Denis W. Harkin

Preliminary results of a prospective randomized trial of restrictive versus standard fluid regime in elective open abdominal aortic aneurysm repair.

Background:Open abdominal aortic aneurysm (AAA) repair is associated with a significant morbidity (primarily respiratory and cardiac complications) and an overall mortality rate of 4% to 10%. We tested the hypothesis that perioperative fluid restriction would reduce complications and improve outcome after elective open AAA repair. Methods:In a prospective randomized control trial, patients undergoing elective open infra-renal AAA repair were randomized to a “standard” or “restricted” perioperative fluid administration group. Primary outcome measure was rate of major complications (MC) after AAA repair and secondary outcome measures included: Sequential Organ Failure Assessment Score; FiO2/PO2 ratio; Urinary Albumin/Creatinine Ratio; Length-of-stay in, intensive care unit, high dependency unit, in-hospital. This prospective Randomized Controlled Trial was registered in a publicly accessible database and has the following ID number ISRCTN27753612. Results:Overall 22 patients were randomized, 1 was excluded on a priori criteria, leaving standard group (11) and restricted group (10) for analysis. No significant difference was noted between groups in respect to age, gender, American Society Anesthesiology class, Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity scores, operation time, and operation blood loss. There were no in-hospital deaths and no 30-day mortality. The cumulative fluid balance on day 5 postoperative was for standard group, 8242 ± 714 mL, compared with restricted group, 2570 ± 977 mL, P < 0.01. MC were significantly reduced in the restricted group (n = 10), 1 MC, compared with standard group (n = 11), 14 MC, P < 0.024. Total and postoperative length-of-stay in-hospital was significantly reduced in the restricted group, 9 ± 1 and 8 ± 1 days, compared with standard group, 18 ± 5 and 16 ± 5 days, P < 0.01 and P < 0.025, respectively. Conclusions:Serious complications are common after elective open AAA repair, and we have shown for the first time that a restricted perioperative fluid regimen can prevent MC and significantly reduce overall hospital stay.

Role of adenosine in immunomodulation: review of the literature.

ObjectiveAdvances in the understanding of sepsis have failed to deliver satisfactory new treatments aimed at attenuating inflammatory-mediated organ dysfunction. Phagocytic cells play a pivotal role in driving the inflammatory response and causing direct tissue injury. Adenoreceptor stimulation may attenuate such inflammatory-mediated damage by down-regulating phagocytic activity and preventing excessive respiratory burst activation. DataA Medline database was used to perform a literature search for all articles relating to the use of adenosine as an immunomodulatory agent. ConclusionThere is convincing evidence to suggest that adenoreceptor modulation can prevent tissue injury through a variety of pathways. The use of adenosine modulation in ischemia/reperfusion injury has been the subject of considerable investigation, although experience with its use in sepsis is limited.

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

ObjectiveTo investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia–reperfusion (I/R) injury. Summary Background DataGut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. MethodsAnesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at −70°C for later determination of plasma tumor necrosis factor (TNF)-&agr;, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar–arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. ResultsBilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. ConclusionsEndotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

Preliminary results of a prospective randomised trial of a restrictive versus standard fluid regime in elective abdominal aortic aneurysm repair

Objective: Military vascular injuries are complex limb and life-threatening wounds which pose significant difficulties in pre-hospital and surgical management. Our aim was to provide a comprehensive description of the epidemiology, treatment and outcome of vascular injury amongst service personnel deployed on operations in Afghanistan and Iraq. Method: Analysis of the British Military Trauma Registry was combined with hospital record and post-mortem review of all cases of vascular trauma in deployed service personnel over a 5-year period ending in January 2008. Results: Of 1203 trauma patients, 121 sustained injuries to named vessels. Seventy-seven of 121 died prior to any opportunity for surgical intervention. All 19 patients who sustained an injury to a named vessel in the abdomen or thorax died; 18 did not survive to undergo surgery, one in extremis casualty underwent a thoracotomy and died. Six out of 15 patients with cervical vascular injuries survived to surgical intervention; two died following surgery. Of 87 patients with extremity vascular injuries, 37 survived to surgery with two postoperative deaths. Interventions on 38 limbs included 19 damage control (15 primary amputations, four vessel ligations) and 19 definitive limb revascularisation procedures (11 interposition vein grafts, eight direct repairs) of which four failed, necessitating three amputations. Conclusion: In operable patients with extremity injury, amputation or ligation is often required for damage control and preservation of life, but favourable limb salvage rates are achievable in casualties able to withstand revascularisation. Despite marked progress in contemporary battle-field trauma care, torso vascular injury is usually not amenable to surgical intervention.

Phagocyte priming as a prognostic indicator in the intensive care unit.

BACKGROUND The purpose of this study was to study the temporal changes in circulating phagocyte respiratory burst activity and its relationship to mortality in intensive care unit (ICU) patients. METHODS Thirty-seven consecutive patients over a 3-week period were studied on their first, third, and seventh day of admission to the regional ICU in Northern Ireland. Blood samples were assayed for respiratory burst activity using luminol-enhanced whole blood chemiluminescence. RESULTS Compared with survivors, nonsurvivors exhibited significantly higher Acute Physiology and Chronic Health Evaluation II scores, a base deficit, and reduced phagocyte activity (median [interquartile range]) (24.00% [18.00%, 56.00%] vs. 38.00% [30.00%, 63.50%], p = 0.047, Mann-Whitney U test) on day 3 of admission to the ICU. CONCLUSION Temporal changes in phagocyte activation dependent on the underlying insult were seen in ICU patients. Furthermore, the degree of phagocyte activation was able to distinguish between survivors and nonsurvivors on day 3 of admission to the ICU. Nonsurvivors exhibited reduced phagocyte activation, suggesting patients at risk of mortality exhibit systemic anergy.

Triglyceride to HDL Ratio is a Reliable Predictor of Adverse Outcomes in Risk Stratification for Candidates Undergoing Abdominal Aortic Surgery

INTRODUCTION The aim of this study was to establish if an elevated triglyceride to high-density lipoprotein (HDL) ratio (THR) is not only a risk factor for cardiovascular and overall morbidity as the updated evidence shows, but could also be employed as a significant predictor for surgical adverse outcomes and hence be a valid tool for risk stratification of candidates undergoing abdominal aortic surgery. METHODS This is a single-centre retrospective analysis of 2224 patients who underwent open abdominal aortic surgery between January 1996 and 2009. This cohort was divided into quartiles of THR. A list of covariates has been entered with THR into a multiple logistic model with forwards stepwise selection. The obtained result is an adjusted model, conceived to establish the association between THR and perioperative adverse events. Discrimination of the model so obtained and comparison with vascular-specific risk stratification scoring systems were evaluated using the area under the receiver operating characteristic (AUROC). RESULTS THR had the highest predictive value for the outcomes of interest. The adjusted odds ratios (ORs) per every 0.1 augmentation of THR were 1.41 (1.08-1.88) for cardiac, 1.38 (1.09-1.84) for respiratory, 1.27 (1.06-1.54) for renal adverse events and 1.02 (0.84-1.23) for mortality. Regarding mortality, either of the scoring systems Vascular Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and customised probability index (CPI) and the THR ranked as moderate discriminators, with THR performing the worst (AUROC 0.71) compared with Vascular POSSUM (AUROC 0.76) and CPI (AUROC 0.78). THR performed as a very strong predictor of morbidity (AUROC 0.86), ranking above Vascular POSSUM (AUROC 0.72). CONCLUSIONS THR is a significant predictor of perioperative morbidity and mortality. THR offers a broad outlook on the metabolic state of patients undergoing major abdominal aortic surgery and hence their propensity to adverse events, allowing us to risk-stratify the prognostic outcome of surgical intervention and possibly intervene preoperatively to optimise results.