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Ann Thorac Surg 2000;69:1490-1495
© 2000 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children

^a Departments of Department of Surgery, Northwestern University Medical School, Chicago, Illinois, USA
^b Department of Pathology, Northwestern University Medical School, Chicago, Illinois, USA
^c Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA
^d Division of Cardiovascular-Thoracic Surgery, Children’s Memorial Hospital, Chicago, Illinois, USA
^e Division of Pediatric Critical Care Medicine, Children’s Memorial Hospital, Chicago, Illinois, USA
^f Department of Pathology, Children’s Memorial Hospital, Chicago, Illinois, USA

Address reprint requests to Dr Backer, Children’s Memorial Hospital, 2300 Children’s Plaza, m/c 22, Chicago, IL 60614
e-mail: c-backer{at}nwu.edu

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. A randomized, prospective, double-blind study of 29 children was performed to evaluate the hypothesis that dexamethasone administration prior to cardiopulmonary bypass would decrease the inflammatory mediator release and improve the postoperative clinical course.

Methods. Fifteen children received dexamethasone (1 mg/kg intravenously) and 14 (controls) received saline solution 1 hour prior to CPB. Serial blood analyses for interleukin-6, tumor necrosis factor-, complement component C3a, and absolute neutrophil count were performed. Postoperative variables evaluated included temperature, supplemental fluids, alveolar-arterial oxygen gradient, and days of mechanical ventilation.

Results. Dexamethasone caused an eightfold decrease in interleukin-6 levels and a greater than threefold decrease in tumor necrosis factor- levels after CPB (p < 0.05). Complement component C3a and absolute neutrophil count were not affected by dexamethasone. The mean rectal temperature for the first 24 hours postoperatively was significantly lower in the group given dexamethasone than in the controls (37.2° ± 0.4°C versus 37.7° ± 4°C; p = 0.007). Dexamethasone-treated patients required less supplemental fluid during the first 48 hours (22 ± 28 mL/kg versus 47 ± 34 mL/kg; p = 0.04). Compared with controls, dexamethasone-treated children had significantly lower alveolar-arterial oxygen gradients during the first 24 hours (144 ± 108 mm Hg versus 214 ± 118 mm Hg; p = 0.02) and required less mechanical ventilation (median duration, 3 days versus 5 days; p = 0.02).

Conclusions. Dexamethasone administration prior to CPB in children leads to a reduction in the postbypass inflammatory response as assessed by cytokine levels and clinical course.

	Introduction

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Cardiopulmonary bypass (CPB) can induce a systemic inflammatory response after cardiac surgical procedures that can lead to organ injury and postoperative morbidity [1, 2]. Clinical manifestations in the postoperative period include fever, low cardiac output, pulmonary insufficiency, fluid retention, and coagulopathy. In children in particular, catastrophic multisystem organ failure can develop from this inflammatory response [3]. Kirklin and colleagues [4] described the link between CPB, complement activation by the foreign surfaces encountered by the blood, and postoperative complications including low cardiac output, renal and pulmonary dysfunction, and abnormal bleeding. Cardiopulmonary bypass is now known to initiate a multifaceted response involving not only complement activation but also cytokine release and endothelial cell activation [5, 6]. This process can be self-perpetuating and yet ultimately is self-limiting. Understanding the triggers, timing, and pattern of this complex cascade is essential to being able to modify or arrest it.

Unlike other triggers associated with whole-body inflammatory reactions such as trauma or sepsis, cardiac surgeons have the advantage of knowing when the trigger will occur (ie, during CPB) and hence have an opportunity for preemptive intervention in an effort to attenuate or minimize the response. A variety of anti-inflammatory treatment modalities have been studied including leukocyte depletion [7], neutrophil adhesion blockade [8], and heparin coating of the CPB circuit to reduce complement and leukocyte activation [9]. In particular, studies in adult patients suggest a role for corticosteroids in reducing the inflammatory response after CPB [10]. Glucocorticoids are potent anti-inflammatory agents that affect multiple pathways of the inflammatory cascade. We hypothesized that glucocorticoid administration prior to CPB would result in less inflammatory mediator release and an improved postoperative clinical course in pediatric patients requiring CPB for intracardiac repair of congenital heart defects. We designed a randomized, prospective, blinded study to test this hypothesis.

	Material and methods

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The study was approved by the Children’s Memorial Hospital Institutional Review Board. Written informed consent was obtained from all parents. Twenty-nine children (12 girls, 17 boys) undergoing open heart surgical procedures for congenital heart defects were enrolled. Patients were randomized to receive either dexamethasone, 1 mg/kg intravenously with a maximum dose of 10 mg/kg (group I, n = 15), or placebo, normal saline solution (group II, n = 14), immediately after induction of anesthesia (approximately 1 hour prior to initiation of CPB). The randomization was done by the pharmacy, and the code was broken only after data accumulation was complete. Exclusion criteria included preoperative use of glucocorticoids or nonsteroid anti-inflammatory agents, isolated atrial septal defect, CPB time greater than 200 minutes, and aortic cross-clamp time greater than 120 minutes.

Anesthesia
All patients had a peripheral arterial line and a central venous line. For perioperative antibiotic prophylaxis, older children (> 6 months old) received cefazolin sodium and younger infants, oxacillin and gentamicin sulfate. Anesthesia induction technique varied but most commonly relied on ket- amine hydrochloride or fentanyl. Maintenance was achieved with fentanyl (50 to 100 µg/kg), pancuronium bromide (100 µg/kg), and inhalation agents (halothane or isoflurane). Intermittent doses of pancuronium were given throughout the procedure. Inhalation agents—either isoflurane or ha- lothane—were used while the patient was on CPB. Heparin sodium (300 U/kg) was administered for anticoagulation before CPB. Activated clotting time was kept at 450 seconds or greater throughout the procedure. To reverse heparin, all patients were given protamine sulfate after discontinuation of CPB and completion of modified ultrafiltration. Inhalation agents were used after CPB; if early extubation was planned, lower doses of narcotic were used than if postoperative ventilation was planned. At the conclusion of CPB, inotropic drugs (dopamine hydrochloride, dobutamine hydrochloride, milrinone lactate) were given if necessary.

Cardiopulmonary bypass
The CPB system consisted of a roller pump (Sarns 9000), a Terumo SX oxygenator, and an arterial filter. The ultrafiltration unit used for patients weighing more than 5 kg was the Minntech HPH 400m, and the Amicon (Minntech) minifilter plus was used for patients weighing less than 5 kg. The priming solution consisted of Plasmalyte-A (Baxter), 50 mL of 25% albumin, 3 ml/kg of mannitol, 3,000 units of heparin, 30 mEq of sodium bicarbonate, 3 mL of calcium gluconate, and packed red blood cells as necessary to raise the hematocrit value of the circuit after initiation of bypass to 25%. In general, crystalloid prime (and no additional calcium) was used for patients weighing more than 45 kg. Cardiopulmonary bypass was instituted with a flow rate of 2.5 L · min^-1 · m^-2. As the patient was cooled, the flow rates were decreased to 2.0 L · min^-1 · m^-2. If the mixed venous oxygen saturation fell to less than 70%, CPB flow rates were increased. Cold blood cardioplegia (600 mL/m² ~ body surface area) was infused at a pressure of 50 to 100 mm Hg by the Gish Biomedical CPS Plus system at 6° to 8°C at a 4:1 blood to crystalized ratio every 20 minutes.

Ultrafiltration was started during rewarming by placing the ultrafiltration unit in the CPB circuit at the cardioplegia outlet port. The cardioplegia recirculating lines were then connected to the outlet of the ultrafiltration unit and cardiotomy reservoir to form a closed loop. Modified ultrafiltration after CPB was achieved by backbleeding through the aortic cannula to the CPB venous reservoir. The blood was then pumped through the oxygenator to the ultrafiltration unit and back to the right atrium. Blood inflow and outflow were balanced using ultrasonic flow monitors (Transonic Systems) on the aortic line and the flow line to the ultrafiltration unit. Inflow and outflow were adjusted to maintain an appropriate blood pressure for the child’s age and body weight. Modified ultrafiltration was performed for 10 minutes in all patients in both groups.

Laboratory tests
Collection of samples
Blood samples were collected for determination of interleukin-6 (IL-6), complement component C3a, tumor necrosis factor- (TNF-), and absolute neutrophil counts. Sample 1 was obtained from the CPB circuit before the circuit was connected to the patient. The other blood samples were drawn from the patient arterial line. Table 1 summarizes the sample times. For each blood draw, 2 mL of blood was placed in an EDTA (ethylenediaminetetraacetic acid)-containing tube for IL-6 and TNF- measurements, 1 mL of blood was placed in an EDTA-containing tube for complete blood cell count, and 2 mL of blood was placed in a tube containing EDTA and futhan (an inhibitor of complement activation) for C3a measurements. Blood was kept on ice until centrifuged at 4°C for 10 minutes at 3,000 rpm. Approximately 1 mL of plasma was placed by pipette into polypropylene tubes for storage at -70°C until analysis.

Clinical variables
Postoperative clinical variables were analyzed retrospectively from the computerized intensive care unit (ICU) data- base. Data collection included temperature profile, supplemental fluid, serial arterial blood gases, oxygen requirement, calculation of alveolar-arterial oxygen gradients, duration of mechanical ventilation, preoperative and postoperative serum creatinine levels, and duration of stay in the ICU.

Statistical analysis
The two-sample t test was used for comparing two means. The Wilcoxon rank-sum test was applied for comparing two medians when the distributions were skewed. Fisher’s exact test was used for comparing two proportions when the sample sizes were small. Results are expressed as either the mean ± the standard deviation or as the median when there was a wide scatter.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Patient age and CPB data are given in Table 2. Operative procedures are listed in Table 3.

View larger version (22K): [in this window] [in a new window]   Fig 1. Mean levels of complement component C3a (± standard deviation) for each sample time. Normal C3a levels are less than 400 ng/mL. There were no sample times that were significantly different between the two groups.

Tumor necrosis factor-

View larger version (15K): [in this window] [in a new window]   Fig 2. Mean tumor necrosis factor- (TNF-) levels (± standard deviation) for each sample time. Normal TNF- levels are lower than 16 pg/mL. For sample 6 (2 minutes after cardiopulmonary bypass and prior to modified ultrafiltration), group I had a significantly lower level than group II (p = 0.03). At sample time 7, although the group II level was more than three times higher than that of group I, this did not reach significance because of the large standard deviation.

View larger version (17K): [in this window] [in a new window]   Fig 3. Mean levels of interleukin-6 (IL-6) (pg/mL) (± standard deviation) for each sample time. Normal IL-6 levels are less than 12 pg/mL. For sample 7 (10 minutes after protamine administration), the level in group I was significantly lower than that in group II (p = 0.03).

View larger version (12K): [in this window] [in a new window]   Fig 4. Mean absolute neutrophil count (x 103 cells/mL) (± standard deviation) for samples 2, 3, 5, and 8. There were no sample times that were significantly different between the two groups.

Respiratory function
The median alveolar–arterial oxygen gradient at 24 hours postoperatively was lower in group I (dexamethasone) versus group II (144 ± 108 mm Hg versus 214 ± 118 mm Hg; (p = 0.02). The median duration of mechanical ventilation was lower in group I than in group II (3 days versus 5 days; p = 0.02).

Supplemental fluid requirement
All patients were placed on a regimen of maintenance intravenous fluids on the basis of body weight: 4 mL · kg · h for body weight of 1 to 10 kg; +2 mL · kg · h for those weighing 11 to 20 kg; +1 mL · kg · h for a weight of more than 20 kg. Supplemental fluids included all fluids (crystalloid, colloid, blood products) administered during the first 48 hours postoperatively in addition to maintenance intravenous fluids. Patients in group I (dexamethasone) required significantly less supplemental fluid than those in group II (22.1 ± 28 mL · kg versus 46.7 ± 34 mL · kg for the first 48 hours; p = 0.04). Only 1 (7%) of the 15 patients in group I required 50 mL · kg or more supplemental fluid in the first 48 hours versus 9 (64%) of the 14 patients in group II (p = 0.002).

Renal function
The number of patients whose postoperative creatinine levels increased by 0.2 mg/dL or greater from the preoperative value was significantly lower in group I (dexamethasone) than in group II (1 of 15 or 7% versus 7 of 14 or 50%; p = 0.014).

Discharge from intensive care unit
The median duration of stay in the ICU was shorter in group I (dexamethasone) compared with group II (4 days versus 7 days; p = 0.01). In group I, 2 (13%) of the 15 patients required 7 or more days in the ICU versus 10 (71%) of the 14 in group II (p = 0.002).

Postoperative morbidity and mortality
There was one postoperative death in group I (dexamethasone). The child had transposition of the great arteries, ventricular septal defect, juxtaposed atrial appendages, and left superior vena cava to coronary sinus. She underwent arterial switch and closure of the ventricular septal defect on day 4 of life. Re- operation was performed for supravalvular pulmonary stenosis, bilateral pulmonary artery Palmaz stent placement, and residual ventricular septal defect closure 7 weeks after arterial switch. The patient died of low cardiac output 2 weeks later; a postmortem examination was not done. There were no postoperative wound infections and no reoperations for bleeding in either group. Sternal dehiscence did not occur in either group. No patient in the dexamethasone-treated group experienced marked glucose intolerance.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
In this prospective, randomized study, we have demonstrated that glucocorticoid administration prior to CPB in children resulted in an attenuated inflammatory response as based on biochemical analysis of serum inflammatory mediators (IL-6, TNF-) and on postoperative clinical courses. The single dose of steroid had no effect on complement levels or the absolute neutrophil count. Children who received steroids prior to CPB had fewer febrile episodes, improved respiratory gas exchange, and better renal function and required less supplemental fluid postoperatively than did controls. As a result, the group given dexamethasone required fewer days of mechanical ventilatory support and was discharged from the ICU sooner. The difference between the two groups was quite striking, and there is a possibility that this may have been influenced by a difference in the distribution of the lesions and procedures for which we did not account. However, we believe that our prospective, randomized protocol protects against this bias. In addition, as will be discussed later, other models and clinical trials have corroborated our results.

The inflammatory response to CPB is extraordinarily complex and variable in its manifestations. Butler and associates [1] summarized the broad categories of pathophysiologic response to CPB: complement activation; initiation of coagulation, fibrinolytic, and kallikrein cascades; neutrophil activation with degranulation and protease enzyme release; oxygen-derived free radical production; and endotoxin and cytokine release. Activation of these various cascades and their interactions cause the systemic inflammatory response syndrome, the clinical syndrome with the acronym SIRS [11]. Our study was designed to examine the effect of a single preoperative dose of corticosteroids on the biochemical and clinical manifestations of the systemic inflammatory response to CPB in children. In particular, we examined the effect of a single dose of dexamethasone on complement activation (C3a), cytokine release (TNF-, IL-6), absolute neutrophil count, and postoperative clinical course (temperature, fluid requirement, alveolar-arterial oxygen gradient, days of ventilation).

The initiation of various inflammatory cascades and the release of bioactive substance during and after CPB mediate multiple pathophysiologic changes. As blood comes into contact with the nonendothelialized CPB circuit, circulating factor XII is activated, which in turn activates the coagulation, fibrinolytic, bradykinin, and complement systems [1, 4]. As the inflammatory cascade proceeds, the expression of cell-surface adhesion molecules on neutrophils and endothelial cells allows for transvascular migration of activated leukocytes into tissues [6, 8]. Concurrently, leukocyte-derived inflammatory mediators and tissue-destructive substances, such as proteases and neutrophil elastase, are released and cause additional vascular and parenchymal damage [1, 3, 5]. As oxygen and substrate are reintroduced into the cardiopulmonary circulations, lymphocytes and macrophages are stimulated to release additional mediators including cytokines (IL-6, TNF-), and the inflammatory response is further amplified [12, 13]. Finally, the administration of protamine and the consequent protamine-heparin complex lead to additional complement activation [14]. Increased microvascular permeability, increased pulmonary vascular resistance, decreased systemic vascular resistance, and increased basal metabolic processes are the results [2, 5, 15, 16].

Seghaye and coworkers [15] related the capillary leak syndrome after CPB in neonates to the postbypass inflammatory reaction and particularly to TNF- levels after protamine administration. The same authors [3] in an earlier study related multiple-system organ failure after CPB in infants and children to complement activation. Cremer and colleagues [2] compared patients with postoperative hyperdynamic circulatory dysregulation to those with stable postoperative hemodynamics, and related cytokine IL-6 to the circulatory dysregulation. Mainwaring and associates [17] demonstrated a threefold to fourfold increase in activated complement C3 and IL-6 in children undergoing a modified Fontan procedure.

Both clinical and laboratory studies have suggested that the use of corticosteroid given prior to CPB may improve the postoperative course after CPB [13]. Glucocorticoids have been shown to blunt neutrophil CD11b upregulation induced by CPB [18]. Glucocorticoids inhibit the expression of adhesion molecules ELAM-1 (endothelial-leukocyte adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) by endotoxin-activated endothelial cells and thereby interfere with the traffic of leukocytes into inflamed areas [19]. Jansen and colleagues [10] conducted an adult study comparing a single dose of dexamethasone and placebo. They found that dexamethasone administration did not inhibit complement activation or elastase release but did inhibit the increase in TNF-, leukotriene B₄, and tissue plasminogen activator activity. This resulted in fewer febrile episodes, less hypotension, and shorter ICU stays. Our study confirmed those conclusions in a pediatric population.

Butler and associates [20] evaluated the cytokine response to CPB in children weighing less than 10 kg and the potential for modification of this response by the intraoperative use of steroids. Interleukin-6 levels and postoperative fevers were significantly higher in CPB patients, and this acute-phase response was abrogated by intraoperative steroid administration. Our study confirms this effect of steroids on IL-6 and postoperative fever. Hill and colleagues [21] compared the effect of aprotinin and methylprednisolone on TNF- levels after CPB in adults. Controls had a significant elevation in the levels of TNF-; this response was equally blunted in the groups receiving either aprotinin or methylprednisolone. Our study confirms the attenuation of the TNF- response in children. Lodge and co-workers [22] evaluated the timing of the preoperative dose of methylprednisolone in a neonatal piglet model. They compared the results of administering methylprednisolone 8 hours before operation with those of giving the dose in the CPB circuit prime. They found that in the group given methylprednisolone 8 hours before bypass, there was a significant improvement in pulmonary compliance, alveolar-arterial O₂ gradient, pulmonary vascular resistance, and extracellular fluid accumulation. Our dosing of steroids is intermediate between these two groups (prime versus 8 hours), as we gave the dose about 1 hour prior to CPB.

Our study confirms the release of activated complement and cytokines in children undergoing CPB. We demonstrated that glucocorticoids had an inhibitory effect on cytokine release (TNF-, IL-6) but no significant inhibitory effect on complement activation or neutrophil counts. We also found significantly less postoperative fever and improved cardiopulmonary function in our patients treated with glucocorticoids. We speculate that the reduced incidence of fever in the treatment group may be due, at least in part, to the lower level of circulating cytokines, which are known pyrogens. This may be clinically important because of the increase in metabolism and heart rate associated with an elevated temperature. Treated patients also had better respiratory gas exchange, required less mechanical ventilation, and needed less supplemental fluid. We attribute this to an attenuation of the inflammatory cascade as a result of the administration of preoperative glucocorticoids, as this preserved microvascular structural integrity, decreased pulmonary and systemic capillary leak, and decreased interstitial edema formation. Children treated with glucocorticoids had a reduced systemic inflammatory response after CPB as assessed by decreased cytokine levels and improved postoperative clinical course. Glucocorticoid administration prior to CPB proved to be safe, inexpensive, and effective. We recommend a single dose of dexamethasone prior to CPB in children.

	Acknowledgments

 
Statistical analysis was provided by Edwin Chen, PhD.

	Footnotes

 
This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/section/atsdiscussion

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Butler J., Rocker G.M., Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:552-559.[Abstract]
2. Cremer J., Martin M., Redl H., et al. Systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 1996;61:1714-1720.[Abstract/Free Full Text]
3. Seghaye M.C., Duchateau J., Grabitz R.G., et al. Complement activation during cardiopulmonary bypass in infants and children. Relation to postoperative multiple system organ failure. J Thorac Cardiovasc Surg 1993;106:978-987.[Abstract]
4. Kirklin J.K., Westaby S., Blackstone E.H., Kirklin J.W., Chenoweth D.E., Pacifico A.D. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:845-857.[Abstract]
5. Downing S.W., Edmunds L.H., Jr Release of vasoactive substances during cardiopulmonary bypass. Ann Thorac Surg 1992;54:1236-1243.[Abstract]
6. Boyle E.M., Jr, Pohlman T.H., Johnson M.C., Verrier E.D. Endothelial cell injury in cardiovascular surgery. Ann Thorac Surg 1997;63:277-284.[Abstract/Free Full Text]
7. Bando K., Pillai R., Cameron D.E., et al. Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:873-877.[Abstract]
8. Friedman M., Wang S.Y., Sellke F.W., Cohn W.E., Weintraub R.M., Johnson R.G. Neutrophil adhesion blockade with NPC 15669 decreases pulmonary injury after total cardiopulmonary bypass. J Thorac Cardiovasc Surg 1996;111:460-468.[Abstract/Free Full Text]
9. Moen O., Høgsen K., Fosse E., et al. Attenuation of changes in leukocyte surface markers and complement activation with heparin-coated cardiopulmonary bypass. Ann Thorac Surg 1997;63:105-111.[Abstract/Free Full Text]
10. Jansen N.J., van Oeveren W., van den Broek L., et al. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. J Thorac Cardiovasc Surg 1991;102:515-525.[Abstract]
11. Taylor K.M. SIRS—the systemic inflammatory response syndrome after cardiac operations. Ann Thorac Surg 1996;61:1607-1608.[Free Full Text]
12. Boyle E.M., Jr, Pohlman T.H., Cornejo C.J., Verrier E.D. Endothelial cell injury in cardiovascular surgery. Ann Thorac Surg 1996;62:1868-1875.[Abstract/Free Full Text]
13. Wan S., LeClerc J.-L., Vincent J.-L. Cytokine responses to cardiopulmonary bypass. Ann Thorac Surg 1997;63:269-276.[Abstract/Free Full Text]
14. Cavarocchi N.C., Schaff H.V., Orszulak T.A., Homburger H.A., Schnell W.A., Jr, Pluth J.R. Evidence for complement activation by protamine-heparin interaction after cardiopulmonary bypass. Surgery 1985;98:525-530.[Medline]
15. Seghaye M.C., Grabitz R.G., Duchateau J., et al. Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operation. J Thorac Cardiovasc Surg 1996;112:687-697.[Abstract/Free Full Text]
16. Oudemans-van Straaten H.M., Jansen P.G., te Velthuis H., et al. Increased oxygen consumption after cardiac surgery is associated with the inflammatory response to endotoxemia. Intensive Care Med 1996;22:294-300.[Medline]
17. Mainwaring R.D., Lamberti J.J., Hugli T.E. Complement activation and cytokine generation after modified Fontan procedure. Ann Thorac Surg 1998;65:1715-1720.[Abstract/Free Full Text]
18. Hill G.E., Alonso A., Thiele G.M., Robbins R.A. Glucocorticoids blunt neutrophil CD11b surface glycoprotein upregulation during cardiopulmonary bypass in humans. Anesth Analg 1994;79:23-27.[Abstract/Free Full Text]
19. Cronstein B.N., Kimmel S.C., Levin R.I., Martiniuk F., Weissmann G. A mechanism for the antiinflammatory effects of corticosteroids. Proc Natl Acad Sci USA 1992;89:9991-9995.[Abstract/Free Full Text]
20. Butler J.B., Pathi V.L., Paton R.D., et al. Acute-phase responses to cardiopulmonary bypass in children weighing less than 10 kilograms. Ann Thorac Surg 1996;62:538-542.[Abstract/Free Full Text]
21. Hill G.E., Alonso A., Spurzem J.R., Stammers A.H., Robbins R.A. Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced inflammation in humans. J Thorac Cardiovasc Surg 1995;110:1658-1662.[Abstract/Free Full Text]
22. Lodge A.J., Chai P.J., Daggett C.W., Ungerleider R.M., Jaggers J. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets. J Thorac Cardiovasc Surg 1999;117:515-522.[Abstract/Free Full Text]

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				D. Shum-Tim, C. I. Tchervenkov, A.-M. Jamal, T. Nimeh, C.-Y. Luo, E. Chedrawy, E. Laliberte, A. Philip, C. P. Rose, and J. Lavoie Systemic steroid pretreatment improves cerebral protection after circulatory arrest Ann. Thorac. Surg., November 1, 2001; 72(5): 1465 - 1472. [Abstract] [Full Text] [PDF]

				T Gourlay Biomaterial development for cardiopulmonary bypass Perfusion, September 1, 2001; 16(5): 381 - 390. [Abstract] [PDF]

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