Development of renal failure during the initial 24 h of intensive care unit stay correlates with hospital mortality in trauma patients.

BACKGROUND: Although multiple organ failure is the leading late cause of death, there is controversy about the impact of acute organ dysfunction and failure on trauma survival. METHODS: Consecutive adult trauma admissions between January 2000 and June 2003, excluding isolated head traumas and burns, were analysed for parameters of organ function during the first 24 h following intensive care unit (ICU) admission using the Sequential Organ Failure Assessment (SOFA) scoring system. A national prospectively collected ICU data registry was used for analysis, including data from 22 ICUs in university and central hospitals in Finland. RESULTS: The study population consisted of 1044 eligible trauma admissions; 32% of the cases were treated at university hospital level, the rest being secondary referral central hospital admissions. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15 (SD8), ICU mortality was 5.6% and a further 1.6% of patients died during their post-ICU hospital stay. Forty-five per cent of the patients were categorized as having multiple traumas. In univariate analysis, APACHE II > or = 25 [odds ratio (OR), 35; 95% confidence interval (CI), 18-66] and renal failure (OR, 29.5; 95% CI, 14-63) produced the highest ORs for ICU mortality. In the APACHE II-, sex- and age-adjusted logistic regression model, renal failure was a significant risk factor for both ICU and hospital mortality (OR, 11.8; 95% CI, 3.9-35.4; OR, 8.2; 95% CI, 2.9-23.2, respectively). CONCLUSION: The development of renal failure during the initial 24 h of ICU stay remained an independent risk factor for mortality in trauma patients requiring intensive care treatment even after adjusting for the APACHE II score, age and sex.

Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery.

BACKGROUND: The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery. METHODS: Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed. RESULTS: High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P= 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P= < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P= 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected. CONCLUSIONS: High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.

Myocardial preservation during coronary surgery with and without cardiopulmonary bypass.

BACKGROUND: There is increased interest in coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB), although the preservation of the myocardium under such circumstances has not been properly investigated. The aim of this randomized study was to compare the changes in myocardial metabolism during CABG with and without CPB. METHODS: Myocardial energy metabolism and tissue injury during CABG was monitored in a series of 22 patients (11 with and 11 without CPB). RESULTS: The maximum myocardial lactate production was significantly higher (p = 0.02) in the group operated with CPB (0.56 mmol/L) than without it (0.17 mmol/L). A similar phenomenon was seen in the transcardiac pH differences (0.085 and 0.034 with and without CPB, p = 0.007). The postoperative peak values of creatine kinase-MB mass (15.1 vs 6.3 microg/L) and troponin I (13.8 vs 5.2 microg/L) were significantly higher (p < 0.001 and p = 0.008) with than without CPB. CONCLUSIONS: CABG on a beating heart is associated with better myocardial energy preservation and less myocardial damage compared with conventional CABG with CPB and intermittent antegrade mild hypothermic blood cardioplegia.

Reversible ischemic inhibition of F(1)F(0)-ATPase in rat and human myocardium.

The physiological role of F(1)F(0)-ATPase inhibition in ischemia may be to retard ATP depletion although views of the significance of IF(1) are at variance. We corroborate here a method for measuring the ex vivo activity of F(1)F(0)-ATPase in perfused rat heart and show that observation of ischemic F(1)F(0)-ATPase inhibition in rat heart is critically dependent on the sample preparation and assay conditions, and that the methods can be applied to assay the ischemic and reperfused human heart during coronary by-pass surgery. A 5-min period of ischemia inhibited F(1)F(0)-ATPase by 20% in both rat and human myocardium. After a 15-min reperfusion a subsequent 5-min period of ischemia doubled the inhibition in the rat heart but this potentiation was lost after 120 min of reperfusion. Experiments with isolated rat heart mitochondria showed that ATP hydrolysis is required for effective inhibition by uncoupling. The concentration of oligomycin for 50% inhibition (I(50)) for oxygen consumption was five times higher than its I(50) for F(1)F(0)-ATPase. Because of the different control strengths of F(1)F(0)-ATPase in oxidative phosphorylation and ATP hydrolysis an inhibition of the F(1)F(0)-ATPase activity in ischemia with the resultant ATP-sparing has an advantage even in an ischemia/reperfusion situation.

Myocardial metabolism and hemodynamics during coronary surgery without cardiopulmonary bypass.

BACKGROUND: Although renewed interest has recently been shown in coronary artery bypass grafting without cardiopulmonary bypass, no reports are available on myocardial metabolism and hemodynamics during temporary coronary occlusion and rotation of the contracting heart. METHODS: Changes in myocardial energy metabolism and hemodynamics were monitored in 12 patients undergoing elective coronary artery bypass grafting without cardiopulmonary bypass, and the postoperative efflux of creatine kinase-MB mass and troponin T were also determined. RESULTS: There was a significant increase in myocardial production of ATP degradation products (p = 0.026) and lactate (p = 0.004) during the operation. Myocardial oxygen extraction decreased (p = 0.012) in correlation with use of the short-acting beta-blocker, esmolol (r = -0.71). Apart from a decrease in mean arterial blood pressure (p = 0.002), there were no significant hemodynamic changes during the operation. The overall postoperative troponin T and creatine kinase-MB mass changes remained nonsignificant during the first two postoperative days. One patient had a myocardial infarction, diagnosed by electrocardiography, on the second postoperative day, but otherwise there were no major complications. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass seems to be well tolerated as only minor changes in myocardial energy metabolism and hemodynamics are observed during the operation.

Ultrastructural changes in myocardium during mild hypothermic retrograde blood cardioplegia.

Uniformity of myocardial protection during retrograde blood cardioplegia is still a controversial area. We conducted a study on electron microscopic changes in the myocardium during mild hypothermic retrograde cardioplegia (31-32 degrees C) in 12 patients undergoing coronary artery bypass grafting. Biopsies for electron microscopy were taken from the right and left ventricular myocardium before and at the end of aortic cross-clamping and after 15 min reperfusion. The intercellular junctions, intracellular and extracellular oedema, mitochondria, capillaries, nuclei and myofibrils were analysed separately in each specimen, using a semiquantative method with scoring from 0 (unchanged) to 3 (severe changes), and the total scores were correlated with the severity of right and left coronary artery disease and with ischaemia time during aortic cross-clamping. Mild to moderate ultrastructural changes occurred in the myocardium during the cardiopolegia, most typically myofibrillar injury and oedema. These changes increased during aortic cross-clamping and reperfusion, especially in the right ventricle. The total ultrastructural score for the right ventricle correlated negatively with the severity of right coronary artery disease at the end of cross-clamping. No such correlation was found in the left ventricle. Apart from one case of perioperative myocardial infarction, the clinical outcome was unproblematic. Myocardial structure thus was by and large well preserved during mild hypothermic retrograde blood cardioplegia, with the right ventricle seemingly somewhat less protected than the left.

Myocardial protection during antegrade versus retrograde cardioplegia.

BACKGROUND: It has been suggested that the right ventricular myocardium is suboptimally protected during retrograde blood cardioplegia. METHODS: Twenty patients undergoing an elective coronary bypass procedure were randomized to receive antegrade or retrograde mild hypothermic blood cardioplegia. Transventricular differences in oxygen extraction, lactate production, and pH were monitored during aortic cross-clamping, and myocardial biopsy specimens were taken from both ventricles before cannulation and 15 minutes after aortic declamping for analysis of adenine nucleotides and their breakdown products. The extent of myocardial injury was estimated by monitoring postoperative leakage of troponin T and the MB isoenzyme of creatine kinase. Hemodynamic recovery and postoperative complications were noted. RESULTS: The preoperative characteristics of the two groups were similar. Oxygen extraction and lactate production in the right ventricular myocardium were higher in the retrograde group. In this group, the right ventricle also extracted more oxygen and produced more lactate and acid than did the left ventricle. Tissue levels of adenine nucleotides tended to decrease in both ventricles during operation, with no differences between them. The level of adenosine catabolites did increase somewhat in the right ventricular myocardium of the retrograde cardioplegia group after aortic declamping. There was a tendency for more prominent efflux of troponin T and the MB isoenzyme of creatine kinase in the retrograde group. Nevertheless, the postoperative course was uneventful in both groups. CONCLUSIONS: Retrograde mild hypothermic blood cardioplegia leads to metabolic changes compatible with right ventricular ischemia. Nevertheless, tissue levels of high-energy phosphates are well preserved, and the postoperative course seems to be unproblematic. Care should be taken when retrograde normothermic blood cardioplegia is provided for patients with right ventricular hypertrophy, poor right ventricular function, or severe preoperative myocardial ischemia.

Normothermic retrograde blood cardioplegia with or without preceding ischemic preconditioning.

BACKGROUND: Preconditioning has been suggested as the most powerful mechanism of myocardial protection against prolonged ischemia. However, whether preconditioning offers additional benefits over cardioplegia during coronary artery bypass grafting is not known. METHODS: Thirty patients undergoing coronary artery bypass grafting were randomized into two groups. After aortic cross-clamping, group 1 received antegrade blood and blood cardioplegia followed by normothermic retrograde blood cardioplegia (controls), whereas group 2 patients were subjected to 5 minutes of global ischemia followed by reperfusion with antegrade and retrograde blood cardioplegia (preconditioned). The transcardiac differences in oxygen saturation, pH, and lactate were measured during cardiopulmonary bypass. Myocardial biopsy specimens were taken from half of the patients for adenosine triphosphate determination. The extent of myocardial injury was estimated by monitoring the postoperative leakage of creatine kinase-MB and troponin T. Immediate hemodynamic recovery and postoperative complications were also observed. RESULTS: The 5-minute preconditioning induced marked lactate and acid production, and myocardial adenosine triphosphate levels tended to decrease. The heart continued to produce lactate and acid during retrograde cardioplegia, but the transcardiac pH and lactate differences were similar in both groups. Adenosine triphosphate level measured at the end of the cross-clamp period was decreased to a half and one third of the preclamp values in the control and preconditioned groups, respectively. The postoperative creatine kinase-MB and troponin T effluxes tended to be more elevated in the preconditioned group, yet hemodynamic recovery and the number of postoperative complications were similar in both groups. CONCLUSIONS: The results show that a 5-minute preconditioning ischemia does not offer any additional benefits over normothermic retrograde blood cardioplegia during coronary artery bypass grafting.

Normothermic versus mild hypothermic retrograde blood cardioplegia: a prospective, randomized study.

BACKGROUND: Continuous retrograde blood cardioplegia has been introduced as a promising alternative for myocardial protection during cardiac operations, although the optimal conditions for its delivery have been poorly studied. METHODS: We randomized a prospective series of 101 patients to receive either retrograde warm (37 degrees C) or mild hypothermic (28 degrees to 29 degrees C) blood cardioplegia during elective coronary artery bypass grafting. Warm blood cardioplegia was delivered to the aortic root until the heart was arrested, after which the regimen was switched to retrograde and continued either as warm or mild hypothermic cardioplegia. Oxygen consumption and transcardiac pH differences during aortic cross-clamping were determined, and postoperative creatine kinase-MB efflux, hemodynamic recovery, and clinical complications monitored. RESULTS: Clinical characteristics, cardioplegia delivery rates, aortic cross-clamp and cardiopulmonary bypass times, and the number of distal anastomoses were similar in both patient groups. Short intermissions in cardioplegia delivery during construction of distal anastomoses were allowed, the ischemia time in the mild hypothermic group being somewhat longer (8.3% +/- 1.1% versus 5.1% +/- 0.8% of cross-clamp time; p = 0.05). Myocardial oxygen consumption was lower in the mild hypothermic group (2.49 +/- 0.23 versus 3.93 +/- 0.33 mL/min at 30 minutes of cross-clamping; p < 0.01), and the transcardiac pH difference was smaller (0.05 +/- 0.01 versus 0.07 +/- 0.01 at 30 minutes of cross-clamping; p < 0.03). Postoperative creatine kinase-MB levels were higher in the normothermic group. Heart rate was higher and left ventricular stroke work index smaller in the warm group, but otherwise there were no major differences between the groups in hemodynamic recovery. The number of postoperative complications was also similar in both groups. CONCLUSIONS: Although both normothermic (37 degrees C) and mild hypothermic (28 degrees to 29 degrees C) retrograde blood cardioplegia, when delivered in near-continuous fashion, will offer safe myocardial protection during coronary artery bypass grafting, mild hypothermia seemed to provide somewhat better protection under the conditions prevailing here. The effects of different cardioplegia temperatures should perhaps be tested further in patients with recent myocardial infarction, unstable angina, or severely depressed left ventricular function.

Ultrastructural changes during continuous retrograde warm and mild hypothermic blood cardioplegia for coronary bypass operations.

Ultrastructural changes in myocardial tissue were studied in 21 patients undergoing elective aorta-coronary bypass operation. The patients were randomized into two groups, with 10 of them receiving continuous retrograde warm and 11 continuous retrograde mild hypothermic blood cardioplegia. Biopsy specimens for electron microscopy were taken from the apical part of the left ventricle before and at the end of the aortic crossclamp period and after reperfusion of the myocardium. The ultrastructural changes were analyzed with use of a semiquantitative scoring system and classified as mild, moderate, or severe. Slight ultrastructural changes were found in both groups even before the aortic crossclamp period. At the end of the aortic crossclamp period the most prominent ultrastructural changes were mitochondrial swelling, damage of capillary endothelium, and clearing of the nucleoplasm or margination of chromatin, but some enlargement in intercalated discs was also discernible. Reperfusion of the myocardium for 15 minutes somewhat further increased the overall score of the ultrastructural changes. Two patients in the warm cardioplegia group had a perioperative myocardial infarction, and this may be one reason for the higher postoperative creatine kinase MB efflux in this patient group. Despite this finding, no major differences in the ultrastructural changes between the two cardioplegia groups could be observed. We conclude that only mild to moderate and principally reversible ultrastructural changes occur in myocardium during continuous retrograde warm and mild hypothermic blood cardioplegia for coronary bypass operation.

Amino acid-enriched glucose-insulin-potassium infusion improves hemodynamic function after coronary bypass surgery. A double-blind study in patients with unstable angina and/or compromised left ventricular function.

OBJECTIVE: The goal of this study was to assess the effects of a combination of glucose-insulin-potassium (GIK) and the amino acids aspartate and glutamate upon perioperative hemodynamics in coronary surgery patients with unstable angina and/or compromised left ventricular function. DESIGN: Prospective, randomized, and double-blind clinical study. SETTING: Operating theatre and intensive care unit (ICU) of a university hospital. PATIENTS: 44 coronary artery bypass graft (CABG) patients with unstable angina and/or compromised left ventricular function. INTERVENTIONS: 22 patients (group A) were given 1l of an infusion with 250g glucose, 100 I.U. fast-acting human insulin, 72 mmol potassium, 32 mmol magnesium, 20 mmol phosphate, 65 mmol aspartate, and 65 mmol glutamate, while another 22 patients (group C) were given 1l of an infusion with 50 g glucose, 72 mmol potassium, 32 mmol magnesium, and 8 mmol phosphate. The infusion rate was 1.2 ml/kg/h from the anesthesia induction onward to the commencement of cardiopulmonary bypass, when it was reduced to 0.8 ml/kg/h. When 11 had been infused, but not later than 4 a.m., the infusion was continued by giving 10% glucose at the same rate to both groups. Additional insulin (median: 14.2 I.U., range: 0-41.5) or saline was given during bypass to the A and C patients, respectively. A blood cardioplegia technique containing aspartate and glutamate was used in both groups. RESULTS: At aortic cannulation, the cardiac index (CI) had increased from the pre-anesthetic level by 15.3% (mean) (SD: 31.7%) in group A and decreased by 7.7% (15.1%) in C patients, p = 0.0069. Also the changes in stroke index (SI; p = 0.022), left (LVSWI; p = 0.0037) and right ventricular stroke work index (RVSWI; p = 0.0097) were more favorable in group A. Despite longer aortic cross-clamp, p = 0.031, and perfusion times, p = 0.042, in A patients, the change in cardiac index was also better in this group after bypass: At decannulation, the difference between mean values was 31.8%, p = 0.0001, and at arrival in the ICU it was 16.1%, p = 0.028. The same was also seen 8 h postoperatively and on the 1st and 2nd postoperative mornings; p = 0.034, 0.040, and 0.037, respectively (Wilcoxon test). Favorable changes were seen for the A patients also regarding SI at decannulation (p = 0.0002) and after 8 h (p = 0.017); LVSWI at decannulation (p = 0.0002), at arrival in the ICU (p = 0.0023), and after 8 h (p = 0.0011); and RVSWI at decannulation (p = 0.0027), at the ICU (p = 0.021), after 8 h (p = 0.014), and on the 1st postoperative morning (p = 0.039). However, the response to a hemodynamic loading test (6% hydroxyethyl starch 5 ml/kg) was similar in the 2 groups, and there was no difference in the need for inotropic support. CONCLUSIONS: Amino acid-enriched GIK infusion improves hemodynamic function in CABG patients with unstable angina and/or compromised left ventricular function.

Prebypass glucose-insulin-potassium infusion in elective nondiabetic coronary artery surgery patients.

Perioperative GIK therapy has been advocated to ensure adequate energy substrate levels during cardiac surgery. However, hyperglycemia should be avoided because it may worsen neurologic outcome after cerebral ischemia. A prospective, randomized, clinical comparison was performed between two prebypass infusion regimens in 32 elective nondiabetic CABG patients. Sixteen patients (GIK group) received glucose, 0.6 g/kg/h, insulin, 0.12 U/kg/h, and KCl, 0.12 mmol/kg/h, from the induction of anesthesia to the start of CPB; while the remaining 16 patients (R group) received only Ringer's acetate. The pump prime was glucose free and a blood cardioplegia technique was used in both groups. No differences were found between the groups with regard to myocardial injury; the CK-MB enzyme fractions were elevated to a similar degree and the frequency of postoperative ECG changes were similar in both groups. Likewise, there were no differences in hemodynamic changes, need for inotropic support, arrhythmia frequency, or duration of ICU stay. The GIK patients had higher blood glucose (P < 0.05) and insulin levels (P < 0.01); blood glucose increased to 12.4 +/- 5.4 mmol/L (mean +/- SD) at cannulation, with a drop after starting bypass. Interindividual variation in GIK patients was great, with glucose values ranging between 20.1 mmol/L at cannulation to 2.0 mmol/L after starting CPB. A hyperglycemic response was seen in both groups during rewarming: 15.0 +/- 4.2 and 15.0 +/- 3.1 mmol/L in GIK and R patients, respectively. It is concluded that prebypass GIK infusion had no clinical benefits for elective CABG patients as compared to Ringer's acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal and umbilical venous plasma immunoreactive beta-endorphin levels during labor with and without epidural analgesia.

Maternal and umbilical venous plasma immunoreactive beta-lipotropin/beta-endorphin levels were determined during labor in 23 healthy parturient women at term. Eleven of the mothers received a segmental epidural analgesic for relief of pain, whereas the other 12 mothers were nearly pain-free and needed no analgesia. Maternal immunoreactive beta-lipotropin/beta-endorphin levels were already significantly elevated at the beginning of labor in both groups in comparison with nonpregnant young women. Maximum levels of immunoreactive beta-lipotropin/beta-endorphin were reached at delivery, and these mean levels were significantly higher than the initial mean levels in the epidural group (p less than 0.05) and in the control group (p less than 0.001). There were statistically no significant differences between the groups at any time. The umbilical venous plasma immunoreactive beta-lipotropin/beta-endorphin levels did not differ from each other in the epidural and the control groups. These results suggest that the stress of labor causes an increase in the maternal secretion of immunoreactive beta-lipotropin/beta-endorphin which is not related to the degree of pain itself. Epidural analgesia has also no effect on umbilical venous plasma immunoreactive beta-lipotropin/beta-endorphin.