摘要:

ObjectiveTo evaluate the hypothesis that splanchnic ischemia and mucosal hypoxia are responsible for lipopolysaccharide-induced intramucosal acidosis in pigs.DesignProspective, randomized, unblinded study.SettingSurgical research laboratory at a large, university-affiliated medical center.SubjectsAnesthetized, mechanically ventilated swine.InterventionsPigs were infused with lactated Ringer's solution (12 mL/kg/hr) and, starting at 30 mins, 25-mL boluses of dextran-70 (maximum 15 mL/kg/hr) to maintain cardiac output at 90% to 110% of the baseline value for each pig. Ileal mucosal hydrogen ion concentration was measured tonometrically. A segment of distal ileum was exteriorized, opened, and placed on a platform to permit measurement of mucosal PO2, using an array of Clark-type microelectrodes and a computerized data acquisition and analysis system. Mucosal perfusion was measured using laser-Doppler flowmetry. The control group (n = 4) received no further interventions. Pigs in the lipopolysaccharide group (n = 6) were infused with 150 micro gram/kg of Escherichia coli lipopolysaccharide over 60 mins. To assess the effect of mucosal acidosis on mucosal PO2in nonendotoxemic animals, intramucosal hydrogen ion concentration, mucosal PO2, and mucosal perfusion were measured in pigs rendered hypercarbic through deliberate hypoventilation (hypercarbia group; n = 4).Measurements and Main ResultsInfusion of lipopolysaccharide resulted in a significant increase in intramucosal hydrogen ion concentration. However, in the lipopolysaccharide group, mucosal perfusion did not change significantly and mucosal PO2increased significantly. In the hypercarbia group, hypercarbia was associated with significant increases in both intramucosal hydrogen ion concentration and mucosal PO2.ConclusionsMucosal hypoxia is not responsible for lipopolysaccharide-induced mucosal acidosis in this normodynamic pig model of septic shock. A rightward shift of the oxyhemoglobin dissociation curve (the Bohr effect) can explain the increase in mucosal oxygenation observed in endotoxemic pigs.(Crit Care Med 1995; 23:1217-1226)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo investigate the effect of sepsis on the intestinal absorption of arginine.DesignControlled, nonintervention study.SettingSurgical research laboratories of Sinai Hospital of Baltimore.SubjectsMale Sprague-Dawley rats.InterventionsExperimental sepsis induced by cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide.Measurements and Main ResultsSepsis assessed by peritoneal and blood cultures. Intestinal absorption estimated by measuring the transfer of3H-arginine by everted jejunal sacs prepared from septic and control animals (n = 6 per group) at multiple time points after the induction of sepsis (6, 12, 24, 48, and 72 hrs after cecal ligation and puncture; 6 and 12 hrs after intraperitoneal injection of lipopolysaccharide). Induction of peritonitis in the rat by cecal ligation and puncture significantly reduced the in vitro uptake of arginine by everted jejunal sacs at 12, 24, and 48 hrs after laparotomy. Arginine transfer by everted jejunal sacs was also significantly reduced in rats as early as 6 hrs after intraperitoneal injection of endotoxin (endotoxin 273 +/- 14; saline 377 +/- 14 nmol/sac/hr). Data are expressed as mean +/- SEM. Recovery from sepsis was associated with normalization of arginine transfer by intestinal sacs.ConclusionsExperimental sepsis, induced by either cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide, resulted in impaired intestinal amino acid uptake. Impaired intestinal arginine absorption may explain the lack of benefit of enteral, compared with parenteral, arginine therapy on survival from a septic insult.(Crit Care Med 1995; 23:1227-1232)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2as predictors of resuscitability after prolonged cardiac arrest.DesignProspective, randomized, controlled animal study.SettingUniversity research laboratory.SubjectsTwenty-one Sprague-Dawley rats, including three groups of seven animals in each group.InterventionsVentricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted.Measurements and Main ResultsAll animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest.ConclusionsThe efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.(Crit Care Med 1995; 23:1233-1236)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesAn extracorporeal bioartificial liver device must maintain viability and differentiated function of hepatocytes cultivated at high cell density. Growth factors, such as hepatocyte growth factor, found in high concentrations in the plasma of patients with fulminant hepatic failure, have the potential to promote hepatocyte dedifferentiation and thus, decrease function. We tested the hypothesis that hepatocyte growth factor would improve viable cell density and decrease biotrans-formation functions of liver cells in monolayer culture and in hepatocytes entrapped in collagen cylindrical gel ``noodles'' as found in the extracorporeal bioartificial liver.DesignIn vitro, controlled study.SettingUniversity research laboratory.SubjectsAdult Sprague Dawley Rats.InterventionsHepatocytes were harvested by a two-step collagenase technique. Harvested hepatocytes were plated onto type 1 collagen coated plates or entrapped in type 1 collagen cylindrical gels and cultured in different concentrations of hepatocyte growth factor. Interval measurements of3H-thymidine incorporation, albumin synthesis, biotransformation functions, and viability were made.Measurements and Main ResultsIn monolayer culture, the addition of hepatocyte growth factor caused a dramatic increase in3H-thymidine incorporation. This increase was accompanied by a decrease in the appearance of the lidocaine metabolite, monoethyglycin-exylidide. Albumin production was unchanged. In cylindrical gel entrapment cultures, hepatocyte growth factor caused a significant increase in 2-day viability but had no effect on the metabolite appearance of lidocaine or 4-methyl umbelliferone or albumin production.ConclusionsHepatocyte growth factor induces dedifferentiation of hepatocytes in monolayer culture. Collagen matrix entrapment appears to abrogate this effect and improve liver cell viability. There may be reciprocal regulation of hepatocyte reproductive and differentiated functions, such as biotransformation, which can be influenced by the entrapment of hepatocytes in an extracellular type 1 collagen matrix.(Crit Care Med 1995; 23:1237-1242)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objective250 mL/min).DesignMultiple part, randomized, controlled study.SettingSurgical research laboratory of a large university medical center.SubjectsTwenty-four units of cold, ready for transfusion in-date packed RBCs ranging in storage age from 6 to 16 days.Interventions500 mL/min. Six separate cold units were warmed at this rate using single channel countercurrent water bath warming. Part III: Microwave and countercurrent technology, inlet vs. outlet, warmed vs. unwarmed. a) Six units of cold packed RBCs was also analyzed biochemically and infused at 5 mL/min through either a microwave or countercurrent water bath warmer. b) Packed RBCs from the units used in part a) were allowed to remain stationary in the microwave heating cartridge for 15 mins with an activated heating element. Parallel stationary flow studies were done using the countercurrent blood warmer. Control unwarmed samples were also tested.Measurements and Main ResultsPart I: No statistical differences in hemolysis parameters were observed between microwave warmed and unwarmed packed RBCs. Part II: At high-flow rates, no statistical increases in hemolysis parameters were seen after in-line microwave or countercurrent water bath warming as compared with prewarmed cold controls. Part III: At slow-flow rates, nonstatistically significant increases were seen by passing the packed RBCs through either test apparatus unwarmed. Packed RBCs remaining stationary within microwave and countercurrent heating cartridges for 15 mins did show biochemical evidence of hemolysis. Mean plasma hemoglobin increased from 14 +/- 1.7 mg/dL in cold prewarmed units to 57.7 +/- 5.8 mg/dL (p < .05), when warmed in the microwave heating cartridge, and to 55.2 +/- 25 mg/dL (p < .05), when warmed in the countercurrent heat exchanger.Outlet Temperature Studies. Part II: The in-line 900-watt microwave device warmed cold units from a mean inlet temperature of 8.3 +/- 0.3 degrees C to a mean outlet temperature of 31.8 +/- 0.5 degrees C within 5 secs at a mean flow rate of 556 mL/min. At 30 secs, the mean outlet temperature was 33.9 +/- 0.4 degrees C (mean inlet temperature = 9.6 +/- 0.2 degrees C) for microwave warmed packed RBCs as compared with 32.1 +/- 0.5 degrees C (mean inlet temperature = 9.6 +/- 0.3 degrees C) in countercurrent water bath warmed blood (p < .05). From 20 to 30 secs, the packed RBCs warmed by microwave were statistically warmer than the countercurrent water bath warmed packed RBCs.Conclusionsa) Both in-line countercurrent warming and in-line microwave warming were associated with small increases in parameters of red cell damage representing statistically and clinically insignificant hemolysis. b) Blood sitting in any blood warming device is subject to statistically significant but clinically irrelevant increases in those parameters. c) At high-flow rates, the in-line microwave device warmed blood to higher outlet temperatures than the single channel countercurrent water bath warmer. This method may represent a clinical blood warming modality of the near future.(Crit Care Med 1995; 23:1243-1250)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveMyocardial depression from verapamil toxicity may result from alterations in carbohydrate metabolism as well as calcium-channel antagonism. We hypothesized that pharmacologic doses of insulin may be effective in reversing both of these deficits.DesignRandomized, controlled, prospective study.SettingLaboratory of an urban hospital.SubjectsThirty mongrel dogs.InterventionsThirty mongrel canines were anesthetized with alpha-chloralose. Toxicity was induced by the administration of 0.1 mg/kg/min iv of verapamil, until there was a 50% reduction in mean arterial pressure, for 30 mins (titration), followed by a continuous verapamil infusion of 1 mg/kg/hr. Animals (n = 6 per group) were randomized to the control group (saline only) or to one of four treatment protocols: a) calcium chloride (20 mg/kg), then 0.6 mg/kg/hr; b) hyperinsulinemia-euglycemia (4.0 U/min of recombinant insulin, with arterial glucose concentration clamped to +/-10 mg/dL [+/-0.5 mmol/L] of the basal value); c) epinephrine, with a starting rate of 1.0 micro gram/kg/min, titrated to maintain left ventricular pressure at basal values; or d) glucagon, a 0.2-mg/kg bolus, followed by a 150-micro gram/kg/hr infusion. Animals were monitored until death or 240 mins; infusate volumes were held constant for all groups.Measurements and Main ResultsDuring verapamil titration, the myocardial respiratory quotient increased from 0.84 +/- 0.05 to 1.07 +/- 0.11 (p < .05, paired t-test) and myocardial glucose uptake doubled, despite a reduction in cardiac work (p < .05, paired t-test). Net myocardial lactate uptake also increased significantly, excluding myocardial ischemia. In controls, this trend continued, indicating preferential carbohydrate metabolism during untreated verapamil toxicity. Despite hyperglycemia, the plasma insulin concentration was not significantly different in controls (basal value 11 +/- 2 vs. 39 +/- 21 mu U/mL at 30 mins). Hyperinsulinemia-euglycemia increased both myocardial glucose and lactate uptake five-fold, and significantly increased the ratio of myocardial oxygen delivery/work, along with superior improvements in maximal left ventricular elastance at end systole compared with other treatments (p < .05 vs. other treatments, contrast analysis).ConclusionsVerapamil toxicity renders the heart dependent on carbohydrate metabolism. Inasmuch as the positive inotropic effects of all treatments were coincident with increased indices of myocardial carbohydrate uptake, adequate treatment of verapamil toxicity appeared to require maximal myocardial carbohydrate utilization. Hyperinsulinemia-euglycemia allows larger increases in myocardial carbohydrate metabolism and myocardial contractility than calcium chloride, epinephrine, or glucagon, resulting in improved survival rates during severe verapamil toxicity.(Crit Care Med 1995; 23:1251-1263)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo locate the specific site (i.e., pulmonary arteries, veins, or capillaries) of increased pulmonary vascular resistance after wood smoke inhalation and to demonstrate whether the prostanoids, thromboxane B2or 6-keto-prostaglandin F1alpha, play a role in these vascular resistance changes.DesignProspective, randomized, controlled trial.SettingLaboratory at a university medical center.SubjectsFive mongrel dogs.InterventionsThe isolated canine left lower lobe preparation was used to measure changes in the pressure drop across the pulmonary arteries, veins, and capillaries. The left lower lobe was surgically isolated and perfused by a pump primed with autologous blood. The arterial and venous occlusion technique and the vascular pressure-flow relationship were used to assess changes in pulmonary vascular resistance. After baseline measurements, the left lower lobe was exposed to wood smoke for 2.5 mins and measurements were repeated.Measurements and Main ResultsSmoke exposure caused an immediate (5 mins postinhalation) increase in the total pressure gradient across the lobe (baseline = 9.8 +/- 0.5 torr [1.3 +/- 0.06 kPa]); smoke inhalation = 24.3 +/- 3.9 torr [3.24 +/- 0.5 kPa]; p < .05). Total pressure drop was partitioned longitudinally into pressure drops across arteries, veins, and the middle vessels. The increase in total pressure drop was associated with a moderate increase in the pressure drop across the middle vessels (baseline = 1.1 +/- 0.2 torr [0.14 +/- 0.02 kPa]; smoke inhalation = 5.2 +/- 1.1 torr [0.69 +/- 0.14 kPa]; p < .05); a large increase in the pressure drop across the veins (baseline = 4.8 +/- 1.3 torr [0.64 +/- 0.17 kPa]; smoke inhalation = 20.7 +/- 3.4 torr [2.7 +/- 0.45 kPa]; p < .05), and no significant change in the pressure drop across the arteries (baseline = 3.7 +/- 0.4 torr [0.49 +/- 0.05 kPa]; smoke inhalation = 4.8 +/- 0.5 torr [0.64 +/- 0.06 kPa]; p = NS). Increases in the pressure drop across the middle and venous vessels were transient and no longer significantly different from baseline 15 mins after smoke inhalation. Similarly, analysis of the pulmonary artery/blood flow data demonstrated that the mean slope and pressure intercept were greater than baseline only at 5 mins postsmoke inhalation (p < .05). Thromboxane B2did not significantly change from baseline values after smoke exposure and prostaglandin F1alpha demonstrated a slight but significant decrease 30 mins postsmoke. Pulmonary edema was measured gravimetrically (wet/dry weight ratio) and smoke significantly increased lung water in the left lower lobe (wet/dry weight ratio = 6.55 +/- 0.4) as compared with the normal left upper lobe (wet/dry weight ratio = 4.97 +/- 0.2).ConclusionsWe conclude that smoke causes an intense but transient increase in the pressure drop across the venous segment that may accelerate the formation of pulmonary edema, which is not mediated by changes in thromboxane B2or prostaglandin F1alpha.(Crit Care Med 1995; 23:1264-1271)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo determine whether, during hemorrhagic shock, the effect of epinephrine on energy metabolism could be deleterious, by enhancing the oxygen requirement at a given level of oxygen delivery (DO2).DesignProspective, randomized, control trial.SettingExperimental laboratory.SubjectsTwo groups of seven mongrel dogs were studied. The epinephrine group received a continuous infusion of epinephrine (1 micro gram/min/kg) while the control group received saline.InterventionDogs were anesthetized with pentobarbital, and shock was produced by stepwise hemorrhage.Measurements and Main ResultsOxygen consumption (VO2) was continuously measured by the gas exchange technique, while DO2was independently calculated from cardiac output (measured by thermodilution) and blood oxygen content. A dual-lines regression fit was applied to the DO2vs. VO2plot. The intersection of the two regression lines defined the critical value of DO2. Values above critical DO2belonged to phase 1, while phase 2 occurred below critical DO2. In the control group, VO2was independent of DO2during phase 1; VO2was dependent on DO2during phase 2. In the epinephrine group, the expected increase in VO2(+19%) and DO2(+50%) occurred under normovolemic conditions. During hemorrhage, VO2immediately decreased, and the slope of phase 1 was significantly (p < .01) different from zero, and was significantly (p < .05) steeper than in the control group (0.025 +/- 0.005 vs. 0.005 +/- 0.010). However, the critical DO2(8.7 +/- 1.7 vs. 9.7 +/- 2.4 mL/min/kg), the critical VO2(5.6 +/- 0.5 vs. 5.5 +/- 0.9 mL/min/kg), and the slope of phase 2 (0.487 +/- 0.080 vs. 0.441 +/- 0.130) were not different from control values.ConclusionsThe administration of pharmacologic doses of epinephrine significantly increased VO2under normovolemic conditions due to the epinephrine-induced thermogenic effect. This effect progressively decreased during hemorrhage. The critical DO2and the relationship between DO2and VO2in the supply-dependent phase of shock were unaffected by epinephrine infusion. These results suggest that during hemorrhagic shock, epinephrine administration did not exert a detrimental effect on the relationship between DO2and VO2.(Crit Care Med 1995; 23:1272-1278)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo determine predictors of survival and functional outcome of pediatric patients requiring mechanical ventilation during therapy for acute bacterial meningitis.DesignRetrospective case series.SettingPediatric intensive care unit (ICU) at a midwestern tertiary care children's hospital.PatientsConsecutive sample of 32 patients (median age 9.8 months; range 9 days to 12 yrs) from 1985 to 1990 with acute bacterial meningitis severe enough to require mechanical ventilation during therapy. Of these patients, 59% were female and 59% were white.InterventionsNone.Measurements and Main ResultsData were analyzed to identify predictors of survival and functional status after hospital discharge. Variables included were vital signs, Pediatric Risk of Mortality (PRISM) score within the first 24 hrs of hospitalization, Glasgow Coma Score, and course of illness. Functional status was assessed at hospital discharge and at follow-up (median follow-up: 41.5 months, range 7 to 77) in the areas of locomotion, self-care, and communication. There were ten inhospital deaths. The 22 survivors formed three groups. At hospital discharge, seven children showed no functional disability. Seven patients were dependent in all three areas of function at discharge, with six still dependent at follow-up evaluation. Eight patients showed mild to moderate impairment in at least one area of function at hospital discharge. At follow-up, four of these eight patients demonstrated no functional disability, one had improved status, two were unchanged, and one was lost to follow-up. The best predictor of death and functional status at follow-up was the admission PRISM score. Hypotension and tachycardia within the first 24 hrs after pediatric ICU admission were strongly associated with poor outcome.ConclusionsAfter bacterial meningitis in children whose care included mechanical ventilation, half of the patients died or survived with severe functional deficits. Patients with mild or moderate functional deficits at hospital discharge improved with time.(Crit Care Med 1995; 23:1279-1283)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo describe system requirements for determination of the oxygen status of the blood using the oxygen status algorithm, a computer program. To define the oxygen extractivity, a term we propose, of the arterial blood and the oxygen extraction tension. To describe the different causes of tissue hypoxia, and the clinical interpretation of mixed venous oxygen tension and oxygen consumption rate.Data SourcesPrevious physiological and clinical studies related to oxygen status of the blood.Data SynthesisThe oxygen status algorithm calculates the oxygen extraction tension and generates the oxygen graph as an aid in interpreting oxygen status of the patient. A cybernetic scheme explains the causes of tissue hypoxia and forms the basis for the interpretation of changes in the mixed venous oxygen tension. A diagram with the mixed venous oxygen tension on the abscissa and the oxygen consumption rate on the ordinate illustrates the oxygen flux dependent oxygen consumption rate. A graph shows the relationship between mixed venous oxygen tension and oxygen delivery.ConclusionsThe oxygen status of arterial blood comprises three groups of quantities related to arterial oxygen tension, hemoglobin oxygen capacity, and hemoglobin oxygen affinity. Disturbances in one of these groups may be compensated by opposite changes in one or both of the other. The oxygen extraction tension indicates the degree of compensation, and mixed venous oxygen tension is the key parameter in evaluating the presence of a state of oxygen flux-dependent oxidative metabolism.(Crit Care Med 1995; 23:1284-1293)

ISSN:0090-3493    

出版商:OVID    

年代:1995

数据来源: OVID