Exogenous Surfactant Preserves Lung Function and Reduces Alveolar Evans Blue Dye Influx in a Rat Model of Ventilation-induced Lung Injury

Background: Changes in pulmonary edema infiltration and surfactant after intermittent positive pressure ventilation with high peak inspiratory lung volumes have been well described. To further elucidate the role of surfactant changes, the authors tested the effect of different doses of exogenous surfactant preceding high peak inspiratory lung volumes on lung function and lung permeability.

Methods: Five groups of Sprague-Dawley rats (n = 6 per group) were subjected to 20 min of high peak inspiratory lung volumes. Before high peak inspiratory lung volumes, four of these groups received intratracheal administration of saline or 50, 100, or 200 mg/kg body weight surfactant; one group received no intratracheal administration. Gas exchange was measured during mechanical ventilation. A sixth group served as nontreated, nonventilated controls. After death, all lungs were excised, and static pressure-volume curves and total lung volume at a transpulmonary pressure of 5 cm H2 O were recorded. The Gruenwald index and the steepest part of the compliance curve (Cmax) were calculated. A bronchoalveolar lavage was performed; surfactant small and large aggregate total phosphorus and minimal surface tension were measured. In a second experiment in five groups of rats (n = 6 per group), lung permeability for Evans blue dye was measured. Before 20 min of high peak inspiratory lung volumes, three groups received intratracheal administration of 100, 200, or 400 mg/kg body weight surfactant; one group received no intratracheal administration. A fifth group served as nontreated, nonventilated controls.

Results: Exogenous surfactant at a dose of 200 mg/kg preserved total lung volume at a pressure of 5 cm H2 O, maximum compliance, the Gruenwald Index, and oxygenation after 20 min of mechanical ventilation. The most active surfactant was recovered in the group that received 200 mg/kg surfactant, and this dose reduced minimal surface tension of bronchoalveolar lavage to control values. Alveolar influx of Evans blue dye was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant.     

External validation of the Canadian CT Head Rule and the New Orleans Criteria for CT scanning in patients with minor head injury

Context  Two decision rules for indications of computed tomography (CT) in patients with minor head injury, the Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC), suggest that CT scanning may be restricted to patients with certain risk factors, which would lead to important reductions in the use of CT scans. Objective  To validate and compare these 2 published decision rules in Dutch patients with head injuries. Design, Setting, and Patients  A prospective multicenter study conducted between February 11, 2002, and August 31, 2004, in 4 university hospitals in the Netherlands of 3181 consecutive adult patients with minor head injury who presented with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. Main Outcome Measures  Primary outcome was any neurocranial traumatic finding on CT scan. Secondary outcomes were neurosurgical intervention and clinically important CT findings. Sensitivity and specificity were estimated for each outcome for the CCHR and the NOC, using both rules as originally derived and also as adapted to apply to an expanded patient population. Results  Of 3181 patients with a GCS score of 13 to 15, neurosurgical intervention was performed in 17 patients (0.5%); neurocranial traumatic CT findings were present in 312 patients (9.8%). Sensitivity for neurosurgical intervention was 100% for both the CCHR and the NOC. The NOC had a higher sensitivity for neurocranial traumatic findings and for clinically important findings (97.7%-99.4%) than did the CCHR (83.4%-87.2%). Specificities were very low for the NOC (3.0%-5.6%) and higher for the CCHR (37.2%-39.7%). The estimated potential reduction in CT scans for patients with minor head injury would be 3.0% for the adapted NOC and 37.3% for the adapted CCHR. Conclusions  For patients with minor head injury and a GCS score of 13 to 15, the CCHR has a lower sensitivity than the NOC for neurocranial traumatic or clinically important CT findings, but would identify all cases requiring neurosurgical intervention, and has greater potential for reducing the use of CT scans.      

Association of early CT abnormalities, infarct size, and apparent diffusion coefficient reduction in acute ischemic stroke

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) imaging is more sensitive for early ischemia than CT, and apparent diffusion coefficient (ADC) mapping permits quantification of the severity of cytotoxic edema. We examined the relationship between early CT findings, ischemic lesion volume on DW images, and edema subtype. METHODS: Patients in whom early signs of ischemia were detected on baseline CT scans were scored CT positive. Baseline DW lesion volumes were compared between the CT-positive and CT-negative patients. In CT-positive patients, we outlined the CT-positive part of the DW lesion and transferred these regions of interest to the corresponding DW sections. The ADC values of the outlined CT-positive areas were then compared with the ADC values of the CT-negative areas within patients. Lesions with significantly increased T2 hyperintensity were excluded to correct for the effect of early vasogenic edema on ADC measurements. RESULTS: Twenty-four patients with cerebral ischemia in whom both CT and DW imaging were performed within 8 hours of symptom onset were entered into the study. Patients with early CT signs of infarction (n = 12) had significantly larger DW lesion volumes than did patients without early CT abnormalities (mean volume, 62.8 versus 14.6 mL; P =. 002). In patients displaying early CT abnormalities, CT-positive regions of the DW lesion had lower relative ADC (rADC) values than did the CT-negative regions, when lesions with significant T2 hyperintensity were excluded (mean rADC, 0.65 versus 0.75; P =.037). CONCLUSION: These findings support the hypothesis that early CT signs of infarction indicate more extensive and severe cerebral ischemia, as reflected by lower ADC.     

Quality of care in stroke prevention: results of an audit study among general practitioners

BACKGROUND: In identifying opportunities to improve the quality of stroke prevention in general practice, insight in areas of suboptimal care is essential. This study investigated the quality of care in stroke prevention in general practice and its relation to the occurrence of stroke. METHODS: Retrospective case-based audit with guideline-based review criteria and final judgment of suboptimal care by an expert panel. RESULTS: A total of 292 stroke patients were identified through stroke registers of two main referral hospitals for stroke in Rotterdam. The general practitioners (GPs) (n = 95) of these patients were approached. The overall response rate from GPs was 81%, and a total of 193 patients from 77 GPs were included in the study. Data on the process of care at patient level were collected by chart review and by structured interviews with GPs during site visits. All cases were presented to a six-member panel of GPs and neurologists. In 44% of the cases, suboptimal care was identified (31% judged as possibly or likely failing to prevent stroke). Of the total number of identified shortcomings, 52% was related to inadequate hypertension control, particularly lack of follow-up after established hypertension. Another 17% of identified shortcomings concerned inadequate cardiovascular risk assessment. CONCLUSIONS: A substantial number of shortcomings in care, particularly in the domain of hypertension control and the assessment of patient's risk profiles for cardiovascular disease (CVD), were identified. This study suggests that improving preventive care delivery in general practice could reduce the occurrence of stroke.     

Methods to assess intended effects of drug treatment in observational studies are reviewed

BACKGROUND AND OBJECTIVE: To review methods that seek to adjust for confounding in observational studies when assessing intended drug effects. METHODS: We reviewed the statistical, economical and medical literature on the development, comparison and use of methods adjusting for confounding. RESULTS: In addition to standard statistical techniques of (logistic) regression and Cox proportional hazards regression, alternative methods have been proposed to adjust for confounding in observational studies. A first group of methods focus on the main problem of nonrandomization by balancing treatment groups on observed covariates: selection, matching, stratification, multivariate confounder score, and propensity score methods, of which the latter can be combined with stratification or various matching methods. Another group of methods look for variables to be used like randomization in order to adjust also for unobserved covariates: instrumental variable methods, two-stage least squares, and grouped-treatment approach. Identifying these variables is difficult, however, and assumptions are strong. Sensitivity analyses are useful tools in assessing the robustness and plausibility of the estimated treatment effects to variations in assumptions about unmeasured confounders. CONCLUSION: In most studies regression-like techniques are routinely used for adjustment for confounding, although alternative methods are available. More complete empirical evaluations comparing these methods in different situations are needed.