The haemostatic effectiveness of autologous platelet rich plasma sequestered after heparin administration and institution of cardiopulmonary bypass.

Preoperative harvesting and postoperative reinfusion of autologous platelet rich plasma (PRP) has been reported to decrease blood loss as well as the requirement for homologous blood transfusion following cardiopulmonary bypass (CPB). We have developed a technique of intraoperative PRP sequestration which occurs during the initial period of CPB after the patient's circulation is supported and heparin has been given (PRP+). This process does not require any additional hardware, personnel or expense and it is performed without difficulty or complication. To evaluate the effect of PRP+ sequestration and reinfusion on blood loss and homologous blood requirement after CPB, we randomly assigned 126 consecutive patients undergoing elective open heart surgery into the experimental group 1 (PRP+) (n = 64) or the control (no platelet pheresis) group 2 (n = 52). A third group (n = 10) were not included in the randomization. Patients in group 3 had PRP prepared by conventional techniques (PRPc) prior to heparin administration and given to the patient after protamine infusion. Aggregation and activation studies were performed on the PRP+, PRPc, and blood bank platelets (BBP). Per cent aggregation of PRP in response to ADP was superior to that of BBP. There were no significant differences in ADP induced aggregation between PRP+ and PEPc. There was no significant difference in platelet activation (CD62) or number between the three groups. Patients infused with PRP+ showed significantly increased aggregation to ADP when compared with untreated patients 120 minutes after return to the ICW. Furthermore, more homologous haemostatic components (platelets/fresh frozen plasma) were required in the control group. We have demonstrated that collection of autologous PRP+ after administration of heparin does not interfere with its haemostatic effectiveness compared with PRPc prepared before the initiation of bypass. Moreover, this can be performed universally in haemodynamically unstable patients without any additional costs.

Cardiopulmonary bypass with adequate flow and perfusion pressures prevents endotoxaemia and pathologic cytokine production.

Endotoxin and cytokine inflammatory mediators comprise the afferent and efferent limbs of the 'acute phase response'. During cardiopulmonary bypass (CPB) there may be gut translocation of endotoxin and contact activation of lymphocytes. It has been hypothesized that the haemodynamic instability encountered following CPB is caused by the 'acute phase response'. In this study we attempted to quantify the acute phase response in patients undergoing open-heart surgery and determine the influence of these cytokines on perioperative morbidity. Four perioperative blood samples were drawn from 20 consecutive patients undergoing coronary artery bypass grafting (CABG). These samples were assayed for endotoxin and four cytokines. In all cases the cardiac index was maintained > 2.4 l/min/m2 during nonpulsatile normothermic bypass (37 degrees C) and > 1.8 l/min/m2 during nonpulsatile hypothermic bypass (28 degrees C), and the perfusion pressure > 60 mmHg. Endotoxin was not detected in any of the test samples despite positive nonpatient controls. Interleukin 6 (IL-6) and tumour necrosis factor (TNF) were not detected despite an assay sensitivity of 80 and 10 pg/ml, respectively. TNF was detectable with an assay sensitivity of 0.5 pg/ml although there were no significant differences within the group. Interleukin 1 (IL-1) was detected (range = 0.98 - 9.09 ng/ml) in patients and again there were no trends within the group. The platelet activating factor (PAF) values peaked at crossclamp release (1.3 ng/ml versus a baseline of 0.2 ng/ml); however, there was no significant difference within the study.

Intraoperative procurement of autologous fibrin glue.

A method of intraoperative procurement of autologous fibrin glue is described. The relative efficacy of our autologous preparation is compared with that of fibrin glue made with homologous cryoprecipitate. Experimentally, the fibrinogen content and the strength are less than those found in cryoprecipitate and appear related to the fibrinogen content of the autologous plasma used as substrate in the fibrin glue reaction. Clinically, no significant differences are noted in the performance of autologous fibrin glue. We believe the absence of the risk of blood-borne infection with the autologous product is a major advantage.

Evaluation of a low molecular weight heparin as an anticoagulant in a model of cardiopulmonary bypass surgery.

Heparin, the classically used anticoagulant in cardiopulmonary bypass surgery, has several disadvantages such that alternate anticoagulants are being sought. Previous reports have described questionable safety with the clinical use of low molecular weight (LMW) heparin in cardiac surgery. The dog cardiopulmonary bypass model described herein may provide a useful means to study the pharmacology of new drugs prior to clinical use. Dogs were given a single loading dose of 250 USP units/kg (1.66 mg/kg) of unfractionated heparin (control) or 250 anti-factor Xa units/kg (2.3 mg/kg) LMW heparin and placed on bypass for 60 minutes. Prior to, during, and following bypass blood samples were taken to measure coagulation and hematological parameters. The dogs remained anesthetized for 150 minutes post-bypass. Post-operative blood loss and fibrin deposition in the arterial line filters were measured. Our findings showed there was no significant blood loss (heparin 452 +/- 67 gms; LMW heparin 289 +/- 82 gms) and no significant fibrin deposition (heparin 22 +/- 3 gms; LMW heparin 28 +/- 7 gms) with the LMW heparin. These findings suggest that this LMW heparin should be safe and effective at the studied bolus dose as an anticoagulant for use in cardiopulmonary bypass surgery, and that protamine should be used to reverse the anticoagulant response after surgery.

Deleterious effects of bretylium on hemodynamic recovery from ventricular fibrillation.

To study the effects of bretylium on the restoration of circulatory function after resuscitation from ventricular fibrillation, closed-chest anesthetized dogs were electrically fibrillated for 1 minute followed by defibrillation (direct-current shock). After one control episode of fibrillation and defibrillation, 16 dogs received a bolus of bretylium (10 mg/kg intravenously). A second episode of fibrillation and defibrillation was induced in eight dogs 3 minutes after bretylium and in eight dogs 4 hours after bretylium. Prior to bretylium, mean arterial blood pressure spontaneously recovered to exceed 200 mm Hg by 2 minutes after defibrillation in all 16 dogs. However, after bretylium, 13 of 16 dogs were in electromechanical dissociation 2 minutes after defibrillation (p less than 0.001). Despite external chest compression, epinephrine, and sodium bicarbonate, a stable blood pressure could not be restored in 6 of 16 dogs. Clofilium, a bretylium analogue lacking sympathetic influences, did not alter the pattern of hemodynamic recovery following defibrillation in five of five dogs. The results suggest that the effects of bretylium on the sympathetic nervous system may profoundly influence the outcome of cardiac resuscitation from fibrillation.