摘要:

ObjectiveTo evaluate the safety, pharmacokinetics, and pharmacodynamics of diaspirin cross-linked hemoglobin solution (DCLHb[TM]) in normal, healthy volunteers.DesignRandomized, double-blind, controlled, crossover study.SettingPhase I research facility of a contract research organization.PatientsTwenty-four healthy adult volunteers.InterventionsDiaspirin cross-linked hemoglobin solution (25, 50, or 100 mg/kg) or equal volume of lactated Ringer's solution was infused on day 1; the alternate solution was infused 6 days later. Laboratory analyses, electrocardiograms, and Holter and telemetry monitoring were performed to assess organ function, pharmacokinetics, and potential toxicity. Vital signs, pulse oximetry, laser Doppler flowmetry, and toe temperature were measured to evaluate diaspirin cross-linked hemoglobin solution's pharmacodynamic effects.Measurements and Main ResultsThere were no serious adverse events associated with diaspirin cross-linked hemoglobin solution infusion. Abdominal pain occurred in three subjects after control infusion and in six subjects after diaspirin cross-linked hemoglobin solution infusion; no treatment was required. A dose-related increase in lactic dehydrogenase (LDH)-5 isoenzyme concentrations was observed in 12 subjects after diaspirin cross-linked hemoglobin solution infusion. There were no associated increases in the circulating concentrations of total LDH, aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase. Total serum creatine kinase concentrations increased significantly after infusion of 100 mg/kg of diaspirin cross-linked hemoglobin solution; the isoenzyme creatine kinase-myocardial band (CK-MB) was not increased, nor were there any abnormal electrocardiogram findings. There were no differences in laser Doppler, pulse oximetry, or toe temperature measurements during or after either infusion. The half-life of diaspirin cross-linked hemoglobin solution was 2.5 hrs for the 25- and 50-mg/kg doses and 3.3 hrs for the 100-mg/kg dose. A dose-related increase in blood pressure occurred with diaspirin cross-linked hemoglobin solution.ConclusionsDiaspirin cross-linked hemoglobin solution doses of 25, 50, and 100 mg/kg are well tolerated, without evidence of organ dysfunction or toxicity. Diaspirin cross-linked hemoglobin solution's pressor effect is without evidence of decreased peripheral perfusion. Further investigations of its use in certain patient populations are warranted. (Crit Care Med 1996; 24:1993-2000)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo study the effects of venovenous extracorporeal membrane oxygenation (ECMO) on cerebral autoregulation in the newborn lamb.DesignAnimal studies, using newborn lambs, with comparison of two randomized treatment groups.SubjectsNewborn lambs of mixed breed, 1 to 7 days of age, were randomized into two study groups: control animals, with jugular vein ligation but no ECMO (n = 6), and ECMO animals placed on venovenous ECMO (n = 6).SettingLaboratory animal facilities of the Department of Anesthesiology and Critical Care Medicine at The Johns Hopkins Medical Institutions, Baltimore, MD.InterventionsAnimals were anesthetized with pentobarbital, intubated, and ventilated, and monitoring catheters were inserted. Control animals had their right jugular vein ligated, and a cerebral autoregulation curve was performed after 1 hr of stabilization. ECMO animals were placed on venovenous ECMO and after 1 hr of stabilization, they had a cerebral autoregulation curve performed. Cerebral autoregulation was examined by increasing intracranial pressure, thereby decreasing cerebral perfusion pressure. Intracranial pressure was increased by infusion of artificial cerebrospinal fluid into the lateral ventricle of the brain.Measurements and Main ResultsFour ranges of cerebral perfusion pressure were evaluated: a) baseline (1 hr after initiation of bypass in venovenous ECMO or completion of surgery in controls); b) cerebral perfusion pressure of 55 to 40 mm Hg; c) cerebral perfusion pressure of 39 to 25 mm Hg; and d) cerebral perfusion pressure of <25 mm Hg. Cerebral blood flow (radiolabeled microspheres), cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period.In ECMO animals, cerebral blood flow (cerebral hemispheres) decreased from a baseline measurement of 46 +/-9 (SD) mL/100 g/min to 29 +/- 12 mL/100 g/min at a cerebral perfusion pressure of <25 mm Hg. In the control group, cerebral blood flow was unchanged from baseline at any range of cerebral perfusion pressure. Cerebral oxygen consumption was unchanged from baseline as cerebral perfusion pressure decreased in either group. When cerebral oxygen consumption was compared between the two groups, it was lower in the ECMO group at baseline and at a cerebral perfusion pressure of <25 mm Hg. At a cerebral perfusion pressure of <25 mm Hg, cerebral blood flow, cerebral oxygen delivery, and metabolic rate were lower in the ECMO group than in the control group, and fractional oxygen extraction and cerebral vascular resistance were higher, indicating that autoregulation was impaired. There was no difference between blood flow in the right and left cerebral hemispheres when autoregulation was impaired in the ECMO animals.ConclusionsThese findings indicate that cerebral autoregulation was altered in animals on venovenous ECMO, with cerebral blood flow decreasing at a cerebral perfusion pressure of <25 mm Hg, compared with control animals which showed no changes at the same cerebral perfusion pressure. This disruption of cerebral autoregulation decreased cerebral oxygen metabolism despite an increased oxygen extraction in ECMO animals. (Crit Care Med 1996; 24:2001-2006)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveSepsis is characterized by systemic vasodilation and hyporesponsiveness to constrictor agents, at a time when the pulmonary circulation exhibits varying degrees of vasoconstriction. Plasma endothelin-1 concentrations are increased, but the role of this potent vasoconstrictor peptide in modulating the vascular response to sepsis is unknown. Therefore, we assessed the effect of endothelin-A receptor antagonism in the response of pulmonary arteries from rats treated with lipopolysaccharide to endothelin-1, and determined the vasomotor role of the endothelin-B receptors that are known to be located on rat pulmonary artery smooth muscle and endothelium.DesignProspective, controlled study.SettingAnimal research laboratory.SubjectsMale Wistar rats (275 to 300 g).InterventionsAnimals were injected with either lipopolysaccharide (20 mg/kg ip) or saline (1 mL ip) 4 hrs before being killed. The main pulmonary arterles were cut into 2-mm rings, and suspended in an organ bath. In the first set of experiments, half of the rings underwent a procedure that removed the endothelium, and the contractile response to cumulative doses of endothelin-1 (10 sup -11 to 10 sup -6 M) was measured. Half of the rings were pretreated with the endothelin-A receptor antagonist, BQ123 (10 sup -5 M or 10 sup -6 M), and the other half of the rings were treated with vehicle. In a separate group of experiments, the contractile response to cumulative concentrations of the selective endothelin-B agonist, sarafotoxin S6c (10 sup -11 to 10 sup -6 M), was measured in rings at baseline tension. Second, the possible dilator effect of endothelin-B receptor activation was tested by the administration of sarafotoxin S6c (10 sup -7 to 10 sup -6 M) to rings preconstricted by 10 sup -6 M of U46619, a thromboxane receptor agonist, either in the presence or absence of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine-methylester (10 sup -4 M). Acetylcholine-induced (10 sup -4 M), endothelium-dependent vasodilation was also measured.Measurements and Main ResultsBQ123 (10 sup -5 or 10 sup -6 M) caused consecutive rightward shifts in the endothelin-1 concentration-contraction curves for all ring types, including the intact rings from endotoxemic animals. Sarafotoxin S6c failed to induce any direct constriction in rings from sham-treated or lipopolysaccharide-treated rats. However, sarafotoxin S6c induced transient vasodilation at the initial dose in rings from sham-treated rats but not lipopolysaccharide-treated rats-an effect that was attenuated by Nomega-nitro-L-arginine-methylester. Acetylcholine induced an Nomega-nitro-L-arginine-methylester-sensitive vasodilation that was reduced in rings from endotoxin-treated rats.ConclusionsEndothelin-A receptor blockade is an effective means of attenuating endothelin-1-induced contraction of isolated pulmonary artery rings, even from rats rendered endotoxemic. Endothelin-B receptors on the pulmonary artery cause vasodilation via the release of nitric oxide, and have no constrictor component. The functional effects of endothelin-B receptors on tone are lost after lipopolysaccharide treatment. The endothelium is involved in both the constrictor and dilator effects of endothelin in rat pulmonary artery, confirming a pivotal role for endothelial cells in the vascular response to sepsis. (Crit Care Med 1996; 24:2007-2013)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveThe administration of vasopressin during cardiopulmonary resuscitation (CPR) provides significantly more vital organ blood flow when compared with epinephrine during cardiac arrest in pigs. The effects of this potent vasoconstrictor on postresuscitation cardiovascular function remain unknown. The purpose of this study was to compare the effects of vasopressin and epinephrine on cardiovascular function in the postresuscitation phase after CPR.DesignProspective, randomized, experimental study.SettingUniversity research laboratory.SubjectsDomestic pigs, 12 to 14 wks of age.InterventionsSixteen pigs were randomly allocated to receive either 0.045 mg/kg of epinephrine or 0.4 U/kg of vasopressin after 4 mins of cardiac arrest.Measurements and Main ResultsHemodynamics, left ventricular contractility, and myocardial blood flow were measured for an interval of 240 mins after successful CPR. Differences between animals treated with epinephrine vs. vasopressin were most pronounced 15 mins after restoration of spontaneous circulation. At this time, mean aortic pressure was 64 +/- 6 (SEM) mm Hg in the epinephrine group and 84 +/- 6 mm Hg (p < .05) in the vasopressin group. Systemic vascular resistance was 1285 +/- 72 dyne [centered dot] sec/cm5in the epinephrine group and 2314 +/- 130 dyne [centered dot] sec/cm5(p < .001) in the vasopressin group. Cardiac index was 140 +/- 9 mL/min/kg in animals treated with epinephrine and 99 +/- 9 mL/min/kg (p < .01) in animals treated with vasopressin. Myocardial contractility (dp/dtmax/P) was 52.8 +/- 3.4/sec with epinephrine as compared with 36.3 +/- 2.9 sec sup -1 (p < .01) with vasopressin. Left ventricular epicardial blood flow was 241 +/- 35 mL/min/100 g with epinephrine and 142 +/- 22 mL/min/100 g (p < .05) with vasopressin. Four hours after CPR, no significant differences were observed between groups.ConclusionsIn the early postresuscitation phase, vasopressin provided higher systemic blood pressures and there was a reversible depressant effect on myocardial function when compared with epinephrine. Overall cardiovascular function was not irreversibly or critically impaired after the administration of vasopressin in this pig model of cardiac arrest. (Crit Care Med 1996; 24:2014-2019)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo evaluate the effects of hemocarboperfusion on hemodynamics, organ blood flow, and survival in endotoxin shock.DesignProspective, placebo-controlled, animal trial.SettingResearch laboratory in a major university teaching hospital.SubjectsPentobarbital-anesthetized pigs.InterventionsTwenty-eight pentobarbital-anesthetized pigs (18.5 to 22.3 kg) received 100 micro g/kg of Escherichia coli endotoxin (lipopolysaccharide 0127) over 30 mins. Group 1 animals (n = 14) were controls and had blood diverted through an extracorporeal circuit without activated charcoal for 60 mins after lipopolysaccharide infusion. Group 2 animals (n = 14) underwent nonpulsatile hemocarboperfusion (activated charcoal SCN-1K).Measurements and Main ResultsMean arterial pressure, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, pulmonary vascular resistance, oxygen delivery, and regional blood flow (radiolabeled microsphere technique) were determined at baseline and every 30 mins for 150 mins. Results are presented as mean +/- SD. Parameters in the two groups were compared by two-way analysis of variance. A p < .05 was considered significant. The survival rate was ten (71%) of 14 animals in group 1 compared with 14 (100%) of 14 animals in group 2 (p < .05, Fisher's exact test). The mean cardiac output at the end of hemocarboperfusion was 1.6 +/- 0.6 L/min in group 1 compared with 3.0 +/- 0.9 L/min in group 2, and remained lower in group 1 animals throughout the experiment. Pulmonary arterial pressure and pulmonary vascular resistance were lower in the hemocarboperfusion-treated animals during and after hemocarboperfusion. Systemic vascular resistance increased by 70% after lipopolysaccharide infusion and returned to baseline values in the hemocarboperfusion group but remained increased in controls. Oxygen delivery was lower in group 1 at 90 and 150 mins (287 +/- 34 vs. 478 +/- 48 mL/min and 251 +/- 24 vs. 356 +/- 21 mL/min, respectively). Blood flow rates to the brain (38.5 +/- 7.5 vs. 27.1 +/- 5.4 mL/min/100 g), large intestine (26.6 +/- 1.1 vs. 17.7 +/- 2.5 mL/min/100 g), and adrenal cortex (200 +/- 45 vs. 139 +/- 41 mL/min/100 g) were higher in the hemocarboperfusion group at the completion of carboperfusion but not at later time points.ConclusionThese data suggest that hemocarboperfusion may be of value in the treatment of septic shock. (Crit Care Med 1996; 24:2020-2026)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that increased cardiac output with continuous positive airway pressure (CPAP) leads to increased myocardial metabolic cost.DesignProspective, repeated-measures, laboratory studies.SettingUniversity-affiliated hospital animal research laboratory.SubjectsEight sedated pigs that had been previously instrumented for collection of hemodynamic data.InterventionsApplication of CPAP at 0, 5, 10, and 15 cm H2O and recovery under conditions of normal blood volume (normovolemia) and after administration of hetastarch 35 mL/kg (hypervolemia).Measurements and Main ResultsWe measured mean arterial pressure, cardiac output, systemic vascular resistance index, the first derivative of the left ventricular pressure at a left ventricular pressure of 50 mm Hg, rate-pressure product, left ventricular tension-time index, stroke work index, myocardial pressure-myocardial segment length area, coronary artery blood flow and coronary vascular resistance, and myocardial oxygen consumption (four pigs).With normovolemia, cardiac output decreased with CPAP (4.9 +/- 1.2 L/min at CPAP of 0 cm H2O to 4.5 +/- 1.3 L/min at CPAP of 15 cm H2O, p <.005) and systemic vascular resistance index increased (2509 +/- 702 to 3095 +/- 1080 dyne [centered dot] sec/cm5[centered dot] m2, p < .01). With hypervolemia, cardiac output increased at low-level CPAP (5.7 +/- 1.4 L/min at CPAP of 0 cm H2O to 6.4 +/- 1.6 L/min at CPAP of 5 cm H2O, p < .05) and systemic vascular resistance index decreased (2412 +/- 552 to 2033 +/- 436 dyne [centered dot] sec/cm sup 5 [centered dot] m2, p < .01). There were no associated significant changes in myocardial oxygen consumption, or its major correlates when cardiac output increased with CPAP (hypervolemic conditions).ConclusionsIn normal pigs, there is no change in myocardial oxygen demand with CPAP, whatever the change in cardiac output. Thus, increased cardiac output with CPAP carries little extra metabolic cost. Increased cardiac output with low-level CPAP in hypervolemia is associated with systemic vasodilation. (Crit Care Med 1996; 24:2027-2034)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesEarlier studies demonstrated that hypertonic buffer agents administered during cardiopulmonary resuscitation (CPR) altered neither myocardial pH nor cardiac resuscitability. The rationale for the routine use of buffer agents for CPR has therefore been challenged. However, when these buffer agents are administered during CPR, they may have favorable effects on the postresuscitation course. Postresuscitation myocardial dysfunction has more recently emerged as a potentially fatal complication after successful cardiac resuscitation. Options for prevention and management of this complication have prompted the present studies, in which the effects of buffer agents administered during CPR are evaluated as to their effects on postresuscitation myocardial function and survival.DesignProspective, randomized, controlled animal study.SettingUniversity animal laboratory.SubjectsForty male Sprague-Dawley rats (450 to 570 g).InterventionsVentricular fibrillation was induced electrically. Mechanical ventilation and precordial compression were initiated after either a 4- or an 8-min interval of untreated cardiac arrest. Sodium bicarbonate as a CO2-generating buffer, Carbicarb [R] and tromethamine as CO2-consuming buffers, or hypertonic saline placebo were injected as a bolus into the right atrium during CPR. Defibrillation after 10 mins of cardiac arrest and CPR was successful in each instance. No differences in the electric power required for successful resuscitation were documented. Left ventricular pressure, rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg (dP/dt40), rate of left ventricular pressure decline (-dP/dt), and end-tidal PCO2were continuously measured for 240 mins after successful resuscitation.Measurements and Main ResultsDecreases in coronary perfusion pressure were observed after each buffer or placebo injection. As anticipated, end-tidal PCO2increased after bicarbonate and decreased after Carbicarb or tromethamine. Postresuscitation left ventricular function was significantly decreased in all animals. However, there was significantly less depression in rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg (dP/dt40), rate of left ventricular pressure decline (-dP/dt), and a lower left ventricular diastolic pressure with both Carbicarb and tromethamine in association with significant increases in postresuscitation survival rate. When the duration of untreated cardiac arrest was increased to 8 mins, the severity of postresuscitation left ventricular dysfunction was magnified and postresuscitation myocardial function and survival were significantly improved with both CO2-generating and CO2-consuming buffer agents.ConclusionAlthough buffer agents may not improve the success of resuscitation when administered during CPR, they may ameliorate postresuscitation myocardial dysfunction and thereby improve postresuscitation survival. (Crit Care Med 1996; 24:2035-2041)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo determine the pharmacologic effect of carcinine (beta-alanyl histamine), a compound that has been shown to be a positive inotrope in the isolated perfused guinea pig heart, on hemodynamics in an intact, anesthetized rat model.DesignProspective dose-response study.SettingAnimal research laboratory of a university medical center.SubjectsMale Sprague-Dawley rats.InterventionsEight male Sprague-Dawley rats were anesthetized with ketamine and midazolam. A tracheostomy tube, and central venous and arterial catheters were inserted. An electromagnetic flow probe was placed around the ascending aorta through a right thoracotomy for measurement of cardiac output. Dosages of carcinine from 0 to 10 mg/kg were infused intravenously over 30 secs, and hemodynamic parameters were measured at baseline and at peak effect.Measurements and Main ResultsAt dosages of 3 mg/kg and 10 mg/kg, carcinine significantly reduced mean arterial blood pressure, systemic vascular resistance index, and left ventricular stroke work index. There was no carcinine-induced effect on heart rate, central venous pressure, cardiac index, or stroke index. Lower doses of carcinine had no effect on the measured variables.ConclusionsIn this open-chest rat model, the primary pharmacologic effect of carcinine is systemic arterial vasodilation. A negative inotropic effect is suggested. Hypotension is secondary to these carcinine-induced actions. These results differ from results previously published using an isolated guinea pig heart preparation. Our model suggests that efforts to develop a clinical role for carcinine should exploit vascular rather than cardiac effects. Species differences may also play a role. (Crit Care Med 1996; 24:2042-2045)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo review the various outcomes from cardiopulmonary resuscitation (CPR), the factors that influence these outcomes, the costs associated with CPR, and the application of cost-analyses to CPR.Data SourcesData used to prepare this article were drawn from published articles and work in progress.Study SelectionArticles were selected for their relevance to the subjects of CPR and cost-analysis by MEDLINE keyword search.Data ExtractionThe authors extracted all applicable data from the English literature.Data SynthesisCost-analysis studies of CPR programs are limited by the high variation in resources consumed and attribution of cost to these resources. Furthermore, cost projections have not been adjusted to reflect patient-dependent variation in outcome. Variation in the patient's underlying condition, presenting cardiac rhythm, time to provision of definitive CPR, and effective perfusion all influence final outcome and, consequently, influence the cost-effectiveness of CPR programs.Based on cost data from previous studies, preliminary estimates of the cost-effectiveness of CPR programs for all 6-month survivors of a large international multicenter collaborative trial are $406,605.00 per life saved (range $344,314.00 to $966,759.00), and $225,892.00 per quality-adjusted-life-year (range $191,286.00 to $537,088.00).ConclusionsReported outcome from CPR has varied from reasonable rates of good recovery, including return to full employment to 100% mortality. Appropriate CPR is encouraged, but continued widespread application appears extremely expensive. (Crit Care Med 1996; 24:2046-2052)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo evaluate the effect of real-time ultrasound guidance using a regular or Doppler ultrasound technique for placement of central venous catheters.Data SourcesWe searched for published and unpublished research using MEDLINE, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants.Study SelectionFrom a pool of 208 randomized, controlled trials of venous and arterial catheter management, eight published randomized, controlled trials were identified.Data ExtractionIn duplicate, independently, we abstracted data on the population, intervention, outcome, and methodologic quality.Data SynthesisUltrasound guidance significantly decreases internal jugular and subclavian catheter placement failure (relative risk 0.32; 95% confidence interval 0.18 to 0.55), decreases complications during catheter placement (relative risk 0.22; 95% confidence interval 0.10 to 0.45), and decreases the need for multiple catheter placement attempts (relative risk 0.60; 95% confidence interval 0.45 to 0.79) when compared with the standard landmark placement technique.ConclusionsWhen used for vessel location and catheter placement real-time, ultrasound guidance or Doppler ultrasound guidance improves success rates and decreases the complications associated with internal jugular and subclavian venous catheter placement. (Crit Care Med 1996; 24:2053-2058)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID