Pulmonary hypertension and its management in patients undergoing non‐cardiac surgery

Pulmonary hypertension is a complex disorder of the pulmonary vasculature that leads to increased peri‐operative morbidity and mortality. Non‐cardiac surgery constitutes a significant risk in patients with pulmonary hypertension. The management of right ventricular failure is inherently challenging and fraught with life‐threatening consequences. A thorough understanding of the pathophysiology, the severity of the disease and its treatment modalities is required to deliver optimal peri‐operative care. This review provides an evidence‐based overview of the definition, classification, pathophysiology, diagnosis and treatment of pulmonary hypertension and focuses on the peri‐operative management and treatment of pulmonary hypertensive crises in a non‐cardiac setting.     

Neuronal damage biomarkers in the identification of patients at risk of long‐term postoperative cognitive dysfunction after cardiac surgery

Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage‐specific biomarkers, including brain fatty acid‐binding protein, neuron‐specific enolase and S100 calcium‐binding protein β, as well as plasma‐free haemoglobin concentration as a measure of haemolysis, could be used to predict the risk of long‐term cognitive decline after coronary artery bypass grafting with or without cardiopulmonary bypass. We assessed cognitive function using the CogState brief computerised cognitive test battery at 3 months and at 15 months after surgery. Blood samples were obtained pre‐operatively, after sternal closure, and at 6 h and 24 h postoperatively. We found signs of cognitive decline at 3 months in 15 of 57 patients (26%), and in 13 of 48 patients (27%) at 15 months. Brain fatty acid‐binding protein was already significantly higher before surgery in patients with postoperative cognitive dysfunction at 15 months, with pre‐operative plasma levels of 22.8 (8.3–33.0 [0–44.6]) pg.ml^?1 compared with 9.7 (3.9–17.3 [0–49.0]) pg.ml^?1 in patients without cognitive dysfunction. This biomarker remained significantly higher in patients with cognitive decline throughout the entire postoperative period. At 3 months after surgery, high levels of plasma‐free haemoglobin at sternal closure were associated with a negative influence on cognitive performance, as were high baseline scores on neuropsychological tests, whereas a higher level of education proved to beneficially influence cognitive outcome. We found that postoperative cognitive dysfunction at 3 months was associated with cognitive decline at 15 months after surgery, and served as a valuable prognostic factor for declines in individual cognitive performance one year later. Classical neuronal injury‐related biomarkers were of no clear prognostic value.     

Cardiac biomarkers in perioperative risk stratification

Objectives

The field of new cardiac biomarkers has triggered physicians’ enthusiasm because of their potential diagnostic and prognostic values for routine clinical practice in the surgical setting. The objective of the present article is to review the role of new cardiac biomarkers and their potential additive clinical value in predicting short- and long-term risk following cardiac and non-cardiac surgery.

Data sources

A PubMed^® database research in English and French languages published until June 2010. Keywords were cardiac biomarkers, troponins, cardiac troponin I (cTnI), natriuretic peptides, B-type natriuretic peptide (BNP), C-reactive protein (CRP), multiple markers approach, risk stratification, clinical risk scores.

Data synthesis

Numerous publications deal with the diagnostic and prognostic values of new cardiac biomarkers in cardiac and non-cardiac surgical settings and provide an increasing evidence of their interest, validating different hierarchical steps which are mandatory before recommending a wide use of biomarkers for routine practice. Even if the first studies demonstrating an additional prognostic value of serum postoperative cTnI and/or preoperative BNP when compared with clinical predictive models are now available, we still lack data concerning an actual positive impact of new biomarkers measurements on clinical decision making or practice, as well as patient care and outcome.

Conclusions

While use of new cardiac biomarkers in the perioperative period appears to be a simple and objective tool for risk stratification at the bedside, we still need to remain cautious concerning their additional clinical value on existing predictive models for routine practice.     

Perioperative hyperoxia and post‐operative cardiac complications in adults undergoing non‐cardiac surgery: Systematic review protocol

Background

Oxygen therapy is used liberally for all patients undergoing anaesthesia. Recent studies have raised concerns that it may not be without complications when arterial oxygen concentrations reach supranormal concentrations (hyperoxia). Studies of oxygen therapy have raised concerns that the risk of myocardial injury and infarction is elevated in patients with hyperoxia due to vasoconstriction and formation of reactive oxygen species. Due to lack of symptoms or silent ischaemia, post‐operative myocardial injury may be missed clinically. In some studies, perioperative hyperoxia has been linked to increased long‐term mortality, but cardiac complications are sparsely evaluated. The aim of this review is to summarize current evidence to assess the risk and benefits of perioperative hyperoxia on post‐operative cardiac complications.

Methods

This systematic review will include meta‐analyses and Trial Sequential Analyses. We will include randomized clinical trials with patients undergoing non‐cardiac surgery if the allocation separates patients into a target of either higher (above 0.60) or lower (below 0.40) inspired oxygen fraction. To minimize the risk of systematic error, we will assess the risk of bias of the included trials using the Cochrane Risk of Bias Tool. The overall quality of evidence for each outcome will be assessed with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE).

Discussion

This systematic review will provide data on a severe, albeit rare, potential risk of oxygen therapy. We will do a trial sequential analysis to assess the robustness of results as well as help estimate the required patient size for future clinical trials.

     

Postoperative hypothermia and patient outcomes after major elective non‐cardiac surgery

Using a multicentre adult patient database from Australia and New Zealand, we obtained the lowest and highest temperature in the first 24 h after admission to the intensive care unit after elective non‐cardiac surgery. Hypothermia was defined as core temperature < 36 °C; transient hypothermia as a temperature < 36 °C that was corrected within 24 h, and persistent hypothermia as hypothermia not corrected within 24 h. We studied 50 689 patients. Hypothermia occurred in 23 165 (46%) patients, was transient in 22 810 (45%), and was persistent in 608 (1.2%) patients. On multivariate analysis, neither transient (OR = 1.07, 95% CI 0.96–1.20) nor persistent (OR = 1.50. 95% CI 0.96–2.33) hypothermia was independently associated with increased hospital mortality.     

Preoperative risk prediction and intraoperative events in cardiac surgery.

OBJECTIVE: To examine the relationship between preoperative risk prediction and intraoperative events. METHODS: A total of 3118 patients operated in 1999 and 2000 at our institution were analysed, all of whom had their EuroSCORE collected prospectively. The intraoperative variables studied were consultant or trainee operating, long bypass time, long ischaemic time, return on bypass in theatre and use of intra-aortic balloon pump at the end of the procedure. The outcomes are reported as hospital mortality, prolonged length of stay in the intensive therapy unit (pLOS-ITU, >48 h) and death or pLOS-ITU. Risk models were constructed by logistic regression for predicting these three outcomes. RESULTS: With the exception of prolonged cross-clamp time, all variables analysed were independently predictive of a negative outcome. Trainee operating had an apparent protective effect. All risk models performed well. The area under the receiver operating characteristic (ROC) curve (95% CI) increased from 0.857 (0.81, 0.90) for EuroSCORE to 0.874 (0.83, 0.92) for the risk of death model. Similarly, the area under the ROC curve for the pLOS-ITU model increased from 0.687 (0.642, 0.732) to 0.734 (0.691, 0.777) and for the death or pLOS-ITU model from 0.717 (0.677, 0.756) to 0.757 (0.719, 0.795). CONCLUSIONS: Knowledge of adverse intraoperative events enhances preoperative risk prediction. This type of analysis could be used for identifying "near miss" outcomes in adult cardiac surgery.     

Statistical prediction of cardiac risk in patients who undergo vascular surgery

Since August 1982, an extensive computerized data base has been developed on all patients admitted to the Division of Vascular Surgery at the Ottawa Civic Hospital. For each patient, 180 variables are recorded, including information about preoperative risk factors and postoperative complications. Since cardiac complications are a major cause of mortality and morbidity, the data file has been used to study postoperative cardiac complications in patients who undergo arterial reconstructive operations. Between August 1982 and December 1983, 353 artery repairs were performed, excluding ruptured aneurysms. Cardiac complications developed following surgery in 56 patients. Risk factors were initially studied using contingency table analysis. Four of these factors were found to be significant: electrocardiographic evidence of previous myocardial infarction (p = 0.0003), nonspecific ST-segment changes (p = 0.0007), New York Heart Association classification of symptoms (p = 0.0003) and age (p = 0.01). A further statistical study was based upon multiple logistic regression. The authors believe that the identification of a high-risk group, using these criteria, is helpful in selecting patients for intensive preoperative investigation, including coronary arteriography.     

Predictive biomarkers for graft rejection in pig‐to‐non‐human primate corneal xenotransplantation

We investigated the predictive biomarkers for graft rejection in pig‐to‐non‐human primate (NHP) full‐thickness corneal xenotransplantation (n = 34). The graft score (0‐12) was calculated based on opacity, edema, and vascularization. Scores ≥ 6 were defined as rejection. NHPs were divided into two groups: (a) graft rejection within 6 months; and (b) graft survival until 6 months. In the evaluation of 2‐week biomarkers, none of the NHPs showed rejection within 2 weeks and the 34 NHPs were divided into two groups: (a) entire rejection group (n = 16); and (b) survival group (n = 18). In the evaluation of 4‐week biomarkers, four NHPs showing rejection within 4 weeks were excluded and the remaining 30 NHPs were divided into two groups: (a) late rejection group (n = 12); and (b) survival group (n = 18). Analysis of biomarker candidates included T/B‐cell subsets, levels of anti‐αGal IgG/M, donor‐specific IgG/M from blood, and C3a from plasma and aqueous humor (AH). CD8⁺IFNγ⁺ cells at week 2 and AH C3a at week 4 were significantly elevated in the rejection group. Receiver operating characteristic areas under the curve was highest for AH C3a (0.847) followed by CD8⁺IFNγ⁺ cells (both the concentration and percentage: 0.715), indicating excellent or acceptable discrimination ability, which suggests that CD8⁺IFNγ⁺ cells at week 2 and AH C3a at week 4 are reliable biomarkers for predicting rejection in pig‐to‐NHP corneal xenotransplantation.     

Postoperative outcomes following cardiac surgery in non‐anaemic iron‐replete and iron‐deficient patients – an exploratory study

Iron deficiency anaemia is strongly associated with poor outcomes after cardiac surgery. However, pre‐operative non‐anaemic iron deficiency (a probable anaemia precursor) has not been comprehensively examined in patients undergoing cardiac surgery, despite biological plausibility and evidence from other patient populations of negative effect on outcome. This exploratory retrospective cohort study aimed to compare an iron‐deficient group of patients undergoing cardiac surgery with an iron‐replete group. Consecutive non‐anaemic patients undergoing elective coronary artery bypass grafting or single valve replacement in our institution between January 2013 and December 2015 were considered for inclusion. Data from a total of 277 patients were analysed, and were categorised by iron status and blood haemoglobin concentration into iron‐deficient (n = 109) and iron‐replete (n = 168) groups. Compared with the iron‐replete group, patients in the iron‐deficient group were more likely to be female (43% vs. 12%, iron‐replete, respectively); older, mean (SD) age 64.4 (9.7) vs. 63.2 (10.3) years; and to have a higher pre‐operative EuroSCORE (median IQR [range]) 3 (2–5 [0–10]) vs. 3 (2–4 [0–9]), with a lower preoperative haemoglobin of 141.6 (11.6) vs. 148.3 (11.7) g.l^?1. Univariate analysis suggested that iron‐deficient patients had a longer hospital length of stay (7 (6–9 [2–40]) vs. 7 (5–8 [4–23]) days; p = 0.013) and fewer days alive and out of hospital at postoperative day 90 (83 (80–84 [0–87]) vs. 83 (81–85 [34–86]), p = 0.009). There was no evidence of an association between iron deficiency and either lower nadir haemoglobin or higher requirement for blood products during inpatient stay. After adjusting the model for pre‐operative age, sex, renal function, EuroSCORE and haemoglobin, the mean increase in hospital length of stay in the iron‐deficient group relative to the iron‐replete group was 0.86 days (bootstrapped 95%CI ?0.37 to 2.22, p = 0.098). This exploratory study suggests there is weak evidence of an association between non‐anaemic iron deficiency and outcome after cardiac surgery after controlling for potentially confounding variables.     

Mortality risk prediction in cardiac surgery: comparing a novel model with the EuroSCORE

Background: Several models for prediction of early mortality after open‐heart surgery have been developed. Our objectives were to develop a local mortality risk prediction model, compare it with the European System for Cardiac Operative Risk Evaluation (EuroSCORE), and investigate whether the addition of intra‐operative variables could enhance the accuracy of risk prediction. Methods: All 5029 patients undergoing open‐heart surgery in 2000–2007 were included in the study. Logistic regression with bootstrap methods was used to develop a pre‐operative risk prediction model for in‐hospital mortality. Next, several intra‐operative variables were added to the pre‐operative model. Calibration and discrimination were assessed, and the model was internally validated for prediction in future datasets. We thereafter compared the pre‐operative model with the additive and logistic EuroSCOREs. Results: Our pre‐operative model included eight risk factors that are routinely registered in our department: age, gender, degree of urgency, operation type, previous cardiac surgery, and renal, cardiac, and pulmonary dysfunction. The model estimated mortality accurately throughout the dataset except in the 1% of patients at extremely high risk, in which mortality was somewhat overestimated. The estimated shrinkage factor was 0.930. The areas under the receiver operating characteristic curve for our pre‐operative model and the logistic EuroSCORE were 0.857(0.823–0.891) and 0.821(0.785–0.857) (P=0.02). There was no significant difference in performance between the pre‐operative and the intra‐operative model (P>0.10). Conclusion: Our pre‐operative model was simple and easy to use, and showed good predictive ability in our population. Internal validation indicated that it would accurately predict mortality in a future dataset.