J.M. Hood

Endotoxaemia, the generation of the cytokines and their relationship to intramucosal acidosis of the sigmoid colon in elective abdominal aortic aneurysm repair

Ischaemia of the large bowel occasionally occurs following abdominal aortic aneurysm repair and may lead to multiple system organ failure (MSOF). Intramucosal acidosis of the sigmoid colon is a good indicator of sigmoid colonic ischaemia. Intramucosal pH of the sigmoid colon was measured using the silicone tonometer in 21 patients undergoing abdominal aortic aneurysmectomy. Samples were taken for plasma endotoxin, tumour necrosis factor (TNF) and interleukin-6 (IL-6) measurements preoperatively, half-hourly during the operation, 2-hourly for the next 12 h, 4-hourly for a further 48 h and 8-hourly thereafter until the fifth day. The intramucosal pH of the sigmoid colon fell to less than 7.00 peri-operatively in 10 patients, four of whom developed diarrhoea; in comparison, this did not occur in any of the 11 whose pH remained greater than 7.00 (p = 0.036). Higher peak concentrations of endotoxin, TNF and IL-6 were found in those patients whose intramucosal pH fell to less than 7.00 compared to those whose pH remained greater than 7.00 (mean +/- S.E.M. pg/ml, endotoxin = 112 +/- 24 vs. 58 +/- 6, p < 0.05; TNF = 26 +/- 8 vs. 7 +/- 2, p < 0.05; IL-6 = 213 +/- 59 vs. 87 +/- 12, p = 0.09). In the two patients who died, both from the group with pH level less than 7.00, concentrations of IL-6 were considerably higher than that in most of the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramucosal acidosis and systemic host responses in abdominal aortic aneurysm surgery

OBJECTIVES To assess the specific host responses to systemic endotoxemia and tumor necrosis factor (TNF) activation after abdominal aortic aneurysm surgery by measuring antiendotoxin core antibodies (EndoCab) immunoglobulin (Ig)G and IgM, and soluble p55TNF receptor concentrations. The role of the gut in initiating these immune responses was evaluated by correlating the systemic markers to changes in the intramucosal pH of the sigmoid colon. DESIGN Retrospective, reevaluation study. SETTING Vascular unit of a university hospital. PATIENTS Eleven patients who underwent abdominal aortic aneurysm repair surgery were selected from a larger patient cohort (n = 42) on the basis of their clinical outcome (four patients had fatal complications and seven patients had an uneventful recovery). INTERVENTIONS After induction of anesthesia, intramucosal pH of the sigmoid colon was measured using tonometry. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, during surgery, and daily until postoperative day 5. MEASUREMENTS AND MAIN RESULTS Those patients who died developed intramucosal acidosis of the sigmoid colon intraoperatively. Significant consumption of both IgG and IgM EndoCab antibodies was found in all patients. By measuring the concentration of antibodies to a neutral antigen, i.e., tetanus toxoid, the consumption of IgG EndoCab antibody concentrations was shown to be a specific host response. In all patients, reciprocal changes in the serum concentrations of p55TNF receptor and interleukin (IL)-6 were observed. The percentage increase in p55TNF receptor and the concentration of IL-6 were significantly higher in the nonsurvivor group by 48 hrs. There were significant correlations between, intramucosal pH and EndoCab antibodies, intramucosal pH and p55 TNF receptor, and p55 TNF receptor and IL-6. CONCLUSIONS The development of colonic ischemia is associated with a significant consumption of IgG EndoCab antibodies and a simultaneous increase in soluble p55TNF receptor. This study provides further support for the concept that gut-derived endotoxin and the generation of TNF may play a role in the pathogenesis of complications after abdominal aortic aneurysm surgery.

Outflow Resistance and Early Occlusion of Infrainguinal Bypass Grafts

Distal outflow vascular resistance (VR) has been measured intra-operatively during 67 infrainguinal bypass procedures to establish whether it might have a role as a predictive test for early graft thrombosis. The graft outflow was popliteal artery above the knee (48), popliteal artery distal to the knee (6) or a single calf vessel (13). VR was measured before anastomosis of the graft, calculated from the relationship between pressure and flow in the outflow artery during infusion of the patients own blood at a constant rate. VR was measured before and after vasodilation with papaverine. Primary graft patency at 30 days was documented. In the 10 limbs in which graft thrombosis occurred, VR was 1167 +/- 367 mPRU, significantly higher than VR in 57 limbs with a patent graft, 850 +/- 310 mPRU (P = 0.02, Mann-Whitney U test). After papaverine, VR was 823 +/- 368 mPRU in the limbs with a thrombosed graft, significantly higher than that of limbs with a patent graft, 463 +/- 211 mPRU (P = 0.001). VR appeared to show most promise as a predictor of early thrombosis in the group of femoro-tibial and femoro-peroneal grafts. In this group, the value of 800 mPRU after papaverine was 92% efficient and was 80% sensitive, 100% specific and had a predictive value of 100% for early thrombosis. Distal outflow VR is an important factor in early graft thrombosis and might have a practical application as a predictor of early thrombosis of femoro-distal bypass grafts.

Reduction of free radical generation minimises lower limb swelling following femoropopliteal bypass surgery

Oxygen-derived free radicals have been implicated as contributors to the development of lower limb oedema observed after femoropopliteal bypass grafting. This study investigates the occurrence of free radical-induced lipid peroxidation after this operation and the possible effects of allopurinol (xanthine oxidase inhibitor) in reducing free radical injury in order to minimise lower leg oedema. Twenty-nine patients undergoing femoropopliteal bypass surgery were randomised in a double blind fashion into two groups; those in one were given allopurinol 200 mg orally (n = 15) at 24 h and 2 h preoperatively and again at 24 h postoperatively, while those in the second group received a placebo (n = 14). Daily lower limb volume was calculated to assess swelling. Blood samples were taken from the femoral vein for measurements of malondialdehyde (MDA), an end product of lipid peroxidation, before the application of the femoral artery clamp, just prior to and immediately after clamp release, and at 20 minute intervals thereafter for 1 hour. The increase in lower limb volume in the placebo group was almost twice (8.9 +/- 1.6%) that of the allopurinol group (4.6 +/- 1%; p = 0.02). Six out of the 14 patients receiving placebo suffered swelling of 10% or more of original lower limb volume in comparison to only one out of 15 in those given allopurinol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The generation of byproducts of lipid peroxidation following carotid endarterectomy

The aim of this study was to determine whether free radical-induced lipid peroxidation occurs following transient carotid clamping. Jugular vein plasma levels of malondialdehyde (MDA) and diene conjugates (DC) were estimated in 24 patients undergoing carotid endarterectomy, at the beginning of the operation (To), just prior to clamping the carotid artery before the shunt was removed for closure of the arteriotomy (Ts), and at 30 (T30), 60 (T60), 120 (T120), 180 (T180) and 300 (T300) seconds after the clamps were released. Carotid clamp times were recorded. Significant elevations in the concentrations of both MDA and DC were observed at T60 after clamp release (MDA = 559 +/- 64 pmol/ml, DC = 428 +/- 32 units/ml), in comparison to concentrations at To (MDA = 408 +/- 34 pmol/ml, p < 0.01; DC = 374 +/- 28 units/ml, p < 0.05), returning to baseline at T300. There was a significant correlation between the percentage rise in MDA concentration and the duration of clamp-induced ischaemia (r = 0.45, p = 0.03). The significance of this burst of MDA and DC is unclear especially as the one patient who sustained a postoperative neurological deficit displayed no rise in the concentration of either. If this rise is related to free radical generation following ischaemia-reperfusion injury it may play an important role in influencing the clinical outcome in the patients.

Lipid peroxidation as a cause of lower limb swelling following femoro-popliteal bypass grafting.

We examined the role of free radical induced lipid peroxidation in lower limb swelling in patients following femoro-popliteal bypass grafting. In 20 patients undergoing this operation blood samples were taken from the femoral vein via a cannula before the femoral artery clamp was applied, just prior to and immediately after clamp release and at 10 min intervals thereafter for 1 h for measurements of malondialdehyde (MDA) and vitamin E. The concentration of MDA was significantly elevated at 40 min after reperfusion (mean +/- S.E.M., 573 +/- 83 pmol/ml) compared to just before clamp release (359 +/- 41 pmol/ml; p < 0.01). This was associated with a corresponding fall in the concentration of vitamin E at the time of peak MDA rise (5.68 +/- 0.28 to 5.29 +/- 0.28 mumol/mM cholesterol, p < 0.05) suggesting its utilisation as an antioxidant. The degree of oedema was related to the changes in MDA and vitamin E. Thus, in the 15 patients with greater than 10% increase in lower limb volume the rise in the concentration of MDA was 364 +/- 44 to 693 +/- 76 pmol/ml (p = 0.0001) while that in the five, whose swelling was less than 10%, was 344 +/- 40 to 559 +/- 243 pmol/ml (p = 0.25). A significant fall in vitamin E was found only in the group with greater than 10% lower limb oedema (5.90 +/- 0.33 to 5.40 +/- 0.34 mumol/mM cholesterol, p < 0.01), in comparison to those with less than 10% swelling (5.01 +/- 0.35 to 5.04 +/- 0.50 mumol/mM cholesterol).(ABSTRACT TRUNCATED AT 250 WORDS)

The use of tonometry to predict mortality in patients undergoing abdominal aortic aneurysm repair

OBJECTIVE To assess the reliability of intramucosal pH (pHi) of the sigmoid colon, IL-6 concentration and the APACHE II score in predicting outcome in patients undergoing elective abdominal aortic aneurysm repair. DESIGN Prospective study. METHODS In 42 patients, measurements were made of the sigmoid pHi with the silicone tonometer and plasma IL-6 by enzyme linked immuno-sorbent assay (ELISA). The daily postoperative APACHE II scores were also calculated. In 29 patients a preoperative left ventricular ejection fraction was determined by gated radionuclide angiography. RESULTS Four out of 42 patients who were studied died. The lowest perioperative pHi, the peak postoperative IL-6 concentration and APACHE II scores were significantly different in the survivors in comparison to the non-survivors. In the non-survivors, the fall in pHi preceded the time of patients demise by at least 4 days. Significant correlations were observed between changes in pHi, IL-6 and APACHE II. Using receiver operating characteristic curves, pHi was shown to be the most predictive of mortality compared to the other variables. The simplicity, speed and practicality of using the tonometer adds to its superiority over the latter measurements. No relationship was found between ventricular ejection fraction, pHi and outcome. CONCLUSION Although the number of patients is small, these results support pHi as a valuable predictor of outcome and also suggest a role for the gut in initiating the IL-6 and physiological responses.

Immediate heparinisation and surgery in the management of saddle embolism.

Twenty-six patients (age range 40-88 years) with saddle embolism, representing 11% of cases of peripheral embolism, were treated during an 8-year period. A proven intra-cardiac source, including atrial fibrillation and post-infarction mural thrombosis, was observed in 22 cases (85%). The ambiguities in the clinical presentation of saddle embolism were sometimes responsible for delayed recognition. On confirmation of the diagnosis an IV heparin regime was immediately commenced followed by surgery. Our practice of initiating treatment of saddle embolism with immediate systemic heparin infusion resembles that of Blaisdell et al. In contrast, we also advocate a policy of early surgical intervention. Bilateral trans-femoral explorations were undertaken in 21 cases and direct aorto-iliac procedures in five cases. Recurrent embolism occurred in 27% of cases despite postoperative anticoagulant therapy. An overall limb salvage rate of 88.5% was recorded. The postoperative mortality of 30% was accounted for by primary cardiac disease and multiple organ failure. The influence of multiple and recurrent embolism and cardiac instability on the eventual outcome is signifcant. A policy of early systemic heparin therapy and surgery in the management of saddle embolism, enhances limb survival and prevents renal failure.

Radial artery mycotic pseudoaneurysm in a haemophiliac: a potentially fatal complication of arterial catheterization

Summary.  We present a case of radial artery pseudoaneurysm formation in a haemophiliac patient, which developed after radial artery cannulation. Haematologists and anaesthetists should be aware of this potentially fatal condition.