Kenneth V. Leeper

Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group.

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.

Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism: A Multicenter Prospective Study (PIOPED III)

BACKGROUND The accuracy of gadolinium-enhanced magnetic resonance pulmonary angiography and magnetic resonance venography for diagnosing pulmonary embolism has not been determined conclusively. OBJECTIVE To investigate performance characteristics of magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism. DESIGN Prospective, multicenter study from 10 April 2006 to 30 September 2008. SETTING 7 hospitals and their emergency services. PATIENTS 371 adults with diagnosed or excluded pulmonary embolism. MEASUREMENTS Sensitivity, specificity, and likelihood ratios were measured by comparing independently read magnetic resonance imaging with the reference standard for diagnosing pulmonary embolism. Reference standard diagnosis or exclusion was made by using various tests, including computed tomographic angiography and venography, ventilation-perfusion lung scan, venous ultrasonography, d-dimer assay, and clinical assessment. RESULTS Magnetic resonance angiography, averaged across centers, was technically inadequate in 25% of patients (92 of 371). The proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 57% (59 of 104) with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. LIMITATION A high proportion of patients with suspected embolism was not eligible or declined to participate. CONCLUSION Magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Magnetic resonance pulmonary angiography and magnetic resonance venography combined have a higher sensitivity than magnetic resonance pulmonary angiography alone in patients with technically adequate images, but it is more difficult to obtain technically adequate images with the 2 procedures.

Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome

Objective To determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Design A prospective, randomized, double-blind, placebo-controlled, multicenter study. Setting Intensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network. Patients A total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group). Interventions Patients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing. Measurements and Main Results The trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure–free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo. Conclusions In this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS.

Noninvasive mechanical ventilation via face mask in patients with acute respiratory failure who refused endotracheal intubation

Objective: To evaluate the response to noninvasive ventilation in a group of terminally ill patients with acute respiratory failure who refused endotracheal intubation. Design: Case series. Setting: Medical intensive care units (ICUs) in a university health science center. Patients: Eleven patients, nine with hypercapnic and two with hypoxemic acute respiratory failure. Mean age of patients was 64 yrs. Intervention: Mechanical ventilation was delivered via a face mask. The initial ventilatory setting was continuous positive airway pressure mode, with pressure‐support ventilation of 10 to 20 cm H2O, titrated to achieve a respiratory rate of <25 breaths/min and a tidal volume of 5 to 7 mL/kg. Ventilatory settings were adjusted based on results of arterial blood gases. Mean duration of mechanical ventilation was 44 hrs. Measurements and Main Results: Mechanical ventilation via face mask was effective in correcting gas exchange abnormalities in seven of 11 patients, all of whom survived and were discharged from the ICU. Four patients with hypercapnic acute respiratory failure died. Mechanical ventilation via face mask was effective in improving respiratory acidosis in three patients and had no effect in one patient. Two of the four patients could not be weaned from mechanical ventilation and opted for discontinuation of this method. Removal of the ventilator while retaining the mask for oxygen supplementation was a nontraumatic experience to the patient and family. Even when respiratory failure did not resolve, mechanical ventilation via face mask was effective in lessening dyspnea and allowed the patient to maintain autonomy and continuous verbal communication. Conclusions: We conclude that mechanical ventilation via face mask offers an effective, comfortable, and dignified method of supporting patients with end‐stage disease and acute respiratory failure. (Crit Care Med 1994; 22:1584–1590)

Nosocomial Sinusitis in Patients in the Medical Intensive Care Unit: A Prospective Epidemiological Study

A prospective observational cohort study of nosocomial sinusitis was carried out in two medical intensive care units. Sinusitis was diagnosed by computed tomographic scanning and the culture of sinus fluid obtained by puncture of a maxillary sinus. Clinical and epidemiological data were collected at the time of admission to the unit and daily thereafter. Specimens from the nares, oropharynx, trachea, and stomach were cultured on admission and daily thereafter. The cumulative incidence of nosocomial sinusitis was 7.7%, and the incidence rates were 12 cases per 1,000 patient-days and 19.8 cases per 1,000 nasoenteric tube-days. Risk factors for nosocomial sinusitis, as determined by multiple logistic regression analysis, included nasal colonization with enteric gram-negative bacilli (odds ratio [OR], 6.4; 95% confidence interval [95% CI], 2.2-18.8; P = .007), feeding via nasoenteric tube (OR, 14.1; 95% CI, 1.7-117.6; P = .015), sedation (OR, 15.9; 95% CI, 1.9-133.5; P = .011), and a Glasgow coma score of < or = 7 (OR, 9.1; 95% CI, 3.0-27.3; P = .0001).

Enlarged Right Ventricle Without Shock in Acute Pulmonary Embolism: Prognosis

OBJECTIVE An unsettled issue is the use of thrombolytic agents in patients with acute pulmonary embolism (PE) who are hemodynamically stable but have right ventricular (RV) enlargement. We assessed the in-hospital mortality of hemodynamically stable patients with PE and RV enlargement. METHODS Patients were enrolled in the Prospective Investigation of Pulmonary Embolism Diagnosis II. Exclusions included shock, critical illness, ventilatory support, or myocardial infarction within 1 month, and ventricular tachycardia or ventricular fibrillation within 24 hours. We evaluated the ratio of the RV minor axis to the left ventricular minor axis measured on transverse images during computed tomographic angiography. RESULTS Among 76 patients with RV enlargement treated with anticoagulants and/or inferior vena cava filters, in-hospital deaths from PE were 0 of 76 (0%) and all-cause mortality was 2 of 76 (2.6%). No septal motion abnormality was observed in 49 patients (64%), septal flattening was observed in 25 patients (33%), and septal deviation was observed in 2 patients (3%). No patients required ventilatory support, vasopressor therapy, rescue thrombolytic therapy, or catheter embolectomy. There were no in-hospital deaths caused by PE. There was no difference in all-cause mortality between patients with and without RV enlargement (relative risk=1.04). CONCLUSION In-hospital prognosis is good in patients with PE and RV enlargement if they are not in shock, acutely ill, or on ventilatory support, or had a recent myocardial infarction or life-threatening arrhythmia. RV enlargement alone in patients with PE, therefore, does not seem to indicate a poor prognosis or the need for thrombolytic therapy.

Early Microbiological Response to Linezolid vs Vancomycin in Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus*

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of ventilator-associated pneumonia (VAP). This prospective, open-label, multicenter clinical trial compared the early microbiological efficacy of linezolid (LZD) therapy with that of vancomycin (VAN) therapy in patients with MRSA VAP. METHODS A total of 149 patients with suspected MRSA VAP were randomized to receive either LZD, 600 mg, or VAN, 1 g every 12 h. Patients with baseline bronchoscopic BAL (BBAL) fluid quantitative culture findings that were positive for MRSA (>or= 10(4) cfu/mL) comprised the study population. The primary outcome was microbiological response (<or= 10(2) cfu/mL) in a second BBAL performed 72 to 96 h following the start of treatment. RESULTS Thirty LZD-treated patients and 20 VAN-treated patients had microbiologically confirmed MRSA at baseline; 23 and 19 patients, respectively, underwent repeat BBAL. While a greater number of LZD-treated patients than VAN-treated patients achieved a microbiological cure (56.5% vs 47.4%, respectively; p = 0.757; 95% confidence interval, -21.1 to 39.4), this difference was not statistically significant. Nonstatistically significant differences were also seen for LZD-treated patients vs VAN-treated patients in terms of clinical cure (66.7% vs 52.9%, respectively), survival rate (86.7% vs 70.0%, respectively), and the mean duration of ventilation (10.4 vs 14.3 d, respectively), hospitalization (18.8 vs 20.1 d, respectively), ICU stay (12.2 vs 16.2 d, respectively), and time spent alive and not receiving mechanical ventilation (15.5 vs 11.1 d, respectively). Three patients who had been extubated prior to undergoing repeat BBAL had been randomized to receive LZD therapy. CONCLUSION Early microbiological cure rates were not statistically significantly higher with LZD therapy than with VAN therapy despite trends in all secondary clinical outcomes favoring LZD therapy. These results suggest that any beneficial effect of LZD therapy may be due to factors other than increased bacterial clearance. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00572559.

Prognostic Value of the Shock Index Along With Transthoracic Echocardiography in Risk Stratification of Patients With Acute Pulmonary Embolism

The initial clinical presentation and echocardiography have key roles in risk stratification of patients with acute pulmonary embolism (PE). To assess the value of shock index and echocardiographic abnormalities as predictors of in-hospital complications and mortality, echocardiographic features of 159 patients diagnosed with acute PE were reviewed. A shock index > or =1, independent of echocardiographic findings, was associated with increased in-hospital mortality. Regardless of shock index, moderate to severe right ventricular (RV) hypokinesis and a ratio of RV to left ventricular (LV) end-diastolic diameter >1 was significantly associated with in-hospital mortality and demonstrated the best predictive values for short-term outcomes. The sensitivity and negative predictive value of diastolic LV impairment (E/A wave <1), RV hypokinesis, RV/LV >1, and end-diastolic RV diameter >3 cm for in-hospital mortality were 100%. Systolic pulmonary artery pressure (PAP) was higher in patients who died before discharge. A cut-off point >50 mm Hg for systolic PAP was significantly associated with increased in-hospital death. In conclusion, among conventional echocardiographic abnormalities attributed to RV dysfunction (E/A wave <1, RV hypokinesis, RV/LV >1, RV end-diastolic diameter >3 cm, and interventricular septal flattening), moderate to severe RV hypokinesis and RV/LV >1 have better predictive values for short-term outcomes of patients with acute PE. In addition, a shock index > or =1 and systolic PAP >50 mm Hg could also be helpful in the triage of these patients.

SPECT in acute pulmonary embolism

The purpose of this review was to evaluate the accuracy of SPECT in acute pulmonary embolism. Sparse data are available on the accuracy of SPECT based on an objective reference test. Several investigations were reported in which the reference standard for the diagnosis of pulmonary embolism was based in part on the results of SPECT or planar ventilation–perfusion (V/Q) imaging. The sensitivity of SPECT in all but one investigation was at least 90%, and specificity also was generally at least 90%. The sensitivity of SPECT in 4 of 5 investigations was higher than that of planar V/Q imaging. The specificity of SPECT was generally higher, equal, or only somewhat lower than that of planar V/Q imaging. Most investigators reported nondiagnostic SPECT V/Q scans in no more than 3% of cases. Methods of obtaining SPECT images, methods of obtaining planar V/Q images, and the criteria for interpretation varied. The general impression is that SPECT is more advantageous than planar V/Q imaging.

Challenges in the Diagnosis Acute Pulmonary Embolism

The state of the art of diagnostic evaluation of hemodynamically stable patients with suspected acute pulmonary embolism was reviewed. Diagnostic evaluation should begin with clinical assessment using a validated prediction rule in combination with measurement of D-dimer when appropriate. Imaging should follow only when necessary. Although with 4-slice computed tomography (CT) and 16-slice CT, the sensitivity for detection of pulmonary embolism was increased by combining CT angiography with CT venography, it is not known whether CT venography increases the sensitivity of 64-slice CT angiography. Methods to reduce the radiation exposure of CT venography include imaging only the proximal leg veins (excluding the pelvis) and obtaining discontinuous images. Compression ultrasound can be used instead. In young women, radiation of the breasts produces the greatest risk of radiation-induced cancer. It may be that scintigraphy is the imaging test of choice in such patients, but this pathway should be tested prospectively. A patient-specific approach to the diagnosis of pulmonary embolism can be taken safely in hemodynamically stable patients to increase efficiency and decrease cost and exposure to radiation.