Jian-Sheng Wang

Monitoring of Heparin-induced Anticoagulation with Kaolinactivated Clotting Time in Cardiac Surgical Patients Treated with Aprotinin

High-dose aprotinin appears to enhance the anticoagulant effects of heparin, as documented by increases in the activated clotting times (ACTs) during cardiopulmonary bypass; hence, some authorities have advocated reducing the dose of heparin in patients treated with aprotinin. An in vitro study by our group suggested that the increase of the ACT in the presence of aprotinin and heparin may be due to the use of celite as surface activator. We compared celite and kaolin as surface activators for the measurement of the ACT in cardiac surgical patients treated with aprotinin and in patients given no aprotinin. This double-blind, randomized, placebo-controlled study included 30 patients, of whom 14 received aprotinin and 16 received a placebo. Before, during, and after cardiopulmonary bypass, the ACT was measured with two Hemochron 400 systems with 12 mg of either celite (C-ACT) or kaolin (K-ACT) used as surface activator and with one Hepcon HMS system (HR-ACT), which uses kaolin as activator. The latter also was used for measurement of the blood heparin concentration. The ACTs of blood without heparin did not differ between aprotinin and control patients. During anticoagulation with heparin and cardiopulmonary bypass, the average C-ACTs were 784 +/- 301 s (aprotinin) and 496 +/- 120 s (control) (P < .001); the K-ACTs were 502 +/- 131 s (aprotinin) and 458 +/- 101 s (control) (P > .05); the HR-ACTs were 406 +/- 87 s (aprotinin) and 423 +/- 82 s (control) (P > .05), which was consistently less than C-ACT and K-ACT.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines.

Cardiopulmonary bypass (CPB) impairs pulmonary endothelial injury in part by increasing expression of adhesion molecules that results in neutrophil influx. Although numerous proinflammatory cytokines up-regulate these responses, the extent to which systemic and pulmonary proinflammatory cytokines increase remains unknown. We therefore examined systemic and pulmonary gene expression and production of proinflammatory cytokines during CPB. Bronchoalveolar lavage and peripheral blood sampling were performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-&agr; (TNF-&agr;) was measured by semiquantitative polymerase chain reaction using &bgr;-actin as an internal standard. We also measured these cytokines in cultured alveolar macrophages and plasma monocytes in standard medium alone, or in the presence of lipopolysaccharide. We found 2- to 20-fold increases in gene expression for these cytokines in both plasma and alveolar leukocytes at the end of surgery. However, the increases were 4–8 times greater in alveolar than plasma leukocytes. Alveolar macrophages obtained at the end of surgery produced 1.5–3 times more IL-6, IL-8, and TNF-&agr; than those obtained at the beginning (P < 0.0001). Although plasma monocytes produced more IL-8 at the end of surgery (P < 0.001), TNF-&agr; and IL-6 did not increase. The production of all cytokines was 1.5–3 times greater in alveolar macrophages obtained at the end of surgery than in plasma monocytes obtained simultaneously (P < 0.005). Our data thus suggest that CPB provokes a greater pulmonary than systemic inflammatory response. Implications Both gene expression and production of proinflammatory cytokines were greater in alveolar than plasma leukocytes after cardiopulmonary bypass. These results suggest that cardiopulmonary bypass provokes more serious pulmonary than systemic inflammatory responses.

Thromboelastogram fails to predict postoperative hemorrhage in cardiac patients

To determine the clinical usefulness of the thromboelastogram in the prediction of postoperative hemorrhage in cardiac patients, we related the results of routine coagulation tests (RCTs) and thromboelastography with the amount of chest tube drainage postoperatively in 101 patients requiring cardiopulmonary bypass. Our data indicated that there was no correlation between RCT results and thromboelastographic variables. No single variable of RCTs and thromboelastography correlated well with the amount of chest tube drainage postoperatively. Before the onset of cardiopulmonary bypass, the most frequent abnormalities detected by thromboelastograms were fibrinolysis and hypocoagulability resulting from factor deficiency. Hypercoagulability detected by thromboelastograms occurred in 13% of patients after cardiopulmonary bypass and usually was not detected by RCTs. The incidence of false-negative thromboelastograms and RCT results in patients who had excessive hemorrhage of unknown cause was 46% and 52%, respectively. The incidence of fibrinolysis as detected by thromboelastograms was similar before and after bypass, but only 2 of the 18 patients with fibrinolysis had excessive hemorrhage postoperatively. Our results indicate that neither RCTs nor thromboelastography predicts the likelihood of excessive hemorrhage in patients after cardiopulmonary bypass. The thromboelastographic results should be interpreted cautiously because of the high rate of unreliable results.

Loss of alveolar macrophages during anesthesia and operation in humans

Pulmonary macrophages play an important role in the host defense against infection, and the importance of this role is probably enhanced when the upper airway defenses are circumvented by endotracheal intubation.Studies in animals suggest that exposure to volatile anesthetics compromises the viability and function of alveolar macrophages. We studied the effect of surgery and anesthesia on the alveolar macrophages of 41 human subjects undergoing lower abdominal procedures of varying lengths during nitrous oxide-isoflurane anesthesia. Alveolar macrophages were harvested from bronchoalveolar lavage fluid obtained before incision and compared to those recovered just before emergence from anesthesia. Macrophages were analyzed for aggregation and viability, assessed by the ability of viable cells to exclude trypan blue dye. Operations lasting 2 h or less led to little aggregation and had little effect on viability. However, there was a strong correlation between loss of macrophages and the duration of surgery and anesthesia. Aggregation increased and viability decreased as a function of procedure length. Studies are needed to determine whether prolonged surgery contributes to the incidence of postoperative pulmonary complications by disturbing the function and survival of alveolar macrophages in humans. (Anesth Analg 1995;81:1255-62)

Neutrophil Number and Interleukin-8 and Elastase Concentrations in Bronchoalveolar Lavage Fluid Correlate with Decreased Arterial Oxygenation After Cardiopulmonary Bypass

Atelectasis is a major cause of decreased arterial oxygenation after cardiopulmonary bypass (CPB). There is a close relationship between atelectasis and inflammatory responses. We therefore tested the hypothesis that neutrophil number and the concentrations of proinflammatory cytokines and elastase in plasma and bronchoalveolar lavage fluid correlate with changes in arterial oxygenation. Bronchoalveolar lavage was performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. Peripheral blood was sampled simultaneously. Arterial oxygenation was quantified by Pao2/fraction of inspired oxygen (Fio2) and intrapulmonary shunt (Qs/ Qt). Pao2/Fio2 and Qs/ Qt decreased significantly at the end of surgery, whereas neutrophil number, interleukin (IL)-6, IL-8, tumor necrosis factor-&agr;, and elastase concentrations in the lavage fluid increased significantly. The increase in neutrophil count from the lavage fluid correlated significantly with the increases in IL-8 and elastase concentrations. The increase in neutrophil number and IL-8 and elastase concentrations in the lavage fluid correlated significantly with Pao2/Fio2 and Qs/ Qt at the end of surgery. In contrast, none of the plasma values correlated with these variables. Significant correlation between immune mediators and decreased arterial oxygenation suggests that inflammatory responses in the distal airway are strongly related to a decrease in arterial oxygenation after CPB. Implications The increases in neutrophil number, interleukin-8, and elastase concentrations in bronchoalveolar lavage correlated significantly with decreases in arterial oxygenation. Our results suggest immunologic responses in the distal airway are closely related to pulmonary gas change.

Comparison of high-dose thrombin time with activated clotting time for monitoring of anticoagulant effects of heparin in cardiac surgical patients

The activated clotting time (ACT) is routinely used for monitoring of heparin effects during cardiopulmonary bypass (CPB). However, ACT is not a specific assay for heparin and may be influenced by several other factors, which may be misleading with regard to the proper administration of heparin and protamine. In this pilot study, we compared a new test, the high-dose thrombin time (HiTT), with the conventional ACT test for both in vitro and in vivo heparin-induced anticoagulation. Our in vitro results showed that there were heparin dose-dependent increases in ACT and HiTT. Data on 30 adult cardiac patients indicated that HiTT correlated well with heparin concentration both after initial heparin administration and during CPB (r = 0.645 and 0.515). Hypothermia and hemodilution occurring during CPB did not alter HiTT results. ACT also correlated well with both heparin concentration and HiTT before CPB, but the linear relationship was lost during CPB. Our results suggest that HiTT is a useful assay for monitoring heparin effects during cardiac surgery, even during hypothermia and hemodilution.

Leakage of disposable breathing circuits

STUDY OBJECTIVE To determine the sites and rates of the leakage of disposable breathing circuits. DESIGN Nonclinical, experimental study. SETTING Experimental laboratory. INTERVENTIONS To identify in vitro the leakage sites by bubble test and to measure the leakage rate by the increased oxygen (O2) flow needed to maintain the circuit pressure provided by an anesthesia machine previously verified to have no leaks. Breathing circuit pressures measured with a sphygmomanometer of 30, 50, 70, and 100 mmHg were studied. MEASUREMENTS AND MAIN RESULTS Ninety-seven disposable and three reusable breathing circuits from seven manufacturers were investigated for leakage. There was a linear relationship between the circuit pressure and O2 flow at which leaks occurred. No leakage was detected in reusable circuits at 30 mmHg of circuit pressure. Leakage was found in two of the six junctions between the patient adapter and the corrugated tubing in the reusable breathing circuits at a circuit pressure of 100 mmHg. In 90% of the disposable circuits tested, the leakage rate was less than 75 ml/min at 30 mmHg of circuit pressure, but there was a wide variation in the amount of leakage among the circuits of different companies. Almost all the leakage sites were located at connections in the circuit and not in the corrugated tubing. The most common site of leakage in the disposable circuits was the junction between the patient adapter end and the corrugated tubing (57%) rather than the swivel piece (40%). CONCLUSIONS Most disposable breathing circuits can be used safely for closed-circuit anesthesia, as the leakage volume is too small to be of clinical importance. The variation in the leakage rates stresses the importance of quality control of the connector seals.

Problems Associated with Coagulation Monitoring during Cardiovascular Surgery

Despite the success of cardiac surgery and the improvement of cardiopulmonary bypass (CPB) instruments, life-threatening bleeding after CPB remains a serious problem that necessitates transfusion of blood components in a high percentage of patients and sometimes requires re-exploration. The incidence of hemorrhage is 5% to 18% in patients who have undergone open-heart procedures (1-4). Many different disorders can occur in patients undergoing CPB; this complicates the identification of specific causes and often delays effective treatment. The modification of routine coagulation tests and the application of new methods of detecting and treating coagulation abnormalities are focused on the reduction of morbidity and mortality in CPB patients. Thromboelastography (TEG) has been utilized for guiding the therapy of postoperative hemorrhage in cardiac patients (5). A system for quantitative determination of heparin concentration is now commercially available, which may obviate the disadvantages of the routine activated clotting time (ACT) measurement. It has recently been reported that, because of the anticoagulation effects of aprotinin, the need for heparin can be reduced in patients given aprotinin (6).

Validity of Continuous Cardiac Output Measured by a Doppler Pulmonary Artery Catheter Versus Thermodilution, and Effect of Distal Angle on the Variance Between Methods

Continuous monitoring of cardiac output in patients with cardiac dysfunction or hemodynamic instability is desirable, especially if the patient is in critical condition. For the anesthesiologist, continuous monitoring of cardiac output may be helpful because it provides information which may allow more appropriate management of events during critical periods, such as weaning from cardiopulmonary bypass in cardiac surgery, or cross-clamping and declamping of the aorta in vascular surgery. A pulmonary artery catheter that allows both intermittent and continuous Doppler measurements of cardiac output has been developed (Flocath, Cardiometrics Inc., CA). In high-risk patients, we tested the hypothesis that the Doppler-estimated cardiac output (DECO) was identical to the thermodilutional cardiac output (TDCO), and that the DECO changed similarly in direction and magnitude when the TDCO changed. Further, we investigated the change in cardiac output with both techniques when the distal angle of the Flocath was altered.