Prophylactic treatment with alkaline phosphatase in cardiac surgery induces endogenous alkaline phosphatase release.

INTRODUCTION: Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. We assessed the effects of the administration of bovine intestinal alkaline phosphatase (bIAP), an endotoxin detoxifier, on alkaline phosphatase levels in patients undergoing coronary artery bypass grafting. METHODS: A total of 63 patients undergoing coronary artery bypass grafting were enrolled and prospectively randomized. Bovine intestinal alkaline phosphatase (n=32) or placebo (n=31) was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was to evaluate alkaline phosphatase levels in both groups and to find out if administration of bIAP to patients undergoing CABG would lead to endogenous alkaline phosphatase release. RESULTS: No significant adverse effects were identified in either group. In all the 32 patients of the bIAP-treated group, we found an initial rise of plasma alkaline phosphatase levels due to bolus administration (464.27±176.17 IU/L). A significant increase of plasma alkaline phosphatase at 4-6 hours postoperatively was observed (354.97±95.00 IU/L) as well. Using LHA inhibition, it was shown that this second peak was caused by the generation of tissue non specific alkaline phosphatase (TNSALP-type alkaline phosphatase). CONCLUSIONS: Intravenous bolus administration plus 8 hours continuous infusion of alkaline phosphatase in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass results in endogenous alkaline phosphatase release. This endogenous alkaline phosphatase may play a role in the immune defense system.

Endotoxin release in cardiac surgery with cardiopulmonary bypass: pathophysiology and possible therapeutic strategies. An update.

Cardiac surgery with cardiopulmonary bypass provokes a systemic inflammatory response syndrome caused by the surgical trauma itself, blood contact with the non-physiological surfaces of the extracorporeal circuit, endotoxemia, and ischemia. The role of endotoxin in the inflammatory response syndrome has been well investigated. In this report, we reviewed recent advances in the understanding of the pathophysiology of the endotoxin release during cardiopulmonary bypass and the possible therapeutic strategies aimed to reduce the endotoxin release or to counteract the inflammatory effects of endotoxin. Although many different strategies to detoxify endotoxins were evaluated, none of them were able to show statistically significant differences in clinical outcome.

Preoperative ejection fraction as a predictor of survival after coronary artery bypass grafting: comparison with a matched general population.

BACKGROUND: Preoperative left ventricular dysfunction is an established risk factor for early and late mortality after revascularization. This retrospective analysis demonstrates the effects of preoperative ejection fraction on the short-term and long-term survival of patients after coronary artery bypass grafting. METHODS: Early and late mortality were determined retrospectively in 10 626 consecutive patients who underwent isolated coronary bypass between January 1998 and December 2007. The subjects were divided into 3 groups according to their preoperative ejection fraction. Expected survival was estimated by comparison with a general Dutch population group described in the database of the Dutch Central Bureau for Statistics. For each of our groups with a known preoperative ejection fraction, a general Dutch population group was matched for age, sex, and year of operation. RESULTS AND DISCUSSION: One hundred twenty-two patients were lost to follow-up. In 219 patients, the preoperative ejection fraction could not be retrieved. In the remaining patients (n = 10 285), the results of multivariate logistic regression and Cox regression analysis identified the ejection fraction as a predictor of early and late mortality. When we compared long-term survival and expected survival, we found a relatively poorer outcome in all subjects with an ejection fraction of < 50%. In subjects with a preoperative ejection fraction of > 50%, long-term survival exceeded expected survival. CONCLUSIONS: The severity of left ventricular dysfunction was associated with poor survival. Compared with the survival of the matched general population, our coronary bypass patients had a worse outcome only if their preoperative ejection fraction was < 50%.

Preoperative atrial fibrillation and elevated C-reactive protein levels as predictors of mediastinitis after coronary artery bypass grafting.

BACKGROUND: Mediastinitis is a serious complication after coronary artery bypass grafting (CABG). We studied the risk factors for the development of postoperative mediastinitis in a large group of patients who underwent isolated CABG at Catharina Hospital, Eindhoven, The Netherlands. METHODS: Data of all patients undergoing an isolated CABG between January 1998 and December 2008 were analyzed. Univariate and multivariate logistic regression analyses were performed to investigate the effect of biomedical variables on the development of mediastinitis. Multivariate analyses were used to test for the confounding effect of various risk factors on outcomes. RESULTS: Mediastinitis was present in 100 out of the 11,748 patients. Preoperative atrial fibrillation [odds ratio = 4.26 (2.26 to 8.02)] and an elevated preoperative C-reactive protein level [odds ratio = 1.013 (1.007 to 1.020)] were important independent predictors of the development of mediastinitis. Other significant risk factors were the following: age, chronic obstructive pulmonary disease, diabetes, morbid obesity, use of extracorporeal circulation, use of bilateral internal mammary arteries, reexploration for ischemia, and perioperative myocardial infarction. CONCLUSIONS: Apart from previously described risk factors for the development of postoperative mediastinitis, we found preoperative atrial fibrillation and an elevated C-reactive protein level to be significant predictors of mediastinitis in patients undergoing CABG.

Effect of body mass index on early and late mortality after coronary artery bypass grafting.

BACKGROUND: The effect of obesity on the long-term outcome after coronary artery bypass graft surgery (CABG) remains controversial. We analyzed data of patients undergoing CABG in a single center, to determine the predictive value of body mass index in combination with comorbidities on early and late mortality. METHODS: Early and late mortality of consecutive patients undergoing isolated CABG from January 1998 until December 2007 were determined. Patients were classified into five groups according to preoperative body mass index: underweight, normal weight, overweight, obese, and morbidly obese. RESULTS: After excluding 122 patients who were lost to follow-up and 236 patients with missing preoperative body mass index, 10,268 patients were studied. Multivariate logistic regression analyses showed that underweight was associated with higher early mortality (hazard ratio 2.63; 95% confidence interval: 1.13 to 6.11, p = 0.025). Multivariate Cox regression analyses did reveal morbid obesity as an independent predictor of late mortality (hazard ratio 1.67, 95% confidence interval: 1.15 to 2.43, p = 0.007). CONCLUSIONS: Among patients undergoing isolated CABG, underweight is an independent predictor for early mortality, and morbid obesity is an independent predictor for late mortality.

Is the use of Steri-StripTM S for wound closure after coronary artery bypass grafting better than intracuticular suture?

Several methods have been used in wound closure after coronary artery bypass grafting (CABG). In this study, the safety and efficacy of one of these methods, Steri-Strip S is compared with the traditional intracuticular suture method. Eighty-one patients undergoing CABG were prospectively randomized into two groups according to the method of skin closure: Steri-Strip S group and traditional suture group. Comparison between the two methods was done with regards to the length of the wound and the time needed to close it. The median closure time with Steri-Strip S was 5.45+/-3.35 min vs. 7.53+/-3.41 min in the suture group. A pain score of >or=6 at the first postoperative day was found in 30% of the patients in the suture group vs. 14% of the patients in the Steri-Strip S group (P=0.07). Cosmetic evaluation showed a non-significant difference in the linear visual analogue score in favor of Steri-Strip S group compared to the intracuticular suture group (73.1 vs. 70.1) (P=0.07). Steri-Strip S is a fast, safe alternative for wound closure of the sternotomy incision and graft harvesting site. A larger study is needed to establish the potential beneficial effect of Steri-Strip S on wound infection prevention.

Risk factors for deterioration of renal function after coronary artery bypass grafting.

OBJECTIVE: Various definitions of impairment of renal function after coronary artery bypass grafting (CABG) are used in the literature. Depending on the definition, several risk factors are identified. We analysed our data to determine the risk factors for postoperative deterioration of the creatinine clearance of 10% or more. METHODS: All patients undergoing isolated coronary surgery in a single centre between January 1998 and December 2007 are included. Clinical data, including demographics and renal risk factors, were prospectively collected in our database. The most recent preoperative serum creatinine level and the maximum serum creatinine level within the first week postoperatively were used to calculate the creatinine clearance. A deterioration of 10% or more was considered to be an endpoint for this study. RESULTS: In 10098 out of a total of 10626 patients, the preoperative as well as the postoperative creatinine clearance could be calculated. In 1053 patients, the deterioration of the creatinine clearance was 10% or more. We could identify the following risk factors: advanced age, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, emergency operation, previous cardiac surgery, low preoperative haemoglobin level, high preoperative C-reactive protein level, perioperative myocardial infarction, re-exploration and the number of blood transfusions. CONCLUSIONS: Risk factors for the deterioration of renal function after revascularisation have been confirmed in this study. In addition, we found peripheral vascular disease, previous cardiac surgery, low preoperative haemoglobin, increased preoperative C-reactive protein level, perioperative myocardial infarction and the number of blood transfusions to be risk factors that have not been described earlier.

Transfusion of red blood cells: the impact on short-term and long-term survival after coronary artery bypass grafting, a ten-year follow-up.

Transfusion of red blood cells (RBC) and other blood products in patients undergoing coronary artery bypass grafting (CABG) is associated with increased mortality and morbidity. We retrospectively analyzed data of patients who underwent an isolated coronary bypass graft operation between January 1998 and December 2007. Mean follow-up was 1696+/-1026 days, with exclusion of 122 patients lost to follow-up and 80 patients who received 10 units of RBC. Of the remaining patients, 8001 (76.7%) received no RBC, 1621 (15.2%) received 1-2 units of RBC, 593 (5.7%) received 3-5 units and 220 (2.1%) received 6-10 units. The number of transfused RBC was a predictor for early but not for late mortality. When compared to expected survival, survival of patients not receiving any blood product was better, while survival of patients receiving >3 units of RBC was worse. Transfusion of RBC is an independent, dose-dependent risk factor for early mortality after revascularization. Compared to expected survival, receiving no RBC improves patient long-term survival, whereas receiving three or more units of RBC significantly decreases patient survival.

Diabetes and survival after coronary artery bypass grafting: comparison with an age- and sex-matched population.

OBJECTIVE: Long-term outcome after coronary artery bypass grafting is worse in diabetic than in non-diabetic patients. No data are currently available regarding survival rates of diabetic and non-diabetic patients after coronary revascularisation compared with cohorts from the general population in the Netherlands, which were matched for age and sex (normal Dutch survival). METHODS: We retrospectively analysed the data from 10626 patients who underwent coronary artery bypass grafting between January 1998 and December 2007. Of these, 8287 patients were non-diabetic, 1587 were non-insulin-dependent and 630 were insulin-dependent diabetic patients (122 patients were lost to follow-up). Survival of these patient groups was compared with the normal Dutch survival. RESULTS: Multivariate analyses revealed non-insulin-dependent diabetes to be a risk factor for early mortality and both insulin-dependent and non-insulin-dependent diabetes as risk factors for late mortality. The 1-, 5- and 10-year survival rates for non-diabetic patients were 94.1%+/-0.3%, 86.8%+/-0.4% and 75.1%+/-1.7%, respectively, which was better than the normal Dutch survival. For insulin-dependent diabetic patients, 1-, 5- and 10-year survival rates were 90.3%+/-1.2%, 78.0%+/-2.0% and 60.5%+/-4.6%, respectively, and for non-insulin-dependent diabetic patients 91.4%+/-0.7%, 79.0%+/-1.3% and 58.9%+/-3.4%, respectively, which was worse than the normal Dutch survival. CONCLUSIONS: Non-insulin-dependent diabetes was a risk factor for early mortality and both types of diabetes were risk factors for late mortality after revascularisation. Compared with age- and sex-matched cohorts from the general Dutch population, the 10-year survival of non-diabetic patients was better; whereas the survival of both types of diabetic patients was worse.

Use of the Seldinger type movement over a J-shaped stylet for left ventricular vent insertion.

Access through the right superior pulmonary vein is a commonly used route for left ventricular vent insertion. Complex reshaping of the stylet and vent into a certain position or external guidance do not guarantee successful placement. In this article we describe a modified technique where the stylet sets up the position to allow consistent atraumatic advancement of the catheter across the mitral valve.

Preoperative renal function as a predictor of survival after coronary artery bypass grafting: comparison with a matched general population.

OBJECTIVE: Preoperative renal dysfunction is an established risk factor for early and late mortality after revascularization. We studied how renal function affects long-term survival of patients after coronary artery bypass grafting. METHODS: Early and late mortality were determined retrospectively among consecutive patients having isolated coronary bypass at a single Dutch institution between January 1998 and December 2007. Patients were stratified into 4 groups according to preoperative renal function. Expected survival was gauged using a general Dutch population group that was obtained from the database of the Dutch Central Bureau for Statistics; for each of our renal function groups, a general population group was assembled by matching for age, gender, and year of operation. RESULTS: After excluding 122 patients lost to follow-up, 10,626 patients were studied; in 10,359, preoperative creatinine clearance could be calculated. Multivariate logistic regression and Cox regression analysis identified renal dysfunction as a predictor for early and late mortality. When long-term survival of patient groups was compared with expected survival, only patients with a creatinine clearance less than 30 mL x min(-1) showed a worse outcome. Patients with a creatinine clearance between 60 and 90 mL x min(-1) had a long-term survival exceeding the expected survival. CONCLUSIONS: Severity of renal dysfunction was related to poor survival. When compared with expected survival, however, patients having coronary bypass had a worse outcome only when severe preoperative renal dysfunction was present.

Preoperative C-reactive protein levels to predict early and late mortalities after coronary artery bypass surgery: eight years of follow-up.

OBJECTIVE: There is limited evidence that increased preoperative levels of C-reactive protein are associated with increased mortality after coronary artery bypass grafting. We retrospectively investigated in 5669 patients the predictive value of preoperative C-reactive protein levels for early and late mortalities after coronary artery bypass grafting. METHODS: Patients undergoing isolated coronary artery bypass grafting between January 2000 and December 2007 (n = 8500) were studied. Preoperative demographic data and risk factors and outcome data (mortality data) were prospectively collected in a database. Preoperative C-reactive protein levels were retrieved from the laboratory data. RESULTS: In 5669 of 8500 cases, the preoperative C-reactive protein level could be retrieved. Seventy-five patients were unavailable for follow-up. A preoperative C-reactive protein level greater than 10 mg/L was an independent risk factor for early mortality, whereas a level greater than 5 mg/L was a risk factor for late mortality. Other risk factors were age, sex, chronic obstructive pulmonary disease, diabetes, left ventricular ejection fraction less than 35%, peripheral vascular disease, and previous cardiac surgery. We found a higher mean C-reactive protein value in patients with a left ventricular ejection fraction less than 35% (18.5 +/- 33 mg/L) than in those with an ejection fraction greater than 35% (P < .0001). CONCLUSIONS: Preoperative C-reactive protein levels can be used in risk stratification in coronary artery bypass grafting surgery. A C-reactive protein level greater than 10 mg/L is a risk factor for early mortality, whereas a level greater than 5 mg/L is a risk factor for late mortality.

Postoperative blood loss in patients undergoing coronary artery bypass surgery after preoperative treatment with clopidogrel. A prospective randomised controlled study.

OBJECTIVE: The optimal timing for discontinuation of clopidogrel before surgery remains under debate. The purpose of this study is to determine the effect of preoperative clopidogrel administration on postoperative blood loss and the total requirements of homologous blood products after coronary artery bypass grafting (CABG). We also evaluated the perioperative complications. METHODS: Consecutive patients (n=130) undergoing elective CABG were recruited and randomised between 2006 and 2007. In 38 patients (group 1), treatment with clopidogrel was discontinued 5 days prior to surgery, in 40 patients (group 2) 3 days before surgery and in 40 other patients (group 3) clopidogrel was stopped on the day of surgery. RESULTS: Significantly more postoperative blood loss was observed in group 3 compared to group 1 (929+/-472 ml vs 664+/-312 ml; p=0.009). Other group comparisons were not significant. Blood loss after 12 h and at drain removal was also significantly higher in group 3. Patients in group 3 also had higher total requirements of homologous blood products (p=0.046) and a significantly higher need for fresh frozen plasma (FFP) transfusion (p=0.034). Univariable regression analyses revealed that continuing clopidogrel till the day of surgery (group 3) was predictive for postoperative blood loss (beta=0.289; p=0.007) and the total requirements of homologous blood products after surgery (beta=0.280; p=0.008). These effects remained the same in multivariable analyses. CONCLUSIONS: Continuation of clopidogrel until the day of surgery induces significantly more postoperative blood loss and increases significantly the total requirements of homologous blood products and FFP transfusion after surgery. The blood loss and the use of blood products in the group that stopped at 3 days preoperatively were similar to that of the group that stopped at 5 days preoperatively.

Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population.

BACKGROUND: The predictive value of the preoperative hemoglobin value after coronary artery bypass grafting (CABG) has not been well established. We studied how the preoperative hemoglobin level affects the survival of patients after CABG. Late mortality was compared with that of a general population. METHODS AND RESULTS: Early and late mortality of all consecutive patients undergoing isolated CABG between January 1998 and December 2007 were determined. Patients were classified into 4 groups stratified by preoperative hemoglobin level. The cutoff point for anemia was 13 g/dL for men and 12 g/dL for women. Expected survival of a matched general Dutch population cohort was obtained from the database of the Dutch Central Bureau for Statistics. After the exclusion of 122 patients who were lost to follow-up and 481 patients with missing preoperative hemoglobin levels, complete data were obtained in 10,025 patients. Multivariate logistic regression analyses revealed anemia to be an independent risk factor for higher early mortality. Cox regression analyses revealed low hemoglobin level, both as a continuous variable and as a dichotomous variable (anemia), to be a predictor of higher late mortality. Compared with expected survival, patients with the lowest preoperative hemoglobin levels had a worse outcome, whereas patients with the highest hemoglobin levels had a better outcome. CONCLUSIONS: A lower preoperative hemoglobin level is an independent predictor of late mortality in patients undergoing CABG, whereas anemia is a risk factor for early and late mortality. Compared with the general population, anemic patients had worse survival than expected, whereas nonanemic patients had better survival than expected.

Anti-inflammatory effects of alkaline phosphatase in coronary artery bypass surgery with cardiopulmonary bypass.

Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. Alkaline phosphatase prevents endotoxin-induced systemic inflammation in animals and humans. We assessed the effects of the administration of bovine intestinal alkaline phosphatase on surgical complications in patients undergoing coronary artery bypass grafting. In a double blind, randomized, placebo-controlled study, a total of 63 patients undergoing coronary artery bypass grafting were enrolled. Bovine intestinal alkaline phosphatase or placebo was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was reduction of post-surgical inflammation. No significant safety concerns were identified. The overall inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass was low in both placebo and bovine intestinal alkaline phosphatase patient group. Five patients in the placebo group displayed a significant TNFalpha response followed by an increase in plasma levels of IL-6 and IL-8. Such a TNFalpha response was not observed in the bovine intestinal alkaline phosphatase group, suggesting anti-inflammatory activity of bovine intestinal alkaline phosphatase. Other variables related to systemic inflammation showed no statistically significant differences. Bovine intestinal alkaline phosphatase can be administered safely in an attempt to reduce the inflammatory response in coronary artery bypass grafting patients with a low to intermediate EuroSCORE. The anti-inflammatory effects might be more pronounced in patients developing more fulminant postoperative inflammatory responses. This will be investigated in a further trial with inclusion of patients undergoing complicated cardiac surgery, demanding extended cardiopulmonary bypass and aortic cross clamp time. In this review article some recent patents related to the field are also discussed.

Long-term results of coronary artery bypass grafting in patients with left ventricular dysfunction.

BACKGROUND: In this prospective study, we investigated the determinants of long-term outcome, symptoms, and left ventricular function after coronary artery bypass grafting in patients with a moderate to severely decreased left ventricular ejection fraction. METHODS: Between 1997 and 1998, 75 consecutive patients with moderate to severe left ventricular dysfunction underwent coronary artery bypass grafting procedures. The operative mortality rate was 4.0%, and the 72 survivors were monitored for 8 years. The end points were mortality, symptomatic status (New York Heart Association [NYHA] functional class), and left ventricular function. RESULTS: The total survival rate after 8 years was 89.3%. During follow-up, 8 patients died. Death was attributed to a cardiac cause in 5 patients and to a noncardiac cause in 3. There was no statistically significant difference between preoperative and late postoperative NYHA functional class, despite a statistically significant improvement that persisted for up to 4 years after CABG. The results of echocardiography showed a statistically significant improvement in the left ventricular ejection fraction (from 0.322 +/- 0.06 preoperatively to 0.463 +/- 0.02 at follow-up, p < 0.001). Multivariate analysis revealed that the left ventricular end-systolic volume index, the presence of angina pectoris, and absence of symptoms of congestive heart failure were preoperative indicators of freedom from heart failure after coronary operations (p < 0.05). CONCLUSIONS: Coronary artery bypass grafting for patients with moderate-to-severe left ventricular dysfunction is associated with acceptable long-term results. The left ventricular end-systolic volume index is a simple noninvasive method to aid in the preoperative decision making in such patients.

Cardiac tamponade: an unusual, lifethreatening complication after transhiatal resection of the esophagus.

Transhiatal resection for carcinoma of the distal esophagus is associated with relative high morbidity and mortality. We present a rare case of cardiac tamponade after transhiatal esophagectomy for which emergency sternotomy was performed. Probably the retraction of the heart during exploration of the mediastinum caused a laceration of an epicardial vein. Although very rare, cardiac tamponade should be considered when hemodynamic instability during or after transhiatal esophagectomy occurs.

Resection of a lipomatous hypertrophic interatrial septum involving the right ventricle.

Lipomatous hypertrophy of the interatrial septum is a rare cardiac lesion that is usually limited to the interatrial septum. We report a case of an extensive lipomatous hypertrophy, which protruded into the right and the left atrium as well as the superior and the inferior vena cava and the right ventricle. A 71-year-old woman was referred to us because of a cardiac mass on a transthoracic echocardiogram, performed on a routine check-up because of a known membranous ventricular septum defect. She underwent surgical resection of the mass and closure of the ventricular septum defect. The postoperative period was complicated by superior vena cava syndrome for which she underwent re-operation. The post mortem histopathological diagnosis was a lipomatous hypertrophic interatrial septum.

Platelet-rich plasma preparation using three devices: implications for platelet activation and platelet growth factor release.

BACKGROUND: In this study, three commercial systems for the preparation of platelet-rich plasma (PRP) were compared and platelet growth factors release was measured. METHODS: Ten healthy volunteers donated whole blood that was fractionated by a blood cell separator, and a table-top centrifuge to prepare PRP. Furthermore, an autologous growth factor filter was used to concentrate PRP fractionated by the blood cell separator. PRP was subsequently activated with autologously produced thrombin to degranulate the platelets to measure platelet-derived growth factor-AB (PDGF-AB), transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF). RESULTS: PRP contained significantly higher platelet counts compared with baseline values (p < 0.001). PDGF-AB concentrations were increased more than 18-fold in the platelet gel supernatant when the cell-separator and GPS were used, whereas only a 3-fold increase was seen with the AGF. CONCLUSION: The three PRP devices enable the preparation of PRP for the release of high concentrations of platelet growth factor, but showed different harvesting capacities for the collection of concentrated platelets. The administration of thrombin for PRP activation resulted in the release of high concentrations of PDGF-AB and TGF-beta but only when PRP had not been activated during the preparation process in vitro.