Intensive Care Unit Patient Population Research Articles

Population Pharmacokinetics of Flucytosine: Comparison and Validation of Three Models Using STS, NPEM, and NONMEM

The objective of this study is to compare and validate three models of flucytosine (5-FC) population pharmacokinetics using three methods of analysis to elucidate which model describes 5-FC pharmacokinetics most accurately and which method is the most suitable for this purpose. Retrospectively, demographic and clinical data of two similar sets of a total of 88 intensive care unit (ICU) patients were gathered for calculation and validation of 5-FC pharmacokinetics respectively. Three pharmacokinetic models were analyzed: a one-compartment with renal elimination (renal model), a one-compartment with renal and metabolic elimination (mixed model), and a two-compartment with renal elimination (two-compartment model). Population pharmacokinetic parameters were calculated using the standard two-stage method (STS), NONMEM, and NPEM. Furthermore, a covariate model was built by NONMEM. Validation of the 10 calculated pharmacokinetic models showed that NONMEM is most suitable for predicting 5-FC population pharmacokinetics. Based upon AIC values, bias and precision, the best results are obtained using a two-compartment model with renal elimination (k(elr) = 0.000858 +/- 0.000143 l/h per mL per min, k12 = 0.0313 +/- 0.0168 h(-1), k21 = 0.0353 +/- 0.0145 h(-1), and Vd = 0.541 +/- 0.084 L/kg; bias = -13.16; 95% CI = -16.77; -9.55; precision = 30.50; 95% CI = 27.47; 33.26) or a two-compartment covariate model as built by NONMEM [Vd (L) = 0.572 x WT, Cl(5FC) (L/h) = 1.69 + 0.0273 x (Cl(cr) (mL/min) - 52.5), k12 = 0.0235 +/- 0.0107 h(-1), and k21 = 0.0375 +/- 0.0147 h(-1); bias = -8.29; 95% CI = -11.63; -4.95; precision = 26.77; 95% CI = 24.24; 29.07]. In conclusion, this study shows that a two-compartment model with renal elimination best describes 5-FC population pharmacokinetics and NONMEM is able to build a two-compartment covariate model that predicts 5-FC levels equally well in our population of ICU patients. Furthermore, NONMEM appeared to be the most suitable method of population pharmacokinetics in our population and for this purpose it offers more reliable and accurate results than NPEM or the STS method.

Emergence and prevention of cross-transmission of vancomycin-resistant E. faecium (VRE) in a level III neonatal intensive care unit (NICU) patient population

Emergence and prevention of cross-transmission of vancomycin-resistant E. faecium (VRE) in a level III neonatal intensive care unit (NICU) patient population

The impact of a multidisciplinary approach on caring for ventilator-dependent patients.

To determine the clinical and financial outcomes of a highly structured multidisciplinary care model for patients in an intensive care unit (ICU) who require prolonged mechanical ventilation. The structured model outcomes (protocol group) are compared with the preprotocol outcomes. Descriptive study with financial analysis. A twelve-bed medical-surgical ICU in a non-teaching tertiary referral center in Ogden, Utah. During a 54 month period, 469 consecutive intensive care patients requiring mechanical ventilation for longer than 72 hours who did not meet exclusion criteria were studied. A multidisciplinary team was formed to coordinate the care of ventilator-dependent patients. Care was integrated by daily collaborative bedside rounds, monthly meetings, and implementation of numerous guidelines and protocols. Patients were followed from the time of ICU admission until the day of hospital discharge. Patients were assigned APACHE II scores on admission to the ICU, and were divided into eight diagnostic categories. ICU length of stay, hospital length of stay, costs, charges, reimbursement, and in-hospital mortality were measured. Mortality in the preprotocol and protocol group, after adjustment for APACHE II scores, remained statistically unchanged (21-23%). After we implemented the new care model, we demonstrated significant decreases in the mean survivor's ICU length of stay (19.8 days to 14.7 days, P= 0.001), hospital length of stay (34.6 days to 25.9 days, P=0.001), charges (US$102500 to US$78500, P=0.001), and costs (US$71900 to US$58000, P=0.001). Implementation of a structured multidisciplinary care model to care for a heterogeneous population of ventilator-dependent ICU patients was associated with significant reductions in ICU and hospital lengths of stay, charges, and costs. Mortality rates were unaffected.

Recognizing and preventing antibiotic-associated complications in the critical care setting.

Antibiotics are commonly used, even overused, in the intensive care unit (ICU) patient population. These agents, though useful and often lifesaving, are associated with many toxicities. These include infusion-related problems, allergic reactions, organ-system toxicities, drug accumulation in patients with renal disease, drug interactions, antibiotic resistance, diarrhea, interference with laboratory tests, and more. Informed vigilance by the ICU nurse can be helpful in increasing the benefit/toxicity ratio associated with these agents.

Infectious Rates of Central Venous Pressure Catheters: Comparison Between Newly Placed Catheters and Those That Have Been Changed

To analyze the rate of infection of de novo, guidewire exchanged, and new site replacement catheters in a cohort of patients in whom catheters were changed on the basis of the clinical discretion of the attending physicians. We conducted an observational cohort study in catheterized patients in the intensive-care unit (ICU). ICU patients admitted between Jan. 1, 1991, and Dec.31, 1992, were eligible for enrollment in the study. Catheter care, replacement, and duration were prospectively documented. Catheter-related infection was prospectively evaluated. Rates of catheter-related infection were determined for de novo, guidewire exchanged, and new site replacement catheters and analyzed relative to the duration of placement of individual catheters and the total duration of central venous catheterization for a specific patient. Fifty catheter-related infections developed in 2,470 patients. When the rate of catheter-associated infection was determined for each type of catheterization, de novo catheters had a lower observed rate of infection than either replacement type (P < or = 0.0001). After controlling for the effect of time, we found that the rate of catheter-related infections associated with a de novo catheter was less than the rate in guidewire exchanged catheters (P = 0.035). Rates of infection were similar between guidewire exchanged catheters and catheters replaced to a new site. In a population of ICU patients in whom catheter change was governed by clinical judgement, no differences were noted between the observed rates of infection of new site replacement catheters and guidewire exchange catheters.

Relationship of changes in cardiac output to changes in heart rate in medical ICU patients.

To determine whether changes in cardiac output are correlated with changes in other commonly measured covariables (heart rate, respiratory rate, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and temperature). Case series. Medical intensive care unit (ICU) in a Veterans Administration Medical Center. Twenty-three patients with Swan-Ganz catheters placed by the primary care team were studied on 25 occasions. Patients were managed by the primary team as clinically indicated. Thermodilution cardiac output and covariables were determined at baseline and at hourly intervals for the next 5 h. Each cardiac output measurement was calculated by averaging the last four of five individual measurements at each time point. The mean cardiac output (9.21/min), heart rate (107/min), and pulmonary artery occlusion pressure (19 mmHg) were elevated. The hourly mean change in cardiac output was 10.2%. Using least-squares linear regression analysis, we found clinically significant changes in cardiac output (> 6.4%) to be most closely correlated with changes in heart rate (R2 = 0.29, p < 0.001). Stepwise linear regression analysis showed that none of the other covariables added significantly to this relationship. No significant relationship was found between changes in cardiac output and changes in pulmonary artery occlusion pressure. Despite these correlations clinically significant changes in cardiac output were accompanied by changes in heart rate in the same direction only 62% of the time. Changes in cardiac output were best correlated with changes in heart rate. Changes in pulmonary artery occlusion pressure were not correlated with changes in cardiac output in this population of medical ICU patients. A change in any of the covariables (alone or in combination) cannot be reliably used to indicate a simultaneous change in cardiac output.

Factors affecting the performance of the models in the Mortality Probability Model II system and strategies of customization: a simulation study.

To 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. Prospective evaluation of model performance, using retrospective data. Data for the simulation were assembled from six adult medical and surgical ICUs in Massachusetts and New York. Consecutive admissions (n = 4,224) to the Massachusetts and New York ICUs were studied. The mortality rate in the database was 18.7%. A 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 database. Ten replications of each mortality rate and samples size were constructed, and model calibration and discrimination were assessed for each replication. Model coefficients were customized, using logistic regression. Vital 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. Mortality 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.

Hemodynamic effects of carbon dioxide pneumoperitoneum during mechanical ventilation and positive end-expiratory pressure.

Laparoscopy is frequently used for diagnosis and treatment of critically ill trauma patients. Its effects on cardiopulmonary performance in the intensive care unit patient population, however, are not well-defined. This study evaluated the effects of positive end-expiratory pressure (PEEP) and carbon dioxide (CO2) pneumoperitoneum on hemodynamic function during mechanical ventilation. Five anesthetized, mechanically ventilated adult swine were monitored with pulmonary artery and arterial catheters at 0, 5, 10, 15, and 20 cm H2O PEEP without, and then with 15 mm Hg CO2 pneumoperitoneum. A hemodynamic profile, analyses of arterial and mixed venous blood gases and mixed venous hemoglobin oxygen saturation values were obtained at each data point. Compared with the non-insufflated group, CO2 pneumoperitoneum significantly increased central venous pressure, mean arterial pressure, mean pulmonary artery pressure, pulmonary vascular resistance index, and stroke index for the range of PEEP levels. With PEEP of 10 cm H2O, hemodynamic changes in non-insufflated animals were not statistically significant, but with CO2 pneumoperitoneum, stroke index and left ventricular stroke work index were decreased at 5 cm H2O PEEP, as was cardiac index at 10 cm PEEP. Pulmonary gas exchange was not affected by CO2 pneumoperitoneum. The results indicate that, in this paradigm, CO2 pneumoperitoneum for laparoscopy increases ventricular afterload and exacerbates the adverse effects of PEEP. These findings could be clinically significant in critically ill patients.

Prediction Instruments and Clinical Judgment in Critical Care

The development and dissemination of powerful, effective, and costly technologies for monitoring and treating lifethreatening illness have resulted in the widespread availability of intensive care units (ICUs) in hospitals. Medical ICUs admit acutely ill patients, chronically ill patients with 'an exacerbation, and, on occasion, terminally ill patients for monitoring and supportive treatment. Patients, their families, physicians, government, and third-party payers have been concerned about the high mortality rates among critically ill patients, the functional outcomes of survivors of intensive care, the costs of care, and decision making for the critically ill. 1 1 Studies of patients in medical ICUs have indicated that the ICU patient population comprises two different groups: critically ill persons who receive intensive therapeutic interventions (eg, the patient with septic shock and multisystem organ failure) and persons with serious conditions who receive intensive monitoring and observation for life-threatening complications amenable to prompt intervention (eg, the patient with