Postoperative systemic inflammatory dysregulation and corticosteroids: a narrative review.

In some patients, the inflammatory-immune response to surgical injury progresses to a harmful, dysregulated state. We posit that postoperative systemic inflammatory dysregulation forms part of a pathophysiological response to surgical injury that places patients at increased risk of complications and subsequently prolongs hospital stay. In this narrative review, we have outlined the evolution, measurement and prediction of postoperative systemic inflammatory dysregulation, distinguishing it from a healthy and self-limiting host response. We reviewed the actions of glucocorticoids and the potential for heterogeneous responses to peri-operative corticosteroid supplementation. We have then appraised the evidence highlighting the safety of corticosteroid supplementation, and the potential benefits of high/repeated doses to reduce the risks of major complications and death. Finally, we addressed how clinical trials in the future should target patients at higher risk of peri-operative inflammatory complications, whereby corticosteroid regimes should be tailored to modify not only the a priori risk, but also further adjusted in response to markers of an evolving pathophysiological response.

Steroids in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I2 = 0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989 patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04-1.31; P=0.008; I2=0%]. New onset atrial fibrillation was lower in the steroid group [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91, 95% CI, 0.86-0.96, P=0.0005, I2=43%]; this beneficial effect was limited to small trials (P for interaction <0.00001). CONCLUSIONS: After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect.

Age and other perioperative risk factors for postoperative systemic inflammatory response syndrome after cardiac surgery.

BACKGROUND: The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic inflammatory response syndrome, during the first 24 h after cardiac surgery. METHODS: This was a retrospective cohort study, using linked data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database and the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database. Data from patients who underwent coronary artery bypass grafting and/or valve surgery were used. The association between age and postoperative SIRS was analysed using Poisson regression, and corrected for other risk factors. Restricted cubic splines were used to determine relevant age categories. Results are expressed as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Data from 28 513 patients were used. In both univariable and multivariable models, increased patient age was strongly associated with reduced postoperative SIRS prevalence. Using 73-83 yr as the reference category, the RRs (95% CI) for the age categories were 1.38 (1.28-1.49) for ≤43 yr, 1.15 (1.09-1.20) for 44-63 yr, 1.05 (1.00-1.09) for 64-72 yr, and 1.03 (0.94-1.12) for >83 yr, respectively. The predictive value for postoperative SIRS of the final model, however, was moderate (c-statistic: 0.61). CONCLUSIONS: We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.

Long-term outcomes and cost effectiveness of high-dose dexamethasone for cardiac surgery: a randomised trial.

Prophylactic intra-operative administration of dexamethasone may improve short-term clinical outcomes in cardiac surgical patients. The purpose of this study was to evaluate long-term clinical outcomes and cost effectiveness of dexamethasone versus placebo. Patients included in the multicentre, randomised, double-blind, placebo-controlled DExamethasone for Cardiac Surgery (DECS) trial were followed up for 12 months after their cardiac surgical procedure. In the DECS trial, patients received a single intra-operative dose of dexamethasone 1 mg.kg-1 (n = 2239) or placebo (n = 2255). The effects on the incidence of major postoperative events were evaluated. Also, overall costs for the 12-month postoperative period, and cost effectiveness, were compared between groups. Of 4494 randomised patients, 4457 patients (99%) were followed up until 12 months after surgery. There was no difference in the incidence of major postoperative events, the relative risk (95%CI) being 0.86 (0.72-1.03); p = 0.1. Treatment with dexamethasone reduced costs per patient by £921 [€1084] (95%CI £-1672 to -137; p = 0.02), mainly through reduction of postoperative respiratory failure and duration of postoperative hospital stay. The probability of dexamethasone being cost effective compared with placebo was 97% at a threshold value of £17,000 [€20,000] per quality-adjusted life year. We conclude that intra-operative high-dose dexamethasone did not have an effect on major adverse events at 12 months after cardiac surgery, but was associated with a reduction in costs. Routine dexamethasone administration is expected to be cost effective at commonly accepted threshold levels for cost effectiveness.

Moderate-to-deep sedation technique, using propofol and ketamine, allowing synchronised breathing for magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids: a pilot study.

BACKGROUND: Magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids is rapidly gaining popularity as a treatment modality. This procedure is generally uncomfortable, painful, and requires minimal or absence of movement and an MR-HIFU synchronised breathing pattern of the patient. Procedural sedation and analgesia protocols have become the standard practice in interventional radiology departments worldwide. The aim of this study was to explore if a sedation regimen with low-dose propofol and ketamine performed by trained non-medical sedation practitioners could result in relief of discomfort for the patient and in adequate working conditions for MR-HIFU treatment for uterine fibroids. METHODS: In this study, conducted from August 2013 until November 2014, 20 patients were subjected to MR-HIFU treatment of uterine fibroids. Patients were deeply sedated using intravenous propofol and esketamine according to a standardised hospital protocol to allow synchronisation of the breathing pattern to the MR-HIFU. The quality of sedation for MR-HIFU and complications were recorded and analysed. The side effects of the sedation technique, the propofol and esketamine consumption rate, the duration of recovery, and patient satisfaction after 24 h were examined. RESULTS: A total of 20 female patients (mean age 42.4 [range 32-53] years) were enrolled. Mean propofol/esketamine dose was 1309 mg/39.5 mg (range 692-1970 mg/ 23.6-87.9 mg). Mean procedure time was 269 min (range 140-295 min). Application of the sedation protocol resulted in a regular breathing pattern, which could be synchronised with the MR-HIFU procedures without delay. The required treatment was completed in all cases. There were no major adverse events. Hypoxemia (oxygen desaturation <92%) and hallucinations were not observed. CONCLUSIONS: The use of a specific combination of IV propofol and esketamine for procedural sedation and analgesia reduced the discomfort and pain during MR-guided HIFU treatments of uterine fibroids. The resulting regular breathing pattern allowed for easy synchronisation of the MR-HIFU procedure. Based on our results, esketamine and propofol sedation performed by trained non-medical sedation practitioners is feasible and safe, has a low risk of major adverse events, and has a short recovery time, avoiding a session of general anaesthesia.

Intraoperative hypotension and delirium after on-pump cardiac surgery.

BACKGROUND: Delirium is a common complication after cardiac surgery and may be as a result of inadequate cerebral perfusion. We studied delirium after cardiac surgery in relation to intraoperative hypotension (IOH). METHODS: This observational single-centre, cohort study was nested in a randomized trial, on a single intraoperative dose of dexamethasone vs placebo during cardiac surgery. During the first four postoperative days, patients were screened for delirium based on the Confusion Assessment Method (CAM) for Intensive Care Unit on the intensive care unit, CAM on the ward, and by inspection of medical records. To combine depth and duration of IOH, we computed the area under the curve for four blood pressure thresholds. Logistic regression analyses were performed to investigate the association between IOH and the occurrence of postoperative delirium, adjusting for confounding and using a 99% confidence interval to correct for multiple testing. RESULTS: Of the 734 included patients, 99 patients (13%) developed postoperative delirium. The adjusted Odds Ratio for the Mean Arterial Pressure <60 mm Hg threshold was 1.04 (99% confidence interval: 0.99-1.10) for each 1000 mm Hg(2) min(2) AUC(2) increase. IOH, as defined according to the other three definitions, was not associated with postoperative delirium either. Deep and prolonged IOH seemed to increase the risk of delirium, but this was not statistically significant. CONCLUSIONS: Independent of the applied definition, IOH was not associated with the occurrence of delirium after cardiac surgery.

The effects of intraoperative dexamethasone on left atrial function and postoperative atrial fibrillation in cardiac surgical patients.

Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and postoperative inflammation may contribute to PNAF by inducing atrial dysfunction. Corticosteroids reduce inflammation and may thus reduce atrial dysfunction and PNAF development. This study aimed to determine whether dexamethasone protects against left atrial dysfunction and PNAF in cardiac surgical patients. Cardiac surgical patients were randomised to a single dose of dexamethasone (1 mg.kg(-1)) or placebo after inducing anaesthesia. Transoesophageal echocardiography was performed in patients before and after surgery. Primary outcome was left atrial total ejection fraction (LA-TEF) after sternal closure; secondary outcomes included left atrial diameter and PNAF. 62 patients were included. Baseline characteristics were well balanced. Postoperative LA-TEF was 36.4 % in the dexamethasone group and 40.2 % in the placebo group (difference -3.8 %; 95 % confidence interval (CI) -9.0 to 1.4 %; P = 0.15). Postoperative left atrial diameter was 4.6 and 4.3 cm, respectively (difference 0.3; 95 % CI -0.2 to 0.7; P = 0.19). The incidence of PNAF was 30 % in the dexamethasone group and 39 % in the placebo group (P = 0.47). Intraoperative high-dose dexamethasone did not protect against postoperative left atrial dysfunction and did not reduce the risk of PNAF in cardiac surgical patients.

Effects of cardiopulmonary bypass on neurocognitive performance and cytokine release in old and diabetic rats.

BACKGROUND: Age and diabetes mellitus have been identified as independent risk factors for cognitive decline after cardiac surgery with cardiopulmonary bypass (CPB). We tested the effects of CPB on cognitive function in aged and diabetic rats utilizing the Morris water maze (MWM). METHODS: Aged rats (26 months) were randomized into a sham group (cannulation but no CPB, n = 11) and a 90 min CPB group (n = 11). In addition, young rats (n = 14) were made diabetic with streptozotocin 9 weeks before experimentation and randomized to a sham or 90 min CPB group. Cytokine release [interleukin (IL-6)] and short-term MWM performance (days 8-14 after operation) were assessed in all animals. Long-term MWM performance (8 weeks after operation) was assessed in aged rats only. RESULTS: There were no differences between the aged groups in short-term (P = 0.58) or long-term MWM performances (P = 0.69). The diabetic animals also showed no differences between the sham and CPB groups in MWM performance (P = 0.64). IL-6 assays showed an increased inflammatory response after CPB in the diabetic animals, but not in the elderly groups. CONCLUSIONS: Ninety minutes of normothermic CPB had no deleterious effect on neurocognitive outcome in elderly or chronically diabetic animals, suggesting that CPB in itself is not a sufficient stressor of the rat central nervous system.

[Postoperative cognitive dysfunction]. / Postoperatieve cognitieve disfunctie.

Memory loss and lack of concentration are symptoms that frequently occur in patients who have undergone a surgical procedure. Although cognitive function can be assessed using neuropsychological tests, diagnosing postoperative cognitive decline (POCD) reliably appears to be difficult. Therefore, the true incidence of POCD is unknown. Severe POCD, which is apparent even without neuropsychological testing, is predominantly reported after cardiac and hip-replacement surgery. In these cases, POCD probably reflects micro embolic brain injury. Apart from the nature of the surgical procedure, advanced age is the most important risk factor for POCD. The anaesthetic technique used is not a determinant: the risks of POCD occurring appear to be similar following both general and local anaesthesia.