Efficacy of remote ischaemic preconditioning on outcomes following non-cardiac non-vascular surgery: a systematic review and meta-analysis.

BACKGROUND: Remote ischaemic preconditioning (RIPC) has been investigated as a simple intervention to potentially mitigate the ischaemic effect of the surgical insult and reduce postoperative morbidity. This review systematically evaluates the effect of RIPC on morbidity, including duration of hospital stay and parameters reflective of cardiac, renal, respiratory, and hepatic dysfunction following non-cardiac non-vascular (NCNV) surgery. METHODS: The electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from their inception date to November 2021. Studies investigating the effect of local preconditioning or postconditioning were excluded. Methodological quality and risk of bias were determined according to the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Calculation of the odds ratios and a random effects model was used for dichotomous outcomes and mean differences or standardised mean differences as appropriate were used for continuous outcomes. The primary outcomes of interest were cardiac and renal morbidity, and the secondary outcomes included other organ function parameters and hospital length of stay. RESULTS: A systematic review of the published literature identified 36 randomised controlled trials. There was no significant difference in postoperative troponin or acute kidney injury. RIPC was associated with lower postoperative serum creatinine (9 studies, 914 patients, mean difference (MD) - 3.81 µmol/L, 95% confidence interval (CI) - 6.79 to - 0.83, p = 0.01, I2 = 5%) and lower renal stress biomarker (neutrophil gelatinase-associated lipocalin (NGAL), 5 studies, 379 patients, standardized mean difference (SMD) - 0.66, 95% CI - 1.27 to - 0.06, p = 0.03, I2 = 86%). RIPC was also associated with improved oxygenation (higher PaO2/FiO2, 5 studies, 420 patients, MD 51.51 mmHg, 95% CI 27.32 to 75.69, p < 0.01, I2 = 89%), lower biomarker of oxidative stress (malondialdehyde (MDA), 3 studies, 100 patients, MD - 1.24 µmol/L, 95% CI - 2.4 to - 0.07, p = 0.04, I2 = 91%)) and shorter length of hospital stay (15 studies, 2110 patients, MD - 0.99 days, 95% CI - 1.75 to - 0.23, p = 0.01, I2 = 88%). CONCLUSIONS: This meta-analysis did not show an improvement in the primary outcomes of interest with the use of RIPC. RIPC was associated with a small improvement in certain surrogate parameters of organ function and small reduction in hospital length of stay. Our results should be interpreted with caution due to the limited number of studies addressing individual outcomes and the considerable heterogeneity identified. TRIAL REGISTRATION: PROSPERO CRD42019129503.

Remote Ischaemic Preconditioning in Intra-Abdominal Cancer Surgery (RIPCa): A Pilot Randomised Controlled Trial.

There is limited evidence on the effect of remote ischaemic preconditioning (RIPC) following non-cardiac surgery. The aim of this study was to investigate the effect of RIPC on morbidity following intra-abdominal cancer surgery. We conducted a double blinded pilot randomised controlled trial that included 47 patients undergoing surgery for gynaecological, pancreatic and colorectal malignancies. The patients were randomized into an intervention (RIPC) or control group. RIPC was provided by intermittent inflations of an upper limb tourniquet. The primary outcome was feasibility of the study, and the main secondary outcome was postoperative morbidity including perioperative troponin change and the urinary biomarkers tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 (TIMP-2*IGFBP-7). The recruitment target was reached, and the protocol procedures were followed. The intervention group developed fewer surgical complications at 30 days (4.5% vs. 33%), 90 days (9.5% vs. 35%) and 6 months (11% vs. 41%) (adjusted p 0.033, 0.044 and 0.044, respectively). RIPC was a significant independent variable for lower overall postoperative morbidity survey (POMS) score, OR 0.79 (95% CI 0.63 to 0.99) and fewer complications at 6 months including pulmonary OR 0.2 (95% CI 0.03 to 0.92), surgical OR 0.12 (95% CI 0.007 to 0.89) and overall complications, OR 0.18 (95% CI 0.03 to 0.74). There was no difference in perioperative troponin change or TIMP2*IGFBP-7. Our pilot study suggests that RIPC may improve outcomes following intra-abdominal cancer surgery and that a larger trial would be feasible.

Does the Implementation of a Quality Improvement Care Bundle Reduce the Incidence of Acute Kidney Injury in Patients Undergoing Emergency Laparotomy?

PURPOSE: Previous work has demonstrated a survival improvement following the introduction of an enhanced recovery protocol in patients undergoing emergency laparotomy (the emergency laparotomy pathway quality improvement care (ELPQuiC) bundle). Implementation of this bundle increased the use of intra-operative goal directed fluid therapy and ICU admission, both evidence-based strategies recommended to improve kidney outcomes. The aim of this study was to determine if the observed mortality benefit could be explained by a difference in the incidence of AKI pre- and post-implementation of the protocol. METHOD: The primary outcome was the incidence of AKI in the pre- and post-ELPQuiC bundle patient population in four acute trusts in the United Kingdom. Secondary outcomes included the KDIGO stage specific incidence of AKI. Serum creatinine values were obtained retrospectively at baseline, in the post-operative period and the maximum recorded creatinine between day 1 and day 30 were obtained. RESULTS: A total of 303 patients pre-ELPQuiC bundle and 426 patients post-ELPQuiC bundle implementation were identified across the four centres. The overall AKI incidence was 18.4% in the pre-bundle group versus 19.8% in the post bundle group p = 0.653. No significant differences were observed between the groups. CONCLUSIONS: Despite this multi-centre cohort study demonstrating an overall survival benefit, implementation of the quality improvement care bundle did not affect the incidence of AKI.

A comparison of the non-invasive ultrasonic cardiac output monitor (USCOM) with the oesophageal Doppler monitor during major abdominal surgery.

BACKGROUND: Perioperative interventions, targeted to increase global blood flow defined by explicit measured goals, reduce postoperative complications. Consequently, reliable non-invasive estimation of the cardiac output could have far-reaching benefit. METHODS: This study compared a non-invasive Doppler device - the ultrasonic cardiac output monitor (USCOM) - with the oesophageal Doppler monitor (ODM), on 25 patients during major abdominal surgery. Stroke volume was determined by USCOM (SVUSCOM) and ODM (SVODM) pre and post fluid challenges. RESULTS: A ≥ 10% change (Δ) SVUSCOM had a sensitivity of 94% and specificity of 88% to detect a ≥ 10% Δ SVODM; the area under the receiver operating curve was 0.94 (95% CI 0.90-0.99). Concordance was 98%, using an exclusion zone of <10% Δ SVODM. 135 measurements gave median SVUSCOM 80 ml (interquartile range 65-93 ml) and SVODM 86 ml (69-100 ml); mean bias was 5.9 ml (limits of agreement -20 to +30 ml) and percentage error 30%. CONCLUSIONS: Following fluid challenges SVUSCOM showed good concordance and accurately discriminated a change ≥10% in SVODM.

Measuring the cardiac output in acute emergency admissions: use of the non-invasive ultrasonic cardiac output monitor (USCOM) with determination of the learning curve and inter-rater reliability.

Traditionally, assessment of the cardiac output has been limited to theatre or the intensive care unit. However, non-invasive cardiac output estimation is now readily available, and its application may have wider benefit in the emergency setting. The non-invasive ultrasonic cardiac output monitor (USCOM) was investigated to determine its learning curve and inter-rater reliability. Four trainee operators each performed stroke volume measurements on 25 volunteers, compared to an experienced operator pre- and post-passive leg raise. Inter-rater reliability was then assessed on 24 acute emergency in-patients. Mean percentage difference in stroke volume decreased from 19% (95% confidence intervals 14-23) across volunteers 1-5, to 6% (4-8) for the last 5 volunteers scanned. Consequently, on acute emergency in-patients, excellent inter-rater reliability (Lin's concordance correlation coefficient (ρc) 0.96 (0.92-0.98)) and agreement of a change ≥10% in stroke volume following passive leg raise on 23/24 cases were found. Following a training period of less than 5 h, USCOM stroke volume measurements demonstrated excellent inter-rater reliability.

The use of dye surrogates to illustrate local anesthetic drug sequestration by lipid emulsion: a visual demonstration of the lipid sink effect.

BACKGROUND AND OBJECTIVES: We hypothesized that by substituting a dye surrogate in place of local anesthetic, we could visually demonstrate dye sequestration by lipid emulsion that would be dependent on both dye lipophilicity and the amount of lipid emulsion used. METHODS: We selected 2 lipophilic dyes, acid blue 25 and Victoria blue, with log P values comparable to lidocaine and bupivacaine, respectively. Each dye solution was mixed with combinations of lipid emulsion and water to emulate "lipid rescue" treatment at dye concentrations equivalent to fatal, cardiotoxic, and neurotoxic local anesthetic plasma concentrations. The lipid emulsion volumes added to each dye solution emulated equivalent intravenous doses of 100, 500, and 900 mL of 20% Intralipid in a 75-kg adult. After mixing, the samples were separated into a lipid-rich supernatant and a lipid-poor subnatant by heparin flocculation. The subnatants were isolated, and their colors compared against a graduated dye concentration scale. RESULTS: Lipid emulsion addition resulted in significant dye acquisition by the lipid compartment accompanied by a reduction in the color intensity of the aqueous phase that could be readily observed. The greatest amount of sequestration occurred with the dye possessing the higher log P value and the greatest amount of lipid emulsion. CONCLUSIONS: Our study provides a visual demonstration of the lipid sink effect. It supports the theory that lipid emulsion may reduce the amount of free drug present in plasma from concentrations associated with an invariably fatal outcome to those that are potentially survivable.