摘要:

Objective:To evaluate a model describing postoperative hypoxemia after cardiac surgery by using two variables, i.e., shunt and resistance to oxygen diffusion (Rdiff).Design:Estimation of these two variables in normal subjects and postoperative cardiac patients.Setting:The pulmonary function laboratory for the normal subjects and the intensive care unit for the cardiac patients.Patients/Subjects:Nine postoperative cardiac patients and six healthy subjects.Interventions:Inspired oxygen fraction was varied in normal subjects and in cardiac patients 3-6 hrs after surgery. This variation occurred in four to seven steps to achieve arterial oxygen saturations in the range 0.90-1.00.Measurements and Main Results:Measurements were taken of arterial oxygen saturation, cardiac output, ventilation, and end-tidal gases at each inspired oxygen fraction. These measurements gave the following estimates for the normal subjects: shunt = 3.9 ± 5.4% (mean ± SD) and Rdiff= −5 ± 16 torr/(L/min) [−0.7 ± 2.2 kPa/(L/min)]; for the cardiac patients: shunt = 7.7 ± 1.8% and Rdiff= 212 ± 230 torr/(L/min) [28.2 ± 30.6 kPa/(L/min)]. The increase in Rdiff(p= .01) was sufficient to explain the observed hypoxemia in these patients. The value for shunt was not significantly increased in the patients (p= .09). The two-variable model (shunt and Rdiff) gave a better prediction of arterial oxygen saturation than a model with shunt as the only variable (p= .02).Conclusions:In cardiac patients requiring supplementary oxygen, the respiratory abnormality could, in our model, be best described by an increased Rdiff, not by an increased shunt value.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To compare the efficacy, safety, and cost of continuous infusions of lorazepam, midazolam, and propofol in a critically ill trauma/surgery patient population.Design:A prospective, randomized, nonblinded, single center.Setting:A 16-bed intensive care unit.Patients:A total of 30 ventilated patients who were 18-70 yrs of age and required pharmacologic sedation. Patients with renal and/or liver failure, a history of alcohol abuse, a head injury, or in a coma were excluded.Interventions:Patients were randomized by block design to receive lorazepam, midazolam, or propofol. Initial boluses and infusion rates were as follows: lorazepam 0.05 mg/kg, then 0.007 mg/kg/hr; midazolam 0.05 mg/kg, then 0.003 mg/kg/hr; and propofol 0.25 mg/kg, then 0.06 mg/kg/hr. Sedation was assessed and agents titrated every 5-10 mins to achieve ≥2 and <5 on the modified Ramsay scale. Once adequate response was achieved, agents were titrated to maintain the desired level of sedation.Measurements and Main Results:Maintenance doses of lorazepam 0.02 ± 0.01 mg/kg/hr, midazolam 0.04 ± 0.03 mg/kg/hr, and propofol 2.0 ± 1.5 mg/kg/hr achieved the desired level of sedation 68%, 79%, and 62% of the time, respectively. Oversedation occurred most often with lorazepam, compared with midazolam and propofol, at 14%, 6%, and 7% of the assessment times, respectively. Undersedation occurred most frequently with propofol compared with lorazepam and midazolam, at 31%, 18%, and 16% of the assessment times, respectively.The mean number of dosage changes per day was 7.8 ± 4.3 for lorazepam, 4.4 ± 2.9 for midazolam, and 5.6 ± 6.0 for propofol (p= .91). Sedation costs per patient day (mean ± SD) were $48 ± $76 (lorazepam), $182 ± $98 (midazolam), and $273 ± $200 (propofol) (p= .005). The potential savings, if all study patients had received lorazepam, is $14,208 compared with $8,808 if all received midazolam.Conclusions:The data suggest that lorazepam appears to be a cost-effective choice for sedation; however, oversedation may be problematic. Midazolam is the most titratable drug in our population, avoiding excessive oversedation or undersedation. Trauma patients may respond inadequately to propofol even at higher doses. Lorazepam may be the sedative of choice in critically ill trauma/surgery patients.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To determine the mechanism for the reduced polymorphonuclear neutrophil exudation to secondary inflammatory sites in critically ill patients with infection and systemic inflammatory response (sepsis).Design:Prospective cohort study.Setting:Research laboratory and integrated intensive care unit of a tertiary care university-affiliated teaching hospital.Patients:Healthy subjects or critically ill patients with confirmed infection and a systemic inflammatory response (septic patients).Measurements and Main Results:We found that polymorphonuclear neutrophil delivery to a secondary inflammatory site (skin window blisters) is reduced by >70% in humans with sepsis, defined as serious infection and a systemic inflammatory response compared with healthy controls. The expression of the endothelial adhesion molecules intercellular adhesion molecule-1, E-selectin and P-selectin in microvessels from skin biopsies was comparable in the two study groups. Also, CD11a and CD11b levels were equal in circulating polymorphonuclear neutrophils (PMNs) from both study groups. Both adhesion molecules were markedly and equally up-regulated during exudation. Circulating PMNs from septic patients showed marked shedding of L-selectin compared to those of healthy controls, with a corresponding increase in their plasma L-selectin levels. An increased concentration gradient between plasma and exudate fluid was found for tumor necrosis factor-α and interleukin-8 in septic patients, but not for C5a. The phagocytic and bactericidal capacity of septic patient circulating PMNs was higher then in healthy control patients, but these differences were lost after exudation. There were no major differences in oxidative burst or intracellular calcium flux of circulating PMNs from the two study groups. Polymorphonuclear neutrophil exudation primed both responses to different extents.Conclusions:Septic patients deliver fewer PMNs to secondary inflammatory sites. In addition, neutrophil exudation results in loss of the small priming effect for phagocytosis and bactericidal function induced by sepsis. Failure to produce a gradient to C5a and intravascular shedding of L-selectin may be responsible for this sepsis-induced reduction in neutrophil exudation to secondary inflammatory sites.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To determine whether pulmonary lactate production in patients with acute lung injury is attributable to lung tissue hypoxia.Design:Prospective, controlled, clinical study.Setting:A multidisciplinary university intensive care unit in a general hospital.Patients:Seventy consecutive critically ill patients requiring mechanical ventilation and invasive hemodynamic monitoring. Of these patients, 18 had no acute lung injury (no ALI); 33 had acute lung injury (ALI) (Lung Injury Score [LIS] ≤2.5); and 19 had acute respiratory distress syndrome (ARDS) (LIS >2.5).Interventions:None.Measurements and Main Results:After hemodynamic measurements, lactate and pyruvate concentrations were assessed in simultaneously drawn arterial (a) and mixed venous (v) blood samples. Pulmonary lactate release was calculated as the product of transpulmonary a-v lactate difference (L[a-v]) times the cardiac index. Two indices of anaerobic metabolism of the lung, i.e., the transpulmonary a-v difference of lactate pyruvate ratio (L/P[a-v]) and excess lactate formation across the lungs (XL), were calculated. L(a-v) and pulmonary lactate release were higher in patients with ARDS than in the other groups (p< .001), and they were also higher in patients with ALI compared with patients with no ALI (p< .001). In patients with ALI and ARDS (n = 52), pulmonary lactate release correlated significantly with LIS (r2= .14,p< .01) and venous admixture (r2= .13,p< .01). When all patients were lumped together (n = 70), pulmonary lactate release directly correlated with LIS (r2= .30,p< .001), venous admixture (r2= .26,p< .001), and P(A-a)O2(r2= .14,p< .01). Neither L/P(a-v) nor XL was significantly different among the three groups.Conclusion:The lungs of patients with ALI produce lactate that is proportional to the severity of lung injury. This lactate production does not seem to be attributable to lung tissue hypoxia.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis.Design:Prospective, controlled study in a sheep model of sepsis.Setting:Animal research facility in a university hospital.Subjects:Adult sheep weighing between 35 and 55 kg.Interventions:Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration ofEscherichia coli(1.5 × 108colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins.Measurements and Main Results:Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins.Conclusions:Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion ofE. coliand potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To define whether the gastric mucosal-arterial PCO2gradient (PCO2gap) reliably reflects hepatosplanchnic oxygenation in septic patients.Design:Prospective observational clinical study.Setting:An adult, 31-bed medical/surgical department of intensive care of a university hospital.Patients:A total of 36 hemodynamically stable, invasively monitored, mechanically ventilated, sedated, paralyzed patients with severe sepsis.Interventions:In each patient, hepatosplanchnic blood flow was determined by the continuous indocyanine green infusion technique and gastric mucosal PCO2by the saline tonometry technique. Suprahepatic venous blood oxygen saturation and PCO2also were measured. The mesenteric veno-arterial PCO2gradient was determined as the difference between the suprahepatic venous blood PCO2and the arterial blood PCO2.Measurements and Main Results:There were significant correlations between the hepatosplanchnic blood flow and the suprahepatic venous blood oxygen saturation (r2= .56;p< .01), between the hepatosplanchnic blood flow and the mesenteric veno-arterial PCO2gradient (r2= .55;p< .01), and also between the suprahepatic venous blood oxygen saturation and the mesenteric veno-arterial PCO2gradient (r2= .64;p< .01). There was no statistically significant correlation between the PCO2gap and the hepatosplanchnic blood flow, the suprahepatic venous blood oxygen saturation or the mesenteric veno-arterial PCO2gradient.Conclusions:In stable septic patients, the PCO2gap is not correlated with global indexes of gut oxygenation. The interpretation of PCO2gap is more complex than previously thought.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:Platelet-activating factor (PAF) and eicosanoids are putative mediators of septic shock that are associated with release of tumor necrosis factor (TNF). The purpose of this investigation was to a) examine temporal patterns of TNF and arachidonic acid metabolite release in a porcine model of bacteremic shock and b) selectively block PAF, thromboxane A2, prostacyclin, and leukotrienes to determine the relationships among these inflammatory response mediators and the alterations in cardiorespiratory dysfunction for which they are required.Design:Prospective, nonrandomized, controlled trial.Setting:Laboratory at a university medical center.Subjects:Thirty-four female Yorkshire swine.Interventions:Animals were divided into six experimental groups: five septic groups receiving an infusion ofAeromonas hydrophilaat 0.2 mL/kg/hr, gradually increasing to 0.4 mL/kg/hr over 4 hrs. Each of four septic groups was pretreated with a specific mediator inhibitor (PAF receptor antagonist, n = 6; prostacyclin antibody, n = 5; leukotriene synthesis inhibitor, n = 5; and thromboxane receptor antagonist, n = 6). One septic group (n = 6) received no mediator inhibitor and served as a septic control, and one anesthesia control group (n = 6) received no intervention.Measurements and Main Results:PAF receptor blockade significantly increased systemic hypotension and mixed venous oxygen saturation and decreased pulmonary artery pressure, oxygen extraction and consumption, hemoconcentration, and levels of TNF and eicosanoids. Leukotriene inhibition increased mean arterial pressure, pulmonary and systemic vascular resistance indices, and arterial and mixed venous oxygen saturation and reduced pulmonary hypertension, oxygen delivery, oxygen extraction, oxygen consumption, and all measured mediators. Thromboxane receptor blockade lowered TNF and leukotriene levels, ameliorated systemic and pulmonary vasoconstriction, and significantly increased arterial and tissue oxygenation compared with septic controls. Prostacyclin antagonism reduced prostacyclin plasma concentrations, arterial hypoxemia, and oxygen consumption during sepsis and increased circulating leukotriene B4.Conclusions:Elevations in plasma TNF predictably precede peak levels of eicosanoids in this model. PAF, leukotrienes, and thromboxane A2are necessary for pulmonary hypertension during bacteremia. Systemic hypotension and increased vascular permeability are mediated by both leukotrienes and PAF. There are complex interactions among mediators during sepsis and further studies are required to define these relationships.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:To determine the accuracy of intramucosal pH (pHi) calculated using arterial bicarbonate instead of mucosal capillary bicarbonate in the Henderson-Hasselbalch equation.Design:Simulation of progressive ischemia in mucosal capillary blood.Setting:University research laboratory.Subjects:Normal human blood diluted with plasma.Interventions:Three venous blood specimens were heparinized and diluted to a mean hemoglobin concentration of 5.0 (±0.9) g/dL by addition of plasma (2:1, vol:vol). Mucosal capillary aerobic flow stagnation was simulated by multiple exposures of each cooled specimen to a gas mixture containing 90% nitrogen and 10% CO2. When PCO2measured at 37°C (98.6°F) was approximately 120 torr (16 kPa), the assigned anaerobic threshold, subsequent anaerobic flow stagnation was simulated by mixing the hypercapnic specimens in sealed syringes with five to six successive small aliquots (<100 μL) of lactic acid (10 g/L).Measurements and Main Results:The relationship between PCO2and pH in the specimens was compared with the relationship between the same PCO2values and pHi calculated by substituting bicarbonate concentrations of 22 and 26 mmol/L in the Henderson-Hasselbalch equation. As PCO2rose from 50 torr (8 kPa), conventionally calculated pHi increasingly underestimated simulated mucosal capillary pH, with bias >0.1 pH unit at the simulated anaerobic threshold of 120 torr (16 kPa). As PCO2rose further the values converged, becoming equivalent at PCO2∼ 150 torr (20 kPa). From PCO2≥ 200 torr (26.7 kPa), conventional pHi progressively overestimated simulated mucosal pH. The difference was >0.3 pH units at PCO2= 250 torr (33.3 kPa).Conclusions:In the mucosal PCO2range usually encountered clinically, the arterial bicarbonate substitution causes underestimation of mucosal capillary pH. With moderate mucosal capillary lactic acidosis the error becomes small, and in severe regional ischemia there is significant overestimation of mucosal capillary pH.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To examine the efficiency of gas exchange, hemodynamic function, and histopathologic evidence of lung protection using high-frequency oscillation of the perfluorocarbon-filled lung in a model of acute lung injury.Setting:An animal research laboratory.Design:A prospective, randomized animal study comparing animals randomized to high-frequency oscillation or high-frequency oscillation and perfluorocarbon administration (perfluoro-octyl bromide, perflubron, or LiquiVent).Subjects:Ten healthy swine (mean weight, 24.6 kg) with saline lavage-induced acute lung injury.Interventions:Animals were treated with repetitive saline lavage to achieve a uniform degree of acute lung injury (PaO2of <90 torr [11.9 kPa] on a FIO2of 1.0). After lung injury, subjects were changed to high-frequency oscillatory ventilation and stabilized for 1 hr. High-frequency oscillation of the perfluorocarbon-filled lung was initiated in five animals with the instillation of 30 mL/kg perflubron and five animals continued receiving high-frequency oscillation for a total duration of 2 hrs after the dosing period. Histopathologic evidence of lung injury was quantified by a pathologist using an eight-variable lung injury scoring system to generate a lung injury score.Measurements and Main Results:Administration of perflubron did not produce acute alterations of gas exchange. After the dosing period, there were no differences in gas exchange, hemodynamic function, or pulmonary vascular resistance between the two groups. The perfluorocarbon-treated animals had a significantly lower histopathologic total lung injury score, primarily manifested by significantly less atelectasis.Conclusions:The combination of high-frequency oscillatory ventilation and partial liquid ventilation with perflubron was well tolerated hemodynamically, was not associated with deterioration of gas exchange during dosing, and did not produce significant differences in either gas exchange or hemodynamic variables over a 2-hr period. There was histopathologic evidence that the combination of high-frequency oscillation and perflubron administration produces improved recruitment in both dependent and nondependent lung regions.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:We tested whether AR-R 17477, a selective inhibitor of neuronal nitric oxide synthase, reduces brain injury in rats subjected to permanent focal ischemia.Design:Randomized within cohort; nonblinded study.Setting:University basic science laboratory.Subjects:Halothane-anesthetized male Wistar rats (n = 53).Interventions:Rats were treated with either intravenous saline (diluent) or AR-R 17477 (1 or 3 mg/kg) 30 mins before or 60 mins after the onset of permanent focal cerebral ischemia. Infarction volume was determined at 18 or 48 hrs of ischemia.Measurements and Main Results:Pretreatment with 1 mg/kg AR-R 17477 was associated with a decreased infarct volume (2,3,5-triphenyltetrazolium chloride staining) in the striatum (saline, 81 ± 7 mm3; AR-R 17477, 55 ± 3 mm3) but not in the cortex at 18 hrs of occlusion (saline, 302 ± 29 mm3; AR-R 17477, 237 ± 36 mm3). However, this therapeutic effect of AR-R 17477 was no longer evident if the rats were allowed to survive for 48 hrs before analysis of infarction volume. In fact, in this separate cohort of animals, three of eight AR-R 17477-treated and five of eight saline-treated rats died before completing 48 hrs of ischemia. Efficacy of AR-R 17477 was completely absent (even at 18 hrs of ischemia) when drug treatment was delayed until 1 hr after the onset of ischemia. Infarction volume at 18 hrs of ischemia was similar between rats treated with saline, 1 mg/kg (cortex, 229 ± 43 mm3; striatum, 67 ± 8 mm3) or 3 mg/kg AR-R 17477 (cortex, 284 ± 34 mm3; striatum, 75 ± 5 mm3). In addition, only one of eight rats treated with 3 mg/kg AR-R 17477 at 1 hr of ischemia survived 48 hrs of occlusion, compared with three of eight rats treated with saline.Conclusions:Neuronally generated nitric oxide is a mediator of brain injury during permanent focal ischemia in rats. However, severity of the ischemic insult appears to limit the therapeutic efficacy of the specific neuronal nitric oxide synthase inhibitor, AR-R 17477.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID