ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Limulus anti-lipopolysaccharide factor, an 11.8-kilodalton peptide isolated from amebocytes ofLimulus polyphemusinhibits the biologic activities of endotoxinin vitro, including gelation ofLimulusamebocyte lysate. A recombinant version ofLimulusanti-lipopolysaccharide factor, termed endotoxin neutralizing protein, has now been expressed in yeast. Endotoxin-neutralizing protein was evaluated for its potential prophylactic and therapeutic effects in rabbits challenged withEscherichia coliendotoxin.Design:Controlled animal trial.Setting:Animal research laboratory.Subjects:A total of 112 New Zealand white rabbits were studied.Interventions:Rabbits were challenged with an LD80 dose ofE. coliendotoxin (100 μg/kg); control animals (n = 52) were treated with saline solution at the time of endotoxin challenge; experimental animals received endotoxin-neutralizing protein 2.5 mg/kg prechallenge (n = 20), 5.0 mg/kg prechallenge (n = 20), or 5.0 mg/kg 30 mins postchallenge (n = 20).Measurements and Main Results:Rabbits treated with endotoxin-neutralizing protein before endotoxin challenge maintained stable mean arterial pressures and arterial pH and bicarbonate values which were significantly higher than controls during a 6–hr observation period. Geometric mean serum endotoxin concentrations were significantly lower in animals treated before endotoxin challenge as compared with controls measured at 30 mins and hourly after endotoxin challenge. Animals treated with endotoxin-neutralizing protein 30 mins after challenge had significantly lower geometric mean serum endotoxin concentrations measured 60 mins and hourly after challenge. Geometric mean serum tumor necrosis factor concentrations were lower in all treated animals compared with controls, but significantly so only in animals treated with endotoxin-neutralizing protein 2.5 mg/kg before endotoxin challenge.Survival to 24 hrs was significantly improved compared with controls in rabbits treated with endotoxin-neutralizing protein 2.5 mg/kg prechallenge (85% vs. 29%,p< .001), and with endotoxin-neutralizing protein 5.0 mg/kg prechallenge (90% vs. 29%,p< .001); animals treated with endotoxin-neutralizing protein 5.0 mg/kg postchallenge demonstrated improved survival compared with controls (55% vs. 29%,p= .055), although not significantly so.Conclusions:Endotoxin-neutralizing protein attenuates the toxic effects ofE. coliendotoxin in rabbits and improves survival, even when administered after endotoxin challenge. Endotoxin-neutralizing protein deserves further evaluation as a potential therapy for Gram-negative sepsis. (Crit Care Med 1994; 22:1211–1218)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To determine which of a series of disposable or interchangeable positive end-expiratory pressure (PEEP) devices functions with the least imposition of inspiratory and expiratory work during continuous positive airway pressure.Design:Prospective laboratory evaluation performed on a lung model.Setting:Research laboratory at a university medical center.Interventions:A spontaneously breathing lung model, created from a training test lung and a volume ventilator, were used to simulate a patient spontaneously breathing at a tidal volume of 0.4 L, peak inspiratory flow of 40 IV min, an inspiration/expiration ratio of 1:2, and a respiratory rate of 20 breaths/min. Ten PEEP valves attached to a continuous high-flow system were evaluated.Measurements and Main Results:All of the PEEP valves studied imposed high levels of both inspiratory and expiratory work of breathing. The BE-171 and BE-142 valves (Instrumentation Industries) imposed the least amount of inspiratory work. In general, imposed inspiratory work accounted for −70% to 80% of total imposed work of breathing.Conclusions:All of the disposable/interchangeable PEEP valves that were studied imposed a considerable amount of both inspiratory and expiratory work, even when the continuous flow provided exceeded the peak inspiratory flow demands of the lung model. The primary reason for the high imposed work levels is the high gas-flow resistance of all of the valves studied. (Crit Care Med 1994; 22:1219–1226)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We sought to determine whether there might be acute changes in hemodynamics attributable to HA-1A, a monoclonal antibody to endotoxin, in patients with presumed Gramnegative sepsis.Design: Post hocanalysis of a multicenter, randomized, double-blind, placebo-controlled study.Patients:A total of 543 patients with severe sepsis presumed to be caused by Gram-negative bacteria who were enrolled in a clinical trial to evaluate the efficacy and safety of HA-1A human monoclonal antibody.Interventions:Patients were randomly assigned to receive either 100 mg of HA-1A or placebo.Measurement and Main Results:Patients were grouped by the study drug, HA-1A, or placebo, and the presence or absence of Gram-negative bacteremia. Hemodynamic variables were monitored from before, until 72 hrs after infusion of the study drug. For the entire study population (n = 543), no changes over time attributable to study drug were noted in the mean arterial pressure (p> .19), heart rate (p> .53) or the need for vasopressor administration (p> .62). One hundred ninety-seven patients underwent pulmonary artery catheterization and had hemodynamic data available from before the infusion of HA-1A or placebo until at least 12 hrs after infusion. Evaluating all 197 patients on an intent to treat basis demonstrated no significant differences over time in cardiac index (p> .15), oxygen delivery index (p> .43), or left ventricular stroke work index (p> .48) between patients who received HA-1A and those patients receiving placebo. Grouping patients by the presence of Gram-negative bacteremia and study drug received also failed to demonstrate any significant difference attributable to HA-1A in mean arterial pressure (p> .54), heart rate (p> .84), cardiac index (p> .13), oxygen delivery index (p> .05), or left ventricular stroke work index (p> .48) between populations.Conclusion:There is no apparent relationship between the administration of HA-1A, the presence of Gram-negative bacteremia, and hemodynamic profiles over the 72-hr study period. (Crit Care Med 1994; 22:1227–1234)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The thermogenic effect of amrinone is unknown and its utilization in patients with severe cardiac failure could potentially increase oxygen requirements and therefore aggravate oxygen debt. Consequently, the present study was undertaken to assess the thermogenic response to amrinone at three different plasma concentrations under controlled conditions and to analyze amrinone's effects on various biochemical variables.Design:A prospective, unblinded, controlled study. The initial control period was followed by three sequential, experimental treatments.Subjects:Ten young, healthy, male volunteers with normal body weight.Interventions:Three experimental periods. Amrinone was administered intravenously in progressive doses: a) 0.5 mg/kg followed by 5 μg/ kg/min; b) 0.5 mg/kg followed by 10 μg/kg/min; and c) 1.0 mg/kg followed by 10 μg/kg/min.Measurements and Main Results:Oxygen consumption (o2) and CO2production were continuously measured by means of a computerized indirect calorimeter. At the highest dose, amrinone produced a slight and significant (p< .01) increase in o2and in resting metabolic rate (+4.5% and +3.7%, respectively), while no change in CO2production or in respiratory quotient occurred throughout the study. At the medium and high doses, amrinone increased plasma free fatty acid concentrations by 38% and 53%, respectively (p< .05). No variation in plasma glucose, lactate, insulin, norepinephrine, or epinephrine concentrations was observed during the study.Conclusions:Amrinone administered intravenously at therapeutic doses has minimal thermogenic and metabolic effects in humans without cardiac failure. (Crit Care Med 1994; 22:1235–1240)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To evaluate the efficacy of continuous infusions of lorazepam vs. midazolam for sedation in the intensive care unit (ICU).Design:Prospective, randomized study.Setting:Large, urban university hospital.Patients:Twenty adult medical ICU patients receiving mechanical ventilatory support.Interventions:Patients were randomized to receive either lorazepam or midazolam. The infusion rate was adjusted at the bedside by the ICU nurse according to a standardized study protocol to achieve and maintain sedation at Ramsay's sedation level 2 or 3.Measurements and Main Results:Ten patients were randomized to receive lorazepam and ten to receive midazolam. The groups were similar in demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, ICU admission diagnosis, underlying disease processes, and supplemental analgesic administration. The mean time to achieve initial adequate sedation was 124 mins for lorazepam and 105 mins for midazolam. The mean infusion rate at the point of initial sedation was 0.06 mg/kg/hr for lorazepam and 0.15 mg/kg/hr for midazolam. The maximum and mean infusion rates for the entire study period were 0.1 and 0.06 mg/kg/hr, respectively, for lorazepam and 0.29 and 0.24 mg/kg/hr, respectively, for midazolam. The number of infusion rate adjustments per day was 1.9 mg/kg/hr for lorazepam and 3.6 mg/kg/hr for midazolam. Of the surviving patients, the mean time to return to baseline mental status after discontinuation of the benzodiazepine infusion was 261 mins for lorazepam and 1815 mins for midazolam. The mean volume of fluid per day required to deliver the maximum dose of benzodiazepine was 1.2 L for lorazepam (maximum 2.4 L) and 1.3 L for midazolam (maximum 3.6 L).Conclusions:While there was a tendency to a longer time required for return to baseline mental status in patients receiving midazolam, this was not statistically signficant. Findings of interest concerning both midazolam and lorazepam were: a) time to achieve sedation in medical ICU patients is often prolonged; b) actual dose requirements necessary to maintain sedation in this patient population are larger than the current literature describes; c) time to awaken after discontinuation of the infusion was occasionally delayed for >24 hrs; d) large volumes of fluid were required to deliver these doses of drug via this route of administration. (Crit Care Med 1994; 22:1241–1247)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To assess the efficacy and hemodynamic safety of intravenous lorazepam as an amnestic and anxiolytic agent in patients undergoing critical care procedures.Design:Prospective study.Setting:Trauma/intensive care unit and coronary care unit of a 524-bed, tertiary, teaching community hospital.Subjects:Ten patients undergoing critical care procedures.Interventions:Intravenous lorazepam was administered at an initial dose of 2 mg, 15 to 20 mins before the critical care procedure (procedures included both invasive and noninvasive techniques) was performed. Anxiety level and memory assessment were evaluated at baseline and at various points following lorazepam administration. Changes in hemodynamic status were evaluated regularly throughout the study.Measurements and Main Results:No significant changes in hemodynamic measurements were observed after administration of intravenous lorazepam. Significant differences were seen in anxiety scores and amnestic effects from preprocedure/pre-lorazepam to post-lorazepam evaluations (allpvalues were <.O3).Conclusions:This study confirms the beneficial anxiolytic and amnestic effects of lorazepam in a subgroup of patients undergoing critical care procedures. The study also substantiates the safety of this drug in this patient population. (Crit Care Med 1994; 22:1248–1252)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To evaluate the efficacy of nasal mechanical ventilation in patients with chronic obstructive pulmonary disease and hypercapnic respiratory failure and to identify predictors of success or failure of nasal mechanical ventilation.Design:Prospective case series.Setting:Medical intensive care unit in Veterans Administration Medical Center.Patients:Twelve chronic obstructive pulmonary disease patients treated during 14 episodes of hypercapnic respiratory failure.Interventions:Nasal mechanical ventilation in addition to conventional therapy to treat hypercapnic respiratory failure. Patients underwent nasal mechanical ventilation for at least 30 mins, or longer if the therapy was tolerated. Responses to therapy and arterial blood gases were monitored.Measurements and Main Results:Half of the episodes were successfully treated with nasal mechanical ventilation. There were no differences hi age, prior pulmonary function, baseline arterial blood gases, admission arterial blood gases, or respiratory rate between those patients successfully treated and those patients who failed nasal mechanical ventilation. Unsuccessfully treated patients appeared to have a greater severity of illness than successfully treated patients, as indicated by a higher Acute Physiology and Chronic Health Evaluation II score (mean 21 × 4 [SD] VS. 15 ±4;p= .02). Unsuccessfully treated patients were edentulous, had pneumonia or excess secretions, and had pursed-lip breathing, factors that prevented adequate mouth seal and contributed to greater mouth leaks than in successfully treated patients (the mean volume of the mouth leak was 314 ±107 vs. 100 ±70 mL;p< .01). Successfully treated patients were able to adapt more rapidly to the nasal mask and ventilator, with greater and more rapid reduction in Paco2, correction of pH, and reduction hi respiratory rate.Conclusions:Patients who failed nasal mechanical ventilation appeared to have a greater severity of illness; they were unable to minimize the amount of mouth leak (because of lack of teeth, secretions, or breathing pattern) and were unable to coordinate with the ventilator. These features may allow identification of poor candidates for nasal mechanical ventilation, avoiding unnecessary delays in endotracheal intubation and mechanical ventilation. (Crit Care Med 1994; 22:1253–1261)

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To study the effect of severe prolonged hypoxia combined with ligation of the carotid artery and jugular vein (simulating preextracorporeal membrane oxygenation [ECMO] events) on cerebral autoregulation in the newborn lamb.Design:Animal studies, using the newborn lamb, with comparison of two randomized treatment groups.Subjects:Newborn lambs of mixed breed, 1 to 7 days of age, were used for the study. Two groups of animals were studied: a normoxic control group (n = 7) and a hypoxic group (n = 8).Setting:Work was conducted in the research laboratories of the Department of Anesthesiology, Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD.Interventions:Animals were anesthetized (pentobarbital), intubated, and mechanically ventilated. We examined the effect of prolonged severe hypoxia combined with carotid artery and jugular vein ligation on cerebral autoregulation during recovery from this insult. Control animals were maintained in a normoxic state (3 hrs) without carotid artery or jugular vein ligation. Hypoxic animals with carotid artery and jugular vein ligation were exposed to a 2-hr period of hypoxia (arterial oxygen saturation 44 ±14%; Pao230 ±3 torr [4 ±0.4 kPa]) followed by a 1-hr normoxic recovery period. Cerebral autoregulation was evaluated at the end of the 1-hr recovery period in hypoxic animals, and after 3 hrs of normoxia in control animals. Cerebral perfusion pressure was decreased by increasing intracranial pressure, with infusion of artificial cerebrospinal fluid into an intracranial pressure catheter in the lateral ventricle of the brain.Measurements:Studies were taken at four ranges of cerebral perfusion pressure: >55 mm Hg; 55 to 40 mm Hg; 39 to 26 mm Hg; and ±25 mm Hg. Cerebral blood flow was measured using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period.Main Results:Two hours of severe hypoxia increased cerebral blood flow by 110%, whereas cerebral oxygen consumption was unchanged. In hypoxic animals, cerebral autoregulation was altered, with both cerebral blood flow and cerebral oxygen consumption decreasing at a cerebral perfusion pressure of 39 to 26 mm Hg compared with unchanged cerebral blood flow or cerebral oxygen consumption at a cerebral perfusion pressure of ±25 mm Hg in control animals. At the point of loss of autoregulation, significant right-to-left hemispheric cerebral blood flow changes occurred in hypoxic animals. In hypoxic animals, cerebellar cerebral blood flow changes were similar to those changes in the total cerebrum, while brain stem and caudate decreased cerebral blood flow only at a cerebral perfusion pressure of ±25 mm Hg.Conclusions:These findings indicate that cerebral autoregulation is disrupted during the recovery phase from an insult caused by prolonged, severe hypoxia with carotid artery and jugular vein ligation. This insult results in significant differences in right and left

ISSN:0090-3493    

出版商:OVID    

年代:1994

数据来源: OVID