Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol
This study proposes to assess the effect of the standard of care, which is continuation of the pre op beta blocker dose into the post operative period compared to the administration of esmolol titrated to a pre determined target HR. The primary outcome will compare postoperative plasma levels of metoprolol in 2 cohorts in a group who has been continued on metoprolol (administrated via a nasogastric tube in NPO patients) to a group who has been withdrawn from metoprolol but given an esmolol infusion titrated to HR. Secondary outcomes will compare a) the hemodynamic responses, documenting the incidence of unplanned hypotension and bradycardia and b) to compare the effects of Heart rate to the incidence of myocardial ischemia, arrhythmias, delirium and infarction.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol: A Study Comparing the Post Op Continuation of the Preoperative Oral Dose Beta Blockers to Intravenous Esmolol Titrated to a Target Heart Rate (HR)|
- The difference between plasma levels of metoprolol within two groups [ Time Frame: 0,1, 2, 4, 8, 12, 24 hours post intervention ] [ Designated as safety issue: Yes ]Comparisons measured in the pre-operative to intra-operative and post operative periods within metoprolol arm as well as between esmolol arm and metoprolol arm. Plasma levels will be correlated with both the hemodynamic response (HR) and the incidence of postoperative ischemia. The covariates (HR, BP, HR variability, etc) on PK/PD correlation will be examined.
- The amount of time the target heart rate is maintained and the incidence of perioperative hypotension and bradycardia. [ Time Frame: Data will be recorded for 48 hours from arrive to the recovery area ] [ Designated as safety issue: Yes ]Additional assessments include cardiovascular morbidity and mortality including 30-day mortality, myocardial infarction, new cardiac arrhythmia, congestive heart failure, and renal failure, the incidence of post operative delirium, transient ischemic attack, stroke, and length of hospital stay.
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||June 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Metoprolol oral dose or Placebo infusion||
The night and morning before surgery, the patients in the metoprolol arm will receive their standard dose of beta blocker metoprolol.These patients will receive their daily beta blockers orally or via nasogastric tube postoperatively if they are NPO (Group A).
|Experimental: Esmolol infusion or Placebo oral dose||
Baseline treatment consists of a bolus of 500ug/kg/min followed by an infusion of 50ug/kg/min for 4 minutes and titrating in increment of 50ug/kg/min up to a maximum of 300ug/kg/min to maintain a HR within 10% of the target HR (≤ 70 bpm), which is 70± 7 bpm.
The number of high-risk patients undergoing non-cardiac surgery has increased continuously over the last two decades. There is a paucity of data exist about the bioavailability of postoperative administrated beta-blockers. One study reported adequate plasma levels of Propanolol after administration via nasogastric tube but not after oral administration in patient undergoing thyroid surgery.Thus it is possible that patients maintained on oral beta blockers may in fact be experiencing a withdrawal syndrome. Because of the importance of avoiding withdrawal of beta blockers, intravenous administration may be the only alternative in cases where oral administration fails to achieve adequate plasma levels perioperatively. Furthermore, due to changes in pharmacodynamics, intravenous dosage may be the optimal way to achieve tight hemodynamic control. There is, however, no data on the post-operative hemodynamic effects of orally administered beta blockers in patients on chronic beta blockers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01404767
|University Heatlh Network, Toronto General Hopsital|
|Toronto, Ontario, Canada, M5G 2C4|
|Principal Investigator:||Scott Beattie, MD, FRCP||University Health Network, Toronto General Hospital|