Potter Chang

Clinical trial of survivors' cardiorespiratory patterns as therapeutic goals in critically ill postoperative patients.

The hypothesis was tested that the median values of survivors of life-threatening postoperative conditions, rather than the norms of unstressed healthy volunteers, are the appropriate therapeutic goals for critically ill postoperative patients. The authors studied prospectively a series of 100 consecutive critically ill postoperative patients; normal values were used as the therapeutic goals of the control patients, while the median values of survivors were used as the goals of therapy for the protocol group. The age, sex, primary illness, surgical operation, lowest mean arterial pressure (MAP), time in hypotension incidence of severe hypotension (MAP greater than 50 mm Hg), and presence of associated severe medical illnesses (defined by predetermined criteria) were comparable in the control and protocol groups; i.e., clinical conditions of the protocol group were at least as severe as those of the control group. The mortality was significantly less in the protocol group (13%) than in the control group (48%); the number of life-threatening complications were also greater in the control group. These data suggest that the cardiorespiratory pattern of survivors are the appropriate goals of therapy for critically ill patients.

Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure

Objective: Volume‐controlled ventilation is frequently chosen as the initial mode of ventilatory support in patients with hypoxic respiratory failure. Recent data, however, suggest that pressure‐limited ventilation, using a rapidly decelerating flow delivery pattern, may produce a more desirable clinical effect through reduced peak airway pressures and increased static compliance, tissue oxygen delivery, and consumption. This study was performed to assess the feasibility and utility of early and sustained use of pressure‐limited ventilation in patients with this clinical syndrome. Design: Randomized, prospective trial. Setting: Medical intensive care unit (ICU) of a university hospital. Patients: The study encompassed all patients (n = 27) receiving care in a medical ICU for acute, severe hypoxic respiratory failure (Pao2/ Fio2 ratio of <150) during a 6‐month period. Interventions: Ventilatory support via either pressure‐limited or volume‐controlled ventilation, initiated within 24 hrs of endotracheal intubation. Measurements: On‐line monitoring of the following ten ventilatory variables at 1‐min intervals for 72 hrs or until extubation or death (maximum of 43,200 data points per patient): peak airway pressure, mean airway pressure, end‐tidal CO2 concentration, CO2 minute excretion, inspiratory tidal volume, expiratory tidal volume, pause pressure, end‐expiratory pressure, static thoracic compliance, and inspiratory resistance. Additionally, Pao2/FIO2 values and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on a daily basis, as were significant clinical events and changes in ventilator settings. Results: Although the severity of illness at study entry as determined by APACHE II score and Pao2/Fio2 was similar in patients treated with pressure‐limited or volume‐controlled ventilation, peak airway pressure was consistently lower in patients randomized to pressure‐limited ventilation (p = .05 at 12 hrs postintubation). The use of pressure‐limited ventilation also was associated with a more rapid increase in static compliance (p = .05) than that found with volume‐controlled ventilation. There was a trend toward more rapid normalization of CO2 minute excretion in patients treated with pressure‐limited ventilation. Pressure‐limited treated patients who survived their illness and were extubated, required fewer days of mechanical ventilation than did patients randomized to volume‐controlled treated ventilation (p = .05). No pneumothoraces occurred in any study patients. One volume‐controlled patient developed subcutaneous emphysema. Pressure‐limited ventilation was well tolerated, and sedation requirements were equivalent in the two groups. Conclusions: Pressure‐limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure. Because the early initiation of pressure‐limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume‐controlled ventilation, pressure‐limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition. (Crit Care Med 1994; 22:22‐32)

Frequency of Selecting Noise Variables in Subset Regression Analysis: A Simulation Study

Abstract This article presents the results of a simulation study of variable selection in a multiple regression context that evaluates the frequency of selecting noise variables and the bias of the adjusted R 2 of the selected variables when some of the candidate variables are authentic. It is demonstrated that for most samples a large percentage of the selected variables is noise, particularly when the number of candidate variables is large relative to the number of observations. The adjusted R 2 of the selected variables is highly inflated.

Comparison of the relative effectiveness of colloids and crystalloids in emergency resuscitation

Summary Over a 2.5 year period, the fluid management of 600 hypotensive patients entering our surgical emergency department was evaluated during a prospective clinical trial of a resuscitation algorithm. The major clinical determinants (low mean arterial pressure, age, severity of illness, primary illness or injury, amount of blood loss, volume of fluids given, use of a protocol or clinical algorithm and satisfactory compliance with the algorithm) were controlled by grouping the patients into specific strata; the resuscitation times were almost always shorter with a regimen of about one-fourth colloids than with crystalloids only. This is consistent with the observations of greater increases in hemodynamic and oxygen transport variables after albumin than after lactated Ringers solution when the latter was given in either 2 or 4 times the volume.

Cardiorespiratory monitoring in postoperative patients: I. Prediction of outcome and severity of illness.

An index for prediction of outcome for use as a measure of the severity of illness was developed by a nonparametric multivariate analysis of cardiorespiratory data from 113 critically ill postoperative general surgical patients. This severity (predictive) index was based on a computerized algorithm that compares a given observed value with the frequency distributions of survivors and nonsurvivors. The difference in the mean values of this index for survivors and nonsurvivors was statistically significant (p less than 0.001) during each stage of shock. Sensitivity of the index in prediction of survival ranged from 70-93% depending upon stage, the specificity of the index ranged from 76-92%, and the predictive accuracy ranged from 87-96%. The severity index is used as a process measure to track the course of critically ill patients and to evaluate the efficacy of alternative therapies.

Classification Based on Dichotomous and Continuous Variables

Abstract A Bayes procedure for classifying an observation consisting of one dichotomous variable (X) and a continuous vector Y is applied to a model assuming that the conditional distribution of Y given X is normal. The procedure reduces to two linear discriminant functions, one for each value of X. An example utilizing data on critically ill patients is given. Extension to one polytomous variable or several dichotomous variables is discussed.

Prediction of outcome and severity of illness by analysis of the frequency distributions of cardiorespiratory variables

Despite the wide variety of illnesses and operations, we observed a common cardiorespiratory pattern of shock that was different for the survivors and nonsurvivors, although no one variable was capable of predicting outcome. Differences between the patterns of survivors and nonsurvivors were defined by range criteria and by cut-points operationally obtained from the frequency distributions of cardiorespiratory variables. The values of each of the 33 variables obtained, at times remote from therapy during each successive stage in the postoperative course, were used to predict survival and death in a series of 113 patients by the range and cut-point methods. An average of 13.5% of all the available variables gave a correct prediction by the range criteria and 35% by the cut-point method. The mean percentage of Right — Wrong classifications throughout all stages for range and cut-point methods was 80 and 85%, respectively. Using the last available stage, the outcome was correctly predicted by the range criteria in 80% and by the cut-point method in 88% of the patients. The high percentage of correct predictions suggests that these methods may provide a measure of the severity of acute illness as well as early warning of impending death.

Tar, CO and Δ9-THC delivery from the 1st and 2nd halves of a marijuana cigarette

Abstract Previous in vitro studies suggest that, with successive puffs from a marijuana cigarette, delta-9-THC becomes concentrated in the remaining uncombusted portion of the cigarette. These observations are consistent with the common practice of smoking marijuana cigarettes to a smaller butt length than that to which tobacco cigarette. are smoked. The purpose of the present study was to compare the delivery of delta-9-THC, as well as total insoluble smoke particulates (tar) and carbon monoxide, from the distal (“first”) versus the proximal (“second”) halves of a standard marijuana cigarette during “natural” smoking of marijuana. On 4 separate days, ten habitual marijuana users smoked nearly all or approximately 1 2 of a standard marijuana cigarette (83 mm length; 800–900 mg; 1.24% THC), as follows: day 1, “whole” cigarette (60 mm smoked, leaving a 23-mm butt); day 2, “first” half (first 30 mm); day 3, “second” half (second 30 mm) after the “first” half was presmoked with a syringe; and day 4, “second” half after the “first” half was excised. A previously described smoking apparatus (20) was used for measurement of puff volume and inhaled tar. Puff volume and number were allowed to vary spontaneously (provided that the specified length of cigarette was consumed), while inhaled volume (1.5 liters), breathholding time (14 s) and interpuff interval (30 s) were held constant. Blood samples were withdrawn prior to smoking and serially after completion of smoking for analysis of blood carboxy-hemoglobin (COHb) and serum delta-9-THC. Heart rate was measured before and 5 min after smoking. Subjects rated their level of “high” 20 min after completion of smoking. Compared to the distal half, smoking the proximal half of a marijuana cigarette delivered more tar, carbon monoxide and THC to the smokers lungs, as indicated by a greater amount of inhaled tar and a larger boost in both blood carboxyhemoglobin and serum THC. In addition, boosts in blood COHb and serum THC were significantly greater following smoking the proximal half after the distal half had been presmoked rather than excised. These findings are probably due to 1) less rod filtration of insoluble particulates, 2) increased concentration in the proximal half of the cigarette of carbonaceous material and THC volatilized by prior combustion of the distal half, and 3) possible differences in burn rate due to effects of precombustion of the distal half on moisture content of the proximal half. Clinical implications of these findings are that smoking fewer marijuana cigarettes down to a shorter butt length to deliver more THC and achieve a greater “high” is potentially more harmful to cardiorespiratory health than consuming a comparable amount of marijuana contained in more cigarettes smoked to a longer butt length.

Robustness of Fisher's Linear Discriminant Function under Two-Component Mixed Normal Models

Abstract Robustness of Fishers linear discriminant function is evaluated when the distributions of the two populations are characterized by two-component mixed normal distributions with known parameters. The results suggest that the linear discriminant function is rather robust when the two distributions do not markedly deviate from normality and are moderately distant, particularly if they are similar in shape.

Clinical trial of an emergency resuscitation algorithm

Clinical trials of a resuscitation algorithm for patients entering the Surgical Emergency Department (ED) with acute hypotension were conducted for a 30-month period. The intent was not to compare good management with bad, but rather university-run county hospital services with and without an algorithm. The study group was comprised of 603 hypotensive patients out of 6833 consecutive admissions. The effects of the policy of using a resuscitation algorithm were evaluated by the outcomes of the patients who were treated by residents given the algorithm (protocol group) versus those treated by residents not given the algorithm (control group). The efficacy of the algorithm, per se, was evaluated by outcomes of patients whose management was in satisfactory compliance with the algorithm as compared with those whose management deviated from the algorithm. The patients were also evaluated by the primary cause of their hypotension and the presence of severe associated illnesses. Outcomes of patients treated by residents given the algorithm were as good and in a number of respects better than those of patients treated by residents without the algorithm. The mean resuscitation time of the protocol group was markedly and significantly less than that of the control group indicating that the policy of using the algorithm facilitated resuscitation even though it was not always properly followed. Patients with trauma, hemorrhage, and sepsis, whose care was in satisfactory compliance with the algorithm had shorter resuscitation times, lower MAP-time deficits, and less shock-related complications. The algorithm which is primarily directed toward fluid resuscitation did not appear to be efficacious for patients whose trauma was primarily head injury, where fluid restriction may be the therapy of choice.