Measurement of intraperitoneal metabolites during hypothermic cardiopulmonary bypass using microdialysis.

OBJECTIVE: Splanchnic hypoxia, with resultant mucosal acidosis during cardiopulmonary bypass (CPB) has been demonstrated using tonometry. Microdialysis is a minimally-invasive method of obtaining peritoneal fluid samples. We measured the intraperitoneal metabolites during peri-operative period following hypothermic CPB and studied the safety of intraperitoneal microdialysis. DESIGN: Eleven consecutive patients undergoing coronary artery bypass grafting (CABG) were included after obtaining ethics committee approval and informed consent. Microdialysis catheters were placed intraperitoneally after sternotomy. Intraperitoneal samples and arterial blood samples were obtained peri-operatively for first 24 hours. The samples were analysed for levels of glucose, lactate, pyruvate and glycerol. Repeated measures ANOVA test was used to compare timed serum and intraperitoneal samples. RESULTS: The study population included nine males and two females with a mean age of 63.7 ± 11 years. The mean CPB and X clamp times were 50.9 ± 7.3 minutes and 27.3 ± 4.9 minutes, respectively. There were no complications related to microdialysis. The intraperitoneal lactate (L), pyruvate (P) and glycerol increased during CPB and four to six hours postoperatively. The L:P ratio was >10:1 during CPB, but in the postoperative period showed evidence of impaired oxygen utilisation. CONCLUSIONS: This prospective study confirms incidence of intraperitoneal anaerobic metabolism of glucose during CPB and impaired utilisation of glucose in the postoperative period. Microdialysis provides a novel and minimally-invasive method to measure real time intraperitoneal events.

The effect of fenoldopam and dopexamine on cytokine and endotoxin release following on-pump coronary artery bypass grafting: a prospective randomized double-blind trial.

BACKGROUND: Surgical trauma, exposure to an external circuit, and reduced organ perfusion contribute to the systemic inflammatory response following cardiopulmonary bypass (CPB). Reduced splanchnic perfusion causes disruption of the gastrointestinal mucosal barrier and the release of endotoxins. Fenoldopam (a new dopamine 1 receptor agonist) has been shown to be a specific renosplanchnic vasodilator in animal and human studies. We studied the effects of fenoldopam on the systemic inflammatory response and the release of endotoxins after CPB and compared the results with those for dopexamine. METHODS: Our prospective randomized study included 42 consecutive patients with good to moderate left ventricular function who were to undergo elective or inpatient coronary artery bypass grafting. We used closed envelope method to randomize patients to receive 0.2 µg/kg per minute of fenoldopam (n = 14), 2 µg/kg per minute of dopexamine (n = 14), or normal saline (n = 14). Patients received their respective treatments continuously from anesthesia induction until the end of the first 24 postoperative hours. Interleukin 1ß (IL-1ß), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor α, complement 3a (C3a), C4a, C5a, and endotoxins were measured during the perioperative period. Repeated-measures analysis of variance was used to evaluate the results for the timed samples. RESULTS: There were no statistical differences between the groups with respect to pre- and intraoperative variables. Release of C3a was attenuated in the fenoldopam group (P = .002), and release of IL-6 and IL-8 was attenuated in the postoperative period in the fenoldopam group (P = .012 and .015, respectively). The other interleukins showed no uniform release in any of the 3 groups. There were no statistically significant differences in serum endotoxin elevation between the 3 groups. CONCLUSION: A partial attenuation in the inflammatory response is possible with fenoldopam infusion. The elevation in serum endotoxin levels was not affected by dopexamine or fenoldopam infusion.

Effect of increased pump flow on hepatic blood flow and systemic inflammatory response following on-pump coronary artery bypass grafting.

UNLABELLED: Reduced organ perfusion during cardiopulmonary bypass (CPB) is responsible for morbidity associated with cardiac surgery. Non-pulsatile flow and hypothermia during CPB have been shown to cause reduced perfusion. During CPB, cardiac output is directly proportional to the pump flow rate. Therefore, we hypothesised that increasing pump flow during hypothermic CPB would improve organ perfusion and reduce the inflammatory response in the post-operative period. METHODS: Ethics committee approval was obtained. Twelve consecutive patients with good or moderate left ventricular function undergoing elective or inpatient coronary artery bypass grafting were included in the study after obtaining informed consent. Patients were randomised to receive either normal flow or higher pump flow (20% more than the usual flow during hypothermia). Hepatic blood flow, cytokines such as interleukins 1ß, 6, 8, 10 and 12, tumour necrosis factor-α and complements C3a, C4a and C5a were measured during the peri-operative period. Data were analysed using SPSS (ver.15). Categorical data were compared using the chi-square test and trends in cytokines were compared using a repeated measures ANOVA test. RESULTS: Both the groups were similar in pre- and peri-operative variables. Hepatic blood flow almost doubled in the high-pump-flow group following an increase in the flow rate during hypothermia(p=0.026). The release of serum complement IL-6 and 8 appeared to be reduced in the high-flow group; however, the difference did not reach statistical significance. CONCLUSIONS: Higher pump flows during hypothermic CPB increase hepatic blood flow. There was a trend towards attenuation of post-operative inflammatory response; however, larger studies will be needed to confirm these findings.

The effect of fenoldopam and dopexamine on hepatic blood flow and hepatic function following coronary artery bypass grafting with hypothermic cardiopulmonary bypass.

BACKGROUND: Hypothermic cardiopulmonary bypass is associated with low perfusion state causing a mismatch between demand and supply to various organs such as gut, kidneys and brain. The consequences are thought to be responsible for postoperative complications like systemic inflammatory response, renal failure, neurological injury, etc. Pharmacological agents like dopamine, dopexamine and dobutamine have been used in an attempt to reduce hypoperfusion and hence complications. Fenoldopam, a dopamine analog (DA-1 receptor agonist), has recently been shown to be specific reno-splanchnic vasodilator in animal studies. We studied the haemodynamic effects of fenoldopam and its effect on hepatic blood flow (HBF) during and after cardiopulmonary bypass and compared these with dopexamine. METHODS: Ethics committee approval was obtained. Forty-two consecutive patients with good/moderate left ventricular function undergoing either elective/urgent coronary artery bypass grafting were included in the study. Patients were randomised to receive either fenoldopam (0.2 microg/kgmin) (F; n=14) or dopexamine (2.0 microg/kgmin) (Dx; n=14) normal saline (NS; n=14) continuously after induction of anaesthesia for 24h following completion of surgery. HBF was measured using the Indocyanine green dye disappearance rate method, before, during and after cardiopulmonary bypass. Data were collected pre-, intra- and postoperatively. Serum liver enzymes were measured during the perioperative period. Repeated measures ANOVA test was used to compare timed samples in both groups. RESULTS: The study groups were comparable in pre- and intraoperative variables. In the fenoldopam and dopexamine groups there was a significant increase in heart rate 15 min following the commencement of the infusion (NS:F:DX::-2.0+/-7.8 beats/min:13.6+/-8.1 beats/min (p=0.007):18.36+/-20.2 beats/min (p=0.004)). However the change in mean arterial blood pressure was similar (NS:F:DX::-12.7+/-14.9:-4.0+/-23.1 (p=0.699):-2.6+/-22.3) (p=0.235). Cardiac index increased and systemic vascular resistance decreased (requiring noradrenaline infusion) in the fenoldopam group, however this did not reach statistical significance. Hepatic blood flow reduced during CPB and returned to near preoperative levels in all three groups with no statistical difference between groups. CONCLUSIONS: Fenoldopam infusion induced transient tachycardia, with no augmentation of hepatic blood flow whereas dopexamine induced tachycardia and did not augment hepatic blood flow. Fenoldopam and dopexamine may have hepato-protective effect.

Can lean body mass be used to reduce the dose of heparin and protamine for obese patients undergoing cardiopulmonary bypass?

Increasing numbers of obese patients are presenting for cardiac surgery. The convention for heparin dose dictates that a bolus of 300 IU heparin per kilogram of total body weight (TBW) is administered before CPB. During CPB, the activated clotting time (ACT) is maintained for longer than 480 seconds. At the end of the procedure, protamine is administered to neutralize heparin and achieve hemostasis. Both of these drugs can have serious side effects: heparin can induce thrombocytopenia, and protamine has been known to cause reactions in patients allergic to fish, vasectomized men, and some patients with insulin-dependent diabetes. The calculation of lean body mass (LBM) may be a more accurate method of determining drug doses as opposed to TBW and may avoid giving obese patients a relative overdose of heparin, which must subsequently be neutralized with protamine. LBM can be determined by different methods. This study used bio-electrical impedance analysis as a simple, quick, and accurate method of calculating LBM. A comparison was made between two groups of patients whose body mass index (BMI) was >27 kg/m2: Group 1, n = 13, mean BMI = 32, mean body fat = 36% received the conventional dose of 300 IU/kg heparin for their TBW. Group 2, n = 14, mean BMI = 31, mean body fat = 35% received a dose of 300 IU/kg heparin for their calculated LBM. ACT was conducted before and after heparin administration. Additional heparin was administered as required to achieve target ACT > 400 s. Mean ACT results and total heparin doses were analyzed using unpaired two tailed t tests. Our results indicate that with care, a reduction of as much as 25% in the doses of heparin (p = 0.0001) and protamine can be achieved for a substantial number of patients classified as overweight or obese.

Normal and abnormal trans-oxygenator pressure gradients during cardiopulmonary bypass.

A prospective study was conducted with the aims of 1) determining the normal trans-oxygenator pressure gradient characteristics for a range of oxygenators and 2) determining the characteristics, incidence and outcome of abnormally raised gradients. The trans-oxygenator pressure gradient was monitored in 3684 patients undergoing open-heart surgery in eight different hospitals. When the normal pressure gradient was measured during cardiopulmonary bypass in mmHg/L blood flow, a constant figure was obtained which was specific for each oxygenator. This gradient was abnormally raised in 16 cases (one in every 230 cases) and was raised to such an extent in three of these cases that an emergency oxygenator changeout was required (one in every 1228 cases). Among the 16 reported incidents, three different patterns of gradient changes occurred, suggesting the possibility that there were three different aetiologies. In nine of these incidents, the pressure gradient was normal immediately upon going on bypass, but rose rapidly to a plateau value, which then returned to the normal value within 40 minutes. In three cases, the pressure gradient was raised immediately upon going on bypass and then rapidly returned to the baseline. In one case, the pressure gradient was raised immediately upon going on bypass and stayed raised throughout the operation.