Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures.

BACKGROUND: Hip fracture patients have a high risk of thrombo-embolic complications following surgical management. OBJECTIVES: To examine the effects of heparin (unfractionated (U), and low molecular weight (LMW) heparins), and physical methods (compression stockings, calf or foot pumps) for prevention of deep venous thrombosis (DVT) and pulmonary embolism after surgery for hip fracture in the elderly. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (up to March 2002), MEDLINE (1966 to March 2002), EMBASE (1980 to March 2002), CINAHL (1982 to February week 4 2002), Current Contents (1993 week 26 to 2002 week 12), reference lists of published articles and contacted trialists and other workers in the field. Date of most recent search: March 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the use of heparins and physical agents for prevention of DVT and pulmonary embolism in patients undergoing surgery for hip fracture. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed methodological quality and extracted data. Trials were grouped into five categories (heparin versus control, mechanical versus control, LMW heparin versus U heparin, heparin versus mechanical, and miscellaneous) and results pooled where possible. MAIN RESULTS: The 31 included trials involved at least 2958 predominantly female and elderly patients. Overall, trial quality was disappointing. Ten trials involving 826 patients which compared U heparin with control, and five trials of 373 patients which compared LMW heparin with control, showed a reduction in the incidence of lower limb DVT (124/474 (26%) versus 219/519 (42%); relative risk (RR) 0.60; 95% confidence interval (CI) 0.50 to 0.71). There were insufficient data to confirm the efficacy of either agent in the prevention of pulmonary embolism. There was no statistically significant difference in overall mortality (42/356 (12%) versus 38/374 (10%); RR 1.16; 95%CI 0.77 to 1.74). Data were inadequate for all other outcomes including wound complications. There is insufficient evidence from five trials, involving 644 patients, to establish if LMW heparin was superior to U heparin. Most trials evaluating heparins had methodological defects. Five trials, involving 487 patients, testing mechanical pumping devices were also methodologically flawed, and so pooled results need to be viewed cautiously. Mechanical pumping devices may protect against DVT (16/221 (7%) versus 52/229 (22%); RR 0.31; 95%CI 0.19 to 0.51) and pulmonary embolism. Data were insufficient to establish any effect on the incidence of fatal pulmonary embolism and overall mortality. Problems with skin abrasion and compliance were reported. REVIEWER'S CONCLUSIONS: U and LMW heparins protect against lower limb DVT. There is insufficient evidence to confirm either protection against pulmonary embolism or an overall benefit, or to distinguish between various applications of heparin. Foot and calf pumping devices appear to prevent DVT, may protect against pulmonary embolism, and reduce mortality, but compliance remains a problem. Good quality trials of mechanical methods as well as direct comparisons with heparin and low dose aspirin should be considered.

Home versus in-patient treatment for deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) affects 1-2/1,000 of the adult population per annum in western societies. It may be associated with pulmonary embolism (PE) which carries a 10% fatality rate. Sufferers may develop post-thrombotic syndrome with swelling of the leg, secondary varicose veins and ulceration. In the initial stages of treatment for DVT patients are traditionally admitted to hospital for intravenous treatment with unfractionated heparin (UH) for three to five days. The dose of UH required to provide a therapeutic level of anticoagulation is unpredictable, so the blood must be closely monitored. Fractionated, or low molecular weight heparin (LMWH), is given subcutaneously once daily and requires no monitoring, so can be given in hospital or at home. OBJECTIVES: To collate all randomised controlled trials (RCTs) comparing a home treatment regime (LMWH) with hospital treatment (LMWH or UH) for the initial phase of treatment for DVT, and to compare the safety, efficacy, patient acceptability and cost implications of home versus in-patient treatment. SEARCH STRATEGY: All published reports of home treatment were traced through MEDLINE, and EMBASE (up to and including December 2000) using the search strategy described by the Cochrane Peripheral Vascular Diseases Group. Additional searches included the Cochrane CCTR/CENTRAL database, handsearching non-listed journals, and personal communication with researchers. SELECTION CRITERIA: RCTs of home versus hospital treatment for DVT in which DVT was clinically confirmed and treated with either LMWH or UH. DATA COLLECTION AND ANALYSIS: One reviewer selected the material for inclusion (IGS): the other (AAM) reviewed the literature and selection of trials. Outcomes included PE, recurrent DVT, gangrene, heparin complications, and death. MAIN RESULTS: Only two major RCTs with comparable treatment arms were found. Both had fundamental problems including high exclusion rates, partial hospital treatment of many in the LMWH arms, and comparison of UH in hospital with LMWH at home. The trials showed that home treatment was no more liable to complications than hospital treatment. Initial results from a smaller RCT comparing LMWH treatment in both home and hospital arms came to the same conclusion. REVIEWER'S CONCLUSIONS: The limited evidence suggests that home management is cost effective, and likely to be preferred by patients. Further large trials comparing these treatments are unlikely to be held. Therefore, home treatment is likely to become the norm, and further research will be directed to resolving practical issues.

Centralisation of oesophageal cancer services; the view from the periphery.

There is debate as to whether patients requiring resection for oesophageal cancer should be referred to specialist centralised units rather than being managed by general surgeons in district general hospitals (DGH). The aim of this study was to determine the effects of centralising oesophageal cancer surgery on outcome and quality of service for patients with oesophageal cancer in a peripheral region. Patients with biopsy proven oesophageal cancer diagnosed over a 4 year period were identified from pathology records. Patients were divided into two groups; Group 1 (n = 60) from the first two years of the study who had any surgery performed by a general surgeon within the DGH and Group 2 (n = 53) from the latter two years of the study who had any surgery performed in a regional cardiothoracic unit. The post-operative mortality rate was lower in the specialist unit, 5.6% vs. 12.5%, but this was not statistically significant. There were no significant differences in survival rates; 3 month, 1 year, 2 year and 3 year survival rates were 63% vs. 62%, 24% vs. 25%, 12% vs. 8% and 7% vs. 6% in Groups 1 and 2, respectively. Referral rates for a surgical opinion were significantly lower in Group 2--92% vs. 63% p < 0.01 by Chi-squared test. Patients waited significantly longer from diagnosis to definitive treatment in Group 2--median 15 days vs. 23 days p = 0.17 by Mann-Whitney test. In conclusion, survival rates are not necessarily improved by centralisation of oesophageal cancer surgery and quality of service may be poorer.

Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures.

BACKGROUND: Hip fracture patients have a high risk of thromboembolic complications following surgical management. OBJECTIVES: To examine the effects of heparin (unfractionated (U), and low molecular weight (LMW) heparins), and physical methods (compression stockings, calf or foot pumps) for prevention of deep venous thrombosis (DVT) and pulmonary embolism after surgery for hip fracture in the elderly. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register, Medline, Embase, and reference lists of published papers and books. We contacted trialists and other workers in the field. Date of most recent search: September 1996. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the use of heparins and physical agents for prevention of DVT and pulmonary embolism in patients undergoing surgery for hip fracture. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed methodological quality and extracted data. Trials were grouped into four categories (heparin versus control, mechanical versus control, LMW heparin versus U heparin, and miscellaneous) and results pooled where possible. MAIN RESULTS: The 26 included trials involved 2600 predominantly female and elderly patients. Overall, trial quality was disappointing. Ten trials involving 826 patients which compared U heparin with control, and four trials of 471 patients which compared LMW heparin with control, showed a reduction in the incidence of lower limb DVT (121/511 (24%) versus 203/519 (39%); Peto odds ratio 0.41; 95% confidence interval 0.31 to 0.55). There were insufficient data to confirm the efficacy of either agent in the prevention of pulmonary embolism. There was a non significant increase in overall mortality in the heparin group (46/420 (11%) versus 35/423 (8%); Peto odds ratio 1.39; 95% confidence interval 0. 86 to 2.23). Data were inadequate for all other outcomes including wound complications. There is insufficient evidence from five trials, involving 644 patients, to establish if LMW heparin was superior to U heparin. Most trials evaluating heparins had methodological defects. Four trials, involving 442 patients, testing mechanical pumping devices were also methodologically flawed, and so pooled results need to be viewed cautiously. Mechanical pumping devices may protect against DVT (12/202 (6%) versus 42/212 (19%); Peto odds ratio 0.24; 95% confidence interval 0.13 to 0.44). Although the limited data indicated a potential benefit, they were inadequate to establish any effect on the incidence of pulmonary embolism and overall mortality. Problems with skin abrasion and compliance were reported. REVIEWER'S CONCLUSIONS: U and LMW heparins protect against lower limb DVT. There is insufficient evidence to confirm either protection against pulmonary embolism or overall benefit, or to distinguish between various applications of heparin. Foot and calf pumping devices appear to prevent DVT, may protect against pulmonary embolism, and reduce mortality, but compliance remains a problem. Good quality trials of mechanical methods as well as direct comparisons with heparin should be considered.

Serum amylase isoenzymes in patients undergoing operation for ruptured and non-ruptured abdominal aortic aneurysm.

OBJECTIVE: Previous work has suggested that hyperamylasemia in patients who undergo operation for ruptured abdominal aortic aneurysm (AAA) is associated with poor outcome. The aims of this study were to determine, for the first time, the source of serum amylase in such patients and to examine the prognostic significance of amylase isoenzyme expression. METHODS: This study was designed as a prospective clinical and laboratory study. The study consisted of 40 patients who underwent operation for ruptured AAA and 10 patients who underwent operation for non-ruptured AAA. The main outcome measures were serum total and pancreatic and salivary amylase activities determined with enzymatic colorimetric assay before operation and 6 hours after aortic clamp release. RESULTS: Five of 40 patients (12.5%) with rupture and one of 10 patients (10%) with non-rupture had elevated total amylase levels before operation, and seven of 31 patients (23%) with rupture and five of 10 patients (50%) with non-rupture had elevated total amylase levels after operation. The preoperative salivary amylase (P =.05) and postoperative pancreatic amylase (P <.02) levels were significantly lower in ruptured AAA as compared with non-ruptured AAA. The preoperative salivary amylase level was significantly lower in non-survivors of rupture, such that a level equal to or less than 45 U/L was associated with death in 11 of 13 patients (85%). CONCLUSION: These data do not support previous works that suggest that hyperamylasemia is associated with poor outcome in ruptured AAA. By contrast, a low preoperative salivary amylase level was associated with increased mortality in ruptured AAA and may be a marker of the severity of shock.

Effects of asymptomatic abdominal aortic aneurysm on the soluble coagulation system, platelet count and platelet activation.

OBJECTIVES: the aim of the study was to determine the effects of infrarenal asymptomatic abdominal aortic aneurysm (AAA) on platelet count and activation. DESIGN: prospective clinical study in a University Department of Vascular Surgery. PATIENTS: one hundred and five patients with AAA. Thirty-two control patients with symptomatic carotid artery stenoses. METHODS: platelet count (PC), plasma glycocalicin levels, prothrombin ratio (PTR), activated partial thromboplastin time (APPT), fibrinogen and D-dimer were measured in 23 patients with AAA and 16 control patients with symptomatic carotid artery stenoses. PC alone was measured in a further 84 patients with AAA and 16 with carotid artery stenoses. RESULTS: PC was below the normal range in 8/105 patients and mean PC (215x10(9)/l, S.D. 47.5) was significantly lower than that of a control population (242x10(9)/l, S.D. 16.8) and patients with carotid disease (269x10(9)/l, S.D. 57). Glycocalicin level was above the normal range in 7/23 patients and the median level (28 fg/plt) was significantly higher than that of a normal population (21.6 fg/plt) and patients with carotid disease (12.3 fg/plt). Fibrinogen levels, PTR and APPT were all within the normal range. One patient had a minimally elevated level of D-dimer. CONCLUSIONS: the combination of low PC and high glycocalicin levels suggests that there is increased platelet destruction, most likely due to activation within the aneurysm sac.

Comparative assessment of surgical training using objective criteria.

The aims of the study were to develop and validate an objective method of assessing the operative experience of surgical trainees. Data were retrieved from a prospectively recorded computer database of operating activity in a single surgical unit over a three-year period. Operations were weighted using intermediate equivalent (IE) values. The number of operations performed (caseload), IE workload, consultant involvement and a subjective assessment of operative ability by consultant was obtained for each of 3 SHO IIIs and 7 SHO Is. The total caseload correlated poorly with subjective grading. The total workload correlated well with the subjective assessment of the SHO IIIs and, excluding minor operations, with the SHO Is. SHO IIIs' workload consisted of a higher number of more complex procedures than SHO Is' and for both types of trainee the degree of complexity increased during the tenure of each one year post. A consultant was the assistant in 50 per cent of the intermediate and major operations performed by the SHO Is in the first quarter of each one year post dropping to 30 per cent in the remaining three-quarters. In conclusion an objective assessment was easily obtained and interpreted. Similar data from other surgical units are required to place this work in perspective and to allow formulation of guidelines.

Plasma glycocalicin levels are not elevated in patients with a history of transient ischaemic event and are normal in aspirinated normal volunteers.

Glycocalicin (GC) is the soluble portion of platelet membrane protein GP1b, and may be cleaved from the platelet surface during platelet activation. Previous study has indicated that plasma glycocalicin/platelet (GC/plt) levels are elevated in patients presenting with acute stroke. The present study was undertaken to determine the GC/plt levels in patients being treated for transient ischaemic episodes, to assess whether the elevated GC/plt level in acute stroke is due to a detectable, constitutive premorbid state of platelet activation. In sixteen consecutive patients attending a vascular surgery clinic, GC levels were measured on a citrated plasma sample, and corrected for circulating platelet count. Since 15 of 16 patients were taking aspirin when seen at clinic, a control study was undertaken to assess the effect of aspirin on sequential plasma GC/plt levels measured over 10 days--5 pre and post daily aspirin for 5 days, 4 acting as non-aspirinated controls. Plasma GC/plt levels in normal plasma were 21.6 +/- 8.0 fg; mean +/- SD. In the 16 patients the GC/plt levels were 13.1 fg/plt; SD 5.4, range 2.9-24.3. All platelet counts were in the normal range in all patients involved. While a masking effect due to aspirin cannot be completely ruled out, these studies indicate that plasma GC/plt level is not useful as a predictor of acute stroke in the premorbid population.

A randomised trial of fibrin sealant in peripheral vascular surgery.

In a prospective randomised trial 39 patients undergoing either arterial bypass surgery with a polytetrafluoroethylene (PTFE) bypass graft (n = 18) or aortic aneurysm repair with a woven Dacron graft (n = 21) were randomised either to receive fibrin sealant as a topical haemostatic agent at the arterial anastomosis or to act as control. The main outcome measure was the time taken to achieve haemostasis at the suture line. The median time to achieve haemostasis was 0.5 min (range 0-11 min) in the treatment group and 4 min (range 0-21 min) in the control group. This difference was statistically significant p < 0.014 by the Mann-Whitney test. Immediate haemostasis on release of the clamps was achieved in 13/21 patients in the treatment group and in 4/18 patients in the control group (p = 0.023 by Fisher's exact test). There was no difference in total operative time or operative blood loss. No patients in the treatment group suffered any perioperative thromboembolic event and 1 patient in the control group suffered an early graft occlusion. There was no evidence of transmission of hepatitis B or C, or parvovirus B19. In conclusion, fibrin sealant is an effective topical haemostatic agent for arterial suture lines involving PTFE or woven Dacron.

Vascular trauma of the upper limb and associated nerve injuries.

In an analysis of vascular audit data on upper limb vascular trauma over a 10 year period in a major UK injury centre it was found that 15 patients required operation for subclavian or axillary artery injuries. Eleven cases were the result of blunt injury. Twelve patients had an ischaemic arm on presentation, all of whom had an associated brachial plexus lesion. Subclavian or axillary artery transections, irrespective of limb viability, also were found to have associated plexus trauma. Twenty-eight patients had brachial artery injuries repaired, 46 per cent of whom had an associated nerve injury. A good functional result was achieved in only half of the patients who underwent repair of a peripheral nerve injured in association with the brachial artery. Vascular reconstruction was successful in all cases. The long-term outcome of brachial plexus lesions was very poor and the role of exploratory surgery is discussed. The long-term outcome of upper limb injury is not dependent on the vascular injury which can be successfully managed, but upon the recognition, treatment, and outcome of the associated nerve injuries.

Induction of leucocyte recruitment and bronchial hyperresponsiveness in the guinea pig by aerosol administration of interleukin-2.

Exposure of guinea pigs to an aerosol of human recombinant interleukin-2 (IL-2; 30 micrograms) resulted in an increase in the numbers of eosinophils and macrophages recovered from bronchoalveolar lavage fluid (BALF) 24 h later. This was accompanied by a bronchial hyperresponsiveness to intravenous acetylcholine. In guinea pigs sensitized to ovalbumin, exposure to IL-2 caused an increase in the number of macrophages, but not eosinophils in BALF and bronchial hyperresponsiveness to acetylcholine did not develop. In guinea pig skin, intradermal injection of IL-2 (10(-14) to 10(-9) mol/site) had no effect on 111In-eosinophil accumulation, measured over 3 h, suggesting that IL-2 does not act directly to recruit eosinophils. The hypothesis that IL-2 may be acting via release of interleukin-5 (IL-5) was tested using an antibody to IL-5 (TRFK-5; 1 mg/kg). Treatment with TRFK-5 1 h before exposure to IL-2 aerosol had no effect on the numbers of macrophages or eosinophils recovered from BALF 24 h later, although there was a tendency for reduced bronchial hyperresponsiveness to acetylcholine. These results suggest that (1) IL-2 is not a directly acting chemoattractant for eosinophils in the guinea pig, (2) the action of IL-2 to increase bronchial hyperresponsiveness is also indirect, partly via generation of IL-5, and (3) immunological sensitization alters the response of both eosinophils and bronchial smooth muscle to IL-2.

Role of the VLA-4 integrin in leucocyte recruitment and bronchial hyperresponsiveness in the guinea-pig.

Guinea-pigs sensitized to ovalbumin develop airway eosinophilia and bronchial hyperresponsiveness to acetylcholine 24 h following ovalbumin challenge. We have used an antibody to the very late antigen-4 (VLA-4) integrin (HP 1/2) to investigate the role of this integrin in the recruitment of leucocytes to the airways and to study the link between eosinophilia and the development of bronchial hyperresponsiveness. In this model, HP 1/2 reduced the number of eosinophils recovered from bronchoalveolar lavage fluid, as well as reducing the activity of the enzyme eosinophil peroxidase in both bronchoalveolar lavage fluid and whole lung extracts. However, HP 1/2 did not reduce bronchial hyperresponsiveness. The results suggest that after antigen challenge, the VLA-4 integrin is involved in the recruitment of leucocytes to the airways at the level of the vascular endothelium, but increased numbers of eosinophils in lavage fluid or in the lung tissue are not an essential correlate of bronchial hyperresponsiveness in this model.

Fibrin sealant reduces suture line bleeding during carotid endarterectomy: a randomised trial.

OBJECTIVES: To determine whether topical fibrin sealant reduced suture line bleeding during carotid endarterectomy with polytetrafluoroethylene (PTFE) patch closure. DESIGN: Prospective randomised non-blinded control trial. SETTING: Regional vascular surgery unit. MATERIALS: Seventeen patients undergoing carotid endarterectomy were randomised either to receive fibrin sealant as a topical haemostatic agent at the arteriotomy suture line or to act as control. OUTCOME MEASURES: Time taken to achieve haemostasis at the suture line. Intraoperative blood loss. Total operative time. RESULTS: The median time to achieve haemostasis was 5.5 min (range 4-31 min) in the treatment group and 19 min (range 10-47 min) in the control group. This difference was statistically significant p < 0.005 by Mann-Whitney test. There was no statistical difference in total operative time. Operative blood loss was lower in the treatment group (median 420ml, range 300-500ml) than in the control group (median 550ml, range 350-1200ml) but this difference was not statistically significant. One patient in the control group suffered a perioperative thrombo-embolic event. CONCLUSION: Fibrin sealant is an effective topical haemostatic agent for arteriotomy suture lines involving PTFE material.

Endothelial cell ultrastructure after aortic aneurysm rupture: an electron microscopy study.

Endothelial cell activation as an early response to hypovolaemic shock may be important in the pathogenesis of coagulopathy and multiple organ failure after aortic aneurysm rupture. The aim of this study was to determine whether any evidence could be found of changes in endothelial cell ultrastructure in patients undergoing operation for ruptured aneurysm and to establish a model for future studies of endothelial cells in these patients. At the start of operation, fat samples from the anterior abdominal wall were taken from five patients with ruptured abdominal aortic aneurysms and in an identical fashion from five control patients undergoing elective surgery. Endothelial cells lining capillaries were examined by transmission electron microscopy. Photomicrographs were taken of all capillaries present and these were assessed blindly by three independent observers. When compared with controls it was found that the luminal surface of the endothelial cells in patients with aneurysm rupture was more convoluted, with more frequent processes projecting into the lumen of the capillary. Budding of the luminal surface of the endothelial cell was seen in 11 of 45 capillaries in the rupture group and in none of 44 capillaries in the control group (P < 0.005). Budding was seen in at least one capillary of all five patients presenting with rupture but in none of the control group (P < 0.05). In conclusion, at the ultrastructural level there are changes within endothelial cells in capillaries at an early stage after ruptured abdominal aortic aneurysm.

Current blood transfusion practice in aortic aneurysm surgery in Scotland. The Scottish Vascular Audit Group.

A questionnaire on current practice in blood transfusion during aortic aneurysm repair was sent to all consultant surgeons with a vascular interest practising in Scotland. Replies were received from 31 surgeons. A blood ordering schedule was operated by 29 surgeons for elective operations and 26 surgeons for emergency operations. The mean number of units of red cell concentrate ordered was 4.7 units for elective operations (range 3-8 units) and 8 units for emergency operations (range 6-12 units). The time estimated to obtain red cell concentrate was 38.2 min (range 15-90 min) for a new request and 8.8 min (range 2-30 min) to obtain further blood in a patient already crossmatched. Blood conservation techniques employed included the use of low porosity or sealed grafts by 86% of surgeons. Autotransfusion was used by six surgeons, but only regularly by three surgeons. One surgeon used pre-deposit autologous transfusion and one used preoperative haemodilution. Intravenous heparin was used by 90% of surgeons during elective operations and by 16% of surgeons during emergency operations. Most surgeons used a standard dose of 5000 units of heparin.