Editor's Choice - The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events.

OBJECTIVE/BACKGROUND: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery. METHODS: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated. RESULTS: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%. CONCLUSION: This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Polymorphisms in the interleukin-1 gene locus and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases.

Chronic periodontitis (CP) and atherosclerotic and aortic aneurysmal vascular diseases (VD) are inflammatory conditions that share a number of predisposing factors. They have a complex genetic heritability and may share genetic risk factors, but a well-defined relationship is still not determined. In addition, distinct genetic patterns of predisposition have been associated with these diseases. Here, we investigated the association of polymorphisms in the IL-1 gene locus with CP in a case-case study analysing VD patients with or without CP. Seventy-four patients with VD of whom 36 had CP were genotyped for single nucleotide polymorphisms in the IL1A -889 (rs1800587), IL1B +3954 (rs1143634) and IL1B at -511 (rs16944) genes and for VNTR polymorphisms in the IL1RN gene. A significantly higher frequency (17%) for allele 1 (four repeats) of the IL1RN VNTR gene was found among the VD patients with CP compared to those without CP. In addition, the frequency of the IL1RN VNTR genotypes 1/1 (4/4 repeats) and 2/2 (2/2 repeats) were significantly higher and lower, respectively, in VD patients with CP. These findings suggest an association of genetic polymorphisms in the IL1-gene locus with risk for CP in patients with VD. The carriage of the risk genotypes, the development and the subsequent influence of CP on systemic health may constitute an additional burden in the pathogenesis of VD. This emphasizes the importance of effective periodontal treatment in patients with VD.

Cost-effectiveness of screening for abdominal aortic aneurysm in the Netherlands and Norway.

BACKGROUND: The aim of this study was to determine the cost-effectiveness of ultrasound screening for abdominal aortic aneurysm (AAA) in men aged 65 years, for both the Netherlands and Norway. METHODS: A Markov model was developed to simulate life expectancy, quality-adjusted life-years, net health benefits, lifetime costs and incremental cost-effectiveness ratios for both screening and no screening for AAA. The best available evidence was retrieved from the literature and combined with primary data from the two countries separately, and analysed from a national perspective. A threshold willingness-to-pay (WTP) of €20,000 and €62,500 was used for data from the Netherlands and Norway respectively. RESULTS: The additional costs of the screening strategy compared with no screening were €421 (95 per cent confidence interval 33 to 806) per person in the Netherlands, and the additional life-years were 0·097 (-0·180 to 0·365), representing €4340 per life-year. For Norway, the values were €562 (59 to 1078), 0·057 (-0·135 to 0·253) life-years and €9860 per life-year respectively. In Norway the results were sensitive to a decrease in the prevalence of AAA in 65-year-old men to 1 per cent, or lower. Probabilistic sensitivity analyses indicated that AAA screening has a 70 per cent probability of being cost-effective in the Netherlands with a WTP threshold of €20,000, and 70 per cent in Norway with a threshold of €62,500. CONCLUSION: Using this model, screening for AAA in 65-year-old men would be highly cost-effective in both the Netherlands and Norway.

Stenting for chronic post-thrombotic vena cava and iliofemoral venous occlusions: mid-term patency and clinical outcome.

OBJECTIVES: The aim of this study was to determine the mid-term patency and the clinical outcome after stenting of chronic occluded caval and iliofemoral venous segments. DESIGN: Observational study. MATERIAL/METHODS: During the period 2000 and 2009, 2400 patients with chronic venous insufficiency (CVI) were evaluated, and 34 with chronic venous occlusions after deep venous thrombosis (DVT) were selected for endovascular treatment. The median age was 41 (range 15-63) years, and 19 were female. The following investigations were undertaken: colour duplex ultrasound (CDU), ascending venography (AV), venous occlusion plethysmography (VOP), venous pressure gradient (VPG) and CT venography or trans-femoral/popliteal venography. The major symptoms were venous claudication, oedema, pain and ulcer. All patients were treated by stenting occluded segments. Self-expanding stents were deployed in 22 iliofemoral, nine iliac and one caval-iliac-femoral. Twenty-one procedures required stenting across the inguinal ligament. RESULTS: Primary recanalisation was accomplished in 32/34 (94%). The median follow-up was 33 months (1-96) with clinical examination, CDU and VOP. Two-year primary patency was 14/21 (67%), primary-assisted patency 16/21(76%), and secondary patency was 19/21 (90%). Venous claudication and oedema resolved in those successfully recanalised. Four of the seven ulcers healed. CONCLUSION: Stenting to treat venous claudication, oedema and recurrent venous ulcer caused by post-thrombotic chronic venous occlusions has positive clinical outcome and good mid-term patency.

Venous valve reconstruction in patients with secondary chronic venous insufficiency.

OBJECTIVES: To evaluate the durability of venous valve reconstruction (VVR) and its benefits in terms of symptom improvement, ulcer healing and symptom/ulcer recurrence among patients with secondary chronic venous insufficiency (SCVI) in whom superficial venous surgery and compression treatment had failed. METHODS: During a ten year period (1993-2004) 1800 patients with chronic venous insufficiency (CVI) were evaluated by colour duplex ultrasound (CDU) and ambulatory venous pressure measurement (AVP). Approximately two thirds of patients had SCVI. Initial treatment consisted of compression therapy for a 6 month period. In addition, superficial vein and perforator surgery was performed in those presenting with reflux in these venous systems. 121 patients who did not improve with this treatment were investigated by ascending venography, descending video venography, air plethysmography and measurement of post-ischaemic venous pressure gradient. Thirty two cases having venous reflux without obstruction were selected for VVR. RESULTS: The ulcer healing rate within three months was 68% (13/19 patients). VVR resulted in valvular competence and a clinical success rate of 47% and 40% after 3 and 7 years respectively. In 8/13 (54%) of patients with a healed leg ulcer, a median post-operative AVP reduction of 33 mm Hg (range 20-38) was recorded. The durability of clinical success was numerically longer in patients with haemodynamic improvement (n=10) median 24 months (12-108), when compared with that in those without haemodynamic improvement (n=22) median 18 months (6-108). Popliteal vein reconstruction was part of the VVR procedure in all patients with haemodynamic improvement (post-op. AVP reduction >or=20 mm Hg). VVR at the popliteal level alone or combined with inguinal reconstruction seemed to be the one significant factor associated with haemodynamic improvement (P=0.014, Chi squared). CONCLUSION: VVR may lead to ulcer healing, but when performed at the popliteal level, haemodynamic improvement can be obtained along with a longer recurrence-free period (durability). VVR should be considered in the treatment of patients with SCVI who do not respond to superficial venous surgery and compression treatment.

Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study.

BACKGROUND AND AIMS: Treatment with autologous, bone marrow mononuclear stem cells has shown effects in patients with chronic limb ischaemia in one randomized clinical study. The aim of the study was to test the potential effect of stem cell treatment in a strict defined group of patients with stable critical limb ischaemia (CLI). DESIGN: A prospective, combined-centre pilot study. MATERIAL: Eight patients with CLI of the lower extremities, and without any other treatment options. METHODS: Bone marrow cells were harvested from the patient's iliac crest and, after separation, injected into the calf muscles of the affected leg. Outcome was evaluated by digital subtraction angiography (DSA), visual analogue scale (VAS) and several non-invasive circulatory physiological tests. RESULTS: There were no complications from the procedures. Two patients were amputated two months after cell injection. Five patients reported pain relief after four months. Five patients could be evaluated at eight months. According to VAS and physiological tests, they were all either stable or showed improvement. CONCLUSION: This method seems to be a safe option for treating patients with CLI. Inclusion of patients took a long time, mainly because many patients with CLI are offered endovascular treatment in our institution. While symptomatic improvement was found in individual patients, larger trials are required to investigate efficacy. This will probably require multi-centre participation.

[Reintroduction of medical abortion in Denmark]. / Reintroduktion af medicinsk abort i Danmark.

Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue (Cervagem) is a fairly new abortion method in surgical and gynaecological departments in Denmark. Sixty-two patients were evaluated during the period December 1, 1997 to the June 10, 1998 at Kalundborg hospital. The success rate was 97%. Side effects were rare. The study illustrates the need for strong analgesics in half of the patients. In conclusion RU 486 followed by a prostaglandin analogue provides an efficient and attractive alternative to surgical abortion methods.

Supervised exercise training reduces plasma levels of the endothelial inflammatory markers E-selectin and ICAM-I in patients with peripheral arterial disease.

Elevated plasma levels of vascular inflammatory markers have been reported in patients with peripheral arterial disease (PAD). We assessed the effect of supervised exercise training (ET) on vascular inflammation, hypothesizing that ET reduces plasma levels of the endothelial adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-I (VCAM-I). Twenty-nine patients with PAD underwent a supervised ET program for 8 weeks. Before and after ET, walking distances (pain-free, PWD; maximal, MWD) were determined by a standard treadmill test. Plasma levels of E-selectin and ICAM-I were significantly reduced (E-selectin: 45.5-40.4 ng/mL, P = .013); ICAM-I: 342.0-298.0 ng/mL, P = .016). VCAM-1 levels were unchanged. Walking distances increased significantly (PWD: median 77-150 m, P < .001; MWD: median 306-535 m, P < .001). In conclusion, 8 weeks of ET in patients with PAD reduces plasma levels of the specific endothelium-derived inflammatory markers E-selectin and ICAM-I.

Health and cost consequences of surgical versus conservative treatment for a comminuted proximal humeral fracture in elderly patients.

OBJECTIVE: This study aims to evaluate the costs and health outcome for surgical and conservative treatment of displaced proximal humeral fractures. DESIGN: This study is a randomised controlled trial. PARTICIPANTS: This study included 50 patients aged 60 or older admitted to hospital with a severely displaced three- or four-part fracture. INTERVENTIONS: The patients were treated surgically with an angular stable interlocking implant (25 patients) or conservative treatment (25 patients). MAIN OUTCOME MEASURE: The outcomes measured included quality-adjusted life years (QALYs) and societal costs. RESULTS: At 12 months' follow-up, the mean difference in the number of QALYs was 0.027 (95% confidence interval (CI)=-0.025, 0.078) while the mean difference in total health-care costs was 597 euro in favour of surgery (95% CI=-5291, 3777). CONCLUSION: There was no significant difference in QALYs or costs between surgical and conservative treatment of severe displaced proximal humeral fractures.

Blood pressure in patients with intermittent claudication increases continuously during walking.

OBJECTIVES: The purpose of this study was to compare the circulatory responses to walking in patients with peripheral atherosclerotic disease (PAD) and healthy controls. METHODS: The participants were eleven patients with diagnosed PAD, and a control group of six healthy age-matched adults. Blood pressure, heart rate (HR), and acral skin perfusion were recorded continuously before, during and after a walking exercise on a treadmill. RESULTS: The patients walked to maximum claudication distance (MCD) on a treadmill, median walking distance 103 (34-223) metres [median (range)], at 3.3 (1.0-4.5) km/h. There was a steep increase in HR and mean arterial pressure (MAP) while the patients were walking. At claudication the median rise in MAP was 46.6 (10.3-61.3) mmHg, systolic blood pressure (SP) increased by 84.9 (31.4-124.9) mmHg, and diastolic blood pressure (DP) by 21.7 (-2.1-31.7) mmHg. HR increased by 34.9 (12.9-48.1) beats/min. The control group walked for 5 minutes at 3.2 (3.0-3.3) km/h. In the control group the blood pressure initially increased moderately but stabilised thereafter. Median rise in MAP during walking was 8.5 (5.6-14.6) mmHg, SP increased by 30.9 (6.6-41.5) mmHg, and DP was reduced by -1.4 (-5.4-1.5) mmHg. HR increased by 27.1 (18.8-34.9) beats/min. We found no significant differences in acral skin perfusion during walking exercise between the patients and control group. CONCLUSIONS: In patients with PAD, blood pressure increased continuously and significantly when walking to MCD (dynamic exercise). The level of increase in blood pressure was similar to that caused in response to isometric exercise.

The Oslo balloon angioplasty versus conservative treatment study (OBACT)--the 2-years results of a single centre, prospective, randomised study in patients with intermittent claudication.

OBJECTIVES: To compare the effect of optimal medical treatment only (OMT) with OMT combined with percutaneous transluminal angioplasty (OMT+PTA) in patients with intermittent claudication (IC). DESIGN: A single centre prospective, randomised study. Quality of life (QoL) was the primary outcome measure. Secondary measures were ankle-brachial-index (ABI), treadmill walking distances and mortality. METHODS: From a total of 434 patients considered for inclusion into the trial, only 56 patients with disabling IC fulfilled the inclusion criteria. The patients were randomised into treatment groups consisting of 28 patients each and followed for 2 years. ABI and treadmill walking distances were measured in addition to the visual analogue scale (VAS) for pain evaluation, and QoL assessment using the Short Form (SF-36 and Claudication Scale (CLAU-S). RESULTS: The demographic data in the 2 groups were almost identical. After 2 years of follow-up the ABI, the treadmill walking distances and the VAS were significant improved in the group treated with OMT+PTA, compared to the group treated with OMT only (p<0.01 for all). Furthermore, some variables from the QoL assessment also showed a significant improvement in favour of the OMT+PTA group (p<0.05 for all). CONCLUSION: The advantage of conducting a single centre study and adhering to very strict inclusion criteria was illustrated by the homogenous demographic data of the two groups. This partly outweighed the disadvantage of having included a relatively small number of patients. Early intervention with PTA in addition to OMT seems to have a generally more positive effect compared to OMT only, on haemodynamic, functional as well as QoL aspects during the first 2 years in patients with IC.

External venous valve plasty (EVVP) in patients with primary chronic venous insufficiency (PCVI).

OBJECTIVES: To evaluate the patency of EVVP and its effect in symptom relief, ulcer healing and ulcer-free period in patients with PCVI. METHODS: Between 1993 and 2004, 1800 patients with CVI were evaluated and seventeen with PCVI were selected for EVVP. They were all investigated with ambulatory venous pressure measurement (AVP), colour duplex ultrasound (CDU), ascending venography and descending video venography. The CEAP classification was used to group the patients. Six patients were C4, four C5 and seven C6. All had deep reflux and high levels of AVP. RESULTS: All procedures were technically successful. The ulcer healing rate was 4/7 (57%) within 3 months. All C4 patients experienced symptom improvement postoperatively and had a median recurrence free period of 72 (range 60-122) months. The C5 group had an median ulcer free period of 61 months (12-72) and the C6 of median 48 (12-72) months. Single valve plasties (4) reached a median competence period of 48 months (12-72), 12 multiple valve plasties at the same level show a median 78 months (63-122) and 10 multilevel repairs median 54 months (12-96). Multiple valve plasties at the same level (multi-station plasties) performed on the C4 group seemed to yield the longest durability with a median of 103 months (84-122). CONCLUSION: EVVP with an ulcer healing rate of 57% and satisfactory symptom improvement seems to be an alternative of surgical treatment for selected patients with PCVI. The durability of this technique seems to be related to clinical severity and the multiplicity of repairs.

Gadolinium-enhanced magnetic resonance angiography, colour duplex and digital subtraction angiography of the lower limb arteries from the aorta to the tibio-peroneal trunk in patients with intermittent claudication.

OBJECTIVES: To evaluate the sensitivity, specificity, positive and negative predictive value of contrast-enhanced (gadolinium) magnetic resonance imaging (CE-MRA) and colour duplex ultrasound (CDU) of lower limb arteries. DESIGN: Prospective, single centre study. MATERIAL AND METHODS: A consecutive series of 58 patients with intermittent claudication (IC) were examined with CE-MRA and CDU from the infrarenal aorta to the tibio-peroneal trunk with digital subtraction angiography (DSA) as reference. The arterial tree was divided into 15 segments, pooled into three regions; suprainguinal, thigh and knee. Sensitivity, specificity, positive and negative predictive values for significant obstructions were calculated. Cohen Kappa statistics was used to establish agreement between the three methods. RESULTS: The sensitivity (specificity in parentheses) for significant obstructions in the suprainguinal region were 96% (94%) for CE-MRA and 91% (96%) for CDU, in the thigh region 92% (95%) for CE-MRA and 76% (99%) for CDU, and in the knee region 93% (96%) for CE-MRA and 33% (98%) for CDU. CDU failed to visualize 10% of suprainguinal, 2% of thigh and 13% of knee-region arterial segments. CONCLUSIONS: Both CE-MRA and CDU are good alternatives to DSA in the suprainguinal- and thigh-region. In the knee region only CE-MRA can be relied upon as an alternative to DSA. Imaging by CDU is not suited to situations were evaluation of runoff vessels is important.

The femoral arterial flow velocity pattern in patients with atherosclerotic obstruction of the femoropopliteal segment. A study based on pulsed Doppler ultrasound flowmetry.

The flow velocity pattern in the common femoral artery was analyzed in 107 limbs with femoropopliteal atherosclerotic obstruction and a normal aortoiliac segment. A pulsed wave Doppler ultrasound flowmeter was used. The highest (Va), the lowest (Vb) and the time average of the mean (V mean) velocities were obtained, and the pulsatility index (PI = Va-Vb/V mean) was calculated. In limbs with occluded (PI = 6.2) or greater than 50% stenotic (PI = 5.8) femoropopliteal segment, the flow velocity curve was slightly damped, with PI lower than in a control group (PI = 8.2). Neither stenosis of the profunda femoris artery nor the number of occluded leg arteries influenced the hemodynamic values in limbs with occluded femoropopliteal segment. Dampening of the femoral arterial flow velocity curve and reduced PI may indicate a stenotic (greater than 50%) or an occluded femoropopliteal segment. This flow pattern is also seen in aortoiliac atherosclerosis. In 76 limbs studied after femoropopliteal bypass, PI normalized when the bypass was patent, but was unchanged when the graft was occluded. Analysis of femoral arterial flow velocity pattern with calculation of PI may be useful in postoperative evaluation of femoropopliteal reconstruction.

[Computer tomography after reconstructive vascular surgery of the abdominal aorta. Can fluid around the aortic prosthesis be considered a normal finding?]. / Computertomografi etter rekonstruktiv karkirurgi på aorta abdominalis. Kan vaeske rundt aortaprotese vaere et "normalt" funn?

15 patients who had elective aortic reconstruction for infra-renal aortic aneurysm (nine patients) or aortoiliac occlusive disease (six patients) were evaluated using postoperative computerized tomography. The assessment was performed 1-2 weeks, 6-8 weeks and 6-8 months after implantation of woven Dacron graft. All patients were without clinical or laboratory signs of infection. The presence or absence of retroperitoneal air or fluid collections was assessed. In patients operated on for aneurysms, perigraft fluid was present in two cases 6-8 weeks after operation, but had disappeared within 6-8 months. Even after only 1-2 weeks, no accumulation of periprosthetic fluid was found in patients operated on for occlusive disease. Retroperitoneal air was not seen in any of the cases. It is concluded that perigraft fluid may be a "normal" phenomenon during the early postoperative period in patients operated on for abdominal aortic aneurysm.

The femoral arterial flow velocity pattern in patients with aortoiliac atherosclerosis. Studies with a pulsed Doppler ultrasound flowmeter.

The femoral arterial flow velocity pattern in 164 limbs with aortoiliac atherosclerosis was analyzed preoperatively, using a pulsed wave Doppler ultrasound flowmeter. Following aortoiliac reconstruction, 32 limbs were studied. The highest (Va), the lowest (Vb) and the time average of the mean velocities (V mean) were obtained, and pulsatility index (PI = Va-Vb/V mean) was calculated. The aortoiliac obstruction was radiologically graded as reduction in cross-sectional area (less than 25%, 25-50%, greater than 50%) or complete occlusion. With increasing grade of stenosis, progressive reduction of PI (from 7.6 to 2.1) was observed. PI differed according to degree of obstruction. In 30 extremities with clinical improvement after vascular reconstruction, PI showed significant postoperative rise (from 2.7 to 6.9). In the two limbs without clinical benefit of surgery, PI was largely unaffected. A monophasic, flattened curve of femoral arterial flow velocity and reduced PI may indicate aortoiliac atherosclerosis. Normalization of PI and biphasic curve following aortoiliac reconstruction suggest successful treatment.

Hemodynamic effect of percutaneous transluminal angioplasty for lower limb atherosclerosis. A study based on pulsed Doppler ultrasound flowmetry.

Measurements of ankle pressure index (API) and arterial flow velocity including calculation of pulsatility index (PI) from the common femoral and pedal arteries were performed in 89 limbs of 75 patients before and after percutaneous transluminal angioplasty (PTA) (63 iliac and 26 femoropopliteal). A pulsed wave Doppler ultrasound flowmeter was used. An increase of API at rest of at least 0.15 or the absence of pressure drop after exercise following PTA was used as criteria for a hemodynamically successful angioplasty. In patients with hemodynamically successful PTA of an iliac obstruction PI increased from 4.2 to 8.6 (p less than 0.001); 91 per cent of these patients improved clinically. When iliac angioplasty was hemodynamically unsuccessful, PI remained unchanged; 11 per cent of these patients improved clinically. All limbs with hemodynamically successful PTA of a femoropopliteal obstruction improved clinically and PI increased from 3.1 to 8.7 (p less than 0.001). After hemodynamically unsuccessful femoropopliteal PTA, PI remained unchanged though 25 per cent of these patients improved clinically. These results illustrate that measurement of arterial flow velocity with calculation of PI may be a useful supplement for the functional evaluation of the effect of PTA, since symptomatic response alone may be unreliable.

Measurements of common femoral artery flow velocity in the evaluation of aortoiliac atherosclerosis. Comparisons between pulsatility index, pressures measurements and pulse-volume recordings.

Blood flow velocity in the common femoral artery was measured in 52 limbs of 45 patients with radiologic signs of aortoiliac atherosclerosis. Group A limbs had significant obstruction of the aortoilac segment; group B had not. 'Significant' implied a transobstruction pressure gradient of greater than or equal to 10 mmHg at rest or greater than or equal to 20 mmHg after intra-arterial injection of papaverine. Pulse-volume recording (PVR) and non-invasive measurement of the common femoral artery pressure (FAP) were also performed. Pulsatility index (PI) less than 3.9 and PVR amplitude less than 13 mm indicated significant obstruction, whereas PI greater than 5.4 and PVR amplitude greater than 20 mm were observed only in limbs without significant pressure gradient across the aortoiliac segment. PI 3.9-5.4 and PVR amplitude 13-20 mm were found in both groups. FAP and flow velocity during reactive hyperemia did not adequately distinguish the two groups, because of value overlap. In assessing the hemodynamic significance of aortoiliac obstruction, PI and PVR in the common femoral artery may be useful supplements to clinical examination, but measurement of the pressure gradient across the aortoiliac obstruction before and after vasodilation probably is most reliable.

Effect of high-dose ampicillin and cloxacillin on bleeding time and bleeding in open-heart surgery.

To determine if platelet dysfunction caused by high doses of penicillin compounds is of practical importance in patients with additional haemostatic defects perioperatively, a study was made of patients undergoing open-heart surgery. They were randomly assigned to prophylactic treatment with ampicillin 8 g plus cloxacillin 4 g daily for three days, or with cephalothin 8 g daily for three days. Fifty patients in each group were evaluated. The median bleeding time preoperatively and on days 1 and 4 postoperatively did not differ between the groups. The bleeding time was prolonged beyond the normal range in eight patients of the ampicillin/cloxacillin group and in three of the cephalothin group (p less than 0.05). Prolonged bleeding time was not associated with lower platelet count or greater blood loss. The total blood loss and the amounts of transfused blood, platelets and cryoprecipitate were all greater in the ampicillin/cloxacillin group, but the difference was not statistically significant. Combined use of ampicillin and cloxacillin in open-heart surgery is associated with increased bleeding, but the increase is without practical importance.