lower GIB in the past Scheduled to have elective colon resection in 2 wks Presented to the office for pre-op clearance Denied CP, SOB, swelling. Case.

aine
Download Presentation

Journal Club

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Journal Club Lei Zhang PGY 3 7/16/09

  2. Case • 55 y.o. F, PMH HTN, DM, TIA, and diverticulosis • Had multitple diverticulitis, lower GIB in the past • Scheduled to have elective colon resection in 2 wks • Presented to the office for pre-op clearance • Denied CP, SOB, swelling

  3. Case • HTN well controlled with Lisinopril and HCTZ • DM well controlled with Glipizide and Metformin • Also taking ASA and Zocor • Good functional status, able to climb 2 flight of stairs carrying grocery • Recent EKG/CXR within normal limits • Recent CBC, Chem 7 within normal limits

  4. Anything Else Needed Pre-operatively? Add Beta-blocker?

  5. Perioperative Beta Blocker use • Circulation, 2006 • Feringa and colleagues performed an observational cohort study of 272 vascular surgery patients • Higher doses of -blockers and tight heart rate (< 70 bpm) control associated with reduced perioperative myocardial ischemia and troponin release and improved long-term outcome

  6. Perioperative Beta Blocker use • J AM Coll Cardio, 2006 • Poldermans and colleagues randomly assigned 770 intermediate-risk patients to cardiac stress testing (n386) or no testing (n384) preoperatively • Concluded that cardiac testing can safely be omitted in intermediate-risk patients if beta blockers aimed at tight heart rate control are prescribed

  7. Perioperative Beta Blocker use • BMJ, 2005 • Donald Redelmeier & colleague performed retrospective cohort study in Canada in 37,151 asymptomatic patients older than 65 admitted for elective surgery (mainly abd & ortho procedure) • Patients receiving long-acting beta-blockers have lower perioperative cardiac risk than short-acting agent

  8. ACC/AHA Guideline for Pre-op Beta-blocker Use

  9. Perioperative Beta Blocker use • Am Heart J. 2006 • Yang & colleague performed a double-blind randomized controlled trial of perioperative metoprolol versus placebo in 496 patients undergoing vascular surgery • Metoprolol was not effective in reducing the 30-day & 6-month postop cardiac event rates. • Concluded that prophylactic use of perioperative beta-blockers in all vascular patients is not indicated

  10. Perioperative Beta Blocker use • BMJ, 2006 • Anne Benedicte Juul & colleague designed a randomized, controlled and blinded multicentre trial in 921 diabetic patients, age > 39, scheduled for major non-cardiac surgery • 100 mg metoprolol extended release or placebo given from the day before surgery to a max of 8 perioperative days • Conclusions: Perioperative metoprolol did not significantly affect mortality and cardiac morbidity

  11. Perioperative Beta Blocker use • BMJ, 2006 • Devereaux & colleague published a meta-analysis of randomized controlled trials in non-cardiac surgery pts • β blockers might prevent major cardiovascular events but increase the risk of hypotension & bradycardia

  12. Peri-operative Use of Beta-blocker Yes or NO

  13. POISE TRIAL • PeriOperative ISchemic Evaluation • Purpose of the trial: • Comparing the effect of extended-release metoprolol with that of placebo on 30-day risk of major cardiovascular events in patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery.

  14. POISE TRIAL • Research question • Does peri-operative β-blocker regimen benefit noncardiac surgery pts without substantial harm? • Double-blinded, randomized, controlled, multi-center trial

  15. POISE TRIAL • Involved 8,351 pts and 190 hospitals in 23 countries • Study period 10/2002 – 7/2007 • Ethical approval for all participating sites obtained • Written informed consent obtained from all pts

  16. POISE TRIAL • Inclusion criteria • undergoing non-cardiac surgery • aged 45 years or older • expected length of hospital stay > 24 h • any one of the following criteria • hx of CAD • hx of PVD • Stroke

  17. POISE TRIAL • hospitalization for CHF within past 3 years • undergoing major vascular surgery • Or, any three of seven risk criteria • undergoing intrathoracic or intraperitoneal surgery • hx of CHF • hx of TIA • hx of diabetes • creatinine >175 μmol/L ( >2.0 mg/dL) • age >70 years • undergoing emergent or urgent surgery

  18. POISE TRIAL • Exclusion criteria • HR < 50 bpm • 2nd or 3rd AVB • Asthma • Receiving β blocker or planned to start one perioperatively • Prior adverse reaction to β blocker • CABG in the preceding 5 years with no ischemia • Low-risk surgical procedure • On verapamil

  19. POISE TRIAL • Patients were randomly assigned to two groups via a 24-h computerized randomization phone service • Participants, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation

  20. Trial Profile… Figure 1

  21. Table 2

  22. Method • 1st dose of the study drug (ie, oral extended-release metoprolol 100 mg or matching placebo) given 2–4 h before surgery • VS checked each time before medication to ensure HR > 50 bpm & SBP > 100 mm Hg

  23. Method • Within 6 h postop, pt received 1st post-op dose • 12 h after 1st post-op dose, start Metoprolol extended-release 200mg or placebo p.o. daily for 30 days • If HR <45bpm or SBP < 100, study drug withheld until recovered • Study drug was then restarted at 100mg daily

  24. Method • If HR consistently 45–49 bpm, SBP >100 mm Hg, delayed taking the study drug for 12 h • If unable to take p.o., study drug given by slow or rapid IV infusion q6h • Investigators were allowed to select either the slow or rapid IV infusion

  25. Method • Slow infusion • 15 mg of study drug in 25 mL NS over 60 min • HR & BP checked at 10, 30, and 60 min into the infusion • If HR/BP drop, study drug reduce to 10mg

  26. Method • Rapid infusion • 5 mg of the study drug IV over 2 min and repeated every 5 min for a total of 15 mg • ECG recorded 6–12 h postoperatively and on the 1st, 2nd , and 30th days • Troponin or CK-MB at 6–12 h postoperatively & on the 1st , 2nd , and 3rd days

  27. POISE TRIAL • Primary outcome • cardiovascular death • non-fatal MI • non-fatal cardiac arrest at 30 days

  28. Statistical Analysis • Study has 85% power to detect a relative risk reduction of 25% • All analyses used Cox proportional hazards models

  29. Table 3

  30. Results • Fewer in the metoprolol group reached the primary endpoint (hazard ratio 0·84, 95% CI 0·70–0·99, p=0·039) • Fewer patients in the metoprolol group had a non-fatal MI (hazard ratio 0·70, 95% CI 0·57–0·86; p=0·0008) • Fewer in the metoprolol group had cardiac revascularisation or developed new A fib

  31. Result • More in the Metoprolol group had a stroke (hazard ratio 2·17, 95% CI 1·26–3·74, p=0·0053) • More people receiving metoprolol died (1·33, 1·03–1·74, p=0·0317) • More pts receiving Metoprolol had significant hypotension and bradycardia

  32. Figure 2 MIs Primary Death Strokes

  33. Results • Median length of hospital stay was 8 (IQR 4–14) days in the Metoprolol group and 8 (4–15) days in the placebo group (p=0·4046) • The number of nights spent in ICU/CCU was much the same in the two groups

  34. Results • At discharge, Metoprolol group had • a lower mean HR(71·6 [SD 12·0]vs 78·6 [11·8]; p<0·0001) • lower mean SBP & DBP (129 [18·9]/72 [11·1] vs 131 [18·2]/74 [11·1]mm Hg; p<0·0001)

  35. Discussion • Why extended-release Metoprolol have increased risk of death and stroke? • Clinically significant hypotension, bradycardia and stroke contribute to the increasing risk of death

  36. Table 5

  37. Discussion • Sepsis or infection was the only cause of death that was significantly more common in Metoprolol group • Hypotension caused by β blockers could have predisposed pts to developing nosocomial infection

  38. Discussion • β blockers suppress tachycardia could delay the recognition of sepsis and infection, therefore delaying treatment, which might increase the risk of death

  39. Discussion • Pts receiving β-blocker who develop sepsis or infection might not have the capacity to mount enough response to sustain life or allow adequate delivery of antibiotics to tissue

  40. Discussion • POISE researchers also performed several meta-analysis of trials of periop Beta-blocker use • Decrease risk of non-fatal MI • Increase risk of death • Increase risk of non-fatal stroke

  41. Figure 4

  42. Conclusion

  43. Summary • Are the results valid? • Yes • Are the results important? • Yes • Can you apply the results to your patient? • Yes

  44. Validity • This is a large, multi-center, randomized, double-blind, controlled clinical trial • Both groups were comparable in terms of back ground information, type of surgery, anesthesia, and medications • Both groups were treated equally

  45. Validity • Confounding criteria were well-accounted between the two groups • Clear inclusion and exclusion criteria • Study has detailed medication administration and side-effect monitoring protocol • Follow-up was complete for majority of pts

  46. Validity • Although involving large of amount of pts and study personnel from 190 hospitals in 23 countries, the study was well regulated by central and on-site monitoring system • Problems found in Iran and Colombia were caught immediately and data excluded from the study

  47. Applicability • This is a large multi-country study, involving different racial, ethnic & economic population; it is safe to generalized the study results to our practice patients

  48. Significance • The study have enormous influence on current medicine practice • It challenged the currently popular concept of perioperative Beta-blocker use

  49. Significance • For every 15 patients in POISE trial, one had a cardiovascular death, non-fatal myocardial infarction, non-fatal cardiac arrest, or non-fatal stroke at 30-day follow-up

More Related