摘要:

ObjectiveRecent estimates of acute respiratory distress syndrome (ARDS) incidence have varied from 1.3 to 22 per 100,000 person years (105person·years); the incidence of acute lung injury (ALI) has varied from 17.9 to 34 cases per 105person·years. Potential reasons for this wide range include differences in the definition of the syndrome, in the populations sampled, and in the assumptions made to estimate incidence. We hypothesized that careful, prospective, protocol-driven case identification that included the milder hypoxemia criterion for ALI would yield incidence numbers greater than previously reported.DesignProspective cohort study with extrapolation to the U.S. population.SettingNational Heart, Lung, and Blood Institute-sponsored ARDS Network composed of 20 hospitals.PatientsAs part of the National Institutes of Health-sponsored ARDS network, 20 hospitals prospectively identified patients with ALI from 1996 to 1999. Screening logs from this study were used to estimate ALI rates per intensive care unit (ICU) bed per year. We used the registry and data from the American Hospital Association to estimate the incidence of ALI in the United States.InterventionsNone.Measurements and Main ResultsThe ALI per ICU bed incidence in the ARDS network registry varied from 0.7 to 5.8 cases of ALI per ICU bed per year with an average of 2.2 cases of ALI per ICU bed per year. We tested the robustness of the incidence estimate by performing a variety of sensitivity analyses. When we used the conservative assumptions that the ARDS network screening logs were complete at each of the participating hospitals and that ALI cases are limited to academic hospitals with ≥20 adult ICU beds, the incidence of ALI in adults in the United States is 22.4 cases per 105person·years. Under the less conservative assumption that ALI cases occurred only at hospitals with ≥20 ICU beds, regardless of their academic status, the incidence of ALI in the United States is estimated at 64.2 cases per 105person·years.ConclusionsBased on this analysis, which used prospective clinical trial screening data and conservative assumptions about where patients with ALI are cared for, the incidence of ALI in the United States appears to be higher than previously reported.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivePlatelet-activating factor (PAF) is a potent proinflammatory mediator implicated in the pathogenesis of both severe sepsis and acute respiratory distress syndrome. One of the regulatory pathways for PAF involves degradation to the inactive metabolite lyso-PAF by the enzyme PAF acetylhydrolase (PAF-AH). Because reduced concentrations of the natural form of PAF-AH have been reported in septic patients, the present study was conducted to determine whether treatment with recombinant human PAF-AH (rPAF-AH, Pafase) was safe when administered after the onset of severe sepsis and whether it decreases the prevalence of acute respiratory distress syndrome and 28-day all-cause mortality.DesignA prospective, randomized, double-blind, placebo-controlled, multicenter trial.SettingThirty-three medical and surgical intensive care units located in the United States.PatientsA total of 127 patients with severe sepsis, but without established acute respiratory distress syndrome, were enrolled in the study. Randomization occurred within 12 hrs of the onset of severe sepsis. Patients then received 1.0 mg/kg rPAF-AH (n = 45), 5.0 mg/kg rPAF-AH (n = 39), or placebo (n = 43) administered intravenously, once daily, for five consecutive days.Measurements and Main ResultsDemographic and baseline clinical characteristics of the three treatment groups were similar, except for a significantly higher prevalence of respiratory tract infections as the cause of severe sepsis in patients treated with 1.0 mg/kg rPAF-AH. There were no treatment-related deaths, and the overall prevalence of adverse events was similar among rPAF-AH-treated and placebo-treated patients. There were no significant differences in the prevalence of acute respiratory distress syndrome among the three treatment groups. However, 28-day all-cause mortality was 21% in the 1.0 mg/kg rPAF-AH group, 28% in the 5.0 mg/kg rPAF-AH group, and 44% in the placebo group (overall chi-squarep= .07; 1.0 mg/kg rPAF-AH vs. placebo,p= .03). A trend toward reduced multiple organ dysfunction also was observed in the 1.0 mg/kg rPAF-AH group compared with the placebo group (p= .11).ConclusionThe results from this study indicate that rPAF-AH was well tolerated and should be pursued as a potential new treatment to decrease mortality in patients with severe sepsis.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveHealth outcomes may be influenced by organizational and management characteristics. We hypothesized that neonatal intensive care unit managerial practices and organizational processes could affect outcomes of births 500–1499 g, and we assessed this in eight neonatal intensive care units.DesignMultiple-center cohort.SettingEight acute care neonatal intensive care units in Washington, DC.PatientsInfants weighing 500–1499 g, born from October 1, 1994, to February 19, 1997, to a resident of Washington, DC.InterventionsNone.Measurements and Main ResultsOutcomes included 28-day survival/death, bronchopulmonary dysplasia (BPD), periventricular/intraventricular hemorrhage or periventricular leukomalacia (PIVH/PVL), retinopathy of prematurity (ROP), length of hospital stay, and days of mechanical ventilation. Managerial practices and organizational processes were rated by nurses (n = 218), physicians (n = 73), and respiratory therapists (n = 77). Risk-adjusted logistic and linear mixed models were used to assess the association of outcomes with the caregiver ratings. A lower incidence of PIVH/PVL was associated with better overall scores (p= .0036) and better subscores for leadership (p< .0001), coordination (p= .047), and conflict resolution (p= .020). Better values of the respiratory therapists’, nurses’, and physicians’ scores were associated with lower mortality rates (p= .045) and BPD (p= .0057), PIVH/PVL (p< .0001), and ROP (p= .049), respectively. In multivariate analysis, the joint effects of the professional groups’ scores were associated with the incidence of PIVH/PVL (p= .0047); the nurses’ scores were associated with lower incidence of PIVH/PVL (p= .0051). The association between the respiratory therapists’ scores and lower mortality rate (p= .025) also remained significant in multivariate analysis.ConclusionsWe found that the organizational processes and managerial practices as rated by healthcare professionals in neonatal intensive care units were associated with the development of mortality and chronic, severe morbidity. We did not identify specific processes or practices that accounted for our results.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo evaluate whether the up-regulation in sepsis-induced gut epithelial apoptosis is balanced by an increase in intestinal proliferation and to assess mechanisms affecting the gut’s regenerative response to overwhelming infection.DesignProspective, randomized, controlled study.SettingAnimal laboratory in a university medical center.InterventionsMice were subjected to intratracheal injection ofPseudomonas aeruginosaand killed between 1.5 and 24 hrs after induction of pneumonia-induced sepsis to assess for gut epithelial proliferation and cell division and for apoptosis. Animals were compared with sham-operation controls, septic transgenic mice that overexpress Bcl-2 throughout their small intestinal epithelium, and septic p53−/-mice.Measurements and Main ResultsProliferation and cell division were assessed by measuring S-phase and M-phase cells in intestinal crypts. The number of S-phase cells showed a progressive decline at all time points measured, with a 5-fold decrease in proliferation between control animals and septic mice 24 hrs after intratracheal injection of pathogenic bacteria (p< .0001). In contrast, cells in M-phase remained constant for the first 12 hrs after the onset of sepsis, but increased nearly 50% at 24 hrs after instillation ofP. aeruginosa(p< .005). Both the decrease in S-phase cells and the increase in M-phase cells were partially suppressible in Bcl-2 overexpressors, but cellular proliferation and division were similar between septic p53−/-and p53+/+mice. Crypt apoptosis was increased at all time points, with maximal death occurring between 12 and 24 hrs.ConclusionsSepsis fromP. aeruginosapneumonia induces a p53-independent decrease in gut epithelial proliferation. Despite an increase in sepsis-induced intestinal apoptosis, there is no compensatory increase in intestinal epithelial proliferation, and there is evidence of a cell cycle block with an accumulation of cells in M-phase. Decreasing gut apoptosis by overexpression of Bcl-2 is associated with a partial reversal of the effect of sepsis on the cell cycle.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ContextComparison of outcome among intensive care units (ICUs) requires risk adjustment for differences in severity of illness and risk of death at admission to the ICU, historically obtained by costly chart review and manual data entry.ObjectiveTo accurately estimate patient risk of death in the ICU using data easily available in hospital electronic databases to permit automation.Design and SettingCohort study to develop and validate a model to predict mortality at hospital discharge using multivariate logistic regression with a split derivation (17,731) and validation (11,646) sample formed from 29,377 consecutive first ICU admissions to medical, cardiac, and surgical ICUs in 17 Veterans’ Health Administration hospitals between February 1996 and July 1997.Main Outcome MeasuresMortality at hospital discharge adjusted for age, laboratory data, diagnosis, source of ICU admission, and comorbid illness.ResultsThe overall hospital death rate was 11.3%. In the validation sample, the model separated well between survivors and nonsurvivors (area under the receiver operating characteristic curve = 0.885). Examination of the observed vs. the predicted mortality across the range of mortality showed the model was well calibrated.ConclusionsAutomation could broaden access to risk adjustment of ICU outcomes with only a small trade-off in discrimination. Broader use might promote valid evaluation of ICU outcomes, encouraging effective practices and improving ICU quality.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundLipopolysaccharide (LPS), the major glycolipid component of Gram-negative bacterial outer membranes, is a potent endotoxin responsible for many of the directly or indirectly induced symptoms of infection. Lipoproteins (in particular, high-density lipoproteins) sequester LPS, thereby acting as a humoral detoxification mechanism.PatientsDifferences in the lipoprotein composition in human plasma and lymph of a control patient group (n = 5) without systemic inflammatory response syndrome (non-SIRS/MOF) and patients with SIRS and multiple organ failure (MOF, n = 9) were studied. The LPS binding capacity of the lipoproteins in SIRS/MOF and non-SIRS/MOF patients was investigated by rechallenge of the plasma and lymph with fluorescently labeled LPSex vivo. The lipoprotein composition was analyzed using immunochemical techniques and high-performance gel permeation chromatography.ResultsIn the non-SIRS/MOF patient group, plasma and lymph levels of apolipoprotein A-I (600 and 450 mg/L, respectively), apolipoprotein B (440 and 280 mg/L, respectively), total cholesterol (2.88 and 1.05 mM, respectively), and total triglycerides (0.67 and 0.97 mM, respectively) were observed. In the SIRS/MOF group, a decrease of apolipoprotein A-I (−55% in plasma and lymph), a decrease of apolipoprotein B (−43% in plasma and −38% in lymph), and a decrease of total cholesterol levels (−54% in plasma and −37% in lymph) were demonstrated. However, the triglyceride levels in the SIRS/MOF group showed a 30% increase in plasma and a 47% decrease in lymph compared with the non-SIRS/MOF patients. In SIRS/MOF patients, a 2.8-fold increase in plasma and a 1.8-fold increase in lymph of the LPS low-density lipoprotein/high-density lipoprotein ratio was observed, indicating that the relative LPS binding capacity of the lipoproteins in the SIRS/MOF patient group showed a trend to be shifted mainly toward low-density lipoproteins. Furthermore, in plasma and lymph of four SIRS/MOF patients, a novel cholesterol-containing high-density lipoprotein–like particle was found that barely had LPS binding capacity (<5%).ConclusionsIn the SIRS/MOF patients, the changes in lipoprotein composition in lymph are a reflection of those in plasma, except for the triglyceride levels. In comparison with the non-SIRS/MOF patients, the SIRS/MOF patients show a shifted LPS binding capacity of high-density lipoproteins toward low-density lipoproteins in plasma and in lymph. Moreover, in plasma and lymph, novel cholesterol-containing particles, resembling high-density lipoprotein, were identified in the SIRS/MOF patient group.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine the blood discard volume, as a multiple of deadspace, that is required for accurate arterial blood gas and electrolyte testing from arterial catheters.DesignProspective, controlled, crossover trial.SettingEighteen-bed intensive care unit of a metropolitan teaching hospital.PatientsA total of 84 critically ill patients with a 20-gauge, radial arterial cannulae, pressure monitoring transducer set, and stable oxygenation.InterventionsSystem deadspace (priming volume from sampling port to catheter tip) was established. Patients had six 0.5-mL arterial blood samples taken sequentially in random order using discard volumes of 1, 1.5, 2, 2.3, and 3.6 times the deadspace (experimental values) and 5.5 times the deadspace (control).Measurements and Main ResultsSamples were analyzed for Pao2, Sao2, pH, Paco2, HCO3−, Na+, and K+. We performed repeated-measures analysis of variance withpost hoclinear contrasts and compared mean experimental and control values. The smallest discard volumes that provided measurements that were statistically equal to control were twice the deadspace (Pao2,p= .563; Sao2,p= .371) and 3.6 times the deadspace (pH,p= .107; Paco2,p= .519; HCO3−,p= .10). All discard volumes tested provided results that were statistically different from control for Na+(p< .003) and K+(p< .001).ConclusionsMany results were statistically different from control, although the actual discrepancies were very small. At clinically relevant levels of measurement, there was minimal variation between values obtained after a discard volume of twice the deadspace and control values. The level of error was clinically acceptable and within or close to the precision limits of the blood gas analyzer. Slight fluctuation in patient variables during sampling could also have contributed to the error. A blood discard volume of twice the deadspace is recommended for all variables. This will provide clinically accurate results and avoid the deleterious effects of unnecessary blood loss.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo assess the effects of different doses of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in patients with septic shock.DesignProspective, randomized, open-label study.SettingA 31-bed, medicosurgical intensive care unit of a university hospital.PatientsConvenience sample of 20 patients with septic shock, separated into two groups according to whether (moderate shock group, n = 10) or not (severe shock, n = 10) dopamine alone was able maintain mean arterial pressure >65 mm Hg.InterventionsDopamine was progressively withdrawn and replaced successively by norepinephrine and then epinephrine (the order of the two agents was randomly determined) to maintain mean arterial pressure constant (moderate shock) or to increase mean arterial pressure above 65 mm Hg (severe shock).Measurements and Main ResultsSystemic circulation (pulmonary artery catheter) and splanchnic circulation (indocyanine green dilution and hepatic vein catheter) and gastric mucosal Pco2(gas tonometry) were measured during dopamine (moderate shock only), norepinephrine, and epinephrine administration (both groups). Data were analyzed with nonparametric tests and are presented as median [percentiles 25–75]. In moderate shock, cardiac index was similar to dopamine and norepinephrine (3.1 [2.7–3.8] vs. 2.9 [2.7–4.1] L/min·m2,p= nonsignificant) but greater with epinephrine (4.1 [3.5–4.4]p< .01 vs. dopamine and norepinephrine). Splanchnic blood flow was similar with the three agents (732 [413–1483] vs. 746 [470–1401] vs. 653 [476–1832] mL/min·m,p= nonsignificant). The gradient between mixed-venous and hepatic venous oxygen saturations was lower with dopamine than with norepinephrine and epinephrine, but the Pco2gap was similar with the three agents. In severe shock, cardiac index was higher, but splanchnic blood flow was lower, with epinephrine than with norepinephrine (4.6 [3.7–5.3] vs. 3.4 [3.0–4.1] L/min·m2,p< .01 and 860 [684–1334] vs. 977 [806–1802] mL/min·m2,p< .05, respectively). Epinephrine increased the mixed-venous and hepatic venous oxygen saturation gradient but did not alter Pco2gap.ConclusionsDopamine and norepinephrine have similar hemodynamic effects, but epinephrine can impair splanchnic circulation in severe septic shock.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo identify the incidence of secondary adrenal insufficiency in severe sepsis.DesignProspective clinical trial testing 100 patients with a 250-&mgr;g adrenocorticotropic hormone (ACTH) stimulation test.SettingCounty-university teaching hospital.PatientsOne hundred patients with sepsis and septic shock. Forty patients had bacteremia and 17% shock.InterventionsACTH, cortisol, aldosterone, and electrolyte concentrations were measured at baseline. Cortisol and aldosterone were measured 30 and 60 mins after ACTH (250 &mgr;g).Measurements and Main ResultsNine of the 100 patients (9%) failed the ACTH stimulation test (all serum cortisol <20 &mgr;g/dL). The 91 patients with sepsis began with a serum cortisol at 29.3 ± 2.5, and it increased to 40.1 ± 2.6 and 46.9 ± 2.7 &mgr;g/dL at times 30 and 60 mins, respectively. Serum cortisol in nine septic patients who failed the ACTH stimulation test had an initial concentration of 11.3 ± 1.8 &mgr;g/dL, and it increased at time 30 mins to 14.0 ± 1.9 &mgr;g/dL and at 60 mins to 15.7 ± 1.8 &mgr;g/dL. Four of the nine patients had secondary adrenal insufficiency as determined by a normal aldosterone response to ACTH. The remaining five patients had an absent aldosterone response to ACTH and baseline ACTH concentrations that were not elevated, suggesting adrenal dysfunction. Serum sodium (128 ± 4 vs. 138 ± 1 mmol/L,p< .05) and glucose concentrations (121 ± 20 vs. 163 ± 11 mg/dL,p< .05) were reduced in the nine patients. Of the four patients with secondary adrenal insufficiency, two had a history of amenorrhea after birth of their children many years earlier.ConclusionsThese data demonstrate that 9% of adults with sepsis fail the ACTH stimulation test due to a mixture of etiologies. A reduced sodium or glucose concentration may be helpful in identifying glucocorticoid (adrenal) insufficiency in patients with sepsis.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID