摘要:

Objective:Nitric oxide (NO), produced by the inducible isoform of NO synthase (NOS) in circulatory shock exerts cytotoxic and vasodilator effects. Part of these effects are mediated by formation of peroxynitrite, a toxic oxidant produced by the rapid reaction of NO and superoxide. Other parts of the vascular actions of NO in shock are thought to be mediated by the action of NO on the soluble guanylyl cyclase (GC) in the smooth muscle and subsequent decrease in the intracellular calcium levels. Using 1H-(1,2,4)oxadiazolo(4,3-α)quinoxalin-1-one (ODQ), a potent inhibitor of GC, we studied the role of GC activation in the NO- and peroxynitrite-related vascular alterations.Design:In vitro:Controlled experiment using cultured rat aortic smooth muscle cells.In vivo:Prospective, randomized, controlled animal study.Setting:Experimental laboratory.Subjects:Male Wistar rats and male Swiss mice.Interventions:In vitro:a) Stimulation of rat aortic smooth muscle cells with bacterial lipopolysaccharide (LPS) and γ-interferon, measurement of the production of nitrite and nitrate (breakdown products of NO), and suppression of mitochondrial respiration for 24 to 48 hrs, in the presence or absence of ODQ; and b) in norepinephrine-precontracted endothelium-denuded thoracic aortic rings, exposure to LPS (10 ng/mL) in the presence or absence of ODQ.In vivo:Rats treatedin vivowith LPS (10 mg/kg iv for 3 hrs) and mice challenged with 60 mg/kg LPS ip, in the presence or absence of ODQ.Measurements and Main Results:Stimulation of rat aortic smooth muscle cells with bacterial LPS and γ-interferon induced the production of nitrite and nitrate (breakdown products of NO) and suppression of mitochondrial respiration for 24 to 48 hrs. The amount of NO produced was slightly enhanced with ODQ (10-100 μM), whereas the suppression of mitochondrial respiration was not affected by ODQ (1-100 μM). ODQ did not affect the degree of suppression of mitochondrial respiration in response to NO donor agents or to peroxynitrite. Exposure to LPS (10 ng/mL) for 6 hrs caused a time-dependent relaxation of norepinephrine-precontracted endothelium-denuded thoracic aortic rings. This response was caused by the expression of inducible NOS and could be blocked by pharmacologic inhibitors of NOS such as NG-methyl-L-arginine. ODQ (1 μM) prevented the LPS-induced loss of vascular tone in this experimental system. Similar to thein vitroresponses, there was a significant suppression of the norepinephrine-induced contractions inex vivoexperiments, in which rings were taken from animals treatedin vivowith LPS (10 mg/kg for 3 hrs). ODQ treatmentin vitro(1 μM) caused a complete restoration of the contractile responses. In mice challenged with 60 mg/kg LPS ip, ODQ (20 mg/kg), given either as a pretreatment or as a 4-hr posttreatment, improved survival at 24-144 hrs.Conclusion:These studies indicate that GC activation does not contribute to NO- or peroxynitrite-induced cytotoxicity but does contribute to the vascular hyporeactivity induced by endotoxinin vitroandin vivo.GC inhibition alone is sufficient to influence survival in a murine model of severe sepsis.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To determine the hemodynamic effects of the combination of norepinephrine-dobutamine in adult patients with septic shock. Specifically, we tested the hypothesis that norepinephrine in addition to dobutamine would improve cardiac index (CI) and stroke volume index (SVI) and increase left-ventricular afterload.Design:Prospective, descriptive, interventional study with no control group.Setting:Intensive care unit of a university hospital.Patients:Fourteen patients (group 1) were transferred to the intensive care unit from other wards with septic shock not responsive to dobutamine infusion, low blood pressure (systolic blood pressure of <90 mm Hg), clinical and laboratory signs of infection, clinical signs of poor organ perfusion, and blood lactate of >2.0 mmol/L. They were enrolled and treated by the addition of norepinephrine, while the dose of dobutamine remained constant. Three of these patients required additional fluid loading to achieve adequate ventricular filling (pulmonary capillary wedge pressure [PCWP], 12-15 mm Hg). These patients were compared with 12 patients with septic shock with high CI (CI > 5/min/m2, and other signs as outlined previously) who were treated with norepinephrine alone (group 2).Interventions:Patients in group 1 were maintained with the same dobutamine dose, and norepinephrine was added (initial dose, 0.5 μg/kg/min, and increments of 0.3 μg/kg/min) until the correction of mean arterial blood pressure (MAP ≥75 mm Hg). Patients in group 2 received norepinephrine following the same protocol.Measurements and Main Results:At study entry, group 1 patients receiving dobutamine had similar MAPs but were significantly older and had significantly lower CIs and SVIs and higher systemic vascular resistance than group 2 patients. In group 1 norepinephrine, in addition to dobutamine, significantly increased MAP, CI, SVI, left ventricular stroke work index (LVSWI), and systemic vascular resistance (SVR). No change in heart rate or PCWP was observed. In group 2, norepinephrine used alone did not modify CI or SVI and it significantly improved MAP, LVSWI, and SVR. No changes in heart rate or PCWP were observed. Blood lactate was significantly decreased in both groups. Comparing the two groups, in response to norepinephrine titrated to increase MAP to a similar concentration, patients with dobutamine-resistant septic shock had a statistically significantly greater increase in CI and SVI than patients treated with norepinephrine alone. There were no other significant differences in hemodynamic and metabolic responses to norepinephrine between groups 1 and 2.Conclusion:The addition of norepinephrine to treatment of patients with septic shock unresponsive to dobutamine significantly improves MAP, CI, SVI, and LVSWI. A different pattern of evolution was observed if norepinephrine was used alone in younger patients with higher CI at study entry, increases in MAP and LVSWI, and no concomitant change in CI or SVI. The use of norepinephrine in dobutamine-resistant septic shock may have some beneficial implications for the treatment of patients with inadequate myocardial performance associated with low SVR.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To identify clinical predictors for tracheostomy among patients requiring mechanical ventilation in the intensive care unit (ICU) setting and to describe the outcomes of patients receiving a tracheostomy.Design:Prospective cohort study.Setting:Intensive care units of Barnes-Jewish Hospital, an urban teaching hospital.Patients:521 patients requiring mechanical ventilation in an ICU for >12 hours.Interventions:Prospective patient surveillance and data collection.Measurements and Main Results:The main variables studied were hospital mortality, duration of mechanical ventilation, length of stay in the ICU and the hospital, and acquired organ-system derangements. Fifty-one (9.8%) patients received a tracheostomy. The hospital mortality of patients with a tracheostomy was statistically less than the hospital mortality of patients not receiving a tracheostomy (13.7% vs. 26.4%;p= .048), despite having a similar severity of illness at the time of admission to the ICU (Acute Physiology and Chronic Health Evaluation [APACHE] II scores, 19.2 ± 6.1 vs. 17.8 ± 7.2;p= .173). Patients receiving a tracheostomy had significantly longer durations of mechanical ventilation (19.5 ± 15.7 days vs. 4.1 ± 5.3 days;p< .001) and hospitalization (30.9 ± 18.1 days vs. 12.8 ± 10.1 days;p< .001) compared with patients not receiving a tracheostomy. Similarly, the average duration of intensive care was significantly longer among the hospital nonsurvivors receiving a tracheostomy (n = 7) compared with the hospital nonsurvivors without a tracheostomy (n = 124; 30.9 ± 16.3 days vs. 7.9 ± 7.3 days;p< .001). Multiple logistic regression analysis demonstrated that the development of nosocomial pneumonia (adjusted odds ratio [AOR], 4.72; 95% confidence interval [CI], 3.24-6.87;p< .001), the administration of aerosol treatments (AOR, 3.00; 95% CI, 2.18-4.13;p< .001), having a witnessed aspiration event (AOR, 3.79; 95% CI, 2.30-6.24;p= .008), and requiring reintubation (AOR, 2.21; 95% CI, 1.54-3.18;p= .028) were variables independently associated with patients undergoing tracheostomy and receiving prolonged ventilatory support. Among the 44 survivors receiving a tracheostomy in the ICU, 38 (86.4%) were alive 30 days after hospital discharge and 31 (70.5%) were living at home.Conclusions:Despite having longer lengths of stay in the ICU and hospital, patients with respiratory failure who received a tracheostomy had favorable outcomes compared with patients who did not receive a tracheostomy. These data suggest that physicians are capable of selecting critically ill patients who most likely will benefit from placement of a tracheostomy. Additionally, specific clinical variables were identified as risk factors for prolonged ventilatory assistance and the need for tracheostomy.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To determine the efficacy and safety of epidural bupivacaine and sufentanil for the management of sympathetic overactivity in tetanus.Design:Retrospective case review.Setting:Sixteen-bed surgical intensive care unit in a tertiary care centre.Patients:All patients referred to the unit during a 63-month period with the diagnosis of tetanus were included in the study.Measurements and Main Results:All patients (n = 11) had severe tetanus and developed sympathetic overactivity, which was managed by epidural blockade. Three patients died, but there were no fatalities directly attributable to sympathetic overactivity. Before epidural blockade, the average difference between the mean maximum and mean minimum systolic blood pressures was 78 ± 28 (SD) mm Hg. After blockade, this difference was reduced to 38 ± 15 (SD) mm Hg (p< .0001). Similar significant reductions in diastolic blood pressure and heart rate were observed. The mean hourly infusion doses of bupivacaine and sufentanil were 17 mg and 21 μg, respectively. Midazolam was the principal adjunctive sedative agent and was used in all patients (mean dose, 9 mg/hr). Additional pharmacologic agents were necessary in two patients in whom epidural blockade alone was insufficient to control sympathetic overactivity. One patient developed renal failure and there were no instances of pneumothorax. One patient developed an epidural abscess of probable hematogenous origin, which was successfully treated without neurologic sequelae.Conclusions:Epidural blockade is effective in controlling sympathetic overactivity and the associated complications (renal failure, cardiac injury, and sudden death). Although a serious complication occurred in one patient, the efficacy of the technique deserves further validation.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose:Periodic diagnostic tests and continuous and intermittent monitoring are integral to critical care medicine. The focus of this article is understanding the impact of existing diagnostic technology, as well as that of new diagnostic technology.Data Synthesis:We use literature about gastric tonometry to illustrate eight steps for assessing the value of diagnostic technology.Methods:These steps focus on how the technology works in the laboratory, its range of uses and diagnostic accuracy, its impact on healthcare workers, the decision making process, and patient outcomes, as well as issues of access, cost, and application in your own setting.Conclusions:Awareness of the scope and quality of research evaluating new and existing diagnostic technology is central to modern critical care practice.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To determine whether pretreatment with intravenous antihistamines attenuates the symptoms of red-man syndrome associated with rapid vancomycin administration.Design:Prospective, randomized, double-blinded, placebo-controlled study of patients undergoing elective arthroplasty.Setting:Preoperative unit in a tertiary care center.Patients:Forty preoperative patients (American Society of Anesthesiologists status I-III, receiving vancomycin prophylaxis for elective prosthetic joint replacement or revision.Interventions:Elective orthopedic patients were randomly allocated to receive intravenous antihistamines (diphenhydramine, 1 mg/kg, and cimetidine, 4 mg/kg) or placebo before rapid vancomycin infusion (1 g over 10 mins). Hemodynamic measurements, symptoms of histamine release, and plasma histamine levels were obtained in each patient during vancomycin administration. Rapid vancomycin infusion was discontinued in cases of decreases in mean blood pressure of ≥20% or intolerable itching.Measurements and Main Results:Clinical symptomatology of red-man syndrome and histamine levels were assessed using Fisher's exact test or Student'st-test. Comparison of baseline and peak histamine levels for both the treated (mean ± SD, 0.2 ± 0.2 vs. 4.7 ± 2.4 mg/mL;p< .0001) and placebo patients (mean ± SD, 0.2 ± 0.1 vs. 3.5 ± 3.4 ng/mL;p= .0002) was statistically significant. Although there was a significant increase in plasma histamine levels during vancomycin infusion, it did not differ between the treatment groups. Only two (11%) of the treated patients developed hypotension, vs. 12 (63%) of the placebo patients (p= .002). Rash was partially attenuated. Twelve (63%) of the treated patients developed rash, compared with 19 (100%) of the placebo patients (p= .008). The rapid infusion was discontinued in two (11%) of the treated patients, compared with 11 (58%) of the placebo patients (p= .005). Four treated patients had no symptoms of histamine release.Conclusions:Pretreatment with intravenous H1and H2antihistamines permitted rapid vancomycin administration in 89% of treated patients. Although protection was incomplete, rash did not predict a need to stop the rapid infusion of vancomycin in our patients.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To assess the degree, source, and patterns of oxidative damage to bronchoalveolar lavage proteins as a modification of amino acid residues in patients with acute respiratory distress syndrome (ARDS).Design:Prospective, controlled study.Setting:Adult intensive care unit of a postgraduate teaching hospital.Patients:Twenty-eight patients with established ARDS were studied and compared with six ventilated patients without ARDS and 11 normal healthy controls.Interventions:Supportive techniques appropriate to ARDS.Measurements and Main Results:Evidence of oxidative modification of bronchoalveolar lavage fluid protein, indicative of the production of specific reactive oxidizing species, was sought using a high-performance liquid chromatography technique. Bronchoalveolar lavage fluid samples from patients with ARDS, ventilated intensive care controls, and normal healthy controls were analyzed. Concentrations of orthotyrosine were significantly higher in the ARDS group than in either control group (7.98 ± 3.78 nmol/mg for ARDS, 0.67 ± 0.67 for ventilated controls, and 0.71 ± 0.22 for healthy controls;p< .05). Chlorotyrosine concentrations were also significantly increased in the ARDS group over either control group (4.82 ± 1.07 nmol/mg for ARDS, 1.55 ± 1.34 for ventilated controls, and 0.33 ± 0.12 for healthy controls;p< .05). Nitrotyrosine concentrations were similarly significantly increased in the ARDS groups compared with each control group (2.21 ± 0.65 nmol/mg for ARDS, 0.29 ± 0.29 for ventilated controls, and 0.06 ± 0.03 for healthy controls;p< .05).Chlorotyrosine and nitrotyrosine concentrations showed significant correlations with myeloperoxidase concentrations in bronchoalveolar lavage fluid, measured using an enzyme-linked immunosorbent assay in patients with ARDS. These findings suggest a possible relationship between inflammatory cell activation, oxidant formation, and damage to proteins in the lungs of these patientsConclusions:Overall, our data strongly suggest heightened concentrations of oxidative stress in the lungs of patients with ARDS that lead to significantly increased oxidative protein damage.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To assess the cytokine expression (tumor necrosis factor-α [TNF-α], interleukin [IL]-1β, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood).Design:Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling.Setting:Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital.Patients:Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10).Interventions:Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-α, IL-1β, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only.Measurements and Main Results:Serum TNF-α levels were significantly higher in patients with pneumonia compared with controls (35 ± 4 vs. 17 ± 3 pg/mL, respectively,p= .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 ± 260 vs. 94 ± 35 pg/mL, respectively,p= .017; BAL fluid, 1176 ± 468 vs. 234 ± 83 pg/mL, respectively,p= .05). On days 1, 3, and 7 in patients with pneumonia, IL-1β levels turned out to be higher in BAL fluid than in serum (71 ± 17 vs. 2 ± 1 pg/mL on day 1; 49 ± 8 vs. 6 ± 2 pg/mL on day 3; and 47 ± 16 vs. 3 ± 2 pg/mL on day 7 for BAL fluid and serum, respectively,p< .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 ± 433 pg/mL) with pneumonia compared with survivors (464 ± 260 pg/mL). In addition, serum TNF-α and IL-6 correlated with multiple organ failure score (r2= .36,p= .004 for both) and with lung injury score (r2= .30,p= .01, and r2= .22,p= .03, for TNF-α and IL-6, respectively).Conclusions:The present study describes the lung and systemic inflammatory response in severe pneumonia. The lung cytokine expression seems to be independent from the lung bacterial burden in the presence of antibiotic treatment. Because of the limited sample size, we did not find a clear relationship between serum and BAL fluid cytokine levels and outcome.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To study the quality, cost, and benefits of intensive care in a public hospital in Bombay, India.Design:Prospective collection of data.Setting:Seventeen-bed medical-neurology-neurosurgery intensive care unit (ICU) of a municipal teaching hospital.Patients:A total of 993 consecutive ICU patients during a 16-month period.Interventions:None.Measurements and Main Results:The 993 patients aged 36.5 ± 16 yrs (mean ± SD) had a day-1 Acute Physiology and Chronic Health Evaluation (APACHE) II score of 14.9 ± 9.6 (mean ± SD), with a predicted mortality of 21.7%; the observed mortality was 36.2% (standardized mortality ratio = 1.67). The day-1 Therapeutic Intervention Scoring System (TISS) points were 17.7 ± 6.2 (mean ± SD), and total TISS points per patient were 87.6 ± 110 (mean ± SD). Nurse-to-patient ratio in the ICU was 3:17 and the average workload per nurse was 64.2 TISS points. The average length of stay was 5.5 days (SD = 7.1 days). The overall cost of treating 993 patients was, in Indian rupees (Rs), Rs 107,79,209 (U.S. $307,997), and cost per patient per day was Rs 1,973 (U.S. $57). The cost per survivor was Rs 17,029 (U.S. $487) and cost per TISS point was Rs 90.14 (U.S. $2.57). The low cost per TISS point was attributable to the reuse of disposable equipment and lower cost of drugs and salaries for medical and paramedical staff.Conclusions:Intensive care in India is cheaper than in the West; however, mortality is 1.67 times that for patients with similar APACHE II scores in ICUs in the United States. This finding may be attributable to the lesser intensity of care per patient (lower day-1 TISS points), lower nurse-to-patient ratio because of shortage of trained personnel and budgetary constraints, and higher workload per nurse (64.2 TISS points per nurse, compared with 40 points per nurse in the West). In addition, the APACHE II scores may underestimate mortality for Indian patients because of differences in case mix, higher lead time between onset of admission and treatment before ICU admission, and possible inappropriateness of age points derived from American patients for Indian subjects because of a higher burden of diseases at lower ages in Indian patients.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To determine the patient-related costs of care for critically ill patients with severe sepsis or early septic shock.Design:Retrospective, longitudinal, observational study during a 10-month period.Setting:Adult general intensive care unit (ICU) in a university hospital located in the United Kingdom.Patients:The study population consisted of 213 patients admitted consecutively to the ICU during a 10-month period. Thirty-six patients were identified using standard definitions as having developed sepsis and analyzed by group (according to the day on which sepsis was diagnosed): Group 1 patients were septic at admission to ICU (n = 16); group 2 patients were septic on their second day in the ICU (n = 10); and group 3 patients developed sepsisaftertheir second day in the ICU (n = 10). One hundred and seventy-seven ICU patients without sepsis were used as the comparative group (group 4).Interveventions:None.Main Results:Patient-related costs of care, length of ICU stay, and ICU and hospital mortality rates were compiled. The median daily costs of care for patients in groups 1, 2, and 3 were $930.74 (interquartile range $851.59-$1,263.96); $814.47 ($650.89-$1,123.06), and $1,079.39 ($705.02-$1,295.96), respectively; these were significantly more than the group 4 patient's daily cost of $750.38 ($644.10-$908.55) (p< .01). The median total cost of treating the group 4 patients was $1,666.87 ($979.71-$2,772.03), significantly less than for the patients with sepsis (p< .01). The difference in total costs of care between the sepsis groups was also significant (p< .05), with a group 1 patient costing $3,801.55 ($1,865.28-$11,676.08), a group 2 patient costing $13,089.17 ($5,792.94-$22,235.18), and a group 3 patient costing $17,962.78 ($13,030.83-$28,546.73). Patients in groups 1, 2, and 3 stayed in the ICU for 3.3 days (1.3-11.3), 16.5 days (8.9-22), and 16.1 days (10.9-9), respectively. Significant differences were found among the three groups (p< 0.05), as well as between the patients with sepsis and those without (p< 0.001), whose median length of stay was 1.9 days (0.9-3.6). The ICU mortality rates were 50% each for groups 1 and 2, 60% for group 3, and 20% for group 4.Only one patient with sepsis and 16 patients without sepsis died in the hospital ward, producing overall mortality rates of 56% for group 1 and 29% for group 4.Conclusions:Patients with severe sepsis or early septic shock had a high mortality rate, spent prolonged periods of time in the ICU, and were significantly more expensive to treat than nonsepsis ICU patients.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID