Start Of Bypass Research Articles

Validation of a Dosing Strategy for Cefazolin for Surgery Requiring Cardiopulmonary Bypass.

A prospective, single center, open-label study was conducted to determine if the standard practice for surgical prophylaxis, which includes standardized dosing of cefazolin, at the University of Maryland Medical Center (UMMC) is adequate for patients placed on bypass during cardiac surgery. All patients were given the same standard dosing regimen regardless of weight: two grams of cefazolin administered within 1 h of incision, an additional one gram injected into the bypass circuit at the onset of bypass, and two grams every 3 h after the initial dose. Cefazolin serum concentrations were collected immediately after incision, after the start of bypass, each hour of bypass, at the end of bypass and at sternal closure. Ten patients were consented and completed the study with an average age of 62 y, average weight of 84.7 kg and average cardiopulmonary bypass time of 116 min. The free serum concentrations of cefazolin stayed above the pre-defined inhibitory threshold of 16 mcg/mL throughout the procedure for 100% of participants. The mean total serum concentration in the blood throughout surgery was 160 mcg/mL. No patients were found to have surgical site infections using standard criteria and no adverse events were observed. For patients undergoing cardiac surgery with cardiopulmonary bypass, the UMMC dosing regimen surpassed targeted cefazolin concentrations during the entire surgical procedure for all patients regardless of weight or time on bypass.

Sivelestat Attenuates Lung Injury in Surgery for Congenital Heart Disease With Pulmonary Hypertension

Pulmonary hypertension associated with congenital heart disease increases the risk of surgery using cardiopulmonary bypass. Sivelestat is a neutrophil elastase inhibitor thought to have a prophylactic effect against lung injury after surgery using bypass. We elucidated that Sivelestat had the protective effect on lung in patients with congenital heart disease and pulmonary hypertension who underwent surgery using bypass. This study was a controlled prospective randomized trial and enrolled 13 neonates or infants with ventricular septal defect and pulmonary hypertension. The patients were assigned to either sivelestat with the dose of 0.2 mg/kg per hour (sivelestat group, n= 7) or saline (placebo group, n= 6) from the start of bypass until 6 hours after bypass. Proinflammatory cytokines and adhesion molecules on leukocytes were measured at 10 time points during the above period. Pulmonary function was assessed perioperatively. Compared with the placebo group, the sivelestat group had significantly lower values of alveolar-arterial oxygen tension gradient at 24 hours (p= 0.038) and at 48 hours (p= 0.028) after bypass, and significantly better balance of hydration at 48 hours after bypass (p=0.012). The sivelestat group also showed significantly lower plasma levels of interleukin-8 immediately after bypass (p= 0.041) and interleukin-10 at 15 minutes after removal of the aortic cross-clamp (p= 0.048), and immediately after bypass (p= 0.037). Administration of sivelestat during bypass prevented pulmonary damage and activities of proinflammatory cytokines at the cardiac operation in neonates or infants. Our results show that sivelestat may be considered to protect pulmonary function against the injury by bypass.

Washing of irradiated red blood cells in paediatric cardiopulmonary bypass: is it clinically useful? A retrospective audit

Despite the introduction of smaller cardiopulmonary bypass (CPB) circuits for paediatrics, it is frequently necessary to add irradiated red blood cell concentrate (IRBC) to maintain adequate haemoglobin levels and the oxygen carrying capacity. Irradiation of blood weakens the cell membranes and results in an increase of lactate and potassium concentration. In addition, prolonged shelf time of IRBC may enhance its lactate level. To avoid the adverse effects of increased lactate and potassium concentration during paediatric bypass, prewashing of homologous blood in a cell-saving device was implemented at our institution. A retrospective audit of clinical data was performed to assess the relevance of this method. Preceding the introduction of the blood pre-washing, we investigated 14 units of IRBC for lactate, potassium levels and shelf time. Afterwards, we evaluated the CPB and laboratory data from 69 patients with body weight <10 kg and the lactate levels in the priming of the bypass circuit. The shelf time of blood units was 7.6 ± 2.7 days (minimum 5, maximum 14 days) with lactate concentration of 12.6 ± 2 mmol/land potassium concentration of 16.2 ± 4.7 mmol/l. In the priming after pre-washing, the lactate concentration was significantly lower than the standard priming (2.5 ± 0.9 vs 4.5 ± 20 mmol/l, p = 0.002). At the start of bypass, the lactate concentration after pre-washing was still lower (1.5 ± 0.4 vs 1.9 ± 0.9 mmol/l; p = 0.04), but at the end of bypass we detected a significant increase of lactate in the pre-washed group (1.5 ± 0.4 vs 2.2 ± 1.1 mmol/l, p = 0.01). There was no significant difference between the groups at the end of bypass (1.8 ± 0.9 vs 2.2. ± 1.1 mmol/l, p = 0.17). Other clinical and patient data were not significantly different. Our retrospective audit shows that pre-washing of IRBCs is not associated with decreased lactate levels at the end of CPB compared with standard use of IRBCs, suggesting that the added value of pre-washing of IRBCs on minimisation of lactate levels during CPB remains doubtful.

Risk factors for low colloid osmotic pressure during infant cardiopulmonary bypass with a colloidal prime

Extensive variations of colloid osmotic pressure (COP) measured in the priming as well as during infant cardiopulmonary bypass motivated us to audit clinical and laboratory data to identify the risk factors for low COP at the end of bypass. Data of 73 consecutive infant patients with body weight <10 kg, who underwent elective, first time open-heart surgery between March 2005 and December 2006 were examined. The following variables were analyzed: COP, blood loss, transfusion requirements and hematological data. Univariate and multivariate analysis of risk factors for low COP (<15 mmHg) was performed. Forty-eight percent of patients had COP <15 mmHg at the end of bypass. Those patients had significantly lower COP before start of bypass, during, and at the end of the operation. Significant univariate predictors of low COP at the end of bypass were: lower patient weight; lower COP before start of bypass, lower priming COP and larger volume of cardioplegia received into the circulation. After multivariable analysis, lower patient COP before bypass remained the only significant predictor for low COP at the end of bypass. Pre-bypass crystalloid dilution during induction should be avoided, as this is the most important cause of low COP during the bypass. Priming COP and COP management strategy should be adapted to the individual patient demand.

Cardiopulmonary bypass for surgical correction of congenital heart disease in children with sickle cell disease: a case series

We present a series of three children with sickle cell disease aged 3 months, 3 weeks and 18 months, all presenting for cardiac surgery requiring cardiopulmonary bypass. The cardiac lesions were atrioventricular septal defect, transposition of the great arteries and ventricular septal defect, with sickle cell loads of 35%, 11% and 39% respectively at presentation. We calculated that the bypass circuit would provide sufficient volume to decrease sickle cell levels to safe values, so we decided to proceed to bypass without pre-operative exchange transfusion, and modified the bypass technique so as to avoid the likely stimulants of a sickle cell crisis. Haemoglobin S levels after the start of bypass were significantly lower than before bypass, and remained low throughout the case and into the second postoperative day. By adopting this approach, we feel that we achieved a successful outcome with minimal distress to the children and their families.

Fluid shift is moderate and short‐lived during acute crystalloid hemodilution and normothermic cardiopulmonary bypass in piglets

Crystalloids are commonly used as priming solutions during cardiopulmonary bypass (CPB). Consequently, hemodilution is a regular occurrence at the start of a CPB. This study describes the time-course variations of hemodynamic parameters, plasma volume (PV) and fluid exchange following crystalloid hemodilution at start of normothermic CPB. Forty-five anesthetized piglets were given 60-min normothermic CPB. Ringer's solution was used as priming solution and maintenance fluid. Fluid input/losses, PV, colloid osmotic pressures (plasma/interstitium), hematocrit, and s-proteins were measured, and fluid extravasation rates (FER) and intravascular protein-masses calculated. Start of CPB resulted in a 25-30% hemodilution. To keep the fluid level of the CPB-reservoir constant after start of bypass, fluid addition [2.08 +/- 0.36 (mean +/- SEM) ml kg(-1) min(-1)] was necessary during the first 5 min. Thereafter the fluid needs to be leveled off [0.17 +/- 0.03 ml kg(-1) min(-1) (10-60 min), P < 0.001]. Fluid extravasation rate increased immediately following hemodilution from a baseline value of 0.08 +/- 0.01 to 1.75 +/- 0.34 ml kg(-1) min(-1) with a delayed decrease compared to fluid additions, to reach a 'steady-state' level of 0.22 +/- 0.03 ml kg(-1) min(-1) after 30 min (P < 0.001). Differences in time-course variations between fluid added and fluid extravasated were accompanied by changes in PV and mean arterial pressure. The colloid osmotic gradient decreased about 50% throughout the study and could partly explain the increased FER. Acute crystalloid hemodilution contributes to fluid overload during normothermic CPB. The resulting increase in fluid extravasation is, however, moderate, short-lived and levels off to baseline values within 30 min.

Ischaemia–reperfusion injury activates matrix metalloproteinases in the human heart

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate matrix remodelling in the heart and play a pivotal role in myocardial dysfunction immediately following ischaemia-reperfusion injury ex vivo in rats. We investigated the changes in MMPs and TIMPs in acute myocardial ischaemia-reperfusion injury in humans. Fifteen patients with stable angina undergoing coronary artery bypass graft surgery with cardiopulmonary bypass were enrolled. Left ventricular stroke work index was monitored prior to bypass and for 24 h following reperfusion. Left atrial biopsy samples were obtained at the start of bypass before cardioplegia and within 10 min after removal of the aortic cross-clamp. Plasma samples were collected from the radial artery and coronary sinus 1, 5, and 10 min following removal of the cross-clamp. In cardiac biopsies there was a marked increase in 72 kDa MMP-2 and 92 kDa MMP-9 activities, and a decrease in TIMP-1 upon reperfusion. Increased MMP activity correlated positively with cross-clamp duration and inversely with cardiac mechanical function 3 h following reperfusion. TIMP-1 correlated inversely with cross-clamp time and positively with cardiac mechanical function. Plasma samples revealed a significant increase in both 92 kDa MMP-9 and 64 kDa MMP-2 activities 1 min following removal of cross-clamp. Reperfusion following cardioplegia activates MMPs in the myocardium and plasma of patients undergoing coronary artery bypass grafting. This is the first correlation of MMP myocardial activity with cardiac function in humans. The early increase in MMP activity produces a proteolytic environment that may contribute to myocardial stunning injury in humans.

The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass

Objective Neuropsychologic disorders are common after coronary artery bypass operations. Air microbubbles are identified as a contributing factor. A dynamic bubble trap might reduce the number of gaseous microemboli. Methods A total of 50 patients undergoing coronary artery bypass operation were recruited for this study. In 26 patients a dynamic bubble trap was placed between the arterial filter and the aortic cannula (group 1), and in 24 patients a placebo dynamic bubble trap was used (group 2). The number of high-intensity transient signals within the proximal middle cerebral artery was continuously measured on both sides during bypass, which was separated into 4 periods: phase 1, start of bypass until aortic clamping; phase 2, aortic clamping until rewarming; phase 3, rewarming until clamp removal; and phase 4, clamp removal until end of bypass. S100β values were measured before, immediately after, and 6 and 48 hours after the operation and before hospital discharge. Results The bubble elimination rate during bypass was 77% in group 1 and 28% in group 2 ( P < .0001). The number of high-intensity signals was lower in group 1 during phase 1 (5.8 ± 7.3 vs 16 ± 15.4, P < .05 vs group 2) and phase 2 (6.9 ± 7.3 vs 24.2 ± 27.3, P < .05 vs group 2) but not during phases 3 and 4. Serum S100β values were equally increased in both groups immediately after the operation. Group 2 patients had higher S100β values 6 hours after the operation and significantly higher S100β values 48 hours after the operation (0.06 ± 0.14 vs 0.18 ± 0.24, P = .0133 vs group 2). Age and S100β values were correlated in group 2 but not in group 1. Conclusion Gaseous microemboli can be removed with a dynamic bubble trap. Subclinical cerebral injury detectable by increases of S100β disappears earlier after surgical intervention.

Use of argatroban as an alternative anticoagulant in cardiopulmonary support with an oxygenator: experimental study

Argatroban, a selective and competitive antithrombin agent synthesized in Japan, was assessed for use as an alternative anticoagulant for partial venoarterial bypass with an oxygenator, by determining serial changes in hemostatic molecular markers. Fourteen dogs were divided into 3 groups in which partial veno-arterial bypass was carried out: a group in which no anticoagulant was used (group N, n = 3), a group in which 200 IU/kg of bolus heparin was used (group H, n = 5), and a group in which 10 μg/kg per min of intravenous argatroban was used (group A, n = 6). Both thrombin-antithrombin complex and fibrinopeptide A increased significantly in group N; they did not increase in group H. Group A showed high thrombin-antithrombin complex levels and significantly high fibrinopeptide A levels throughout the bypass procedure in comparison to levels in group H. However, plasma fibrinogen was maintained at higher levels in group A than in group H. Platelet count decreased significantly immediately after the start of bypass in groups N and H, but no significant change in platelet count was observed in group A. In conclusion, argatroban at a dose that prolongs activated clotting time to 200 s suppressed thrombin and fibrin generation less effectively than did full-dose heparin. However, excessive consumption of fibrinogen and accelerated fibrinolysis were not observed, and more platelets were preserved, suggesting that argatroban can be used safely in partial cardiopulmonary bypass with an oxygenator.

Cerebral embolisation during modern cardiopulmonary bypass.

Cerebral microembolisation still occurs during cardiopulmonary bypass and may cause both stroke and postoperative cognitive impairment. We investigated the frequency of cerebral embolisation during coronary artery bypass surgery with modern cardiopulmonary bypass and related these to ascending aortic atherosclerosis. Transcranial Doppler monitoring for cerebral embolisation to both middle cerebral arteries was performed in 65 patients undergoing coronary artery surgery with non-pulsatile alpha-stat hypothermic bypass. Epicardial ultrasound imaging of ascending aortic atherosclerosis was performed in 14 patients. Thirty patients (56.9%) had more than 200 emboli entering the middle cerebral artery territories during surgery; most at the start of bypass and during defibrillation. Readjustment of aortic clamps and aortic cannulation also caused a large number of emboli which were probably particulate. Aortic disease was mild (mean plaque thickness 1 mm, interquartile range 0.9-1.2 mm) and did not relate to the number of cerebral emboli produced by aortic manipulation. Cerebral embolisation remains common during coronary surgery despite advances in filter and bypass pump technology. Aortic manipulation and clamping was associated with emboli but epicardial ultrasound imaging was of little help in its prediction.

Neutrophil degranulation and complement activation during fetal cardiac bypass

Background. Fetal cardiac bypass results in dysfunction of the fetoplacental unit (FPU) characterized by increased placental vascular resistance and respiratory acidosis. However the mechanisms of this dysfunction are not completely understood. To test the hypothesis that complement activation and neutrophil degranulation may contribute to the placental dysfunction associated with fetal bypass, we compared placental hemodynamics, complement activation, and neutrophil degranulation among fetuses exposed to cardiac bypass with a miniaturized bypass circuit including an in-line axial flow pump (Hemopump), fetuses undergoing bypass with a conventional roller pump circuit, and control fetuses that were similarly exposed but did not undergo bypass. Methods. Twenty-six Western Cross sheep fetuses (median 122 days gestation) were randomly assigned to undergo cardiac bypass for 30 minutes with the Hemopump circuit (n = 8), to undergo bypass for 30 minutes with the conventional (roller pump) circuit (n = 10), or to undergo identical exposure and cannulation but not bypass (n = 8, controls). Blood samples were collected to measure white cell count and differential, and C3a and lactoferrin levels prior to bypass, at the end of bypass, and 1 and 2 hours after bypass. Hemodynamics and blood gases were also monitored. Results. There was a fall in white cell count over time that continued after bypass in all groups; neutrophils and lymphocytes were affected similarly. C3a levels rose significantly from prebypass to postbypass in the roller pump group ( p < 0.0001) but not in either of the other groups. Lactoferrin levels rose significantly from start of bypass in both bypass groups (Hemopump p = 0.01; roller pump p < 0.0001) but not in controls. The elevation in lactoferrin level coincided with worsening placental gas exchange and deteriorating cardiac function. Conclusions. Complement and neutrophil activation occurred with fetal cardiac bypass but only neutrophil activation mirrored the FPU and cardiac dysfunction, suggesting that products of neutrophil activation may be important contributing factors. Improved FPU function with a bypass circuit that has less extracorporeal surface and does not require a large priming volume may be due in part to a reduction in the magnitude of this inflammatory response.

Coagulofibrinolysis during heparin-coated cardiopulmonary bypass with reduced heparinization

Background. We examined the safety of reduced systemic heparinization during heparin-coated cardiopulmonary bypass by measuring coagulofibrinolitic indices, including fibrinopeptide A, which directly reflects fibrinogenesis. Methods. Twenty-four patients who had elective cardiac operations were perfused using a circuit coated with covalently bonded heparin. Twelve patients received 300 U/kg of heparin and the remaining 12 patients received 150 U/kg. Blood was obtained for the measurement of thrombin-antithrombin III complexes, fibrinopeptide A, plasmin-alpha 2 plasmin inhibitor complexes, and d-dimer preoperatively; after heparin administration; 10, 60, and 90 minutes after the start of bypass; after protamine administration; and 1, 3, 6, 12, and 24 hours after the end of bypass. Results. Preoperative, intraoperative, and postoperative variables including postoperative bleeding were not significantly different between the two groups. Further, there were no complications in either group. No significant differences between the two groups were noted for any hematologic index at any time point. Conclusions. Reduced systemic heparinization combined with a heparin-coated cardiopulmonary bypass circuit is biochemically and clinically safe but does not reduce postoperative bleeding.

Avoiding Hyperoxemia at the Start of Cardiopulmonary Bypass While Optimizing Gas Flow and Temperature

There seems to be a wide range of practice in relation to the optimum oxygen setting before, and at the start of, cardiopulmonary bypass. Even manufacturers of blood oxygenators vary in their suggestions for this phase of extracorporeal circulation. Most of these suggestions are based on peak performance, Association for the Advancement of Medical Instrumentation (AAMI) standards, experience, and legal considerations. Therefore, suggested gas:blood flow ratios will vary from no gas flow at the start of bypass, to a ratio setting of 1:1. On the other hand, suggested inspired oxygen concentrations will generally vary between 0.80 to 1.0 at the start of cardiopulmonary bypass. In regard to perfusate temperatures before going on bypass, there are no clearly defined standards other than those of clinical preference. The manufacturer of the oxygenator used in this study clearly states in the operating instructions that gas flow should be proportional to blood flow at the start of bypass, and gas flow should be turned off when there is no fluid flow through the oxygenator. The presence of hyperoxic perfusates and wide patient/perfusate temperature gradients at the start of bypass has been suspected in the appearance of gaseous microemboli during this critical period. Hyperoxemia during the bypass period is also implicated in the introduction of oxygen free radicals and nitric oxide into the hypoxic myocardium during cardioplegia delivery. Presented here are the results of a randomized clinical study involving 39 adult patients undergoing cardiopulmonary bypass for the surgical treatment of coronary artery disease. All patients were randomly selected into five groupings. The first group had 1 L of gas flow through the perfusate before bypass, and bypass was then started with an FIO2 of 0.80. The second two groups had no gas flow through the perfusate prior to bypass and a starting FIO2 of 0.21. Groups 4 and 5 had 1 L of gas flowing through the perfusate and a starting FIO2 of 0.21. Results indicate that gas flow through Normosol R/Albumin perfusates will prevent the acidosis that is found in this solution when the system is previously flushed with carbon dioxide. Also, suggested high FIO2 settings will produce hyperoxic perfusates at the start of cardiopulmonary bypass. However, the use of an FIO2 of 0.21 at the start of bypass will produce normoxemic conditions that are both safe and reliable for the conduct of initiating cardiopulmonary bypass.

Retrograde Autologous Priming For Cardiopulmonary Bypass: A Safe And Effective Means Of Decreasing Hemodilution And Transfusion Requirements

Objectives: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion. Methods: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 ± 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups. Results: The lowest hematocrit value during cardiopulmonary bypass was 22% ± 3% versus 20% ± 3% in patients subjected to retrograde autologous priming and in control patients, respectively ( p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation ( p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) ( p = 0.03). Conclusions: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations. (J Thorac Cardiovasc Surg 1998;115:426-39)

Histamine release during cardiopulmonary bypass in neonates and infants.

Histamine release has been previously documented in adults and children during cardiopulmonary bypass (CPB). It has not been studied in neonates nor during deep hypothermic circulatory arrest (DHCA). Histamine effects could explain many perioperative complications of congenital cardiac surgery such as dysrhythmias and massive oedema. Therefore, documentation of histamine release in the perioperative period is of clinical importance. The source of histamine can be determined by measurement of tryptase which is released with histamine from mast cells but not basophils. Blood samples for histamine and tryptase were taken before and after specific events eg. cross-clamp removal, during anaesthesia and CPB in 14 infants and seven neonates undergoing complex congenital heart repairs and were analysed by commercial radioimmunoassays. Haemodynamic variables and pre and post-op weights were recorded to look for correlation between pathophysiological events and histamine release. Histamine concentration decreased at the start of bypass (0.69 to 0.38 ng.ml-1 at five minutes, (P < .005). There were no changes associated with DHCA and a small rise with reventilation (P < 0.02). Histamine concentration was lower in neonates than in infants (P < 0.05) during CPB. Plasma histamine and tryptase concentrations did not correlate, suggesting histamine release was from basophils and not from mast cells. Haemodynamic variables did not correlate with histamine concentrations. There was no major histamine release during CPB in infants and neonates. There was no relationship between histamine concentrations and clinical variables. Histamine released during CPB appears to come from basophils and may be a function of age.

Magnesium Substitution in Elective Coronary Artery Surgery

Magnesium may be beneficial in the control of ventricular ectopy and supraventricular tachyarrhythmias after coronary artery bypass graft (CABG) surgery, but it is not known whether a high-dose magnesium regimen is superior to a regimen keeping the patient normomagnesemic. A prospective randomized and double-blind clinical comparison was performed in 81 elective CABG patients in order to assess the effects of two different magnesium infusion regimens on electrolyte balance and postoperative arrhythmias. Forty-one patients (high-dose group, H) received 4.2 ± 0.7 g (mean ± SD), of magnesium sulfate before cardiopulmonary bypass, followed by an infusion of 11.9 ± 2.8 g of magnesium chloride until the first postoperative (PO) morning, and a further 5.5 ± 1.0 g until the second PO morning. Forty patients (low-dose group, L) received magnesium sulfate only after bypass to a total of 2.9 ± 0.5 g at the first, and 1.4 ± 0.1 g at the second PO morning. A blood cardioplegia technique was used in both groups, including bolus doses of magnesium chloride to a total of 2.4 ± 0.6 g and 2.3 ± 0.6 g to H and L patients, respectively. Continuous Holter tape-recording was used for 12 to 15 hours preoperatively, and for 48 hours postoperatively. Serum magnesium peaked in H patients on the first PO morning at 1.60 ± 0.25 mmol/L, whereafter it declined to the normal level on the third PO morning. Patients in the L group were normomagnesemic, except after the start of bypass. Recovery to spontaneous rhythm after declamping of the aorta was better in the H patients; only one patient had ventricular fibrillation (VF), whereas in the L group, four patients had VF and five patients needed a temporary pacemaker ( p = 0.016). Atrial fibrillation (AF) was detected in 3 H (7.3%), and 10 L patients (25%) within the first 48 PO hours ( p = 0.037). Ten H (24.3%) and 18 L patients (45.0%) had a total of 19 and 41 episodes of AF during the first PO week ( p p = 0.013).

Intrinsic pathway–dependent activated clotting time is not reliable for monitoring anticoagulation during cardiopulmonary bypass in neonates

The conventional activated clotting time (ACT) stimulated by celite is often prolonged during neonatal or pediatric cardiopulmonary bypass operations. 1'2 This prolonged ACT may lead to insufficient use of heparin during bypass and result in serious consequences such as intravascular coagulation after the operation. 3 Dilution of the clotting factors because of high-degree hemodilution during bypass is often blamed for the prolongation of ACT, 2' 4 but it is still unknown whether the total clotting capacity in the circulating blood is similarly affected by the extreme hemodilution. Because the celite ACT is a clotting test dependent on the intrinsic pathway, we postulate that it is the intrinsic pathway (rather than the extrinsic and the common pathways) that fails to respond properly under highdegree hemodilution during neonatal bypass operations. As a first step, we studied the in vitro effect of dilution on celite ACT by using heparinized blood taken from 10 adults having coronary artery bypass. The samples were taken after a 300 IU/kg dose of bovine heparin was given before the start of bypass. These patients received no drugs known to affect clotting and had a normal clotting profile before the operation. Blood samples were diluted in the laboratory to 25%, 50%, and 75% with saline solution or were left undiluted as control samples. Three different types of stimuli were used to initiate clotting: celite (final concentration 3 mg/ml) stimulating clotting through the intrinsic pathway, rabbit brain thromboplast in (final concentration 4 mg/ml) through the extrinsic pathway, and high-dose thrombin (final concentration 9 U/ml) through the common pathway. All measurements were performed with a Hemochron 8000 machine (International Technidyne Co., Edison, N.J.). An ACT longer than 1000 seconds was stopped and recorded as 1000 seconds. In blood samples stimulated by celite, ACT was prolonged significantly when the blood was diluted to 75% compared with the ACT of control samples (p < 0.01), whereas in samples stimulated by thromboplast in no significant change was observed. Furthermore, in blood samples stimulated by thrombin a significant reduction of ACT was found in proport ion to the dilution of blood (p < 0.01, Table I). These results

Magnesium substitution in elective coronary artery surgery: A double-blind clinical study

Magnesium may be beneficial in the control of ventricular ectopy and supraventricular tachyarrhythmias after coronary artery bypass graft (CABG) surgery, but it is not known whether a high-dose magnesium regimen is superior to a regimen keeping the patient normomagnesemic. A prospective randomized and double-blind clinical comparison was performed in 81 elective CABG patients in order to assess the effects of two different magnesium infusion regimens on electrolyte balance and postoperative arrhythmias. Forty-one patients (high-dose group, H) received 4.2 +/- 0.7 g (mean +/- SD), of magnesium sulfate before cardiopulmonary bypass, followed by an infusion of 11.9 +/- 2.8 g of magnesium chloride until the first postoperative (PO) morning, and a further 5.5 +/- 1.0 g until the second PO morning. Forty patients (low-dose group, L) received magnesium sulfate only after bypass to a total of 2.9 +/- 0.5 g at the first, and 1.4 +/- 0.1 g at the second PO morning. A blood cardioplegia technique was used in both groups, including bolus doses of magnesium chloride to a total of 2.4 +/- 0.6 g and 2.3 +/- 0.6 g to H and L patients, respectively. Continuous Holter tape-recording was used for 12 to 15 hours preoperatively, and for 48 hours postoperatively. Serum magnesium peaked in H patients on the first PO morning at 1.60 +/- 0.25 mmol/L, whereafter it declined to the normal level on the third PO morning. Patients in the L group were normomagnesemic, except after the start of bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood compatibility of two different types of membrane oxygenator during cardiopulmonary bypass in infants

The contact of blood with the artificial extracorporeal circuit causes a systemic inflammatory response due to blood activation. In this study, we compared two different paediatric membrane oxygenators used for extracorporeal circulation: a hollow fibre membrane oxygenator (Dideco Masterflo D-701, n = 10), and a flat sheet silicone membrane oxygenator (Avecor Kolobow 800-2A, n = 10). Blood compatibility was indicated by measuring complement activation as well as leukocyte and platelet activation. In patients perfused with a flat sheet membrane oxygenator, concentrations of complement split products C3a were significantly increased 30 minutes after the start of bypass (p < 0.01), whereas only a mild increase of C3a was found in patients perfused with a hollow fibre membrane oxygenator. Leukocyte and platelet counts dropped uniformly in both groups after the start of bypass mainly due to hemodilution. Activation of leukocytes and platelets identified by both plasma beta-glucuronidase and beta-thromboglobulin was similar in both groups. Infants perfused with a flat sheet membrane oxygenator received significantly more donor blood than those perfused with a hollow fibre oxygenator (p < 0.05). These results indicate that when used during paediatric cardiopulmonary bypass, a flat sheet membrane oxygenator has a higher complement activity than a hollow fibre membrane oxygenator, which is probably due to the relatively larger blood-surface contacting area of the oxygenator.

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)