Effects of differing rates of protamine reversal of heparin anticoagulation.
BACKGROUND
Protamine sulfate reversal of heparin anticoagulation may be associated with adverse cardiovascular side effects. The purpose of this study was to determine whether diminished systemic oxygen consumption and hemodynamic changes were more likely to accompany rapid versus slow protamine administration.


METHODS
Fifteen patients undergoing abdominal aortic aneurysm resection in a prospective randomized double-blinded study received intravenous protamine (1.5 mg/kg) rapidly during a 3-minute period (group I, n = 7) or slowly during a 15-minute period (group II, n = 8). Systemic oxygen consumption (VO2) and hemodynamic parameters were assessed for up to 20 minutes after protamine administration began.


RESULTS
Blood pressure declines (millimeters of mercury) were greatest in group I with rapid protamine administration (-19 systolic and -9 diastolic) compared with group II with slow protamine administration (-12 systolic and -1 diastolic). Heart rate fell markedly in both groups I and II. Cardiac output (CO) declined in group I at virtually all time periods. Similar CO declines in group II occurred 10 minutes after protamine infusion had begun and persisted for 3 minutes after protamine administration was complete. Maximum VO2 decreases were -16% (60 seconds into protamine infusion) and -13% (1.5 minutes after protamine infusion) in groups I and II, respectively, with statistically significant declines (p < 0.05) occurring only in group I compared with baseline values. Statistically significant differences (p < 0.01), however, were found when mean declines during and after protamine infusion were compared with controls for both CO and VO2 in both groups.


CONCLUSIONS
Significant declines in systemic VO2 and hemodynamic perturbations accompany protamine reversal of heparin anticoagulation during aortic surgery. Rapid protamine administration increases the magnitude of these adverse responses.
Wakefield
T W
TW
Department of Surgery, University of Michigan Medical School, Ann Arbor, USA.
Hantler
C B
CB
Wrobleski
S K
SK
Crider
B A
BA
Stanley
J C
JC
D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D011446:Prospective Studies; D011479:Protamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin