Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients

OBJECTIVE: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). METHODS: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-deltadeltaG(v - a)) and hepato-venous and arterial (-deltadeltaG(hv - a)) compartments were calculated. MEASUREMENTS AND RESULTS: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p = 0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p = 0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p = 0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p = 0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p = 0.001, 0.033, respectively). CONCLUSION: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.

Benefits of cardiac surgery in octogenarians--a postoperative quality of life assessment

OBJECTIVE: Assessment of postoperative quality of life in patients over 80 years after cardiac surgery including coronary artery bypass grafting (CABG), aortic valve replacement (AVR) and combined procedures. METHODS: Quality of life of n=136 patients over 80 years at operation (82.3+/-2.1 years), undergoing isolated CABG in 61 patients (45%), isolated AVR in 34 patients (25%) and a combination of CABG and AVR in 41 patients (30%) between January 1999 and December 2003 was reviewed. Preoperatively 66.2% presented in NYHA-class III/IV or CCS-class III/IV. Mean ejection fraction (EF) was 59.5%+/-14.0 (range 25-90%). Quality of life assessment was performed via a Seattle Angina Questionnaire. Follow-up was 100% complete for a total of 890 days (69-1853 days). RESULTS: Five-year survival was 70% for the CABG group, 75% for the AVR group and 65% for the CABG/AVR group. Quality of life was remarkable in all of the three groups after surgery. Overall 97 patients (81%) were not or little disabled in their daily activity. One hundred and twelve patients (93%) were free or considerably less symptomatic. Seventy-eight patients or 65% reported to be very satisfied with their current quality of life and 112 patients (93%) felt very reassured to have continuous full access to medical treatment despite of their advanced age. CONCLUSIONS: A remarkable quality of life and important improvement in the functional status after cardiac surgery in patients over 80 paired with a satisfactory medium-term survival justify early intervention for heart disease in this age group. Therefore, referral practice for patients over 80 years for heart surgery should be handled liberally.

Methylprednisolone Fails to Preserve Pulmonary Surfactant and Blood-Air Barrier Integrity in a Porcine Cardiopulmonary Bypass Model

BACKGROUND: Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model. MATERIALS AND METHODS: After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology). RESULTS: Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO(2) and PaO(2)/FiO(2) were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05). CONCLUSION: Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.

Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation

Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.

Acute pulmonary embolectomy three days following a coronary artery bypass graft procedure

Pulmonary embolism is very rarely reported early after cardiac surgery, most probably due to full heparinisation during cardiopulmonary bypass. We report a 66-year-old man without thromboembolic history who presented three days after a coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic instability. A CT scan confirmed paracentral bilateral pulmonary embolism requiring an urgent and successful embolectomy. Review of the literature confirms that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass patients. The possibility of pulmonary embolism must be taken into consideration in post-cardiopulmonary bypass patients with acute onset of chest pain and respiratory insufficiency.

Minimal extracorporeal circulation is a promising technique for coronary artery bypass grafting

BACKGROUND: Minimal extracorporeal circulation (MECC) is a promising perfusion technology, taking the advantage of an ECC while having a significantly reduced priming volume. We analyzed the actual possible benefits of using MECC in patients undergoing CABG procedures and compared the results with conventional extracorporeal circulation (CECC). METHODS: One thousand fifty-three consecutive patients underwent CABG surgery using the MECC perfusion technique. Subgroup analyses focused on perioperative myocardial markers (cardiac troponin I [cTnI]), incidence of atrial fibrillation (AF), and perioperative evaluation of inflammatory markers and data were compared with those of patients who underwent CABG using CECC. A propensity score analysis was performed. RESULTS: Patient characteristics and distribution of EuroSCORE risk were similar in both groups. Severity of coronary artery disease and extent of revascularization were also comparable in both groups (number of distal anastomoses: 3.2 +/- 1.1 in CECC vs 3.2 +/- 0.9 in MECC; p = not significant [ns]). The cTnI was significantly lower in the MECC group (11.0 +/- 10.8 microg/L in MECC vs 24.7 +/- 25.3 microg/L in CECC; p < 0.05). Incidence of AF was 11.1% in MECC and 39.0% in CECC (p < 0.05). Inflammatory markers (interleukin-6, SC5b-9) were lower in MECC patients (p < 0.05). Propensity score analysis confirmed faster recovery in MECC patients and lower incidence of AF. CONCLUSIONS: Minimal extracorporeal circulation is a safe perfusion technique for CABG and may therefore concurrence OPCAB and traditional CABG under CECC.

Minimized cardiopulmonary bypass combined with a smart suction device: the future of cardiopulmonary bypass?

OBJECTIVE: The standard heart-lung machine is a major trigger of systemic inflammatory response and the morbidity attributed to conventional extracorporeal circulation (CECC) is still significant. Reduction of blood-artificial surface contact and reduction of priming volume are principal aims in minimized extracorporeal circulation (MECC) cardiopulmonary bypass systems. The aim of this paper is to give an overview of the literature and to present our experience with the MECC-smart suction system. METHODS AND RESULTS: At our institution, 1799 patients underwent isolated coronary artery bypass grafting (CABG) surgery, 1372 with a MECC-smart suction system and 427 with CECC. All in-hospital data were assessed and the results were compared between the 2 groups. Patient characteristics and the distribution of EuroSCORE risk profile in our collective were similar between both groups. Average age in the MECC collective was 67.5 +/- 11.4 years and average EuroSCORE was 5.0 +/- 1.5. Average number of distal anastomoses was similar to the average number encountered in patients undergoing CABG surgery with CECC (3.3 +/- 1.0 for MECC versus 3.2 +/- 1.1 for CECC; P = ns). Myocardial protection is superior in MECC patients with lower postoperative maximal cTnI values (11.0 +/- 10.8 micromol/L for MECC versus 24.7 +/- 25.3 micromol/L for CECC; P < .05). Postoperative recovery was faster in patients operated on with the MECC-smart suction system and discharge from the hospital was earlier than for CECC patients (7.4 +/- 1.9 days for MECC versus 8.8 +/- 3.8 days for CECC; P < .05). CONCLUSIONS: The MECC-smart suction system is a safe perfusion technique for CABG surgery. In patients operated on with this system, the clinical outcome seems to be better than in patients operated on with CECC. This promising and less damaging perfusion technology has the potential to replace CECC systems in CABG surgery.

Off-pump extraanatomic aortic bypass for the treatment of complex aortic coarctation and hypoplastic aortic arch

BACKGROUND: Despite advances in surgical and interventional techniques, the optimal surgical treatment of severe aortic (re) coarctation and hypoplastic aortic arch is still controversial. Anatomic repair may require extensive dissection, cardiopulmonary bypass, and deep hypothermic circulatory arrest with their inherent risks. The aim of this study was to analyze the outcome of off-pump extraanatomic aortic bypass as a surgical alternative to local repair. METHODS: From February 2000 to December 2005, ten consecutive patients (median age 20 years; range, 11 to 38 years) with severe aortic (re) coarctation (n = 4) and (or) hypoplastic aortic arch (n = 7) underwent off-pump extraanatomic aortic bypass through median sternotomy. All but three patients had undergone previous surgery for coarctation and angioplasty or stenting. Three patients underwent concomitant replacement of the ascending aorta because of an aneurysm using cardiopulmonary bypass. RESULTS: Postoperative hospital course was uneventful in all patients. There was no perioperative mortality or significant morbidity. During a mean follow-up of 48 +/- 22 months no patient required additional procedures. All patients were free of symptoms; no patient showed signs of heart failure after follow-up. At last follow-up, no patient presented with claudication, nor any patient experienced orthostatic problems due to a steal phenomenon. During follow-up, hypertension resolved in all patients with residual mild hypertension in two patients. CONCLUSIONS: Off-pump extraanatomic aortic bypass is an attractive treatment option for complex aortic (re) coarctation and hypoplastic aortic arch. Perioperative risks are minimized, hypertension is influenced favorably, and midterm survival is event-free.

Addition of dextran sulfate to blood cardioplegia attenuates reperfusion injury in a porcine model of cardiopulmonary bypass

OBJECTIVE: Contact of blood with artificial surfaces and air as well as ischemia/reperfusion injury to the heart and lungs mediate systemic and local inflammation during cardiopulmonary bypass (CPB). Activation of complement and coagulation cascades leads to and accompanies endothelial cell damage. Therefore, endothelial-targeted cytoprotection with the complement inhibitor and endothelial protectant dextran sulfate (DXS, MW 5000) may attenuate CBP-associated myocardial and pulmonary injury. METHODS: Eighteen pigs (DXS, n=10; phosphate buffered saline [PBS], n=8) underwent standard cardiopulmonary bypass. After aortic cross-clamping, cardiac arrest was initiated with modified Buckberg blood cardioplegia (BCP), repeated after 30 and 60 min with BCP containing either DXS (300 mg/10 ml, equivalent to 5mg/kg) or 10 ml of PBS. Following 30 min reperfusion, pigs were weaned from CPB. During 2h of observation, cardiac function was monitored by echocardiography and invasive pressure measurements. Inflammatory and coagulation markers were assessed regularly. Animals were then sacrificed and heart and lungs analyzed. RESULTS: DXS significantly reduced CK-MB levels (43.4+/-14.8 ng/ml PBS, 35.9+/-11.1 ng/ml DXS, p=0.042) and significantly diminished cytokine release: TNFalpha (1507.6+/-269.2 pg/ml PBS, 222.1+/-125.6 pg/ml DXS, p=0.0071), IL1beta (1081.8+/-203.0 pg/ml PBS, 110.7+/-79.4 pg/ml DXS, p=0.0071), IL-6 (173.0+/-91.5 pg/ml PBS, 40.8+/-19.4 pg/ml DXS, p=0.002) and IL-8 (304.6+/-81.3 pg/ml PBS, 25.4+/-14.2 pg/ml DXS, p=0.0071). Tissue endothelin-1 levels were significantly reduced (6.29+/-1.90 pg/100mg PBS, 3.55+/-1.15 pg/100mg DXS p=0.030) as well as thrombin-anti-thrombin formation (20.7+/-1.0 microg/ml PBS, 12.8+/-4.1 microg/ml DXS, p=0.043). Also DXS reduced cardiac and pulmonary complement deposition, neutrophil infiltration, hemorrhage and pulmonary edema (measured as lung water content, 81+/-3% vs 78+/-3%, p=0.047), indicative of attenuated myocardial and pulmonary CPB-injury. Diastolic left ventricular function (measured as dp/dt(min)), pulmonary artery pressure (21+/-3 mmHg PBS, 19+/-3 mmHg DXS, p=0.002) and right ventricular pressure (21+/-1 mmHg PBS, 19+/-3 mmHg DXS p=0.021) were significantly improved with the use of DXS. CONCLUSIONS: Addition of DXS to the BCP solution ameliorates post-CPB injury and to a certain extent improves cardiopulmonary function. Endothelial protection in addition to myocyte protection may improve post-CPB outcome and recovery.

Different anticoagulation strategies in off-pump coronary artery bypass operations: a European survey

In order to determine anticoagulation strategies in OPCAB a questionnaire survey among 750 European cardio-thoracic surgeons was performed. Questions addressed volume of OPCAB procedures performed, intra- and perioperative heparinization and antiplatelet therapy, as well as perioperative management. A total of 325 (43.7%) questionnaires were returned and validated. Perioperative protocols for administration of antiplatelets differed among the respondent surgeons. Perioperative prophylaxis of thrombosis (low or high molecular weight heparin) is performed by 78%. Intraoperative heparin dosage range between 70 U/kg to 500 U/kg, 60% of respondents prefer a low-dose regimen (< or = 150 U/kg). Correspondingly, the lowest activated clotting time (ACT) during surgery is accepted to be 200 s by 24%, 250 s by 18% and 300 s by 26% of surgeons. Protamine is used by 91% of respondents, while 52% perform a 1:1 reversal. A cell-saver and antifibrinolytics are used by 70% and 40%, respectively. Interestingly, 56% of respondents think bleeding in OPCAB patients is not reduced when compared to on-pump CABG. In addition, 34% of respondents believe there is an increased risk of early graft occlusion following OPCAB. This survey demonstrates widely different intra- and perioperative anticoagulation strategies for OPCAB procedures among European surgeons.

Aprotinin in cardiac surgery: a different point of view

Aprotinin is widely used in cardiac surgery to reduce postoperative bleeding and the need for blood transfusion. Controversy exists regarding the influence of aprotinin on renal function and its effect on the incidence of perioperative myocardial infarction (MI) and cerebrovascular incidents (CVI). In the present study, we analyzed the incidence of these adverse events in patients who underwent coronary artery bypass grafting (CABG) surgery under full-dose aprotinin and compared the data with those recently reported by Mangano et al [2006]. For 751 consecutive patients undergoing CABG surgery under full-dose aprotinin (>4 million kalikrein-inhibitor units) we analyzed in-hospital data on renal dysfunction or failure, MI (defined as creatine kinase-myocardial band > 60 iU/L), and CVI (defined as persistent or transient neurological symptoms and/or positive computed tomographic scan). Average age was 67.0 +/- 9.9 years, and patient pre- and perioperative characteristics were similar to those in the Society of Thoracic Surgeons database. The mortality (2.8%) and incidence of renal failure (5.2%) ranged within the reported results. The incidence rates of MI (8% versus 16%; P < .01) and CVI (2% versus 6%; P < .01) however, were significantly lower than those reported by Mangano et al. Thus the data of our single center experience do not confirm the recently reported negative effect of full-dose aprotinin on the incidence of MI and CVI. Therefore, aprotinin may still remain a valid option to reduce postoperative bleeding, especially because of the increased use of aggressive fibrinolytic therapy following percutaneous transluminal coronary angioplasty.

Off-pump coronary artery bypass operation does not increase procoagulant and fibrinolytic activity: preliminary results

BACKGROUND: This study analyzes the effects on coagulation and fibrinolysis comparing off-pump coronary artery bypass (OPCAB) and on-pump CABG operations. METHODS: In a prospective, nonrandomized, comparative evaluation, patients scheduled for elective myocardial revascularization were studied. Due to possible confounding factors patients with postoperative retransfusion of mediastinal shed blood were excluded. Nine patients underwent OPCAB operation and 16 underwent on-pump CABG. Activated clotting time (ACT) was adjusted to 250 seconds in OPCAB (81 +/- 18 [mean +/- SD] IU/kg heparin) and to more than 480 seconds in on-pump CABG (400 IU/kg heparin, additional 10,000 IU in pump prime). Perioperatively blood samples were collected and hematologic and hemostatic variables including fibrinopeptide A (FPA), fibrin monomer (FM), thrombin-antithrombin complex (TAT), and D-dimer were analyzed. RESULTS: Both groups showed comparable demographic variables. Number of grafts per patient was slightly higher in the on-pump group (3.6 +/- 0.6 versus 3.0 +/- 1.1, p = 0.23). The FPA levels did not differ significantly between the groups. The FM, TAT, and D-dimer values were significantly higher in on-pump CABG (p < 0.0001, p < 0.01, and p < 0.0001, respectively), reflecting increased coagulant and fibrinolytic activity. This was also the case when values were corrected for hemodilution. CONCLUSIONS: Despite lower systemic anticoagulation activation of coagulation and fibrinolysis is reduced in OPCAB compared with on-pump CABG. Reduced thrombin generation and reduced fibrinolytic activity in OPCAB indicates better preservation of hemostasis. We suggest the term "preserved hemostasis" instead of "hypercoagulant activity" with respect to OPCAB.

[Role of coronary artery bypass grafting in the treatment of coronary artery disease - a well-balanced information of the patients and objective decision making are welcome]

Most recently discussion about the optimal treatment for different subsets of patients suffering from coronary artery disease has re-emerged, mainly because of the uncertainty caused by doctors and patients regarding the phenomenon of unpredictable early and late stent thrombosis. Surgical revascularization using multiple arterial bypass grafts has repeatedly proven its superiority compared to percutaneous intervention techniques, especially in patients suffering from left main stem disease and coronary 3-vessels disease. Several prospective randomized multicenter studies comparing early and mid-term results following PCI and CABG have been really restrictive, with respect to patient enrollment, with less than 5% of all patients treated during the same time period been enrolled. Coronary artery bypass grafting allows the most complete revascularization in one session, because all target coronary vessels larger than 1 mm can be bypassed in their distal segments. Once the patient has been turn-off for surgery, surgeons have to consider the most complete arterial revascularization in order to decrease the long-term necessity for re-revascularization; for instance patency rate of the left internal thoracic artery grafted to the distal part left anterior descending artery may be as high as 90-95% after 10 to 15 years. Early mortality following isolated CABG operation has been as low as 0.6 to 1% in the most recent period (reports from the University Hospital Berne and the University Hospital of Zurich); beside these excellent results, the CABG option seems to be less expensive than PCI with time, since the necessity for additional PCI is rather high following initial PCI, and the price of stent devices is still very high, particularly in Switzerland. Patients, insurance and experts in health care should be better and more honestly informed concerning the risk and costs of PCI and CABG procedures as well as about the much higher rate of subsequent interventions following PCI. Team approach for all patients in whom both options could be offered seems mandatory to avoid unbalanced information of the patients. Looking at the recent developments in transcatheter valve treatments, the revival of cardiological-cardiosurgical conferences seems to a good option to optimize the cooperation between the two medical specialties: cardiology and cardiac surgery.

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.