Hemodynamic changes after protamine administration: association with mortality after coronary artery bypass surgery.
BACKGROUND
Protamine sulfate is standard therapy to reverse heparin anticoagulation. Hemodynamic responses to protamine are common, ranging from minor perturbations to cardiovascular collapse. Although severe fatal reactions occur, the relation of less extreme responses with postoperative mortality is unknown. Therefore, the authors tested the hypothesis that hemodynamic "protamine reactions" (systemic hypotension and pulmonary hypertension) are associated with mortality after cardiac surgery.


METHODS
In a university hospital setting, the authors studied 6,921 coronary bypass patients using automated anesthesia record-keeping data and quality assurance databases. Degree/duration integrals of systemic hypotension (< 100 mmHg) and pulmonary hypertension (> 30 mmHg) for the 30-min after protamine administration were assessed for linear associations with mortality using multiple logistic regression models adjusting for risk factors.


RESULTS
Overall mortality was 2%; greater hemodynamic responses were associated with increased mortality by odds ratios of 1.28 (systemic hypotension: 95% confidence interval, 1.14-1.43; P < 0.001) and 1.27 (pulmonary hypertension: 95% confidence interval, 1.06-1.48; P < 0.001) per 150-mmHg . min increment. Proximity of the response to protamine administration strengthened the relation, which persisted after exclusion of major hemodynamic disturbances. Tests for linearity confirmed an association even at the lowest range of values for both pressure effects.


CONCLUSIONS
Hemodynamic perturbations after protamine administration are independently related to in-hospital mortality after primary coronary artery bypass surgery; the relation is present even in the lowest observed range of values for both systemic hypotension and pulmonary hypertension. Although randomized trials are necessary to address causality, this evidence suggests that strategies that avoid or attenuate these reactions may improve patient care.
Welsby
Ian J
IJ
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA.
Newman
Mark F
MF
Phillips-Bute
Barbara
B
Messier
Robert H
RH
Kakkis
Emil D
ED
Stafford-Smith
Mark
M
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D016001:Confidence Intervals; D001026:Coronary Artery Bypass / Q000401:mortality*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011479:Protamines / Q000008:administration & dosage* / Q000009:adverse effects*; D012189:Retrospective Studies
D011479:Protamines