摘要:

ObjectiveInhibition of tumor necrosis factor (TNF) or interleukin 1 (IL-1) alone has not improved sepsis survival in human clinical trials; therefore, it has been suggested that blockade of both may be successful. We tested whether combination immunotherapy would improve survival in mice subjected to a lethal lipopolysaccharide (LPS) challenge or the sepsis model of cecal ligation and puncture.DesignMice were treated with the combination immunotherapy and challenged with either a lethal dose of lipopolysaccharide or a septic challenge induced by cecal ligation and puncture.SettingUniversity research laboratory.SubjectsAdult, female Balb/c mice.InterventionsMice were treated with the combination of the IL-1 receptor antagonist plus a polyethylene glycol-linked dimer of the TNF soluble receptor.Measurements and Main ResultsLPS lethality was reduced in the treated mice with a decrease in biologically active TNF in the plasma and peritoneal fluid. In the cecal ligation and puncture (CLP) model of sepsis, this combination immunotherapy for 1 day decreased plasma and peritoneal levels of IL-6 and the murine chemokines KC and MIP-2. However, treatment did not result in a reduction in the hypothermia or peripheral blood alterations that occur after CLP, and the 1-day therapy did not result in an improvement in survival. In contrast, when combination immunotherapy was extended to 3 days there was a significant improvement in survival.ConclusionsThese data demonstrate that inhibition of both TNF and IL-1 will decrease the lethality of sepsis initiated by CLP if the combination immunotherapy is provided for a sufficient amount of time.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveDuring spontaneous circulation, nonspecific inhibition of nitric oxide synthase by NG-nitro-l-arginine methyl ester (L-NAME) increases systemic vascular resistance and, therefore, mean arterial pressure. If this effect can be extrapolated to cardiopulmonary resuscitation (CPR), administering L-NAME during CPR may be beneficial by maintaining or even improving coronary perfusion pressure, and hence successful defibrillation.DesignProspective, randomized laboratory investigation using an established porcine model with instrumentation for hemodynamic variables, blood gases, and defibrillation attempt.SettingUniversity medical center experimental laboratory.SubjectsTen domestic pigs.InterventionsAfter 4 mins of ventricular fibrillation, ten animals were randomly assigned to receive L-NAME (25 mg/kg; n = 5) or saline placebo (n = 5) (given in two doses) after 3 and 13 mins of CPR, respectively. Defibrillation was provided 5 mins after the second dose of active drug or placebo.Measurements and Main ResultsMean ± sem coronary perfusion pressure was significantly (p< .05) higher 90 secs (27 ± 3 vs. 17 ± 3 mm Hg), 10 mins (28 ± 3 vs. 14 ± 2 mm Hg), and 15 mins (21 ± 5 vs. 7 ± 3 mm Hg) after the first L-NAME administration compared with saline placebo. Mean ± sem coronary perfusion pressure remained significantly higher 90 secs and 5 mins after the second L-NAME vs. saline placebo administration (19 ± 4 vs. 6 ± 4 mm Hg, and 17 ± 3 vs. 4 ± 4 mm Hg). After 22 mins of cardiac arrest, including 18 mins of CPR, four of five pigs in the L-NAME group were successfully defibrillated, and survived the 60-min postresuscitation phase. In the placebo group, none of five pigs could be defibrillated successfully (p< .05).ConclusionsNonspecific blockade of nitric oxide synthase with L-NAME during CPR was associated with an increase in coronary perfusion pressure and resulted in significantly better initial resuscitation when compared with saline placebo.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo investigate the physiologic effects of exogenous vasopressin as a potential alternative to traditional high-dose catecholamine therapy for septic patients with vascular hyporeactivity to catecholamines.DesignProspective, case-controlled study.SettingIntensive care unit of a university hospital.PatientsVasopressin was infused in 16 critically ill septic patients who remained persistently hypotensive despite infusions of pharmacologic doses of catecholamines.InterventionContinuous intravenous infusion of vasopressin at 0.04 units/min for 16 hrs, in place of escalating the amount of catecholamines being infused.Measurements and Main ResultsAfter administration of vasopressin, systemic vascular resistance and mean arterial pressure were immediately and significantly increased in comparison with the values obtained just before vasopressin. When the vasopressin infusions were discontinued, mean arterial pressure decreased immediately and dramatically. We did not detect any obvious adverse cardiac effects during the vasopressin infusions. Vasopressin had no effect on other hemodynamic parameters or any of the metabolic parameters studied, including measures of oxygenation, plasma glucose, or electrolytes. Urine output increased significantly during the administration of vasopressin, although this effect may be nonspecific. Lactate concentrations decreased, particularly in the survival group, but the decreases were not significant. Overall survival was 56%.ConclusionsLow-dose vasopressin infusions increased mean arterial pressure, systemic vascular resistance, and urine output in patients with vasodilatory septic shock and hyporesponsiveness to catecholamines. The data indicate that low-dose vasopressin infusions may be useful in treating hypotension in these patients.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine the ability of somatosensory evoked potentials (SEP) compared with clinical findings to monitor and predict recovery in patients suffering from closed head injury with predominantly diffuse axonal injury (DAI).DesignProspective cohort study.SettingNeurologic intensive care unit (ICU) of a university hospital.PatientsSerial SEP recordings were obtained from 31 consecutive patients with closed head injury. The first SEP was recorded within 48 hrs after trauma, followed by recordings after another 2 days, after which the time interval for each consecutive recording was doubled. Clinical examinations were performed every 6 hrs during the ICU stay and daily after transfer to a general neurologic ward.InterventionsNone.Measurements and Main ResultsTwenty-three of 31 patients demonstrated pathologic SEP findings at initial examination. Of these patients, 11 recovered clinically, two remained vegetative, and ten died. In all 11 patients with clinical recovery, SEP also recovered. In 8 of 31 patients, initial SEPs were normal and remained normal until discharge, all eight had a good outcome. Initial SEP findings were related with outcome at 6 months (p= .02), and follow-up studies increased the predictive value of SEP studies (p= .009). Other factors related to outcome included age, severity of DAI, and length of ICU/hospital stay. In the 11 patients with SEP and clinical recovery, early (day 2) and late (≥2 months) recovery was documented. Early and reliable SEP indicators of improvement included N20-P25-Amplitudes (mean recovery, 8.5 days) and central conduction time (9.6 days). Pupillary light reaction (6.4 days), Babinski reflex (12.4 days), and Glasgow Coma Score (9.6 days) were the most valuable clinical findings. Recovery of the Glasgow Coma Score frequently coincided with reduction of sedatives. In most patients, recovery was detected with SEP before clinical recovery (7/11 patients, time difference 1 wk).ConclusionsInitial SEP findings correlate with long-term outcome in patients with closed head injury with DAI. Initial bilaterally absent cortical responses in the SEP reliably predicted death, whereas completely normal SEP findings predicted good long-term outcome. Early recovery after DAI can be detected with serial SEP recordings despite sedative medications. Electrophysiologic recovery frequently precedes clinical recovery.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivePhase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock.DesignMulticenter, double-blind, phase III, placebo-controlled, randomized study.SettingA total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42).PatientsA total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration.InterventionAfter randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided.Measurements and Main ResultsThe primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17–96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor &agr; concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave apvalue of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population.ConclusionLenercept had no significant effect on mortality in the study population.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine the influence of changes in acute physiology scores (APS) and other patient characteristics on predicting intensive care unit (ICU) readmission.DesignSecondary analysis of a prospective cohort study.SettingSingle large university medical intensive care unit.PatientsA total of 4,684 consecutive admissions from Janu-ary 1, 1994, to April 1, 1998, to the medical ICU.InterventionsNone.Measurements and Main ResultsThe independent influence of patient characteristics, including daily APS, admission diagnosis, treatment status, and admission location, on ICU readmission was evaluated using logistic regression. After accounting for first ICU admission deaths, 3,310 patients were “at-risk” for ICU readmission and 317 were readmitted (9.6%). Hospital mortality was five times higher (43% vs. 8%;p< .0001), and length of stay was two times longer (16 ± 16 vs. 32 ± 28 days;p< .001) in readmitted patients. Mean discharge APS was significantly higher in the readmitted group compared with the not readmitted group (43 ± 19 vs. 34 ± 18;p> .01). Significant independent predictors of ICU readmission included discharge APS >40 (odds ratio [OR] 2.1; 95% confidence interval [CI] 1.6–2.7;p< .0001), admission to the ICU from a general medicine ward (Floor) (OR 1.9; 95% CI 1.4–2.6;p< .0001), and transfer to the ICU from other hospital (Transfer) (OR 1.7; 95% CI 1.3–2.3;p< .01). The overall model calibration and discrimination were (H-L &khgr;2 = 3.8,df= 8;p= .85) and (receiver operating characteristic 0.67), respectively.ConclusionsPatients readmitted to medical ICUs have significantly higher hospital lengths of stay and mortality. ICU readmissions may be more common among patients who respond poorly to treatment as measured by increased severity of illness at first ICU discharge and failure of prior therapy at another hospital or on a general medicine unit. Tertiary care ICUs may have higher than expected readmission rates and mortalities, even when accounting for severity of illness, if they care for significant numbers of transferred patients.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveWhen a cancer patient becomes critically ill, mechanical ventilation (MV) is often considered futile. However, recent studies have found that outcomes of critically ill cancer patients have been improving over the years and that classic predictors of high mortality have lost their relevance.DesignWe retrospectively determined outcomes and predictors of 30-day mortality in 237 mechanically-ventilated cancer patients admitted to the intensive care unit (ICU).PatientsThe 132 (55.7%) patients who were admitted between 1990 and 1995 were compared with 105 (44.3%) patients who were admitted between 1996 and 1998. The malignancy was leukemia/lymphoma in 119 (50.3%) patients, myeloma in 50 (21%), and a solid tumor in 68 (28.7%). Forty-two (17.7%) patients had bone marrow transplantation, and 91 (38.4%) were neutropenic. Median Simplified Acute Physiology Score II (SAPS II) was 58 (range, 40–75). Reasons for MV were acute hypoxemic respiratory failure in 148 (62.5%) patients, coma in 54 (22.8%), and cardiogenic pulmonary edema in 35 (14.7%). Conventional MV was used first in 189 (79.8%) patients, and noninvasive MV (NIMV) was used in 48 (20.2%). Overall mortality rate was 72.5% (172 deaths).ResultsLogistic regression identified three variables associated with mortality: ICU admission between 1996 and 1998 (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.12–0.50) and the use of NIMV (OR, 0.34; 95% CI, 0.16–0.73) were protective, and the SAPS II was aggravating (OR, 1.04 per point; 95% CI, 1.02–1.06). To better define the impact of NIMV, we performed a pairwise-matched exposed–unexposed analysis. Forty-eight patients who did and 48 who did not receive NIMV as the first ventilation method were matched for SAPS II, type of malignancy, and period of ICU admission. Crude ICU mortality rates from exposed patients and controls were 43.7% and 70.8%, respectively. NIMV remained protective from mortality after adjustment for matching variables (OR, 0.31; 95% CI, 0.12–0.82).ConclusionOur results confirm that mortality has improved over the past decade in critically ill cancer patients, even those who require MV, and suggest that this may be, in part, because of a protective effect of NIMV.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether serial, noninvasive assessment of afterload, contractility, and Doppler-derived cardiac output reliably detects variations in cardiac function in unstable pediatric patients.DesignProspective, blinded clinical trial.SettingThe pediatric intensive care unit at Massachusetts General Hospital.PatientsFourteen critically ill pediatric patients.InterventionsPediatric patients meeting criteria for hemodynamic instability underwent serial echocardiograms every 6 hrs until they met exit criteria, generating 75 studies.Measurements and Main ResultsShortening fraction, cardiac index (CI), end-systolic wall stress (ESWS), and corrected velocity of circumferential shortening (Vcfc) were measured in each patient. Data points were plotted as a stress-velocity relationship, compared with published normal values, then correlated with changes in vital signs and pharmacologic interventions. Fourteen of 16 patients who were enrolled completed the study. A strong negative correlation between ESWS and Vcfc was confirmed (p< .001). As an internal measure of validity, Vcfc had a strong positive correlation with CI measurements (p= .012). An increase in dopamine infusion was associated with a fall in ESWS (p= .02), an increase in Vcfc (p= .03), and an increase in the CI as measured by Doppler (p= .035). The infusion of dopamine above renal perfusion levels moved patients from zones of normal or compensated contractility for afterload on a modified stress-velocity relationship to a zone of high contractility for afterload. Urine output was the only clinical index of cardiac function that had a significant correlation with the echocardiographic indices. Hemodynamically unstable patients followed similar patterns of deterioration and recovery on the modified stress-velocity graph. All surviving patients returned to a normal or compensated zone.ConclusionsWall-stress analysis of cardiac function is easily and safely performed on mechanically ventilated pediatric patients with the production of consistently high-quality data. For internal validity, Vcfc and CI measurements were correlated and were strongly positive. Wall-stress indices reliably detected patient deterioration, recovery, and response to changes in dopamine infusion. Patients who failed to return to areas of normal or compensated levels of contractility and afterload did poorly in this study. Noninvasive measures of afterload and contractility appear useful for monitoring cardiac function of critically ill children in an intensive care setting.

ISSN:0090-3493    

出版商:OVID    

年代:2001

数据来源: OVID