Methemoglobin as a marker of acute anemic stress in cardiac surgery.

Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.

Restrictive versus liberal transfusion in patients with diabetes undergoing cardiac surgery: An open-label, randomized, blinded outcome evaluation trial.

AIM: To characterize the association between diabetes and transfusion and clinical outcomes in cardiac surgery, and to evaluate whether restrictive transfusion thresholds are harmful in these patients. MATERIALS AND METHODS: The multinational, open-label, randomized controlled TRICS-III trial assessed a restrictive transfusion strategy (haemoglobin [Hb] transfusion threshold <75 g/L) compared with a liberal strategy (Hb <95 g/L for operating room or intensive care unit; or <85 g/L for ward) in patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate-to-high risk of death (EuroSCORE ≥6). Diabetes status was collected preoperatively. The primary composite outcome was all-cause death, stroke, myocardial infarction, and new-onset renal failure requiring dialysis at 6 months. Secondary outcomes included components of the composite outcome at 6 months, and transfusion and clinical outcomes at 28 days. RESULTS: Of the 5092 patients analysed, 1396 (27.4%) had diabetes (restrictive, n = 679; liberal, n = 717). Patients with diabetes had more cardiovascular disease than patients without diabetes. Neither the presence of diabetes (OR [95% CI] 1.10 [0.93-1.31]) nor the restrictive strategy increased the risk for the primary composite outcome (diabetes OR [95% CI] 1.04 [0.68-1.59] vs. no diabetes OR 1.02 [0.85-1.22]; Pinteraction  = .92). In patients with versus without diabetes, a restrictive transfusion strategy was more effective at reducing red blood cell transfusion (diabetes OR [95% CI] 0.28 [0.21-0.36]; no diabetes OR [95% CI] 0.40 [0.35-0.47]; Pinteraction  = .04). CONCLUSIONS: The presence of diabetes did not modify the effect of a restrictive transfusion strategy on the primary composite outcome, but improved its efficacy on red cell transfusion. Restrictive transfusion triggers are safe and effective in patients with diabetes undergoing cardiac surgery.

An Evaluation of Severe Anesthetic-Related Critical Incidents and Risks From the South African Paediatric Surgical Outcomes Study: A 14-Day Prospective, Observational Cohort Study of Pediatric Surgical Patients.

BACKGROUND: Severe anesthetic-related critical incident (SARCI) monitoring is an essential component of safe, quality anesthetic care. Predominantly retrospective data from low- and middle-income countries (LMICs) report higher incidence but similar types of SARCI compared to high-income countries (HIC). The aim of our study was to describe the baseline incidence of SARCI in a middle-income country (MIC) and to identify associated risk for SARCI. We hypothesized a higher incidence but similar types of SARCI and risks compared to HICs. METHODS: We performed a 14-day, prospective multicenter observational cohort study of pediatric patients (aged <16 years) undergoing surgery in government-funded hospitals in South Africa, a MIC, to determine perioperative outcomes. This analysis described the incidence and types of SARCI and associated perioperative cardiac arrests (POCAs). We used multivariable logistic regression analysis to identify risk factors independently associated with SARCI, including 7 a priori variables and additional candidate variables based on their univariable performance. RESULTS: Two thousand and twenty-four patients were recruited from May 22 to August 22, 2017, at 43 hospitals. The mean age was 5.9 years (±standard deviation 4.2). A majority of patients during this 14-day period were American Society of Anesthesiologists (ASA) physical status I (66.4%) or presenting for minor surgery (54.9%). A specialist anesthesiologist managed 59% of cases. These patients were found to be significantly younger (P < .001) and had higher ASA physical status (P < .001). A total of 426 SARCI was documented in 322 of 2024 patients, an overall incidence of 15.9% (95% confidence interval [CI], 14.4-17.6). The most common event was respiratory (214 of 426; 50.2%) with an incidence of 8.5% (95% CI, 7.4-9.8). Six children (0.3%; 95% CI, 0.1-0.6) had a POCA, of whom 4 died in hospital. Risks independently associated with a SARCI were age (adjusted odds ratio [aOR] = 0.95; CI, 0.92-0.98; P = .004), increasing ASA physical status (aOR = 1.85, 1,74, and 2.73 for ASA II, ASA III, and ASA IV-V physical status, respectively), urgent/emergent surgery (aOR = 1.35, 95% CI, 1.02-1.78; P = .036), preoperative respiratory infection (aOR = 2.47, 95% CI, 1.64-3.73; P < .001), chronic respiratory comorbidity (aOR = 1.75, 95% CI, 1.10-2.79; P = .018), severity of surgery (intermediate surgery aOR = 1.84, 95% CI, 1.39-2.45; P < .001), and level of hospital (first-level hospitals aOR = 2.81, 95% CI, 1.60-4.93; P < .001). CONCLUSIONS: The incidence of SARCI in South Africa was 3 times greater than in HICs, and an associated POCA was 10 times more common. The risk factors associated with SARCI may assist with targeted interventions to improve safety and to triage children to the optimal level of care.

Development of a Clinical Prediction Model for In-hospital Mortality from the South African Cohort of the African Surgical Outcomes Study.

BACKGROUND: Data on the factors that influence mortality after surgery in South Africa are scarce, and neither these data nor data on risk-adjusted in-hospital mortality after surgery are routinely collected. Predictors related to the context or setting of surgical care delivery may also provide insight into variation in practice. Variation must be addressed when planning for improvement of risk-adjusted outcomes. Our objective was to identify the factors predicting in-hospital mortality after surgery in South Africa from available data. METHODS: A multivariable logistic regression model was developed to identify predictors of 30-day in-hospital mortality in surgical patients in South Africa. Data from the South African contribution to the African Surgical Outcomes Study were used and included 3800 cases from 51 hospitals. A forward stepwise regression technique was then employed to select for possible predictors prior to model specification. Model performance was evaluated by assessing calibration and discrimination. The South African Surgical Outcomes Study cohort was used to validate the model. RESULTS: Variables found to predict 30-day in-hospital mortality were age, American Society of Anesthesiologists Physical Status category, urgent or emergent surgery, major surgery, and gastrointestinal-, head and neck-, thoracic- and neurosurgery. The area under the receiver operating curve or c-statistic was 0.859 (95% confidence interval: 0.827-0.892) for the full model. Calibration, as assessed using a calibration plot, was acceptable. Performance was similar in the validation cohort as compared to the derivation cohort. CONCLUSION: The prediction model did not include factors that can explain how the context of care influences post-operative mortality in South Africa. It does, however, provide a basis for reporting risk-adjusted perioperative mortality rate in the future, and identifies the types of surgery to be prioritised in quality improvement projects at a local or national level.

Natriuretic peptide-directed medical therapy: a systematic review.

Natriuretic peptides (NP) are strongly associated with perioperative cardiovascular events. However, in patients with raised NP, it remains unknown whether treatment to reduce NP levels prior to surgery results in better perioperative outcomes. In this systematic review and meta-analysis, we investigate NP-directed medical therapy in non-surgical patients to provide guidance for NP-directed medical therapy in surgical patients. The protocol was registered with PROSPERO (CRD42017051468). The database search included MEDLINE (PubMed), CINAHL (EBSCO host), EMBASE (EBSCO host), ProQuest, Web of Science, and Cochrane database. The primary outcome was to determine whether NP-directed medical therapy is effective in reducing NP levels within 6 months, compared to standard of care. The secondary outcome was to determine whether reducing NP levels is associated with decreased mortality. Full texts of 18 trials were reviewed. NP-directed medical therapy showed no significant difference compared to standard care in decreasing NP levels (standardized mean difference - 0.04 (- 0.16, 0.07)), but was associated with a 6-month (relative risk (RR) 0.82 (95% confidence interval (CI) 0.68-0.99)) reduction in mortality.

National priorities for perioperative research in South Africa.

BACKGROUND: Perioperative research is currently unco-ordinated in South Africa (SA), with no clear research agenda. OBJECTIVE: To determine the top ten national research priorities for perioperative research in SA. METHODS: A Delphi technique was used to establish consensus on the top ten research priorities. RESULTS: The top ten research priorities were as follows: (i) establishment of a national database of (a) critical care outcomes, and (b) critical care resources; (ii) a randomised controlled trial of preoperative B-type natriuretic peptide-guided medical therapy to decrease major adverse cardiac events following non-cardiac surgery; (iii) a national prospective observational study of the outcomes associated with paediatric surgical cases; (iv) a national observational study of maternal and fetal outcomes following operative delivery in SA; (v) a stepped-wedge trial of an enhanced recovery after surgery programme for (a) surgery, (b) obstetrics, (c) emergency surgery, and (d) trauma surgery; (vi) a stepped-wedge trial of a surgical safety checklist on patient outcomes in SA; (vii) a prospective observational study of perioperative outcomes after surgery in district general hospitals in SA; (viii) short-course interventions to improve anaesthetic skills in rural doctors; (ix) studies of the efficacy of simulation training to improve (a) patient outcomes, (b) team dynamics, and (c) leadership; and (x) development and validation of a risk stratification tool for SA surgery based on the South African Surgical Outcomes Study (SASOS) data. CONCLUSIONS: These research priorities provide the structure for an intermediate-term research agenda.