Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients

OBJECTIVE: To determine the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) concentration after pediatric cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, clinical cohort study. SETTING: A fifteen-bed tertiary-care pediatric intensive care unit. PATIENTS: Fourteen pediatric patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum PCT and CRP were measured before cardiopulmonary bypass (CPB); after CPB; and on the first, second, and third days after surgery by means of immunoluminometry and nephelometry, respectively. Reference values for systemic inflammatory response syndrome are 0.5 to 2.0 ng/mL for PCT and <5 mg/L for CRP. Baseline serum PCT and CRP concentrations were 0.24 +/- 0.13 ng/mL and 4.06 +/- 3.60 mg/L (median 25th percentile-75th percentile), respectively. PCT concentrations increased progressively from the end of CPB (0.62 +/- 0.30 ng/mL), peaked at 24 hours postoperatively (POD1) (0.77 +/- 0.49 ng/mL), and began to decrease at 48 hours or POD2 (0.35 +/- 0.21 ng/mL). CRP increased just after CPB (58.82 +/- 42.23 mg/L) and decreased after 72 hours (7.09 +/- 9.81 mg/L). CONCLUSION: An increment of both PCT and CRP was observed just after CPB. However, PCT values remained within reference values, whereas CRP concentrations increased significantly after CPB until the third day. These preliminary results suggest that PCT was more effective than CRP to monitor patients with SIRS and a favorable outcome.     

A single nucleotide polymorphism of macrophage migration inhibitory factor is related to inflammatory response in coronary bypass surgery using cardiopulmonary bypass.

OBJECTIVE: Cardiac surgery causes induction and release of inflammatory mediators that may be regulated by genetic background. Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator that is known to be up-regulated in patients undergoing cardiac operations. Here we analyzed genotype distribution and allele frequency of the MIF-173*G/C single nucleotide polymorphism (SNP) and MIF plasma levels in patients undergoing surgical revascularization with (on-pump, n=45) and without (off-pump, n=34) cardiopulmonary bypass (CPB). METHODS: Genotyping was performed using a real-time PCR-based system with a hybridization probe system specific for the MIF-173*G/C SNP. In on-pump patients, blood samples were drawn before start of CPB, after termination of CPB and 12h postoperatively. In off-pump patients, blood samples were collected before stabilizer placement, after removal of the stabilizer and 12h postoperatively. MIF levels were measured using ELISA technique. RESULTS: Genotype distribution and allele frequencies were comparable between on-pump and off-pump patients. When comparing patients according to MIF genotype, a significant increase of MIF plasma levels after completed coronary bypass grafting using CPB was found in patients heterozygous for the MIF-173*G/C SNP (p<0.05). Moreover, on-pump patients showed significantly decreased MIF plasma levels after 12h postoperatively (p<0.05). In off-pump patients, MIF plasma levels were not significantly different over the time-course and were independent of the genotype. CONCLUSIONS: Patients carrying the C-allele showed significantly increased levels of the proinflammatory cytokine MIF compared to G/G homozygous when revascularization was carried out using CPB. The G/C genotype may be associated with a severe inflammatory reaction and therefore preoperative screening could be beneficial for patients undergoing cardiac surgery using CPB.     

Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery

BACKGROUND: Cardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha), and interleukin 1beta (IL-1beta) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery. METHODS: Twenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha1-microglobulin/creatinine ratios. RESULTS: Plasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and alpha1-microglobulin/creatinine ratios were also elevated. Plasma TNFalpha at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05). CONCLUSIONS: Cardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.     

Atelectasis Is a Major Cause of Hypoxemia and Shunt after Cardiopulmonary Bypass

Background: Respiratory failure after cardiopulmonary bypass (CPB) remains a major complication after cardiac surgery. The authors tested the hypothesis that atelectasis is an important factor responsible for the increase in intrapulmonary shunt after CPB.

Methods: Six pigs received standard CPB (bypass group). Six other pigs had the same surgery but without CPB (sternotomy group). Another six pigs were anesthetized for the same duration but without any surgery (control group). The ventilation-perfusion distribution was measured with the inert gases technique, extravascular lung water was quantified by the double-indicator distribution technique, and atelectasis was analyzed by computed tomography.

Results: Intrapulmonary shunt increased markedly after bypass but was unchanged over time in the control group (17.9 +/- 6.2% vs. 3.5 +/- 1.2%; P < 0.0001). Shunt also increased in the sternotomy group (10 +/- 2.6%; P < 0.01 compared with baseline) but was significantly lower than in the bypass group (P < 0.01). Extravascular lung water was not significantly altered in any group. The pigs in the bypass group showed extensive atelectasis (32.3 +/- 28.7%), which was significantly larger than in the two other groups. The pigs in the sternotomy group showed less atelectasis (4.1 +/- 1.9%) but still more (P < 0.05) than the controls (1.1 +/- 1.6%). There was good correlation between shunt and atelectasis when all data were pooled (R2 = 0.67; P < 0.0001).     

Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute-phase protein responses in patients undergoing cardiac surgery

Background : Cardiac surgery with cardiopulmonary bypass (CPB) evokes a systemic inflammatory response involving the proinflammatory cytokines tumor necrosis factor-α (TNFα), interleukin (iL)-1, IL-6, IL-8 and anti-inflammatory cytokines such as IL-10. Like IL-10, opioids downregulate the immune responses in vivo and in vitro, including the activity of the cytokine-producing monocytes and granulocytes. The proinflammatory cytokines are potent inducers of the hepatic acute-phase protein synthesis. The aim of the present study was to investigate if choice of anaesthesia, based on high-dose opioids (fentanyl) versus low-dose opioids influenced the release of IL-6, IL-8, and IL-10. Secondly, it was investigated whether serum amyloid P-component (SAP) is an acute-phase protein in man such as C-reactive protein (CRP), with which it is physically and structurally related. Methods : Sixteen patients submitted to elective coronary artery bypass grafting (CABG) surgery were randomized to either low-dose opioid anaesthesia consisting of thoracic epidural analgesia combined with inhalational anaesthesia (group I) or high-dose fentanyl anaesthesia (group II). From each patient 18 blood samples were taken perioperatively. Cytokine analyses were performed with ELISA, CRP and SAP mere measured with rocket immunoelectrophoresis (REI). Results : Surgery and CPB elicited a marked, transient and almost simultaneous proinflammatory and anti-inflammatory cytokine response with no differences between the groups. The cytokine levels returned to preoperative levels 1–3 d after operation. Anaesthesia and surgery did not affect SAP plasma levels while patients showed a major increase in CRP concentrations preceding the cytokine responses. Conclusion : CABG performed during two different anaesthetic techniques, high-dose fentanyl versus low-dose opioid anaesthesia, elicited a well-defined cytokine response with minor variation in the time course of each cytokine. The cytokine production was not modified by type of anaesthesia. Finally, SAP is not an acute-phase protein in men.     

Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and impaired neutrophil chemotaxis in neonatal pigs

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and organ dysfunction, especially in children. Plasma concentration of inflammatory markers are increased in response to the trauma of cardiac surgery and CPB. The aim of the present study was to investigate whether the CPB procedure in itself elicits increased levels of inflammatory markers in neonatal pigs. METHODS: The inflammatory response was measured in piglets undergoing sternotomy alone (sham group, n=13) or sternotomy and CPB (n=14). Inflammatory mediators were measured at baseline and at fixed time-points during and after CPB. IL-8, IL-10 and TNF-alpha levels and C-reactive protein (CRP) concentrations were measured in plasma samples. Polymorphonuclear neutrophils (PMN) chemotaxis was measured ex vivo, and CD-18 expression using an immunofluorescence technique. RESULTS: Immediately after the CPB procedure increased IL-8 levels were found in the CPB group, but not in sham operated animals (P=0.005). Simultaneously, a marked IL-10 response was measured in the CPB group. Concurrently, PMN chemotaxis decreased in CPB animals but not in the sham group (P=0.04). CD-18 expression and CRP levels were not significantly different between groups and TNF-alpha showed no changes in either group. The chemotactic response did not correlate with plasma IL-8 or IL-10, nor with CD-18 expression. CONCLUSION: The CPB procedure elicited a systemic inflammatory response in terms of significantly elevated plasma levels of IL-8 and IL-10. Furthermore, a temporary and simultaneous decrease in PMN chemotaxis was observed immediately after CPB.     

Normothermic beating heart surgery with assistance of miniaturized bypass systems: the effects on intraoperative hemodynamics and inflammatory response

The use of miniaturized cardiopulmonary bypass (CPB) circuits and avoidance of cardioplegic arrest are attempts to reduce the inflammatory response to cardiac surgery. We studied the effects of beating heart surgery (BHS) with assistance of simplified bypass systems (SBS) on global hemodynamics, myocardial function and the inflammatory response to CPB. We hypothesized that the use of SBS was associated with less hemodynamic instability after CPB resulting from attenuation of the inflammatory response when compared with surgery performed with a conventional CPB (cCPB) circuit. Forty-five patients undergoing coronary artery bypass grafting were prospectively studied. Fifteen patients were randomized to the use of a cCPB circuit, cold crystalloid cardioplegia, and moderate hypothermia. Two groups of 15 patients underwent BHS during normothermia with assistance of two different SBS consisting of only blood pump and oxygenator. Hemodynamic variables were assessed with transpulmonary thermodilution and transesophageal echocardiography. Plasma levels of proinflammatory and antiinflammatory mediators were measured perioperatively. After CPB, variables of global hemodynamics and systolic ventricular function did not differ among groups. Left ventricular diastolic function was impaired after CPB equally in all groups (P < 0.01 versus pre-CPB). At the end of surgery, there was more need for vasopressor (norepinephrine) support in both SBS groups than in the cCPB group (P < 0.01). After CPB, the release of interleukin (IL)-6 did not differ significantly among groups, whereas plasma levels of IL-10 were higher in the cCPB group (P < 0.01 versus SBS). The extent of myocardial necrosis (Troponin T) was comparable in all groups. We conclude that in our study, miniaturizing bypass systems and avoidance of cardioplegic arrest were not effective in improving hemodynamic performance and in attenuating the proinflammatory immune response after CPB.     

冠心病患者围手术期炎症反应的研究

目的　探讨体外循环或非体外循环下冠状动脉搭桥和激光心肌打孔治疗冠心病时围手术期炎症因子变化的特点 ,为冠心病围手术期的临床治疗提供参考。　方法　测定 37例冠心病患者及 10例瓣膜病患者术前 ,搭桥或打孔前 ,主动脉开放时 (搭桥结束时或打孔后 )及术后 3、6、2 4h的血浆肿瘤坏死因子 (TNF α)、白介素 6 (IL 6 )、C反应蛋白 (CRP)的水平。　结果　术后患者血浆TNF α、IL 6、CRP水平均有一定程度升高 ,使用体外循环患者TNF α为 (4 10± 0 71)pg/ml,显著高于不使用者的 (1 34± 0 2 9)pg/ml,差异有显著性意义 (P <0 0 5 ) ;两者IL 6差异无显著性意义 (P >0 0 5 )。冠状动脉搭桥患者术后CRP为 (12 89± 0 2 9) μg/ml,高于瓣膜病患者的 (12 0± 0 31) μg/ml,差异有显著性意义 (P <0 0 5 )。　结论　冠心病患者 ,冠状动脉搭桥、激光打孔手术后 ,围手术期均有一定程度的炎症反应 ,体外循环者反应较重     

Patients with poor preoperative ejection fraction have a higher plasma response of adrenomedullin in response to open heart surgery

BACKGROUND: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM levels are increased in heart diseases and in sepsis. Heart surgery under cardiopulmonary bypass (CPB) induces a systemic inflammatory response. METHODS: We measured plasma AM, cAMP (the second messenger of AM), C-reactive protein (CRP) and haemodynamic parameters in 29 patients undergoing elective open heart surgery, before, during and after anaesthesia and CPB as well as on the first morning after surgery. RESULTS: Basal AM levels were higher than normal and correlated with systolic pulmonary pressure and pulmonary capillary pressure, but not with other haemodynamic parameters. AM increased during CPB and remained elevated 24 h after the start of surgery. Plasma cAMP increased only at the end of CPB. CRP was increased only in the last sample. At the end of CPB and at the end of surgery AM levels were higher in patients with basal ejection fraction<40% compared with those with ejection fraction >60% [456+/-386 vs 252+/-343 (P<0.03) and 832+/-781 vs 391+/-356 pg/ml (P<0.05), respectively]. CONCLUSION: We conclude that AM, as inflammation-related cytokines, increases during and after CPB, that cAMP response is unrelated to AM and that AM response is higher in those patients with worse basal ejection fraction.     

The release of systemic inflammatory mediators is independent of cardiopulmonary bypass temperature

OBJECTIVE: The aim of this study was to investigate the effect of systemic CPB temperature on the production of the key mediators of the systemic inflammatory response to coronary artery bypass graft (CABG) surgery. DESIGN: Randomized clinical study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing first-time CABG surgery. INTERVENTIONS: The patients were randomized to hypothermic (32 degrees C, n = 15) or normothermic (36 degrees C, n = 15) CPB. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), cortisol, and neutrophils were measured the day before operation, at closure of the sternum, and 4, 16, and 44 hours later. The cytokine, CRP, cortisol, and neutrophil responses were independent of temperature during CPB with peak concentrations of IL-10 at closure of the sternum followed by IL-6, IL-8, cortisol, neutrophils, and finally CRP. A correlation between maximal plasma concentrations of IL-10 and cortisol was seen in both groups after surgery (p = 0.02). Drainage after surgery was lower after normothermic CPB (p=0.02), with no difference in the requirement for blood transfusion. All patients were discharged from the intensive care unit within 24 hours after surgery. CONCLUSIONS: The release of systemic inflammatory mediators after cardiac surgery was independent of mild hypothermia (32 degrees C) versus normothermia (36 degrees C) during CPB.     

Effect of cardiopulmonary bypass on serum procalcitonin and C-reactive protein concentrations

We have measured serum procalcitonin (PCT) concentrations after cardiac surgery in 36 patients allocated to one of three groups: group 1, coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) (n = 12); group 2, CABG without CPB (n = 12); and group 3, valvular surgery with CPB (n = 12). Serum PCT and C-reactive protein (CRP) concentrations were measured before operation, at the end of surgery and daily until postoperative day 8. Serum PCT concentrations increased, irrespective of the type of cardiac surgery, with maximum concentrations on day 1: mean 1.3 (SD 1.8), 1.1 (1.2) and 1.4 (1.2) ng ml-1 in groups 1, 2 and 3, respectively (ns). Serum PCT concentrations remained less than 5 ng ml-1 in all patients. Concentrations returned to normal by day 5 in all groups. To determine the effect of the systemic inflammatory response (SIRS) on serum PCT concentrations, patients were divided post hoc, without considering the type of cardiac surgery, into patients with SIRS (n = 19) and those without SIRS (n = 17). The increase in serum PCT was significantly greater in SIRS (peak PCT 1.79 (1.64) ng ml-1 vs 0.34 (0.32) ng ml-1 in patients without SIRS) (P = 0.005). Samples for PCT and CRP measurements were obtained from 10 other patients with postoperative complications (circulatory failure n = 7; active endocarditis n = 2; septic shock n = 1). In these patients, serum PCT concentrations ranged from 6.2 to 230 ng ml-1. Serum CRP concentrations increased in all patients, with no differences between groups. The postoperative increase in CRP lasted longer than that of PCT. We conclude that SIRS induced by cardiac surgery, with and without CPB, influenced serum PCT concentrations with a moderate and transient postoperative peak on the first day after operation. A postoperative serum PCT concentration of more than 5 ng ml-1 is highly suggestive of a postoperative complication.      

Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass

BACKGROUND: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding. METHODS: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests. RESULTS: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032). CONCLUSIONS: Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.     

Efficacy of a Simple Intraoperative Transfusion Algorithm for Nonerythrocyte Component Utilization after Cardiopulmonary Bypass

Background: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.

Methods: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests.

Results: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8%vs. 0%;P = 0.032).     

High-dose cimetidine reduces proinflammatory reaction after cardiac surgery with cardiopulmonary bypass

Background. Cimetidine, which is usually used for gastric ulcer, enhances cellular immunity. The effect of cimetidine on perioperative proinflammatory response after cardiac surgery with cardiopulmonary bypass was investigated.

Methods. Elective coronary artery bypass graft cases in which CPB was performed were placed randomly in a cimetidine (C) group (n = 20) or a no-treatment (N) group (n = 20). The time course of plasma levels of neutrophil elastase, interleukin (IL)-6 and IL-8, leukocyte counts, lymphocyte recovery ratio, C-reactive protein, creatine-kinase-MB, and oxygenation index were analyzed.

Results. The plasma levels of neutrophil elastase and IL-8 were inhibited in the C groups at 2 hours after CPB termination. In a comparison of the two groups, the C group demonstrated higher lymphocyte recovery ratio and lower C-reactive protein on postoperative day 5 and shorter intubation time. No intergroup differences were observed in IL-6, leukocyte counts, creatine-kinase-MB levels, or oxygenation index.

Conclusions. Cimetidine may reduce surgical stress and augment the immune system after cardiac surgery with cardiopulmonary bypass.     

Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery patients

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of organ injury after cardiopulmonary bypass (CPB). Elderly patients appear to be especially prone to develop general inflammation. Use of pentoxifylline (PTX) before surgery may be a promising approach to minimize the negative effects of CPB in these patients. METHODS: In a prospective, randomized study, patients more than 80 years old undergoing aortocoronary artery bypass grafting received either PTX (n = 15) after induction of anesthesia (initial bolus of 300 mg followed by a continuous infusion of 1.5 mg.kg(-1).h(-1) during the next 2 days) or saline as placebo (control group; n = 15). Polymorphonuclear neutrophil (PMN) elastase, C-reactive protein (CRP), and interleukins (IL-6, IL-8, IL-10) were measured from arterial blood samples before surgery (T0), at the end of surgery (T1), 5 hours after surgery (T2), and at the morning of the first (T3) and second (T4) postoperative day. RESULTS: Postoperatively, PTX-treated patients less often needed catecholamines and were extubated earlier than the control patients (p < 0.05). On the intensive care unit, cardiac index inceased more in the PTX-treated (from 1.95 +/- 0.3 to 3.26 +/- 0.4 L.min(-1).m(-2)) than in the control patients (from 1.89 +/- 0.2 to 2.78 +/- 0.3 L.min(-1).m(-2)). Increase in CRP and PMN-elastase was significantly higher in the untreated control than in the PTX patients. After CPB, IL-6, IL-8, and IL-10 increased in both groups showing a significantly higher increase in the untreated control patients (IL-8 control: from 11.3 +/- 2.6 to 154.4 +/- 57 pg/mL [T1]); IL-8 PTX: from 10.9 +/- 2.7 to 71.8 +/- 23 pg/mL [T1]). CONCLUSIONS: In elderly cardiac surgery patients, use of PTX before surgery and continued after CPB resulted in less inflammatory response than in an untreated control group. The value of attenuating the inflammatory process by PTX on outcome in this patient population needs to be evaluated in further controlled studies.     

Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass

PURPOSE: The precise mechanism of neutrophilia after cardiac surgery is unknown. Granulocyte colony stimulating factor (G-CSF) can increase the number of leukocytes. The purpose of this study was to evaluate the relationship between serum G-CSF levels and peripheral blood leukocyte counts after cardiac surgery. METHODS: We prospectively studied 10 patients undergoing cardiac surgery (coronary artery bypass grafting) using cardiopulmonary bypass (CPB). Plasma G-CSF levels and neutrophil count were measured before induction of anaesthesia, at the end of surgery, and on the first postoperative day. These changes were compared with those in patients undergoing non-cardiac major surgery (control group). RESULTS: At the end of surgery, G-CSF levels increased (P < 0.01) in both groups, but were higher in the control than in the cardiac group (3,250 +/- 690 vs 194 +/- 29.5 pg ml(-1), respectively, mean +/- SEM, P < 0.01). On the first postoperative day, G-CSF levels were still high in both groups, and were still higher in the control (710 +/- 179 vs 122 +/- 19.9, respectively, P < 0.01). However, neutrophilia was greater in the cardiac group than in the control. G-CSF response correlated positively with neutrophilia in the control group (r = 0.656, P < 0.05) but not in the cardiac group. CONCLUSIONS: Our results indicate that changes in leukocyte count following cardiac surgery are unique to patients undergoing CPB. G-CSF plays an important role as the mediator of neutrophilia after non-cardiac surgery, but not after cardiac surgery with CPB.     

Postoperative hyperthermia following off-pump versus on-pump coronary artery bypass surgery

OBJECTIVE: Hyperthermia is common in the first 24 hours following coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). An inflammatory response to CPB is often implicated in the pathophysiology of this fever. Unlike CABG with CPB, the temperature pattern after off-pump CABG (OPCAB), where CPB is avoided, has not yet been described. The purpose of this study was to describe the postoperative temperature pattern following OPCAB and to compare it with that following on-pump cardiac surgery. DESIGN: Retrospective, observational study. SETTING: Tertiary care university hospital. PARTICIPANTS: Consenting patients undergoing CABG or OPCAB procedures. INTERVENTIONS: Observational. MEASUREMENTS AND MAIN RESULTS: Of the CABG patients, 89% had temperature elevations above 38 degrees C, versus 44% of the OPCAB patients (P = 0.04). Peak body temperature was higher in the on-pump patients (CABG 38.5 degrees C +/- 0.4 degrees C versus OPCAB 37.9 degrees C +/- 0.5 degrees C; P = 0.002), as was the area under the curve for temperatures greater than 38 degrees C (CABG 1.6 +/- 1.7 degrees C/hr versus OPCAB 0.4 +/- 1.2 degrees C/hr; P = 0.02). CONCLUSIONS: Off-pump CABG surgery patients experience less hyperthermia compared with on-pump CABG patients. The reasons for a lower incidence and severity of hyperthermia after OPCAB surgery are not known, but may be related to a reduced inflammatory response.     

Cardiopulmonary bypass induces significant platelet activation in children undergoing open-heart surgery

BACKGROUND AND OBJECTIVES: To evaluate the effects of cardiopulmonary bypass (CPB) on platelet function in children undergoing open-heart surgery. METHODS: Data from 16 consecutive children undergoing cardiac surgery with CPB were prospectively collected. Blood samples of 10 mL were collected via the central venous line immediately before and after CPB for CD62 measurements by flow cytometry. RESULTS: Ten children had acyanotic heart disease (median age 3 yr, range 1.8-14) and six had a cyanotic defect (median age 4yr, range 2-14). The platelet count decreased significantly with CPB in both groups: from 163.5 (130-201) to 93.5 (57-186) x 10(3) microL(-1) in acyanotic children and from 139.5 (77-212) to 75 (43-99) x 10(3) microL(-1) in cyanotic children (P < 0.0001). The percentage of activated platelets was significantly lower in acyanotic children at baseline: 1% (0-23%) vs. 5% (3-8%) (P = 0.07). CPB increased the percentage of activated platelets significantly in both groups: post-bypass the values were 10% (range 1-17%) in acyanotic children and 7% (range 1-30%) in cyanotic children (P = 0.03). The increase in the percentage of activated platelets did not differ between the two study groups (P = 0.11). CONCLUSION: CPB induces significant platelet activation in children undergoing open-heart surgery.     

Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells

BACKGROUND: Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation. METHODS: Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively. RESULTS: Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients. CONCLUSIONS: The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.