Effect of remote ischaemic preconditioning on mortality and morbidity after non-cardiac surgery: meta-analysis.

BACKGROUND: Remote ischaemic preconditioning (RIPC) has been shown to have a protective role on vital organs exposed to reperfusion injury. The aim of this systematic review was to evaluate the effects of non-invasive RIPC on clinical and biochemical outcomes in patients undergoing non-cardiac surgery. METHODS: A systematic literature search of PubMed, EMBASE, Scopus, and Cochrane databases was carried out in February 2020. RCTs investigating the effect of non-invasive RIPC in adults undergoing non-cardiac surgery were included. Meta-analyses and trial sequential analyses (TSAs) were performed on cardiovascular events, acute kidney injury, and short- and long-term mortality. RESULTS: Some 43 RCTs including 3660 patients were included. The surgical areas comprised orthopaedic, vascular, abdominal, pulmonary, neurological, and urological surgery. Meta-analysis showed RIPC to be associated with fewer cardiovascular events in non-cardiac surgery (13 trials, 1968 patients, 421 events; odds ratio (OR) 0.68, 95 per cent c.i. 0.47 to 0.96; P = 0.03). Meta-analyses of the effect of RIPC on acute kidney injury (12 trials, 1208 patients, 211 events; OR 1.14, 0.78 to 1.69; P = 0.50; I2 = 9 per cent), short-term mortality (7 trials, 1239 patients, 65 events; OR 0.65, 0.37 to 1.12; P = 0.12; I2 = 0 per cent), and long-term mortality (4 trials, 1167 patients, 9 events; OR 0.67, 0.18 to 2.55; P = 0.56; I2 = 0 per cent) showed no significant differences for RIPC compared with standard perioperative care in non-cardiac surgery. However, TSAs showed that the required information sizes have not yet been reached. CONCLUSION: Application of RIPC to non-cardiac surgery might reduce cardiovascular events, but not acute kidney injury or all-cause mortality, but currently available data are inadequate to confirm or reject an assumed intervention effect.

Cardiovascular events in patients undergoing hip fracture surgery treated with remote ischaemic preconditioning: 1-year follow-up of a randomised clinical trial.

Remote ischaemic preconditioning reduces the risk of myocardial injury within 4 days of hip fracture surgery. We aimed to investigate the effect of remote ischaemic preconditioning on the incidence of major adverse cardiovascular events 1 year after hip fracture surgery. We performed a phase-2, multicentre, randomised, observer-blinded, clinical trial between February 2015 and September 2017. We studied patients aged ≥ 45 years with a hip fracture and a minimum of one cardiovascular risk factor. Patients were allocated randomly to remote ischaemic preconditioning applied just before surgery or no treatment (control group). Remote ischaemic preconditioning was performed on the upper arm with a tourniquet in four cycles of 5 min ischaemia and 5 min reperfusion. Primary outcome was the occurrence of major adverse cardiovascular events within 1 year of surgery. A total of 316 patients were allocated randomly to the remote ischaemic preconditioning group and 309 patients to the control group. Major adverse cardiovascular events occurred in 43 patients (13.6%) in the remote ischaemic preconditioning group compared with 51 patients (16.5%) in the control group (adjusted hazard ratio (95%CI) 0.83 (0.55-1.25); p = 0.37). Fewer patients in the remote ischaemic preconditioning group had a myocardial infarction (11 (3.5%) vs. 22 (7.1%); hazard ratio (95%CI) 0.48 (CI 0.23-1.00); p = 0.04). Remote ischaemic preconditioning did not reduce the occurrence of major adverse cardiovascular events within 1 year of hip fracture surgery. The effect of remote ischaemic preconditioning on clinical cardiovascular outcomes in non-cardiac surgery needs confirmation in appropriately powered randomised clinical trials.

Endothelial dysfunction in the early postoperative period after major colon cancer surgery.

BACKGROUND: Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively. METHODS: Patients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four. RESULTS: Preoperative RHI was 1.86 (1.64 - 2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations. CONCLUSIONS: RHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine - nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT02344771.

Troponin elevations after non-cardiac, non-vascular surgery are predictive of major adverse cardiac events and mortality: a systematic review and meta-analysis.

BACKGROUND: Patients undergoing non-cardiac, non-vascular surgery are at risk of major cardiovascular complications. In non-cardiac surgery, troponin elevation has previously been shown to be an independent predictor of major adverse cardiac events and postoperative mortality; however, a majority of studies have focused on vascular surgery patients. The aim of this meta-analysis was to determine whether troponin elevation is a predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery. METHODS: A systematic review and meta-analysis was conducted in January 2016 according to the Meta-analysis Of Observational Studies in Epidemiology guidelines. Both interventional and observational studies measuring troponin within the first 4 days after surgery were eligible. A systematic search was performed in PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials. RESULTS: Eleven eligible clinical studies (n=2193) were identified. A postoperative troponin elevation was a predictor of 30 day mortality, odds ratio (OR) 3.52 [95% confidence interval (CI) 2.21-5.62; I2=0%], and an independent predictor of 1 yr mortality, adjusted OR 2.53 (95% CI 1.20-5.36; I2=26%). A postoperative troponin elevation was associated with major adverse cardiac events at 30 days, OR 5.92 (95% CI 1.67-20.96; I2=86%), and 1 yr after surgery, adjusted OR 3.00 (95% CI 1.43-6.29; I2=21%). CONCLUSIONS: Postoperative myocardial injury is an independent predictor of major adverse cardiac events and mortality within 30 days and 1 yr after non-cardiac, non-vascular surgery. The meta-analysis provides evidence that supports troponin monitoring as a cardiovascular risk stratification tool.