The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation

STUDY OBJECTIVE: To determine whether the use of continuous i.v. sedation is associated with prolongation of the duration of mechanical ventilation. DESIGN: Prospective observational cohort study. SETTING: The medical ICU of Barnes-Jewish Hospital, a university-affiliated urban teaching hospital. PATIENTS: Two hundred forty-two consecutive ICU patients requiring mechanical ventilation. INTERVENTIONS: Patient surveillance and data collection. MEASUREMENTS AND RESULTS: The primary outcome measure was the duration of mechanical ventilation. Secondary outcome measures included ICU and hospital lengths of stay, hospital mortality, and acquired organ system derangements. A total of 93 (38.4%) mechanically ventilated patients received continuous i.v. sedation while 149 (61.6%) patients received either bolus administration of i.v. sedation (n=64) or no i.v. sedation (n=85) following intubation. The duration of mechanical ventilation was significantly longer for patients receiving continuous i.v. sedation compared with patients not receiving continuous i.v. sedation (185+/-190 h vs 55.6+/-75.6 h; p<0.001). Similarly, the lengths of intensive care (13.5+/-33.7 days vs 4.8+/-4.1 days; p<0.001) and hospitalization (21.0+/-25.1 days vs 12.8+/-14.1 days; p<0.001) were statistically longer among patients receiving continuous i.v. sedation. Multiple linear regression analysis, adjusting for age, gender, severity of illness, mortality, indication for mechanical ventilation, use of chemical paralysis, presence of a tracheostomy, and the number of acquired organ system derangements, found the adjusted duration of mechanical ventilation to be significantly longer for patients receiving continuous i.v. sedation compared with patients who did not receive continuous i.v. sedation (148 h [95% confidence interval: 121, 175 h] vs 78.7 h [95% confidence interval: 68.9, 88.6 h]; p<0.001). CONCLUSION: We conclude from these preliminary observational data that the use of continuous i.v. sedation may be associated with the prolongation of mechanical ventilation. This study suggests that strategies targeted at reducing the use of continuous i.v. sedation could shorten the duration of mechanical ventilation for some patients. Prospective randomized clinical trials, using well-designed sedation guidelines and protocols, are required to determine whether patient-specific outcomes (eg, duration of mechanical ventilation, patient comfort) can be improved compared with conventional sedation practices.     

Intestinal permeability correlates with severity of injury in trauma patients

BACKGROUND: Increased intestinal permeability (IP) and the release of toxic intraluminal materials have been implicated in the systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) observed in patients after severe trauma. Previous studies of intestinal permeability have failed to demonstrate a correlation between early measurements of IP and indicators of injury severity. This study examines the relationship between standard measures of injury severity and the early (day 1) and delayed (day 4) changes in IP. Associations between IP and the development of SIRS, MOF, and infectious complications were also studied. METHODS: The metabolically inactive markers lactulose (L) and mannitol (M) were used to measure IP in 29 consecutive patients who sustained injuries that required admission to the surgical intensive care unit and in 10 healthy control subjects. Measurements were made within 24 hours of admission and on hospital day 4. Severity of injury was assessed by A Severity Characterization of Trauma (ASCOT), Trauma and Injury Severity Score (TRISS), Injury Severity Score (ISS), Revised Trauma Score (RTS), and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Postinjury infections and parameters of SIRS and MOF were recorded. RESULTS: The IP of healthy volunteers (L/M, 0.025 +/- 0.008) was within the normal range (L/M < or = 0.03), whereas the average IP in injured patients was increased both within 24 hours (L/M, 0.139 +/- 0.172) and on the fourth hospital day (L/M, 0.346 +/- 0.699). No significant correlation between severity of injury and increased IP was seen within 24 hours of injury. A significant correlation was seen on hospital day 4, however, with all severity indices measured (ASCOT: r = 0.93, R2 = 0.87, p < 0.001; TRISS: r = 0.93, R2 = 0.87, p < 0.001; ISS: r = 0.84, R2 = 0.70, p < 0.001; RTS: r = 0.68, R2 = 0.47, p = 0.002; APACHE II score: r = 0.51, R2 = 0.26, p = 0.04). Patients with markedly increased IP (L/M > or = 0.100) experienced a significant increase in the development of SIRS (83 vs. 44%; p = 0.03) and subsequent infectious complications (58 vs. 13%; p = 0.01) and showed close correlation with the multiple organ dysfunction scores (r = 0.87, R2 = 0.76, p < 0.001). CONCLUSION: These observations demonstrate that the increased IP observed after trauma correlates with severity of injury only after 72 to 96 hours and not within the initial 24 hours of injury. A large increase in IP is associated with the development of SIRS, multiple organ dysfunction, and an increased incidence of infectious complications.     

Presyncope during progressive hypovolaemia simulated by lower body negative pressure is not prevented by high-dose naloxone

STUDY OBJECTIVE: We set the hypothesis that follow-up surveys of occupational asthma (OA) could now show better improvement in the asthmatic condition because of a more prolonged interval since removal from exposure than in previously reported studies. PATIENTS/METHODS: Ninety-nine subjects with OA were assessed and were separated into two groups according to the duration of cessation of exposure: (1) group removed for > or = 5 years: 48 subjects studied 8.9+/-2.2 years after cessation of exposure; (2) group removed for <5 years: 51 subjects with OA, comparable in terms of history and functional results at time of diagnosis, with a time lapse from last exposure of 3.1+/-1.2 years. On the follow-up visit, questionnaires including information on the current and previous use of inhaled steroids, spirometry, and methacholine tests were administered and results were compared with those obtained at the time of diagnosis. RESULTS: At the follow-up visit, no significant changes in spirometry were observed in the two groups. However, a significant improvement in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) from a mean value of 1.5 to 3.7 mg/mL was documented (p<0.001). The proportion of subjects having normal PC20 at the follow-up visit was significantly higher in the group removed from exposure for >5 years than in the group removed for < or = 5 years (16/33 vs 8/42; p=0.01). Stepwise logistic regression showed that follow-up PC20 could be predicted from baseline PC20 (p<0.001, odds ratio [OR]=4.1, 95% confidence interval [CI]=1.8 to 9.1), duration of exposure (p=0.04, OR=0.9, 95% CI=0.8 to 1.0), the interval since removal from exposure (p=0.002, OR=1.7, 95% CI=1.2 to 2.5), and the type of agent; subjects with OA due to high-molecular-weight agent showed a less favorable outcome (p=0.04, OR=0.2, 95% CI=0.03 to 1.0). Current and past treatments with inhaled steroids were not significant predictors. CONCLUSION: Results obtained in the group of this study removed for >5 years show better prognostic figures than those reported in most previous studies. Comparison with the group removed for a shorter interval and the stepwise logistic regression analysis suggest that the longer duration of the interval from cessation of exposure appears to be a factor determining this difference.     

Cardiovascular prevention, primary or secondary, in high risk patients

Two groups of patients admitted to hospital consecutively for coronary artery disease in 36 university hospital departments were interrogated about the advice received and followed concerning cardiovascular prevention both before the clinical onset of the disease (Group I), those with disease of less than one month duration (primary prevention), or after this period (Group II), those with disease for over six months (secondary prevention). The follow-up of risk factors or medical advice concerning prevention (dietary and/or treatment) was more common, and compliance to the advice was better, in secondary prevention. However, in both groups, with the exception of hypertension, the diagnosis and follow-up of the risk factors were incomplete with 19% vs 41% (p < or = 0.001) of serum cholesterol levels unmeasured before the onset of clinical disease; during the last 5 years, 41% vs 12% (cholesterol, p < or = 0.001) and 27% vs 9% (serum glucose, p < or = 0.001) were not checked. At least one measure of prevention had been advised to 66% vs 80% (p < or = 0.001) of patients and the measures taken concern 53 vs 75% (p < or = 0.001) of patients: serum cholesterol 27% vs 51% (p < or = 0.001), hypertension 32% vs 36% (NS) and serum glucose 14% vs 21% (p < or = 0.05). Compliance with advice was mediocre with regards to diet and cholesterol lowering drugs. A large proportion of patients in both groups had higher than recommended levels, including those on diet or treatment. These observations, confirmed in France and abroad, suggest that cardiovascular prevention should be better organised.     

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation

OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial. SETTING: One university hospital intensive care department. PATIENTS AND PARTICIPANTS: 122 patients with ARDS, consecutively admitted to the ICU. INTERVENTIONS: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. MEASUREMENTS AND RESULTS: The groups differed in both APACHE II (16 +/- 5 vs 18 +/- 5 points, p = 0.01) and Murray scores (3.2 +/- 0.3 vs 3.4 +/- 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 +/- 9 vs 13 +/- 9 days, p = 0.0151), and length of ICU stay in Berlin (31 +/- 17 vs 50 +/- 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 +/- 27 mm Hg in AT-sine-ECMO patients that improved to 165 +/- 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 +/- 28 mm Hg and improvement to 160 +/- 102 mm Hg was not reached until ICU day 13. QS/QT was significantly higher in the ECMO-treated group and exceeded 50% during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75%. Survival rates were 89% in the AT-sine ECMO group and 55% in the ECMO treatment group (p = 0.0000). CONCLUSIONS: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.     

Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients

BACKGROUND: Cytomegalovirus infection threatens pulmonary allograft survival and function. This retrospective study details the experience of ganciclovir prophylaxis against cytomegalovirus infection and its sequelae. METHODS: Eight-nine lung and heart-lung transplant recipients with positive cytomegalovirus serology were analyzed. The 37 recipients who underwent transplantation before September 1989 received no prophylaxis. The 52 subsequent recipients received ganciclovir prophylaxis. RESULTS: Thirty-six non-prophylaxed versus 42 prophylaxed patients had cytomegalovirus events with cumulative incidences of 100% and 86% (p < < 0.01), and median onsets of 37 +/- 21 versus 85 +/- 35 days, respectively (p < < 0.01); 22 non-prophylaxed versus 27 prophylaxed patients had cytomegalovirus pneumonitis with cumulative incidences of 60% and 55% (p < < 0.01), and median onsets of 34 +/- 14 and 84 +/- 26 days, respectively (p < < 0.01). Respiratory failure caused by cytomegalovirus pneumonitis developed in nine of the non-prophylaxed versus two of the prophylaxed patients (p < < 0.01). The significant estimated survival benefit in patients who received prophylaxis (p = 0.04) was not apparent when reanalysis was performed after exclusion of patients with respiratory failure (p = 0.36). Ganciclovir prophylaxis produced a significant delay in the development of obliterative bronchiolitis with a median time to onset of 1072 +/- 280 days versus 432 +/- 189 days for the non-prophylaxis cohort (p < < 0.01). CONCLUSIONS: Ganciclovir prophylaxis (1) improves recipient survival by reducing the severity of disease and essentially eliminating respiratory failure caused by cytomegalovirus pneumonitis, (2) reduces the incidence and delays the onset of cytomegalovirus events and pneumonitis, and (3) delays the onset of obliterative bronchiolitis.     

Influence of ergometric parameters on the results of myocardial perfusion tomographic scintigraphy

BACKGROUND: The percentage of peak predicted heart rate that is accepted to consider as sufficient a given exercise test is 85%. However, the optimal value of such rate and other exercise parameters for the purposes of myocardial single-photon emission tomography is not well established. PATIENTS AND METHODS: With the aim of establishing the minimal levels of maximal heart rate, product heart rate x systolic blood pressure and ventilatory oxygen uptake to obtain an adequate diagnostic efficacy of myocardial perfusion scintigraphy, 159 patients with coronary artery disease or suspicion of this without previous myocardial infarction were studied with stress test single photon emission tomography with 99mTc-methoxi-isobutil-isonitrile. All the patients were coronary angiography tested. RESULTS: Sensitivity and negative predictive value were significantly higher at levels of heart rate > 80% (93 vs 78%; p = 0.002 and 94 vs 56%; p = 0.0004), product heart rate x systolic blood pressure > 18,000 (88 vs 78%; p = 0.04 and 84 vs 52%; p = 0.004) and > 5 METs (85 vs 77%; p = 0.002 and 74 vs 69%; p = 0.03). CONCLUSIONS: Sensitivity and negative predictive value of stress test single photon emission tomography with 99mTc-methoxi-isobutil-isonitrile are low if levels higher than 80% of heart rate, 18,000 of product of heart rate x systolic blood pressure and 5 METs have not been achieved.     

Granulocytic Ehrlichia infection in ixodid ticks and mammals in woodlands and uplands of the U.K

BACKGROUND: The number of patients waiting lung transplantation greatly exceeds the supply of donors. This study was conducted to determine the effect of high-dose steroid administration on oxygenation and donor lung recovery after brain death. METHODS: A retrospective analysis was conducted on 118 consecutive organ donors from January 1 through December 31, 1995. Eighty donors received high-dose steroids (methylprednisolone, mean 14.5+/-0.06 mg/kg) after organ procurement organization management began; a second group was composed of 38 patients who received no steroids. PaO2/FiO2 ratios were used to evaluate oxygenation. The number of single and double lungs transplanted served as the endpoint. RESULTS: No differences were noted in hemodynamics, most clinical or demographic variables and initial values of PaO2/FiO2 between groups. However, nonsteroid-treated donors showed an overall decrease in oxygenation (mean decrease in PaO2/FiO2 -34.2+/-14), whereas steroid-treated donors had a significant and progressive increase in oxygenation (mean increase in PaO2/FiO2: 16+/-14) before aortic cross-clamping (p = 0.01). Time before cross-clamping was longer in the steroid-treated patients (p = 0.003). The number of procured lungs was markedly greater in steroid-treated than nonsteroid-treated donors (25/80 patients vs 3/38; p < 0.01). CONCLUSIONS: High-dose methylprednisolone given during donor management results in improved oxygenation at organ recovery. This treatment resulted in a significant increase in the number of lungs transplanted and may have enabled donors to be treated longer.     

Cardiac pacing following surgery for acquired heart disease

BACKGROUND: This study is comprised of 3493 consecutive patients who underwent open heart surgery at our institution. Data on all patients were collected prospectively. METHODS: In 45 patients (Group P) (1.3%), a permanent pacemaker (PP) was inserted postoperatively. For the purpose of the study, these patients were compared to 3448 patients (Group NP) who did not require insertion of a PP after surgery. Mean follow-up was 33 months (range 1.5 to 66). RESULTS: We found Group P patients were older (64.8 +/- 11.0 vs 61.0 +/- 11.0 years, p < 0.05), had a higher proportion of elderly (> 70 years) 36% vs 19%, p = 0.01), and of female patients (48.8% vs 22.7%, p < 0.001) compared to Group NP. Group P also had a higher incidence of preoperative rhythm abnormalities (26.6% vs 5.7%, p < 0.0001), redo surgery (13.3% vs 4.6%, p = 0.02), aortic valve surgery (48.8% vs 10.8%, p < 0.001), and tricuspid valve surgery (repair 3, replacement 1) (8.8% vs 0.5%, p < 0.001), in addition to a higher proportion of patients in whom cold (vs warm) blood cardioplegia was used (68.8% vs 52.3%, p = 0.03). Indication for postoperative PP was sick sinus syndrome (SSS) in nine patients; atrial fibrillation in eight patients; atrioventricular block (AVB) in 27 patients; and combined AVB/SSS in 1 patient. There were no operative deaths in Group P. Necessity for PP after heart surgery had a significant impact on resource utilization resulting in prolonged ventilation (3.1 +/- 7.5 vs 1.4 +/- 3.3 days, p < 0.01), intensive care unit (5.1 +/- 10.2 vs 2.5 +/- 4.0 days, p < 0.01), and postoperative hospital stay (18.0 +/- 13.4 vs 8.1 +/- 9.4 days, p < 0.01). CONCLUSIONS: By multivariate logistic regression (odds ratio and p value in parentheses), aortic valve surgery (8.23, p = 0.001), the absence of preoperative sinus rhythm (5.60, p = 0.001), postoperative myocardial infarction (3.46, p = 0.024), and female gender (2.52, p = 0.003), were found to be independent predictors for PP requirement post surgery.     

Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells

In this study we addressed whether the proportion and the function of antigen presenting cells (APC), T and NK lymphocytes are modified in the apheresis product of six healthy donors who received a stem cell mobilizing treatment with glycosylated G-CSF at 10 microg/kg/day x 5 days s.c. Flow cytometry analysis showed comparable percentages of HLA-DR+, CD19+, CD86+, CD80+ and CD1a+ cells in preG-CSF-peripheral blood mononuclear cells (preG-PBMC) and after mobilization in G-PBMC, whereas the proportion of CD14+ monocytes significantly increased in G-PBMC (3+/-1% vs 17+/-8%, P = 0.003). Analysis of lymphocyte subsets in preG-PBMC and G-PBMC showed similar proportions of CD3+, CD4+, CD8+ and CD28+ T cells, but a significantly lower percentage of CD16+ (11+/-7% vs 4+/-1%, P=0.01), CD56+ (15+/-6% vs 5+/-2%, P= 0.008), CD57+ (16+/-9% vs 5+/-2%, P=0.04), CD25+ (19+/-2% vs 9+/-6%, p=0.009) and CD122+ (5+/-2% vs 2+/-1%, P = 0.05) cells in G-PBMC. Unfractionated preG-PBMC and G-PBMC were irradiated and tested in primary mixed leukocyte culture (MLC) with two HLA-incompatible responders and induced efficient alloresponses in four of six cases, whereas G-PBMC stimulated poorly in the remaining two cases. Also, in allo-MLC with irradiated G-PBMC we detected lower amounts of IFN-gamma (P = 0.04) and of IL-2 (P = 0.06) than in allo-MLC with preG-PBMC. Furthermore, freshly isolated preG-PBMC and G-PBMC from each donor exerted comparable allogeneic responses to HLA-incompatible irradiated mononuclear cells in all cases. However, G-PBMC showed no NK activity against K562 target cells at any effector:target ratio tested. These data suggest that normal G-PBMC may prevent Thl alloresponses, maintain efficient alloreactivity to HLA mismatched antigens and have impaired NK activity.     

Effects of different protective agents on the phototoxicity of fluoranthene to Daphnia magna

OBJECTIVE: To determine if a risk prediction model for patients with unstable angina would predict resource utilization. METHODS AND RESULTS: Four hundred sixty-five consecutive patients admitted for unstable angina to a tertiary care university-based medical center were prospectively evaluated from June 1, 1992, to June 30, 1995. The proportion of patients receiving coronary angiography, coronary angioplasty, and coronary artery bypass grafting were analyzed according to four risk groups on the basis of a previously published model: Group 1, <2% risk of major complication; Group 2, 2.1% to 5% risk; Group 3, 5.1 % to 15% risk; and Group 4, >15.1 % risk. Hospital length of stay and estimated cost of hospitalization based on DRG and specific payer ratio of cost-to-charge were also compared between groups. Multiple linear regression analysis was used to determine the influence of estimated risk and procedures on hospital costs. The four groups were well matched for gender, hypertension, tobacco history, and previous percutaneous transluminal coronary angioplasty and myocardial infarction. Group 4 had a higher incidence of previous coronary bypass grafting (35% vs 10%, p=0.001) and triple vessel or left main coronary artery disease compared with Group 1 (44% vs 13%, p=0.041). Group 4 patients were more likely to be admitted to the coronary care unit compared with Group 2 or Group 1 patients (80% vs Group 1: 51% [p= 0.001]; and vs Group 2: 53% [p=0.001]), more likely to receive heparin (87% vs 71%, p=0.007), and more likely to receive a beta-blocker or calcium channel blocker (89% vs 74%, p=0.008) than Group 1. Coronary angioplasty rates were similar for all groups, but Group 4 patients were more likely to receive coronary bypass grafting than Group 2 or Group 1 (27% vs Group 2: 12%, p=0.004 and vs Group 1: 8%, p=0.002). Hospital length of stay was highest in Group 4 and lowest for Group 1. Average hospital costs were significantly less in Group 3 than in Group 4, but higher than in Group 1. Multivariate analysis determined a dependency of costs on risk group with Group 2 having costs 31.4% (95% CI=9.8 to 57.2), Group 3 46.7% (24, 3 to 73.1), and Group 4 75% (46.9 to 110.7) higher than Group 1. The use of procedures also significantly increased costs, with PTCA-treated patients having a 44.9% (26.7 to 65.7) increase in costs compared with medically treated patients, and surgically treated patients having a 204.7% increase in costs. CONCLUSION: Resource utilization as assessed by the use of revascularization procedures, length of stay, and hospital costs are influenced by patient acuity estimated from a prediction model on the basis of estimated risk of cardiac complications. The model exerts independent influence on cost even after adjustment for various procedures. The use of revascularization procedures, especially coronary artery surgery, remains a large determinant of hospital cost.     

Mechanical resilience of skin: a function of blood supply and lymphatic drainage

Diabetic ketoacidosis occurs more frequently in the young adult population than in any other age group. In a 3-year retrospective casenote review of all patients admitted with ketoacidosis to this hospital, we have defined the clinical characteristics of ketoacidosis in this age group. Young adults (< 25 years) had worse preceding glycaemic control (median HbA1 14.6 vs 10.1%, p = 0.0001) and more frequent episodes of ketoacidosis in the previous 5 years (3 vs 0, p = 0.0001) than older adults (> 25 years); on admission they had lower blood urea concentrations (p = 0.0001) and had a lower incidence of systolic hypotension (6% vs 32%, p = 0.007). There were fewer complications of ketoacidosis in the young adults, and the duration of hospital stay was less than that in the older age group (4 vs 8 days, p = 0.0003). Young adults were less likely to have a proven underlying infective or other organic precipitant for ketoacidosis, but were investigated and treated in a similar way to older adults. Insulin error or manipulation was identified in 42% of young adults; abnormal insulin treatment behaviour is likely to be the major cause of ketoacidosis in this age group.     

Comparison of 2D and 3D algorithms for adding a margin to the gross tumor volume in the conformal radiotherapy planning of prostate cancer

OBJECTIVE: To determine whether electron beam computed tomography (CT) adds to conventional risk factor assessment in the prediction of angiographic coronary artery disease. BACKGROUND: Electron beam CT scanning can be used to predict the severity of coronary atherosclerosis, but whether it does so independently of conventional risk factors is unclear. METHODS: Electron beam CT scans were performed and conventional risk factors were measured in 290 men and women undergoing coronary arteriography for clinical indications. The association of the electron beam CT-derived coronary artery calcium score and conventional risk factors with the presence and severity of angiographically defined coronary atherosclerosis was analyzed by logistic regression and receiver-operator characteristics analysis. RESULTS: Age, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol and the coronary calcium score were significantly and independently associated with the presence of any coronary disease and obstructive coronary disease. In association with any coronary disease, odds ratios for age, the ratio of total cholesterol to HDL cholesterol and calcium score, highest quartile vs. lowest quartile, were 6.01 (95% confidence interval 2.87 to 12.56), 3.14 (1.56 to 6.31) and 94.08 (21.06 to 420.12), respectively. For obstructive coronary disease, highest quartile vs. lowest quartile, the respective odds ratios for age, the ratio of total cholesterol to HDL and calcium score were 3.86 (1.86 to 8.00), 4.11 (1.98 to 8.52) and 34.12 (12.67 to 91.86). Male gender was also significantly associated with any coronary disease (odds ratio 2.19, p=0.04) and obstructive coronary disease (odds ratio 2.07, p=0.04). Cigarette smoking was significantly associated with any coronary disease (odds ratio=2.74, p=0.004), and diabetes was significantly associated with obstructive disease (odds ratio 3.16, p=0.01). After adjustment for the coronary calcium score and other risk factors, it was determined that triglycerides, family history and hypertension were not significantly associated with any disease state. A coronary calcium score >80 (Agatston method) was associated with an increased likelihood of any coronary disease regardless of the number of risk factors, and a coronary calcium score > or = 170 was associated with an increased likelihood of obstructive coronary disease regardless of the number of risk factors (p < 0.001). CONCLUSIONS: Electron beam CT scanning offers improved discrimination over conventional risk factors in the identification of persons with any angiographic coronary disease or angiographic obstructive coronary disease.     

Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex

The role of percutaneous needle aspiration for therapy of uncomplicated, large amoebic liver abscess (ALA) is not defined. Twenty nine patients of ALA with a cavity larger than 5 cm were randomised to two groups: (i) metronidazole 800 mg tid for 10 days combined with needle aspiration (group A, n = 15) and (ii) metronidazole therapy alone (group B, n = 14). Clinical parameters, viz, fever, pain and abdominal tenderness were recorded daily and graded 0 to 3 (in order of increasing severity). A statistically significant benefit was demonstrated in group A for clinical parameters evaluated. Group A patients took less time to become afebrile from the grade 2 level as compared to group B (3.8 +/- 1.7 days and 5.6 +/- 2.2 days respectively; p < 0.05). Reduction in pain intensity and abdominal tenderness from grade 2 to 1 also occurred earlier in group A (0.7 +/- 0.7 days vs 2.9 +/- 0.9 days for pain, P < 0.001 and 1.7 +/- 0.8 days vs 2.9 +/- 1.2 days for abdominal tenderness, p < 0.001). The mean duration of hospitalization was significantly shorter in group A as compared to group B (5.8 +/- 0.8 days vs 7.4 +/- 1.5 days, p < 0.001). Improvement in haematological and biochemical variables was similar in both groups. We conclude that percutaneous therapeutic needle aspiration of uncomplicated, large ALA hastens clinical recovery.     

Outcome of cardiac valve ring abscesses after medical treatment: attempt to identify criteria of favorable prognosis

OBJECTIVES: Identify factors predicting favorable outcome after medical management of valve ring abscesses in order to propose a surveillance schedule for conservative treatment. METHODS: A multicentric study conducted from July 1989 to February 1996 included 28 patients (mean age 64 +/- 16 years, range 26-83) hospitalized for active endocarditis and valve ring abscesses diagnosed at transthoracic or transesophageal echography. Conservative medical therapy was given because of a decision of the medico-surgical team (n = 9), high surgical risk (n = 12), or patient refusal of surgery (n = 7). Outcome was favourable in 18 patients (Group I) and unfavorable in 10 (Group II) due to death (n = 9) or subsequent surgery (n = 1). Univariate and multivariate analysis were used to determine differences between the groups in terms of clinical and laboratory data. RESULTS: Mean follow-up in Group I was 33 +/- 18 months and 15 +/- 10 months in Group II. Univariate analysis showed significant differences between Group I and II respectively for age (59 +/- 18 yr vs 72 +/- 10, p = 0.04), delay to apyrexia after antibiotics (4.3 +/- 2.8 vs 8.3 +/- 2.4 days, p < 0.0008), heart failure (5% vs 70%, p = 0.003), grade III or IV valvular regurgitation (5% vs 60%, p < 0.04), and mean surface area of the abscess (1.5 +/- 1.2 vs 5.4 +/- 6.4 cm2, p < 0.03). Independent factors at multivariate analysis were by decreasing order: lack of heart failure at admission, delay to apyrexia, abscess surface area, and age. Outcome was favorable (mean follow-up 33 +/- 10 months) in all patients with an abscess surface area < 1.5 cm2, no signs of heart failure, no grade III or IV valvular regurgitation, apyrexia after less than 8 days on antibiotics and no staphylococcus positive blood culture. CONCLUSION: Medical management of valve ring abscesses may be indicated in selected patients in care units with rigorous surveillance facilities. Further studies are needed to precisely identify surveillance and treatment criteria.     

Determinants of myocardial performance after blunt chest trauma

OBJECTIVE: This study investigates whether factors that determine myocardial performance (preload, afterload, heart rate, and contractility) are altered after isolated unilateral pulmonary contusion. METHODS: Catheters were placed in the carotid arteries, left ventricles, and pulmonary arteries of anesthetized, ventilated (FiO2=0.5) pigs (31.2+/-0.6 kg; n=26). A unilateral, blunt injury to the right chest was delivered with a captive bolt gun (n=17) followed by tube thoracostomy. To control for anesthesia and instrumentation at FiO2 of 0.5, one group received tube thoracostomy only (sham injury; n=6). To control for effects of hypoxia without chest injury, an additional sham-injury group (n=3) was ventilated with FiO2 of 0.12. To generate cardiac function (i.e., Starling) curves, lactated Ringer's solution was administered in three bolus infusions at serial time points; the slope of stroke index versus ventricular filling pressure defines cardiac contractility. RESULTS: By 4 hours after pulmonary contusion, pulmonary vascular resistance, airway resistance, and dead space ventilation were increased, whereas PaO2 (72+/-6 mm Hg at FiO2=0.5) and dynamic compliance were decreased (all p < 0.05). Despite profound lung injury, arterial blood pressure, heart rate, cardiac filling pressures, and output remained within the normal range, which is inconsistent with direct myocardial contusion. The slope of pulmonary capillary wedge pressure versus left ventricular end-diastolic pressure (LVEDP) regression was reduced by more than 50% from baseline (p < 0.05), but there was no significant change in the slope of the central venous pressure versus LVEDP regression. By 4 hours after contusion, the slope of the stroke index versus LVEDP curve was reduced by more than 80% from baseline (p < 0.05). By the same time after sham injury with FiO2 of 0.12 (PaO2 < 50 mm Hg), the regression had decayed a similar amount, but there was no change in the slope after sham injury with FiO2 of 0.5 (PaO2 > 200 mm Hg). CONCLUSION: After right-side pulmonary contusion, the most often used estimate of cardiac preload (pulmonary capillary wedge pressure) does not accurately estimate LVEDP, probably because of changes in the pulmonary circulation or mechanics. Central venous pressure is a better estimate of filling pressure, at least in these conditions, probably because it is not directly influenced by the pulmonary dysfunction. Also, ventricular performance can be impaired by depressed myocardial contractility and increased right ventricular afterload even with normal left ventricular afterload and preload. It is thus conceivable that occult myocardial dysfunction after pulmonary contusion could have a role in the progression to cardiorespiratory failure even without direct cardiac contusion.     

Popliteal artery trauma. Systemic anticoagulation and intraoperative thrombolysis improves limb salvage

OBJECTIVE: This study was conducted to evaluate those factors associated with popliteal artery injury that influence amputation, with emphasis placed on those that the surgeon can control. SUMMARY BACKGROUND DATA: Generally accepted factors impacting amputation after popliteal artery injury include blunt trauma, prolonged ischemic times, musculoskeletal injuries, and venous disruption. Amputation ultimately results from microvascular thrombosis and subsequent tissue necrosis, predisposed by the paucity of collaterals around the knee. METHODS: Patients with popliteal artery injuries over the 10-year period ending November 1995 were identified from the trauma registry. Preoperative (demographics, mechanism and severity of injury, vascular examination, ischemic times) and operative (methods of arterial repair, venous repair-ligation, anticoagulation-thrombolytic therapy, fasciotomy) variables were studied. Severity of extremity injury was quantitated by the Mangled Extremity Severity Score (MESS). Amputations were classified as primary (no attempt at vascular repair) or secondary (after vascular repair). After univariate analysis, logistic regression analysis was performed to identify the independent risk factors for limb loss. RESULTS: One hundred two patients were identified; 88 (86%) were males and 14 (14%) were females. Forty injuries resulted from blunt and 62 from penetrating trauma. There were 25 amputations (25%; 11 primary and 14 secondary). Patients with totally ischemic extremities (no palpable or Doppler pulse) more likely were to be amputated (31% vs. 13%; p < 0.04). All requiring primary amputations had severe soft tissue injury and three had posterior tibial nerve transection; the average MESS was 7.6. Logistic regression analysis identified independent factors associated with secondary amputation: blunt injury (p = 0.06), vein injury (p = 0.06), MESS (p = 0.0001), heparin-urokinase therapy (p = 0.05). There were no complications with either heparin or urokinase. CONCLUSIONS: Minimizing ischemia is an important factor in maximizing limb salvage. Severity of limb injury, as measured by the MESS, is highly predictive of amputation. Intraoperative use of systemic heparin or local urokinase or both was the only directly controllable factor associated with limb salvage. The authors recommend the use of these agents to maximize limb salvage in association with repair of popliteal artery injuries.     

The impact of nosocomial infections on patient outcomes following cardiac surgery

STUDY OBJECTIVE: To evaluate the relationship between nosocomial infections and clinical outcomes following cardiac surgery, and to identify risk factors for the development of nosocomial infections in this patient population. DESIGN: Prospective cohort study. SETTING: Barnes-Jewish Hospital, St. Louis, a university-affiliated teaching hospital. PATIENTS: Six hundred five consecutive patients undergoing cardiac surgery. INTERVENTIONS: Prospective patient surveillance and data collection. MAIN OUTCOME MEASURES: Occurrence of nosocomial infections, multiorgan dysfunction, hospital mortality, and risk factors for the acquisition of nosocomial infections. RESULTS: One hundred thirty-one (21.7%) patients acquired at least one nosocomial infection following cardiac surgery. Four independent risk factors for the development of a nosocomial infection were identified: the duration of mechanical ventilation, postoperative empiric antibiotic administration, the duration of urinary tract catheterization, and female gender. Thirty (5.0%) patients died during their hospitalization. The mortality rate of patients acquiring a nosocomial infection (11.5%) was significantly greater than the mortality rate of patients without a nosocomial infection (3.2%) (odds ratio [OR]=4.0; 95% confidence interval [CI]=2.7 to 5.8; p<0.001). Multiorgan dysfunction was found to be the most important independent determinant of hospital mortality (adjusted OR=23.8; 95% CI=13.5 to 42.1; p<0.001) along with the aortic cross-clamp time (adjusted OR=2.3; 95% CI=1.7 to 3.0; p=0.002) and severity of illness as measured by APACHE II (acute physiology and chronic health evaluation) (adjusted OR=1.1; 95% CI=1.1 to 1.2; p=0.019). Ventilator-associated pneumonia, clinical sepsis, female gender, the cardiopulmonary bypass time, and severity of illness were identified as independent risk factors for the development of multiorgan dysfunction. Among hospital survivors, patients acquiring a nosocomial infection had longer hospital lengths of stay compared to patients without a nosocomial infection (20.1+/-13.0 days vs 9.7+/-4.5 days; p<0.001). CONCLUSIONS: Nosocomial infections, which are common following cardiac surgery, are associated with prolonged lengths of hospitalization, the development of multiorgan dysfunction, and increased hospital mortality. These data suggest potential interventions for the prevention of nosocomial infections following cardiac surgery that could substantially improve patient outcomes and decrease medical care costs.     

Relationship of admission thyroid function tests to outcome in critical illness

One hundred and eighty patients had serum thyrotropin, total triiodothyronine and free thyroxine concentrations measured within 3 h of admission to the Intensive Therapy Unit to assess whether thyroid function tests could predict outcome in critical illness. Overall mortality was 30.6%. Nonsurvivors were older (p = 0.001), and had higher APACHE II scores (p < 0.001) and predicted mortalities (p < 0.001). There was no difference in the median values of thyrotropin, total triiodothyronine and free thyroxine concentrations between survivors and nonsurvivors. Thyrotropin concentration was subnormal in 15 patients, normal in 152 and elevated in 13 patients. In contrast, 80 patients had subnormal triiodothyronine concentration. Free thyroxine was subnormal in five patients. Thyrotropin, total triiodothyronine and free thyroxine concentrations were not related to outcome (p = 0.360, p = 0.622, p = 0.726, respectively). No variable independently predicted death. Total triiodothyronine concentrations were lower in patients who received dopamine before admission to the intensive therapy unit than those who did not (p = 0.008); thyrotropin and free thyroxine concentrations were not influenced by dopamine administration. Serum concentrations of thyrotropin, total triiodothyronine and free thyroxine measured within 3 h of admission to the intensive therapy unit are not predictive of outcome.