摘要:

ObjectiveThe purpose of this study was to determine the role of nitric oxide and poly(ADP-ribose) synthase on impaired mitochondrial function in septic shock.DesignHuman umbilical vein endothelial cells were incubated with serum from ten healthy controls, 20 patients with septic shock, and seven critically ill patients who were not septic. The experiment was repeated after pretreatment with 3-aminobenzamide, a poly(ADP-ribose) synthase inhibitor, orNG-methyl-l-arginine, a nonspecific nitric oxide synthase inhibitor.MeasurementsMitochondrial respiration was measured using a modified MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay.SettingResearch laboratory.Main ResultEndothelial cell mitochondrial respiration was significantly depressed by septic serum and averaged 61% ± 6% of control values (p< .05). Incubation with septic serum as compared with control serum also significantly decreased cellular adenosine triphosphate levels (6.7 ± 1.2 nM vs. 13.5 ± 1.9 nM,p< .01). The level of mitochondrial respiration in endothelial cells exposed to septic serum did not correlate with arterial lactate concentration but was correlated with both cardiac output (rs= .52,p< .05) and mixed venous oxygen saturation (rs= .61,p< .05). Pretreatment withNG-methyl-l-arginine significantly increased mitochondrial respiration in endothelial cells treated with septic serum from 63% ± 6% of normal to 88% ± 6% (p< .05) of normal values. Similarly, pretreatment with 3-aminobenzamide increased mitochondrial respiration in endothelial cells treated with septic serum from 64% ± 6% to 100% ± 4% (p< .01) of normal values. Endothelial cells incubated with serum from nonseptic critically ill patients did not demonstrate a significant decrease in mitochondrial respiration.ConclusionIn vitromitochondrial respiration was significantly depressed by septic serum. The addition ofNG-methyl-l-arginine, a nitric oxide synthase inhibitor, and 3-aminobenzamide, a blocker of the poly(ADP-ribose) synthase pathway, significantly attenuated this suppression. These data suggest that nitric oxide and poly(ADP-ribose) synthase activation may play an important role in the inhibition of mitochondrial respiration in septic shock.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesMaintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients. Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits.DesignA prospective, randomized, controlled trial.SettingA 56-bed predominantly surgical intensive care unit in a tertiary teaching hospitalPatients and InterventionA total of 1,548 patients were randomly assigned to either strict normalization of blood glucose (80–110 mg/dL) with insulin infusion or the conventional approach, in which insulin is only given to maintain blood glucose levels at 180–200 mg/dL.Measurements and Main ResultsIt was feasible and safe to achieve and maintain blood glucose levels at <110 mg/dL by using a titration algorithm. Stepwise linear regression analysis identified body mass index, history of diabetes, reason for intensive care unit admission, at-admission hyperglycemia, caloric intake, and time in intensive care unit as independent determinants of insulin requirements, together explaining 36% of its variation. With nutritional intake increasing from a mean of 550 to 1600 calories/day during the first 7 days of intensive care, normoglycemia was reached within 24 hrs, with a mean daily insulin dose of 77 IU and maintained with 94 IU on day 7. Insulin requirements were highest and most variable during the first 6 hrs of intensive care (mean, 7 IU/hr; 10% of patients required >20 IU/hr). Between day 7 and 12, insulin requirements decreased by 40% on stable caloric intake. Brief, clinically harmless hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median day 6 (2–14) vs. 0.8% of conventionally treated patients on day 11 (2–10). The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding. Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality (p< .0001), critical illness polyneuropathy (p< .0001), bacteremia (p= .02), and inflammation (p= .0006) but not to prevention of acute renal failure, for which the insulin dose was an independent determinant (p= .03). As compared with normoglycemia, an intermediate blood glucose level (110–150 mg/dL) was associated with worse outcome.ConclusionNormoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines. Metabolic control, as reflected by normoglycemia, rather than the infused insulin doseper se, was related to the beneficial effects of intensive insulin therapy.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine the safety and efficacy of filgrastim (r-metHuG-CSF) in combination with intravenous antibiotics to reduce the rate of mortality in patients with pneumonia and sepsis.DesignThis study was multicenter, double-blind, and randomized.SettingIntensive care unitsPatientsAdult patients with bacterial pneumonia, either acquired or nosocomial, as confirmed by chest radiograph and positive culture or Gram-negative stain, and severe sepsis, defined as sepsis-induced hypotension or organ dysfunction.InterventionsStandard antibiotic therapy with or without filgrastim (300 &mgr;g/day) or placebo administered as a 30-min intravenous infusion. The study drug was started within 24 hrs of enrollment and was continued for 5 days or until the white blood cell count reached >75.0 × 109cells/L.Measurements and Main ResultsThe primary end point was the occurrence of mortality through day 29; secondary end points included occurrence of subsequent organ dysfunction, time to discharge from intensive care unit, number of days on mechanical ventilatory support, and time to death. Study-related observations were recorded through day 10 and included vital signs, onset of organ dysfunction, clinical laboratory variables, and adverse events. Filgrastim increased the white blood cell count to a median peak of 31.7 × 109cells/L from a baseline of 12.3 × 109cells/L. The two groups were well matched and did not differ significantly with regard to severe adverse events, time to death, occurrence of end-organ dysfunction, days of intensive care unit hospitalization, or days on mechanical ventilatory support. Mortality was low in both treatment groups; the mortality rate in patients with adult respiratory distress syndrome was similar between the two groups.ConclusionsThe addition of filgrastim to the antibiotic and supportive care treatment of patients with pneumonia complicated by severe sepsis appeared to be safe, but not efficacious in reducing mortality rates or complications from this infection.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesThe instruments used for measuring nursing workload in the intensive care unit (e.g., Therapeutic Intervention Scoring System-28) are based on therapeutic interventions related to severity of illness. Many nursing activities are not necessarily related to severity of illness, and cost-effectiveness studies require the accurate evaluation of nursing activities. The aim of the study was to determine the nursing activities that best describe workload in the intensive care unit and to attribute weights to these activities so that the score describes average time consumption instead of severity of illness.DesignTo define by consensus a list of nursing activities, to determine the average time consumption of these activities by use of a 1-wk observational cross-sectional study, and to compare these results with those of the Therapeutic Intervention Scoring System-28.SettingA total of 99 intensive care units in 15 countries.PatientsConsecutive admissions to the intensive care units.InterventionDaily recording of nursing activities at a patient level and random multimoment recording of these activities.ResultsA total of five new items and 14 subitems describing nursing activities in the intensive care unit (e.g., monitoring, care of relatives, administrative tasks) were added to the list of therapeutic interventions in Therapeutic Intervention Scoring System-28. Data from 2,041 patients (6,451 nursing days and 127,951 multimoment recordings) were analyzed. The new activities accounted for 60% of the average nursing time; the new scoring system (Nursing Activities Score) explained 81% of the nursing time (vs. 43% in Therapeutic Intervention Scoring System-28). The weights in the Therapeutic Intervention Scoring System-28 are not derived from the use of nursing time.ConclusionsOur study suggests that the Nursing Activities Score measures the consumption of nursing time in the intensive care unit. These results should be validated in independent databases.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo prospectively evaluate the oxygenation effect of inhaled nitric oxide (INO) delivered during high-frequency oscillatory ventilation in adult patients with the acute respiratory distress syndrome and oxygenation failure.DesignProspective, clinical study.SettingIntensive care unit of a university teaching hospital.PatientsA total of 23 adults (14 women, 9 men, 44.9 ± 17.5 yrs, Acute Physiology and Chronic Health Evaluation II score of 28.6 ± 7.1) with acute respiratory distress syndrome (lung injury score, 3.5 ± 0.4) with Fio2of ≥0.6 and mean airway pressure of ≥28 cm H2O.InterventionsINO was initiated at a dose of 5 ppm, and subsequently titrated according to a protocol, to determine the dose (5, 10, or 20 ppm) resulting in the greatest increase in Pao2/Fio2. Blood gas measurements were obtained 10–15 mins after initiation or any increase in INO dosage to assess the effect on Pao2/Fio2.Measurements and Main ResultsArterial blood gases and ventilator settings were recorded at four time points: during conventional ventilation just before initiating high-frequency oscillatory ventilation, during high-frequency oscillatory ventilation just before initiating INO, after 30 mins on the optimal dose of INO, and 8–12 hrs after starting INO. Oxygenation index ([Fio2× mean airway pressure × 100]/Pao2) and Pao2/Fio2ratios were calculated at the same time intervals. At 30 mins after INO initiation, 83% of patients had a significant increase in blood oxygen tension, defined as ≥20% increase in Pao2/Fio2. The mean change in Pao2/Fio2at 30 mins was 38%. In these 19 patients, Pao2/Fio2was highest at 20 ppm in four patients, at 10 ppm in eight patients, and at 5 ppm in seven patients. Compared with baseline measurements, Pao2/Fio2improved significantly at both 30 mins (112 ± 59 vs. 75 ± 32,p= .01) and 8–12 hrs after INO initiation (146 ± 52 vs. 75 ± 32,p< .0001). In addition, oxygenation index was reduced at 8–12 hrs compared with baseline measurements (26 ± 13 vs. 40 ± 17,p= .08).ConclusionsINO delivered at doses of 5 to 20 ppm during high-frequency oscillatory ventilation increases Pao2/Fio2and may be a safe and effective rescue therapy for patients with severe oxygenation failure.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine whether changes have occurred at our center in the incidence, patterns of organ dysfunctions, prognostic factors, and case-fatality rate of bacteremic sepsis.DesignRetrospective comparative study (1984–1988 vs. 1994–1997).SettingUniversity hospital surgical intensive care unit.PatientsA total of 372 critically ill patients with sepsis and positive blood cultures.InterventionNone.Measurements and Main ResultsIn the 1984–1988 study, 176 patients developed bacteremic sepsis (3.2 per 100 admissions), with a fatality rate of 35% at 28 days, whereas in the 1994–1997 study, 196 patients had bacteremic sepsis (4.3 per 100 admissions), with a 28-day fatality rate of 37%. The frequency of primary bacteremia increased from 21% to 47% (p< .001), paralleled by an increase in the proportional frequency of Gram-positive microorganisms. In 1984–1988, 69% (n = 120) of patients had at least one organ dysfunction, compared with 80% (n = 156) in 1994–1997 (p= .02). The prevalence of pulmonary and cardiac dysfunction increased. The case- fatality rate of septic shock remained high (69% vs. 68%). For both cohorts, the two strongest predictors of mortality remained the Acute Physiology and Chronic Health Evaluation II score at the onset of sepsis and the number of evolving organ dysfunctions.ConclusionThe fatality rate of bacteremic sepsis remained constant over the study period, despite an increased incidence of bacteremia and associated organ dysfunction. Continued efforts need to be directed toward the prevention of bacteremic sepsis, given the magnitude and poor prognosis of this syndrome.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveAn increased oxidative stress in the lower respiratory tract of individuals with acute respiratory distress syndrome is considered to be one mechanism of lung injury in these patients. Cell and tissue damage resulting from an oxidative stress can ultimately be the consequence of a disruption of normal iron metabolism and an increased availability of catalytically active metal. Using bronchoalveolar lavage fluid, we quantified concentrations of iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers.DesignA clinical study to quantify iron and iron-related proteins in the lower respiratory tract in patients with acute respiratory distress syndrome and healthy volunteers.PatientsWe studied 14 patients with acute respiratory distress syndrome and 28 healthy volunteers.Main ResultsComparable to previous investigation, protein, albumin, and cytokine concentrations in the bronchoalveolar lavage fluid were significantly increased in acute respiratory distress syndrome patients. The concentrations of total and nonheme iron were also increased in the lavage fluid of patients. Concentrations of hemoglobin, haptoglobin, transferrin, transferrin receptor, lactoferrin, and ferritin in the bronchoalveolar lavage fluid were all significantly increased in acute respiratory distress syndrome patients.ConclusionsWe conclude that bronchoalveolar lavage fluid indices reflect a disruption of normal iron metabolism in the lungs of acute respiratory distress syndrome patients. Increased concentrations of available iron in acute respiratory distress syndrome may participate in catalyzing oxidant generation destructive to the tissues of the lower respiratory tract. However, increased metal availability is also likely to elicit an increased expression of transferrin receptor, lactoferrin, and ferritin in the lower respiratory tract which will function to diminish this oxidative stress.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo evaluate primary success rate and effectiveness of direct-current cardioversion in postoperative critically ill patients with new-onset supraventricular tachyarrhythmias.DesignProspective intervention study.SettingTwelve-bed surgical intensive care unit in a university teaching hospital.PatientsThirty-seven consecutive, adult surgical intensive care unit patients with new-onset supraventricular tachyarrhythmias without previous history of tachyarrhythmias.InterventionsDirect-current cardioversion using a monophasic, damped sinus-wave defibrillator. Energy levels used were 50, 100, 200, and 300 J for regular supraventricular tachyarrhythmias (n = 6) and 100, 200, and 360 J for irregular supraventricular tachyarrhythmias (n = 31).Measurements and Main ResultsNone of the patients was hypoxic, hypokalemic, or hypomagnesemic at onset of supraventricular tachyarrhythmia. Direct-current cardioversion restored sinus rhythm in 13 of 37 patients (35% primary responders). Most patients responded to the first or second direct-current cardioversion shock. Only one of 25 patients requiring more than two direct-current cardioversion shocks converted into sinus rhythm. Primary responders were significantly younger and demonstrated significant differences in arterial Po2values at onset of supraventricular tachyarrhythmias compared with nonresponders. At 24 and 48 hrs, only six (16%) and five (13.5%) patients remained in sinus rhythm, respectively.ConclusionsIn contrast to recent literature, direct-current cardioversion proved to be an ineffective method for treatment of new-onset supraventricular tachyarrhythmias and, in particular, atrial fibrillation with a rapid ventricular response in surgical intensive care unit patients.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo evaluate the time course of hemoglobin concentrations in nonbleeding intensive care unit patients.DesignProspective, observational study.SettingMultidisciplinary (medicosurgical) department of intensive care.PatientsNinety-one patients with no evidence of recent or active blood loss, no history of hematologic disease or chronic renal failure, and no need for extracorporeal epuration techniques.InterventionsNone.Measurements and Main ResultsData collection included primary diagnoses, Acute Physiology and Chronic Health Evaluation II and sepsis-related organ failure assessment scores, signs of sepsis, 24-hr fluid balance, and hemoglobin concentrations. For the entire intensive care unit stay, the fall in hemoglobin concentrations (calculated from the mean of individual slopes of hemoglobin concentrations over time) averaged 0.52 ± 0.69 g/dL/day. For the 33 patients who stayed in the intensive care unit for >3 days, this decline was larger for the first 3 days than for subsequent days (0.66 ± 0.84 g/dL/day vs. 0.12 ± 0.29 g/dL/day;p< .01). After the third intensive care unit day, the change in hemoglobin concentrations was inversely related to the severity of the disease, as reflected by the Acute Physiology and Chronic Health Evaluation II and the sepsis-related organ failure assessment scores. Hemoglobin concentrations decreased by 0.44 ± 0.70 g/dL/day in the nonseptic and 0.68 ± 0.66 g/dL/day in the septic patients (p= .13). After the third intensive care unit day, hemoglobin concentrations continued to decrease in the septic patients but not in the nonseptic patients (−0.29 ± 0.19 vs. 0.006 ± 0.3 g/dL/day;p= .0016). The fall in hemoglobin concentrations was not significantly related to the fluid balance. The volume of blood drawn daily for laboratory studies was 40.3 ± 15.4 mL: 49.0 ± 11.3 mL in the septic patients and 36.7 ± 14.9 mL in the nonseptic patients (p= .04).ConclusionsHemoglobin concentrations typically decline by >0.5 g/dL/day during the first days of intensive care unit stay in nonbleeding patients. Beyond the third day, hemoglobin concentrations can remain relatively constant in nonseptic patients but continue to decrease in septic patients, as well as patients with high sepsis-related organ failure assessment or Acute Physiology and Chronic Health Evaluation II scores. These observations may help in the interpretation of hemoglobin concentrations in critically ill patients.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo assess how the level of positive end-expiratory pressure (PEEP) (antiderecruitment strategy), etiological category of diffuse lung injury, and body position of the patient modify the effect of the alveolar recruitment maneuver (ARM) in acute respiratory distress syndrome (ARDS).DesignProspective clinical trial.SettingMedical intensive care unit at a tertiary hospital.PatientsForty-seven patients with early ARDS, including 19 patients from our preliminary study.InterventionFrom baseline ventilation at a tidal volume of 8 mL/kg and PEEP of 10 cm H2O, the ARM (a stepwise increase in the level of PEEP up to 30 cm H2O with a concomitant decrease in the magnitude of tidal volume down to 2 mL/kg) was given with (ARM + PEEP, n = 20) or without (ARM only, n = 19) subsequent increase of PEEP to 15 cm H2O. In eight other patients, PEEP was increased to 15 cm H2O without a preceding ARM (PEEP only).Measurements and ResultsIn all three groups, Pao2was increased by the respective intervention (allp< .05). In the ARM-only group, Pao2at 15 mins after intervention was lower than Pao2immediate after intervention (p= .046). In the ARM + PEEP group, no such decrease in Pao2was observed, and Pao2at 15, 30, 45, and 60 mins after intervention was higher than in the ARM-only group (allp< .05). Compared with the PEEP-only group, Pao2of the ARM + PEEP group was higher immediately after intervention and at the later time points (allp< .05). Compared with patients with ARDS associated with direct lung injury (pulmonary ARDS), patients with ARDS associated with indirect lung injury (extrapulmonary ARDS) showed a greater increase in Pao2(27 ± 21% vs. 130 ± 112%;p= .002) and a greater decrease in radiologic scores (1.0 ± 2.4 vs. 3.4 ± 1.5;p= .005) after the ARM. The increase in Pao2induced by the ARM was greater for patients in the supine position than for patients in the prone position (61 ± 82% vs. 21 ± 14%;p= .028). Consequently, Pao2immediately after the ARM was similar in the two groups of patients in different positions.ConclusionsAfter the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID