Paul L. Appel

Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma.

The objective was to test prospectively supranormal values of cardiac index (CI), oxygen delivery index (DO2I), and oxygen consumption index (VO2I) as resuscitation goals to improve outcome in severely traumatized patients. We included patients > or = 16 years of age who had either (1) an estimated blood loss > or = 2000 mL or (2) a pelvic fracture and/or two or more major long bone fractures with > or = four units of packed red cells given within six hours of admission. The protocol resuscitation goals were CI > or = 4.5 L/min/m2, DO2I > or = 670 mL/min/m2, and VO2I > or = 166 mL/min/m2 within 24 hours of admission. The control resuscitation goals were normal vital signs, urine output, and central venous pressure. The 50 protocol patients had a significantly lower mortality (9 of 50, 18% vs. 24 of 65, 37%) and fewer organ failures per patient (0.74 +/- 0.28 vs. 1.62 +/- 0.45) than did the 75 control patients. We conclude that increased CI, DO2I, and VO2I seen in survivors of severe trauma are primary compensations that have survival value; augmentation of these compensations compared to conventional therapy decreases mortality.

Tissue oxygen debt as a determinant of lethal and nonlethal postoperative organ failure.

The aim of this study was to evaluate the concept that tissue oxygen debt reflected by inadequate oxygen consumption (VO2) in the intraoperative and immediate postoperative periods is a common determinant of multisystem organ failure and death. We measured the cumulative tissue oxygen debt during and immediately after 100 consecutive high-risk surgical operations in 98 patients and correlated these data with the subsequent development of lethal and nonlethal organ failure complications. The tissue VO2 deficit was calculated as the measured VO2 minus the estimated VO2 requirements corrected for both temperature and anesthesia; the net cumulative VO2 deficit was calculated as the integrated area under the VO2 deficit-time curve. The maximum cumulative VO2 deficit averaged 33.5 +/- 36.9 (SD) L/m2 in nonsurvivors, 26.8 +/- 32.1 L/m2 in survivors with organ failure, and 8.0 +/- 10.9 L/m2 in survivors without organ failure. The time postoperatively to reach the maximal cumulative VO2 deficit and the duration of the VO2 deficit was greatest in nonsurvivors, less in survivors with organ failure, and least in survivors without organ failure. Although many associated clinical conditions as well as innumerable physiologic mechanisms and biochemical mediators play important roles in tissue injury, tissue oxygen debt reflected by insufficient VO2 appears to be the primary event as well as a major determinant of organ failure and outcome.

Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness

ObjectiveTo evaluate the reliability of the vital signs to evaluate circulatory stability as reflected by cardiac index. DesignDescriptive analysis based on data gathered prospectively, using a predetermined protocol. SettingUniversity-run county hospital, with a large trauma service. PatientsSixty-one high-risk trauma patients with accidental injury who were studied immediately after admission to the Emergency Department, and subsequently, 163 critically ill postoperative ICU patients. InterventionsStandard fluid therapy, usually crystalloids, but occasionally packed red cell transfusions and colloids, as indicated by clinical criteria. Measurements and ResultsArterial BP was measured by pressure transducer and arterial catheter; heart rate (HR) was measured by electrocardiograph signal, and cardiac output was measured by thermodilution. In sudden severe hypovolemic hypotension, the mean arterial pressure (MAP) nadir (lowest) roughly correlated (r2 = .25) with flow, but there was poor correlation (r2 s .0001) when all pressure and flow values were evaluated. The pressure and flow values were obtained throughout the course of the hypotensive episodes during the initial resuscitation in ICU patients and during terminal illnesses. ConclusionsObservations at the time of acute severe hypotensive crises that show rough correlation of MAP and cardiac index should not be extrapolated throughout the entire hypotensive period or to other less extreme clinical situations. The stress response to hypovolemia, with endogenous catecholamines and neural mechanisms, tends to maintain arterial pressure in the face of decreasing flow for a variable period of time. However, when these mechanisms are overwhelmed by prolonged hypovolemia, the pressure decreases precipitously, but not synchronously, with flow. We conclude that blood flow cannot reliably be inferred from arterial pressure and heart rate measurements until extreme hypotension occurs. (Crit Care Med 1993; 21:218–223)

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.

Hemodynamic and oxygen transport responses in survivors and nonsurvivors of high-risk surgery

ObjectivesTo describe temporal hemodynamic and oxygen transport patterns in a large series of high-risk surgical patients in order to document physiologic patterns, to develop therapeutic goals for a wide range of surgical conditions, and to propose a mechanistic model for acute postoperative circulatory failure. DesignProspective, longitudinal study. Patients identified as high risk were studied prospectively. The data were analyzed immediately after they were acquired, again on formal rounds twice daily, and at a formal data review after completion of monitoring. SettingA university-run county hospital. PatientsThe patient series consisted of 708 consecutively monitored high-risk surgical patients. InterventionsHemodynamic and oxygen transport values and their responses to surgical trauma are known to vary widely with age and prior medical conditions; they may be used to predict outcome with a high degree of accuracy. Temporal hemodynamic and oxygen transport patterns in a large series of high-risk surgical operations were treated by one group, using a well-developed protocol. Measurements and Main ResultsHemodynamic and oxygen transport monitored variables were analyzed before, during, and at frequent intervals after surgical operations. We stratified the temporal patterns of survivors and nonsurvivors in each of the following groups: a) patients without evidence of cardiovascular disease whose preoperative baseline cardiac index values were normal; and b) patients with high or low preoperative baseline cardiac index values due to the presence of preoperatively identified medical conditions that affect the circulatory status. In addition, we stratified patients in various age ranges who were without known cardiovascular diseases. The present study analyzed over 20,000 data sets with up to 32 variables in each data set or >500,000 values.The major findings were intraoperatively reduced circulatory functions, principally cardiac index values, oxygen delivery (Do2), and oxygen consumption (Vo2). These reductions in circulatory functions intraoperatively were followed, in the early postoperative period, by increases in these variables. The postoperative increases in cardiac index, Do2, and Vo2 values were greater in survivors than in nonsurvivors; these findings were more apparent when the postoperative patterns of each strata were related to their own preoperative control values. ConclusionsThe data indicate that there are increased metabolic requirements after surgical trauma and that the changes in cardiac index and Do2 represent compensatory increases in circulatory functions stimulated by increased metabolic needs. However, these metabolic needs change with age, gender, severity of illness, type of operation, associated medical conditions, duration of shock, complications, organ failure, and outcome.

Use of physiologic monitoring to predict outcome and to assist in clinical decisions in critically ill postoperative patients

A predictive index based on cardiorespiratory-monitored values of an earlier series of postoperative critically ill patients was tested in prospective clinical trials and found to be reasonably accurate, sensitive, and specific. The hypothesis was tested that the median values of patients who survived life-threatening postoperative conditions, rather than the norms of unstressed, healthy volunteer subjects, constitute a first approximation to the optimal therapeutic goals for critically ill postoperative patients. In a prospective series of 223 consecutive, critically ill postoperative patients, normal values were used as the therapeutic goals of the control patients, whereas the median values of surviving patients were used as the goals of therapy for the protocol group. The clinical conditions of the protocol group were at least as severe as those of the control group, but the mortality was significantly less in the protocol group (12.5 percent) than in the control group (35 percent); the number of life-threatening complications were also greater in the control group. These data suggest that at least half and possibly as much as two thirds of postoperative deaths may be due to physiologic problems that can be identified, described, predicted, and prevented. Therapy for the critically ill patient should be defined by physiologic criteria, and administration of therapy should be monitored to attain prophylactically optimal physiologic goals rather than giving therapy after a deficiency has occurred to attain normal values.

Comparison of measurements of cardiac output by bioimpedance and thermodilution in severely ill surgical patients

In order to evaluate a new thoracic electrical bioimpedance (TEB) system for measurement of stroke volume based on the Sramek-Bernstein equation, 391 paired values of cardiac output were measured simultaneously with the standard thermodilution method. These values were obtained from 16 patients selected for having the most severe illness during a 6-month period; the intent was to evaluate the bioimpedance method in the worst possible situations. The correlation coefficient (r) was 0.83, slope was 0.87, intercept was 1.53, and the mean difference between the two methods was 16.2 ± 11.8 (SD)% in the total series. In 285 paired samples where satisfactory conditions were met, r was 0.90, slope was 0.98, intercept was 0.34, and the mean difference was 11.8 ± 8.9%. The data indicate satisfactory correlations between these two methods. When the TEB waveform is satisfactory, the agreement between TEB and thermodilution is as good as the agreement between serial thermodilution methods. Difficulties may arise with dysrhythmias, tachycardia (heart rate greater than 150 beat/min), metal in the chest or chest wall, sepsis, hypertension, and extremely oily skin. Mechanical ventilation did not appear to be a problem.

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.

Therapy of critically ill postoperative patients based on outcome prediction and prospective clinical trials.

An objective physiologic approach to therapy of high-risk postoperative patients was developed using survival as the criterion to determine the relative importance of variables and optimal goals for these variables. A protocol, based on a branch chain decision tree, also was developed from outcome data. When tested prospectively against the standard of care, this protocol markedly reduced mortality and morbidity.

Hemodynamic and oxygen transport effects of dobutamine in critically ill general surgical patients

The effects of dobutamine on hemodynamic and oxygen transport were evaluated in 43 studies on 34 critically ill general (noncardiac) surgical patients. Dobutamine, beginning at a low dose (2.5 μg/kgċmin) significantly increased cardiac index (CI), oxygen delivery (Do2), and oxygen consumption (Vo2), while decreasing mean arterial pressure, pulmonary artery and wedge pressures, and systemic and pulmonary vascular resistances; blood gases, pH, and pulmonary shunt were not significantly changed. These effects were seen in postoperative and septic patients, as well as in patients with normal, low, and high control CI. These responses were poor in terminally ill and hypovolemic patients; however, when the latter were given additional fluids, their responses were markedly improved. The hemodynamic effects of dobutamine are well known, but the Do2 and Vo2 effects, which suggest improved tissue perfusion, have not been appreciated.