Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of cardiopulmonary bypass (CPB) with hypothermia and systemic heparinization on ceftriaxone disposition were evaluated in seven male patients. A bolus dose of drug (14 mg/kg of body weight) was given, and blood and urine specimens were collected before, during, and after CPB for 96 h. Creatinine, albumin, and total and free ceftriaxone concentrations in plasma were measured. The ceftriaxone free fraction (ff) in vitro was estimated by equilibrium dialysis, and the in vivo ff was obtained by the ratio of renal clearance due to filtration to creatinine clearance. Pharmacokinetic parameters were based on concentrations of total drug and free drug. Albumin decreased from 3.10 +/- 0.29 g/dl presurgery to 1.42 +/- 0.17 g/dl and recovered to 2.46 +/- 0.26 g/dl on postoperative day 4. CPB markedly increased the in vitro ff, which was reversed by protamine post-CPB (ff pre-CPB, 0.15 +/- 0.01; during CPB, 0.53 +/- 0.20; post-CPB, 0.16 +/- 0.02). The in vitro ff exceeded the in vivo ff (0.53 +/- 0.20 versus 0.24 +/- 0.07), probably due to continued free fatty acid release caused by heparin during dialysis. Clearances based on free drug decreased, and the renal clearance due to filtration increased (7.6 +/- 2.8 versus 15.0 +/- 4.5 ml/min) while the creatinine clearance decreased (114 +/- 29 versus 72 +/- 28 ml/min) during CPB. Diminished binding owing to low albumin and free fatty acids explain this behavior. Lower binding also increased the volume of distribution (154 +/- 41 ml/kg) and extended the half-life (15 +/- 6 h). In summary, ceftriaxone disposition was significantly altered by CPB, resulting in marked increases in free drug concentrations, half-life, and volume of distribution and in decreased intrinsic clearance.
 ...
PMID:Ceftriaxone disposition in open-heart surgery patients. 276 36

The present study was designed to determine if the addition of albumin or mannitol to the priming solution of the pump oxygenator would diminish edema in organs, without diminishing some of the beneficial effects of hemodilution on blood flow and renal function. Tissue blood flow (15 mu spheres), water content, and renal clearances were determined in 8 animals during cardiopulmonary bypass. A 2(2) factorial, completely fixed experimental design was used. All animals were placed on cardiopulmonary bypass with hemodilution (hematocrit 25 +/- 2%) and hypothermia (25 degrees +/- 1 degree C). Albumin decreased flow to the midmyocardium of the left ventricle and to the spleen, and increased flow to the inner cortex of the kidney. Albumin caused decreased urine flow and decreased urine sodium, and also diminished renal osmolar, sodium, and free-water clearances. both mannitol and albumin decreased lung water. Mannitol decreased water content of the outer renal cortex, and decreased flow to the inner cortex and medulla of the kidney and to the spleen. Mannitol had no significant effect on urine flow, renal plasma flow, or renal clearances. Neither albumin nor mannitol had any effect on water content of the intestine, stomach, liver, or myocardium where the greatest accumulation of water occurs with hemodilution. The effect of albumin on renal function is potentially deleterious during cardiopulmonary bypass because it decreases urine flow, and osmolar and free-water clearance.
 ...
PMID:Effect of albumin and mannitol on organ blood flow, oxygen delivery, water content, and renal function during hypothermic hemodilution cardiopulmonary bypass. 680 88