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.

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 95 year-old suffering circulatory arrest after accidental hypothermia: a case report.

BACKGROUND: The elderly are vulnerable to cold and prone to accidental hypothermia, both because of environmental and endogenous factors. The incidence of severe accidental hypothermia among the elderly is poorly described, but many cases probably go unrecorded. Going through literature one finds few publications on severe hypothermia among the elderly, and, to our knowledge, nothing about extracorporeal re-warming of geriatric hypothermia victims. CASE PRESENTATION: We present a case were a 95 year-old man with severe accidental hypothermia and circulatory arrest was brought to our hospital under on-going CPR, and was successfully resuscitated with extracorporeal circulation. He was discharged to his home without physical sequelae a few weeks later. CONCLUSION: The decision whether or not to continue resuscitation of a nonagenarian can be difficult in many respects. Knowing that resuscitation with extracorporeal circulation is resource intensive may complicate the discussion. In light of our experience with this case we discuss medical and ethical aspects of modern treatment of severe accidental hypothermia.

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.

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.

Tranexamic acid reduces blood transfusions in elderly patients undergoing combined aortic valve and coronary artery bypass graft surgery: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of tranexamic acid on postoperative blood loss and transfusion requirements in elderly patients undergoing combined aortic valve replacement and coronary artery bypass graft surgery (CABG). DESIGN: A prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. SETTING: A university hospital (single institution). PARTICIPANTS: Sixty-four patients 70 years or older undergoing combined aortic valve replacement and CABG surgery were included. One patient was withdrawn from the study after randomization by the attending surgeon because of a change in the surgical procedure. The remaining 63 patients were analyzed as intention to treat. INTERVENTIONS: The included patients were randomized to treatment with either tranexamic acid, 10 mg/kg, as a bolus injection before surgery followed by 1 mg/kg/h as an infusion during surgery, or a corresponding volume of 0.9% sodium chloride. MEASUREMENTS AND MAIN RESULTS: Postoperative blood loss was recorded for 16 hours. The transfusion of blood products was recorded during the entire hospital stay. The number of packed red cell transfusions given to the patients was significantly lower in the tranexamic acid group compared with the placebo group (median, 3.0 [interquartile range, 2-5] v 5.0 [3-7], p = 0.049). CONCLUSION: Tranexamic acid reduced the number of packed red cell transfusions given to patients 70 years or older undergoing combined aortic valve replacement and CABG surgery.

Effect of serotonin reuptake inhibitors on pulmonary hemodynamics in humans.

BACKGROUND: Serotonin promotes pulmonary arterial vasoconstriction and pulmonary arterial smooth muscle cell proliferation, thereby having the potential to increase pulmonary arterial blood pressure. Although serotonin reuptake inhibitors (SRIs) might inhibit further deterioration in patients with manifest pulmonary arterial hypertension, they may induce pulmonary hypertension in healthy newborns after fetal exposure. As it is unclear whether treatment with SRIs affects pulmonary hemodynamics in adults without pulmonary hypertension, the aim of the present study was to investigate the effect of SRIs on pulmonary hemodynamics in such subjects. METHODS: Sixteen patients with stable angina pectoris scheduled for first time coronary artery bypass grafting were included in the study. Of these 8 were currently treated with an SRI (the SRI group) and 8 were not (the control group). Pulmonary arterial pressures were measured before induction of anesthesia by means of a pulmonary artery catheter. Serotonin transporter and 5-HT(2A) receptor gene polymorphisms and platelet 5-HT(2A) receptor expression were studied to elucidate their possible role as modifying factors. RESULTS: No patients in any of the groups had pulmonary arterial hypertension. Mean pulmonary artery pressure was 15.0 mmHg in the SRI group and 14.5 mmHg in the control group (P = 0.50; 95% confidence interval for the difference, -2.9 to +3.9 mmHg). Neither were there any significant differences between the groups for any of the other hemodynamic variables studied. The various gene polymorphisms and the extent of platelet 5-HT(2A) receptor expression did not influence the hemodynamic variables. CONCLUSIONS: SRI treatment did not significantly influence pulmonary hemodynamics in patients without pulmonary hypertension. KEYWORDS: Serotonin; Selective serotonin reuptake inhibitors; Pulmonary hemodynamics; Pulmonary hypertension.

[A 76-year-old man with a murmur after myocardial infarction]. / En 76 år gammel mann med bilyd etter hjerteinfarkt.

A 76-year-old, previously healthy man who presented with acute onset of central chest pain is described. An ECG taken in the ambulance showed ST-elevation in chest leads V1 to V4, whereupon thrombolysis was initiated before hospitalization. A new ECG taken on admission at the local hospital showed reduced ST-elevation. Shortly afterwards, auscultation followed by eccocardiography revealed a ventricular septal rupture. The patient was transferred to the regional hospital, and emergency repair of the ventricular septum was performed successfully. On the 6th postoperative day, the patient suffered septal rupture recurrence and subsequently died of multi-organ failure. Postinfarction ventricular septal rupture is a serious complication with a high mortality. Cardiac surgery is indicated in most cases. Delayed diagnosis may result in early death for a considerable number of patients. The present case underscores the importance of cardiac auscultation in patients with suspected myocardial infarction before angiography or primary coronary intervention is performed.