Topical Tranexamic Acid on Donor Wounds in Burn Patients: A Randomized Placebo-controlled Trial.

Background: Patients with major burn injuries are prone to massive blood loss owing to tangential excision of burn wounds and donor skin harvesting. In general, topical application of the antifibrinolytic drug tranexamic acid (TXA) to surgical wounds reduces bleeding; however, its effect on bleeding and re-epithelialization in superficial wounds of burns has not been explored. Methods: This study aimed to investigate the therapeutic potential of topical TXA in reducing blood loss and its effect on wound re-epithelialization in burn surgery. Split-thickness skin graft donor wounds in burn patients were paired and randomized to topical application of either TXA (25 mg/mL) or placebo. Endpoints were postoperative bleeding as measured by dressing weight gain per cm2 wound area, blood stain area per wound area, and visual evaluation of bleeding in the dressings. Healing time was recorded to analyze the effect on wound re-epithelialization. Results: There was no significant difference in bleeding or time to re-epithelialization between the TXA and placebo wounds. A post hoc subanalysis of wounds with dressing weight gain above the median, showed a significant difference in favor of TXA. However, use of tumescence may have influenced end points. No significant adverse events related to the study drugs were observed. Conclusions: This study demonstrates that topical application of TXA (25 mg/mL) to split-thickness skin graft donor wounds does not delay re-epithelialization. Although a reduction in bleeding is suggested, further studies are needed to determine the role of topical TXA in reducing bleeding in burn surgery.

Findings of the neuromuscular blocking agent rocuronium in blood from deceased subjects several months after exposure: A report of two cases.

Rocuronium is a neuromuscular blocking agent mainly used in anesthetic procedures. Two patients who died 53 and 76 days, respectively, after their last rocuronium exposure had low (0.002-0.007 mg/L) levels of the drug in femoral blood, urine and vitreous humor samples obtained at autopsy. In neither case, the cause of death was related to the exposure to rocuronium. Here, these two cases are presented and the implications of the findings discussed.

Topical tranexamic acid for prophylaxis of bleeding. / Lokal bruk av traneksamsyre som blødningsprofylakse.

Uncertainty surrounding possible thromboembolic events may prevent widespread use of tranexamic acid in surgery. Topical application may be an alternative.

Safety and Efficacy of Local Tranexamic Acid for the Prevention of Surgical Bleeding in Soft-Tissue Surgery: A Review of the Literature and Recommendations for Plastic Surgery.

BACKGROUND: Although high-bleed surgery routinely utilizes the antifibrinolytic drug tranexamic acid, most plastic surgical procedures are conducted in soft tissue with low-volume bleeding. Unease regarding possible systemic adverse effects prevents widespread systemic use, but local use of tranexamic acid is gaining popularity among plastic surgeons. Randomized controlled trials on topical use of tranexamic acid are mainly from high-bleed surgeries, and few studies address the effect in soft tissue. This article reviews the scientific evidence regarding local use of tranexamic acid in soft-tissue surgery, discusses pharmacological effects and possible adverse reactions, and presents recommendations for use in plastic surgery. METHODS: A systematic search of databases for studies on local use of tranexamic acid in soft-tissue surgery was performed. Randomized controlled trials were included for a systematic review on effect; a narrative review regarding other clinically relevant aspects is based on extensive literature searches combined with the authors' own research. RESULTS: Fourteen randomized controlled trials, including 1923 patients, were included in the systematic review on local use of tranexamic acid in soft-tissue surgery. CONCLUSIONS: Local use of tranexamic acid may reduce blood loss comparably to intravenous prophylactic use with negligible risk of systemic adverse effects, but high-quality randomized controlled trials are few. Prolonged exposure to high local concentrations is discouraged, and direct contact with the central nervous system may cause seizures. No single superior means of administration or dosage is supported in the literature, and lowest effective dose is unknown. There may not be one single ideal dosing regimen, but rather many possibilities adaptable for different surgical situations.

Desflurane consumption with automated vapour control systems in two different anaesthesia machines. A randomized controlled study.

BACKGROUND: In general anaesthesia practice a fresh gas flow (FGF) of ≥0.5 L/min is usually applied. Automated gas delivery devices are developed to reduce volatile anaesthetic consumption by limiting gas flow. This study aimed to compare desflurane consumption between automated gas control devices compared to conventional low flow anaesthesia in the Flow-I and Aisys anaesthesia machines, and to compare desflurane consumption between the two automated gas delivery devices. We hypothesised that desflurane consumption would be lower with automated gas delivery compared to conventional low flow anaesthesia, and that desflurane consumption could differ between the different gas delivery devices. METHODS: We allocated 160 patients undergoing robot-assisted laparoscopic surgery into four groups, Flow-I with automated gas control, Flow-i with conventional low-flow (1 L/min), Aisys with end tidal gas control and Aisys with conventional low flow. Patients were maintained at minimum alveolar concentration (MAC) 0.7-0.8. Desflurane consumption was recorded after 9, 30 and 60 minutes of anaesthesia. RESULTS: After 60 minutes, compared to conventional low flow anaesthesia, automated gas delivery systems reduced desflurane consumption from 25.8 to 15.2 mL for the Aisys machine (P < .001) and from 22.1 to 16.8 mL for the Flow-I (P < .001). Time to MAC 0.7 and stable FGF was shorter with Aisys endtidal control compared to Flow-I automated gas control. CONCLUSION: Under clinical conditions, we found a reduction in desflurane consumption when using automated gas delivery devices compared to conventional low flow anaesthesia. Both devices were reliable in use.

Relative impact of red blood cell transfusion and anaemia on 5-year mortality in cardiac surgery.

OBJECTIVES: The aim was to compare the relative effects of red blood cell (RBC) transfusion and preoperative anaemia on 5-year mortality following open-heart cardiac surgery using structural equation modelling. We hypothesized that patient risk factors associated with RBC transfusion are of larger importance than transfusion itself. METHODS: This prospective cohort study, part of the Cardiac Surgery Outcome Study at St. Olavs University Hospital, Trondheim, Norway, included open-heart on-pump cardiac surgery patients operated on from 2000 through 2017 (n = 9315). Structural equation modelling, which allows for intervariable correlations, was used to analyse pathway diagrams between known risk factors and observed mortality between 30 days and 5 years postoperatively. Observation times between 30 days and 1 year, and 1-5 years postoperatively were also compared with the main analysis. RESULTS: In a simplified model, preoperative anaemia had a larger effect on 5-year mortality than RBC transfusion (standardized coefficients: 0.17 vs 0.09). The complete model including multiple risk factors showed that patient risk factors such as age (0.15), anaemia (0.10), pulmonary disease (0.11) and higher creatinine level (0.12) had larger effects than transfusion (0.03). Results from several sensitivity analyses supported the main findings. The models showed good fit. CONCLUSIONS: Preoperative anaemia had a larger impact on 5-year mortality than RBC transfusion. Differences in 5-year mortality were mainly associated with patient risk factors.

Limited effect of red blood cell transfusion on long-term mortality among anaemic cardiac surgery patients.

OBJECTIVES: Our goal was to investigate long-term mortality associated with red blood cell (RBC) transfusion among patients with anaemia undergoing cardiac surgery when adjusting for known risk factors. METHODS: Adults with preoperative anaemia as defined by World Health Organization criteria undergoing open-heart surgery from 2000 through 2017 were included. Cox regression was performed for long-term mortality (30 days-5 years), comparing patients who received ≥1 unit of RBC with those who did not. Unadjusted and multivariable analyses adjusted for risk factors were performed. RESULTS: The study included 1859 patients, 1525 (82%) of whom received RBC transfusion. A total of 370 (19.9%) deaths were registered between 30 days and 5 years; 88 patients (23.8%) died between 30 days and 1 year. The unadjusted hazard ratio (HR) associated with RBC transfusion was 2.09 (1.49-2.93, P < 0.001) from 30 days to 5 years postoperatively. The HR for RBC transfusion were 4.70 (1.72-12.81, P = 0.002) and 1.77 (1.23-2.55, P = 0.002) for 30 days-1 year and 1-5 years, respectively. Adjusting for perioperative risk factors, which included postoperative complications, the HR decreased to 1.16 (0.80-1.68, P = 0.43), 1.79 (0.63-5.12, P = 0.28) and 1.11 (0.75-1.65, P = 0.61) for observation time from 30 days to 5 years, 30 days to 1 year and 1 to 5 years, respectively. Results were similar when postoperative complications were excluded from the adjustment variables. CONCLUSIONS: No statistically significant association between RBC transfusion and long-term mortality was found when we adjusted for known risk factors. This study suggests that the observed difference in mortality in this patient group is largely due to patient-related risk factors.

Perioperative Factors Associated With Changes in Troponin T During Coronary Artery Bypass Grafting.

OBJECTIVE: Investigate important clinical and operative variables associated with increases in cardiac troponin T (cTnT) as indicators of myocardial injury after coronary artery bypass grafting (CABG). DESIGN: Prospective cohort study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 626 patients undergoing isolated CABG from April 2008 through April 2010 with a validation cohort (n = 686) from 2015-2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Perioperative variables were registered prospectively. The extent of diffuse coronary atherosclerosis and significant stenoses were assessed with preoperative coronary angiography. Mixed model analysis was used to construct a statistical model explaining the course of cTnT concentrations. The model was adjusted for preoperative and intraoperative/postoperative myocardial infarction (MI) for independent assessment of additional variables. Clinical factors associated with increased cTnT concentrations during and after CABG were longer duration of cardiopulmonary bypass (p < 0.001), higher preoperative creatinine (p < 0.001), New York Heart Association functional classification IV (p = 0.006), reduced LVEF (p = 0.034), higher preoperative C-reactive protein (p = 0.049), and intraoperative/postoperative MI (p < 0.001). Factors associated with decreasing cTnT concentrations during CABG were higher BSA (p < 0.001) and a recent preoperative MI (p < 0.001). The extent of diffuse coronary atherosclerosis and significant stenoses were not associated with changes in cTnT (p = 0.35). Results were similar in the validation cohort. CONCLUSIONS: Left ventricular ejection fraction, New York Heart Association classification, kidney function, inflammation status, duration of cardiopulmonary bypass, body surface area, and preoperative MI were associated with the cTnT rise-and-fall pattern related to myocardial injury after CABG. Information regarding these variables may be valuable when using cTnT in the diagnostic workup of postoperative MI.

Serum Concentrations and Pharmacokinetics of Tranexamic Acid after Two Means of Topical Administration in Massive Weight Loss Skin-Reducing Surgery.

BACKGROUND: Topical administration of tranexamic acid to reduce bleeding is receiving increasing attention, as it is inexpensive, simple, and possibly beneficial in most surgery. Concerns regarding potential systemic adverse effects such as thromboembolic events and seizures may prevent general use of tranexamic acid. Although serum concentrations after topical application are assumed to be low, proper pharmacokinetic studies of tranexamic acid after topical application are lacking. METHODS: The authors have investigated systemic absorption of tranexamic acid after two means of topical administration in patients undergoing abdominoplasty after massive weight loss: a bolus of 200 ml of 5 mg/ml into the wound cavity versus moistening the wound surface with 20 ml of 25 mg/ml. Twelve patients were recruited in each group. Serum concentrations achieved were compared with those after administration of 1 g as an intravenous bolus to arthroplasty patients. Serial blood samples for tranexamic acid analysis were obtained for up to 24 hours. RESULTS: After intravenous administration, the peak serum concentration was 66.1 ± 13.0 µg/ml after 6 ± 2 minutes. Peak serum concentration after topical moistening was 5.2 ± 2.6 µg/ml after 80 ± 33 minutes, and in the topical bolus group, it was 4.9 ± 1.8 µg/ml after 359 ± 70 minutes. Topical moistening resulted in homogenous and predictable absorption across the individuals included, whereas topical bolus administration caused variable and unpredictable serum concentrations. CONCLUSION: Topical administration of tranexamic acid in patients undergoing abdominoplasty results in low serum concentrations, which are highly unlikely to cause systemic effects.

Transfusion of red blood cells in coronary surgery: is there an effect on long-term mortality when adjusting for risk factors and postoperative complications?

OBJECTIVES: The aim of this study was to compare long-term mortality in patients undergoing primary isolated coronary artery bypass grafting who received ≥1 units of red blood cells (RBCs) or no RBCs. We hypothesized that a possible difference in long-term mortality was due to preoperative morbidity and/or postoperative morbidity. METHODS: This prospective cohort study, part of the Cardiac Surgery Outcome Study (CaSOS) at St. Olavs University Hospital, Trondheim, Norway, included patients operated on from 2000 through 2014 (n = 4014) and excluded those with large intra- or postoperative blood loss or 30-day mortality. Observed mortality from 30 days to 15 years postoperatively was compared between patients who received RBC transfusion and those who did not. Cox regression analysis was performed with unadjusted models, adjusting for pre- and intraoperative covariates, and with further adjustment for postoperative complications. Sensitivity analyses were performed with propensity score matching or including 30-day mortality. RESULTS: The unadjusted hazard ratio (HR) for long-term mortality was 2.10 (1.81-2.43; P < 0.01) for transfused patients. After adjusting for pre- and intraoperative variables, the HR was 1.26 (1.04-1.53; P = 0.02). With further adjustment for postoperative complications, RBC transfusion was no longer significant and the HR was 1.19 (0.98-1.44; P = 0.08). These results were supported by the sensitivity analyses. CONCLUSIONS: The study indicated that most of the association between RBC transfusion and long-term mortality following primary isolated coronary artery bypass grafting was due to confounders, especially from postoperative complications.

A Preoperative Multimarker Approach to Evaluate Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: To investigate whether a multimarker strategy combining preoperative biomarkers representing distinct pathophysiologic pathways enhances preoperative risk assessment of acute kidney injury after cardiac surgery (CSA-AKI) and increases knowledge of underlying pathogenesis. DESIGN: Prospective, cohort study. SETTING: Single-center tertiary referral hospital. PARTICIPANTS: The study comprised 1,015 adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: CSA-AKI was defined as≥50% increase in serum creatinine concentration, absolute increase≥26 µmol/L, or new requirement for dialysis. Preoperative and perioperative information until hospital discharge was recorded. Preoperative plasma levels of C-reactive protein, terminal complement complex, neopterin, lactoferrin, N-terminal pro-brain natriuretic peptide, and cystatin C were determined using enzyme immunoassays. Biomarkers were selected based on causal hypotheses of underlying mechanisms and were related to inflammatory, hemodynamic, or renal signaling pathways. MEASUREMENTS AND MAIN RESULTS: One hundred patients (9.9%) developed CSA-AKI. Higher baseline plasma concentrations of neopterin and N-terminal pro-brain natriuretic peptide were associated independently with CSA-AKI (p = 0.04 and p<0.001, respectively). Lower baseline plasma lactoferrin concentrations were observed in patients with CSA-AKI (p = 0.05). Compared with clinical risk assessment, addition of these biomarkers provided a slight, but significant, increment in predictive utility (area under the curve 0.81-0.83, likelihood ratio test p<0.001). A net of 12% of patients were reclassified correctly, and improved prediction was demonstrated, especially in patients with intermediate risk (56% correct reclassification). CONCLUSIONS: Preoperative hemodynamic, renal, and immunologic function play central roles in the pathogenesis of CSA-AKI. These findings add evidence to the potential of a multimarker approach to improve preoperative prediction of CSA-AKI.

Reduced Long-Term Relative Survival in Females and Younger Adults Undergoing Cardiac Surgery: A Prospective Cohort Study.

OBJECTIVES: To assess long-term survival and mortality in adult cardiac surgery patients. METHODS: 8,564 consecutive patients undergoing cardiac surgery in Trondheim, Norway from 2000 until censoring 31.12.2014 were prospectively followed. Observed long-term mortality following surgery was compared to the expected mortality in the Norwegian population, matched on gender, age and calendar year. This enabled assessment of relative survival (observed/expected survival rates) and relative mortality (observed/expected deaths). Long-term mortality was compared across gender, age and surgical procedure. Predictors of reduced survival were assessed with multivariate analyses of observed and relative mortality. RESULTS: During follow-up (median 6.4 years), 2,044 patients (23.9%) died. The observed 30-day, 1-, 3- and 5-year mortality rates were 2.2%, 4.4%, 8.2% and 13.8%, respectively, and remained constant throughout the study period. Comparing observed mortality to that expected in a matched sample from the general population, patients undergoing cardiac surgery showed excellent survival throughout the first seven years of follow-up (relative survival ≥ 1). Subsequently, survival decreased, which was more pronounced in females and patients undergoing other procedures than isolated coronary artery bypass grafting (CABG). Relative mortality was higher in younger age groups, females and patients undergoing aortic valve replacement (AVR). The female survival advantage in the general population was obliterated (relative mortality ratio (RMR) 1.35 (1.19-1.54), p<0.001). Increasing observed long-term mortality seen with ageing was due to population risk, and younger age was independently associated with increased relative mortality (RMR per 5 years 0.81 (0.79-0.84), p<0.001)). CONCLUSIONS: Cardiac surgery patients showed comparable survival to that expected in the general Norwegian population, underlining the benefits of cardiac surgery in appropriately selected patients. The beneficial effect lasted shorter in younger patients, females and patients undergoing AVR or other procedures than isolated CABG. Thus, the study identified three groups that need increased attention for further improvement of outcomes.

Neopterin predicts cardiac dysfunction following cardiac surgery.

OBJECTIVES: Oxidative stress following ischaemia and reperfusion, as well as inflammation, are thought to be important for the development of cardiac dysfunction after cardiac surgery. Our main objective was to investigate whether the inflammatory biomarkers C-reactive protein (CRP), lactoferrin, neopterin and the terminal complement complex (TCC) were associated with cardiac dysfunction after cardiac surgery. Another objective was to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables only. METHODS: Blood samples and clinical data from 1018 consecutive patients undergoing cardiac surgery from 1 April 2008 to 19 April 2010 at St. Olavs University Hospital, Trondheim, Norway, were collected prospectively. The end-point was postoperative cardiac dysfunction, defined as the need for more than one inotropic agent or an intra-aortic balloon pump occurring after the operation and until the patient was discharged from the department. CRP, lactoferrin, neopterin and TCC were analysed in plasma, and we used logistic regression to evaluate the association of the biomarkers with postoperative cardiac dysfunction. We adjusted for the following clinical variables previously associated with postoperative cardiac dysfunction: urgent operation, operation type, previous cardiac surgery, chronic heart failure, pulmonary hypertension, previous myocardial infarction and haemoglobin. The likelihood ratio test, the integrated discrimination improvement and receiver operating characteristic (ROC) curves were used to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables alone. RESULTS: Neopterin was the only biomarker significantly associated with postoperative cardiac dysfunction (odds ratio 2.73, 95% confidence interval 1.65-4.51) after adjustment for clinical variables. Neopterin improved risk prediction of cardiac dysfunction following heart surgery compared with clinical variables alone according to the likelihood ratio test (P < 0.0001) and the integrated discrimination improvement (P = 0.02), particularly for patients with intermediate risks. CONCLUSIONS: Neopterin was associated with cardiac dysfunction following cardiac surgery, and improved the accuracy of risk prediction of postoperative cardiac dysfunction. At present, we do not suggest that neopterin should be measured routinely before heart surgery, but our findings support the hypothesis of the role of oxidative stress and inflammation in development of cardiac dysfunction following heart surgery.

Prediction of bleeding after cardiac surgery: comparison of model performances: a prospective observational study.

OBJECTIVES: Primary aims were to (1) perform external validation of the Papworth Bleeding Risk Score, and (2) compare the usefulness of the Dyke et al universal definition of perioperative bleeding with that used in the Papworth Bleeding Risk Score. A secondary aim was to use a locally developed logistic prediction model for severe postoperative bleeding to investigate whether prediction could be improved with inclusion of the variable "surgeon" or selected intraoperative variables. DESIGN: Single-center prospective observational study. SETTING: University hospital. PARTICIPANTS: 7,030 adults undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Papworth Bleeding Risk Score could identify the group of patients with low risk of postoperative bleeding, with negative predictive value of 0.98, when applying the Papworth Score on this population. The positive predictive value was low; only 15% of the patients who were rated high risk actually suffered from increased postoperative bleeding when using the Papworth Score on this population. Using the universal definition of perioperative bleeding proposed by Dyke et al, 28% of patients in the Papworth high-risk group exceeded the threshold of excessive bleeding in this population. The local models showed low ability for discrimination (area under the receiver operating characteristics curve<0.75). Addition of the factor "surgeon" or selected intraoperative variables did not substantially improve the models. CONCLUSION: Prediction of risk for excessive bleeding after cardiac surgery was not possible using clinical variables only, independent of endpoint definition and inclusion of the variable "surgeon" or of selected intraoperative variables. These findings may be due to incomplete understanding of the causative factors underlying excessive bleeding.

Comparison of three point-of-care testing devices to detect hemostatic changes in adult elective cardiac surgery: a prospective observational study.

BACKGROUND: Bleeding complications in cardiac surgery may lead to increased morbidity and mortality. Traditional blood coagulation tests are not always suitable to detect rapid changes in the patient's coagulation status. Point-of-care instruments such as the TEG (thromboelastograph) and RoTEM (thromboelastometer) have been shown to be useful as a guide for the clinician in the choice of blood products and they may lead to a reduction in the need for blood transfusion, contributing to better patient blood management. METHODS: The purpose of this study was to evaluate the ability of the TEG, RoTEM and Sonoclot instruments to detect changes in hemostasis in elective cardiac surgery with cardiopulmonary bypass and to investigate possible correlations between variables from these three instruments and routine hematological coagulation tests. Blood samples from thirty-five adult patients were drawn before and after surgery and analyzed in TEG, RoTEM, Sonoclot and routine coagulation tests. Data were compared using repeated measures analysis of variance and Pearson's test for linear correlation. RESULTS: We found significant changes for all TEG variables after surgery, for three of the RoTEM variables, and for one variable from the Sonoclot. There were significant correlations postoperatively between plasma fibrinogen levels and variables from the three instruments. CONCLUSIONS: TEG and RoTEM may be used to detect changes in hemostasis following cardiac surgery with CPB. Sonoclot seems to be less suitable to detect such changes. Variables from the three instruments correlated with plasma fibrinogen and could be used to monitor treatment with fibrinogen concentrate.

How can we best predict acute kidney injury following cardiac surgery?: a prospective observational study.

BACKGROUND: Several models for predicting acute kidney injury following cardiac surgery have been published, and various end-point definitions have been used. OBJECTIVES: Our aim was to investigate how acute kidney injury following cardiac surgery could be most accurately predicted. DESIGN: Single-centre prospective observational study. SETTING: St Olav's University Hospital, Trondheim, Norway, from 2000 to 2007. PATIENTS: All 5029 adult patients undergoing cardiac surgery were considered eligible for participation. Patients who required preoperative dialysis and patients with missing information on preoperative or maximum postoperative serum creatinine concentration were excluded (n=51). A total of 4978 patients were entered into the statistical analyses. MAIN OUTCOME MEASURES: Logistic regression with bootstrapping methods was applied for model development and validation, together with the area under the receiver operating characteristic curve and Hosmer-Lemeshow test. We tested different end-points, exchanged serum creatinine concentration with creatinine clearance or estimated glomerular filtration rate and added intraoperative variables. The main end-point was at least 50% increase in serum creatinine concentration, an increase in concentration by at least 26.4 µmol l(-1) (0.3 mg dl(-1)) or a new requirement for dialysis after surgery. RESULTS: The final model consisted of 11 preoperative predictors of acute kidney injury: age, BMI, lipid-lowering treatment, hypertension, peripheral vascular disease, chronic pulmonary disease, haemoglobin concentration, serum creatinine concentration, previous cardiac surgery, emergency operation and operation type. The area under the receiver operating characteristic curve was 0.819 (95% confidence interval 0.801 to 0.837), and the Hosmer-Lemeshow test P value was 0.17. Exchanging serum creatinine concentration with glomerular filtration rate or creatinine clearance slightly reduced model discrimination and the addition of intraoperative variables improved discrimination somewhat. Slight end-point definition changes had little impact. CONCLUSION: The risk of acute kidney injury can be accurately predicted using preoperative variables. Serum creatinine concentration was more accurate than estimated glomerular filtration rate or creatinine clearance. Intraoperative variables slightly improved the model, but did not seem to outweigh the advantages of a preoperative model.

Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting.

OBJECTIVES: Acetylsalicylic acid (ASA) is a cornerstone in the treatment of coronary artery disease (CAD) due to its antiplatelet effect. Cessation of aspirin before coronary artery bypass grafting (CABG) is often recommended to avoid bleeding, but the practice is controversial because it is suggested to worsen the underlying CAD. The aims of the present prospective, randomized study were to assess if ASA administration until the day before CABG decreases the oxidative load through a reduction of inflammation and myocardial damage, compared with patients with preoperative discontinuation of ASA. METHODS: Twenty patients scheduled for CABG were randomly assigned to either routine ASA-treatment (160 mg daily) until the time of surgery (ASA), or to ASA-withdrawal 7 days before surgery (No-ASA). Blood-samples were taken from a radial artery and coronary sinus, during and after surgery and analysed for 8-iso-prostaglandin (PG) F2α; a major F2-isoprostane, high-sensitivity C-reactive protein (hs-CRP), cytokines and troponin T. Left ventricle Tru-Cut biopsies were taken from viable myocardium close to the left anterior descending artery just after connection to cardiopulmonary bypass, and before cardioplegia were established for gene analysis (Illumina HT-12) and immunohistochemistry (CD45). RESULTS: 8-Iso-PGF2α at baseline (t1) were 111 (277) pmol/l and 221 (490) pmol/l for ASA and No-ASA, respectively (P = 0.065). Area under the curve showed a significantly lower level in plasma concentration of 8-iso-PGF2α and hsCRP in the ASA group compared with the No-ASA group with (158 pM vs 297 pM, P = 0.035) and hsCRP (8.4 mg/l vs 10.1 mg/l, P = 0.013). All cytokines increased during surgery, but no significant differences between the two groups were observed. Nine genes (10 transcripts) were found with a false discovery rate (FDR) <0.1 between the ASA and No-ASA groups. CONCLUSIONS: Continued ASA treatment until the time of CABG reduced oxidative and inflammatory responses. Also, a likely beneficial effect upon myocardial injury was noticed. Although none of the genes known to be involved in oxidative stress or inflammation took a different expression in myocardial tissue, the genetic analysis showed interesting differences in the mRNA level. Further research in this field is necessary to understand the role of the genes.

Length of intensive care unit stay following cardiac surgery: is it impossible to find a universal prediction model?

OBJECTIVES: Accurate models for prediction of a prolonged intensive care unit (ICU) stay following cardiac surgery may be developed using Cox proportional hazards regression. Our aims were to develop a preoperative and intraoperative model to predict the length of the ICU stay and to compare our models with published risk models, including the EuroSCORE II. METHODS: Models were developed using data from all patients undergoing cardiac surgery at St. Olavs Hospital, Trondheim, Norway from 2000-2007 (n = 4994). Internal validation and calibration were performed by bootstrapping. Discrimination was assessed by areas under the receiver operating characteristics curves and calibration for the published logistic regression models with the Hosmer-Lemeshow test. RESULTS: Despite a diverse risk profile, 93.7% of the patients had an ICU stay <2 days, in keeping with our fast-track regimen. Our models showed good calibration and excellent discrimination for prediction of a prolonged stay of more than 2, 5 or 7 days. Discrimination by the EuroSCORE II and other published models was good, but calibration was poor (Hosmer-Lemeshow test: P < 0.0001), probably due to the short ICU stays of almost all our patients. None of the models were useful for prediction of ICU stay in individual patients because most patients in all risk categories of all models had short ICU stays (75th percentiles: 1 day). CONCLUSIONS: A universal model for prediction of ICU stay may be difficult to develop, as the distribution of length of stay may depend on both medical factors and institutional policies governing ICU discharge.

Preoperative and intraoperative prediction of risk of cardiac dysfunction following open heart surgery.

CONTEXT: Cardiac dysfunction following open heart surgery is a major determinant of subsequent morbidity and mortality. OBJECTIVES: To develop a specific risk prediction model for postoperative cardiac dysfunction based on preoperative variables, to investigate whether prediction could be improved by inclusion of selected intraoperative variables and to compare our model with five previously published risk scores. DESIGN: Single-centre prospectively collected data. SETTING: Tertiary care centre, Middle Norway. PATIENTS: Four thousand nine hundred and eighty-nine patients (all eligible) undergoing open cardiac surgery from 2000 to 2007. MAIN OUTCOME MEASURES: Logistic regression models for postoperative cardiac dysfunction: predictive accuracy/calibration, discrimination as shown by area under the receiver operating characteristics curve, internal validity as indicated by bootstrapping, comparison of goodness-of-fit with predictions based on alternative risk scores. RESULTS: The preoperative model included chronic cardiac insufficiency, previous myocardial infarction, previous cardiac operation, pulmonary hypertension, renal dysfunction, low haemoglobin concentration, urgent operation and operation type other than isolated coronary artery bypass surgery. The area under the curve was 0.838 [95% confidence interval (CI) 0.812-0.864]. Risk prediction was accurate apart from a slight overestimation in the 2% of highest risk patients. Inclusion of a few intraoperative variables (inotropic or vasoconstrictor drugs, plasma or red cell transfusion) improved the model slightly, increasing the area under the curve to 0.875 (95% CI 0.854-0.896) or 0.890 (95% CI 0.863-0.902) for two equivalent models. On the basis of estimated shrinkage factors of 0.94, 0.97 and 0.98, respectively, the models should behave with 6% or less error in future datasets. Our preoperative model was significantly better than the previously published risk scores (P < 0.0002 for comparison of area under the curves). CONCLUSION: The preoperative model including variables obtained easily in routine clinical work performed well and was improved only slightly by inclusion of intraoperative variables. Performance was better than those of the five previously published risk scores.