Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.

BACKGROUND: A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes. METHODS: We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme. RESULTS: Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program that is institution based, accepted by all health care providers, and that involves well thought out transfusion algorithms to guide transfusion decisions. CONCLUSIONS: Based on available evidence, institution-specific protocols should screen for high-risk patients, as blood conservation interventions are likely to be most productive for this high-risk subset. Available evidence-based blood conservation techniques include (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease postoperative bleeding (eg, antifibrinolytics), (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing interventions), (3) interventions that protect the patient's own blood from the stress of operation (eg, autologous predonation and normovolemic hemodilution), (4) consensus, institution-specific blood transfusion algorithms supplemented with point-of-care testing, and most importantly, (5) a multimodality approach to blood conservation combining all of the above.

Controlled ventilation using isoflurane with an in-circle vaporiser.

We studied 19 patients anaesthetised for routine surgery using isoflurane delivered from a Komesaroff vaporiser mounted within a circle system. Their lungs were ventilated using a Penlon Nuffield ventilator attached to the circle system by a trunk of tubing. Fresh gas flow rates of 1, 2 or 31.min-1 were used. The inspired agent concentration was measured using a Datex Ultima multigas analyser and was found to be stable and easily controlled.

Respiratory feedback effects on vaporisers in circle systems.

We studied a group of spontaneously breathing patients anaesthetised for routine orthopaedic surgery using a circle system and isoflurane in a Komesaroff vaporiser within the circle. We observed and recorded: (1) the change in inspired isoflurane concentration caused by changing the fresh gas flow, (2) the increased respiration produced by surgical stimulus and the resulting increase in isoflurane concentration, (3) the respiratory depression produced by opioids and the consequent decrease in isoflurane concentration. We consider this regulation of anaesthetic uptake by the patient to be beneficial.

Isoflurane concentrations using uncompensated vaporisers within circle systems.

In a series of studies designed to investigate the need for a temperature-compensated vaporiser for use in a circle system, we first studied temperature changes within and isoflurane concentration delivered by a Komesaroff vaporiser during bench tests using different gas flows. Agent temperature and vapour concentration decreased as predicted by the Antoine equation. Using the vaporiser within a circle system during clinical anaesthesia, we then studied 20 patients breathing spontaneously and a further 10 patients receiving controlled ventilation, measuring the temperature of the agent within the vaporiser and the concentration of agent inspired by a the patient. In clincial use with the frest gas flows of 1-3.min-1, the inspired agent concentration did not decrease despite the decrease in temperature of the liquid isoflurane in the vaporiser.

Components of the inspiratory-arterial isoflurane partial pressure difference.

We have measured the partial pressure of isoflurane simultaneously in inspired gas (PIiso), end-expired gas (PE'iso), mixed-expired gas (PEiso), arterial (Paiso) and mixed venous blood (Pviso) in six patients (aged 57-79 yr) anaesthetized with nitrous oxide, oxygen and isoflurane before surgery and after PE'iso had been stable for at least 15 min. We related these changes to the various indices of pulmonary maldistribution to determine if they were sufficient to explain reported differences between PE'iso and Paiso. Alveolar deadspace dilution of end-expired gas was calculated for carbon dioxide and this dilution factor used to calculate the "ideal" alveolar Piso (PAiso) from the observed inspired and end-expired concentrations. Shunt fraction was measured for oxygen and then used to calculate the partial pressure of isoflurane in the pulmonary end-capillary blood (Pc'iso) from the partial pressure in arterial and mixed venous blood. Mean (SE) values were: PIiso 0.69 (0.05) kPa; PE'iso 0.52 (0.04) kPa; PAiso 0.50 (0.04) kPa; Pc'iso 0.38 (0.04) kPa; Paiso 0.35 (0.03) kPa and Pviso 0.22 (0.02) kPa; Paiso: PE'iso 0.66 (0.02) kPa. The mean "ideal" alveolar to pulmonary end-capillary Piso difference was 0.12 (0.01) kPa and highly significant (P < 0.001). Paiso was substantially less than PE'iso but, for isoflurane, the difference was reasonably constant (range 0.14-0.22 kPa). The difference was attributable in part to the effects of shunt and deadspace, but also a failure of equilibration of isoflurane between the alveolar gas and pulmonary end-capillary blood. It is likely to be different for other anaesthetics. We conclude that, while PE'iso may adequately reflect Paiso for isoflurane, it cannot be assumed that the relation between end-expiratory gas and arterial partial pressures is the same for all anaesthetics.

Aprotinin inhibits platelet adhesion to endothelial cells.

Studies were conducted to assess the effect of the serine protease inhibitor aprotinin on platelet adherence to both thrombin-stimulated and unstimulated human umbilical vein endothelial cells. Aprotinin treatment reduced significantly the adherence of platelets to endothelium pretreated or not with thrombin. In addition, aprotinin similarly reduced the adherence of platelets to plastic or collagen-coated tissue culture wells suggesting that the main site of action of the drug in this system is on the platelets. The role of endothelium-derived relaxing factor (EDRF; nitric oxide) in these platelet-endothelium reactions was investigated by prior incubation of both platelets and endothelial cells with NG-monomethyl-L-arginine (L-NMMA) which prevents the production of nitric oxide. The results demonstrated that nitric oxide was a significant inhibitor of the thrombin-induced platelet adherence in this assay system. Treatment with aprotinin in the presence or absence of L-NMMA reduced adherence of platelets to equivalent levels suggesting that aprotinin acts directly on the platelets via a mechanism that is EDRF-independent, to inhibit adherence.

Aprotinin does not inhibit the release of PGI2 or vWF from cultured human endothelial cells.

The release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin had any effects on these endothelial cell reactions. These end-points were chosen to indicate if this serine protease inhibitor caused alterations in the control of haemostatic function by endothelium, in the light of the improvement in haemostasis seen in patients given aprotinin therapy at the time of open heart surgery. Stimuli used to promote secretion of prostacyclin and vWF were human alpha-thrombin, histamine, protamine sulphate, poly-L-lysine and phorbol myristate acetate. Aprotinin (30 microMs) had no significant effect on the basal or stimulated release of PGI2 or vWF from HUVEC.

Comparison of oxygen consumption measurements: indirect calorimetry versus the reversed Fick method.

OBJECTIVE: To compare measurement of oxygen consumption (VO2) by spirometry and the reversed Fick method. DESIGN: Within-patient comparison using simultaneous measurements by the two methods, one previously calibrated on a metabolic simulator. PATIENTS: Twenty sets of observations on eight patients (57 to 83 yrs) requiring mechanical ventilation in a critical care unit. INTERVENTIONS: None during or immediately before the measurements. MEASUREMENTS AND MAIN RESULTS: Duplicate pairs of measurements of VO2 were made with a previously validated spirometric technique and the reversed Fick method (Qt[CaO2 - CVO2]), where Qt is cardiac output, CaO2 is arterial oxygen content, and CVO2 is mixed venous oxygen content. The coefficient of variation of the difference between duplicate measurements by the former technique was only 2.53% compared with 10.4% for the latter. The mean VO2 measurement by the spirometric method was 285.7 +/- 40.7 (SD) mL/min standard temperature and pressure, dry (STPD) and for the reversed Fick method, the mean VO2 measurement was 249.3 +/- 38.5 mL/min STPD. The mean difference was 36.4 +/- 28.5 mL/min STPD (p less than .001). CONCLUSIONS: The repeatability of the spirometric method was four times better than the reversed Fick method. The latter gave a significantly lower value that probably, in part, reflects the VO2 of the lung, which is included in the spirometric method but not in the reversed Fick measurement.

Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen.

Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema. The time course of development of increased solute flux was assessed by the clearance of 99mTc-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung. These end points were related to the development of pulmonary edema by the measurement of the wet-to-dry weight ratio of the lung and the weight of fluid in the pleural cavity. No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred. By 60 h of exposure, pleural effusions had developed. The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux.

Evaluation of metabolic measuring instruments for use in critically ill patients.

We evaluated three commercial indirect calorimetry devices which are used during artificial ventilation. Commercial butane, which had an RQ of 0.615, consumes 6.40 ml oxygen, and produces 3.94 ml CO2/1 ml, was burned in a gas-tight combustion chamber in conjunction with the ventilation of a lung model. During combustion, the flow rate of butane was measured with a soapfilm flowmeter for the calculation of reference values of oxygen consumption (VO2) and CO2 production (VCO2). To investigate the effect of oxygen concentration on the accuracy of these instruments, measurements were carried out at FIO2 values of 0.3, 0.4, 0.5, and 0.6 with a fixed ventilation mode (tidal volume 500 ml; respiratory rate 16 breath/min, intermittent positive-pressure ventilation). For the Datex Deltratrac Metabolic Monitor, the mean relative errors of measured VO2, VCO2, and RQ were all within 4.0%, 2.9%, and 4.0%, respectively. For the Engstrom Metabolic Computer, the corresponding values were 1.4%, 5.7%, and 6.0%, and for the SensorMedics MMC Horizon, 5.7%, 2.9%, and 5.9%.

Validation of oxygen consumption measurements during artificial ventilation.

We describe a system for the absolute calibration of indirect calorimeters, under the conditions of artificial ventilation and increased inspired O2 concentration, in which butane, at a measured flow rate, is burned downstream of an artificial lung. One milliliter of butane requires 6.4 ml O2 for its combustion, and the respiratory quotient is 0.615. With the closed-circuit O2-replenishment method there was no significant systematic error in the measurement of either O2 consumption or CO2 output and a random error with a SD of 8.3 ml/min for O2 consumption and 6.3 ml/min for CO2 output. There were no significant differences in the errors with inspired O2 concentrations between 23.8 and 59.5% and O2 consumptions between 89 and 366 ml/min.

Short term effect of nitrous oxide on methionine and S-adenosyl methionine concentrations.

Concentrations of methionine and S-adenosyl methionine (SAM) have been measured in various tissues of rats exposed to 50% nitrous oxide for periods up to 80 min, a time by which there is detectable interference with thymidine synthesis in bone marrow. There were no significant changes of either SAM or methionine in plasma, whole blood or brain. Hepatic SAM was unchanged, but there was a highly significant reduction in hepatic methionine, to 62% of control, after 80 min exposure to nitrous oxide.

Rate of inactivation of human and rodent hepatic methionine synthase by nitrous oxide.

The rate of inactivation of hepatic methionine synthase by nitrous oxide has been determined in 22 patients undergoing laparotomy during general anesthesia, including 70% nitrous oxide. Mean half-time of inactivation was 46 min. Metabolic consequences of nitrous oxide are, thus, critically dependent on the duration of anesthesia, and are unlikely to be significant during exposures of less than 40 min. Inactivation of methionine synthase is very much more rapid in the rat exposed to 50% nitrous oxide, with a half-time of 5.4 min.