摘要:

ObjectiveTo describe various aspects of prognostic and therapeutic importance in patients treated for acute chloroquine poisoning.DesignRetrospective study.SettingToxicology intensive care unit (ICU) of a university hospital.InterventionsNone.PatientsOne hundred sixty-seven consecutive patients with acute chloroquine overdose admitted to our toxicology ICU.Measurements and Main ResultsThe mean amount ingested by history was 4.5 plus minus 2.8 g, and 43 (26%) of 167 patients ingested more than 5 g. The mean blood chloroquine concentration on admission was 20.5 plus minus 13.4 micro mol/L. The majority (87%) of our patients received at least one arm of a combination therapy regimen (epinephrine, mechanical ventilation, diazepam). Cardiac arrest occurred in 25 patients before hospital arrival; in seven of these patients, cardiac arrest occurred immediately after injection of thiopental. The mortality rate was 8.4% overall, and was 9.3% in patients with massive ingestions (NS vs. the group as a whole). We did not find a meaningful correlation between the amount ingested as estimated by history and the peak blood chloroquine concentration; the latter was highly correlated with the mortality rate.ConclusionsThe mortality rate in patients with acute chloroquine poisoning, including those patients sick enough to be referred to a specialty unit such as ours, can be limited to less than equals 10%. This finding appears to be true even in patients with massive ingestions. We were not able to correlate mortality with amount ingested by history, although the mortality rate does correlate with blood chloroquine concentration. While early use of diazepam, epinephrine, and mechanical ventilation in most of our patients may have contributed to the excellent overall results, these elements, either singly or in combination, do not appear to have a truly antidotal effect in acute chloroquine poisoning. Thiopental, on the other hand, should be used with great caution, if at all, in such cases.(Crit Care Med 1996; 24:1189-1195)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo investigate the alterations in circulating proinflammatory cytokines and cytokine production by peritoneal macrophages during the development of multiple organ dysfunction syndrome.DesignProspective, controlled laboratory study on zymosan-induced generalized inflammation in mice. Single intraperitoneal administration of zymosan induces, over a 12-day period, a triphasic illness in mice: the third phase, from day 6 onward, resembles multiple organ dysfunction syndrome.SettingAnimal research laboratory.SubjectsC57BL/6CRW mice received a single intraperitoneal dose of zymosan on day 0, and standard numbers of animals were killed at different time points up until day 12.Measurements and Main ResultsPlasma concentrations of interleukin (IL)-1 alpha and IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured from 3 hrs to 12 days after administration of zymosan. At the same time points, both lipopolysaccharide-stimulated and unstimulated production of these cytokines by peritoneal macrophages were measured in vitro.Plasma TNF and IL-6 concentrations transiently increased during the first 24 hrs after administration of zymosan. After 8 days, a prominent peak of biologically inactive TNF was observed. Both unstimulated and lipopolysaccharide-stimulated cytokine production by peritoneal cells showed profound changes during the experimental period.ConclusionsThese findings seem to confirm our hypothesis that the macrophages are in a continuously activated state and altered in their function, when the animals develop multiple organ dysfunction syndrome. Further studies are needed to elucidate what happens with these cytokines at the tissue level, to better understand the pathophysiology of multiple organ dysfunction syndrome.(Crit Care Med 1996; 24:1196-1202)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo assess the benefit of a recombinant endotoxin neutralizing protein from Limulus polyphemus in treating Gram-negative bacterial sepsis in rabbits.DesignProspective, blinded, controlled, laboratory trial.SettingAnimal research laboratory.SubjectsNew Zealand White rabbits.InterventionsWe established a rabbit model of Escherichia coli peritonitis and bacteremia, with high mortality rate, despite treatment with gentamicin and ceftriaxone. Twenty-five pairs of male New Zealand White rabbits were challenged intraperitoneally with E. coli O18ac K1 in 5% porcine mucin (mean 7 times 109colony-forming units). All animals were treated with intravenous gentamicin (2.5 mg/kg) and ceftriaxone (100 mg/kg), and with either intravenous endotoxin neutralizing protein (50 mg/kg) or saline 1 hr after E. coli challenge.Measurements and Main ResultsAll animals were bacteremic 1 hr after challenge (mean 3.6 times 105colony-forming units/mL). Animals in both groups developed tachycardia, hypotension, and acidosis (NS). Geometric mean serum endotoxin and tumor necrosis factor (TNF) concentrations were significantly (p less than .001) higher 1 hr after challenge compared with baseline prechallenge concentrations in both groups. From 1 to 2 hrs after challenge, endotoxin concentrations increased 2.5-fold in control animals (95% confidence interval equals 13.1 to 32.9 endotoxin units/mL, p equals .024), whereas endotoxin concentrations increased only 1.2-fold in endotoxin neutralizing protein-treated animals (95% confidence interval equals 20.4 to 23.8 endotoxin units/mL, NS). TNF concentrations increased significantly (p less than .001) in both groups from 1 to 2 hrs after challenge. Eighteen (72%) of 25 endotoxin neutralizing protein-treated animals vs. 11 (44%) of 25 controls survived 24 hrs (p equals .032).ConclusionsTreatment with endotoxin neutralizing protein had the following effects: a) the increase in serum endotoxin was blunted, but not TNF concentrations measured 1 hr after antibiotic treatment; and b) survival in rabbits with E. coli sepsis was improved.(Crit Care Med 1996; 24:1203-1207)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo demonstrate the efficacy of partial perfluorocarbon liquid ventilation in a large animal model of acute respiratory failure.DesignProspective, randomized, controlled trial.SettingAnimal laboratory at a university medical center.SubjectsTen adult sheep, weighing 53.0 plus minus 2.8 kg.InterventionsAfter assessment of baseline physiologic data, acute respiratory failure was induced by right atrial injection of oleic acid (0.2 mL/kg). Five animals (partial liquid ventilation group) underwent sequential intratracheal dosing of 10 mL/kg of perflubron at 30-min intervals to the following cumulative doses: 10, 20, 30, 40, and 50 mL/kg. The remaining five animals were gas ventilated (control group). Physiologic data were assessed at 30-min intervals in both groups for the 2.5-hr experimental period or until death.Measurements and Main ResultsWhen compared with control animals, intratracheal perfluorocarbon instillation resulted in significant improvements in arterial oxygen saturation (arterial oxygen saturation after 50 mL/kg: partial liquid ventilation, 96 plus minus 3%; control, 55 plus minus 8%; p equals .001) and physiologic shunt (physiologic shunt after 50 mL/kg dose: partial liquid ventilation, 22 plus minus 8%; control, 64 plus minus 5%; p equals .004). Oxygen delivery improved with perfluorocarbon instillation, but this improvement was not significant. No significant difference in pulmonary compliance was observed during partial liquid ventilation when compared with controls (pulmonary compliance: partial liquid ventilation, 0.43 plus minus 0.04 mL/cm H2O/kg; control, 0.53 plus minus 0.03 mL/cm H2O/kg; p equals .102).ConclusionsPartial liquid ventilation with perflubron provides effective improvement in gas exchange in an adult animal model of respiratory failure.(Crit Care Med 1996; 24:1208-1214)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesCO2content can be determined from the PCO2in an acidified (forces all CO2into solution) and diluted blood sample. However, PCO2concentrations measured in conventional blood gas analyzers are only correct for samples with a significant buffer capacity (such as whole blood), so that mixing with the PCO2in the rinse solution and tubing walls does not significantly change the sample PCO2. This study describes a calibration method and validation data for the Radiometer Medical ABL2 CO2electrode system to accurately measure unbuffered blood samples used in the determination of blood CO2content (or other aqueous fluids).DesignProspective, criterion standard.SettingLaboratory.Measurements and Main ResultsBlood samples (0.4 mL) were acidified and diluted with 0.2 M lactic acid. After measuring PCO2, CO2content was calculated using the CO2solubility coefficient and the dilution factor of 20. CO2content was determined in a series of sodium carbonate (Na2CO2) solutions spanning the physiologic range of CO2content. Regression of the measured vs. the actual CO2content data generated a straight line with a slope of 0.796 and y-intercept of 12.5 (r2equals .99; n equals 48). These coefficients were successfully used to correct CO2content determined in blood samples into which graduated amounts of sodium carbonate were added.ConclusionsThis calibration procedure allows accurate measurement of PCO sub 2 in aqueous samples using the Radiometer ABL2 electrode system, and should be applicable to other blood gas analyzers. Necessary syringes and chemicals are readily available, the method is fast and simple, and the sample volume is small. In the practice of critical care medicine, accurate PCO2measurement in aqueous acidified and diluted blood provides direct determination of blood CO2content (useful in calculations of modified Fick cardiac output or tissue CO2production). Determinations of absolute CO2content in blood requiring complex methodology are not necessary. In addition, accurate measurement of aqueous gastric PCO2can help determine gastric pH, which is an important marker of tissue perfusion.(Crit Care Med 1996; 24:1215-1218)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveEndotoxin and cytokines have been reported to have both stimulatory and inhibitory effects on endothelial cell-derived nitric oxide release. This discrepancy may be explained by differential regulation of the endothelial and inducible types of nitric oxide synthase gene expression. This study aimed to investigate the differential effect of lipopolysaccharide treatment in vivo on the three isoforms (endothelial, brain-type, and inducible) of nitric oxide synthase gene expression in the rat.DesignProspective, controlled, animal trial.SettingExperimental laboratory of a postgraduate medical research institution.SubjectsNormal, anesthetized rats.InterventionsAnimals were treated with lipopolysaccharide (15 mg/kg ip), saline (1 mL/kg ip), or lipopolysaccharide plus dexamethasone (3 mg/kg ip, 50 mins before lipopolysaccharide administration) in vivo 4 hrs before experimentation.Measurements and Main ResultsThe expression of endothelial, brain-type, and inducible nitric oxide synthase mRNAs was quantified by Northern blot analysis using bovine, rat, and mouse cDNA probes, respectively. An endothelial nitric oxide synthase mRNA was detected at 4.3 kilobase in the heart, lung, and aorta, and a 10-kilobase brain-type nitric oxide synthase mRNA was detected in the brain. The endothelial and brain-type signals were strong in tissues from animals treated with saline, but were reduced by three- to four-fold in tissues from lipopolysaccharide-treated rats as estimated by optical density ratio. The 4.4-kilobase inducible nitric oxide synthase mRNA detected using the murine cDNA probe was absent or negligible in the heart, lung, and brain from saline-treated rats, but was markedly increased in the same tissues from lipopolysaccharide-treated animals. Dexamethasone significantly inhibited lipopolysaccharide-induced inducible nitric oxide synthase mRNA expression, but had no effect on the down-regulation of endothelial and brain nitric oxide synthase mRNAs.ConclusionsRats treated with lipopolysaccharide in vivo display down-regulation of endothelial nitric oxide mRNA in the heart, lung, and aorta, and brain-type nitric oxide synthase mRNA in the brain. There was a parallel up-regulation of inducible nitric oxide synthase mRNA in all tissues except in the aorta. Dexamethasone prevents the induction of inducible nitric oxide synthase mRNA, but has no effect on the down-regulation of endothelial and brain-type nitric oxide synthase mRNAs induced by lipopolysaccharide. Thus, endotoxin regulates constitutive and inducible nitric oxide synthase mRNA differentially.(Crit Care Med 1996; 24:1219-1225)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesA 2400-mOsm/L hypertonic solution (Isosal) with a lower sodium content, compared with conventional 7.5% hypertonic saline, was formulated using a mixture of sodium chloride, glucose, and mixed amino acids. This solution was developed to minimize hypernatremia during resuscitation. We assessed the effects of Isosal on hemodynamics, brain edema, and plasma sodium concentration after head injury associated with hemorrhagic shock.DesignProspective, randomized laboratory study.SettingUniversity research laboratory.SubjectsTwenty-one adult female Suffolk sheep, weighing 39 to 49 kg.InterventionsAnimals were subjected to a 2-hr period of hemorrhagic shock to a mean arterial pressure (MAP) of 40 to 45 mm Hg in the presence of a freeze injury to the cerebral cortex. The hemorrhagic shock/head injury phase was followed by 2 hrs of resuscitation with Isosal, a new 2400-mosm/L low-sodium hypertonic fluid, 2400 mosm/L of 7.5% hypertonic saline, or lactated Ringer's solution. Initial resuscitation was with a bolus injection of 8 mL/kg of the study solution; subsequent resuscitation in all three groups was with lactated Ringer's solution as needed to maintain baseline cardiac output.Measurements and Main ResultsSerial hemodynamics, intracranial pressure, electrolytes, and osmolarity were measured. At the end of resuscitation, the animals were killed and brain water content (mL H2O/g dry weight) of the injured and uninjured areas was determined.Resuscitation volumes were significantly lower in the Isosal (19 plus minus 5 mL/kg) and 7.5% hypertonic saline (14 plus minus 2 mL/kg) groups compared with the lactated Ringer's solution (35 plus minus 5 mL/kg) group. Intracranial pressure after 2 hrs of resuscitation was significantly lower in the Isosal (7 plus minus 1 mm Hg) and hypertonic saline groups (4 plus minus 1 mm Hg), compared with the lactated Ringer's solution group (11 plus minus 2 mm Hg). Water content in all areas of the brain was significantly lower in the hypertonic saline group compared with the lactated Ringer's solution group. Brain water content in the Isosal group was lower than in the lactated Ringer's solution group only in the cerebellum. Plasma sodium content was lower in the Isosal group than in the hypertonic saline group.ConclusionsAfter combined head injury and shock, Isosal and 7.5% hypertonic saline have similar effects on hemodynamics and intracranial pressure. Hypertonic saline induces a greater degree of brain dehydration; Isosal resuscitation results in smaller increases in plasma sodium.(Crit Care Med 1996; 24:1226-1232)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo determine the influence of dopexamine, a synthetic catecholamine ligand for dopaminergic and beta2-adrenergic receptors, on alterations of the intestinal villus microcirculation in a model of normotensive endotoxemia.DesignRandomized, controlled trial.SettingExperimental laboratory.SubjectsTwenty-one male Wistar rats.InterventionsRats were treated with a continuous infusion of dopexamine (2.5 micro gram/kg/min; n equals 7; group A) or 0.9% saline (n equals 7; group B) during a study period of 120 mins. Both groups were given endotoxin (Escherichia coli lipopolysaccharide; 1.5 mg/kg iv) over 60 mins. Animals in the control group (n equals 7; group C) received a volume-equivalent infusion of 0.9% saline. Total volume substitution in all groups was 15 mL/kg/hr.Measurements and Main ResultsBlood flow in the intestinal villi of the distal ileum was determined using in vivo videomicroscopy at baseline, and 60 and 120 mins after the endotoxin challenge. These blood flow determinations were done by an observer who was unaware of the previous treatment of the animals. In addition, mean arterial pressure was monitored at baseline, and 15, 30, 45, 60, 75, 90, 105, and 120 mins later.The administration of 1.5 mg/kg endotoxin alone (group B) resulted in a reduction of the intestinal villus blood flow to 74.8 plus minus 9.5% of baseline after 60 mins, and to 61.1 plus minus 8.5% of baseline after 120 mins (baseline: 7.4 plus minus 0.6 nL/min; 60 mins: 5.3 plus minus 0.8 nL/min; 120 mins: 4.4 plus minus 0.5 nL/min; p less than .05). This reduction of blood flow was associated with a decrease in the arteriolar diameters by 13.8 plus minus 2.5% after 60 mins, and by 17.1 plus minus 4.3% after 120 mins (p less than .05 vs. baseline). In contrast, villus blood flow in the dopexamine group (group A) did not show statistically significant changes during the entire study period, despite the administration of endotoxin (baseline: 8.2 plus minus 0.6 nL/min; 60 mins: 7.3 plus minus 0.8 nL/min; 120 mins: 7.8 plus minus 0.5 nL/min). No vasoconstriction of the villus arterioles was noted in this group. In control animals (group C), the blood flow (baseline: 8.1 plus minus 1.6 nL/min; 60 mins: 7.6 plus minus 1.4 nL/min; 120 mins: 7.8 plus minus 1.4 nL/min) and the arteriolar diameters remained unchanged throughout the observation period. Mean arterial pressure did not differ between groups; it remained unaltered in all groups during the entire study period.ConclusionsDopexamine maintains intestinal villus arterial perfusion and prevents the vasoconstriction in villus arterioles during early normotensive endotoxemia. Therefore, further studies in critically ill patients will have to determine whether the early prophylactic use of dopexamine can limit gut ischemia and prevent the development of multiple organ failure.(Crit Care Med 1996; 24:1233-1237)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectiveTo determine if the early inflammatory response correlates with the severity of injury in a blunt trauma model in rats.DesignProspective, randomized, controlled trial.SettingResearch laboratory.SubjectsMale Sprague-Dawley rats, weighing 250 to 400 g.InterventionsTwenty-two male Sprague-Dawley rats were divided randomly into single hindlimb fracture, bilateral hindlimb fracture, and no fracture groups. At 90 mins, all animals underwent midline laparotomy and aspiration of blood from the inferior vena cava. Venous blood gas, plasma lactate, and plasma concentrations of tumor necrosis factor (TNF), prostaglandin F (6-keto-PGF1alpha), and interleukin (IL)-6 were sampled. Statistical analysis was done via one-way analysis of variance and Scheffe post hoc analysis. In a second part of this experiment, the effect of hemorrhage on the release of IL-6 was evaluated. Animals in this group were compared with control and bilateral hindlimb fracture animals, using the Student's t-test.Measurements and Main ResultsThere were no significant differences in venous pH or base deficit among the groups. Oxygen saturation was significantly decreased in the bilateral hindlimb fracture group when compared with the control group. In the hemorrhage plus bilateral fracture group, oxygen saturation was significantly decreased when compared with the bilateral fracture group. Lactate concentrations in plasma were increased in both fracture groups as well as the hemorrhaged groups. Plasma TNF concentrations were increased in the injured groups but there was no significant difference between single and bilateral hindlimb fracture groups. The 6-keto-PGF sub 1 alpha concentrations were increased in both of the fracture groups when compared with the control group and there was a significant difference between single and bilateral hindlimb fracture groups. Similarly, circulating IL-6 concentrations were significantly higher in the bilateral fracture group than in the single fracture group; both fracture groups were significantly higher than the control group. Hemorrhaged animals had even higher IL-6 concentrations.ConclusionsPlasma lactate and TNF concentrations were affected by injury, however their concentrations did not correlate with degree of injury. IL-6 concentrations were increased early postinjury and correlated with severity of injury. The 6-keto-PGF sub 1 alpha concentrations in plasma also correlated with the severity of injury and this phenomenon may represent early endothelial activation which may be the source of IL-6 release.(Crit Care Med 1996; 24:1238-1242)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

ObjectivesTo measure cerebrospinal fluid and plasma nitrlte and nitrate concentrations as indicators of nitric oxide production in adults after severe closed-head injury. To determine if there is an association between cerebrospinal fluid and plasma nitrite and nitrate concentrations, and cerebral blood flow, arterio-jugular oxygen content difference, injury severity, and outcome after severe closed-head injury.DesignA prospective, clinical study.SettingMultidisciplinary intensive care unit.PatientsFifteen comatose (Glasgow Coma Scale score of less than equals 7) adult patients with severe closed-head injury were studied during the prospective, randomized evaluation of the effect of moderate hypothermia (32 degrees C for 24 hrs) on neurologic outcome after closed-head injury. Seven patients were in the hypothermic group and eight patients were in the normothermic treatment group.InterventionsNone.Measurements and Main ResultsPatients were examined sequentially, every 12 hrs for 2 days. Intraventricular cerebrospinal fluid was assayed for nitrite and nitrate concentrations. Cerebral blood flow was measured by the133xenon intravenous method. Simultaneous blood samples were obtained for measurements of arterio-jugular oxygen content difference and plasma nitrite and nitrate concentrations. Cerebral metabolic rate for oxygen was calculated. Cerebrospinal fluid nitrite and nitrate concentrations were highest at 30 to 42 hrs vs. 6 to 18, 18 to 30, and 42 to 54 hrs (26.4 plus minus 3.3 vs. 17.3 plus minus 2.1, 20.0 plus minus 2.2, and 18.8 plus minus 2.4 micro Meter, respectively, p less than .05). There was no difference over time in plasma nitrite and nitrate concentrations. Cerebral blood flow was increased and arterio-jugular oxygen content difference was reduced at 18 to 30, 30 to 42, and 42 to 54 hrs vs. 6 to 18 hrs (p less than .05). At 30 to 42 hrs, cerebrospinal fluid nitrite and nitrate concentrations were 80% higher in patients who died vs. survivors (36.4 plus minus 3.2 vs. 20.2 plus minus 3.6, p less than .05). Using a generalized, multivariate, linear regression model, both plasma nitrite and nitrate concentrations and Injury Severity Score independently predicted cerebrospinal fluid nitrite and nitrate concentrations (p less than .00001 and p equals .0053, respectively). Cerebral blood flow and arterio-jugular oxygen content difference were not associated with cerebrospinal fluid or plasma nitrite and nitrate concentrations using this model.Cerebrospinal fluid nitrite and nitrate concentrations were increased over time in hypothermic vs. normothermic patients. But, where this difference occurred could not be determined by multiple comparisons (p equals .03). The hypothermic patients had lower admission Glasgow Coma Scale scores than normothermic patients (p equals .04) and tended to have higher Injury Severity Scores (p equals .09).ConclusionsIncreases in cerebrospinal fluid nitrite and nitrate concentrations peaked at 30 to 42 hrs after severe closed-head injury. This increase in cerebrospinal fluid nitrite and nitrate concentrations was greater in nonsurvivors. Also, cerebrospinal fluid and plasma nitrite and nitrate concentrations were associated with Injury Severity Score, suggesting that increased nitric oxide production in the brain is associated with injury severity and death. Hypothermia did not prevent the increase in cerebrospinal fluid nitrite and nitrate concentrations. Further study is required to determine the source of this increase in cerebrospinal fluid nitrite and nitrate concentrations and to further define the relationship to outcome and the effect of hypothermia on this process.(Crit Care Med 1996; 24:1243-1251)

ISSN:0090-3493    

出版商:OVID    

年代:1996

数据来源: OVID