Perioperative Myocardial Infarction in Non-Cardiac Surgery Patients: A Prospective Observational Study.

BACKGROUND AND AIMS: Perioperative myocardial infarction is an underdiagnosed complication causing morbidity, mortality, and considerable costs. However, evidence of preventive and therapeutic options is scarce. We investigated the incidence and outcome of perioperative myocardial infarction in non-cardiac surgery patients in order to define a target population for future interventional trials. MATERIAL AND METHODS: We conducted a prospective single-center study on non-cardiac surgery patients aged 50 years or older. High-sensitivity troponin T and electrocardiograph were obtained five times perioperatively. Perioperative myocardial infarction diagnosis required a significant troponin T release and an ischemic sign or symptom. Perioperative risk calculator was used for risk assessment. RESULTS: Of 385 patients with systematic ischemia screening, 27 patients (7.0%) had perioperative myocardial infarction. The incidence was highest in vascular surgery-19 of 172 patients (11.0%). The 90-day mortality was 29.6% in patients with perioperative myocardial infarction and 5.6% in non-perioperative myocardial infarction patients ( p < 0.001). Perioperative risk calculator predicted perioperative myocardial infarction with an area under curve of 0.73 (95% confidence interval: 0.64-0.81). CONCLUSION: Perioperative myocardial infarction is a common complication associated with a 90-day mortality of 30%. The ability of the perioperative risk calculator to predict perioperative myocardial infarction was fair supporting its routine use.

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.

INTRODUCTION: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. MATERIALS AND METHODS: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. RESULTS: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). CONCLUSIONS: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.

Platelet transfusions in adult patients with particular reference to patients undergoing surgery.

Descriptive information on platelet (PLT) recipients, particularly during surgery, is limited. A description of the current epidemiology of PLT-transfused patients is required to optimize platelet transfusion care and to follow trends in PLT use. In 2004 and 2005, information was combined from several computerized medical systems. Participating hospitals (9 hospital districts of 21) handled approximately 64% of annual Finnish hospital admissions. A total of 6321 adult patients were transfused with 37,761 PLT products. Most PLT products (43.1%) were transfused to patients suffering from haematological malignancies. Only 1.0% of all surgical patients received PLTs (53.8% of PLT recipients and 35.8% of transfused PLTs). The most common single operation connected with PLT transfusion was coronary artery bypass while 27.1% of surgery-related PLTs were given to patients having an operation involving the digestive system or spleen. Only 36.4% of all PLT-transfused (operated and conservatively treated) patients were discharged directly home; in-hospital mortality was 9.5%. PLTs were given 40 products per 1000 hospital admissions requiring an operation in 2004, and 38 products in 2005. Perioperative PLT use is slightly decreasing in adult patients. As a single-operation type, coronary artery bypass patients receive most of the PLT products and have experienced no decline in PLT use over the years. Overall, PLT recipients have high in-hospital mortality.

Diabetes care for patients with peripheral arterial disease.

The number of diabetics will increase almost 70% in developed countries during the next 20 years: peripheral arterial disease is a common and costly complication. The incidence of cardiovascular disease (mortality and morbidity) due to atherosclerosis, is higher among patients with diabetes than in those without diabetes. Intensive management of diabetes, including glycaemic control, treatment of hypertension and dyslipidemia, as well as nonpharmacological interventions, decreases both micro- and macrovascular complications. Aspirin and clopidogrel have less antiplatelet effect in patients with diabetes. Metformin therapy is considered a risk factor for lactic acidosis if not withdrawn 2 days before angiography, but this risk is extremely low in patients with normal renal function. Peri-operative hyperglycaemia and large fluctuations in plasma glucose increase postoperative mortality and morbidity and careful measures are required to minimise these effects.

Acute renal injury and dysfunction following elective abdominal aortic surgery.

OBJECTIVES: To evaluate the incidence of kidney injury and acute renal dysfunction (ARD) and associated risk factors in open abdominal aortic surgery. MATERIALS AND METHODS: 69 patients undergoing elective infrarenal aortic repair were included in a prospective study. Anaesthesia and haemodynamic management were standardised targeting a mean arterial pressure (MAP) of 70-90 mmHg, pulmonary artery occlusion pressure of 12-14 mmHg and cardiac index >or=2.4 l/min/m(2). Urinary albumin-creatinine and N-acetyl-B-D-glucosaminidase-creatinine ratios were measured as indicators of kidney injury. The definition of ARD was based on the RIFLE criteria. RESULTS: Kidney injury was found in most patients. ARD developed in 22% of the patients, and acute renal failure in 4%. The patients with ARD were older, and had lower plasma creatinine and estimated GFR before surgery. ARD was associated with intraoperative hypotension (MAP <60 mmHg >15 min), low cardiac index (<2.4 l/min/m(2)), rhabdomyolysis, and early reoperation. Intraoperative hypotension and postoperative low cardiac output were independent risk factors for ARD in multivariate analysis. CONCLUSIONS: Kidney injury occurs in most patients undergoing infrarenal aortic surgery, but only 22% develop acute renal dysfunction. Hypotension and low cardiac output are risk factors that could be avoided by optimizing perioperative management.

Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery.

BACKGROUND: Pre-existing chronic renal failure is a significant risk factor for acute renal failure (ARF) after cardiac surgery. N-acetylcysteine (NAC) has been shown to prevent contrast media-induced ARF. Our objective was to evaluate whether i.v. NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery. METHODS: In this prospective, randomized, double-blind study, 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited. All received either i.v. NAC (n=38) or placebo (n=39) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase (NAG) and urine creatinine ratio, plasma creatinine, and serum cystatin C levels indicated renal function. RESULTS: Levels of urinary NAG/creatinine ratio, plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days. Urine NAG/creatinine ratio increased over 30% in 100% of patients in the NAC group vs 92.3% in the placebo group (P=0.081). Plasma creatinine increased by 25% from baseline or over 44 mumol litre(-1) in 42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serum cystatin C exceeded 1.4 mg litre(-1) in 78.9% in NAC group vs 61.5% in placebo group (P=0.096). CONCLUSIONS: Prophylactic treatment with i.v. N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery.

The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery.

BACKGROUND: Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery. METHODS: Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used. RESULTS: Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti-thrombin III complexes 33.7 +/- 3.6, 53.6 +/- 7.0 and 44.2 +/- 5.3 microg/l 2 h after CPB and F1 + 2 fragment 1.50 +/- 0.10, 2.37 +/- 0.37 and 2.04 +/- 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti-fibrinolytic drugs (D-dimers 0.427 +/- 0.032, 0.394 +/- 0.039 and 2.808 +/- 0.037 mg/l 2 h after CPB, respectively). The generation of d-dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti-plasmin complexes 0.884 +/- 0.095, 2.764 +/- 0.254 and 1.574 +/- 0.185 mg/l 2 h after CPB, respectively). CONCLUSION: Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery.

Brain injury after adult cardiac surgery.

Despite remarkable progress in surgical, cardiopulmonary bypass and anaesthetic techniques during the last three decades, brain damage remains an important complication of adult cardiac surgery. Effective brain protection strategies are already implemented today, but ongoing research is needed to meet the challenges faced in operating on increasingly old and disabled patients. The incidence of brain injury may be reduced by modifying the surgical procedure according to carotid duplex scanning and epiaortic echocardiography, by using techniques to reduce microembolization during cardiopulmonary bypass and by optimizing patient temperature during and after surgery. Increased knowledge will aid in choosing the best procedure or combination of procedures in each case to ensure that risks do not outweigh benefits.

No effect of cardiopulmonary bypass on hypnosis in patients anaesthetized with propofol and alfentanil.

BACKGROUND: The effect of cardiopulmonary bypass (CPB) on the level of anaesthetic depth has not been studied previously in a randomized way. METHODS: We assessed the effect of CPB on the propofol needed to maintain a fixed bispectral index score, and on the recovery from anaesthesia in 22 patients undergoing coronary artery bypass graft surgery with CPB (on-pump) compared with 18 patients operated on without CPB (off-pump). Anaesthesia was induced and maintained with propofol and alfentanil. Throughout the procedure, the infusion rate of propofol was adjusted to keep the BIS value at 40 +/- 5. RESULTS: With the off-pump technique, the duration of surgery and anaesthetic administration were significantly greater. The need for propofol in proportion to time was exactly the same in both groups. During anaesthesia and the first 3 h thereafter, the BIS recordings were similar in both groups. No differences were detected in the time to awakening or tracheal extubation. CONCLUSIONS: CPB does not affect propofol requirements or immediate postoperative recovery compared with the off-pump technique.

Myocardial metabolism on off-pump surgery; a randomized study of 50 cases.

OBJECTIVE: To study the inflammatory reaction and myocardial metabolism in off-pump and on-pump coronary artery bypass patients. DESIGN: Fifty coronary artery bypass patients were randomized to off-pump or on-pump operations. Myocardial biopsies were taken to determine myocardial metabolism and inflammation (glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MP)) and plasma samples for indicators of oxidative stress (conjugated dienes (s-BDC), oxidative products of proteins (s-ox-Prot) and low-density lipoprotein (LDL)-total peroxyl radical trapping antioxidant potential (s-TRAP)). RESULTS: s-ox-Prot 10 min was 2.11 +/- 0.75 vs 2.69 +/- 0.60 (p = 0.014), s-TRAP 5 min was 861 +/- 180 vs 969 +/- 192 (p = 0.032) and s-TRAP 10 min 857 +/- 176 vs 985 +/- 166 (p = 0.011), GSH 10 min 0.55 +/- 0.19 vs 0.72 +/- 1.16 (p = 0.007) (off-pump vs on-pump). The monobasic (MB) fraction of the creatinine kinase 24 h after the operation was significantly lower in the off-pump group, 20.5 +/- 24.2 vs 61.8 +/- 84.6 (p = 0.023). CONCLUSION: GSH levels from the biopsies were increased in the perfusion group early in the reperfusion time showing that myocardial tissue was well protected and recovered more rapidly after cross-clamping than after the occlusion of the coronary arteries. However, release of creatinine kinase was lower in the off-pump group showing that cardiopulmonary bypass has more deleterious effects later after the operation.

On-site coagulation monitoring does not affect hemostatic outcome after cardiac surgery.

BACKGROUND: Rapid coagulation tests are now available for monitoring of bleeding patients after cardiac surgery. As inappropriate blood use in these patients may be due to lack of timely coagulation data, we studied the effect of an algorithm with on-line coagulation monitoring on transfusions in these patients. METHODS: Prospectively, patients bleeding (>1.5 ml kg(-1) 15 min(-1)) after cardiac surgery were randomly assigned to two groups: in group A (n=28), hemostatic treatment during the immediate recovery period (1 h after surgery) was based on an algorithm with on-site hemostasis monitoring, whereas during the same period group B patients (n=30) were managed solely according to the clinician's judgement; laboratory tests other than activated clotting time after heparin neutralization were prohibited. RESULTS: Cumulative chest tube drainage up to 16 h and total transfusion requirements did not differ between the groups. Using a platelet transfusion trigger of 100x10(9)/l, significantly more patients received platelets during the immediate recovery period in the algorithm group than in the control group (14 vs. 3 patients, P=0.001). Desmopressin acetate was administered more often in group A than in group B (8 vs. 2 patients, P=0.04). CONCLUSIONS: Algorithm-based therapy increased utilization of hemostatic interventions during the immediate recovery period without any obvious benefit to the hemostatic outcome. Re-evaluation of the platelet transfusion trigger seems warranted.

Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery.

We have studied the pharmacokinetics and pharmacodynamics of alfentanil, fentanyl and sufentanil together with propofol in patients undergoing coronary artery bypass graft surgery (CABG). Sixty patients (age 40-73 yr, 56 male) were assigned randomly to receive alfentanil, fentanyl or sufentanil and propofol. Plasma concentrations of these drugs and times for the plasma concentration to decrease by 50% (t50) and 80% (t80) after cessation of the infusion were determined. Times were recorded to awakening and tracheal extubation. Total dose and plasma concentrations of propofol were similar in all groups. Mean total doses of alfentanil, fentanyl and sufentanil were 443, 45 and 4.4 micrograms kg-1, respectively. Time to awakening did not differ significantly. In patients receiving fentanyl, the trachea was extubated on average 2 h later than in those receiving sufentanil and 3 h later than in those receiving alfentanil (P < 0.05). The t80 of fentanyl was longer (P < 0.05) than that of alfentanil or sufentanil, and there was a linear correlation between the t80 of the opioid and the time to tracheal extubation (r = 0.51; P < 0.01). However, the t50 values for these opioids were similar and did not correlate with recovery time. In conclusion, patients undergoing CABG and who were anaesthetized with fentanyl and propofol needed mechanical ventilatory support for a significantly longer time than those receiving alfentanil or sufentanil and propofol. On the basis of the interindividual variation observed, the time to tracheal extubation was most predictable in patients receiving alfentanil and most variable in patients receiving fentanyl, a finding which may be important if the patients are transferred to a step-down unit on the evening of the operation.

A comparison of remifentanil and alfentanil for use with propofol in patients undergoing minimally invasive coronary artery bypass surgery.

UNLABELLED: Most patients undergoing minimally invasive direct coronary artery bypass surgery can be awakened and tracheally extubated in the operating room. We have compared two techniques of total IV anesthesia in this patient population: 30 patients (aged 44 to 74 yr; 24 male) premedicated with temazepam were randomly assigned to receive either remifentanil-propofol or alfentanil-propofol. Anesthesia was induced with remifentanil 2 microg/kg or with alfentanil 40 microg/kg, with propofol, and maintained with remifentanil at 0.25 or 0.5 microg x kg(-1) x min(-1) or alfentanil at 0.5 or 1 microg x kg(-1) x min(-1). The stable maintenance infusion rate of propofol was adjusted for age. Times to awakening and tracheal extubation were recorded. Postoperatively, IV morphine provided by patient-controlled analgesia was used for 48 h. Times to awakening and tracheal extubation (mean +/- SD) were shorter (P < 0. 01) in patients receiving remifentanil, and interpatient variations in times to awakening and tracheal extubation smaller (awakening 25 +/- 7 vs 74 +/- 32 min, and extubation 27 +/- 7 vs 77 +/- 32 min). Analysis of variance revealed that postoperative consumption of morphine was dependent on both the intraoperative opioid and the time elapsed after surgery (P < 0.05): patient-controlled analgesia morphine use during the first 3 h after awakening was more in patients receiving remifentanil (P < 0.01). IMPLICATIONS: Recovery of patients undergoing Minimally Invasive Direct Coronary Artery Bypass Surgery is significantly shorter and more predictable after total IV anesthesia with remifentanil-propofol than with alfentanil-propofol, which may be important if the goal is that patients will be awakened and tracheally extubated in the operating room.

Minimally invasive coronary artery bypass grafting: one-year follow-up.

BACKGROUND: Use of the minimally invasive direct coronary artery bypass grafting (MIDCAB) technique has been associated with excellent primary results, and sparing of resources has been assumed. There is, however, a limited amount of information available concerning the results of mid-term follow-up. The purpose of this study was to present 1-year follow-up results of our first 130 consecutive MIDCAB patients. METHODS: MIDCAB operations, defined as no sternotomy, no cardiopulmonary bypass, and no aortic manipulation were started in our clinic in February 1996. One hundred thirty patients requiring invasive treatment of coronary artery disease who were not suitable for percutaneous transluminal angioplasty were included in this series. The main outcome measures were mortality, the need for subsequent invasive treatment, and 1-year NYHA classification. RESULTS: There was one hospital death, but during the first-year follow-up, four additional deaths occurred and three patients were reoperated on with conventional techniques. Five percutaneous transluminal coronary angioplasties (PTCAs) had to be performed, two because of anastomosic stenosis. Additionally, cardiac- or operation-related symptoms caused a total of 27 hospital visits among 23 patients during the first-year follow-up. Angiographic left internal thoracic artery (LITA)-left anterior descending artery (LAD) patency was 97.4% (37/38) (confidence interval [CI] ranged from 86.2% to 99.9%) at 3 months. After 1 year, 86.9% (113/130) of the patients were without symptoms. A clear improvement of the follow-up results was observed to be associated with increased experience during the study period. CONCLUSIONS: MIDCAB operations, after some experience, can be performed with relatively good outcome. However, special attention should be directed to determination of correct anastomosic site and to avoiding anastomosic stenosis. We also recommend extended mobilization of the ITA and use of specific stabilizers.

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.

AIMS: The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocardial substrate utilization of a new calcium sensitizer, levosimendan, after coronary artery bypass grafting. METHODS AND RESULTS: Twenty-three low-risk patients were included in this randomized and double-blind study. They received placebo (n = 8), 8 (n = 8) or 24 (n = 7) micrograms.kg-1 of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min-1 after the higher dose (P < 0.05). Cardiac output increased by 0.7 and 1.61.min-1 (P < 0.05 for both) after 8 and 24 micrograms.kg-1 of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42 ml/(P = 0.054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. CONCLUSION: Despite improved cardiac performance, levosimendan did not increase myocardial oxygen consumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.

Association between R-wave amplitude of the electrocardiogram and myocardial function during coronary artery bypass grafting.

OBJECTIVE: The recovery of R-wave amplitude in the V5 lead of the electrocardiogram (ECG) was recently found to be worse in nonsurvivors than in survivors after coronary artery bypass grafting (CABG). On the contrary, an increase in R-wave amplitude has been found to reflect myocardial dysfunction in exercise testing. The purpose of this study was to examine whether the changes in R-wave amplitude are associated with changes of myocardial function during CABG. DESIGN: A prospective clinical study. SETTING: Cardiothoracic division of surgery in a university hospital. PARTICIPANTS: Ten consecutive patients undergoing CABG. MEASUREMENTS: R-wave amplitude was measured at eight different time points. Left ventricular end-systolic wall tension, wall stress at isovolumic contraction (afterload), end-diastolic wall stress (preload), end-systolic wall stress per end-systolic area (contractility), and stroke work were calculated using transesophageal echocardiography and arterial pressure. MAIN RESULTS: Linear regression was calculated between changes in R-wave amplitude and echo parameters. A weak positive association within subjects was noted among R amplitude and all measured cardiac function parameters except preload. R2 value varied from 0.101 to 0.266, and R2 for preload was 0.017. CONCLUSIONS: These results suggest that only 10% to 27% of variation in R-wave amplitude can be explained by left ventricular function indices measured by echocardiography in patients with CABG. Thus, R-wave amplitude changes in an individual patient undergoing CABg have very limited utility as a noninvasive measure of left ventricular function.

Cardiopulmonary bypass with heparin-coated circuits and reduced systemic anticoagulation.

BACKGROUND: The improved biocompatibility of the cardiopulmonary bypass circuits made possible by the use of surface-immobilized heparin may allow for a reduction in the amount of heparin administered systemically. This study was performed to elucidate the effects of cardiopulmonary bypass using heparin-coated circuits and reduced heparinization on hemostatic variables and clinical outcome. METHODS: Thirty patients scheduled to undergo myocardial revascularization were randomized to have either a heparin-coated or an uncoated cardiopulmonary bypass circuit. Anticoagulation was induced with heparin (100 IU/kg in the coated group and 300 IU/kg in the uncoated group) and the activated clotting time was kept over 200 and 480 seconds in the coated and uncoated groups, respectively. RESULTS: The postoperative overnight loss of hemoglobin through the drains was lower in the heparin-coated group (43.6 g; range, 18.5-69.0 g) than in the uncoated group (73.0 g; range, 32.2-137.7 g) (p = 0.0015). Plasma concentrations of prothrombin fragment 1 + 2 and D-dimer were significantly more elevated after cardiopulmonary bypass in the coated group than they were in the uncoated group. Two patients in the coated group had a stroke postoperatively. CONCLUSIONS: The reduction in systemic heparinization was associated with thrombin formation, which may predispose to intravascular and cardiopulmonary bypass circuit clotting. Therefore, generous systemic heparinization may still be prudent despite the improved biocompatibility offered by heparin-coated surface.

Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting.

BACKGROUND: Alpha 2-adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha 2-adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting. METHODS: Eighty patients scheduled for elective coronary artery bypass grafting received, in a double-blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng.kg-1.min-1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng.kg-1.min-1 unit the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs. RESULTS: Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl-induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients). CONCLUSIONS: Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension.

Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting.

BACKGROUND: Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia. They are metabolized by cytochrome P450 3A (CYP3A) enzymes. These isozymes are inhibited by concurrent medications, including the calcium channel antagonist diltiazem, which may have an effect on recovery from anesthesia. METHODS: Thirty patients having coronary artery bypass grafting were randomly assigned to receive either diltiazem (60 mg orally 2 h before induction of anesthesia and an infusion of 0.1 mg.kg-1.h-1 started at induction and continued for 23 h) or placebo in a double-blind study. Anesthesia was induced with 0.1 mg/kg midazolam, 50 micrograms/kg alfentanil, and 20 to 80 mg propofol and maintained with infusions of 1 microgram.kg-1.min-1 of both midazolam and alfentanil supplemented with isoflurane. Plasma midazolam and alfentanil concentrations and areas under the plasma concentration-time curves were determined. The terminal half-life and the time for the drug plasma level to decrease 50% after cessation of the infusion (t50) were calculated for midazolam and alfentanil. Separation from mechanical ventilation and tracheal extubation were performed according to the study protocol. RESULTS: Diltiazem increased the mean concentration-time curves (from end of anesthesia until 23 h) of midazolam by 24% (P < 0.05) and that of alfentanil by 40% (P < 0.05). The mean half-life of midazolam was 43% (P < 0.05) and that of alfentanil was 50% (P < 0.05) longer in patients receiving diltiazem. The mean t50 of alfentanil was 40% longer (P < 0.05) in patients receiving diltiazem, but the change in the mean t50 of midazolam (25%) was not statistically significant. In patients receiving diltiazem, tracheal extubation was performed on average 2.5 h later (P = 0.054) than in those receiving placebo. CONCLUSIONS: Diltiazem slows elimination of midazolam and alfentanil and may delay tracheal extubation after large doses of these anesthetic adjuncts. CYP3A-mediated drug interactions should be considered as confounders when recovery from anesthesia with midazolam and alfentanil infusions is assessed.