Kristen J. Price

Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model.

PURPOSE To develop prospectively and validate a model for probability of hospital survival at admission to the intensive care unit (ICU) of patients with malignancy. PATIENTS AND METHODS This was an inception cohort study in the setting of four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 1,483 patients and then validated on an additional 230 patients. Multiple logistic regression modeling was used to develop the models and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analysis. The main outcome measure was hospital survival after ICU admission. RESULTS The observed hospital mortality rate was 42%. Continuous variables used in the ICU admission model are PaO2/FiO2 ratio, platelet count, respiratory rate, systolic blood pressure, and days of hospitalization pre-ICU. Categorical entries include presence of intracranial mass effect, allogeneic bone marrow transplantation, recurrent or progressive cancer, albumin less than 2.5 g/dL, bilirubin > or = 2 mg/dL, Glasgow Coma Score less than 6, prothrombin time greater than 15 seconds, blood urea nitrogen (BUN) greater than 50 mg/dL, intubation, performance status before hospitalization, and cardiopulmonary resuscitation (CPR). The P values for the fit of the preliminary and validation models are .939 and .314, respectively, and the areas under the ROC curves are .812 and .802. CONCLUSION We report a disease-specific multivariable logistic regression model to estimate the probability of hospital mortality in a cohort of critically ill cancer patients admitted to the ICU. The model consists of 16 unambiguous and readily available variables. This model should move the discussion regarding appropriate use of ICU resources forward. Additional validation in a community hospital setting is warranted.

Outcome for cancer patients requiring mechanical ventilation.

PURPOSE To describe hospital survival for cancer patients who require mechanical ventilation. MATERIALS AND METHODS A prospective, multicenter observational study was performed at five academic tertiary care hospitals. Demographic and clinical variables were obtained on consecutive cancer patients at initiation of mechanical ventilation, and information on vital status at hospital discharge was acquired. RESULTS Our analysis was based on 782 adult cancer patients who met predetermined inclusion criteria. The overall observed hospital mortality was 76%, with no statistically significant differences among the five study centers. Seven variables (intubation after 24 hours, leukemia, progression or recurrence of cancer, allogeneic bone marrow transplantation, cardiac arrhythmias, presence of disseminated intravascular coagulation, and need for vasopressor therapy) were associated with an increased risk of death, whereas prior surgery with curative intent was protective. The predictive model based on these variables had an area under the receiver operating characteristic curve of 0.736, with Hosmer-Lemeshow goodness-of-fit statistics of 7.19; P = .52. CONCLUSION This model can be used to estimate the probability of hospital survival for classes of adult cancer patients who require mechanical ventilation and can help to guide physicians, patients, and families in deciding goals and direction of treatment. Prospective independent validation in different medical settings is warranted.

Dyspnea in cancer patients: Etiology, resource utilization, and survival-Implications in a managed care world

Dyspnea is the fourth most common symptom of patients who present to the emergency department (ED) at The University of Texas M. D. Anderson Cancer Center and may, in some patients with advanced cancer, represent a clinical marker for the terminal phase of their disease. This retrospective study describes the clinical characteristics of these patients, the resource utilization associated with the management of dyspnea, and the survival of patients with this symptom.

Characteristics of cardiac arrest in cancer patients as a predictor of survival after cardiopulmonary resuscitation.

Despite advances in cardiopulmonary resuscitation and the education of its providers, survival remains dismal for cancer patients suffering in‐hospital cardiac arrest. In an effort to determine if characteristics of cardiac arrest would represent a useful parameter for prognostication and recommendations regarding the suitability of ongoing resuscitation for various groups, this review was undertaken for patients who experienced in‐hospital cardiac arrest.

NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, reverses interleukin-2-induced hypotension

OBJECTIVE To evaluate the role of NG-methyl-L-arginine as a modulator of the hyperdynamic shock induced by the administration of interleukin-2 (IL-2). DESIGN A prospective, pilot clinical study. SETTING Intensive care unit of a tertiary care center. PATIENTS Three sequential patients with metastatic renal cell carcinoma who developed hypotension during their first course of treatment with high-dose IL-2 (18 x 10(6) IU/m2/day by continuous infusion for 5 days). INTERVENTIONS Upon developing hypotension during their subsequent therapy with IL-2, patients were administered 12 mg/kg of NG-methyl-L-arginine. Thereafter, a dose of 4 mg/kg was given every 4 hrs, as needed, to maintain the systolic blood pressure above 100 mm Hg. MEASUREMENTS AND MAIN RESULTS Invasive hemodynamic monitoring was instituted before the initiation of treatment with IL-2. Differences noted before, and 15 mins after, the administration of NG-methyl-L-arginine were analyzed using the paired t-test. NG-methyl-L-arginine (12 mg/kg) induced a significant antihypotensive effect (mean blood pressure increased from 87 +/- 4 to 121 +/- 7 mm Hg), accompanied by an increase of the systemic vascular resistance (549 +/- 51 to 860 +/- 167 dyne.sec/cm5) and pulmonary vascular resistance (81 +/- 16 to 117 +/- 29 dyne.sec/cm5). A decrease in the cardiac index was also documented (4.5 +/- 0.5 to 3.6 +/- 0.3 L/min/m2). No significant changes in pulmonary artery occlusion and central venous pressures were observed. Maintenance doses of 4 mg/kg of NG-methyl-L-arginine induced similar hemodynamic results, although the duration of the antihypotensive effect of NG-methyl-L-arginine decreased with sequential doses. CONCLUSIONS The hemodynamic effects induced by IL-2 administration are reversed by NG-methyl-L-arginine, a nitric oxide synthesis inhibitor. These results provide evidence for the biological activity of NG-methyl-L-arginine when administered alone to hypotensive patients. While no adverse effects were observed in this preliminary study, issues of toxicity and effectiveness need to be defined further in formal clinical trials. NG-methyl-L-arginine may play a therapeutic role in the modulation of the extreme vasodilation induced by cytokine administration or in septic shock.

Influence of an advance directive on the initiation of life support technology in critically ill cancer patients

Objective To determine whether the presence of an advance directive at admission to an intensive care unit (ICU) influenced the decision to initiate life support therapy in critically ill cancer patients. Design Matched-pairs case-control design. Setting The University of Texas M. D. Anderson Cancer Center ICU. Patients Of 872 patients treated in the ICU from 1994 to 1996, 236 (27%) were identified as having advance directives. One hundred thirty five patients who had advance directives were successfully matched to 135 patients who did not on the basis of type of malignancy, reason for admission to ICU, severity of illness, and age. These pairs comprised the study group. Interventions Life-supporting interventions were compared between the matched groups using the McNemar and Wilcoxon matched-pairs signed ranks tests. Measurements and Main Results No significant difference was found in the frequency with which the following interventions were applied in patients with and without advance directives (respectively): mechanical ventilation, 44% vs. 42%; inotropic support, 31% vs. 31%; pulmonary artery catheterization, 11% vs. 12%; cardiopulmonary resuscitation, 7% vs. 12%; and renal dialysis, 3% vs. 7%. There were also no differences in ICU (75% vs. 73%, respectively) or hospital (56% vs. 59%, respectively) survival. More patients with advance directives than those without had do-not-resuscitate orders within the first 72 hrs (19% vs. 11%, p = .046) and patients with advance directives had shorter ICU durations and lower ICU charges than patients without advance directives. Conclusions After controlling for type of malignancy, reason for admission to the ICU, severity of illness, and age, the decision to initiate life-supporting interventions did not differ significantly among patients with and without advance directives. The presence of an advance directive, however, may have helped guide decisions earlier regarding duration of therapy and resuscitation status.

Hematopoietic Cell Transplantation–Specific Comorbidity Index Predicts Inpatient Mortality and Survival in Patients Who Received Allogeneic Transplantation Admitted to the Intensive Care Unit

PURPOSE To investigate the prognostic value of the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients who received transplantation admitted to the intensive care unit (ICU). PATIENTS AND METHODS We investigated the association of HCT-CI with inpatient mortality and overall survival (OS) among 377 patients who were admitted to the ICU within 100 days of allogeneic stem-cell transplantation (ASCT) at our institution. HCT-CI scores were collapsed into four groups and were evaluated in univariate and multivariate analyses using logistic regression and Cox proportional hazards models. RESULTS The most common pretransplantation comorbidities were pulmonary and cardiac diseases, and respiratory failure was the primary reason for ICU admission. We observed a strong trend for higher inpatient mortality and shorter OS among patients with HCT-CI values ≥ 2 compared with patients with values of 0 to 1 in all patient subsets studied. Multivariate analysis showed that patients with HCT-CI values ≥ 2 had significantly higher inpatient mortality than patients with values of 0 to 1 and that HCT-CI values ≥ 4 were significantly associated with shorter OS compared with values of 0 to 1 (hazard ratio, 1.74; 95% CI, 1.23 to 2.47). The factors associated with lower inpatient mortality were ICU admission during the ASCT conditioning phase or the use of reduced-intensity conditioning regimens. The overall inpatient mortality rate was 64%, and the 1-year OS rate was 15%. Among patients with HCT-CI scores of 0 to 1, 2, 3, and ≥ 4, the 1-year OS rates were 22%, 17%, 18%, and 9%, respectively. CONCLUSION HCT-CI is a valuable predictor of mortality and survival in critically ill patients after ASCT.

Identifying risk factors for imminent death in cancer patients with acute dyspnea.

A substantial proportion of cancer patients presenting to an emergency center (EC) or clinic with acute dyspnea survives fewer than 2 weeks. If these patients could be identified at the time of admission, physicians and patients would have additional information on which to base decisions to continue therapy to extend life or to refocus treatment efforts on palliation and/or hospice care alone. The purpose of this study was to identify risk factors for imminent death (survival </= 2 weeks) and short-term survival (1, 3, or 6 months) in cancer patients presenting to an EC with acute dyspnea and to combine these factors into a model to help clinicians identify patients with short life expectancies. A random sample of 122 patients presenting to an EC with acute dyspnea was selected for a retrospective analysis. Data that were available to physicians during the initial EC visit included patient histories, triage and discharge vital signs, chest radiographs, and laboratory results. These variables were used in univariate and logistic regression models to develop predictive models for imminent death and short-term survival. Variables and interactions meeting a univariate criterion of P < 0.10 were included in stepwise regression by using forward and backward stepping. Models were compared with the use of Hosmer-Lemeshow statistics and receiver operating characteristics curves. Underlying cancers were 30% breast, 37% lung, and 34% other cancers. Triage respiration greater than 28/min., triage pulse greater than or equal to 110 bpm, uncontrolled progressive disease, and history of metastasis were found to be statistically significant predictors (alpha </= 0.05) of imminent death. Patients with uncontrolled progressive disease had a relative risk of imminent death of 21.93. Relative risks for triage respiration, pulse, and metastases were 12.72, 4.92, and 3.85, respectively. Cancer diagnosis was not predictive of imminent death but was predictive when longer time periods were modeled. It may be possible to identify patients whose death is imminent from a group of cancer patients with acute dyspnea. Some factors that predict imminent death (triage pulse and respiration) differ from those (cancer diagnosis) that predict short-term survival. Extent of disease/response to treatment is common to all models. These factors need further examination and validation. If these findings are confirmed, this quantified information can help physicians in making difficult end-of-life decisions.

Outcome Analyses After the First Admission to an Intensive Care Unit in Patients With Advanced Cancer Referred to a Phase I Clinical Trials Program

PURPOSE This study assessed outcomes of individuals with advanced cancer who required admission to an intensive care unit (ICU) after referral for an early clinical trial because they did not respond to conventional therapy. PATIENTS AND METHODS Outcome analyses were conducted for 212 consecutive patients admitted to The University of Texas MD Anderson Cancer Center ICU after being seen in the phase I clinic starting on May 1, 2007. All data were obtained by a review of electronic medical records of patients. RESULTS The median survival of 212 patients with advanced cancer referred to phase I care after the initial ICU admission was 3.2 weeks (95% CI, 2.5 to 4.9 weeks). Patients who underwent cardiopulmonary resuscitation (CPR) succumbed within a median survival of 1 day (75% and 25% estimated survival of 1 and 3 days, respectively). Patients admitted for a postsurgical intervention did better than patients admitted for a nonsurgical intervention (median survival, 21.5 versus 2.1 weeks; P < .0001). The multivariate analysis revealed that a nonsurgical intervention, hypoalbuminemia, and higher Acute Physiology and Chronic Health Evaluation II scores were associated with poor overall survival. CONCLUSION The outcome of patients in a phase I clinic after initial ICU admission was poor, particularly when admission was for a nonsurgical intervention and/or when CPR was needed.

Sustained Low Efficiency Dialysis in the Continuous Mode (C-SLED): Dialysis Efficacy, Clinical Outcomes, and Survival Predictors in Critically Ill Cancer Patients

BACKGROUND AND OBJECTIVES Oliguric, hypotensive patients who require large amounts of fluids may benefit from sustained low-efficiency dialysis performed continuously (C-SLED). C-SLED through higher clearance may improve survival, or through greater nutritional loss may worsen survival. No studies have assessed survival on C-SLED. The objective was to examine patient outcomes and survival predictors on C-SLED. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The data of 199 consecutive cancer patients treated with C-SLED were analyzed. The median duration of C-SLED was 50 h. With 48 h of C-SLED, the blood urea nitrogen (BUN) and serum creatinine levels had decreased by 80% and 73%, respectively. The mean arterial pressure (MAP) was maintained despite higher ultrafiltration and reduced vasopressor use. The 30-d mortality rate was 65%. Despite excellent dialysis, the sequential organ failure assessment (SOFA) score remained predictive of mortality. In the univariate model, higher SOFA scores and lower values for MAP, blood pH, and serum albumin and creatinine levels were associated with higher mortality. Administration of total parenteral nutrition (TPN) was, however, associated with lower mortality. RESULTS In the multivariate model, the higher SOFA score and lower blood pH, MAP and C-SLED duration were associated with higher mortality. In a subset analysis of 129 patients who received C-SLED for at least 48 h, those with higher BUN levels, which were associated with higher TPN infusion, had a lower mortality risk. CONCLUSION This first detailed report on C-SLED indicates that C-SLED can be effective and suggests a link between nutrition and survival.