摘要:

ObjectiveTo compare the potential therapeutic effect of liposomal vs. free cefoxitin.DesignRandomized, controlled study, using a rat model of peritonitis.SettingGovernment research facility.SubjectsMale Sprague-Dawley rats.InterventionsRats were infused intraperitoneally with 6.5 x 108colony forming units of Escherichia coli over 12 hrs. Animals were then randomized to receive intravenous saline, free cefoxitin, liposomal cefoxitin, or plain liposomes twice daily until they were killed.Measurements and Main ResultsFree cefoxitin significantly reduced the number of E. coli after 24 hrs compared with saline treatment in both liver and spleen. However, liposomal cefoxitin further decreased the bacterial content by five-fold to ten-fold in these organs. Minimal bactericidal effect was observed in animals injected with plain liposomes. Although administration of liposomal cefoxitin for 7 days further reduced bacterial counts in liver and spleen, there was no apparent beneficial bactericidal effect of free cefoxitin over saline at 7 days. There was approximately a ten-fold reduction in bacterial content in the lungs after 24 hrs in all three treatments, but no further reduction was observed after 7 days. There was no difference in 7-day survival rate in animals treated with plain liposomes or saline (45% vs. 39%). Although survival tended to increase with free cefoxitin treatment (64%), this outcome was significantly improved with the use of liposomal cefoxitin (82%).ConclusionsLiposomal cefoxitin enhanced bacterial killing in liver and spleen in this model of E. coli peritonitis. It also improved survival outcome relative to no treatment but not compared with free cefoxitin. (Crit Care Med 1999; 27:1153-1158)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveMagnesium sulfate (MgSO4) has been reported to produce bronchodilation in asthmatic patients. In vitro studies have suggested that divalent cations inhibit L-type voltage-sensitive calcium ion (Ca2+) channels in cardiac and smooth muscles. In this study, we evaluated the in vitro and in vivo effects of magnesium ion (Mg (2+)) and zinc ion (Zn2+) on the airway contracted by histamine.SettingA university research laboratory.SubjectsIn vitro: Tracheal smooth muscle from guinea pigs. In vivo: Mongrel dogs.Measurements and Main ResultsIn vitro study: The tension of isolated guinea pig tracheal strips was measured isometrically with a force displacement transducer. The specimen was contracted with histamine (10 [micro sign]M). Then, MgSO4(n = 6), zinc sulfate (ZnSO4, n = 6), or sodium sulfate (Na2SO4, n = 6) was cumulatively added to the organ bath. In vivo study: The bronchial cross-sectional area of mongrel dogs was measured by a direct visualization method demonstrated previously. The dogs were randomly assigned to three groups: group Mg (n = 7), group Zn (n = 7), and group Na (n = 7). Bronchoconstriction was elicited with histamine (10 [micro sign]g/kg plus 500 [micro sign]g/kg/hr iv). Thirty minutes after the start of histamine infusion, 0 (saline), 1, 10, and 100 [micro sign]mol/kg ZnSO4or 1, 10, 100, and 1000 [micro sign]mol/kg MgSO4or Na2SO4were administered intravenously in group Zn, Mg, or Na, respectively. The bronchial cross-sectional area was assessed before (basal) and 30 mins after the start of histamine infusion and 5 mins after each dose of ZnSO4, MgSO4, or Na2SO4. Arterial blood was also obtained to measure plasma levels of epinephrine and norepinephrine by gas chromatography-mass spectrometry. All data are expressed as mean +/- SEM. The doses of the divalent cations that reversed histamine-induced contraction by 50% were calculated by GraphPad Prism. MgSO4and ZnSO4(9.38 +/- 0.28 and 1.84 +/- 0.30 mM, respectively) relaxed histamine-contracted tracheal strip in a concentration-dependent manner, whereas Na2SO4did not. Similarly, the in vivo study showed that MgSO4and ZnSO4dose-dependently reversed histamine-induced bronchoconstriction (potency, ZnSO4MgSO4), whereas Na2SO4did not. In groups Mg and Zn, the plasma catecholamine levels also dose-dependently increased except when 1000 [micro sign]mol/kg MgSO4was administered.ConclusionBecause the divalent cations tested produced a spasmolytic effect on the contracted airway, infusion of divalent cations might be effective against asthmatic attack. However, high concentrations of these cations produce significant toxicity, so dosage will be an important concern in development of these agents. (Crit Care Med 1999; 27:1159-1163)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-alpha release in experimental endotoxemia.DesignProspective, randomized, controlled animal study.SettingExperimental laboratory.SubjectsTwenty-one male Wistar rats weighing 190 +/- 40 g.InterventionsThe rats were divided equally into 3 groups: a) control; b) endotoxemia (5 mg/kg lipopolysaccharide [LPS] from Escherichia coli 055:B5); and c) endotoxemia and U-74389G administration 30 mins before (3 mg/kg) and 60 mins after (1.5 mg/kg) endotoxin challenge.Measurements and Main ResultsAt 0, 120, and 240 mins, serum levels of TNF-alpha were measured using a specific rat TNF-alpha ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-alpha release 120 mins after endotoxin challenge (control, 2.5 +/- 2.1 pg/mL; LPS, 4041 +/- 871 pg/mL; U-74389G, 1627 +/- 474 pg/mL [p < .05]). Two hundred forty minutes after LPS administration, TNF-alpha levels decreased, whereas values in the untreated LPS group remained twice as high as those in the U-74389G group (LPS, 863 +/- 182 pg/mL; U-74389G, 369 +/- 54 pg/mL [p < .05]).ConclusionsThe study demonstrated that administration of U-74389G, which has radical-scavenging and membrane-stabilizing properties, decreased TNF-alpha release during endotoxemia. Thus, 21-aminosteroids may lend themselves to evaluation in the treatment of septic states. (Crit Care Med 1999; 27:1164-1167)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an in vivo model.DesignProspective, randomized, controlled, experimental study.SettingUniversity experimental pharmacology laboratory.SubjectsMechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs.InterventionsThe piglets were randomly assigned either to a treatment group receiving 20 ppm inhaled NO from the onset of ventilation (n = 5) or to a control group (n = 6) receiving no treatment.Measurements and Main ResultsThe main variables studied were gas exchange (PaO2/FIO2ratio, lung diffusing capacity), respiratory mechanics (static compliance of the respiratory system, stat, quasi-static hysteresis area, functional residual capacity), and pulmonary vascular permeability assessed by simultaneous intravenous administration of iodine-125-labeled albumin and chromium-51-labeled red blood cells. Extravascular albumin space of the lung and dry lung weight were significantly higher in the NO group vs. the control group (albumin space, 1.08 +/- 0.16 vs. 0.70 +/- 0.26 [SD] mL/kg body weight [p < .05]; dry lung weight, 3.20 +/- 0.34 vs. 2.66 +/- 0.14 g/kg body weight [p < .05]). Moreover, the hysteresis area was higher from 24 hrs of NO exposure. Conversely, NO inhalation altered neither the extravascular lung water content (12.98 +/- 2.79 mL/kg body weight in the NO group vs. 12.18 +/- 2.26 mL/kg body weight in the control group [not significant]) nor the main respiratory mechanical variables (static compliance, functional residual capacity) and gas exchange (lung diffusing capacity, PaO2/FIO2ratio).ConclusionThese results do not support the hypothesis that NO inhalation combined with hyperoxia can alter the main lung-function variables in neonates. However, it may induce an increase in lung vascular protein leakage. The pathophysiologic consequences of this finding remain to be elucidated. (Crit Care Med 1999; 27:1168-1174)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo characterize the incidence and severity of splanchnic ischemia, as defined by gastric tonometry, in patients with isolated severe head injury and to examine the relationship between cerebral hemodynamics and splanchnic ischemia.DesignProspective observational study.SettingNeurosurgical intensive care unit in a tertiary referral center.PatientsTen patients with severe neurotrauma.InterventionsNone.Measurements and Main ResultsThe mean arterial pressure, intracranial pressure, and gastric mucosal PCO2measurements were recorded at 15-min intervals. Intramucosal pH was calculated every 3 hrs. All patients received stress ulcer prophylaxis. Nine patients received noradrenaline infusions to maintain a target cerebral perfusion pressure of 70 mm Hg. The mean baseline gastric mucosal PCO2and intramucosal pH were 38 +/- 10 torr and 7.38 +/- 0.1 pH units, respectively. Nine patients manifested low intramucosal pH during the study period. Gastric mucosal PCO2values ranged from 36 to 132 torr. Intramucosal pH measurements ranged from 6.9 to 7.47. The mucosal gap ranged from -12 to +93 torr (mean +/- SD, 17 +/- 17 torr). The pH gap ranged from -0.1 to +0.54 pH units (mean +/- SD, 0.14 +/- 0.11 pH units). There was no statistically significant relationship between cerebral hemodynamics, the use of inotropes, and gastric mucosal PCO2, or intramucosal pH.ConclusionsSplanchnic ischemia (intramucosal pH, <7.3) occurs commonly in isolated neurotrauma, with a statistically nonsignificant trend toward development of mucosal ischemia with decreased cerebral perfusion. (Crit Care Med 1999; 27: 1175-1180)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesTo assess the prognosis of pediatric bone marrow transplant recipients requiring mechanical ventilation and to identify risk factors for mortality.DesignRetrospective chart review.SettingPediatric intensive care unit (PICU), tertiary care center.PatientsInclusion criteria were endotracheal intubation and mechanical ventilation after bone marrow transplantation; patients with perioperative ventilation were excluded. Outcome measures were extubation, PICU discharge, and 6-month survival. The 39 patients who met the inclusion criteria were ventilated on 41 occasions.InterventionsNone.Measurements and Main ResultsOverall survival rate to PICU discharge was 44% (17 of 39 patients). Six months after PICU discharge, 14 of these children were still alive, for a medium-term survival rate of 36%. Preexisting conditions (primary disease, bone marrow engraftment, or graft-vs.-host disease) had no significant effect on survival. Multiple organ failure, especially pulmonary failure and neurologic deterioration, were significant determinants of patient survival.ConclusionsThe observed prognosis is improved over previous reports. Early initiation of aggressive intensive care treatment is warranted in this patient group. Decisions regarding intensity of treatment must be based on aspects of the acute illness rather than on the primary conditions. (Crit Care Med 1999; 27:1181-1186)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesMeningococcal disease is a homogeneous and well-characterized form of sepsis. Cardiovascular collapse is prominent in severe meningococcal disease. Nitric oxide overproduction may be a mediator of cardiovascular collapse. We relate the level of nitric oxide metabolites, nitrates and nitrites, to disease severity in meningococcal disease.DesignProspective, nonrandomized study.SettingTertiary referral pediatric intensive care unit.PatientsChildren admitted with a clinical diagnosis of meningococcal disease.InterventionsBlood was sampled from children with meningococcal disease. Disease severity was scored using the Glasgow meningococcal septicemia prognostic score and pediatric risk of mortality score. Plasma nitrates and nitrites were measured in stored plasma using the Greiss reaction after conversion of all the nitrate to nitrite.Measurements and Main Resultsor=to8 (severe). Three children died, all of these being in the severely affected group. Higher levels of nitrates and nitrites were seen in the more severely affected children (median admission nitrates and nitrites, 27.5 vs. 59.7 nmol/mL; p = 0.063; median peak nitrates and nitrites, 49.9 vs. 114 nmol/mL; p = .01) or those with an increased predicted mortality using pediatric risk of mortality (Spearman's rho 0.742; p = .0003).ConclusionsHigher levels of nitrates and nitrites are seen in sicker children with meningococcal disease. (Crit Care Med 1999;27:1187-1190)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID