Hetastarch and Bleeding Complications After Off-Pump Coronary Bypass Surgery

Recruitment

• Eligibility screening:

a. All adult Kaiser Permanente members admitted to Summit Hospital (Oakland, CA) for coronary bypass graft surgery which is planned to be conducted off-pump.

• Recruitment period: 9/1/2004 through 7/27/05

• At recruitment, each subject who agrees to participate is assigned a study number

• The study number is assigned sequentially and is totally independent of the medical record number or other personal identifying information
• The linkage between the study number and all personal identifying information is kept in a locked file separate from other project data
• Exclusion criteria:

• pregnancy
• patients scheduled to undergo on-pump procedures
• patients with a history of any of:

• cardiac surgery
• primary bleeding disorders
• end-stage renal disease.
• Statistical power analysis

• This study is designed as an equivalence trial
• Target outcome rates are based on those published in Sade RM, Stroud MR, Crawford FA Jr, et al. J Thorac Cardiovasc Surg 1985 May;89(5):713-22.
• Statistical power is calculated using the confidence-interval-based technique for normally distributed interval variables.

• The confidence interval is set at 95%
• The range of equivalence is defined as +100 milliliters
• Power is set at 90%
• The target sample size which results from this analysis is 165 patients in each arm (i.e., hetastarch and albumin).
• Analytic strategy

• All project analyses are conducted by intention-to-treat
• Bivariate comparisons between the study (i.e., hetastarch) and control (i.e., albumin) group measurements use the Fisher exact test or Student's t test for independent samples as appropriate given the nature of the measurement were used to conduct bivariate comparisons of study group measures with control group measures.

• Confidence intervals are calculated using the exact techniques
• Multivariate comparisons: Analysis of variance and general linear modeling are used to conduct multivariate comparisons of measures between the study and control groups while controlling for covariates.
• Intervention process

• When the patient is in the operating room, the anesthesiologist opens the envelope containing the study group assignment (i.e., hetastarch or albumin).

• The attending anesthesiologist administers 1 liter of 6% hetastarch intraoperatively to patients from the study group.
• The attending anesthesiologist administers 1 liter of albumin intraoperatively to patients from the study group.
• After the first liter of colloid is administered, the patients receive only albumin if more colloid is needed to meet additional requirements for fluid replacement.
• All patients receive the remaining standard operative regimen of crystalloids and blood products at the discretion of the anesthesiologist.
• All patients are transferred postoperatively to the Intensive Care Unit.

• The attending intensivists are blinded to the patient's randomization assignment
• The attending intensivists use standard fluid replacement at their clinical discretion.
• No hetastarch is administered in the intensive care unit.
• Measurements

• Preoperative

• age
• gender
• body mass index
• type of surgery

a) (elective vs. urgent/emergent)

• serum albumin level
• serum creatinine level
• blood urea nitrogen level
• hematocrit
• platelet count
• prothrombin time
• partial thromboplastin time
• preoperative administration of anticoagulants
• preoperative administration of antiplatelet medications
• preoperative administration of thrombolytic agents
• Perioperative

• identity of the surgeon
• identity of the anesthesiologist
• lowest body temperature
• highest activated clotting time
• volume of crystalloids
• volume of colloids
• volume of cell-saver
• number of units of blood products administered
• Postoperative

• hourly chest tube drainage in the first 12 postoperative hours
• volume of crystalloid delivered
• volume of albumin delivered
• number of units of blood products transfused
• whether reoperation for postoperative bleeding was required
• duration of mechanical ventilation
• duration of stay in the intensive care unit
• total length of hospital stay
• mortality rates for patients treated in the ICU
• mortality rates for patients treated in other inpatient areas of the hospital.

Inclusion criteria

• Scheduled coronary bypass graft surgery that is planned to be conducted on adults off-pump (i.e., without use of cardio-pulmonary bypass).

Exclusion criteria

• Scheduled coronary bypass graft surgery that is planned to be conducted on adults on-pump (i.e., with use of cardio-pulmonary bypass).
• A history of cardiac surgery
• A history of primary bleeding disorders
• End-stage renal disease