Scand J Thor Cardiovasc Surg 24: 53-58, 1990
INFLAMMATORY SYSTEM ACTIVATION DURING CARDIOPULMONARY BYPASS AS AN INDICATOR OF BIOCOMPATIBILITY: A RANDOMIZED COMPARISON OF BUBBLE AND MEMBRANE OXYGENATORS Leif Nilsson.' Ulf Nilsson.' Per Venge,' Ove J o h a n ~ s o n ,Hans ~ Tyden,3 Torkel Aberg' and Sven-Olov Nystrom'
Scand Cardiovasc J Downloaded from informahealthcare.com by Flinders University of South Australia on 01/13/15 For personal use only.
From the Departmenrs of 'Thoracic Sirrgen. 'Clinical C h e m i s r y and 'Anaesthesioloyy, University Hospitril. Uppsala, Sweden
(Accepted for publication June 5, 1989)
Abstract. As the exposure of blood to foreign material
during cardiopulmonary bypass (CPB) leads to triggering of inflammatory systems, the inflammatory response was used as an indicator of the biocompatibility of oxygenators. Activation of complement and neutrophil granulocytes during CPB was studied in 96 patients undergoing coronary bypass, with randomized comparisons between four different oxygenators, two of bubble and two of membrane type. Seven patients undergoing thoracotomy without CPB served as controls. During CPB there was significant complement activation, measured as changes in the ratio C3dlC3, with no demonstrable difference between the bubble and membrane oxygenator groups. Such change was not seen in the controls. Neutrophil granulocytes released significant amounts of the granule proteins lactoferrin and myeloperoxidase during CPB, but not during thoracotomy without CPB. The plasma concentrations of lactoferrin and myeloperoxidase were significantly lower in the membrane oxygenator groups, possibly indicating better biocompatibility. The strong inflammatory response with both oxygenator types, however, indicates that presently used CPB devices have unsatisfactory biocompatibility.
Key words: cardiopulmonary bypass. extracorporeal circulation, biocompatibility, oxygenator, inflammation. complement system, granulocytes.
massive release of potent mediators, such as the anaphylotoxins C3a and CSa, may cause organ damage and contribute to postoperative morbidity (10). Elevated levels of lactoferrin, a granule protein of neutrophil granulocytes, were found in patients with adult respiratory distress syndrome (ARDS), leading to the assumption that the degranulation process is involved in the syndrome's development (8, 11). Membrane oxygenators are increasingly used worldwide. Many clinics, however, still prefer the cheaper and simpler bubble oxygenator, claiming that no clear evidence has been published t o demonstrate clinical superiority of membrane oxygenators in short routine operations. The aim of this study was to compare the biocompatibility of bubble and membrane oxygenators (BO and MO). using inflammatory parameters. A small group of patients undergoing thoracotomy without CPB served as controls. MATERIAL AND METHODS
Extracorporeal circulation implies nonphysiologic conditions for the blood. Contact of the blood with foreign materials triggers different defence reactions, which can be recognized as inflammatory response in the patient. Several authors (5. 10. 13) have reported complement activation during cardiopulmonary bypass (CPB). Recent reports described activation of neutrophil granulocytes with release of inflammatory mediators (12, 20. 23). This inflammatory reaction may be regarded principally as a beneficial defence mechanism, but there are also indications that it may be harmful. Sudden
Pafients. Ninety-six men scheduled for myocardial revascularisation were randomized to four groups, and thereby to one of the following oxygenators:
I : 24 patients. Cobe Optiflo 11. BO 2: 25 patients, Cobe CML, MO. flat sheet. polypropylene 3: 24 patients. Harvey H F 4000, MO. hollow fibre. polyethylene 4: 23 patients, Harvey 1700. BO. Groups 1 and 4 formed group B . i.e. 47 patients with BO. Groups 2 and 3 formed group M . i.e. 49 patients with MO. Patients with markedly poor left ventricular function. insulin-dependent diabetes or a history of neurologic or psychiatric disorders were excluded, as were those taking acetyl salicylic acid or other antiinflammatory drugs.
54
L . Nilsson et al.
Table I. Levels of complement activation expressed as C 3 d l C 3 ~ 1 0 0 0( m e a n s f S E M )
1
PreoperaGroups tive
3 3 hours post-CPB
2 3 4
4.520.4 4.8f0.4 4.5f0.3 5.5f0.6
9.4f0.9 10.6f0.8 11.7f0.9 9.8f0.9
12.8f1.7 10.7k0.8 12.6k1.0 12.2f1.0
8.0k0.9 8.1k0.9 7.721.2 8.320.8
B M
5.0f0.3 4.6f0.2
9.650.6 ll.lf0.6
12.5k1.0 11.7f0.7
8.150.6 7.950.7
1
Scand Cardiovasc J Downloaded from informahealthcare.com by Flinders University of South Australia on 01/13/15 For personal use only.
2 End of CPB
4 Postoperative morning
No significant intergroup differences. Calculated for the total patient series, the following sampling-time values were significantly @
INFLAMMATORY SYSTEM ACTIVATION DURING CARDIOPULMONARY BYPASS AS AN INDICATOR OF BIOCOMPATIBILITY: A RANDOMIZED COMPARISON OF BUBBLE AND MEMBRANE OXYGENATORS Leif Nilsson.' Ulf Nilsson.' Per Venge,' Ove J o h a n ~ s o n ,Hans ~ Tyden,3 Torkel Aberg' and Sven-Olov Nystrom'
Scand Cardiovasc J Downloaded from informahealthcare.com by Flinders University of South Australia on 01/13/15 For personal use only.
From the Departmenrs of 'Thoracic Sirrgen. 'Clinical C h e m i s r y and 'Anaesthesioloyy, University Hospitril. Uppsala, Sweden
(Accepted for publication June 5, 1989)
Abstract. As the exposure of blood to foreign material
during cardiopulmonary bypass (CPB) leads to triggering of inflammatory systems, the inflammatory response was used as an indicator of the biocompatibility of oxygenators. Activation of complement and neutrophil granulocytes during CPB was studied in 96 patients undergoing coronary bypass, with randomized comparisons between four different oxygenators, two of bubble and two of membrane type. Seven patients undergoing thoracotomy without CPB served as controls. During CPB there was significant complement activation, measured as changes in the ratio C3dlC3, with no demonstrable difference between the bubble and membrane oxygenator groups. Such change was not seen in the controls. Neutrophil granulocytes released significant amounts of the granule proteins lactoferrin and myeloperoxidase during CPB, but not during thoracotomy without CPB. The plasma concentrations of lactoferrin and myeloperoxidase were significantly lower in the membrane oxygenator groups, possibly indicating better biocompatibility. The strong inflammatory response with both oxygenator types, however, indicates that presently used CPB devices have unsatisfactory biocompatibility.
Key words: cardiopulmonary bypass. extracorporeal circulation, biocompatibility, oxygenator, inflammation. complement system, granulocytes.
massive release of potent mediators, such as the anaphylotoxins C3a and CSa, may cause organ damage and contribute to postoperative morbidity (10). Elevated levels of lactoferrin, a granule protein of neutrophil granulocytes, were found in patients with adult respiratory distress syndrome (ARDS), leading to the assumption that the degranulation process is involved in the syndrome's development (8, 11). Membrane oxygenators are increasingly used worldwide. Many clinics, however, still prefer the cheaper and simpler bubble oxygenator, claiming that no clear evidence has been published t o demonstrate clinical superiority of membrane oxygenators in short routine operations. The aim of this study was to compare the biocompatibility of bubble and membrane oxygenators (BO and MO). using inflammatory parameters. A small group of patients undergoing thoracotomy without CPB served as controls. MATERIAL AND METHODS
Extracorporeal circulation implies nonphysiologic conditions for the blood. Contact of the blood with foreign materials triggers different defence reactions, which can be recognized as inflammatory response in the patient. Several authors (5. 10. 13) have reported complement activation during cardiopulmonary bypass (CPB). Recent reports described activation of neutrophil granulocytes with release of inflammatory mediators (12, 20. 23). This inflammatory reaction may be regarded principally as a beneficial defence mechanism, but there are also indications that it may be harmful. Sudden
Pafients. Ninety-six men scheduled for myocardial revascularisation were randomized to four groups, and thereby to one of the following oxygenators:
I : 24 patients. Cobe Optiflo 11. BO 2: 25 patients, Cobe CML, MO. flat sheet. polypropylene 3: 24 patients. Harvey H F 4000, MO. hollow fibre. polyethylene 4: 23 patients, Harvey 1700. BO. Groups 1 and 4 formed group B . i.e. 47 patients with BO. Groups 2 and 3 formed group M . i.e. 49 patients with MO. Patients with markedly poor left ventricular function. insulin-dependent diabetes or a history of neurologic or psychiatric disorders were excluded, as were those taking acetyl salicylic acid or other antiinflammatory drugs.
54
L . Nilsson et al.
Table I. Levels of complement activation expressed as C 3 d l C 3 ~ 1 0 0 0( m e a n s f S E M )
1
PreoperaGroups tive
3 3 hours post-CPB
2 3 4
4.520.4 4.8f0.4 4.5f0.3 5.5f0.6
9.4f0.9 10.6f0.8 11.7f0.9 9.8f0.9
12.8f1.7 10.7k0.8 12.6k1.0 12.2f1.0
8.0k0.9 8.1k0.9 7.721.2 8.320.8
B M
5.0f0.3 4.6f0.2
9.650.6 ll.lf0.6
12.5k1.0 11.7f0.7
8.150.6 7.950.7
1
Scand Cardiovasc J Downloaded from informahealthcare.com by Flinders University of South Australia on 01/13/15 For personal use only.
2 End of CPB
4 Postoperative morning
No significant intergroup differences. Calculated for the total patient series, the following sampling-time values were significantly @
