Left ventricular hypertrophy and myocardial protection with perhexiline during cardiac surgery

Myocardial protective strategies during cardiac surgery continue to improve yet they remain imperfect. Patients with left ventricular hypertrophy (LVH) are considered to be at greater risk of myocardial injury post cardiac surgery. Perhexiline is an anti-anginal agent known to modulate myocardial metabolism towards a more efficient glucose metabolic pathway. This metabolic modulation may improve myocardial protection. In this thesis I present a multi-centre double-blind randomised placebo controlled trial evaluating the role of perhexiline as an adjunct to standard myocardial protection in patients with LVH secondary to aortic stenosis undergoing an aortic valve replacement. Perhexiline does not augment myocardial protection. Magnetic Resonance Spectroscopy based energetic studies, echocardiographic and functional assessments in a homogenous patient cohort show no added benefit with perhexiline therapy in LVH. Therefore perhexiline should be limited to those patients refractory to maximum medical therapy. Metabolomic assessment of LVH has shown no change in the metabolomic profile within the myocardium. However any changes that do exist may be subtle. In LVH there is an increased activity of some innate cardioprotective mechanistic pathways in patients that do not sustain a low cardiac output episode post cardiac surgery. Further examination of these cardioprotective regulators is warranted

Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels

© 2021 The Authors. Published by Springer Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s13019-021-01620-wBackground: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20–60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. Results: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14–4.27, p = 0.02). Conclusions: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946.This work was supported by a research grant from RenalGuard Solutions and by the National Institute of Healthcare Research (NIHR), Clinical Research Network, UK [Ref: NIHR CRN No. 32769].Accepted versio

Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial

© 2020 The Authors. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/ejcts/ezaa395OBJECTIVES Our goal was to investigate the efficacy of balanced forced diuresis in reducing the rate of acute kidney injury (AKI) in cardiac surgical patients requiring cardiopulmonary bypass (CPB), using the RenalGuard® (RG) system. METHODS Patients at risk of developing AKI (history of diabetes and/or anaemia; estimated glomerular filtration rate 20–60 ml/min/1.73 m2; anticipated CPB time >120 min; log EuroSCORE > 5) were randomized to the RG system group (n = 110) or managed according to current practice (control = 110). The primary end point was the development of AKI within the first 3 postoperative days as defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) criteria. RESULTS There were no significant differences in preoperative and intraoperative characteristics between the 2 groups. Postoperative AKI rates were significantly lower in the RG system group compared to the control group [10% (11/110) vs 20.9% (23/110); P = 0.025]. This effect persisted even after controlling for a number of potential confounders (odds ratio 2.82, 95% confidence interval 1.20–6.60; P = 0.017) when assessed by binary logistic regression analysis. The mean volumes of urine produced during surgery and within the first 24 h postoperatively were significantly higher in the RG system group (P < 0.001). There were no significant differences in the incidence of blood transfusions, atrial fibrillation and infections and in the median duration of intensive care unit stays between the groups. The number needed to treat with the RG system to prevent AKI was 9 patients (95% confidence interval 6.0–19.2). CONCLUSIONS In patients at risk for AKI who had cardiac surgery with CPB, the RS RG system significantly reduced the incidence of AKI and can be used safely and reproducibly. Larger studies are required to confirm cost benefits.This work was supported by RenalGuard Solutions; and National Institute of Healthcare Research (NIHR), Clinical Research Network, UK [Ref: NIHR CRN No 32769].Published onlin

Balanced forced‐diuresis as a renal protective approach in cardiac surgery: Secondary outcomes of electrolyte changes

© 2021 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/jocs.15925Objectives Forced-diuresis during cardiopulmonary bypass (CPB) can be associated with significant electrolyte shifts. This study reports on the serum electrolyte changes during balanced forced-diuresis with the RenalGuard® system (RG) during CPB. Methods Patients at risk of acute kidney injury (AKI)—(history of diabetes &/or anaemia, e-GFR 20–60 ml/min/1.73 m2, anticipated CPB time >120 min, Log EuroScore >5)—were randomized to either RG (study group) or managed as per current practice (control group). Results The use of RG reduced AKI rate (10% for RG and 20.9% in control, p = .03). Mean urine output was significantly higher in the RG group during surgery (2366 ± 877 ml vs. 765 ± 549 ml, p < .001). The serum potassium levels were maintained between 3.96 and 4.97 mmol/L for the RG group and 4.02 and 5.23 mmol/L for the controls. Median potassium supplemental dose was 60 (0–220) mmol (RG group) as compared to 30 (0–190) mmol for control group over first 24 h (p < .001). On Day 1 post-op, there were no significant differences in the serum sodium, potassium, calcium, magnesium, phosphate, and chloride levels between the two groups. Otherwise, postoperative clinical recovery was also similar. Conclusions Balanced forced-diuresis with the RG reduced AKI rates after on-pump cardiac surgery compared to controls. Although the RG group required higher doses of IV potassium replacement in the postoperative period, normal serum levels of potassium were maintained by appropriate intravenous potassium supplementation and the clinical outcomes between groups were similar.This work was supported by a research grant from RenalGuard Solutions and by the National Institute of Healthcare Research (NIHR), Clinical Research Network, UK (Ref: NIHR CRN No 32769)Published onlin

Is the Venner-PneuX Endotracheal Tube System a Cost-Effective Option for Post Cardiac Surgery Care?

BACKGROUND: Ventilator-associated pneumonia (VAP) is common and costly. In a recent randomized controlled trial, the Venner-PneuX (VPX) endotracheal tube system (Qualitech Healthcare Limited, Maidenhead, United Kingdom) was found to be superior to standard endotracheal tubes (SET) in preventing VAP. However, VPX is considerably more expensive. We evaluated the costs and benefits of VPX to determine whether replacing SET with VPX is a cost-effective option for intensive care units. METHODS: We developed a decision analytic model to compare intubation with VPX or SET for patients requiring mechanical ventilation after cardiac operations. The model was populated with existing evidence on costs, effectiveness, and quality of life. Cost-effectiveness and cost-utility analyses were conducted from a National Health Service hospital perspective. Uncertainty was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: Compared with SET, VPX is associated with an expected cost saving of £738 per patient. VPX led to a small increase in quality-adjusted life years, indicating that the device is overall less costly and more effective than SET. The probability of VPX being cost-effective at £30,000 per quality-adjusted life year is 97%. VPX would cease to be cost-effective if (1) it led to a risk reduction smaller than 0.02 compared with SET, (2) the acquisition cost of VPX was as high as £890, or (3) the cost of treating a case of VAP was lower than £1,450. CONCLUSIONS: VPX resulted in improved outcomes and savings that far offset the cost of the device, suggesting that replacing SET with VPX is overall beneficial. Findings were robust to extreme values of key variables

Distal Repair After Total Aortic Arch Replacement With Frozen Elephant Trunk in Patients With Chronic Multilevel Thoracic Aortic Disease.

ObjectiveTo examine the management of distal aortic disease after total arch replacement with the frozen elephant trunk (TAR + FET) in patients with chronic thoracic aortic disease.MethodsTwo centre retrospective study of consecutive patients treated between January 2010 and December 2019. Primary endpoint was 30 day/in hospital mortality. Secondary end point was mid-term survival. Data are presented as median (IQR). Chi squared or Fisher's exact test was used as appropriate. Estimated survival (standard error) was assessed by the calculating Kaplan-Meier product limit estimator with right censoring of survival data. A p value of ResultsA total of 158 patients (72 men; median age 70, IQR 64, 75; median distal aortic diameter 58 mm (46, 68; 127 aneurysmal disease, 31 chronic dissection) underwent TAR + FET. Peri-operative mortality was 10.1% (9/107 elective, 7/51 non-elective). Of 74 (46.8%) patients with a primary distal seal, seven (9.5%) died peri-operatively, distal seal was maintained during follow up in 51, nine underwent late distal repair (two planned, seven unplanned; one open, eight endovascular; one peri-operative death) with a median interval to unplanned repair of 777 days (462, 1480), and seven with loss of seal had no intervention. Distal seal failed in 2/28 (7%) patients with a distal seal length > 30 mm and device oversizing > 10%, compared with 12/39 (31%) patients who did not meet these criteria (p = .031). In 84 patients without primary distal seal, nine (10.7%) died peri-operatively, the distal aorta remained below the size threshold for repair during follow up in 12 patients, 44 had distal repair (median aortic diameter 64 mm, 60, 75; eight open, one hybrid, 35 endovascular repairs; no mortality) at a median of 256 days (135, 740), and 19 did not have distal repair at the end of the follow up period: six died before planned repair at a median interval of 115 days (85, 120); eight were considered unfit; one was assessed as fit but declined; and four patients were awaiting assessment). Median follow up was 46 months (26, 75): no patients were lost to follow up. Estimated ± standard error five year survival was 61.5 ± 4.1%: elective 70.6 ± 4.7%, non-elective 43.2 ± 7.2%.ConclusionTAR + FET achieved primary distal seal in 47% of patients, but late failure occurred in 21% of patients. Distal repair was ultimately indicated in 84% of survivors without primary distal seal and of these 70% underwent repair, almost 10% died before planned repair, and 13% were considered unfit. Earlier distal endovascular repair and better assessment of patient fitness may improve mid-term outcomes

Chest Wall Mechanics In Vivo With a New Custom-Made Three-Dimensional-Printed Sternal Prosthesis.

PURPOSE Reconstruction after sternal resection is performed according to surgeon intuition; physiologic evidence for selection of prostheses is lacking. We present our experience of the in vivo function of a novel device for sternal reconstruction. DESCRIPTION A three-dimensional-printed titanium and porous polyethylene sternal prosthesis was made according to the patient's computed tomographic scan. The titanium arms slot over adjacent ribs and are fixed in place with screws. The porous element allows ingrowth of native tissue while preventing lung herniation around the narrow titanium bars. EVALUATION We performed optoelectronic plethysmography to assess the physiologic function of the device compared with a muscle flap reconstruction. Asynchronous and paradoxical movements of the thoracoabdominal surface were apparent with the muscle flap reconstruction but not with the new device. Considerably higher tidal volumes and a lower respiratory rate achieved the same minute volume with the new device compared with the muscle flap. CONCLUSIONS Rigid sternal reconstruction with a three-dimensional-printed prosthesis demonstrated superior respiratory mechanics compared with reconstruction with an autologous muscle flap