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11. |
Factors affecting the performance of the models in the Mortality Probability Model II system and strategies of customizationA simulation study |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 57-63
Bao-Ping Zhu,
Stanley Lemeshow,
David Hosmer,
Janelle Klar,
Jill Avrunin,
Daniel Teres,
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摘要:
ObjectivesTo examine the impact of hospital mortality and intensive care unit (ICU) size on the performance of the Mortality Probability Model II system for use in quality assessment, and to examine the ability of model customization to produce accurate estimates of hospital mortality to characterize patients by severity of illness for clinical trials.DesignProspective evaluation of model performance, using retrospective data.SettingData for the simulation were assembled from six adult medical and surgical ICUs in Massachusetts and New York.PatientsConsecutive admissions (n equals 4,224) to the Massachusetts and New York ICUs were studied. The mortality rate in the database was 18.7%.InterventionsA computer simulation of several different hospital mortality rates and ICU sample sizes, using a multicenter database of consecutive ICU admissions, was utilized. We simulated 20 different mortality rates by randomly changing the outcomes at hospital discharge from "survived" to "deceased" and from "deceased" to "survived." Four sample size simulations used 75%, 50%, 25%, and 10% of the total database. Ten replications of each mortality rate and sample size were constructed, and model calibration and discrimination were assessed for each replication. Model coefficients were customized, using logistic regression.Measurements and Main ResultsVital status at hospital discharge was the outcome measure among the ICU patient population. Model performance was assessed using the Hosmer-Lemeshow C statistic for calibration, and the area under the receiver operating characteristic curve for discrimination.Goodness-of-fit tests and receiver operating characteristic curve areas demonstrated that the models were sensitive to differences in hospital mortality, indicating that they are useful quality assurance tools. Goodness-of-fit tests were more sensitive than the receiver operating characteristic curve areas. The further the hospital mortality rate diverged from the original rate, the worse the performance of the model. Sample size had an impact on these results. The smaller the sample size, the less likely the model was to perform poorly. Model coefficients were successfully customized to demonstrate that improved model performance can be achieved when necessary for clinical trial stratification.ConclusionMortality Probability Model II models can be used to assess quality of care in ICUs, but the size of the sample should be considered when assessing calibration and discrimination.(Crit Care Med 1996; 24:57-63)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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12. |
Simplified Therapeutic Intervention Scoring SystemThe TISS-28 items--Results from a multicenter study |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 64-73
Dinis Reis Miranda,
Angelique de Rijk,
Wilmar Schaufeli,
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摘要:
ObjectivesTo validate a simplified version of the Therapeutic Intervention Scoring System, the TISS-28, and to determine the association of TISS-28 with the time spent on scored and nonscored nursing activities.DesignProspective, multicenter study.SettingTwenty-two adult medical, surgical, and general Dutch intensive care units (ICUs).PatientsA total of 903 patients consecutively admitted to the ICUs.InterventionsTISS-28 was constructed from a random sample of 10,000 records of TISS-76 items. The respective weights were calculated using multivariable regression analysis through the origin; TISS-76 scores were used as predicted values. Cross validation was performed in another random sample of 10,000 records and the scores of TISS-76 were compared with those scores obtained with TISS-28 (r equals .96, r sup 2 equals .93).Nursing activities in the ICU were inventoried and divided into six categories:a) activities in TISS-28; b) patient care activities not in TISS-28; c) indirect patient care (activities related to but not in direct contact with the patient, such as contact with family, maintaining supplies); d) organizational activities (e.g., meetings, trainee supervision, research); e) personal activities (for the nurse him/herself, such as taking a break, going to the bathroom); f) other.During a 1-month period, TISS-76 and TISS-28 scores were determined daily from the patient's records by independent raters. During a 1-wk period, all of the nurses on duty scored their activities using a method called "work sampling."Measurements and Main ResultsThe analysis of validation included 1,820 valid pairs of TISS-76 and TISS-28 records. The mean value of TISS-28 (28.8 plus minus 11.1) was higher (p less than .00) than that value of TISS-76 (24.2 plus minus 10.2). TISS-28 explained 86% of the variation in TISS-76 (r equals .93, r2equals .86)."Work sampling" generated 10,079 registrations of nursing activities, of which 5,530 could be matched with TISS-28 records. Samples were taken from medical (19.3%), surgical (19.1%), and general (61.6%) ICUs. Of these samples, 51.1% originated from university hospitals, 35.8% from hospitals with more than 500 beds, 7.1% from hospitals with 300 to 500 beds, and 5.8% from hospitals with less than 300 beds. Samples were scored in the morning (43.0%), evening (32.9%), and night shifts (24.1%). This sample of work activities was divided into four groups, according to their matched TISS scores (0 to 20, 20 to 35, 35 to 60, and more than 60 points). In the successive groups of TISS scores, there was a significant increase in the proportion of time spent on the activities scored with TISS-28. In the lower TISS score group (0 to 20 points), there was a significantly larger proportion of time allocated to patient care activities not in TISS-28. There was no significant difference in the proportion of time spent when associating indirect patient care and organizational activities with the level of TISS score. There was a significant decrease in the proportion of time spent on personal activities in the successive groups of TISS scores. The mean time spent per shift with personal activities varied between 1 hr and 40 mins (group 0 to 20 points TISS), and 1 hr and 16 mins (group more than 60 points TISS). Significantly more time was used for patient care activities during the evening shift than during the day or the night shift. Conversely, nurses spent significantly less time on activities regarding their personal care during the evening shift. The time consumed for the activities of indirect patient care did not differ significantly among the three shifts.A typical nurse was capable of delivering work equal to 46.35 TISS-28 points per shift (one TISS-28 point equals 10.6 mins of each nurse's shift).ConclusionsThe simplified TISS-28 explains 86% of the variation in TISS-76 and can therefore replace the original version in the clinical practice in the ICU.Per shift, a typical nurse is capable of delivering nursing activities equal to 46 TISS-28 points. This information, together with the information concerning the association of TISS score with the time spent in the various nursing activities within the ICU, is relevant to the management of nursing manpower in the ICU.(Crit Care Med 1996; 24:64-73)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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13. |
Frequency of variable measurement in 16 pediatric intensive care unitsInfluence on accuracy and potential for bias in severity of illness assessment |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 74-77
Murray Pollack,
Kantilal Patel,
Urs Ruttimann,
Timothy Cuerdon,
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摘要:
ObjectivesWe evaluated: a) whether the frequency of variable measurement could influence the performance of the Pediatric Risk of Mortality (PRISM) score; b) whether measurement frequency of physiologic variables varied between individual pediatric intensive care units (ICUs), and c) if so, how much of this variability could be attributed to institution-level and patient-level factors.DesignProspective cohort.SettingSixteen pediatric ICUs, chosen for their diversity.PatientsConsecutive admissions (n equals 5,415).InterventionsNone.Measurements and Main ResultsFirst, the measurement frequency of the 14 physiologic variables in the PRISM score was included in the logistic regression model predicting mortality risk. Measurement frequency was not significant, alone or in its interaction with the PRISM score. Second, the presence or absence of measurement of each physiologic variable was included in the logistic model using indicator variables; none was significant. Finally, the contribution of the individual pediatric ICUs and patient factors in explaining the variability in the frequency of physiologic variable measurement were investigated with linear regression analysis. In this analysis, the separation of severity of illness from measurement frequency was accomplished by computing the PRISM score from the first 4 hrs and measurement frequencies from hours 5 through 24. Overall, 70.22% (r2) of the variability of measurement frequency could be explained by the factors included in the linear regression model. The individual ICUs accounted for a total of only 6.23% of the explained variability and no individual hospital accounted for more than 1.44% of the variability. Other variables positively correlated with measurement frequency included the presence or absence of a pediatric intensivist, and whether the institution was a children's hospital or not. Variables negatively correlated with measurement frequency included larger ICUs and house officers assigned to the ICU.ConclusionsAlthough measurement frequency is associated with unit-level factors, their contribution to the overall variability is small and unlikely to influence the accuracy or reliability of the PRISM score. It is unlikely that there are routine biases associated with differences in measurement frequency of PRISM variables within the spectrum of care practices that now exist.(Crit Care Med 1996; 24:74-77)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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14. |
Prediction of three outcome states from pediatric intensive care |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 78-85
Urs Ruttimann,
Murray Pollack,
Debra Fiser,
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摘要:
ObjectiveTo develop a method based on admission day data for predicting patient outcome status as independently functional, compromised functional, or dead.DesignProspectively acquired development and validation samples.SettingA pediatric intensive care unit located in a tertiary care center.PatientsConsecutive admissions (n equals 1,663) for predictor development, and consecutive admissions (n equals 1,153) for predictor validation.MethodsPediatric Risk of Mortality score, baseline Pediatric Overall Performance Category score, age, operative status, and primary diagnosis classified into ten organ systems and nine etiologies were recorded at the time of intensive care unit admission. Predictor was developed by stepwise polychotomous logistic regression analysis for the outcomes functional, compromised, and dead. Model fit was evaluated by chi-square statistics; prediction performance was measured by the area under the receiver operating characteristic curve, and classification table analysis of observed vs. predicted outcomes.Measurements and Main ResultsThe resulting predictor included Pediatric Risk of Mortality, baseline Pediatric Overall Performance Category, operative status, age, and diagnostic factors from four systems (cardiovascular, respiratory, neurologic, gastrointestinal), and six etiologies (infection, trauma, drug overdose, allergy/immunology, diabetes, miscellaneous/undetermined). Its application to the validation sample yielded good agreement between the total number expected and the observed outcomes for each state (chi-square equals 3.16, 2 degrees of freedom, p equals .206), with area indices of 0.96 plus minus 0.01 for discrimination of fully functional vs. the combination of the two poor outcome states (compromised or death), and 0.94 plus minus 0.02 for discrimination of fully or compromised functional vs. death. The 3 times 3 classification resulted in correct classification rates of 83.2%, 74.4%, and 81.3%, for the outcomes functional, compromised, and death, respectively.ConclusionsPrediction of three outcome states using physiologic status, baseline functional level, and broad-based diagnostic groupings at admission is feasible and may improve the relevance of quality of care assessment.(Crit Care Med 1996; 24:78-85)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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15. |
Oxygen consumption calculated from the Fick equation has limited utility |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 86-90
M. Stock,
Marqueta Ryan,
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摘要:
ObjectiveTo determine if oxygen consumption (VO2) calculated using the Fick relationship (calculated VO2) determines total body VO2accurately and precisely enough to employ this method during clinical assessment of oxygen transport.DesignMethods comparison, using repeated measures during four physiologic states: normal heart/normal lungs, heart failure/normal lungs, normal heart/acute lung injury, heart failure/acute lung injury.SettingsUniversity research laboratory.SubjectsThirteen adult Yucatan pigs.InterventionsOleic acid-induced acute lung injury; heart failure was induced with a continuous infusion of esmolol.Measurements and Main ResultsCalculated VO2was determined by multiplying thermodilution cardiac output by the arterialvenous oxygen content difference in anesthetized, spontaneously breathing animals. Conditions were tightly controlled so that calculated VO2would be as accurate as possible. "True" VO2was measured simultaneously with a water-sealed spirometer (spirometry VO2). Calculated VO2and spirometry VO2were determined and analyzed during the four physiologic states listed above. Pooled data also were evaluated. Mean spirometry VO2and calculated VO2differed significantly during all four physiologic states and when data were pooled (spirometry VO2273 plus minus 70, calculated VO2178 plus minus 58 mL/min; p less than .01). Calculated VO2consistently underestimated spirometry VO2, as demonstrated by the large, positive bias in pooled data (95 plus minus 59 mL of oxygen/min) and in the four physiologic states. Linear regression of data from all four states yielded slopes that were indistinguishable from 1, but y intercepts that varied from minus 152 to plus 182. For pooled data, the following equation was used: calculated VO2equals 0.5 times (spirometry VO2plus 46); r2equals .35. Precision in pooled data was 22% of the mean spirometry VO2. Data analysis for the four physiologic states demonstrated results similar to those results obtained when data were pooled.ConclusionsEven in a tightly controlled, clinical simulation in the laboratory, calculated VO2from the Fick relationship systematically underestimated VO2measured with a water-sealed spirometer. If true VO2changes, the magnitude and direction of change will be reflected by calculated VO2but with approximate 20% error in the absolute value. Heart failure, acute lung injury, and their combination did not affect the accuracy of calculated VO2. Therefore, calculating VO2using the Fick relationship is too inaccurate to be used for research purposes. Because assessment of the directional change of VO2may be clinically useful, calculated VO2can be employed with discretion during clinical oxygen transport evaluation, bearing in mind the calculation's inherent imprecision.(Crit Care Med 1996; 24:86-90)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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16. |
Spirometric versus Fick-derived oxygen consumptionWhich method is better? |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 91-95
David Thrush,
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摘要:
ObjectiveOxygen consumption (VO2) is often measured in critically ill patients using the Fick equation: VO2equals cardiac output times arterial-venous oxygen content difference. To determine if this method is accurate, it was compared with a spirometric technique.DesignProspective study.SettingUniversity laboratory.SubjectsNineteen large adult pigs.InterventionsCardiac output, measured with bolus thermodilution technique, and arterial and venous oxygen content values, determined with the galvanic fuel cell method, were used to determine VO2with the Fick equation. The spirometrically determined VO2was the rate of disappearance of oxygen from a water-sealed spirometer. Dobutamine and labetalol were titrated to vary VO2(range 204 to 584 mL/min).Measurements and Main ResultsThe bias between the Fick and spirometrically determined VO2values was 58 mL/min. The precision (SD of the bias) between the Fick and spirometrically determined VO2was 35 mL/min. Fick-derived VO2was greater than VO2measured spirometrically. The correlation coefficient was 0.90.ConclusionsDespite all attempts to reduce measurement error, there was an unexplained difference in Fick-derived and spirometrically measured VO2. Therefore, I feel that the two methods are not interchangeable, and that calculations of VO sub 2 using the Fick method should be used cautiously when therapeutic maneuvers are based on these data.Crit Care Med 1996; 2491-95)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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17. |
Single breath CO sub 2 analysisDescription and validation of a method |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 96-102
John Arnold,
John Thompson,
Lucy Arnold,
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摘要:
ObjectivesTo evaluate the performance of a newly developed single breath CO2analysis station in measuring the airway deadspace in a lung model (study 1), and then to quantify the bias and precision of the physiologic deadspace measurement in a surfactant-depleted animal model (study 2).DesignA prospective bench validation of a new technique of airway deadspace measurement using a criterion standard (study 1); a prospective, animal cohort study comparing a new technique of physiologic deadspace measurement with a reference method (Bohr-Enghoff method) (study 2).SettingA bench laboratory and animal laboratory in a university-affiliated medical center.SubjectsA lung model (study 1), and adult sheep with induced surfactant deficiency (saline lavage) (study 2).MethodsThe single breath CO2analysis station consists of a mainstream capnometer, a variable orifice pneumotachometer, a signal processor, and computer software with capability for both on- and off-line data analysis. Study 1: We evaluated the accuracy of the airway deadspace calculation using a plexiglass lung model. The capnometer and pneumotachometer were placed at the ventilator Y-piece with polyvinyl chloride tubing added to simulate increased airway deadspace. Segments of tubing were sequentially removed during each testing session to simulate decreasing deadspace. The calculated airway deadspace was derived from the single breath CO2plot and compared with the actual tubing volume using least-squares linear regression and paired t-tests. Study 2: The accuracy of the physiologic deadspace measurement was examined in a saline-lavaged animal model by comparing the physiologic deadspace calculated from the single breath CO2analysis station with values obtained using the Enghoff modification of the Bohr equation: deadspace/tidal volume ratio equals (PaCO2minus mixed expired PCO2)/PaCO2.Measurements and Main ResultsStudy 1: Thirty-six measurements of calculated airway deadspace were made and compared with actual circuit deadspace during four different testing conditions. Measured airway deadspace correlated significantly with actual circuit deadspace (r2equals .99). The proportional error of the method was minus 0.8% with a 95% confidence interval from minus 3.6% to 1.9%. Study 2: A total of 27 pairs of measurements in four different animals were available for analysis. The derived physiologic deadspace/tidal volume ratio significantly correlated with the value obtained using the Bohr-Enghoff method (r2equals .84). The bias and precision of our physiologic deadspace calculation were .02 and .02, respectively, and the mean percent difference for the physiologic deadspace calculated from the single breath CO2analysis station was 2.4%.ConclusionsOur initial experience with the single breath CO2analysis station indicates that this device can reliably provide online evaluation of the single-breath CO2waveform. In particular, estimation of the airway and physiologic deadspace under a variety of testing conditions was consistently within 5% of actual values. We feel that with further application and refinement of the technique, single breath CO2analysis may provide a noninvasive, on-line monitor of changes in pulmonary blood flow.(Crit Care Med 1996; 24:96-102)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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18. |
Enhanced recovery of brain electrical activity by adenosine 3 prime,5 prime-cyclic monophosphate following complete global cerebral ischemia in dogs |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 103-108
Thomas Toung,
Jeffrey Kirsch,
Richard Traystman,
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摘要:
ObjectiveTo test the hypothesis that adenosine 3 prime,5 prime-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period.DesignRandomized, controlled, prospective study.SettingUniversity research laboratory.SubjectsTwenty-five male beagle dogs.InterventionsNine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n equals 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60, 90, and 120 mins of reperfusion, n equals 9).Measurements and Main ResultsTotal and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion.Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 plus minus 6; cAMP 56 plus minus 9; dibutyl-cAMP 67 plus minus 10 mL/min/100 g [mean plus minus SEM, p less than .05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 plus minus 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 plus minus 4% of preischemic baseline value in the cAMP-pretreated group (p less than .05), and to 70 plus minus 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p less than .05).ConclusionscAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP-and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circulatory effects.(Crit Care Med 1996; 24:103-108)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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19. |
Hypertonic saline does not improve cerebral oxygen delivery after head injury and mild hemorrhage in cats |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 109-117
Douglas DeWitt,
Donald Prough,
Dwight Deal,
Scott Vines,
Helena Hoen,
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摘要:
ObjectivesTo investigate the effects of hypertonic saline for resuscitation after mild hemorrhagic hypotension combined with fluid-percussion traumatic brain injury. Specifically, the effects of hypertonic saline on intracranial pressure, cerebral blood flow (radioactive microsphere method), cerebral oxygen delivery (cerebral oxygen delivery equals cerebral blood flow times arterial oxygen content), and electroencephalographic activity were studied.DesignRandomized, controlled, intervention trial.SettingUniversity laboratory.SubjectsThirty-four mongrel cats of either sex, anesthetized with 1.0% to 1.5% isoflurane in nitrous oxide/oxygen (70:30).InterventionsAnesthetized (isoflurane) cats were prepared for traumatic brain injury, and then randomly assigned to the following groups: moderate traumatic brain injury only (2.7 plus minus 0.2 atmospheres [atm], group 1); mild hemorrhage (18 mL/kg) only, followed immediately by resuscitation with 10% hydroxyethyl starch in 0.9% saline in a volume equal to shed blood (group 2); or both traumatic brain injury (2.7 plus minus 0.1 atm) and mild hemorrhage, followed immediately by replacement of a volume equal to shed blood of 10% hydroxyethyl starch in 0.9% saline (group 3); or 3.0% saline (group 4).Measurements and Main ResultsData were collected at baseline, at the end of hemorrhage, and at 0, 60, and 120 mins after resuscitation (or at comparable time points in group 1). Intracranial pressure in group 1 was significantly increased by traumatic brain injury at the end of hemorrhage, immediately after resuscitation, and 60 mins after resuscitation (p less than .02 vs. baseline). In group 2, intracranial pressure increased significantly only immediately after resuscitation (p less than .0001 vs. baseline). Groups 3 and 4 exhibited higher, although statistically insignificant, intracranial pressure increases at 60 and 120 mins after resuscitation. During resuscitation, cerebral blood flow increased significantly (p less than .02 vs. baseline) in the uninjured cats. In contrast, cerebral blood flow failed to increase during resuscitation in the cats subjected to traumatic brain injury before hemorrhage and resuscitation. Although cerebral oxygen delivery in group 2 decreased significantly immediately, 60 mins, and 120 mins after resuscitation (p less than .001 vs. baseline) both groups 3 and 4 had significantly lower cerebral oxygen delivery at 60 and 120 mins after resuscitation (p less than .01 and p less than .005, respectively, vs. group 1 at 60 mins after resuscitation, and p less than .01 and p less than .01, respectively, vs. group 1 at 120 mins after resuscitation).ConclusionsAfter a combination of hemorrhage and traumatic brain injury, neither 10% hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral oxygen delivery. Although neither trauma alone nor hemorrhage alone altered electroencephalographic activity, the combination produced significant decreases in electroencephalographic activity at 60 and 120 mins after resuscitation in groups 3 and 4, suggesting that cerebral oxygen delivery is inadequately restored by either resuscitation fluid. Therefore, traumatic brain injury abolished compensatory cerebral blood flow increases to hemodilution, and neither hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral blood flow, cerebral oxygen delivery, or electroencephalographic activity after hemorrhagic hypotension after traumatic brain injury.(Crit Care Med 1996; 24:109-117)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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20. |
Burn injury alters beta-adrenergic receptor and second messenger function in rat ventricular muscle |
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Critical Care Medicine,
Volume 24,
Issue 1,
1996,
Page 118-124
Chen Wang,
J A Martyn,
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摘要:
ObjectivesThe molecular pharmacologic bases for the attenuated cardiovascular and metabolic responses to catecholamines, after burn injury, have not been elucidated. In the present study, myocardial tissues were used as a model of beta-adrenergic receptors to study burn injury-induced alterations in receptors and in signal transduction.DesignProspective study, randomized to treatment and control groups.SettingUniversity-hospital research laboratory.SubjectsMale Sprague-Dawley rats (180 to 210 g).InterventionsA 50% body surface area burn or sham-burn was administered to the rats.Measurements and Main ResultsMyocardial membranes were isolated at 24 hrs, 7 days and 14 days after 50% body surface area scald or sham injury. (minus)125I-iodocyanopindolol was used to assess maximal binding capacity and affinity of the beta-adrenergic receptor. Basal and stimulated concentrations of second messenger, cyclic adenosine monophosphate (cAMP), were also assessed. Production of cAMP during isoproterenol stimulation tested the integrity of the beta-adrenergic receptor-mediated signal transduction. Forskolin, which stimulates adenylate cyclase enzyme directly (bypassing the receptor and G protein) to produce cAMP, tested the efficacy of the enzyme itself. Maximal binding capacity was unaltered between the experimental and control groups, but the affinity (mean plus minus SEM) was significantly decreased in burned animals at 7 days (125.4 plus minus 15.5 picomoles [pmol]; p equals .01) and at 14 days (216.7 plus minus 50.7 pmol; p equals .001) compared with controls (75.5 plus minus 8.4 pmol). In different set experimental and control groups, basal concentrations of cAMP in myocardial membranes were significantly decreased in burned animals at 7 days (control 38.6 plus minus 4.2 vs. 5.8 plus minus 0.9 pmol/mg of protein/min; p equals .003) and at 14 days (control 47.4 plus minus 3.2 vs. 28.3 plus minus 6.6 pmol/mg of protein/min; p equals .002). The forskolin (direct)-stimulated synthesis of cAMP was decreased in burned animals at 24 hrs (control 339.0 plus minus 40.5 vs. 214.4 plus minus 16.6 pmol/mg of protein/min; p equals .01), at 7 days (control 289.0 plus minus 34.4 vs. 32 plus minus 13.0 pmol/mg of protein/min; p equals .01), and at 14 days (control 322.9 plus minus 28.6 vs. 137.0 plus minus 46.1 pmol/mg of protein/min; p equals .01). The isoproterenol or receptor-mediated stimulation of cAMP production was also significantly (p less than .001) impaired in burned animals compared with controls at 24 hrs (control 134.7 plus minus 11.9 vs. 83.1 plus minus 13.3 pmol/mg of protein/min), and at 14 days (control 128.2 plus minus 7.2 vs. 92.8 plus minus 17.7 pmol/mg of protein/min).ConclusionThe etiology of the decreased responses in the myocardium, to exogenous and endogenous beta-adrenergic receptor agonists after burn injury may be attributed to decreased affinity for ligands, and also to impaired receptor-mediated signal transduction and to decreased adenylate cyclase enzyme activity, resulting in decreased basal and stimulated second messenger (cAMP) production.(Crit Care Med 1996; 24:118-124)
ISSN:0090-3493
出版商:OVID
年代:1996
数据来源: OVID
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