摘要:

ObjectiveGram-negative septic shock has a clinical mortality rate approaching 50%. The cause of death is secondary to a systemic inflammatory response syndrome with resulting cardiovascular collapse, ischemic damage to vital organs, and multiple-organ systems failure. Renal tubule cell injury occurs early in septic shock but is not clinically appreciated. Since renal tubule cells appear to play a critical role in the immunoregulation of stress states, renal cell therapy during septic shock may alter the detrimental multiple-organ consequences of systemic Gram-negative infection. The development of a tissue-engineered bioartificial kidney consisting of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 109renal proximal tubule cells may be a new therapeutic approach to this clinical disorder.DesignLaboratory study.SettingUniversity medical school.SubjectsPigs weighing 30–35 kg.InterventionsTo assess the effect of the bioartificial kidney and the RAD in septic shock, pigs were administered 30 × 1010bacteria/kg body weight ofEscherichia coliinto the peritoneal cavity and within 1 hr were immediately placed in a continuous venovenous hemofiltration extracorporeal circuit with either a sham RAD without cells or a RAD with cells.Measurements and Main ResultsIn this animal model, septic shock resulted within hours in acute tubule necrosis in the kidneys of all animals. Renal cell therapy resulted in significantly higher cardiac outputs and renal blood flow rates in treated animals compared with sham controls. RAD treatment also was associated with significantly lower plasma circulating concentrations of interleukin-6 and interferon-&ggr; compared with sham-treated animals. IL-6 release rates from peripheral blood mononuclear cells isolated from RAD-treated animals were significantly higher after endotoxin stimulation than those isolated from control animals. These physiologic and molecular alterations were associated with nearly a doubling of the average survival time in the RAD-treated group compared with the sham control group.ConclusionThese results demonstrate that renal cell therapy ameliorates cardiac and vascular dysfunction, alters systemic cytokine abnormalities, and improves survival time in a large animal model of Gram-negative septic shock. A cell therapeutic approach with a tissue-engineered bioartificial kidney may be a new treatment modality for this current unmet medical need.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveRecent experimental evidence suggests that activation of adenosine triphosphate (ATP)-sensitive potassium channels contributes to vascular failure and early mortality after hemorrhagic shock. The present investigation evaluated the effects of the water-soluble sodium salt of glipizide, an inhibitor of ATP-sensitive potassium channels, in anesthetized and awake rats subjected to severe controlled hemorrhage.DesignProspective, randomized, controlled study.SettingAnimal research laboratory.SubjectsMale Wistar rats.InterventionsAnesthetized rats were subjected to bleeding to reduce mean arterial pressure to either 40 or 35 mm Hg, which was maintained constant for 60 mins. In addition, awake rats underwent blood withdrawal of 4.25 mL/100 g over 20 mins. At the end of the hemorrhage period and 30 mins later, the animals received intravenous (5 and 20 mg/kg) or intramuscular (10 and 40 mg/kg) injections of glipizide sodium salt or vehicle.Measurements and Main ResultsIn anesthetized rats subjected to pressure-controlled hemorrhage, glipizide sodium salt improved mean arterial pressure in a dose-dependent manner. Compared with the vehicle-treated animals, mean arterial pressure increased from 41.6 ± 4.6 to 63.1 ± 3.1 mm Hg in the 20 mg/kg intravenous group and from 33.2 ± 4.9 to 54.0 ± 4.7 mm Hg in the 40 mg/kg intramuscular group 60 mins after a 40-mm Hg shock. Furthermore, the drug did not affect the hemorrhage-induced changes in blood glucose concentrations. However, the higher doses of glipizide sodium salt attenuated the increments in plasma concentrations of lactate, alanine aminotransferase, creatinine, and amylase. Moreover, the higher doses markedly improved short-term survival after pressure- and volume-controlled bleeding. Overall, the intramuscular injections of the drug exerted salutary effects that were comparable to the intravenous administration.ConclusionsIn rats, parenteral administration of the water-soluble glipizide sodium salt attenuates vascular and end-organ dysfunction associated with severe hemorrhagic shock and prolongs short-term survival. The intramuscular administration provides comparable benefits as obtained by the intravenous injection.

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:

ObjectiveEnteral glutamine supplements have been shown to reduce infectious morbidity in trauma patients, but their effect on burn patients is not known. The objective of this study was to measure the impact of enteral glutamine supplementation on infectious morbidity, length of care, and the immune system in burn patients.DesignDouble-blinded, randomized clinical trial.SettingBurn center.PatientsForty-five adults with severe burns.InterventionsPatients were randomized to receive either glutamine or an isonitrogenous control mixture until complete healing occurred. Length of care, incidence of positive blood culture, and mortality were recorded. Phagocytosis by circulating polymorphonuclear cells was measured every 3 days.Measurements and Main ResultsPatient characteristics were similar in both groups. Four patients were excluded from the analysis, because three of them died within 72 hrs and the fourth could not receive enteral nutrition and amino acid supplements for the first 10 days. Of the remaining 41 patients, length of care in the survivors was not different between groups (0.9 vs. 1.0 days/percent total body surface area for glutamine vs. control, respectively), positive blood culture was three times more frequent in control than in glutamine treatment (4.3 vs. 1.2 days/patient,p< .05), andPseudomonas aeruginosawas detected in six patients on control and zero on glutamine (p< .05). Phagocytosis by polymorphonuclear cells was not different between groups. Mortality rate was significantly lower in glutamine than in control: intention to treat, two vs. 12 (p< .05); per protocol analysis, zero vs. eight (p< .01).ConclusionsEnteral glutamine supplementation in adult burn patients reduces blood infection by a factor of three, prevents bacteremia withP. aeruginosa, and may decrease mortality rate. It has no effect on level of consciousness and does not appear to influence phagocytosis by circulating polymorphonuclear cells.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo investigate pharmacokinetics and metabolism of sodium citrate in critically ill patients. To determine the risk of citrate accumulation in the setting of liver dysfunction (cirrhosis, hepatorenal syndrome).DesignProspective cohort study.SettingIntensive Care Unit, Department of Medicine IV, University Hospital Vienna.PatientsConsecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16).InterventionsInfusion of sodium citrate (0.5 mmol·kg−1·hr−1) and calcium chloride (0.17 mmol·kg−1·hr−1) for 2 hrs. Analysis of serial arterial blood samples.Measurements and Main ResultsTotal body clearance of citrate was normal in noncirrhotic critically ill patients but significantly reduced in cirrhotic patients (710 vs. 340 mL/min,p= .008). Citrate peak concentrations and concentration over time were increased by 65% and 114% in cirrhotic patients (p< .001), respectively; volumes of distribution were similar. Net metabolic changes were quantitatively similar, with pH and plasma bicarbonate concentrations increasing more slowly in cirrhotic patients. No citrate-related side effects were noted. Citrate clearance could not be predicted by standard liver function tests and was not appreciably influenced by renal function and Acute Physiology and Chronic Health Evaluation II scores.ConclusionsThis first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo evaluate the effectiveness of a rehabilitation program following critical illness to aid physical and psychological recovery.DesignRandomized controlled trial, blind at follow-up with final assessment at 6 months.SettingTwo district general hospitals and one teaching hospital.PatientsPatients were 126 consecutively admitted intensive care patients meeting the inclusion criteria.InterventionsControl patients received ward visits, three telephone calls at home, and clinic appointments at 8 wks and 6 months. Intervention patients received the same plus a 6-wk self-help rehabilitation manual.Measurements and Main ResultsWe measured levels of depression and anxiety (Hospital Anxiety and Depression Scale), phobic symptoms (Fear Index), posttraumatic stress disorder (PTSD)-related symptoms (Impact of Events Scale), and scores on the Short-Form Health Survey physical dimension 8 wks and 6 months after intensive care unit (ICU) treatment. Memory for ICU was assessed at 2 wks post-ICU discharge using the ICU Memory Tool.The intervention group improved, compared with the control patients, on the Short-Form Health Survey physical function scores at 8 wks and 6 months (p= .006), and there was a trend to a lower rate of depression at 8 wks (12% vs. 25%). However, there were no differences in levels of anxiety and PTSD-related symptoms between the groups. The presence of delusional memories was correlated significantly with both anxiety and Impact of Events Scale scores.ConclusionsA self-help rehabilitation manual is effective in aiding physical recovery and reducing depression. However, in those patients recalling delusional memories from the ICU, further psychological care may be needed to reduce the incidence of anxiety and PTSD-related symptoms.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveSevere injury compromises functions of the antigen-presenting immune cells, resulting in an increased vulnerability toward bacterial sepsis. Support of the immune capabilities contributes a desirable therapeutic option in high-risk patients. Factors possessing immunostimulating properties such as granulocyte-macrophage colony-stimulating factor (GM-CSF) may serve as potential tools to compensate immunosuppression caused by severe trauma. In the present study, therefore, GM-CSF was examined with regard to its capacity to overcome trauma-induced down-regulation of immune functions.DesignProspective clinical experimental study.SettingUniversity hospital intensive care unit and research facility.PatientsSeverely injured patients with >25 points on the Injury Severity Score.InterventionsBlood samples of severely injured patients were incubatedin vitrowith 10 ng/mL GM-CSF for 6 hrs.MeasurementsHuman leukocyte antigen (HLA)-DR expression on monocytes was analyzed by flow cytometry, lipopolysaccharide-induced tumor necrosis factor (TNF)&agr; and interleukin-10 production of blood samples was measured by means of enzyme-linked immunoabsorbent assay.Main ResultsCompared with blood specimens of healthy donors,ex vivoendotoxin-induced TNF&agr; production and HLA-DR expression on monocytes were significantly reduced in blood of trauma patients.Ex vivotreatment of blood specimens with GM-CSF increased HLA-DR expression and TNF&agr; production stimulated by lipopolysaccharides in both healthy volunteers and patients on day 1 after trauma. Blood samples of patients with an uneventful recovery showed nearly normal TNF&agr; synthesis and HLA-DR expression after 2–3 wks, whereas TNF&agr; production and HLA-DR expression of patients with sepsis and multiple organ failure remained at low levels. In the sepsis/multiple organ failure group, GM-CSF also enhanced HLA-DR expression and TNF&agr; production, although the levels of the volunteers’ blood were not reached.ConclusionsThe presented data show that trauma- and sepsis-induced depression of monocyte functions can be counteracted by GM-CSFin vitro, suggesting that this substance may serve as support of immune functions in severely injured patients.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveMany sedative regimens are used in the intensive care setting, but none are wholly without adverse effect. Xenon is a noble gas with sedative and analgesic properties. It has been used successfully as a general anesthetic and has many desirable properties, not least of which is a minimal effect on the myocardium. In theory, xenon may provide sedation without adverse effect for certain groups of critically ill patients. The objective of this study was to assess the feasibility of using xenon as an intensive care sedative.DesignDouble-blind, randomized study.SettingTertiary-level intensive care unit.SubjectsTwenty-one patients admitted to an intensive care unit following elective thoracic surgery.InterventionsA standard intensive care sedation regimen (intravenous propofol at 0–5 mg·kg−1·hr−1and alfentanil 30 &mgr;g·kg−1·hr−1) was compared with a xenon sedation regimen delivered using a novel bellows-in-bottle delivery system.Measurements and Main ResultsEach sedative regimen was continued for 8 hrs. The hemodynamic effects, additional analgesic requirements, recovery from sedation, and effect on hematological and biochemical variables were compared for the two sedation regimens. All patients were successfully sedated during the xenon regimen. The mean ± sd end-tidal xenon concentration required to provide sedation throughout the duration of the study was 28 ± 9.0% (range, 9–62%). Arterial systolic, diastolic, and mean pressures showed a greater tendency for negative gradients in patients receiving the propofol regimen (p< .05,p< .1, andp< .01, respectively). Recovery following xenon was significantly faster than from the standard sedation regimen (p< .0001). Hematological and biochemical laboratory markers were within normal clinical limits in both groups.ConclusionsXenon provided satisfactory sedation in our group of patients. It was well tolerated with minimal hemodynamic effect. Recovery from this agent is extremely rapid. We have demonstrated the feasibility of using xenon within the critical care setting, without adverse effect.

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 determine whether ventilator-associated pneumonia caused byAcinetobacter baumannii(VAPAB) is associated with increased mortality rate.DesignA retrospective matched case-control study in which all intensive care unit adult patients with microbiologically documented VAPAB were defined as cases.SettingFour intensive care units from teaching hospitals.PatientsSixty patients were matched to sixty controls.Measurements and Main ResultsControls were matched based on stay before pneumonia onset, disease severity (Acute Physiology and Chronic Health Evaluation II) at admission, and diagnostic category. Population characteristics and intensive care unit mortality rates of patients with VAPAB and their controls were compared. Attributable mortality was determined by subtracting the crude mortality rate of the controls from the crude mortality rate of the case patients. Twenty-four of the 60 case patients died, representing a crude mortality rate of 40%, whereas 17 of the 60 controls died, a crude mortality rate of 28.3% (p= .17). Crude intensive care unit mortality was the same (12 of 35, 34.2%) in patients with VAPAB caused by strains sensitive to imipenem and in their matched controls. It was 44% for the 25 patients with imipenem-resistant strains with an estimated attributable mortality rate of 20.0% (95% confidence interval, −5.6% to 45.7%). Mean intensive care unit stay of patients and controls was 35.3 and 36.6 days, respectively (p= nonsignificant).ConclusionIn intubated patients, pneumonia byA. baumanniiis not significantly associated with attributable mortality rate or an increased length of intensive care unit stay.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID