Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial.

BACKGROUND: Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection. METHODS: In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, omega3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol. FINDINGS: Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge. INTERPRETATION: Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.

Impedance cardiography in cardiac surgery patients: abnormal body weight gives unreliable cardiac output measurements.

BACKGROUND: To study the accuracy of cardiac output measurement by means of Electrical Impedance Cardiography (EIC) in post-cardiac surgery patients. METHODS: In a prospective study, we compared cardiac output measurements by means of thermodilution (COTD) with impedance cardiographic-derived values (COEIC) in 37 mechanically ventilated patients after cardiac surgery. Both methods were used simultaneously. RESULTS: COEIC values were weakly correlated with COTD in the total group when the equation of Sramek-Bernstein was employed to calculate COEIC (r = 0.60, P < 0.001, mean difference and standard deviation: -0.06 +/- 1.25 l.min-1). After exclusion of the 12 patients whose body weight differed > 15% from their ideal body weight, no significant difference was found between the mean values (5.40 +/- 1.80 l.min-1 (COEIC) vs 5.31 +/- 1.69 l.min-1, n = 25) while the correlation coefficient increased substantially (r = 0.85, P < 0.001, mean difference and standard deviation: 0.09 +/- 0.96 l.min-1). CONCLUSIONS: The results of this study indicate that weight is a very important factor in unreliable measurement of CO by impedance cardiography in cardiac surgery patients. The calculation equation as proposed by Sramek and Bernstein is not accurate enough in patients with more than 15% of weight deviation. Therefore, the use of impedance cardiography in these patients is of limited value until an accurate correction factor has been developed.

Increased oxygen consumption after cardiac surgery is associated with the inflammatory response to endotoxemia.

OBJECTIVE: The aim of this study was to determine whether the increase in post-operative oxygen consumption (delta VO2) in cardiac surgery patients is related to endotoxemia and subsequent cytokine release and whether delta VO2 can be used as a parameter of post-perfusion syndrome. DESIGN: Prospective study. SETTING: Operating room and intensive care unit of a university hospital. PATIENTS: Twenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids. MEASUREMENTS AND RESULTS: Plasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high delta VO2 (> or = median value of the entire group) were compared with measurements from patients with low delta VO2 (< median). Patients with high delta VO2 had higher levels of circulating endotoxin (P = 0.004), TNF (P = 0.04) and IL-6 (P = 0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low delta VO2. Several hours after delta VO2 the patient's body temperature rose. Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of delta VO2. CONCLUSIONS: This study demonstrates that patients with high post operative oxygen consumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO2 might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO2 provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.

Intestinal permeability, circulating endotoxin, and postoperative systemic responses in cardiac surgery patients.

OBJECTIVES: To determine whether intestinal permeability increases during cardiac operations, and whether the degree of endotoxemia is related to this increase. Furthermore, to determine whether intestinal permeability is related to the hemodynamic state during operation and to postoperative systemic responses. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty-three male patients undergoing elective coronary artery bypass surgery. INTERVENTIONS: Before surgery and during the fifth postoperative day, 100 mL of a solution containing L-rhamnose and cellobiose were administered orally. MEASUREMENTS AND MAIN RESULTS: Intestinal permeability was assessed by measuring the urinary excretion of L-rhamnose and cellobiose. Endotoxin concentrations in blood and prime fluid, hemodynamics, oxygen consumption, gas exchange, fluid balance, and the dose of vasoactive drugs were measured. Systemic responses were assessed by measuring hypermetabolism, circulatory support, and gas exchange. Intestinal permeation of cellobiose, reflecting paracellular transport, significantly increased during operation (p < 0.01), and correlated with the amount of circulating endotoxin (r2 = 0.46; p < 0.01). A high dose of ephedrine administered during operation, low baseline central venous pressure, and a less positive fluid balance during operation were associated with high intestinal permeability (r2 = 0.7; p < 0.01). Intestinal permeability was related to postoperative systemic responses (r2 = 0.49; p < 0.01). CONCLUSIONS: This study shows that during elective coronary artery bypass operations intestinal permeability between cells may increase. The degree of endotoxemia is related to this increase. Increased intestinal permeability is related to the use of ephedrine, especially during hypovolemia, and to postoperative systemic responses. Although a causative relation is not shown, these results might indicate that hypovolemia and vasoconstriction should be avoided during the operation.

Oxygen consumption after cardiopulmonary bypass--implications of different measuring methods.

OBJECTIVE: To determine whether intra-pulmonary oxygen consumption or whole body oxygen consumption is the main determinant of the hypermetabolic response after cardiopulmonary bypass. Secondly, which method of measuring oxygen consumption best quantifies this hyperdynamic response. DESIGN: We measured oxygen consumption by analysing respiratory gas (VO2-gas), carbon dioxide excretion (VCO2), and respiratory exchange ratio (RER = VCO2/VO2), and calculated oxygen consumption using the Fick-method (VO2-Fick) and intra-pulmonary oxygen consumption (VO2-gas - VO2-Fick) in patients at fixed times before and after elective cardiac surgery. Next, comparisons were made between methods and also between measurements at different times before and after bypass. SETTING: University hospital. PATIENTS: 10 elective cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: VO2-gas, VCO2 and RER were measured with an open circuit indirect calorimeter. VO2-Fick was calculated: VO2-Fick = cardiac index x (arterial - mixed venous oxygen content). Intrapulmonary oxygen consumption was calculated as the difference between VO2-gas and VO2-Fick. Both VO2-gas and VO2-Fick were about 20% higher after bypass than after induction of anaesthesia. Absolute values of VO2-gas were about 30% higher than VO2-Fick. Intra-pulmonary oxygen consumption accounted for 32% of whole body oxygen consumption after induction of anaesthesia and did not increase after bypass. CONCLUSION: Whole body oxygen consumption and not intra-pulmonary oxygen consumption is the main determinant of the hypermetabolic response after bypass. Increased intra-pulmonary oxygen consumption is not related to bypass. VO2-gas best quantifies this hypermetabolic response directly after bypass, and not VO2-Fick, VCO2 or intra-pulmonary oxygen consumption, since VO2-Fick excludes intra-pulmonary oxygen consumption and VCO2 does not reflect metabolism directly after bypass.

Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass.

A placebo-controlled double-blind study of patients undergoing cardiopulmonary bypass was conducted, comparing the effects of dexamethasone and a placebo on the activation of the plasmatic systems and blood cells and on the postoperative course after cardiopulmonary bypass. In the placebo group two patterns of blood activation could be distinguished. From the start of bypass, blood-material interaction caused an increase in complement C3a and elastase concentration. After release of the aortic cross-clamp, a statistically significant increase was observed in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Dexamethasone treatment was not able to inhibit complement activation and elastase release during cardiopulmonary bypass. However, dexamethasone treatment effectively inhibited the increase in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity after release of the crossclamp (p less than 0.01 compared with the placebo group). In the postoperative period the patients in the placebo group had hyperthermia and hypotension and required considerable intravenous fluid administration and cardiotonic treatment. The dexamethasone-treated patients, however, showed normothermia (p less than 0.01), had significantly higher blood pressures (p less than 0.01) without supportive treatment, and consequently were in the intensive care unit for a shorter period of time. We conclude that dexamethasone prevents the hemodynamic instability after cardiopulmonary bypass and thus improves the postoperative course by inhibition of the leukocyte and tissue plasminogen activator activity generated after release of the aortic crossclamp.

The role of different types of corticosteroids on the inflammatory mediators in cardiopulmonary bypass.

In a placebo-controlled double-blind study on patients undergoing cardiopulmonary bypass (CPB) we studied the inhibiting effects of dexamethasone, a high dose of methylprednisolone, and a low dose of prednisolone on the inflammatory reaction induced by CPB. During CPB two episodes of blood activation were noticed. First, the blood-material interaction caused a significant increase in complement C3a and elastase concentrations after the start of bypass (p less than 0.01). Secondly, the reperfusion of the ischemic heart, lungs, and peripheral tissue, after release of the aortic cross-clamp, caused an additional increase in C3a and elastase concentration and a statistically significant increase in leukotriene B4 (LTB4) concentration and tissue plasminogen activator (t-PA) activity (p less than 0.01, p less than 0.05, respectively). Dexamethasone treatment effectively inhibited the increase in LTB4 concentration and t-PA activity after release of the cross-clamp (significant differences to the placebo group, p less than 0.01, p less than 0.05, respectively). High-dose methylprednisolone treatment was almost as effective as dexamethasone treatment, whereas low-dose prednisolone treatment was less effective than methylprednisolone in the inhibition of the inflammatory mediators (DM greater than MP greater than P). None of the corticosteroid regimens was able to inhibit the increase in complement C3a and elastase. We therefore conclude that corticosteroids do not have an effect on complement activation during CPB. However, leukocyte activation and t-PA activity after release of the aortic cross-clamp are effectively inhibited by corticosteroid treatment, in a dose-dependent way. The inhibition of this inflammatory reaction will have a favourable effect on the postoperative course in patients who have undergone CPB.

Reduced platelet activation and improved hemostasis after controlled cardiotomy suction during clinical membrane oxygenator perfusions.

Platelet damage and postoperative blood loss are less severe after cardiopulmonary bypass performed with a membrane oxygenator than with a bubble oxygenator. However, this advantage of the membrane oxygenator can be partly negated by the platelet damage caused by cardiotomy suction, which implies the aspiration of air along with suction of blood. In order to reduce platelet damage by cardiotomy suction, we developed an automatic controlled cardiotomy suction system by which the aspiration of air was prevented. We evaluated platelet damage in a group of 28 patients (uncontrolled suction, n = 13; controlled suction, n = 15), and we studied the relationship between increasing volumes of cardiotomy suction and postoperative blood loss in a second group of 80 patients (uncontrolled suction, n = 47; controlled suction, n = 33). All patients underwent a coronary artery bypass operation with a membrane oxygenator. We measured significantly lower beta thromboglobulin concentrations during perfusions of approximately 2 hours and we observed a tendency toward shorter postoperative bleeding times if controlled cardiotomy suction was used. There were no significant differences between uncontrolled and controlled cardiotomy suction in platelet number and adenosine diphosphate-induced platelet aggregation. However, blood loss 18 hours postoperatively was significantly less in the controlled than in the uncontrolled suction group when the total volume of cardiotomy suction exceeded 65 L., which corresponded to perfusion times of over 3 hours. In conclusion, prevention of the aspiration of air along with suction of blood significantly reduced platelet activation and postoperative blood loss, particularly when large volumes of blood were aspirated.

Thoracotomy as a staging procedure after chemotherapy in the treatment of Stage III nonseminomatous carcinoma of the testis.

Of 108 patients with a nonseminomatous testicular carcinoma, 28 with lung metastases were studied. After combination chemotherapy with cisplatin, vinblastine, and bleomycin (PVB), 11 patients underwent exploratory thoracotomy. Viable carcinomatous tissue, along with fibrosis, necrosis, and mature teratoma, was found in 4 patients. Three of these patients were successfully retreated with VP 16-213, cisplatin, and actinomycin D. In patients with residual pulmonary or mediastinal masses after chemotherapy, resection of the lesions is mandatory to demonstrate viable carcinoma so that treatment can be readministered. Thus, in our view, thoracotomy is a diagnostic procedure.