摘要:

ObjectiveThein vivoeffects of anti-interleukin-6 (anti-IL-6) and anti-interleukin-6-&agr; receptor (anti-IL-6R) monoclonal antibodies on immune response and survival rate of a burn with subsequent infection were assessed.SubjectsTen-week-old C 57 BL/6J mice received a standardized contact burn; 48 hrs later endotoxin (LPS) was injected intraperitoneally to induce systemic inflammation. Ten different groups were studied. Groups I–IV sustained a burn and/or a LPS-stimulus but did not receive any anti-cytokines and served as controls. Treatment groups V–X sustained the same injuries but also received anti-IL-6 and anti-IL-6R intravenously either before or after the LPS stimulus. In a further part of the study, a lethal dose of LPS was injected (LPS-LD100group) followed by an injection of anti-IL-6 antibody and/or anti-IL-6R antibody.MeasurementsSerum concentrations of IL-6, tumor necrosis factor (TNF)-&agr;, interferon (IFN)-&ggr;, and white blood cell and platelet counts were determined, and the survival rate over a 2-wk period was assessed.ResultsTreatment with anti-IL-6 slightly decreased the inflammatory response when it was given before or after LPS application. The inflammatory response was not decreased after treatment with anti-IL-6R. In the groups that received a combination of anti-IL-6 and anti-IL-6R, there was a significant reduction of the inflammatory response. This was more pronounced when the anti-cytokines were applied after LPS application. A significant reduction in mortality could be shown with both antibodies in the treatment groups and the groups that had received a lethal dose of LPS (LPS-LD100group).ConclusionsIL-6 has a low inflammatory potential, and IL-6R has no inflammatory potential by itself.In contrast, the IL-6/IL-6R complexes have a higher inflammatory potential. Mortality could be reduced by each antibody alone as well as by the combination, supporting the hypothesis that the inflammatory and lethal potentials of IL-6 are not identical. The study suggests that the use of antibodies against IL-6 or IL-6R is effective in the prevention of systemic inflammation in a murine burn model.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo determine the effects of titrated arginine vasopressin (AVP) alone or in combination with norepinephrine (NE) on hemodynamics and oxygen transport in healthy and endotoxemic sheep.DesignProspective controlled trial.SettingUniversity research laboratory.SubjectsSix adult ewes.InterventionsHealthy sheep received AVP as a titrated infusion, initiated with 0.6 units/hr and increased by 0.6 units/hr every 15 mins, either until mean arterial pressure was increased by 20 mm Hg vs. baseline or a maximum of 3.6 units/hr was administered. After 90 mins, AVP infusion was continued with the investigated dosage, and NE (0.2 &mgr;g·kg−1·min−1) was also infused for 90 mins. After a 24-hr period of recovery, endotoxemia was induced and maintained (Salmonella typhosaendotoxin, 10 ng·kg−1·min−1) in the same sheep for the next 19 hrs. After 16 hrs of endotoxemia, AVP and NE were administered as described previously.Measurements and Main ResultsHemodynamics were obtained at baseline, every 15 mins during the titration period, and 60 and 90 mins after additional NE infusion. Variables of oxygen transport were calculated before and after the titration period. In healthy and endotoxemic sheep, AVP reduced heart rate and cardiac index (p< .001) and compromised oxygen delivery (p< .001) and oxygen consumption (healthy sheep,p= .003; endotoxemic sheep,p< .001). Vasopressin infusion did not alter mean pulmonary arterial pressure but increased pulmonary vascular resistance index in both groups (p< .001). Additional infusion of NE further augmented mean arterial pressure and increased cardiac index during endotoxemia (p< .001). This was accompanied by an increase in oxygen delivery and consumption (p< .05 each).ConclusionsDuring ovine endotoxemia, AVP decreased cardiac index, compromised oxygen delivery, and increased pulmonary vascular resistance index. These side effects may limit its use as a sole vasopressor during sepsis. Potentially, a simultaneous infusion of AVP and NE could represent a useful therapeutic option.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe derangement of the nitric oxide pathway is an important contributing factor to the pathogenesis of septic shock. The aim of this study was to investigate potential differences in modulation of such a pathway in two experimental models of endotoxemia.DesignProspective, randomized, placebo-controlled animal investigation.SettingCardiovascular research laboratory.SubjectsMale, anesthetized, and mechanically ventilated New-Zealand rabbits (n = 24) and Sprague-Dawley rats (n = 24).InterventionsAfter pretreatment with 1400W (1 mg kg−1subcutaneously), an inhibitor of inducible nitric oxide synthase, animals received an intravenous bolus ofEscherichia Colilipopolysaccharides (5 mg kg−1). After 4 hrs, lungs, myocardial left ventricles, and aortas were collected.Measurements and Main ResultsBlood mean arterial pressure, pH, and nitrite/nitrate were monitored. Nitric oxide in the exhaled air was measured by chemiluminescence. Tissue activity of both constitutive nitric oxide synthase and inducible nitric oxide synthase was determined by measuring the conversion of [3H]l-arginine to [3H]l-citrulline. In lipopolysaccharide-treated animals, both mean arterial pressure (after 60 to 90 mins) and blood pH (after 4 hrs) decreased with respect to baseline values. 1400W prevented lipopolysaccharide-induced hypotension only in rats (p< .01). Exhaled nitric oxide decreased in lipopolysaccharide-treated rabbits by 120 mins (from 12.6 ± 0.6 to 8.4 ± 0.6 ppb,p< .01) and remained low until the end of the experiment (p< .01 vs. baseline). Conversely, exhaled nitric oxide increased in lipopolysaccharide-treated rats by 120 mins (from 0.4 ± 0.1 to 5.3 ± 1.7 ppb,p< .01) and reached aplateauby 210 mins (19.8 ± 3.1 ppb,p< .01 vs. baseline). 1400W prevented the lipopolysaccharide-induced increase in exhaled nitric oxide and blood nitrite/nitrate in rats (p< .05). Inducible nitric oxide synthase activity increased in endotoxemic rabbit heart (0.19 ± 0.05 vs. 0.07 ± 0.02 pmol l-citrulline/min/mg protein in the control group,p< .05) and in all rat tissues, being more striking in the lungs (25.00 ± 0.01 vs. 0.19 ± 0.04 pmol l-citrulline/min/mg protein in the control group,p< .001).ConclusionsThe nitric oxide pathway is differently modulated between endotoxemic rabbits and rats.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Rationale and HypothesisAcute lung injury is a frequent complication of severe sepsis or blood loss and is often associated with an excessive inflammatory response requiring mechanical ventilation. We tested the hypothesis that the types of fluids used during early resuscitation have an important effect on the evolution of lung injury.MethodsRats were subjected to either hemorrhage or endotoxemia for 1 hr, followed by resuscitation to a controlled mean blood pressure with Ringer’s lactate, 5% albumin, or 25% albumin for 1 hr. After resuscitation, blood cytokine levels were measured. The lung was then excised and ventilated with a tidal volume of 30 mL/kg for 2 hrs.ResultsThe volume of fluids required was significantly smaller in the albumin-treated groups than in the Ringer’s lactate groups. In the hemorrhagic shock model, plasma concentrations of tumor necrosis factor-&agr;, interleukin-6, and macrophage inflammatory protein-2 were significantly lower and interleukin-10 was significantly higher in the albumin-treated groups compared with the Ringer’s lactate–treated group. The levels of tumor necrosis factor-&agr; and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were lower and interleukin-10 was higher in the albumin-treated groups than in the Ringer’s lactate group. The decreased cytokine production was associated with a reduction of hydrogen peroxide formation with albumin resuscitation. The lung wet/dry ratio was lower in the 5% albumin (0.54 ± 0.01) and 25% albumin (0.55 ± 0.02) groups than in the Ringer’s lactate group (0.62 ± 0.02; bothp< .05). These effects of albumin seen in the hemorrhagic shock model were not observed in the endotoxic shock model.ConclusionsWe conclude that resuscitation with albumin may have utility in reducing ventilator-induced lung injury after hemorrhagic shock, but not after endotoxic shock. These findings suggest that the mechanisms leading to ventilator-induced lung injury after hemorrhage differ from those after endotoxemia.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesThis study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60–120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest.DesignProspective experimental comparison of three arrest times, without randomization.SettingUniversity research laboratory.SubjectsTwenty-seven custom-bred hunting dogs (17–25 kg).InterventionsDogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2°C (at a rate of 1 L/min), until tympanic temperature reached 20°C (for 60 mins of cardiac arrest), 15°C (for 60 mins of cardiac arrest), or 10°C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34°C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs.Measurements and Main ResultsWe assessed overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0–40, mild; 40–100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20°C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0–27%); and median total HDS, 28 (range, 4–36). Tympanic temperature of 15°C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0–3%), and HDS 8 (0–48). Tympanic temperature 10°C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2–18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10°C was achieved after flush of 15 mins and resulted in all six dogs with OPC 1, NDS 0%, and HDS 8 (0–37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10°C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22.ConclusionsIn a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10°C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest—which rarely can be resuscitated effectively with current methods—can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveTo characterize surfactant kineticsin vivoin two groups of premature infants on different levels of mechanical ventilation and at different risk of developing bronchopulmonary dysplasia.DesignControlled observational study in two independent groups of infants.SettingNeonatal intensive care unit.PatientsThirteen preterm infants (26 ± 0.5 wks, birth weight 801 ± 64 g) on high ventilatory setting and who finally all developed bronchopulmonary dysplasia (MechVentBPD), and eight (26 ± 0.5 wks, birth weight 887 ± 103 g) who had minimal or no lung disease and of whom none developed bronchopulmonary dysplasia (MechVentNoBPD).Measurements and Main ResultsEndotracheal13C-labeled dipalmitoyl-phosphatidylcholine was administered and subsequent measurements of the13C enrichment of surfactant-disaturated phosphatidylcholine (DSPC) from serial tracheal aspirates were made by gas chromatography-mass spectrometry. We calculated disaturated phosphatidylcholine pharmacokinetic variables in terms of half-life and apparent pool size from the enrichment decay curves over time. DSPC concentration from tracheal aspirates was expressed as milligrams/milliliter epithelial lining fluid (ELF-DSPC). Data are presented as mean ± se. In MechVentBPD infants vs. MechVentNoBPD, ELF-DSPC was much reduced, 2.9 ± 0.6 vs. 9.4 ± 3.0 mg/mL ELF (p= .03), half-life was shorter, 19.4 ± 2.8 vs. 42.5 ± 6.3 hrs (p= .002), and apparent pool size larger, 136 ± 21 vs. 65.8 ± 16.0 mg/kg (p= .057). In MechVentBPD, apparent DSPC pool size positively correlated with mean airway pressure × Fio2and inversely correlated with ELF-DSPC. ELF-DSPC was inversely correlated with mean airway pressure × Fio2. No significant correlations were found in the MechVentNoBPD group.ConclusionsMechVentBPD infants showed profound alteration of surfactant kinetics compared with preterm infants with minimal lung disease, and these alterations were correlated with severity of ventilatory support.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveIntracranial pressure (ICP) monitoring is frequently used in intensive care treatment of patients with intracranial hemorrhage. Data demonstrating an improved outcome from this intervention are lacking. We analyzed standardized mortality ratios in patients with and without ICP monitoring to determine its efficacy.DesignA nonrandomized study of case records of consecutively admitted intensive care unit (ICU) patients with intracranial hemorrhage.SettingGeneral and medical ICU of a 900-bed tertiary-care hospital.PatientsA total of 225 patients with intracranial hemorrhage (mainly nontraumatic) admitted consecutively between April 1997 and March 2000.MeasurementsSimplified Acute Physiology Score (SAPS) II, diagnosis, age, sex, use of ICP monitoring, and in-hospital mortality rates were collected from the hospital’s ICU database. Expected mortality was provided by means of SAPS II. Standardized mortality ratios were calculated and compared in 119 patients with ICP monitoring and 106 patients without ICP monitoring.Main ResultsThe case mix-adjusted hospital mortality in the group with ICP monitoring was in the expected range (standardized mortality ratio, 1.09 [95% confidence interval (CI), 0.87–1.31]). Patients without ICP monitoring had a significantly higher standardized mortality ratio than expected (1.26 [95% CI, 1.06–1.46]).ConclusionsA beneficial effect of ICP monitoring in patients with intracranial hemorrhage may be reflected in an improved standardized mortality ratio.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundIn 1976, the first hospital policies on orders not to resuscitate were published in the medical literature. Since that time, the concept has continued to evolve and evoke much debate. Indeed, few initials in medicine today evoke as much symbolism or controversy as the Do-Not-Resuscitate (DNR) order.ObjectiveTo review the development, implementation, and present standing of the DNR order.DesignReview article.Main ResultsThe DNR order concept brought an open decision-making framework to the resuscitation decision and did much to put appropriate restraint on the universal application of cardiopulmonary resuscitation for the dying patient. Yet, even today, many of the early concerns remain.ConclusionsAfter 25 yrs of DNR orders, it remains reasonable to presume consent and attempt resuscitation for people who suffer an unexpected cardiopulmonary arrest or for whom resuscitation may have physiologic effect and for whom no information is available at the time as to their wishes (or those of their surrogate). However, it is not reasonable to continue to rely on such a presumption without promptly and actively seeking to clarify the patient’s (or surrogate’s) wishes. The DNR order, then, remains an inducement to seek the informed patient’s directive.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ContextEnd-of-life care remains a challenging and complex activity in critical care units. There is little information concerning the influence of administrative models of care delivery on end-of-life care.ObjectiveTo compare and contrast end-of-life care delivery in intensive care units using “semiclosed,” “open,” and “closed” administrative models.DesignEthnographic study of three critical care units.SettingUniversity hospitals in the United States and New Zealand.SubjectsApproximately 600 physicians, nurses, allied health personnel, patients, family members, and friends.Measurements and Main ResultsEthnographic observations were made at three sites for 75, 3, and 10 wks, respectively. Eighty end-of-life care episodes were observed. The interactions among care personnel and families varied according to the administrative model, depending on whether surgeons or intensivists had primary patient responsibility. This led to differential timing on the shift from “cure” to “comfort,” and differential decision-making power for families.ConclusionsEnd-of-life care varies according to the administrative model. When surgeons have primary responsibility for the patient, the most important goal is defeating death. When intensivists have sole patient responsibility, scarce resources are considered and quality of life is a significant variable. Discussions about improving the way end-of-life decisions are carried out in intensive care units rarely consider the administrative models and personal, professional, and national values affecting such decisions. To improve care at the end of life, we must critically examine these features.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundSepsis is not a single disease but a complex and heterogeneous process. Its expression is variable, and its severity is influenced by the nature of the infection, the genetic background of the patient, the time to clinical intervention, the supportive care provided by the clinician, and a number of factors as yet unknown. The evaluation of effective therapies has been hampered by limitations in our ability to characterize the process and to stratify patients into more homogeneous groups with respect to pathogenesis.ObjectivesTo develop a taxonomy of markers relevant to clinical research in sepsis and to propose a testable candidate system for stratifying patients into more therapeutically homogeneous groups.Data SourceAn expert roundtable discussion and a MEDLINE review using search terms “marker” and “sepsis.”ResultsMarkers provide information in one or more of three domains: diagnosis, prognosis, and response to therapy. More than 80 putative markers of sepsis have been described. All correlate with the risk of mortality (prognosis), yet none has shown utility in stratifying patients with respect to therapy (diagnosis) or in titrating that therapy (response). Their limitations arise from the challenges of establishing causality in a complex disease process such as sepsis and of stratifying patients into more homogeneous populations. The former limitation may be addressed through a modification of Koch’s postulates to differentiate causality from simple association. The latter suggests the need for a staging system analogous to those used in other complex disease processes such as cancer. A candidate framework for such a system, based on the infection, the host response, and the extent of organ dysfunction (the IRO system) is described.ConclusionsAdvances in the understanding and management of patients with sepsis will necessitate more rigorous approaches to disease description and stratification. Models should be developed, tested, and modified through clinical studies rather than through consensus.

ISSN:0090-3493    

出版商:OVID    

年代:2003

数据来源: OVID