Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial.
In this prospective, randomized, placebo-controlled, double-blinded study, we determined the effects of two commonly used adjuncts, mannitol and dopamine, on beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M excretion rate has been described as a sensitive marker of proximal renal tubular function. One-hundred patients with a preoperative serum creatinine level <or=1.5 mg/dL were prospectively randomized into 4 groups: 1). placebo, 2). mannitol 1 g/kg added to the CPB prime, 3). dopamine 2 microg kg(-1x. min(-1) from the induction of anesthesia to 1 h post-CPB, or 4). mannitol plus dopamine. The primary outcome measure was beta(2)M excretion rate at 1 h post-CPB. Secondary outcome measures included beta(2)M excretion rate at 6 and 24 h post-CPB; urinary flow rate and creatinine clearance at 1, 6, and 24 h post-CPB; and the highest postoperative serum creatinine level. Length of intensive care stay and hospitalization, as well as adverse events, were also considered secondary outcomes. Dopamine significantly increased beta(2)M excretion rate at 1 h post-CPB (2.48 +/- 3.61 microg/min) compared with placebo (0.59 +/- 1.04 microg/min; P = 0.001). This effect was not ameliorated by the addition of mannitol (beta(2)M excretion rate, 2.05 +/- 2.77 microg/min; P = 0.007 compared with placebo). beta(2)M excretion rate was similar in patients given placebo or mannitol alone (P = 0.831). Rather than being a protective drug in the setting of CPB, dopamine alone or in combination with mannitol increases beta(2)M excretion rate, which may be a measure of renal tubular dysfunction. The clinical implications of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation.


CONCLUSIONS
In many clinical settings, an increased beta-2-microglobulin (beta(2)M) excretion rate indicates renal tubular injury. In this cardiopulmonary bypass (CPB) study, a dopamine infusion (alone or with mannitol) resulted in an increased beta(2)M excretion rate. It is unclear whether this dopamine-related increase implies renal injury after CPB, and further investigations are required to examine the mechanism/clinical relevance of this observation.
*Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut; †Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; ‡Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN; and §Department of Internal Medicine (Section of Nephrology), Yale University School of Medicine, New Haven, Connecticut.
Olivia V
OV
Carcoana
Joseph P
JP
Mathew
Elizabeth
E
Davis
Daniel W
DW
Byrne
John P
JP
Hayslett
Roberta L
RL
Hines
Susan
S
Garwood
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004234:Diuretics, Osmotic / Q000009:adverse effects / Q000627:therapeutic use*; D004298:Dopamine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control*; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects; D007902:Length of Stay; D008297:Male; D008353:Mannitol / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D014563:Urodynamics / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000378:metabolism / Q000652:urine
D002316:Cardiotonic Agents; D004234:Diuretics, Osmotic; D001613:beta 2-Microglobulin; D008353:Mannitol; D005665:Furosemide; D003404:Creatinine; D004298:Dopamine