Periarterial papaverine application improves intraoperative kidney function during laparoscopic donor nephrectomy

BACKGROUND: Laparoscopic donor nephrectomy decreases disincentives to donation frequently associated with the disadvantages of open surgery. However, concerns have been raised regarding graft quality, since the incidence of delayed graft function is higher when compared with open procedures. This may be caused by amelioration of kidney perfusion due to the elevated intraabdominal pressure and to a mechanically induced renal angiospasm during donation. This study was addressed to reveal whether the renal periarterial application of papaverine is able to enhance renal blood flow during laparoscopic nephrectomy. MATERIALS AND METHODS: Twelve male piglets underwent left laparoscopic donor nephrectomy after endoscopic occlusion of the right renal vessels and ureter. Urine output and creatinine clearance were determined as indicators of renal blood flow. In the treatment group (n = 6) papaverine hydrochloride was administered to the tissue surrounding the renal artery prior to preparation of the vessels and results were compared with those of controls (n = 6). Free sodium excretion was measured to preclude prerenal failure. RESULTS: In the control group the mean urine output was 0.015 ml/min/kg and the mean creatinine clearance was 0.95 ml/min/kg. In pigs treated with papaverine the mean urine output was 0.052 ml/min/kg and the mean creatinine clearance was 2.22 ml/min/kg. The differences were significant (urine output, P = 0.02; creatinine clearance, P = 0.038). CONCLUSIONS: Papaverine improves renal function during laparoscopic kidney harvest when applied in the vicinity of the renal artery prior to vascular preparation.     

A new technique for establishing dry weight in hemodialysis patients via whole body bioimpedance

BACKGROUND: Quantitative techniques are necessary to achieve dry weight (DW) in patients with kidney failure. Bioimpedance spectroscopy (BIS) is a non-invasive method that determines the volume of body fluid compartments. The current work evaluates the use of BIS data in hemodialysis patients for the prediction of DW. METHODS: A new technique has been devised for the estimation of DW that involves the intersection of two slopes, slope normovolemia (SNV) and slope hypervolemia (SHV). These slopes characterize the variation in extracellular water (ECW) with body weight (BW) in the states of normovolemia and hypervolemia, respectively. SNV was established via measurements of ECW and BW in 30 healthy subjects. In a longitudinal study in new hemodialysis patients, successive reduction of post-dialysis weight (PDW) was attempted until clinical signs of normovolemia were presented. Measurements of ECW and BW that were acquired at the beginning of each treatment were used to determine SHV. RESULTS: SNV was found to be 0.239 L/kg and 0.214 L/kg for male and female healthy subjects, respectively. A significant DeltaPDW predicted by the new method (-4.98 kg) was highly correlated to the DeltaPDW achieved in the study (-5.85 kg, R = 0.839). Blood pressure was reduced (P < 0.001) and an 86% decrease in antihypertensive agents was achieved. CONCLUSION: The method of intersecting slopes (SHV with SNV) via BIS is a new method for the prediction DW. This approach will offer considerable improvement for the routine management of DW in the dialysis setting.     

Hemostatic activation and inflammatory response during cardiopulmonary bypass: impact of heparin management

BACKGROUND: Cardiac surgery involving cardiopulmonary bypass (CPB) leads to fulminant activation of the hemostatic-inflammatory system. The authors hypothesized that heparin concentration-based anticoagulation management compared with activated clotting time-based heparin management during CPB leads to more effective attenuation of hemostatic activation and inflammatory response. In a randomized prospective study, the authors compared the influence of anticoagulation with a heparin concentration-based system (Hepcon HMS; Medtronic, Minneapolis, MN) to that of activated clotting time-based management on the activation of the hemostatic-inflammatory system during CPB. METHODS: Two hundred elective patients (100 in each group) undergoing standard cardiac surgery in normothermia were enrolled. No antifibrinolytic agents or aprotinin and no heparin-coated CPB systems were used. Samples were collected after administration of the heparin bolus before initiation of CPB and after conclusion of CPB before protamine infusion. RESULTS: There were no differences in the pre-CPB values between both groups. After CPB there were significantly higher concentrations ( < 0.05) for heparin and a significant reduction in thrombin generation (25.2 +/- 21.0 SD vs. 34.6 +/- 25.1), d-dimers (1.94 +/- 1.74 SD vs. 2.58 +/- 2.1 SD), and neutrophil elastase (715.5 +/- 412 SD vs. 856.8 +/- 428 SD), and a trend toward lower beta-thromboglobulin, C5b-9, and soluble P-selectin in the Hepcon HMS group. There were no differences in the post-CPB values for platelet count, adenosine diphosphate-stimulated platelet aggregation, antithrombin III, soluble fibrin, Factor XIIa, or postoperative blood loss. CONCLUSION: Compared with heparin management with the activated clotting time, heparin concentration-based anticoagulation management during CPB leads to a significant reduction of thrombin generation, fibrinolysis, and neutrophil activation, whereas there is no difference in the effect on platelet activation. The generation of fibrin even in the presence of high heparin concentrations most likely has to be attributed to the reduced antithrombin III concentrations or reduced inhibition of clot-bound thrombin. Therefore, in addition to maintenance of higher heparin concentrations, monitoring and substitution of antithrombin III should be considered to ensure more efficient antithrombin activity during CPB.     

The effect of isoflurane on neutrophil selectin and beta(2)-integrin activation in vitro

Isoflurane is reported to reduce ischemia-reperfusion injury. Lower expression of CD11b may be responsible for attenuated postischemic neutrophil adhesion to vascular endothelium. However, neutrophil adhesion to vascular endothelium is a multistep process involving several selectins and beta(2)-integrins. Therefore, we assessed whether isoflurane affects the activation of the selectins P-selectin glycoprotein ligand-1 (PSGL-1) and L-selectin and the beta(2)-integrins CD11a and CD11b. Whole blood was incubated for 60 min with 0.5 or 1 minimum alveolar anesthetic concentration (MAC) isoflurane. After incubation, neutrophils were activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol-12-myristate-13-acetate (PMA). Activation of adhesion molecules was evaluated via flow cytometry, and 1 MAC isoflurane reduced the expression of CD11a in the unstimulated samples. After stimulation with FMLP and PMA, shedding of L-selectin was lower in the presence of isoflurane. Furthermore, 1 MAC isoflurane reduced FMLP-induced activation of CD11a and CD11b compared with unexposed blood samples. These results demonstrate that isoflurane affects the activation of three adhesion molecules involved in the multistep process of neutrophil recruitment. First, isoflurane inhibits the activation of L-selectin, which mediates the neutrophil tethering and rolling on the vascular endothelium. Second, isoflurane attenuates the activation of both beta(2)-integrins-CD11a and CD11b-which mediate firm adhesion and transendothelial migration. IMPLICATIONS: Adhesion of neutrophils to endothelial cells in reperfusion injury is mediated by different adhesion molecules. This study indicates that the inhibiting effect of isoflurane on neutrophil recruitment may be mediated by a decreased activation of the L-selectin and by attenuation of the activation of the beta(2)-integrins CD11a and CD11b.     

Isoflurane preconditions myocardium against infarction via release of free radicals

BACKGROUND: Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals. METHODS: Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7). RESULTS: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001). CONCLUSION: Isoflurane-induced preconditioning depends on the release of free radicals.     

Factors influencing intensive care unit length of stay after surgery for acute aortic dissection type A

BACKGROUND: Operative mortality after acute aortic dissection type A is still high, and prolonged stay at the intensive care unit is common. Little has been documented about factors influencing the intensive care unit length of stay. The aim of this study was to determine such variables. METHODS: During a 10-year period, 67 patients (47 male, 20 female) were operated on for acute aortic dissection type A. In 42 patients (63%), an ascending aortic replacement was performed, 23 patients (34%) underwent a Bentall procedure, and 2 patients (3%) received a valve-sparing David type of operation. In 14 of these cases (20%), an additional partial or total arch replacement was performed. RESULTS: Hospital mortality was 9 of 67 (14%). Median postoperative intensive care unit length of stay was 5 days (range, 1 to 72 days). Intensive care unit stay was in univariate analysis significantly influenced by the following factors: age (p = 0.008), body mass index (p = 0.039), cardiopulmonary bypass time (p = 0.018), aortic cross-clamp time (p = 0.031), postoperative low cardiac output syndrome (p < 0.001), and postoperative lactate levels (p = 0.01). By multivariate analysis, age (p = 0.012), cardiopulmonary bypass time (p = 0.037), and the presence of a postoperative low cardiac output syndrome (p < 0.001) significantly influenced intensive care unit stay. CONCLUSIONS: Stay in the intensive care unit after operation for acute aortic dissection type A seems to be determined by age, cardiopulmonary bypass time, and the postoperative presence of a low cardiac output syndrome.