The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function.

BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass elicits a potent reperfusion injury and inflammatory response, more intense in patients with impaired myocardial function. Propofol has antioxidant properties which may attenuate such a response. METHODS: In total, 27 patients with impaired left ventricular function undergoing CABG were randomly allocated to receive either target-controlled infusion propofol (P) or saline (S) immediately before aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18 expression) were measured. RESULTS: Propofol decreased MDA coronary sinus concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after reperfusion a significant difference between the two groups in systemic MDA concentrations was also seen. IL-6 concentration increases were significantly greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs 228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase significantly in either group. Compared with baseline values IL-10 concentrations decreased after reperfusion but the values were higher in the propofol group than in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in leucocyte function or urinary isoprostane concentrations was demonstrated. CONCLUSION: Propofol attenuates free-radical-mediated lipid peroxidation and systemic inflammation in patients with impaired myocardial function undergoing CABG.

Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting.

Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin-mediated systemic inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine receptor agonist, would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects, and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We examined the effects of fenoldopam on haemodynamic parameters, creatinine clearance, fractional excretion of sodium, urine output, free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation. Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1 microg x kg(-1) x min(-1) (n = 16) or placebo (n = 15). Renal parameters were measured: during a 24-h period before hospital admission, during cardiopulmonary bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass. Gastric intramucosal pH was measured using a gastric tonometer before, during and after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group, mean (SD) creatinine clearance decreased after separation from cardiopulmonary bypass, from 107 (36) to 71 (22) ml x min(-1) (p < 0.01) and from 107 (36) to 79 (26) ml x min(-1) (p < 0.01) for the 0-4 h and 4-8 h intervals after cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in both groups. The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.

The effects of fenoldopam on coronary conduit blood flow after coronary artery bypass graft surgery.

OBJECTIVE: To quantify the effects of fenoldopam, 0.1 microg/kg/min, on left internal mammary artery (LIMA) and saphenous vein blood flow after coronary anastomosis. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: University teaching hospital, single institution. PARTICIPANTS: Thirty-one American Society of Anesthesiologists III patients undergoing elective coronary revascularization. INTERVENTIONS: A perivascular ultrasonic flow probe (Linton Instrumentation, Norfolk, UK) was placed around the LIMA and saphenous vein graft after coronary anastomosis. MEASUREMENTS AND MAIN RESULTS: Immediately before and at 5-minute intervals for 15 minutes after starting the infusion, blood flow was measured in the LIMA and one saphenous vein graft using a transit time ultrasonic flow probe. Heart rate, blood pressure, and central venous pressure were documented at these time points. Administration of fenoldopam, 0.1 microg/kg/min, did not alter heart rate or blood pressure. A small, nonsignificant increase in LIMA blood flow occurred during the 15-minute study period (30 +/- 12 to 35 +/- 10 mL/min) in patients who received fenoldopam. No significant changes occurred in the placebo group. CONCLUSIONS: The findings indicate that fenoldopam, 0.1 microg/kg/min, did not influence coronary conduit blood flow to a clinically significant extent. The small increase in LIMA blood flow may be of greater importance in high-risk patients or in the prevention of coronary arterial spasm.

Comparison of epidural anaesthesia with ropivacaine 0.5% and bupivacaine 0.5% for caesarean section.

PURPOSE: To compare ropivacaine 0.5% with bupivacaine 0.5% for epidural anaesthesia for Caesarean section. METHODS: Healthy pregnant women, scheduled for elective Caesarean section were enrolled into this randomized, double-blind, parallel-group study. Epidural block was obtained with 20-30 ml of ropivacaine (group R) or bupivacaine (group B) and surgery started when anaesthesia was reached T6. Maternal heart rate and blood pressure and fetal heart rate were assessed before the test dose and at five minute intervals until the end of surgery. At the same intervals, sensory and motor block characteristics were determined. Apgar scores and Neurologic and Adaptive Capacity Scores (NACS) were determined after delivery. Adverse events were recorded. RESULTS: Sixty-five patients were enrolled and data from 61 were available for analysis; 30 ropivacaine and 31 bupivacaine. Time from the end of the last injection to the start of surgery was 46 +/- 13 min (mean +/- SD) in gp R and 53 +/- 25 min in gp B (P:NS). The median duration of analgesia varied between 1.7 and 4.2 hr in gp R and between 1.8 and 4.4 hr in gp B (P:NS). In patients who developed Bromage 4 block, it persisted longer in those in gp B (2.5 hr) than in gp R (0.9 hr) (P < 0.05). The quality of analgesia was satisfactory in 27/29 patients (93%) in gp R and 27/31 patients (87%) in gp B (P:NS), although supplemental i.v. opioid was required in ten and seven patients, respectively. The most common adverse events in the mother were hypotension (63% gp R and 61% in gp B) (NS) and nausea (30% and 58%, in group R and B, respectively) (P = 0.05). Apgar scores were 7 after five minutes in all neonates. CONCLUSION: Ropivacaine 0.5% and bupivacaine 0.5% provided effective epidural anaesthesia for Caesarean section although supplementation with i.v. opioid was commonly required.

A double-blind comparison of ropivacaine 0.5%, 0.75%, 1.0% and bupivacaine 0.5%, injected epidurally, in patients undergoing abdominal hysterectomy.

PURPOSE: Ropivacaine is a new long-acting, injectable local anaesthetic currently undergoing clinical investigation world wide. It is structurally very similar to bupivacaine, but with less potential for central nervous system or cardiac toxicity. The purpose of this double-blind study was: to investigate the dose-response relationship of increasing doses of ropivacaine on the quality of anaesthesia and the duration of both motor and sensory blockade, and to compare these results with an established local anaesthetic, bupivacaine. METHODS: One hundred and twenty five patients were randomly assigned to one of four treatment groups and 116 completed the study. Epidural anaesthesia was established using 25 ml test solution, injected over three minutes following a satisfactory test dose. Sensory onset, spread and duration, using the pin prick method, and motor scores using a modified Bromage scoring system were compared. RESULTS: A dose/response relationship was observed with increasing doses of ropivacaine for all variables tested except analgesia and muscle relaxation (P < 0.01). There were differences in: (i) motor onset (Levels 1 and 2), when ropivacaine 1.0% was compared with ropivacaine 0.75% and 0.5% (P < 0.05); (ii) in sensory duration at all levels except T6 when ropivacaine was compared with ropivacaine 0.5% (P < 0.05); (iii) differences in sensory duration at T12 and S1 when ropivacaine 1.0% was compared with bupivacaine 0.5% (P < 0.05); (iv) differences in motor duration at all levels when ropivacaine 1.0% was compared with ropivacaine 0.5% (P < 0.05). No serious adverse events were reported in this study. CONCLUSION: Increasing doses of ropivacaine were associated with an increased clinical effect. The most consistent differences occurred when ropivacaine 1.0% was compared with 0.5% and the least consistent between ropivacaine 0.5%, 0.75% and bupivacaine 0.5%. The main difference between ropivacaine 1.0% and bupivacaine was in sensory duration. No serious adverse events were reported.