Beginning Of Bypass Research Articles

Clinical Evaluation of the Accuracy and Precision of the CDI 500 In-line Blood Gas Monitor With and Without Gas Calibration

During cardiopulmonary bypass blood gases can be analyzed with laboratory equipment or with an in-line monitor giving instant results. The manufacturer of the CDI 500 in-line blood gas monitor recommends gas calibration before use. In acute cases there may not be time to perform a gas calibration. We hypothesized that after calibration against laboratory results, the CDI values of pH, pO2, and pCO2 will keep the same level of accuracy, whether the CDI has been gas calibrated or not. We performed a prospective randomized observational study using a study group without gas calibration (29 patients) and a control group with gas calibration (29 patients). Blood sampling was done at the beginning of bypass, and 30 minutes later. After each blood sample the CDI was in-vivo calibrated to the values simultaneously obtained from the ABL. Before in-vivo calibration values from the CDI without gas calibration were significantly different from the ABL-values in accuracy as well as precision, whereas the results from the gas calibrated CDI were largely consistent with the ABL. Before in-vivo calibration, the CDI without gas calibration was completely unreliable. After in-vivo calibration there was no statistical difference between the values of the CDI with and without calibration. We recommend gas calibration of the CDI before use in the period before in-vivo calibration.

Altered gene expression following cardiopulmonary bypass and circulatory arrest.

This study investigated the effects of normothermic cardiopulmonary bypass (CPB) and circulatory arrest (DHCA) on expression of specific genes in neonatal piglet brain. CPB was performed through the chest at 100 ml/kg/min for 2 hrs at 37 degrees C. In the second group of animals, CPB was begun as described above and then animals were cooled to a nasopharyngeal/brain temperature of 18 degrees C. When the brain temperature reached 18 degrees C, the CPB circuit was turned off. After 60 min of circulatory arrest (DHCA), CPB was resumed at 100 ml/kg/min, and the piglets were rewarmed to a temperature of 36 degrees C. In both groups, the animals remain sedated, paralyzed, mechanically ventilated, and continuously monitored throughout a four hour study period after CPB. Oxygen pressure in the microvasculature of the cortex was measured by oxygen dependent quenching of phosphorescence. The aRNA technique was used to assess mRNA steady-state levels in the brain tissue. Control oxygen pressure (pre-bypass) was 61 +/- 5 Torr and during CPB this decreased to 32 +/- 7 Torr on the beginning of bypass and to 36 +/- 5 Torr at the end of bypass. During the recovery period, cortical oxygenation steadily decreased, reaching 29 +/- 8 Torr at the end of the four hours period. Cortical oxygen decreased during DHCA to near zero and during rewarming and recovery increased to 35 +/- 6 Torr. Measurements of gene expression following CPB revealed significantly increased levels of mRNA for NMDAR1, DARPP-32, CamKII, GluR1, and D1AR. DHCA caused changes similar to those for CPB in levels of mRNA for NMDAR1, DARPP-32, CamKII and GluR1. In contrast, DHCA caused significantly increased levels of mRNA for GluR6 and GABRB1. There was no significant alteration in the level of D1AR following DHCA. The results showed that DHCA caused much larger alterations in gene expression in the critical metabolic signaling pathways tested than did CPB.

Brain oxygenation during cardiopulmonary bypass and circulatory arrest.

Quantitative measurements of oxygen distribution in the microcirculation of the brain cortex of newborn piglets were made during different modes of cardiopulmonary bypass. Three groups of animals, anesthetized and mechanically ventilated, were studied. The first group of animals were maintained on normothermic cardiopulmonary bypass (CPB) at a flow of 100 ml/kg/min, while the second and third groups underwent low flow hypothermic cardiopulmonary bypass (40 ml/kg/min at 18 degrees C) (LFCPB) and deep hypothermic (18 degrees C) circulatory arrest (DHCA), respectively. After bypass, the piglets were monitored for a two hours post-bypass recovery period. CPB caused a decrease in the cortical oxygen from 62 +/- 3 mm Hg to 32 +/- 7 mm Hg at the beginning of bypass and to 36 +/- 5 mm Hg at the end of bypass. During the recovery period, cortical oxygenation steadily decreased, reaching 29 +/- 8 mm Hg at the end of the experiment. With initiation of LFCPB, cortical oxygen decreased to 22 +/- 7 mm Hg. Upon rewarming cortical oxygen increased to 37 +/- 5 mm Hg and then decreased again to about 30 mm Hg at the end of two hours of post-bypass recovery. Similar changes in cortical oxygenation were observed during DHCA. In DHCA cortical oxygen decreased to 19 +/- 4 mm Hg and during rewarming and recovery increased to 35 +/- 6 mm Hg. In conclusion, it has been shown that in newborn piglets recovering from CPB, LFCPB and DHCA, when the blood pressure remained above 55 mm Hg and therefore total blood flow should be well maintained, oxygen pressure in the microvasculature is significantly lower than for pre-bypass. It is suggested that the decreased oxygenation is due to increased heterogeneity in resistance in the microcirculatory units, resulting in broadened distribution of flow rates and oxygen levels.

Jugular venous bulb oxygen saturation in patients with preexisting diabetes mellitus or stroke during normothermic cardiopulmonary bypass.

The authors hypothesized that patients with cerebrovascular abnormalities or metabolic disorders may experience abnormality in cerebral circulation more frequently than patients without these risks. The current study attempted to assess jugular venous bulb oxygen saturation (SjvO2) in patients with preexisting diabetes mellitus or stroke undergoing normothermic cardiopulmonary bypass. Thirty-nine patients undergoing elective coronary artery bypass graft surgery were studied, including 19 age-matched control patients, 10 diabetic patients, and 9 patients with preexisting stroke A 4.0-French fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor internal SjvO2. Hemodynamic parameters and arterial and jugular venous blood gases were measured at seven time points: (1) after the induction of anesthesia and before the start of surgery, (2) just after the beginning of cardiopulmonary bypass, (3) 20 min after the beginning of bypass, (4) 40 min after the beginning of bypass, (5) 60 min after the beginning of bypass, (6) just after the cessation of bypass, and (7) at the end of the operation. No significant differences were seen in mean arterial pressure, arterial carbon dioxide tension (PaCO2), or hemoglobin concentration among the three groups during the study. The SjvO2 value did not differ among the three groups after anesthesia induction and before surgery, just after the beginning of cardiopulmonary bypass, 60 min after the beginning of bypass, just after the end of bypass, or at the end of the operation. Significant differences between the control group and the diabetic and stroke groups were observed, however, at 20 min and 40 min after the beginning of bypass (at 20 min: control group 62.2 +/- 6.8%, diabetes group 48.4 +/- 5.1%, stroke group 45.9 +/- 6.3%; at 40 min: control group 62.6 +/- 5.2%, diabetes group 47.1 +/- 5.2%, stroke group 48.8 +/- 4.1% [values expressed as the mean +/- SD]; P < 0.05). Also, values in the diabetes and stroke groups were decreased at 20 min and 40 min after the beginning of bypass compared with before the start of surgery. A reduced SjvO2 value was observed more frequently in patients with preexisting diabetes mellitus or stroke during normothermic cardiopulmonary bypass. It is possible that cerebral circulation during normothermic bypass is altered in patients with risk factors for cerebrovascular disorder.

EVALUATION OF A NEW BEDSIDE ANALYZER FOR BLOOD COAGULATION DURING OPEN HEART SURGERY

S77 INTRODUCTION: In open heart surgery complex alterations of coagulation arise through heparinization, excessive foreign surface exposure to blood and hemodilution. Management of coagulation is thus still a problem. In various current studies thrombelastography (TEG), as a functional method for coagulation analysis, had a better predictive value in respect to bleeding complications that standard laboratory tests or other assays of platelet function [1,2]. However application of TEG is limited by complicated handling, high cost and low transportability. For the first time we have evaluated the ROTEG analyzer (NOBIS, Germany), an advancement of TEG, in open heart surgery. METHODS: Analogous to TEG the ROTEG continuously registers clot firmness. Parameters are coagulation time (r), clot formation time (k) and maximum clot firmness (MA). Through a new detection method the ROTEG is easily transportable and well suited to bedside operation. Up to four samples are analyzed in parallel and displayed on the screen. Citrated blood was sampled from 40 patients undergoing open heart surgery following informed consent. Timepoints were before induction of anesthesia, 45[prime] after beginning of bypass and at the end of the operation. Preund post-operatively intrinsically activated TEG (InTEG) was performed using Dapttin (an intrinsic activator, Immuno). During bypass due to high-dose heparinisation determination of InTEG is not possible. Therefore activation was performed using Ecarin (a heparin-unsusceptible activator, NOBIS, Germany). RESULTS: (p=0,05 vs. pre-op, Wilcoxon) (Table 1)Table 1DISCUSSION: Preoperative coagulation lied within the normal range. During and after bypass a significant prolongation of k and reduction of MA in comparison to preoperative test corresponds to the drop in platelet count and quality. The prolongation of r in the postoperative InTEG is attributed to residual heparin due to incomplete reversal or to own effects of protamin. ROTEG analysis could easily be performed inside the OR. This is a promising approach to improving coagulation management in cardiac surgery.

Clotting and fibrinolytic disturbance during lung transplantation: Effect of low-dose aprotinin

Patients undergoing lung transplantation are often confronted with a bleeding problem that may be due in part to the use of cardiopulmonary bypass and its activation of blood clotting and fibrinolysis. Objective: We performed a prospective study to determine whether and to what extent the clotting and fibrinolytic systems are being activated and whether low-dose aprotinin is effective in inhibiting blood activation during lung transplantation. Methods: Thirty lung transplantations performed on 29 patients were divided into a group with cardiopulmonary bypass alone ( n = 12), a group with cardiopulmonary bypass and 2 × 10 6 KIU aprotinin administered at the beginning of bypass in the pump prime ( n = 12), and a group without cardiopulmonary bypass ( n = 6). Serial blood samples were taken from the recipient before anesthesia, seven times during the operation, and 4 and 24 hours thereafter. Results: Results show that in the group having cardiopulmonary bypass alone, the concentration of the clotting marker thrombin/antithrombin III complex increased significantly during the early phase of the operation ( p < 0.01) and remained high until the end of the operation. Levels of tissue-type plasminogen activator, a trigger of fibrinolysis released by injured endothelium, also increased sharply in the early phase of the operation in the cardiopulmonary bypass group ( p < 0.01), followed by a significant increase in fibrin degradation products ( p < 0.01). In the aprotinin group, a significant reduction of thrombin/antithrombin III complex ( p < 0.05), tissue-type plasminogen activator ( p < 0.05), and fibrin degradation products ( p < 0.05) was observed in the early phase of the operation compared with levels in the bypass group, but these markers increased late during bypass associated with a significant drop ( p < 0.05) of plasma aprotinin level monitored by plasmin inhibiting capacity. In the nonbypass group, concentrations of thrombin/antithrombin III complex and tissue-type plasminogen activator also rose significantly ( p < 0.05) in the early phase of the operation, but the levels were significantly lower than those of the bypass group ( p < 0.05). Blood loss during the operation was 2521 ± 550 ml in the bypass group, 1991 ± 408 ml in the aprotinin/bypass group, and 875 ± 248 ml in the nonbypass group. Conclusion: These results suggest that clotting and fibrinolysis are activated during lung transplantation, especially in patients undergoing cardiopulmonary bypass. Aprotinin in a low dose significantly reduced activation of clotting and fibrinolysis in the early phase of the operation but not during the late phase of lung transplantation. (J T HORAC C ARDIOVASC S URG 1996;112:599-606)

A clinical study on the effects of pulsatile cardiopulmonary bypass on the blood endotoxin levels

Levels of endogenous endotoxins have been reported to increase after cardiopulmonary bypass. Endotoxin levels have also been implicated in multiple organ failure and may contribute to the immunocompromised state seen after bypass. We evaluated the effects of pulsatile cardiopulmonary bypass circulation on endogenous endotoxin levels. The study population consisted of 15 consecutive adult patients who underwent cardiac operations with cardiopulmonary bypass. Pulsatile flow was used during aortic crossclamping in eight patients (group I) and nonpulsatile flow was used in the remaining seven patients (group II). Changes in blood endotoxin levels were monitored during aortic crossclamping, after release of the clamp, and after weaning from bypass. The blood endotoxin level at each stage was expressed as a percentage of the level at the beginning of bypass. Group I patients a significantly lower blood endotoxin percentage than group II (from 20 to 120 minutes after the initiation of aortic crossclamping). In group I, the blood endotoxin percentage was nearly constant during aortic crossclamping. After release of aortic crossclamping, group I also had a lower blood endotoxin percentage than group II. Endogenous endotoxin levels appear to increase in the presence of intestinal congestion and ischemia. Improvement in intestinal circulation by pulsatile cardiopulmonary bypass may prevent increases in endogenous endotoxin levels by reducing these factors. (J THORAC CARDIOVASC SURG 1994;108:620-5)

Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass

To determine the cytokine release during normothermic cardiopulmonary bypass, we have measured plasmatic levels of tumor necrosis factor-α and interleukins-1β, 6, and 8 in 10 patients during the first 24 hours after the start of bypass. Arterial blood samples were collected at intervals before, during, and after bypass. Interleukin-1β was not detectable in the plasma, and traces of tumor necrosis factor-α were detected in only three patients at times independent of the cardiopulmonary bypass procedure. Circulating endotoxin remained undetectable. Plasma interleukin-6 and interleukin-8 rose significantly from 2 until 24 hours after the start of bypass (p < 0.05) and peaked respectively at 4 and 2 hours after the beginning of bypass (interleukin-6, 268.1 ± 131.43 pg/ml; interleukin-8, 370 ± 420 pg/ml; mean peak ± standard deviation). Peak values of interleukin-6 and interleukin-8 were correlated neither with the duration of aortic crossclamping or the bypass procedure nor with the hemodynamic parameters recorded at the same times. This study shows that normothermic cardiopulmonary bypass does not induce systemic release of tumor necrosis factor-α and interleukin-1β. A local production of these cytokines cannot be excluded, because interleukin-6 and interleukin-8 are produced by stimulated macrophages and monocytes in response to tumor necrosis factor-α and interleukin-1β. Our results, at normothermia, show a similar pattern of interleukin-6 and interleukin-8 release when compared with release during hypothermic cardiopulmonary bypass. Interleukin-8, an important chemotactic neutrophil factor, might play a role in reperfusion injuries observed in lungs and heart after cardiopulmonary bypass. (J THORAC CARDIOVASC SURG 1994;108:636-41)

Myeloperoxidase and elastase as markers of leukocyte activation during cardiopulmonary bypass in humans

To assess leukocyte activation during cardiopulmonary bypass, we measured white blood cell and neutrophil counts and lysosomal enzyme release, especially myeloperoxidase and elastase, throughout the operation and for 5 days postoperatively. A newly developed double antibody radioimmunoassay of myeloperoxidase and an enzyme-linked immunosorbent assay for detection of the polymorphonuclear elastase-alpha 1-proteinase inhibitor complex were used to determine their plasma levels in 15 patients undergoing elective aorta-coronary bypass grafting. Preoperatively white blood cell counts and plasmatic levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor were normal. Because no correlation has yet been established between levels of myeloperoxidase and elastase-alpha 1-proteinase inhibitor, the aim of this prospective study was to evaluate the use of these enzyme levels as markers for leukocyte activation in vivo. We addressed the clinical situation of cardiopulmonary bypass because it offered the possibility of monitoring the comparative evolution of blood levels of these enzymes in parallel to white blood cell counts through well-defined steps corresponding to known events. We document the advantages of myeloperoxidase blood levels over elastase measurement as reflecting more rapidly the in vivo activation of leukocytes. The time course kinetics of these three measurements were not parallel. White blood cell counts remained stable at the beginning of bypass, whereas myeloperoxidase levels increased sharply and continuously as soon as bypass was instituted until the end of bypass. Elastase levels also increased, but later than myeloperoxidase, beginning when the patients was rewarmed. High elastase plasma levels persisted later than myeloperoxidase after bypass, in parallel with white blood cell counts. It thus clearly appears that changes in myeloperoxidase levels more rapidly reflect the activation state of leukocytes induced by cardiopulmonary bypass and surgery, whereas peak levels of elastase were delayed and parallel to white blood cell counts. From this model, in which the evolution of leukocyte numbers could be followed in relation with known steps of stimulation, it appears that myeloperoxidase is a sensitive marker for monitoring in vivo activation of white blood cells.

Prostaglandin E2, prostacyclin, and thromboxane changes during nonpulsatile cardiopulmonary bypass in humans

To study the effect of lung bypass on the production of prostaglandin E2, prostacyclin, and thromboxane A2, we measured simultaneously arterial and venous plasma concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin), and thromboxane B2 (stable metabolite of thromboxane A2) before, during, and after cardiopulmonary bypass. Seventeen patients (age range 46 to 69 years) undergoing aorta-coronary bypass grafts were investigated. The prostaglandin E2 production rose sharply immediately after the onset of bypass (baseline: 9.7 +/- 2.9 pg/ml to 85 +/- 16.6 pg/ml in venous and 87 +/- 12 pg/ml in arterial plasma, p less than 0.03) and rapidly decreased after pulmonary reperfusion (53 +/- 6.4 and 57 +/- 20 pg/ml, respectively, in venous and arterial plasma at the end of bypass). The increase in prostaglandin E2 was influenced by the heart-lung machine itself (as demonstrated by a closed "bypass" circuit) and by lung bypass. Pulmonary metabolism of prostaglandin E2 was maintained after bypass. The prostacyclin production rose significantly at the beginning of bypass (154 +/- 26 pg/ml venous prebypass level to 361 +/- 94 pg/ml after aortic clamping, p less than 0.03). Prostacyclin decreased progressively during rewarming of the patient, pulmonary reperfusion, and discontinuation of bypass. When prostacyclin decreased, thromboxane B2 production rose significantly and reached peak arterial levels when the lungs were reperfused (112 +/- 33 pg/ml prebypass levels to 402 +/- 101 pg/ml, p less than 0.01). Except for prostaglandin E2, there were no significant differences between arterial and venous plasma levels of these substances. The same prostanoids were also measured in five patients undergoing major orthopedic operations, and no significant changes in prostanoids were observed. Our data demonstrate significant production of prostaglandin E2 in the systemic circulation during cardiopulmonary bypass in humans. They further indicate that lung bypass disturbs the plasma prostaglandin/thromboxane balance.

Ceftriaxone levels in blood and tissue during cardiopulmonary bypass surgery.

One gram of ceftriaxone was given intravenously to 15 patients approximately 2 h before cardiopulmonary bypass surgery. Ceftriaxone levels in plasma (mean +/- standard deviation) were 60.4 +/- 18.8 micrograms/ml (range, 17.0 to 96.0 micrograms/ml) at the beginning of bypass, 44.2 +/- 16.6 micrograms/ml (range, 9.4 to 78.6 micrograms/ml) at the end of bypass, and 19.6 +/- 9.6 micrograms/ml (range, 4.2 to 47.1 micrograms/ml) the following morning, 18.1 to 24.7 h after infusion of ceftriaxone. Concentrations in the sternal bone were 4.7 +/- 2.1 micrograms/g (range, 1.0 to 10.1 micrograms/g; tissue-to-plasma ratios, 0.066 +/- 0.036). Concentrations in the atrial appendage were 7.7 +/- 1.8 microgram/g (range, 3.6 to 10.2 micrograms/g; tissue-to-plasma ratios, 0.143 +/- 0.062). These data suggest that a single dose of ceftriaxone might be useful for prevention of infection due to susceptible pathogens.

Cellular chemical indices of right ventricular protection in children.

Myocardial preservation during open heart surgery in children was studied using biopsies of the right ventricle taken at the beginning and end of a bypass with a Tru-Cut biopsy needle. Three assessments were used: (1) semi-quantitative cytochemical grading of Baker's acid haematein reaction, and the distribution of succinate dehydrogenase and myosin ATPase; (2) microdensitometry of the succinate dehydrogenase activity; and (3) quantitative birefringence measurements to assess the response of the myocardial fibres to ATP and calcium. For each assessment, the values at the beginning and end of the bypass were compared. In a series of 42 children, two died in low cardiac output and three others required substantial inotropic support. No patient showed deterioration in the overall cytochemical assessment. Two patients showed deterioration in birefringence, one died and one had low cardiac output. The remaining three patients who had post-operative problems had low birefringence values at the beginning of bypass. Thirty-two patients were used for the microdensitometric assays, one died and three required substantial inotropic support. Succinate dehydrogenase activity decreased significantly during bypass in only two patients. One of these died and the other required substantial inotropic support.

Effects of systemic hypothermia on myocardial metabolism and coronary blood flow in the fibrillating heart

Ventricular fibrillation during normothermic cardiopulmonary bypass is deleterious to the myocardium. This study was undertaken to determine if moderate systemic hypothermia would protect the myocardium during ventricular fibrillation. Fourteen mongrel dogs were subjected to 1 hour, 15 minutes of total cardiopulmonary bypass. Ventricular fibrillation was induced by a continuous electrical alternating current applied at the beginning of bypass and lasting for 1 hour. Six animals were maintained at normothermia (Group I), and eight were cooled to 30 degrees C. for 1 hour (Group II). The hypothermic group (Group II) demonstrated lower myocardial oxygen consumption and metabolism, decreased coronary blood flow, and less myocardial lactate production during ventricular fibrillation than did Group I. It is concluded that hypothermia does offer some protection, although not complete, against the deleterious effects of ventricular fibrillation described previously.

The influence of anaesthetics on systemic vascular resistance during cardiopulmonary bypass.

The influence of various anaesthetic techniques was studied during total cardiopulmonary bypass with a disc oxygenator, high flow perfusion and mild hypothermia. Data were obtained from 52 adult patients undergoing corrective surgery for congenital or acquired heart disease. The material was randomly divided in two groups with 28 and 24 patients, respectively. Before perfusion, the same anaesthetic technique was applied to all patients. During perfusion, halothane was vapourized into the oxygenator at concentrations of 1.0–1.5% in group I. In group II, no halothane was used but 5–10 mg diazepam was supplied into the oxygenator at the beginning of bypass. To both groups small amounts of fentanyl were given during bypass.There were no significant differences in mean perfusion time and perfusion blood flow between the groups. Systemic vascular resistance increased in both groups during cardiopulmonary bypass and hypothermia. In group I, a significant increase did not occur until after 60 minutes (13%), where...