M.C. Barry

Plasma factors augment neutrophil and endothelial cell activation during aortic surgery

Lung injury following reperfusion results from endothelial damage caused by release of cytotoxic products by activated neutrophils (PMN) in the pulmonary microvasculature. This process is facilitated by the release of pro-inflammatory cytokines and arachidonic metabolites following the outset of reperfusion. This study aimed to evaluate the effect of plasma obtained before and after revascularisation on neutrophil and endothelial cell activation. Plasma (IR-plasma) was obtained from venous blood samples taken before and during aortic cross-clamping, and 5, 40 and 60 min following clamp removal in seven patients undergoing elective infrarenal aortic aneurysm resection. PMN from healthy volunteers (n = 5) were incubated with these plasma samples or with fMLP (N-formylmethionyl-leucyl-phenylalanine) as positive control for 30 min and assessed flow-cytometrically for CD11b expression. Human endothelial cells (ECV-304) were incubated with IR plasma for 2, 4 and 6 h or with tumour necrosis factor (TNF) (20 ng/ml) as positive control and assessed for ICAM-1 expression. Incubation with IR plasma resulted in a significant increase from pre-clamp in PMN CD11b expression. A similar trend was seen in endothelial cell ICAM-1 expression following 2 h incubation. These results indicate that reperfusion-induced endothelial dysfunction may be mediated by plasma factors released upon revascularisation which facilitate neutrophil-endothelial interaction through up-regulation of adhesion receptor expression.

Quality of Life Following Repair of Ruptured and Elective Abdominal Aortic Aneurysms

OBJECTIVE To find out whether patients undergoing repair of ruptured abdominal aortic aneurysms (AAA) had more emotional problems and limitations of lifestyle than those listed for elective resection. DESIGN Retrospective study SETTING Teaching hospital, Eire. SUBJETS: 28 patients, 14 in each group, matched for age, sex, duration of stay in the intensive care unit (ICU), hospital stay postoperatively, and length of time since operation. INTERVENTIONS Application of structured questionnaire. MAIN OUTCOME MEASURES Emotional problems, mobility, activities of daily living, ability to sleep, degree of psychological stress, presence of symptoms, and Rosser index to measure quality of life (QoL). RESULTS There were no significant differences between the groups in any measure. CONCLUSIONS Patients have few emotional difficulties or disturbances of QoL after emergency or elective repair of AAA. Survivors after repair of ruptured AAA can expect as good a quality of life as those operated on electively. These results support an aggressive approach to the treatment of ruptured AAA.

Treatment of surgical patients is evidence-based.

OBJECTIVES To assess the type of evidence that supported our management of surgical patients. DESIGN Retrospective audit. SETTING Teaching hospital, Republic of Ireland. PATIENTS All 222 patients admitted by two surgical teams during one month. Patients admitted for diagnostic procedures were included if they were treated as a result. MAIN OUTCOME MEASURES Diagnosis and treatment were established from the notes. Evidence for each intervention was then sought in MEDLINE 1986-1999, Best Evidence 1991-1999, and the Cochrane Database of Systematic Reviews Issue 3, 1999, and graded into one of five categories: systematic review, meta-analysis, randomised controlled trial, prospective study, or retrospective study. RESULTS Treatment was supported by systematic review in 14, by meta-analysis in 12, by randomised controlled trial in 75, by prospective studies in 55, by retrospective studies in 58, and by no evidence in 8. CONCLUSIONS Everyday surgical practice in our unit is supported by good quality evidence from recent publications.

Ruptured abdominal aortic aneurysm — Can treatment costs and outcomes be predicted by using clinical or physiological parameters?

Mortality rates for patients undergoing surgery for ruptured abdominal aortic aneurysm (RAAA) remain high. The high cost of providing care for these patients mandates that proposed treatment protocols be evaluated for their cost-effectiveness. This study assessed costs related to outcome in different groups of patients with RAAA. From July 1987 to December 1993, 140 patients underwent emergency surgery for RAAA. Complete data on preoperative haemodynamic status, blood transfusion requirements, intensive care unit (ICU) stay and other hospital costs was available for 94 patients. Seventy-seven males (mean age 71.6(6)) and 17 females (mean age 77.2(6)) underwent surgery. Known risk factors including age (< or > 70 years), shock on admission (systolic blood pressure (BP) < or > 90 mm Hg), sex, and acute renal failure were analysed. For the purpose of comparison, costs (Pounds) were assessed by the ESRI (Economic and Social Research Institute of Ireland) based on 1992 prices. The overall survival rate was 48%: 53% among males and 24% among females (p < 0.05, Chi-squared test). In addition to having a significantly worse outcome than males, female patients with RAAA also had longer hospital and ICU stays and this was reflected in significantly greater expenditure. Similarly, male patients > 70 years old presenting with haemodynamic instability had significantly longer hospital and ICU stays than younger male patients. The average cost per RAAA survival (12,945 Pounds) in this series is not prohibitive, and the greater cost in high risk groups should not discourage intervention.

Differential effects of lower limb revascularisation on organ injury and the role of the amino acid taurine

Lower torso revascularisation following ischaemia results in a systemic inflammatory response. Endothelial barrier function is disrupted by neutrophil-derived proteases and oxidants. Taurine, an amino acid found in large quantities in neutrophils, is a powerful endogeneous anti-oxidant. The aims of this study were to investigate the systemic effects of reperfusion following lower limb revascularisation and to evaluate the role of taurine administration in preventing this injury. A rat model of aortic occlusion (30 min) followed by 2 h of reperfusion was used. Animals were randomised to one of three groups (n = 10 per group): control; ischaemia reperfusion untreated (IR) and taurine-treated. Taurine (4% solution) was administrated orally for 48 h prior to the experiment. Neutrophil infiltration and microvascular permeability were assessed by measuring tissue myeloperoxidase activity and wet/dry weights respectively in lung, liver, kidney, and in cardiac and skeletal muscle. Statistical analysis was by means of analysis of variance (ANOVA). Reperfusion resulted in pulmonary and renal microvascular injury as assessed by organ oedema. Hepatic tissue, skeletal and cardiac muscle were unaffected by lower limb revascularisation. Taurine was effective in preventing neutrophil-mediated pulmonary but not renal microvascular injury. These data suggest that, whilst reperfusion-induced pulmonary injury is predominantly neutrophil-mediated, agents other than neutrophil-derived oxidative metabolites, capable of independently causing organ injury through direct endothelial damage, are produced during reperfusion.

Nutritional, Respiratory, and Psychological Effects of Recombinant Human Growth Hormone in Patients Undergoing Abdominal Aortic Aneurysm Repair

BACKGROUND Recombinant human growth hormone (rhGH) has been shown to have powerful anabolic effects and to reduce or even prevent nitrogen catabolism in stressed patients. The effects of rhGH on functional parameters are less clearly defined. The aim of this study was to assess the effects of perioperative rhGH on nutritional markers, skeletal muscle function, and psychological well-being in patients undergoing infrarenal, abdominal aortic aneurysm repair. METHODS Thirty-three patients undergoing elective infrarenal abdominal aortic aneurysm repair were randomized to one of three groups: (1) control (n = 12): placebo for 6 days before and after surgery; (2) preop + postop (n = 10): rhGH (Genotropin; Pharmacia Ltd, Uppsala, Sweden) 0.3 IU/kg/d for 6 days before and after surgery; and (3) postop (n = 11): placebo for 6 days before and rhGH 0.3 IU/kg/d for 6 days after surgery. Patients were assessed on days -7 and -1 before surgery and days 7, 14, and 60 after surgery. RESULTS Administration of rhGH resulted in increased insulin-like growth factor 1 levels, the increase being significantly more marked in the group given rhGH preoperatively. Preoperative and postoperative rhGH reduced the postoperative decrease in both serum transferrin and grip strength at day 7 by 30% and 70%, respectively. Postoperative respiratory function and arterial oxygenation also were improved, with significant differences in arterial oxygenation between rhGH-treated and untreated groups. No difference in mood was seen between groups after surgery, nor was there any difference between subjective assessment of fatigue scores between groups. CONCLUSIONS This pilot study indicates that rhGH administered preoperatively has beneficial effects on skeletal muscle and respiratory function and may be more useful than postoperative rhGH administration alone.

Taurine Prevents Interleukin-2-Induced Acute Lung Injury in Rats

Background: The therapeutic efficacy of interleukin-2 (IL-2) has been limited by a dose-dependent vascular leak syndrome. This may be related to neutrophil-mediated endothelial injury. Taurine has been shown to decrease this injury in vitro. This study investigates the role of taurine in preventing IL-2-induced lung injury, and the role of neutrophil-endothelial interactions in mediating this injury. Methods:Study 1: Sprague-Dawley rats (n = 12/groups) were randomised to controls, IL-2-treated (1 × 106 units), and IL-2-treated with taurine (4% solution, orally for 48 h prior to IL-2 therapy). Lung injury was measured by extravascular lung water (wet/dry weight) and bronchoalveolar lavage protein concentration. Neutrophil infiltration was evaluated by measuring myeloperoxidase activity and bronchoalveolar lavage neutrophil concentration. Study 2: Rats (n = 10/group) were randomised into the same groups as study 1. Neutrophil-endothelial interactions in mesenteric vessels were assessed by intravital microscopy at half-hourly intervals. Results: Taurine reduced IL-2-induced acute lung injury as reflected by a decrease in wet-to-dry lung weight ratio from 7.2 ± 0.5 in the IL-2 group to 4.7 ± 0.3 in the taurine group (p < 0.05), and a decrease in bronchoalveolar neutrophil concentration from 823 ± 19.5 in the IL-2 group to 538 ± 18 in the taurine group (p < 0.05). Intravital microscopy demonstrated that IL-2 increased leucocyte adhesion and migration in mesenteric vessels, and that this was significantly reduced by taurine. Conclusion: These data suggest that taurine prevents IL-2-induced tissue injury in part by decreasing neutrophil-endothelial interactions.

An “all comers” policy for ruptured abdominal aortic aneurysms: how can results be improved?

OBJECTIVE To review our experience of a non-selective policy for the treatment of ruptured abdominal aortic aneurysm to see if the policy was justified, and to identify any preoperative risk factors that adversely influenced outcome. DESIGN Retrospective study. SETTING Teaching hospital, Republic of Ireland. SUBJECTS 258 patients admitted with abdominal aortic aneurysms between January 1982 and December 1993. INTERVENTIONS Definitive surgical treatment. MAIN OUTCOME MEASURES Morbidity, mortality, and risk factors. RESULTS In-hospital mortality for all patients was 43% (110/258). Overall, women did worse than men (28/44, 64%, died, compared with 96/214, 45%, p=0.03). The mortality among patients over the age of 80 (23/45, 51%) was not significantly different from that among younger patients (97/202, 48%). Blood pressure, platelet count, and haemoglobin concentration were all significantly lower preoperatively among those who died (p < 0.05). CONCLUSIONS Age alone cannot be used to justify witholding definitive surgical treatment. Treatment should be aimed towards reversing haematological and haemodynamic abnormalities preoperatively to try to improve outcome.

Aorto-enteric fistula: changing management strategies

BackgroundTraditionally treatment of aorto-enteric fistulae involved placement of an extra-anatomic bypass and graft excision. This is associated with limb loss (10–40%) and high mortality (10–70%). More recentlyin situ revascularisation has been advocated.AimsTo examine our experience with the changing management of aorto-enteric fistulae over a 22-year period.MethodsDemographic, clinical, operative and pathological data were recorded retrospectivelyResultsTwenty-one patients were included. Seven had primary fistulae. Six died prior to intervention. Five had an extra-anatomical bypass (60% mortality 40% limb loss),four hadin-situ revascularisation (25% mortality), four had a primary repair (25% mortality) and two had insertion of a tube graft (primary fistulae). The overall survival rate was 38%. The postoperative survival rate was 60%.ConclusionTechniques for operative management continue to evolve. The current trend is towards a local surgical approach with prolonged and intensive postoperative antimicrobial therapy. In our experience this approach has yielded acceptable outcomes.

Effects of human recombinant growth hormone (rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.

Background: Human recombinant growth hormone (rhGH) has been shown to increase skeletal muscle protein synthesis and improve nitrogen balance in critically ill patients and those undergoing surgery. rhGH effects on hepatic protein turnover in critically ill patients are less clearly understood.Objective: To examine rhGH effects on hepatic acute phase protein responses and inflammatory cytokine release in patients undergoing major surgery.Design: Prospective double blind randomised trial.Setting: Tertiary referral university teaching hospital.Patients: Patients undergoing elective abdominal aortic aneurysm repair.Intervention: Patients received rhGH (Genotropin, 0.3 IU/kg per day, n=8) or placebo (n=10) for 6 days prior to surgery.Results: Blood levels of growth hormone (GH) and insulin-like growth factor (IGF-1) were measured following rhGH treatment and C-reactive protein (CRP), serum amyloid A (SAA) and the cytokines interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1ra) were measured for up to 24 h following surgery. Significant increases in plasma rhGH (0.84 ± 0.3, mean (sem) versus 52 ± 20 mU/1, p<0.0008) and IGF-1 levels (119 ± 13 versus 644 ± 110 ng/ml, p<0.0001) were seen prior to surgery following rhGH administration. No differences in acute phase protein or cytokine levels were seen following surgery in patients receiving rhGH.Conclusions: These results indicate that pre-operative administration of rhGH does not alter acute phase protein or inflammatory cytokine release in response to major surgery.