Pharmacokinetics of tranexamic acid in patients undergoing cardiac surgery with use of cardiopulmonary bypass.

We conducted a study to assess pharmacokinetics of high-dose tranexamic acid for 24 h after administration of the drug in patients undergoing cardiac surgery with cardiopulmonary bypass. High-dose tranexamic acid involved a bolus of 30 mg.kg(-1) infused over 15 min followed by a 16 mg.kg(-1) .h(-1) infusion until chest closure with a 2 mg.kg(-1) load within the pump prime. Tranexamic acid followed first-order kinetics best described using a two-compartment model, with a total body clearance that approximated the glomerular filtration rate. Mean plasma tranexamic acid concentrations during the intra-operative period and in the first 6 postoperative hours were consistently higher than the suggested threshold to achieve 100% inhibition and 80% inhibition of tissue plasminogen activator. With recent studies implicating high-dose tranexamic acid as a possible aetiology of postoperative seizures following cardiac surgery, the minimum effective yet safe dose of tranexamic acid in high-risk cardiac surgery needs to be refined.

Fast-track cardiac anaesthesia in the elderly: effect of two different anaesthetic techniques on mental recovery.

Elderly patients may be considered for 'fast-track' cardiac anaesthesia, but can suffer psychological complications and slow recovery of mental function after surgery, which can interfere with recovery. Reduced metabolism and changed distribution of anaesthetic and sedative agents can cause poor recovery. We made a prospective randomized comparison of mental function, haemodynamic stability and extubation and discharge times in elderly patients (65-79 yr) receiving two premedication, anaesthetic and sedative techniques. Patients received either propofol (n=39) (fentanyl 10-15 microg kg(-1) and propofol 2-6 mg kg(-1) intraoperatively and a propofol infusion for 3 h postoperatively) or premedication with lorazepam followed by midazolam for anaesthesia (n=39) (fentanyl 10-15 microg kg(-1) and midazolam 0.05-0.075 mg kg(-1) intraoperatively and a midazolam infusion for 3 h postoperatively). Impairment of mental function was noted in 41% of patients in the propofol group and 83% in the lorazepam and midazolam group (P=0.001) 18 h after extubation. Patients in the propofol group were extubated earlier [1.4 (SD 0.6) vs 1.9 (0.8) h, P=0.02]; and reached standard intensive care unit discharge criteria [7.6 (4.6) vs 14.2 (13) h, P=0.02] and hospital discharge criteria [4.3 (1.0) vs 4.9 (1.1) days, P=0.04) sooner than patients in the lorazepam and midazolam group, but actual discharge times did not differ between the groups. Haemodynamic values were stable in both groups.

Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after cardiac surgery.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are used as analgesic in postoperative pain to reduce opioid side effects, such as drowsiness and nausea. However, NSAIDs have not been used extensively in cardiac surgical patients due to the fear of untoward effects on gastric, renal, and coagulation parameters. This study will evaluate the efficacy and safety of three NSAIDs for pain control in CABG patients. METHODS: One hundred and twenty patients scheduled for elective CABG surgery were enrolled in randomized, double blind, controlled study. Standardized fast track cardiac anesthesia was used. One dose of drug (75 mg diclofenac, 100 mg ketoprofen, 100 mg indomethacin, or placebo) was given pr one hour before tracheal extubation and a second dose 12 hr later. Pain was treated with morphine iv and acetaminophen po. Visual analogue pain scores were recorded at baseline, 3, 6, 12 and 24 hr after the first dose of drug. RESULTS: There were no differences among the groups in pain scores. Only patients who received diclofenac required less morphine than patients in the control group (P < 0.05). When the total amounts of pain medications were computed to morphine equivalents, only patients in the diclofenac group received less pain medications than the placebo group (P < 0.05). Proportion of patients with postoperative increase of creatinine level (20% and over) did not differ between placebo and drug groups. CONCLUSION: Non-steroidal anti-inflammatory drugs may be used for analgesia management post CABG surgery in selected patients. Diclofenac appears to have the best analgesic effects by reducing the morphine and other analgesic requirement postoperatively.

Etiology of preoperative anemia in patients undergoing scheduled cardiac surgery.

PURPOSE: Ten percent of our cardiac surgical patients have preoperative anemia. Anemia diagnosed before scheduled cardiac surgery is a strong predictor of the need for homologous blood transfusion (RBC) perioperatively but the cause of this preoperative anemia is not known. The purpose of this study was to evaluate the etiology of preoperative anemia. METHODS: Seventy-five consecutive anemic cardiosurgical patients (Hb = < 120 g x L(-1) the day before surgery) were studied prospectively. All had multiple diagnostic blood tests done in the preoperative period to diagnose the cause of the anemia and subsequently underwent non-emergency cardiac surgery. Anesthesia and RBC transfusion were standardized according to the protocol. Data in respect to operation, RBC and other blood product transfusion during operation and hospital stay were recorded. RESULTS: Hospital-acquired anemia was present in 37.3% of anemic patients (hemoglobin decrease during hospitalization before surgery > or =9 g x l(-1)). The second most common diagnosis was iron deficiency anemia (29.3% patients) followed by anemia of chronic renal disease (10.7% patients). When coronary angiography was performed close to operation time, patients had a higher decrease in hemoglobin concentration during hospitalization --suggesting that blood loss during angiography was, in part, responsible for anemia. Seventy-five percent of anemic patients were transfused with RBC perioperatively compared with our overall transfusion rate of 30% of cardiac surgery patients. CONCLUSIONS: In the majority of patients, preoperative anemia is potentially preventable. Investigation and treatment of anemia before cardiac surgery should be a priority in preparing the patient for surgery.

Fast-track cardiac anesthesia in patients with sickle cell abnormalities.

UNLABELLED: We conducted a retrospective review of 10 patients with sickle cell trait (SCT) and 30 patients (cohort control) without SCT undergoing first-time coronary artery bypass graft surgery with cardiopulmonary bypass. Demographic, perioperative management, and outcome data were collected. Both groups were matched according to age, weight, duration of surgery, and preoperative hemoglobin (Hb) concentration. Distribution of gender, medical conditions, pharmacological treatment, and preoperative left ventricular function were similar between the groups. The comparisons were analyzed in respect to postoperative blood loss and transfusion rates, as well as duration of intubation, intensive care unit, and hospital length of stay (LOS). All patients underwent fast-track cardiac anesthesia. A combination of cold crystalloid and blood cardioplegia was used. The lowest nasopharyngeal temperature was 33 degrees C. There were no episodes of significant hypoxemia, hypercarbia, or acidosis. None of the patients had sickling crisis during the perioperative period. The postoperative blood loss was 687 +/- 135 vs 585 +/-220 mL in the SCT and control groups, respectively. The trigger for blood transfusion during cardiopulmonary bypass was hematocrit <20% and Hb <75 g/L postoperatively. Three SCT patients (30%) and 10 control patients (33%) received a blood transfusion. Median extubation time was 4.0 vs 3.9 h; intensive care unit LOS was 27 vs 28 h; and hospital LOS was 6.0 vs 5.5 days in the SCT and control groups, respectively. There were no intraoperative deaths. One patient in the SCT group died from multiorgan failure 2 mo after surgery. IMPLICATIONS: Fast-track cardiac anesthesia can be used safely in patients with sickle cell trait undergoing first-time coronary artery bypass graft surgery. Extubation time and intensive care unit and hospital length of stay are comparable to those of matched controls, and blood loss and transfusion requirements are not increased. A hematocrit of 20% seems to be a safe transfusion trigger during cardiopulmonary bypass in these patients.

Morbidity outcome in patients with hypertrophic obstructive cardiomyopathy undergoing cardiac septal myectomy: early-extubation anesthesia versus high-dose opioid anesthesia technique.

OBJECTIVE: Anesthetic management of patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myectomy is challenging. The morbidity outcome of early-extubation anesthesia (EEA), or fast tracking, versus high-dose opioid (HDO) anesthesia was studied. DESIGN: Retrospective study. SETTING: University teaching hospital. PARTICIPANTS: One hundred seventy-five cardiac septal myectomy patients (EEA, n = 53; HDO, n = 122). INTERVENTIONS: EEA technique consisted of low-dose fentanyl, 10 to 15 microg/kg; propofol infusion; midazolam; and inhalation agent. HDO technique consisted of fentanyl, 50 to 100 microg/kg, and benzodiazepines, with or without an inhalation agent. Demographic data, preoperative symptoms, and data on anesthesia management and postoperative complications were recorded. MEASUREMENTS AND MAIN RESULTS: There were no differences between the groups (EEA v HDO, respectively) regarding age, sex, preoperative symptoms (dyspnea, 89% v 79%; palpitations, 28% v 26%; angina, 47% v 61%; syncope, 47% v 41%), redo surgery, or combined surgery. Mean +/- standard deviation time to tracheal extubation was 7.2 +/- 5.3 hours in EEA versus 19.4 +/- 10.5 hours in HDO patients (p < 0.0001). Intensive care unit (ICU) stay was significantly shorter in EEA versus HDO patients (2.2 v 3.0 days; p < 0.005), with the trend toward earlier hospital discharge (9.7 v 11.3 days; p = 0.09). There was a high requirement for temporary pacing in both groups immediately postoperatively (EEA, 60% v HDO, 48%; p > 0.08). Permanent pacemaker insertion postoperatively was required in 7 of 53 patients (13%) in the EEA group and 11 of 122 patients (9%) in the HDO group (p > 0.25). Atrial arrhythmias occurred postoperatively in 25% of EEA patients versus 34% of HDO patients (p > 0.08). CONCLUSION: EEA facilitates earlier tracheal extubation by 12 hours in patients with HOCM undergoing septal myectomy, significantly shortening ICU stay by 1 day without increasing perioperative cardiac morbidity or mortality.

The effect of three different doses of tranexamic acid on blood loss after cardiac surgery with mild systemic hypothermia (32 degrees C).

OBJECTIVE: Prophylactic administration of tranexamic acid (TA), an antifibrinolytic agent, decreases bleeding after cardiac surgery with systemic hypothermia (25 degrees C to 29 degrees C). Warmer systemic temperatures during cardiopulmonary bypass (CPB) may reduce bleeding and thus alter the requirement for TA. The effect of three different doses of TA on bleeding after cardiac surgery with mild systemic hypothermia (32 degrees C) is evaluated. DESIGN: Double-blind, prospective, randomized study. SETTING: University hospital. PARTICIPANTS: One hundred fifty adult patients undergoing aortocoronary bypass or valvular cardiac surgery. INTERVENTIONS: Patients received TA, 50 (n = 50), 100 (n = 50), or 150 (n = 50) mg/kg intravenously before CPB with mild systemic hypothermia. MEASUREMENTS AND MAIN RESULTS: Blood loss through chest drains over 6, 12, and 24 hours after surgery and total hemoglobin loss were measured. Autotransfused blood, transfused banked blood and blood products, and coagulation profiles were measured. Analysis of variance on log-transformed data for blood loss and confidence intervals (CIs) of 0.95 were calculated and transformed to milliliters of blood. No patient was re-explored for bleeding. Blood loss at 6 hours was statistically greater in the 50-mg/kg group compared with the other two groups (p = 0.03; p = 0.02). Total hemoglobin loss was statistically greater in the 50-mg/kg group compared with the 150-mg/kg group (p = 0.04). There was no statistical difference in blood tranfusion rate or coagulation profiles among the three groups. However, preoperative hemoglobin level was statistically lower in the 150-mg/kg group compared with the other two groups (p = 0.01). CONCLUSION: Of the three doses of TA studied, the most efficacious and cost-effective dose to reduce bleeding after cardiac surgery with mild hypothermic systemic perfusion is 100 mg/kg.

Intraoperative awareness in fast-track cardiac anesthesia.

BACKGROUND: Fast-track cardiac anesthesia, using low-dose narcotics combined with short-acting anesthetic and sedative agents, facilitates early tracheal extubation after cardiac surgery. The incidence of awareness with this anesthetic technique has not been investigated previously. The purpose of this study was to prospectively investigate the incidence of intraoperative awareness with explicit memory of events during fast-track cardiac anesthesia. METHODS: Data were collected prospectively over a 4-month period from 617 consecutive adult patients undergoing cardiac surgery at a university hospital. All patients received a fast-track cardiac anesthetic regimen. Patients underwent a structured interview by a research nurse 18 h after extubation. A standard set of questions was asked during this interview to determine if the patient had explicit memory of any event from induction of anesthesia to recovery of consciousness. RESULTS: Nine patients did not complete a postoperative interview because of death (n = 7) or postoperative confusion (n = 2). The last memory before surgery reported in 420 (69.1%) patients was waiting in the holding area at the operating suite, and in the remaining 188 (30.9%) patients it was lying on the operating table before induction of anesthesia. Two patients (0.3%) had explicit memory of intraoperative events. One of the two patients also had explicit memory of pain. Neither patient reported adverse psychological sequelae. CONCLUSIONS: The authors report an incidence of awareness in fast-track cardiac anesthesia of 0.3%. This is the lowest incidence of awareness currently reported during cardiac surgery. This low incidence of awareness may be related to the use of a balanced anesthetic technique involving the continuous administration of volatile (isoflurane) or intravenous (propofol) anesthetic agents before, during, and after cardiopulmonary bypass.

Routine chest roentgenography on admission to intensive care unit after heart operations: is it of any value?

The need for routine immediate postoperative chest roentgenography after heart operations has recently been questioned. In this study we investigated the impact of routine postoperative chest roentgenography on treatment instituted in the cardiovascular intensive care unit immediately after heart operations done via median sternotomy. A total of 404 random patients admitted to the cardiovascular intensive care unit underwent clinical (positioning of endotracheal tube, nasogastric tube, and pulmonary artery catheter) and laboratory (oxygenation) assessment by a cardiovascular intensive care unit physician according to a strict protocol. After clinical assessment, chest roentgenography was done for all admitted patients and the findings reviewed by the same physician. Pathologic conditions noted were recorded on the study form together with any required treatment. Eighteen patients (4.5%) out of 404 required intervention because of abnormalities detected by the chest x-ray film but not predicted by the initial physical and laboratory assessment. None of the pathologic conditions detected was life threatening. We conclude that chest roentgenography done on admission to the cardiovascular intensive care unit should be done only if clinical and laboratory assessment indicate the possibility of underlying pathologic conditions that can only be confirmed or diagnosed by chest roentgenography.

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial.

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.

Thyrotoxicosis factitia in a post-aortocoronary bypass patient.

A 52-yr-old man presented with an evolving myocardial infarction and unstable angina. Previously, he had undergone aortocoronary bypass surgery for triple vessel disease and at that time was diagnosed as hypothyroid. He had been refractory to thyroxine treatment and now required 0.3 mg thyroxine daily. On admission, he was hypertensive, tachycardic and found to be thyrotoxic secondary to excess thyroid hormone ingestion. Treatment with iopanoic acid was started. Despite medical therapy he continued to have unstable angina. Coronary angiography confirmed further triple vessel disease with blockage to his previous grafts. He was taken to surgery for coronary revascularization. On arriving in the intensive care unit he developed a thyroid storm. His temperature increased from 36.5 to 39.5 degrees C requiring a cooling blanket and cold irrigation down a nasogastric tube. An esmolol infusion was started to control his persistent tachycardia but this depressed his myocardial contractility. He required amrinone and noradrenaline infusions as further inotropic support. For sedation and muscle relaxation, intravenous propofol infusion and doxacurium were given. Over the following 20 hr the patient's condition stabilized. In conclusion, we describe the use of a short-acting beta blocker to avoid compromising an impaired myocardium during a thyroid storm which we could stop if the patient's cardiac condition deteriorated. In addition, amrinone, a phosphodiesterase inhibitor, was our inotrope of choice as it does not act on the already blocked beta adrenergic system.

Prevention of postbypass bleeding with tranexamic acid and epsilon-aminocaproic acid.

In this institution, two antifibrinolytic agents have been in routine use before cardiopulmonary bypass (CPB) to prevent bleeding due to fibrinolysis; epsilon-aminocaproic acid (EACA) or tranexamic acid (TA) are administered as intravenous infusions over 2 hours, from the time of anesthetic induction until the onset of CPB. TA is 10 times more potent and binds more strongly to plasminogen than EACA. Data were collected retrospectively on 411 patients undergoing first-time coronary artery bypass grafting with cardiopulmonary bypass who had received one of four therapy regimens: 10 g of EACA (65 patients), 15 g of EACA (60 patients), 6 g of TA (100 patients), or 10 g of TA (75 patients). Patients who did not receive any drug (91) served as controls. Anesthetic technique and the heparin/protamine protocol did not differ. Blood collected by mediastinal and pleural tubes was autotransfused up to 6 hours postoperatively. Both TA and EACA reduced post-CPB bleeding in the first 24 hours. Ten grams of TA was the most effective, resulting in a 52% and 36% reduction in blood loss over controls at 6 and 24 hours, respectively. Although 10 g of TA was more effective than 6 g of TA in blood loss control for the first 6 hours, the difference was not significant at 24 hours. A significantly lower number of patients in the 10 g TA group received blood products than in control (28% v 49%) patients (P = 0.02). Pretreatment with 10 g of TA prevented excessive (over 750 mL in 6 hours) bleeding after CPB.