Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.

BACKGROUND: Single-dose human fibrinogen concentrate (FCH) might have haemostatic benefits in complex cardiovascular surgery. METHODS: Patients undergoing elective aortic surgery requiring cardiopulmonary bypass were randomly assigned to receive FCH or placebo. Study medication was administered to patients with a 5 min bleeding mass of 60-250 g after separation from bypass and surgical haemostasis. A standardized algorithm for allogeneic blood product transfusion was followed if bleeding continued after study medication. RESULTS: 519 patients from 34 centres were randomized, of whom 152 (29%) met inclusion criteria for study medication. Median (IQR) pretreatment 5 min bleeding mass was 107 (76-138) and 91 (71-112) g in the FCH and placebo groups, respectively (P=0.13). More allogeneic blood product units were administered during the first 24 h after FCH, 5.0 (2.0-11.0), when compared with placebo, 3.0 (0.0-7.0), P=0.026. Fewer patients avoided transfusion in the FCH group (15.4%) compared with placebo (28.4%), P=0.047. The FCH immediately increased plasma fibrinogen concentration and fibrin-based clot strength. Adverse event rates were comparable in each group. CONCLUSIONS: Human fibrinogen concentrate was associated with increased allogeneic blood product transfusion, an unexpected finding contrary to previous studies. Human fibrinogen concentrate may not be effective in this setting when administered according to 5-minute bleeding mass. Low bleeding rates and normal-range plasma fibrinogen concentrations before study medication, and variability in adherence to the complex transfusion algorithm, may have contributed to these results. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier no. NCT01475669; EudraCT trial no. 2011-002685-20.

Anemia increases the risk of renal cortical and medullary hypoxia during cardiopulmonary bypass.

INTRODUCTION: Anemia is an independent predictor of acute kidney injury (AKI) following cardiopulmonary bypass (CPB), possibly due to inadequate renal oxygen delivery. The objective of this study was to investigate the effects of CPB and anemia on tissue oxygen tension (pO2) and blood flow in the renal cortex and medulla. METHODS: Rats (n=6/group) underwent 1 hr of normothermic cardiopulmonary bypass (CPB), with target hemoglobin concentrations (Hb) of 10 g/dL (CPB) or 6.5 g/dL (anemia-CPB). Renal blood flow (RBF) and tissue PO2 were measured before, during and after 1 hr of CPB. To confirm the observed differences in renal cortical and medullary PO2, HIF-1α (ODD) luciferase mice were exposed to 8% O2 (hypoxia) and HIF-1α dependent luminescence was measured in the renal cortex and medulla (n=5). RESULTS: Renal tissue PO2 values decreased initially and returned towards baseline, however, values at the end of CPB. Anemia-CPB resulted in a significant increase in both renal cortical and medullary blood flow, PO2 remained significantly reduced throughout anemia-CPB. Renal medullary HIF-1α-dependent luminescence confirmed a greater degree of hypoxia in the renal medulla. DISCUSSION: During CPB, renal O2 delivery was transiently jeopardized, but recovered after 1 hr. Anemia-CPB resulted in a dramatic and sustained reduction in renal cortical and medullary PO2, which suggests an increased risk of renal hypoxic injury with anemia. CONCLUSION: The clear difference in the degree of hypoxia in the renal cortex and medulla may be useful in understanding the progress of medullary hypoxia during CPB with anemia and the potential development of AKI. Further studies should aim at identifying early markers of medullary hypoxia and potential agents that may decrease the work and O2 consumption in the renal medulla to reduce the risk of hypoxic damage during CPB and anemia.

Quantitative assessment of brain microvascular and tissue oxygenation during cardiac arrest and resuscitation in pigs.

Cardiac arrest is associated with a very high rate of mortality, in part due to inadequate tissue perfusion during attempts at resuscitation. Parameters such as mean arterial pressure and end-tidal carbon dioxide may not accurately reflect adequacy of tissue perfusion during cardiac resuscitation. We hypothesised that quantitative measurements of tissue oxygen tension would more accurately reflect adequacy of tissue perfusion during experimental cardiac arrest. Using oxygen-dependent quenching of phosphorescence, we made measurements of oxygen in the microcirculation and in the interstitial space of the brain and muscle in a porcine model of ventricular fibrillation and cardiopulmonary resuscitation. Measurements were performed at baseline, during untreated ventricular fibrillation, during resuscitation and after return of spontaneous circulation. After achieving stable baseline brain tissue oxygen tension, as measured using an Oxyphor G4-based phosphorescent microsensor, ventricular fibrillation resulted in an immediate reduction in all measured parameters. During cardiopulmonary resuscitation, brain oxygen tension remained unchanged. After the return of spontaneous circulation, all measured parameters including brain oxygen tension recovered to baseline levels. Muscle tissue oxygen tension followed a similar trend as the brain, but with slower response times. We conclude that measurements of brain tissue oxygen tension, which more accurately reflect adequacy of tissue perfusion during cardiac arrest and resuscitation, may contribute to the development of new strategies to optimise perfusion during cardiac resuscitation and improve patient outcomes after cardiac arrest.

The evidence for the use of recombinant factor VIIa in massive bleeding: development of a transfusion policy framework.

A review of the recent randomized control trial evidence of the use of recombinant factor VIIa (rFVIIa) in massive bleeding. rFVIIa is a recombinant genetically engineered clotting factor that has been used for the management of haemophilia patients with inhibitors. There has been increasing use in patients with massive bleeding, even when there is no underlying coagulation disorder present. In November 2006, the Canadian National Advisory Committee on Blood and Blood Products engaged in a consultation and review process with several leading Canadian experts to review and discuss the current evidence up to November 2006. There is little evidence to support the routine use of rFVIIa in massive bleeding on review of 13 randomized controlled trials. rFVIIa should only be considered as part of a transfusion policy framework for massive bleeding after all other transfusion and supportive measures are considered. An example of a policy framework is presented.

Storage of strain-specific rat blood limits cerebral tissue oxygen delivery during acute fluid resuscitation.

BACKGROUND: The effect of blood storage on tissue oxygen delivery has not been clearly defined. Some studies demonstrate reduced microvascular oxygen delivery, whereas others do not. We hypothesize that storage of rat blood will limit its ability to deliver oxygen to cerebral tissue. METHODS: Anaesthetized rats underwent haemorrhage (18 ml kg(-1)) and resuscitation with an equivalent amount of fresh or 7 day stored strain-specific whole blood. Arterial blood gases, co-oximetry, red cell counts and indices, and blood smears were performed. Hippocampal tissue oxygen tension (PBr(O2)), regional cerebral blood flow (rCBF), and mean arterial pressure (MAP) were measured before and for 60 min after resuscitation (n=6). Data [mean (SD)] were analysed by anova. RESULTS: After 7 days, there was a significant reduction in pH, Pa(O2), an increase in Pa(CO2), but no detectable plasma haemoglobin in stored rat blood. Stored red blood cell morphology demonstrated marked echinocytosis, but no haemolysis in vitro. MAP and PBr(O2) in both groups decreased after haemorrhage. Resuscitation with stored blood returned MAP [92 (SD 16) mm Hg] and PBr(O2) [3.2 (0.7) kPa] to baseline, whereas rCBF remained stable [1.2 (0.1)]. Resuscitation with fresh blood returned MAP to baseline [105 (16) mm Hg] whereas both PBr(O2) [5.6 (1.5) kPa] and rCBF [1.9 (0.4)] increased significantly (P<0.05 for both, relative to baseline and stored blood group). There was no evidence of haemolysis in vivo. CONCLUSIONS: Although resuscitation with stored blood restored cerebral oxygen delivery to baseline, fresh blood produced a greater increase in both PBr(O2) and rCBF. These data support the hypothesis that storage limits the ability of RBC to deliver oxygen to brain tissue.

Coenzyme Q10 in patients undergoing CABG: Effect of statins and nutritional supplementation.

BACKGROUND: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are effective cholesterol lowering medications, however, statins may interfere with CoQ(10) biosynthesis. We examined the effect of statin therapy as well as nutritional supplements on plasma, cardiac and skeletal muscle concentrations of CoQ(10). METHODS: Forty patients with left ventricular dysfunction had fasting blood samples collected at baseline and following four weeks of supplementation (150mg/day of CoQ(10)). Cardiac and skeletal muscle biopsies were collected at the time of surgery and frozen in liquid nitrogen until analyzed for CoQ(10) levels by high performance liquid chromatography. RESULTS: Nutrient supplementation significantly increased plasma [(1.8 (1.2, 2.7) vs 0.8 (0.6, 0.94) mug/ml plasma, median+IQR; p=0.001)] and cardiac tissue concentrations of CoQ(10) [(120.5 (76.5, 177.1) vs 87.3 (60.5, 110.8) nmol/g wet weight, p=0.04)]. No effect of supplementation was seen on samples of skeletal muscle from the chest wall. Statin therapy was not found to influence plasma, cardiac or chest wall levels of CoQ(10). CONCLUSION: Nutrient supplementation significantly increased plasma and cardiac tissue levels of CoQ(10) but did not influence chest wall muscle concentrations. Statin therapy did not significantly influence tissue concentrations of CoQ(10). Longer term studies are needed to confirm this observation.

Risk factors for red cell transfusion in adults undergoing coronary artery bypass surgery: a systematic review.

BACKGROUND AND OBJECTIVE: Identifying factors that can predict adults at high risk of receiving red blood cell transfusion during coronary artery bypass graft (CABG) surgery may aid in more efficient blood banking practices and may tailor blood conservation strategies for these adult patients. The objective was to identify clinical factors associated with increased red cell transfusion in adults undergoing CABG surgery. METHODS: A systematic review of the MEDLINE and HealthSTAR databases from 1966 to December 2005 was conducted. Citations containing the medical subject heading or textwords 'coronary artery bypass graft', 'CABG' and 'cardiovascular surgery' were combined with the medical subject headings or textwords 'transfusion' and 'blood transfusion'. RESULTS: A total of 2461 abstracts were retrieved. Twenty-one studies met the inclusion/exclusion criteria. Transfusion rates ranged from 7 to 97%. Several variables were identified that were associated with increased red cell transfusion rates including older age, female sex, low haemoglobin concentration or haematocrit value, renal insufficiency and urgent/emergent surgery. The strongest risk factor was the urgency of surgery (urgent or emergent surgery), which was associated with a 4x to 8x increase in transfusion rates compared to elective surgery. Increasing age and female sex increased the likelihood of transfusion by 1x to 3x and 2x, respectively. CONCLUSIONS: Increasing patient age, female sex, lower preoperative haemoglobin levels, as well as the urgency of the CABG surgery were associated with higher transfusion rates. Identifying risk factors for transfusion may allow for targeted use of blood conservation strategies, improved efficiency in blood utilization and informing adults at risk of transfusion.

Beta2 adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats.

BACKGROUND: Haemodilution has been associated with neurological morbidity in surgical patients. This study tests the hypothesis that inhibition of cerebral vasodilatation by systemic beta2 adrenergic blockade would impair cerebral oxygen delivery leading to tissue hypoxia in severely haemodiluted rats. METHODS: Under general anaesthesia, cerebral tissue probes were placed to measure temperature, regional cerebral blood flow (rCBF) and tissue oxygen tension (P(Br)O2) in the parietal cerebral cortex or hippocampus. Baseline measurements were established before and after systemic administration of either a beta2 antagonist (10 mg kg(-1) i.v., ICI 118, 551) or saline vehicle. Acute haemodilution was then performed by simultaneously exchanging 50% of the estimated blood volume (30 ml kg(-1)) with pentastarch. Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry), mean arterial blood pressure (MAP) and heart rate (HR) were also measured. Data were analysed using a two-way anova and post hoc Tukey's test [mean (sd)]. RESULTS: Haemodilution reduced the haemoglobin concentration comparably in all groups [71 (9) g litre(-1)]. There were no differences in ABGs, co-oximetry, HR and MAP measurements between control and beta2 blocked rats, either before or 60 min after drug or vehicle administration. In rats treated with the beta2 antagonist there was a significant reduction in parietal cerebral cortical temperature, regional blood flow and tissue oxygen tension, relative to control rats, 60 min after haemodilution (P<0.05 for each). These differences were not observed when probes were placed in the hippocampus. CONCLUSION: Systemic beta2 adrenergic blockade inhibited the compensatory increase in parietal cerebral cortical oxygen delivery after haemodilution thereby reducing cerebral cortical tissue oxygen tension.

A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery.

BACKGROUND: We performed this study to determine the dose-response of hemoglobin raffimer administered in conjunction with intraoperative autologous donation in patients undergoing coronary artery bypass grafting surgery. A secondary objective was to evaluate hemoglobin raffimer for reducing the incidence of allogeneic red blood cell transfusions. METHODS: This was a phase II, single-blind, multicenter, placebo-controlled, open-label study. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation were randomized to receive a single dose of hemoglobin raffimer or control (10% pentastarch). Patients were sequentially enrolled in a dose block of 250, 500, 750, and 1000 mL. RESULTS: Sixty patients received hemoglobin raffimer (n = 30) or control (n = 30). Hemoglobin raffimer was well tolerated. Most (98%) adverse events were mild or moderate in severity. There was an expected dose-dependent increase in the incidence of blood pressure increases and jaundice in hemoglobin raffimer-treated patients. In a dose-pooled analysis of hemoglobin raffimer versus control, increased blood pressure (43% vs 17%), nausea (37% vs 33%), and atrial fibrillation (37% vs 17%) were the most frequently reported adverse events. All serious adverse events were considered unrelated or unlikely to be related to study drug. No hemoglobin raffimer-treated patient required an intraoperative allogeneic red blood cell transfusion, compared with 5 (17%) pentastarch-treated patients (P =.052). This advantage of hemoglobin raffimer was maintained at 24 hours after surgery (7% vs 37%; P =.010) and up to 5 days after surgery (10% vs 47%; P =.0034). CONCLUSIONS: Hemoglobin raffimer was not associated with any serious adverse events in patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation in a dose-response study up to 1000 mL. Hemoglobin raffimer was effective in facilitating decreased exposure or avoidance of allogeneic red blood cell transfusions when used in conjunction with intraoperative autologous donation.

Effect of NaHCO3 on cardiac energy metabolism and contractile function during hypoxemia.

OBJECTIVE: To examine the impact of administration of NaHCO3 on contractility and energy metabolism of the myocardium during hypoxemia. METHODS: Regional myocardial hypoxia was induced in the left anterior descending (LAD) artery myocardium in anesthetized, open-chest dogs, using a perfusion circuit between the right atrium and the LAD artery, and a membrane oxygenator. The rate of flow in LAD artery was maintained constant with the use of a roller pump. During hypoxia, eight dogs were administered isotonic NaHCO3 in the circuit and six other dogs received equimolar NaCl. Myocardial contractile function was assessed using sonomicrometry for measurement of percentage of systolic shortening and preload recruitable stroke work. Oxygen consumption and the rate of appearance of lactate were measured. Clamp-frozen tissue samples were obtained at the end of the experiment from the hypoxic LAD myocardium and the nonhypoxic circumflex myocardium for measurement of tissue lactate level. RESULTS: During hypoxia, there was a significant decrease in oxygen consumption by the LAD myocardium (35 +/- 7 micromol/min in the NaCl group and 40 +/- 7 micromol/min in the NaHCO3 group during hypoxia vs. 131 +/- 11 micromol/min during aerobic perfusion). There was also a significant decrease in myocardial contractility as measured by percentage of systolic shortening (14 +/- 3% to -8 +/- 3%); NaHCO3 infusion during hypoxia did not improve myocardial contractility (-7 +/- 2%). Similar results were obtained with measurements of preload recruitable stroke work. The rate of production of lactate during hypoxia was substantially lower than expected, based on the calculated oxygen deficit, and was not significantly increased by the administration of NaHCO3 (33 +/- 9 micromol/min in the NaCl group and 51 +/- 5 micromol/min in the NaHCO3 group). Tissue lactate was not statistically different in the hypoxic myocardium supplied by the LAD artery and the nonhypoxic myocardium supplied by the circumflex artery in either group. CONCLUSION: The response of the myocardium to hypoxia is to decrease its mechanical work and metabolic demand. The infusion of NaHCO3 did not enhance myocardial contractile function or flux in glycolysis during hypoxia. We speculate that this diminished mechanical work and metabolic demand may represent an adaptive response to preserve cellular integrity until oxygen delivery is restored.

Distribution of pulmonary blood flow in the perfluorocarbon-filled lung.

OBJECTIVE: Partial liquid ventilation (PLV) improves gas exchange in animal studies of lung injury. Perfluorocarbons (PFCs) are heavy liquids and are therefore preferentially delivered to the most dependent areas of lung. We hypothesised that improved oxygenation during PLV might be the consequence of a redistribution of pulmonary blood flow away from poorly ventilated, dependent alveoli, leading to improved ventilation/perfusion (V/Q) matching. This study investigated whether partially filling the lung with PFC would result in a redistribution of pulmonary blood flow. DESIGN: Prospective experimental study. SETTING: Hospital research institute laboratory. PARTICIPANTS: Six anaesthetised pigs without lung injury. INTERVENTIONS: Animals were anaesthetised and ventilated (gas tidal volume 12 ml/kg, PEEP 5, FIO2 1.0, rate 16). Whilst the pigs were maintained in the supine position, regional pulmonary blood flow was measured during conventional gas ventilation and repeated during PLV. Flow to regions of lung was determined by injection of radioactive microspheres (Co(57), Sn(113), Sc(46)). Measurements were performed with ventilation held at end-expiratory pressure and, in two PLV animals only, repeated with ventilation held at peak inspiratory pressure. RESULTS: During conventional gas ventilation, blood flow followed a linear distribution with the highest flow to the most dependent lung. In the lung partially filled with PFC a diversion of blood flow away from the most dependent lung was seen (p = 0.007), resulting in a more uniform distribution of flow down the lung (p = 0.006). Linear regression analysis (r2 = 0.75) also confirmed a difference in distribution pattern. On applying an inspiratory hold to the liquid-containing lung, blood flow was redistributed back towards the dependent lung. CONCLUSIONS: Partially filling the lung with PFC results in a redistribution of pulmonary blood flow away from the dependent region of the lung. During PLV a different blood flow distribution may be seen between inspiration and expiration. The clinical significance of these findings has yet to be determined.

Death in two Canadian intensive care units: institutional difference and changes over time.

OBJECTIVE: To study and compare the mode of death in two different institutions' intensive care units (ICUs) for the two time periods, 1988 and 1993. DESIGN: Retrospective chart review. SETTING: Medical/surgical/trauma ICUs in two tertiary care teaching hospitals. PATIENTS: Patients dying in the medical/surgical/trauma ICUs between January 1, 1988 and December 31, 1988; and January 1, 1993 and December 31, 1993. Data collection included demographics, origin of admission, date of ICU admission, date of death, Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic categories, APACHE II physiologic variables, organ system failures present at the time of admission and 24 hrs before death, and mode of dying. APACHE II scores and mortality risk were calculated. Data analysis included a multiple analysis of variance to assess overall effect, with subsequent analyses of variance to assess the effect of institution and year on each individual dependent variable. All results are reported as mean +/- SEM values. RESULTS: A total of 439 charts were reviewed. Gender, age, and origin of admission were not different between the 2 yrs or the two institutions. Mean APACHE II scores and organ system failures were lower at Hospital A in 1998 vs. Hospital B, as was predicted mortality. These factors increased at Hospital A in 1993 and were similar to those at Hospital B. Withdrawal of support was much more common in 1993 than 1988 at both institutions (43% at Hospital A and 46% at Hospital B in 1988 vs. 66% at A and 80% at B in 1993), increasing to a greater extent in 1993 at Hospital B (p<.05). Length of stay in the ICU was significantly longer at Hospital A than at Hospital B in 1988 (9.4+/-1.4 vs. 4.3+/-0.6 days; p<.05) and in 1993 (8.2+/-2.9 vs. 3.8+/-0.5 days; p < .05). CONCLUSIONS: There has been an increase in withdrawal of life support, in recent years, at both the institutions studied. Differences exist between institutions with respect to end-of-life decisions in the ICU. These differences are likely representative of widely prevalent regional differences and are the result of many factors.

The use of transesophageal echocardiography for preload assessment in critically ill patients.

UNLABELLED: IV volume is often administered to patients in an intensive care unit (ICU) to improve cardiovascular function. We investigated the relationship between stroke volume (SV) and left ventricular (LV) size by using transesophageal echocardiography (TEE) in a population of 20 ICU patients and 21 postoperative cardiac surgical patients. We also examined whether LV end diastolic area (EDA), by TEE, could identify patients who increased SV by 20% or more (responders) after 500 mL of pentastarch administration. There was only a modest relationship (r = 0.60) between the EDA and the SV in all patients. No relationship could be found between the pulmonary capillary wedge pressure (PCWP) and the EDA in all patients. Both responder and nonresponder PCWP increased significantly after volume administration. Only responder EDA increased significantly after volume administration. Responders had significantly lower EDA (15.3 +/- 5.4 cm(2)) and PCWP (12.2 +/- 2.2 mm Hg) when compared with nonresponders (20.2 +/- 4.8 cm(2)) and 15.9 +/- 3.1 mm Hg, respectively). Few ICU patients and only those with a small EDA responded to volume administration. It was not possible to identify an overall optimal LV EDA below which most patients demonstrate volume-recruitable increases in SV. IMPLICATIONS: In a ventilated intensive care unit and cardiac surgical population, transesophageal echocardiography and pulmonary artery catheter are sensitive in detecting changes in preload after volume administration. Few patients demonstrate volume-recruitable increases in stroke volume when compared to cardiac surgical patients. It is not possible to establish an overall end diastolic threshold below which a large proportion of ventilated patients respond to volume administration.

Phase 2 studies of adenosine cardioplegia.

BACKGROUND: Laboratory evidence supports the use of adenosine-supplemented cardioplegia. An initial phase 1 dose-ranging clinical evaluation demonstrated that an adenosine concentration of 15 mumol/L could be safely administered with warm blood cardioplegia and suggested that phase 2 studies were warranted. METHODS AND RESULTS: Two separate double-blind, randomized, placebo-controlled trials were performed in patients undergoing primary, isolated, nonemergent coronary artery bypass graft surgery. Patients were randomized to receive adenosine 15 mumol/L versus placebo in the first study (n = 200) and adenosine 50 or 100 mumol/L versus placebo in the second study (n = 128). Adenosine was infused with both initial and final doses of warm antegrade blood cardioplegia. The data from the 2 trials were combined using the methods of Mantel and Haenszel, and the results of the meta-analysis are presented as the relative risk with their associated 95% confidence intervals (CI). The different study groups were comparable with respect to all preoperative clinical characteristics, angiographic findings, and intraoperative variables. In both trials 1 and 2, no differences were found between groups in the incidence of the individual primary or secondary outcomes. Similarly, when both studies were combined, there was no significant evidence of any consistent treatment benefit (primary: death: relative risk [RR] = 1.02, 95% CI = 0.06, 16.6; myocardial infarction by CK-MB: RR = 0.84, CI = 0.54, 1.31; low output syndrome: RR = 1.38, CI = 0.29, 6.42; any of the above: RR = 0.98, CI = 0.78, 1.25; secondary: Q-wave myocardial infarction: RR = 1.30, CI = 0.41, 4.13; myocardial infarction by troponin T: RR = 0.7, CI = 0.40, 1.21; inotrope requirement: RR = 0.9, CI = 0.46, 1.79; intra-aortic balloon pump requirement: RR = 0.6, CI = 0.07, 4.81; P > 0.20). CONCLUSIONS: Despite promising experimental data, adenosine supplementation of warm blood cardioplegia did not demonstrate any statistically significant benefit in patients undergoing elective coronary artery bypass graft surgery. Although sample sizes were relatively small, based on our interim analyses, it is unlikely that increased patient enrollment would reveal any substantive clinical differences between groups.

Hyperglycemia during normothermic cardiopulmonary bypass: the role of the kidney.

BACKGROUND: Hyperglycemia commonly occurs during cardiopulmonary bypass. We studied the quantitative impact of glucose input and its renal excretion on hyperglycemia during cardiopulmonary bypass. METHODS: The quantity of glucose infused and metabolite and hormone concentrations in plasma, as well as oxygen consumption, carbon dioxide production, and renal glucose excretion, were determined before, during, and after cardiopulmonary bypass in 8 patients. RESULTS: Hyperglycemia (14 to 29 mmol/L) was accompanied by an increase in plasma insulin levels. The degree of hyperglycemia was directly related to the amount of glucose infused. The rate of oxygen consumption did not decrease and the rate of urea appearance (gluconeogenesis) did not rise. Despite a very high filtered load of glucose, there was very little glucosuria, indicating a markedly enhanced renal absorption of glucose. CONCLUSIONS: Hormonal and metabolic factors permit the development of hyperglycemia during cardiopulmonary bypass but its severity depends on the quantity of glucose infused and, what appears to be a new finding, a markedly enhanced renal reabsorption of filtered glucose. Thus the kidney plays an important role in the development of severe hyperglycemia during cardiopulmonary bypass.

Effect of aortic cannula characteristics and blood velocity on transcranial doppler-detected microemboli during cardiopulmonary bypass.

OBJECTIVES: Cerebral microemboli are responsible to a large extent for the neuropsychiatric deficits after cardiac surgery. Differences in cannula size during cardiopulmonary bypass (CPB) will result in different velocities of blood exiting the aortic cannula. This study determined whether the number of transcranial Doppler (TCD)-detected emboli in the middle cerebral artery (MCA) during CPB correlated with blood speed or the direction of flow as determined by the shape of the aortic cannula. DESIGN: Patients were studied prospectively for evidence of TCD-detected emboli. If patients met the inclusion criteria, the choice of cannula was determined by surgical preference. SETTING: All studies were conducted at a single tertiary care academic cardiac surgery hospital by a single observer. PARTICIPANTS: Thirty-two patients undergoing first-time elective aortocoronary bypass surgery who were free of neurologic dysfunction or peripheral vascular disease and weighed 60 to 85 kg were studied. Patients who had other concurrent cardiac operations or who were in cardiogenic shock were excluded. INTERVENTIONS: Three aortic cannula types for elective aortocoronary bypass surgery were used: 24F curved (n = 19), 24F straight (n = 6), and 22F straight (n = 7), with internal diameters (IDs) of 7.2, 6.6, and 5.9 mm, respectively. TCD-detected emboli were identified in the MCA. MEASUREMENTS AND MAIN RESULTS: The rate of TCD-detected emboli (0.02 to 11.4 emboli per minute) was not related to the velocity of blood (46 to 77 cm/s) and was not affected by the choice of either a straight or curved aortic cannula. CONCLUSIONS: The choice of a straight or curved aortic cannula or of a 24F versus 22F cannula may not be important with respect to the number of cerebral microemboli.