Alfred H. Stammers

Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass–induced inflammation in humans ☆ ☆☆ ★ ★★

Cardiopulmonary bypass induces an inflammatory state characterized by tumor necrosis factor-alpha release. Integrin CD11b is a neutrophil surface adhesive glycoprotein integrin that is rapidly and permanently unregulated by tumor necrosis factor-alpha exposure. The CD11b integrin is known to be the primary neutrophil integrin responsible for neutrophil lung and myocardial entrapment after cardiopulmonary bypass and subsequent reperfusion injury. Twenty-four adults admitted to the hospital for myocardial revascularization were equally randomized to one of three groups: group A (control), group B (methylprednisolone before cardiopulmonary bypass), and group C (low-dose aprotinin protocol). Blood was collected at three times: (1) baseline, (2) 50 minutes of cardiopulmonary bypass duration, and (3) 30 minutes after cardiopulmonary bypass termination. Neutrophil CD11b integrin expression was measured by fluorescence-activated cell sorter analysis and plasma tumor necrosis factor-alpha levels measured by enzyme-linked immunosorbent assay. Group A demonstrated significant (p < 0.05) increases in CD11b expression at times 2 and 3 when results were compared with those of the same group baseline and with those of groups B and C at similar times. No significant changes were noted between groups B and C at any time. Group A demonstrated a significant (p < 0.05) increase in levels of tumor necrosis factor-alpha at time 3 when results were compared with those of the same group baseline and of groups B and C at the same time. No significant changes were noted between B and C at any time. These results demonstrate low-dose aprotinin has a similar antiinflammatory effect to that of methylprednisolone in blunting cardiopulmonary bypass-induced systemic tumor necrosis factor-alpha release and neutrophil integrin CD11b upregulation.

A retrospective study on perfusion incidents and safety devices

Despite the acceptance of extracorporeal circulation as an effective modality to facilitate cardiac surgery, patient outcomes can be negatively influenced by the occurrence of perfusion incidents. A perfusion survey was conducted to identify safety techniques and incidents related to cardiopulmonary bypass (CPB). An 80-question survey was mailed to chief perfusionists of all 1030 USA cardiac surgical centers using CPB. The survey was designed to examine practices and incidents that occurred during a 2-year period (July 1996 to July 1998). Five-hundred-and-fifty-two (54% response rate) surveys were returned, which accounted for 797 hospitals (79% of all cardiac centers) and 653 621 surgical procedures. Of the 27 identified CPB safety devices, the highest utilization was arterial line filters (98.5%) and the lowest arterial line bubble traps (3.4%). Of the reported cases, a CPB incident occurred once every 138 cases. The most common occurring incidents were protamine reactions (1:783), coagulation problems (1:771), and heater/cooler failures (1:1809). The rate of occurrence of an incident resulting in a serious injury or death was one for every 1453 procedures. Although techniques and safety devices create a relatively secure environment for CPB, lower incident rates may be achieved with further improvements in coagulation monitoring and incident reporting.

Aprotinin Enhances the Endogenous Release of Interleukin-10 After Cardiac Operations

BACKGROUND Cardiopulmonary bypass (CPB) is characterized by the systemic release of proinflammatory cytokines, such as tumor necrosis factor-alpha and the interleukins 1 and 6, as well as endogenous antiinflammatory cytokines, including interleukin-10 (IL-10). Glucocorticoids reduce tumor necrosis factor-alpha plasma concentrations while enhancing IL-10 plasma concentrations after CPB. Aprotinin, a serine protease inhibitor used primarily to reduce blood loss after CPB, reduces CPB-induced proinflammatory cytokine tumor necrosis factor-alpha release similarly to glucocorticoids. This study evaluates the effect of full-dose aprotinin on the plasma concentrations of IL-10 after CPB. METHODS Twenty adults were randomized into a control (group C, n = 10) and a full-dose aprotinin-treated group (group A, n = 10). Plasma levels of IL-10 were measured by enzyme-linked immunosorbent assay technique at baseline (before anesthetic induction), and at 1 and 24 hours after CPB termination. RESULTS A significant (p < 0.05) increase of IL-10 occurred in both groups at 1 and 24 hours after termination of CPB when compared with the same group at baseline. In group A, the increase in IL-10 was significantly greater than in group C (p < 0.05) at 24 hours after CPB. CONCLUSIONS These results demonstrate an endogenous antiinflammatory response generated after CPB, characterized by IL-10 release, that is enhanced by aprotinin therapy. This study demonstrates a unique antiinflammatory activity of aprotinin that may be of clinical significance.

An update on perfusion safety: does the type of perfusion practice affect the rate of incidents related to cardiopulmonary bypass?

Cardiopulmonary bypass (CPB) techniques vary among adult and pediatric patients undergoing cardiac surgery. This may result in a differential conduct of CPB between various aged patients. The present study reports on perfusion incidents occurring in hospitals using extracorporeal circulation. An 80 question survey was mailed to chief perfusionists at all 1030 US cardiac surgical centers. Respondents were asked to report on device use and incidents occurring during a 2-year period from July 1996 to June 1998. Five hundred and twenty-four completed surveys were returned with the age of surgical patients operated on at each hospital defined as either an adult (n=407), pediatric (n=17), or combined-adult and pediatric (n=100). Centrifugal pumps were used as the primary systemic pumps in 54% of adult, 12% of pediatric, and 36% of combined centers. In-line blood gas monitoring was used in 76% of all pediatric hospitals, but in only 30% of adult facilities. Incident rates occurred once per every 120.9, 83.9, and 220.2 cases in adult, pediatric, and combined centers, respectively. Mortality rates related to CPB occurred 2.7 times higher in adult and pediatric centers as compared to combined hospitals. Arterial dissection was the number one cause of death in both pediatric and combined hospitals, while coagulation disturbances resulted in the highest mortality for adult procedures. Results of this study show that the lowest incident rates occur at hospitals performing combined adult and pediatric CPB.

Historical aspects of cardiopulmonary by pass: From antiquity to acceptance

Cardiopulmonary bypass has evolved from an extremely risky procedure into a safe systematic process, and is practiced daily in thousands of centers throughout the world. Numerous individuals, from diverse specialities, have contributed to the knowledge of the processes of extracorporeal flow. The developmental sequence of advances in cardiopulmonary bypass has been divided into three nonexclusive periods based on the major changes observed during the time: (1) a conceptual and developmental period, consisting of events that occurred before 1950; (2) an applied technological period, 1950 to 1970; and (3) a refinement period, 1970 to present. Within each time frame, the major findings regarding biological and technical challenges, extracorporeal device development, and applied clinical practice will be explored. Technological advances in cardiopulmonary bypass have permitted surgeons to treat patients with both congenital and acquired heart disease, and anesthesiologists to identify appropriate mixtures of treatment regimens, whereby the risks associated with managing this challenging patient population could be minimized.

Utilization of rapid-infuser devices for massive blood loss

Rapid volume replacement for severe hemorrhage continues to challenge the clinician involved in the care of the patient suffering hemorrhagic shock. We report on the development and utilization of two rapid-infuser systems for volume replacement in critically ill patients presenting in extremis. We have developed rapid-infusion circuits by using commercially available devices available at our institution. The primary pumping mechanism is either a centrifugal pump (Revolution™COBE Cardiovascular, Arvada, CO, USA), or the Myocar-dial Protection System (MPS™ - Quest Medical, Allen, TX, USA), and offers advantages over commercially available devices. Both circuits consist of a cardiotomy reservoir, a cardioplegia delivery set, assorted tubing and connectors, and a heater-cooler system. Between January and October of 2003, 15 procedures were performed which utilized one of these two devices. There were nine ruptured aneurysms, five traumas and one radical nephrectomy. The rapid infusion time averaged 228.59±105.7 min where 10.49±9.4 L of autotransfusion volume was processed, with 3.99±4.2 L of red cell volume reinfused. The allogeneic blood products that were transfused included packed red blood cells and fresh frozen plasma, as well as 5% albumin. There were no intraoperative deaths and the rapid-infuser was considered lifesaving in all instances. Mechanical rapid infusion systems may be lifesaving when severe hypovolemia or hemorrhagic shock is encountered. While both devices are able to meet the requirements of rapid fluid replacement, the MPS offers the most safety features and has become the standard of care at our institution.

Coagulopathic-induced membrane dysfunction during extracorporeal membrane oxygenation: a case report.

This paper describes an unusual complication of membrane dysfunction during extracorporeal membrane oxygenation (ECMO) for treatment of neonatal respiratory distress. A 2.8-kg term infant presented to our facility in severe respiratory distress and was diagnosed with primary pulmonary hypertension. After routine priming of the extracorporeal circuit, the patient was placed on veno-arterial ECMO with 8 F arterial and 12 F venous cannulae. Transfusion criteria were established which included trigger values of the following: platelet count 100 000/μl, fibrinogen 150 mg/dl, haematocrit 40%. The ECMO course was uneventful until approximately the 132nd hour on support when the patient developed a consumptive coagulopathy, as evidenced by 55-60% reductions in both platelet count and fibrinogen concentrations, despite transfusion therapy. Total autogeneic blood product transfusion during the first 120 h of ECMO averaged 4.4 ± 2.2 ml/h, while the transfusion rate for the final 35 h was 7.8 ± 3.5 ml/h. Coinciding with this rise in transfusion requirements was an increase in transmembrane pressure from 0.29 to 1.52 mmHg/ml blood flow. The patient was separated from ECMO after 175 h due to a continuing coagulopathy and haemothorax. The patient was then treated with nitric oxide therapy before succumbing on the twelfth postoperative day due to refractory respiratory failure. The circuit was dissected and significant clots found in both the venous bladder and oxygenator. In addition, approximately one-third of the membrane compartment had a ‘fused’ circumferential pattern of dessicated clot which interrupted blood path continuity. In conclusion, this report describes an unusual complication of the ECMO oxygenator that occurred during long-term extracorporeal life support which most likely resulted from a coagulopathy.

Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study

Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1°C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation - DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) •106 s, platelet count 30 000 mm3, fibrinogen 15 mg dL-1 and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient’s DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.

Clinical evaluation of a new generation membrane oxygenator: a prospective randomized study

A new generation hollow-fibre membrane oxygenator (Spiral Gold™) has been introduced by Baxter Healthcare (Irvine, CA, USA). The purpose of this study was to evaluate the operational performance of this device under clinical conditions and to compare it to the Univox® Gold™ membrane oxygenator. Following institutional review board approval, and the obtainment of informed consent, 26 patients undergoing coronary artery bypass grafting were randomly assigned to either a Spiral Gold™ (Spiral) (n = 13) or Univox® Gold™ (Univox) (n = 13) group. Study parameters were grouped into the following categories: haematological, haemodynamic, oxygenator performance and perioperative outcomes. All patients received identical surgical, anaesthesia and postoperative care. There were no statistically significant differences in either preoperative or operative parameters between groups. During cardiopulmonary bypass, the Spiral group had a significantly lower pressure drop (26.9 ± 8.2 vs 46.7 ± 16.2 mmHg, p < 0.001). The Spiral group had significantly lower plasma free haemoglobin levels during all time periods of CPB compared to the Univox group. Heat exchange coefficients were higher during the rewarming period in the Spiral patients (0.59 ± 0.28) compared to the Univox group (0.36 ± 0.19), p = 0.06. There were no differences in oxygen transfer between groups, but ventilation gas sweep rates and FiO2 levels were statistically lower in the Spiral group at two of the three sampling time periods. The ratio of ventilating gas sweep rate to blood flow rate was lower in the Spiral group (0.56 ± 0.12) compared to the Univox group (0.74 ± 0.23), p < 0.03. The Spiral Gold™ oxygenator had superior oxygen transfer efficiency and lower haemolysis rates than the Univox® Gold™ oxygenator.

The effect of priming techniques of ultrafiltrators on blood rheology: an in vitro evaluation.

The increased interest of using ultrafiltration during cardiopulmonary bypass (CPB) has mandated a re-evaluation of the hematological effects of this blood conservation process. ‘Rinse-free’ ultrafiltrators can be primed using either crystalloid or blood prior to use. It is unknown whether one priming technique results in superior results in ultrafiltration quality. An in vitro circuit was designed to evaluate the Sorin/COBE HC1400 (n=6), the Lifestream HC70 (n=6), and the Terumo/Sarns HC11 (n=6). All test conditions were conducted at a blood flow rate of 250 ml/min and a transmembrane pressure of 250 mmHg. Samples were drawn and analyzed at four distinct time points for hematocrit, total protein, plasma free hemoglobin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNFα). The HC11 had significantly greater percent increases in hematocrit under the blood priming protocol (29.2 ± 7.9) than either the HC1400 (11.0 ± 7.8, p<0.03) or the HC70 (11.9 ± 7.8, p<0.04). When crystalloid priming was compared to blood priming, the HC1400 and HC70 produced significant percent increases in hematocrit and total protein levels. The HC1400 devices produced significantly less plasma free hemoglobin when primed with crystalloid rather than blood (43.6 ± 38.3 vs 21.3 ± 5.6, p<0.01). There were no significant differences between devices or priming techniques for IL-6, IL-8 or TNF levels. In conclusion, the efficiency of the ultrafiltrators was elevated when primed with crystalloid before use. Cytokine levels were relatively unchanged with priming techniques, while plasma free hemoglobin levels were reduced with those devices previously primed with crystalloid.