Does hypothermia prevent cerebral ischaemia during cardiopulmonary bypass?

It is believed that moderate hypothermia (25-32 degrees C) during cardiopulmonary bypass provides cerebral protection by reducing the cerebral metabolic rate (CMRO2). Nevertheless episodes of ischaemia do occur and thus it has been suggested that cerebral oxygenation should be monitored by jugular venous oximetry. However, this technique is cumbersome and invasive. Near infrared spectroscopy (NIRS) provides a non-invasive assessment of cerebral oxygenation and this was used together with continuousjugular venous oximetry in 21 patients undergoing hypothermic cardiopulmonary bypass. During the hypothermic period, jugular venous oximetry indicated reduced oxygen extraction consistent with a reduction in CMRO2 (increase from 61 +/- 2.5% to 74 +/- 2.5%). In contrast, near infrared spectroscopy demonstrated increased oxygen extraction (HbO2 - 11.5 +/- 1 microM, HHb + 3.2 +/- 0.3 microM) and a fall in the cerebral concentration of oxidized cytochrome oxidase ( - 1.7 +/- 0.3 microM) indicating ischaemia. These results suggest that cerebral ischaemia occurs during hypothermic cardiopulmonary bypass with a spurious rise in jugular venous oxygen saturation, which represents arterio-venous shunting. Thus if hypothermia does facilitate cerebral protection it does not appear to be a direct result of a reduction in CMRO2 and oxygen requirement.     

Can hypocapnia reduce cerebral embolization during cardiopulmonary bypass?

BACKGROUND: Cerebral embolization is a major cause of central nervous dysfunction after cardiopulmonary bypass. Experimental studies demonstrate that reductions in arterial carbon dioxide tension (PaCO2) can reduce cerebral embolization during cardiopulmonary bypass. This study examined the effects of brief PaCO2 manipulations on cerebral embolization in patients undergoing cardiac valve procedures. METHODS: Patients were prospectively randomized to either hypocapnia (PaCO2 = 30 to 32 mm Hg, n = 30) or normocapnia (PaCO2 = 40 to 42 mm Hg, n = 31) before aortic cross-clamp removal. With removal of the aortic cross-clamp embolic signals were recorded by transcranial Doppler ultrasonography for the next 15 minutes. RESULTS: Despite significant differences in PaCO2, groups did not differ statistically in total cerebral emboli counts. The mean number of embolic events was 107 +/- 100 (median, 80) in the hypocapnic group and 135 +/- 115 (median, 96) in the normocapnic group, respectively (p = 0.315). CONCLUSIONS: Due to the high between-patient variability in embolization, reductions in PaCO2 did not result in a statistically significant decrease in cerebral emboli. In contrast to experimental studies, the beneficial effect of hypocapnia on cerebral embolization could not be demonstrated in humans.     

Perioperative renal failure: hypoperfusion during cardiopulmonary bypass?

Acute renal failure is one of the most frequent and life-threatening complications after cardiac surgery. There is a recent growing deal of information suggesting that during the time of cardiopulmonary bypass kidneys may suffer from an imbalance between oxygen supply and oxygen needs. A low hematocrit during cardiopulmonary bypass is associated with an increase risk of acute renal failure, mainly due to a low oxygen delivery. An inadequate oxygen delivery during cardiopulmonary bypass is associated with lactate production, and under normothermic conditions, hyperlactatemia appears for an oxygen delivery below 260 mL min(-1) m(-2). The risk of acute renal failure significantly increases for an oxygen delivery approximately at the same value (272 mL min(-1) m(- 2)). During cardiopulmonary bypass, the pump flow should be coupled with the hematocrit to avoid falling below this critical oxygen delivery.     

Superoxide generation during cardiopulmonary bypass: Is there a role for vitamin E?

The cytotoxic metabolites of oxygen [superoxide (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl (OH^•)] have been demonstrated to be involved in the peroxidation of membrane lipids consequently altering membrane composition, morphology, and function. Of all the lines of defense adopted by living organisms against toxic oxygen free radicals, vitamin E is most effective in the prevention of membrane damage. Cardiopulmonary bypass (CPB) has been shown to activate complement and cause sequestration of leukocytes which can recruit, adhere, and stimulate release of cytotoxic oxygen radicals. A prospective study of 30 patients evaluated the effects of CPB with and without an exogenous free radical scavenger (Group I, N = 20, control) and (Group II, N = 10, vitamin E) on H₂O₂ (a marker of oxygen free radicals) malonaldehyde (a marker of lipid peroxidation), transpulmonary leukosequestration, and plasma levels of vitamins E and C. Group I showed a progressive increase in H₂O₂ during CPB from 65 ± 6 to 130 ± 11 μm/ml (P < 0.0001); plasma vitamin E decreased from 15 ± 3 to 6 ± 1 mg/liter (P < 0.0001) while vitamin C increased from 1.6 ±.3 to 2.3 ±.3 mg/dl (P < 0.0001). Group II showed no significant increase in H₂O₂ (from 78 ± 8 to 93 ± 5 μm/ml) during CPB and a significant reduction in H₂O₂ levels compared to Group I (P < 0.001); plasma vitamins E and C did not change significantly in Group II. Transpulmonary leukosequestration, expressed as median cell difference (MCD), occurred in Group I (MCD = 1700) and Group II (MCD = 1900) (P < 0.001 vs pre-CPB). We conclude that (1) cytotoxic oxygen radicals liberated during CPB can be reduced by pretreatment with vitamin E despite complement activation and pulmonary sequestration of white blood cells. (2) Vitamin E pretreatment prevented a clinically overt vitamin E deficiency during CPB. (3) The rise in vitamin C post-CPB demonstrates the direct effect on oxidized vitamin E by vitamin C in vivo.     

Does isoflurane optimize myocardial protection during cardiopulmonary bypass?

OBJECTIVE: To investigate the possible myocardial protective effect of isoflurane during aortic cross-clamp and cardioplegic cardiac arrest in patients undergoing conventional coronary artery bypass graft surgery. DESIGN: Prospective, randomized. SETTING: University medical center. PARTICIPANTS: Forty-nine patients undergoing elective coronary artery bypass graft surgery divided into 2 groups: control group (n = 21) and isoflurane group (n = 28). INTERVENTION: Isoflurane was administered in the pre-cardiopulmonary bypass (CPB) period to the isoflurane group. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and ST- segment variations were monitored in the pre-CPB period and after weaning from CPB in both groups. Incidence of reperfusion arrhythmias after release of aortic cross-clamp was compared. In the isoflurane group, the mean cardiac index after CPB was significantly higher than the pre-CPB value, whereas no difference between the 2 values was found in the control group. The higher cardiac index in the isoflurane group was associated with a lesser degree of ST- segment changes than in the control group. There was no significant difference between the 2 groups in the incidence of reperfusion arrhythmias after release of aortic cross-clamp. CONCLUSION: The present report suggests that administration of isoflurane before aortic cross-clamping in patients undergoing coronary artery bypass graft surgery may optimize the myocardial protective effect of cardioplegia. Isoflurane may be particularly advantageous whenever prolonged periods of aortic cross-clamping or inadequate delivery of cardioplegia is expected.     

Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed?

BACKGROUND: Hemodilutional anemia during cardiopulmonary bypass can lead to inadequate oxygen delivery and, consequently, to ischemic organ injury. In adult bypass, the nadir hematocrit can vary widely with body size and prebypass hematocrit variations, yet its effects on perioperative organ dysfunction and patient outcomes remain largely unknown. METHODS: To elucidate these effects, we retrospectively analyzed operative results and resource utilization data from 5000 consecutive cardiac operations with cardiopulmonary bypass performed on adults (1994 to 2000). Rolling decile groups (500 patients each; 75% overlapping) of increasing lowest hematocrit values were used to characterize hemodilution-outcome relationships. Intermediate-term (0 to 6 years) survival was assessed for coronary artery bypass patients (n = 3800) via Kaplan-Meier analysis in quintile subgroups based on lowest hematocrit. Multivariate logistic regression (operative mortality and morbidity) and Cox proportional hazard model (0- to 6-year mortality) analyses were used to determine independent predictors of poor outcomes. RESULTS: Stroke, myocardial infarction, low cardiac output, cardiac arrest, renal failure, prolonged ventilation, pulmonary edema, reoperation due to bleeding, sepsis, and multiorgan failure were all significantly and systematically increased as lowest hematocrit value decreased below 22%. Consequently, intensive care requirements, hospital stays, operative costs, and operative deaths were also significantly greater as a function of hemodilution severity. Longer-term survival was improved systematically for increasing lowest hematocrit coronary artery bypass grafting quintiles; for example, 6-year survival was 80.5% and 92.3% for quintiles I (lowest hematocrit = 16.1%) and V (lowest hematocrit = 27.5%). The continuous variable lowest hematocrit was an independent predictor of (1) operative mortality, (2) prolonged cardiovascular intensive case (>2 days) and postoperative hospital (>8 days) stays, and (3) worse 0- to 6-year survival. CONCLUSIONS: Increased hemodilution severity during cardiopulmonary bypass was associated with worse perioperative vital organ dysfunction/morbidity and increased resource use, as well as greater short- and intermediate-term mortality. We speculate that these results derive from inadequate oxygen delivery causing ischemic and/or inflammatory vital organ injury, as recently demonstrated intravitally in cerebral tissues. Although this analysis of a large observational study offers evidence linking low on-pump hematocrit values to these adverse outcomes, prospective randomized trials are needed (1) to establish whether a causal effect of hemodilution on poor outcomes actually exists and (2) to test the potential efficacy of maintaining on-pump hematocrit above 22% for improving outcomes of cardiopulmonary bypass.     

Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass?

OBJECTIVES: Vasoplegia is a frequent complication after cardiopulmonary bypass that often requires the application of norepinephrine. In a number of cases, however, vasoplegia is refractory to norepinephrine. The guanylate cyclase inhibitor methylene blue could be an attractive treatment alternative in such cases. This study examines the results of methylene blue therapy for norepinephrine-refractory vasoplegia after cardiopulmonary bypass. METHODS: A total of 54 patients with norepinephrine-refractory vasoplegia after cardiopulmonary bypass were treated with methylene blue (2 mg/kg) administered intravenously through a period of 20 minutes. The effects on hemodynamics, norepinephrine dosage, and clinical outcome were evaluated. RESULTS: Three patients (5.6%) died during the hospital stay. A clinically relevant increase in systemic vascular resistance and a decrease in norepinephrine dosage were observed in 51 patients within 1 hour after methylene blue infusion. Four patients (7.4%) had no response to methylene blue. No adverse effects related to methylene blue were observed. CONCLUSIONS: A single dose of methylene blue seems to be a potent approach to norepinephrine-refractory vasoplegia after cardiopulmonary bypass for most patients, with no obvious side effects. Guanylate cyclase inhibitors could be a novel class of agents for the treatment of norepinephrine-refractory vasoplegia after cardiopulmonary bypass. A controlled clinical trial is now needed to evaluate the role of methylene blue in this situation.     

Is hyperglycemia seen in children during cardiopulmonary bypass a result of hyperoxia?

OBJECTIVE: We sought to identify whether elevated PaO (2) itself can directly cause hyperglycemia in newborns and to document any additional effects of cardiopulmonary bypass on this response. METHODS: Piglets were exposed to either normoxia (88 +/- 6 mm Hg) or hyperoxia (470 +/- 28 mm Hg) in the following studies. Anesthetized 3-day-old neonatal pigs were either ventilated for 2 hours of normoxia (n = 5) or hyperoxia (n = 5) or placed on normothermic, normoxic cardiopulmonary bypass (n = 6) and then randomly assigned to either undergo a 2-hour normoxic period or a 1-hour hyperoxic episode, followed by a return to normoxia for an additional hour. Blood glucose levels were measured in all animals. RESULTS: No significant changes were observed in blood glucose levels in neonatal pigs that underwent 2 hours of normoxic ventilation (5.0 +/- 0.6 mmol/L) or cardiopulmonary bypass (6.6 +/- 1.6 mmol/L). However, the ventilatory model showed a significant and sustained (P <.001) hyperglycemic response after both 1 hour (8.6 +/- 1.0 mmol/L) and 2 hours (9.8 +/- 1.6 mmol/L) of hyperoxia. In the cardiopulmonary bypass model, exposure to 1 hour of hyperoxia elicited a significant (P <.05) hyperglycemic response (10.3 +/- 1.2 mmol/L), followed by a return to normal blood glucose levels (6.6 +/- 1.6 mmol/L) with a return to normoxia. This hyperoxia-mediated hyperglycemic response was confirmed when data examined from children undergoing cardiopulmonary bypass for primary repair of their congenital defects also identified a significant positive correlation (r = 0.72, P =.02) between oxygen levels and blood glucose levels measured before and at the end of cardiopulmonary bypass. CONCLUSIONS: Hyperoxia triggers a hyperglycemic response in both ventilatory and bypass models. Cardiopulmonary bypass does not exacerbate this response, as shown by the similar levels of hyperglycemia sustained for the duration of the hyperoxic exposure in both experimental models. Therefore, not only may hyperoxia play a crucial role in the hyperglycemic response seen during neonatal cardiopulmonary bypass, but its effect on glucose homeostasis should be considered whenever children are exposed to hyperoxia.     

Is prophylactic haemofiltration during cardiopulmonary bypass of benefit during cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic haemofiltration during cardiopulmonary bypass is of benefit during cardiac surgery? Altogether 273 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that haemofiltration will increase the haematocrit, reduce some inflammatory markers and may increase the variability of heparin levels. It may also reduce post-operative blood transfusion and possibly increase BP and cardiac index immediately after haemofiltration, although no differences in morbidity or mortality has ever been shown.     

What is a normal lactate level during cardiopulmonary bypass?

Blood lactate levels during cardiopulmonary bypass are often used to verify adequacy of perfusion. The present investigation aimed to propose a threshold for hyperlactatemia. Blood lactate levels in 5 121 cardiac surgical patients were retrospectively analysed by a review of database records. Hyperlactatemia was defined as a value equal to the 90th percentile of the identified lactate distribution at weaning from cardiopulmonary bypass. Patient demographics, background and outcome statistics were performed stratified on presence of hyperlactatemia. The threshold for hyperlactatemia was found to equal 2 mmol/l. Significant predictors of hyperlactatemia based on logistic regression modelling were age, complex surgery, duration of cardiopulmonary bypass, blood transfusion, acid base level, emergency operations, diabetes, vasoactive intervention, venous-blood-return to the heart-lung machine and renal function. Patients with hyperlactatemia required longer intensive care and postoperative ventilatory support. Complications were more frequent, especially: renal dysfunction, infections, respiratory and circulatory disorders. Hospital mortality was 13.3% compared to an overall level at 2.2%. The threshold for hyperlactatemia during cardiopulmonary bypass attained 2 mmol/l and predicted increased morbidity and mortality.