Michael E. Gaunt

Remote Ischemic Preconditioning Reduces Myocardial and Renal Injury After Elective Abdominal Aortic Aneurysm Repair A Randomized Controlled Trial

Background— Myocardial and renal injury commonly contribute to perioperative morbidity and mortality after abdominal aortic aneurysm repair. Remote ischemic preconditioning (RIPC) is a phenomenon whereby brief periods of ischemia followed by reperfusion in one organ provide systemic protection from prolonged ischemia. To investigate whether remote preconditioning reduces the incidence of myocardial and renal injury in patients undergoing elective open abdominal aortic aneurysm repair, we performed a randomized trial. Method and Results— Eighty-two patients were randomized to abdominal aortic aneurysm repair with RIPC or conventional abdominal aortic aneurysm repair (control). Two cycles of intermittent crossclamping of the common iliac artery with 10 minutes ischemia followed by 10 minutes reperfusion served as the RIPC stimulus. Myocardial injury was assessed by cardiac troponin I (>0.40 ng/mL), myocardial infarction by the American College of Cardiology/American Heart Association definition and renal injury by serum creatinine (>177 &mgr;mol/L) according to American Heart Association guidelines for risk stratification in major vascular surgery. The groups were well matched for baseline characteristics. RIPC reduced the incidence of myocardial injury by 27% (39% versus 12% [95% CI: 8.8% to 45%]; P=0.005), myocardial infarction by 22% (27% versus 5% [95% CI: 7.3% to 38%]; P=0.006), and renal impairment by 23% (30% versus 7%; [95% CI: 6.4 to 39]; P=0.009). Multivariable analysis revealed the protective effect of RIPC on myocardial injury (OR: 0.22, 95% CI: 0.07 to 0.67; P=0.008), myocardial infarction (OR: 0.18, 95% CI: 0.04 to 0.75; P=0.006) and renal impairment were independent of other covariables. Conclusions— In patients undergoing elective open abdominal aortic aneurysm repair, RIPC reduces the incidence of postoperative myocardial injury, myocardial infarction, and renal impairment.

Endovascular stenting versus open surgery for thoracic aortic disease : Systematic review and meta-analysis of perioperative results

BACKGROUND Endovascular stenting has emerged as an alternative to open repair in patients requiring surgery for thoracic aortic pathology. A number of comparative series have been published but, to date, there has been no meta-analysis comparing outcomes following stenting as opposed to open surgery. METHODS Electronic abstract databases and conference proceedings were searched to identify relevant series. Pooled odds ratios were calculated using random effects models for perioperative mortality, neurological injury, and major reintervention. RESULTS The search identified 17 eligible series, totaling 1109 patients (538 stenting). Stenting was associated with a significant reduction in mortality (pooled odds ratio 0.36; 95% CI 0.228-0.578; P < .0001) and major neurological injury (pooled odds ratio 0.39; 95% CI 0.25-0.62; P = .0001). There was no difference in the major reintervention rate (pooled odds ratio 0.91; 95% CI 0.610-1.619). There was a reduction in hospital and critical care stay although there was evidence of heterogeneity and bias with respect to these outcomes. Subgroup analyses suggested that endovascular repair reduced mortality (pooled odds ratio 0.25; 95% CI 0.09-0.66) and neurological morbidity (pooled odds ratio 0.28; 95% CI 0.13-0.61) in stable patients undergoing repair of thoracic aortic aneurysms. There was no effect on mortality in patients with thoracic aortic trauma but neurological injury was reduced (pooled odds ratio 0.17; 95% CI 0.03-1.03). Endovascular repair did not confer any apparent benefit over open surgery in patients with thoracic aortic rupture. CONCLUSION Endovascular thoracic aortic repair reduces perioperative mortality and neurological morbidity in patients with descending thoracic aortic aneurysms. There may be less benefit in other thoracic aortic conditions.

Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide–Enhanced MRI

Background and Purpose— It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. Methods— Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. Results— There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007). Conclusions— This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials

Numerous small trials have been conducted to confirm the existence of the ischaemic preconditioning (IP) mechanism in the human heart and to clarify whether it can be induced in a clinical situation. The effect on clinical end-points remains unclear. Most of the available trials reported some clinical outcomes. We performed a systematic review and meta-analysis in order to determine whether IP produces any clinical benefit in cardiac surgery. The systematic review identified 22 eligible trials containing 933 patients. All patients undergoing on-pump surgery also received cardioplegia or intermittent cross-clamp fibrillation (ICCF) with or without adjunctive cooling. IP was mainly performed after initiation of cardiopulmonary bypass, before any additional myocardial protection was initiated. Overall, IP was associated with significant reductions in ventricular arrhythmias (pooled odds ratio 0.11; 95% CI 0.04-0.29; p=0.001), inotrope requirements (pooled odds ratio 0.34; 95% CI 0.17-0.68; p=0.002) and intensive care unit stay (weighted mean difference -3h; 95% CI -4.6 to -1.5h; p=0.001). These effects persisted when the analyses were restricted to those patients receiving cardioplegia. The effect disappeared when the analyses were restricted to patients receiving ICCF. IP may provide additional myocardial protection over cardioplegia alone, but a large-scale clinical trial may be required to determine the role of IP with any certainty.

Remote Ischemic Preconditioning for Renal and Cardiac Protection during Endovascular Aneurysm Repair: A Randomized Controlled Trial

Purpose: To report a randomized clinical trial designed to determine if remote ischemic preconditioning (IP) has the ability to reduce renal and cardiac damage following endovascular aneurysm repair (EVAR). Methods: Forty patients (all men; mean age 76±7 years) with abdominal aortic aneurysms averaging 6.3±0.8 cm in diameter were enrolled in the trial from November 2006 to January 2008. Eighteen patients (mean age 74 years, range 72–81) were randomized to preconditioning and completed the full remote IP protocol; there were no withdrawals. Twenty-two patients (mean age 76 years, range 66–80) were assigned to the control group. Remote IP was induced using sequential lower limb ischemia. Serum and urinary markers of renal and cardiac injury were compared between the groups. Results: Urinary retinol binding protein (RBP) levels increased 10-fold from a median of 235 µmol/L to 2356 µmol/L at 24 hours (p=0.0001). There was a lower increase in the preconditioned group, from 167 µmol/L to 413 µmol/L at 24 hours (p=0.04). The median urinary albumin:creatinine ratio was significantly lower in the preconditioned group at 24 hours (5 versus 8.8, p=0.06). There were no differences in the rates of renal impairment or major adverse cardiac events. Conclusion: Remote preconditioning reduces urinary biomarkers of renal injury in patients undergoing elective EVAR. This small pilot trial was unable to detect an effect on clinical endpoints; further trials are warranted.

Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: A comparison of symptomatic and asymptomatic individuals

BACKGROUND AND PURPOSE Inflammation is a risk factor the vulnerable atheromatous plaque. This can be detected in vivo on high-resolution magnetic resonance (MR) imaging using a contrast agent, Sinerem, an ultra-small super-paramagnetic iron oxide (USPIO). The aim of this study was to explore whether there is a difference in the degree of MR defined inflammation using USPIO particles, between symptomatic and asymptomatic carotid plaques. We report further on its T(1) effect of enhancing the fibrous cap, which may allow dual contrast resolution of carotid atheroma. METHODS Twenty patients with carotid stenosis (10 symptomatic and 10 asymptomatic) underwent multi-sequence MR imaging before and 36 h post-USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change across all quadrants were compared between the two groups. RESULTS Symptomatic patients had significantly more quadrants with a signal drop than asymptomatic individuals (75% vs. 32%, p<0.01). Asymptomatic plaques had more quadrants with signal enhancement than symptomatic ones (68% vs. 25%, p<0.05); their mean signal change was also higher (46% vs. 15%, p<0.01) and this appeared to correlate with a thicker fibrous cap on histology. CONCLUSIONS Symptomatic patients had more quadrants with signal drop suggesting larger inflammatory infiltrates. Asymptomatic individuals showed significantly more enhancement possibly suggesting greater stability as a result of thicker fibrous caps. However, some asymptomatic plaques also had focal areas of signal drop, suggesting an occult macrophage burden. If validated by larger studies, USPIO may be a useful dual contrast agent able to improve risk stratification of patients with carotid stenosis and inform selection for intervention.

Radiation exposure during endovascular aneurysm repair

The 42nd Annual Scientific Meeting of the Vascular Society of Great Britain and Ireland was held in Manchester, UK on 28th–30th November 2007, under the presidency of Professor George Hamilton. The abstracts of original work presented at the meeting have been published in a BJS supplement online (www.bjs.co.uk; Br J Surg 95(S1): 1–12), and the prize abstracts were published in the February 2008 issue of BJS (Br J Surg 95:265–268). The following articles are based on presentations from the Manchester meeting and have been accepted for publication after peer review by the Journals referees. Other papers from the meeting will appear in subsequent issues. Copyright

Remote Ischemic Preconditioning for Cerebral and Cardiac Protection During Carotid Endarterectomy: Results From a Pilot Randomized Clinical Trial

Remote ischemic preconditioning (RIPC) is a physiological mechanism whereby brief ischemia—reperfusion episodes attenuate damage by subsequent prolonged ischemic insults. It reduces myocardial injury following cardiac and aortic aneurysm surgery. We aimed to determine whether RIPC affects neurological or cardiac injury following carotid endarterectomy (CEA). Patients were preconditioned using 10 minutes of lower limb ischemia—reperfusion. The primary neurological outcome was saccadic latency deterioration. The primary cardiac outcome measure was increased in serum troponin I >0.15 mg/dL. In all, 70 patients were randomized, of whom 55 completed the neurological surveillance protocol. Although there were fewer saccadic latency deteriorations in the RIPC arm, this did not reach statistical significance (32% versus 53%; P = .11). The primary cardiac outcome occurred in 1 patient in each arm (P = .97). There were no adverse events related to the preconditioning protocol. Remote ischemic preconditioning appears safe in patients with CEA. Large-scale trials are required to determine whether RIPC confers clinical benefits.

Remote Ischemic Preconditioning for Renal Protection During Elective Open Infrarenal Abdominal Aortic Aneurysm Repair: Randomized Controlled Trial

We aimed to determine whether remote ischemic preconditioning (IP) reduces renal damage following elective open infrarenal abdominal aortic aneurysm (AAA) repair. Sequential common iliac clamping was used to induce remote IP in randomized patients. Urinary retinol binding protein (RBP) and albumin-creatinine ratio (ACR) were measured following induction and 3, 24, and 48 hours postoperatively. In controls (n = 22), median urinary RBP increased from 112 µg/mL (interquartile range [IQR] 96-173 µg/mL) preoperatively to 5919 µg/mL (IQR 283-17 788 µg/mL) at 3 hours. Preoperative urinary RBP in preconditioned patients was 96 µg/mL (IQR 50 to 229 µg/mL) preoperatively, rising to 1243 µg/mL (IQR 540 to 15400 µg/mL) at 3 hours. Although control patients’ median urinary RBP level was 5 times greater at 3 hours, there were no statistically significant differences in renal outcome indices. This trial could not confirm that remote IP reduces renal injury following elective open aneurysm surgery.

Doppler-guided intra-operative fluid management during major abdominal surgery: systematic review and meta-analysis.

Background:  Peri‐operative fluid therapy is a controversial area with few randomised trials to guide practice. Recently, a number of trials have suggested that intra‐operative therapy guided by oesophageal Doppler acquired haemodynamic variables may improve postoperative outcome.