Short-chain fatty acid enemas stimulate plasminogen activator inhibitor-1 after abdominal aortic graft surgery: a double-blinded, placebo-controlled study.

Colonic ischaemia may complicate aortic graft surgery with high mortality from associated colonic necrosis. Loss of the mucosal barrier function due to ischaemia may promote translocation of endotoxins with secondary systemic disseminated coagulation leading to multiple organ failure. Short-chain fatty acids (SCFAs) stimulate the microcirculation in the human rectum. The aim of this study was to investigate whether SCFA enemas influence systemic endotoxinaemia and fibrinolytic activity during and after elective aortic graft surgery for arteriosclerosis. Thirty-two patients were randomized to SCFA or placebo enemas twice daily from the day before surgery to 7 days after. Blood samples for endotoxin, plasminogen activator inhibitor-1 (PAI-1) activity, tissue-type plasminogen activator (t-PA) antigen, and cross-linked fibrin degradation products (XL-FDP) were drawn before, during, and 7 days after surgery. Four patients, two in each treatment group, developed postoperative endotoxinaemia. PAI-1 was significantly higher on days 2 and 4 in SCFA-treated patients, whereas t-PA was comparable Petween the groups. During the postoperative course, a progressive and near-identical XL-FDP increase was found in the two groups. In elective aortic graft surgery for arteriosclerosis, SCFA enemas likely stimulate systemic PAI-1 activity by promoting colonic tissue reperfusion following aortic unclamping. Endotoxinaemia and fibrinolytic shutdown are uncommon findings.

[Low molecular heparin in prevention of thrombosis in orthopedic surgery]. / Tromboseprofylakse med lavmolekylaert heparin i ortopaedkirurgien.

The review encompasses all published clinical studies of prophylactic treatment with low molecular weight (LMW) heparins marketed in Denmark when used to prevent thrombosis in patients undergoing elective or emergency orthopaedic operations. In elective hip surgery, LMW-heparin was more effective than placebo in reducing the incidence of deep vein thrombosis. There was significantly better anti-thrombotic effect of LMW-heparin, given in recommended doses, than of Dextran 70. When compared to low-dose heparin, the incidence of deep vein thrombosis was lowest using LMW-heparin, but only one study found the difference significant. LMW-heparin compared to low-dose heparin in combination with dihydroergotamine showed no significant difference with respect to either effect of safety. The use of LMW-heparin as prophylactic treatment for patients with either trochanteric or femoral neck fractures is as yet not nearly so well-documented. The relatively few studies that have been carried out show large variation between the different LMW-heparins. There is need for a study comparing the effect of LMW-heparin with that of low-dose heparin in these patients, both with respect to thrombosis prevention and influence on total mortality.

Biologic tolerance of two different low molecular weight heparins.

Heparin preparations have been used for prophylaxis and treatment of deep vein thrombosis for many years. Several biologic effects of heparin are known. Since 1978, there have been several reports about reversible elevation in serum values of AST and ALT in patients and healthy volunteers given heparin in small and high doses. Few studies report similar events in patients given LMW heparins. Results of two randomized studies (A and B) comprising 456 patients undergoing THR are presented. Two different compounds of LMW heparin (Logiparin or Enoxaparin) were used for thromboprophylaxis. Significant elevation during the postoperative period of AST and AP in study A, and AST, ALT, AP, LDH, and CK in study B were demonstrated in patients given LMW heparins in both studies. In study A the percentages of patients with normal preoperative values who reached pathologic values were 35% for AST and 15% for AP. In study B the percentages of patients with normal preoperative values who reached pathologic values were 36% for AST, 17% of ALT, 14% for AP, and 36% for LDH. The possible biologic mechanisms and the clinical perspectives are discussed. In all cases the changes in the liver enzymes returned to preoperative levels within 14 days.

[Femoral fractures treated with intramedullary nailing by Küntscher's method. A review of results in 100 patients treated during a period of 10 years]. / Femurfrakturer behandlet med marvsømning a.m. Küntscher. En opgørelse af resultater hos 100 patienter behandlet over en periode på 10 år.

The records of 100 patients with 102 fractures of the femur treated with intramedullary nailing by Küntscher's method are reviewed. Eighty-eight of the patients were followed-up with interviews and clinical examination. Fifty-six of the patients had multiple traumata. Primary boney union was achieved within one year in 94 fractures (92%). At follow-up, the majority of the patients had no residual shortening of the affected extremity and no angulation at the fracture, and most of the patients had regained full movement of the knee and hip and good quadriceps function. In spite of this, 49% of the patients seen at follow-up had problems with their previous employment and/or performance in sports and daily activities. It is concluded, that some of the problems are probably due to the associated injuries and others are probably due to residual shortening of the affected extremity and restriction in knee movement.

Prevention of thromboembolism in 190 hip arthroplasties. Comparison of LMW heparin and placebo.

Prophylactic efficacy and safety of a low molecular weight (LMW) heparin against postoperative thromboembolic complications were investigated in a double-blind, randomized study. Totally, 210 consecutive patients undergoing total hip replacement were allocated to two groups. Patients in the heparin group received 50 IU anti-Xa per kilo body weight of Logiparin once daily, and patients in the placebo group received one daily injection of saline. Additional prophylaxis in all the patients was thigh-length compression stockings beginning on the day of the operation. Deep vein thrombosis was diagnosed by bilateral ascending phlebography between Days 8 and 10 after the operation. Twenty patients were excluded from the evaluation. Thirty of 93 patients in the heparin group compared with 45 of 97 patients in the placebo group suffered a thromboembolic complication during the study (P = 0.02). The postoperative blood loss and total number of blood transfusions in the heparin group were higher than in the placebo group. However, the observed differences were of no clinical importance. Adverse effects, including bleeding complications and wound hematomas, were observed in 13 heparin patients and 7 placebo patients (NS). One patient in each group died. Thrombo-prophylaxis with LMW heparin once daily was safe and more effective than the placebo in patients undergoing total hip replacement.

Clinical trials with low molecular weight heparins in the prevention of postoperative thromboembolic complications: a meta-analysis.

Several clinical studies have evaluated the efficacy and safety of LMWH in the prevention of postoperative thromboembolic complications. We subjected 42 studies to a statistical meta-analysis in order to evaluate the efficacy of different prophylactic regimens compared with LMWH prophylaxis. In general surgery LMWH was more effective than LDH three times daily and placebo, but comparable with LDH twice daily. In elective hip surgery, thromboprophylaxis with LMWH was more effective than placebo, LDH, and dextran 70, but comparable with LDH in combination with dihydroergotamine. In patients undergoing surgery for hip fractures LMWH was more effective than placebo, but the studies comparing LMWH with LDH were too small to show any clinically relevant difference, although there was a trend toward a better efficacy of LMWH. This study demonstrated that LMWH is clinically effective and safe to use in the prevention of thromboembolic complications after general and orthopedic surgery.

Biological tolerance of Logiparin, a low molecular weight heparin used in patients undergoing total hip replacement.

Two hundred ten patients scheduled for THR were randomized into two groups. Group A (105 patients) received Logiparin (Novo-Nordisk, Denmark) 50 mg/kg body weight once daily, and group B (105 patients) received placebo once daily. Injections started 2 hr preoperatively and continued for 7 days. Blood samples were collected preoperatively before medication and 3 hr after last injection on the seventh postoperative day. Two hundred three patients completed the study: 103 in group A, 100 in group B. In group A there was a significantly higher increase in ASAT (p = 0.0006) and APH (p = 0.0137) compared with group B. Significantly more patients in group A showed an increase from normal preoperative values to pathological postoperative values in ASAT (p = 0.0012) and APH (p = 0.025) compared with group B. All changes were found to be reversible within 2 weeks of termination of drug treatment. Although no conclusion about the mechanism leading to the increase in ASAT and APH is possible from this data, there is very good suggestive evidence that the liver is influenced by this agent.

Real-time B-mode ultrasonography in the diagnosis of postoperative deep vein thrombosis in non-symptomatic high-risk patients. The Venous Thrombosis Group.

In a prospective study of 61 patients who were undergoing elective total hip replacement, the accuracy of real-time B-mode ultrasonography (B-US) in the diagnosis of postoperative deep vein thrombosis (DVT) was compared with blindly assessed bilateral ascending phlebography. The overall sensitivity and specificity of ultrasound was 71 and 94%, and the positive and negative predictive values were 77 and 92%, respectively. The sensitivity and specificity for diagnosis of proximal DVT was 73 and 96%, respectively. Thrombi smaller than 1 cm were not detected. It is concluded that B-US may be used as a screening test for postoperative DVT after elective hip surgery.

Levels of thrombin--antithrombin-III complex and factor VIII activity in relation to post-operative deep vein thrombosis and influence of prophylaxis with a low-molecular-weight heparin.

In a randomized doubled-blind placebo-controlled study, plasma levels of thrombin-antithrombin-III (TAT) and factor VIII activity (VIII:C) were measured pre-operatively and on days 1, 3, 5 and 7 post-operatively in 70 consecutive patients undergoing total hip replacement. Patients received either a subcutaneous injection of low-molecular-weight heparin (LMWH) or placebo once daily. Post-operative deep vein thrombosis (DVT) was diagnosed by bilateral phlebography. The levels of TAT and VIII:C both increased significantly after operation and were not significantly influenced by LMWH. Thirty-three patients in whom post-operative DVT developed had a significantly lower level of VIII:C on day 7, compared with patients without DVT.

Association between plasma levels of tissue plasminogen activator and postoperative deep vein thrombosis--influence of prophylaxis with a low molecular weight heparin. The Venous Thrombosis Group.

In a prospective, randomized controlled study, tissue plasminogen activator (t-PA) and tissue plasminogen activator antigen (t-PA:ag) were measured pre- and postoperatively in 40 consecutive patients undergoing total hip replacement. Patients received either a subcutaneous injection of low molecular weight heparin or placebo once daily. Deep vein thrombosis was diagnosed by bilateral phlebography. Patients who developed postoperative thromboembolic complications had significantly lower preoperative t-PA activity levels than patients who did not develop such complications. No difference was observed between the two groups with respect to t-PA:ag. Thromboprophylaxis with low molecular weight heparin did not cause any significant changes in t-PA activity and t-PA:ag. This study in high risk patients indicates that impaired fibrinolysis may be associated with development of thromboembolic complications after operation.

[Dihydroergotamine and orthostatic hypotension in elective hip surgery]. / Dihydroergotamin og ortostatisk blodtryksfald ved elektiv hoftekirurgi.

The authors undertook a prospective double-blind, controlled trial to investigate the effect of prophylactic low-dose heparin/dihydroergotamine, low-molecular heparin/dihydroergotamine and a placebo on the blood pressure and postural hypotension on postoperative mobilization. A material of 120 patients admitted for hip surgery was subdivided at random into three groups. Examination for postural hypotension was undertaken on the fifth postoperative day. No significant differences were present between the three groups as regards age distribution, systolic and diastolic blood pressures and pulse rates. This investigation did not reveal any significant effect of the antithrombotic combined treatment with heparin/dihydroergotamine on the blood pressure or postural hypotension on postoperative mobilization following elective hip surgery. No cases of ischaemic side effects were observed. However, this investigation cannot disprove a slight hypotensive effect and, for this reason, this treatment should be contraindicated in patients with circulatory disturbances.

Comparison of real-time B-mode ultrasonography and bilateral ascending phlebography for detection of postoperative deep vein thrombosis following elective hip surgery. The Venous Thrombosis Group.

A prospective study compared real-time B-mode ultrasound examination with bilateral ascending phlebography in the diagnosis of postoperative deep vein thrombosis in 60 patients undergoing elective total hip replacement. The overall sensitivity and specificity of the ultrasound method were 54 and 91%, respectively, and the positive and negative predictive values were 83 and 69%, respectively. The rather low overall sensitivity of the ultrasound method in this study was due to difficulty in detecting thrombi smaller than 1 cm wherever they were located in the deep veins, and in diagnosing thrombi in the calf, regardless of their size. We conclude that real-time B-mode ultrasonography is a technique that can easily be used routinely for detection of postoperative DVT in hip surgery, but its sensitivity for proximal thrombosis (63%) is too low for it to be used alone.

[Low-molecular weight heparin. A new agent to prevent thrombosis]. / Lavmolekylaert heparin. Et nyt tromboseprofylaktikum.

The theory for employment of low molecular weight heparin and the material concerning employment of low molecular weight heparin hitherto published is reviewed. To date, it has been demonstrated that low molecular weight heparin has the same antithrombotic efficacy as unfractionated heparin and its half life is approximately twice as long. This implies that adequate thrombosis prophylaxis can be obtained with a single daily dose.

Prevention of thromboembolism in hip-fracture patients. Comparison of low-dose heparin and low-molecular-weight heparin combined with dihydroergotamine.

In a prospective, double-blind, controlled study, we compared the antithrombotic efficacy of low-dose heparin with dihydroergotamine (A), low-molecular-weight heparin with dihydroergotamine (B), and placebo (C). Two hundred and thirteen patients surgically treated for fractures of the hip were randomly divided into three groups. One hundred and sixty-one patients were analyzed. All thrombi were verified by ascending phlebography. Nine patients died within 1 month after operation. A and B proved to be equally safe but failed to provide any protection against deep-vein thrombosis, although B showed a tendency to reduce the incidence. Mortality within 1 month of operation was unaffected by the type of prophylaxis.

Heparin/dihydroergotamine for venous thrombosis prophylaxis: comparison of low-dose heparin and low molecular weight heparin in hip surgery.

In a prospective, double-blind controlled study we have compared the prophylactic efficacy against deep vein thrombosis of low-dose heparin + dihydroergotamine (A), low molecular weight heparin + dihydroergotamine (B) and placebo (C). A total of three hundred and fifty-six patients undergoing total hip replacement were randomized into three groups and 316 patients were analysed. All thrombi were verified by ascending phlebography. One-third of the patients developed deep vein thrombosis in group A and B, differing significantly from group C. The operative blood loss in group B was higher than that in groups A and C. However, the number of patients transfused and their transfusion requirements did not differ. Severe bleeding occurred in one patient in each group. No deaths were registered during the study. Our study indicates that prophylactic treatment against postoperative deep vein thrombosis with low molecular weight heparin + dihydroergotamine once daily is as effective and safe as conventional low-dose heparin + dihydroergotamine twice daily in patients undergoing total hip replacement. The once-daily regimen has the advantage of better patient acceptance and less nursing time.

Prophylactic antibiotics in transurethral prostatectomy.

The study included 88 patients with sterile urine prior to transurethral prostatectomy. Forty-five received a preoperative dose of 2 g of cefotaxime (Claforan) and the remaining 43 were given 10 ml of 0.9% NaCl. The two groups did not differ in frequency of postoperative urinary infection (greater than 10(5) colonies per ml urine); 6 patients (13.3%) in the cefotaxime group had postoperative infections during hospital stay as compared to 8 patients (18.6%) in the control group (0.5 greater than p greater than 0.3). Those in the cefotaxime group who had infections were tested for resistance. They were all fully sensitive to cefotaxime except one, who was infected with enterococci. There was no growth of bacteria from either venous blood or bladder irrigating fluid taken during the operations. Nor were any serious complications observed in any of the patients. In view of the relatively low risk of infection and the few side effects of the infections that did occur, prophylactic treatment with an antibiotic is not indicated for transurethral prostatectomy in patients with sterile urine.