When Should the Cancer Patient Get an ICU Bed?

Cristina Gutierrez, MD*
Fellow, Critical Care Medicine
Memorial Sloan-Kettering Cancer Center
New York, New York, USA

Stephen M. Pastores, MD, FCCM**
Professor of Medicine in Clinical Anesthesiology
Weill Cornell Medical College
Attending Physician
Memorial Sloan-Kettering Cancer Center
New York, New York, USA

Major advances in anticancer therapies and supportive management of organ dysfunctions have improved survival rates for cancer patients admitted to the intensive care unit (ICU).(1-5) Throughout the 1980s and early 1990s, the dismal outcomes of critically ill cancer patients requiring life support prompted some clinicians to support either denial of ICU admission or early treatment-limitation decisions for these patients.(1,6-9) Given the recent outcome improvements in select ICU cancer patients seen in the last decade, it is vital to reassess how decisions about ICU admission or denial are made. While the American College of Critical Care Medicine’s Guidelines for Admission, Discharge and Triage may be used as a reference,(10) specific recommendations for which cancer patients should be admitted into the ICU, and when, still are not well defined.

Diagnosis on ICU Admission
Acute respiratory failure (ARF), sepsis, acute kidney injury (AKI), bleeding, oncologic emergencies, and postoperative care after complex or large tumor resection are the most common reasons for ICU admission in patients with cancer. Respiratory failure usually is caused by pneumonia, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), diffuse alveolar hemorrhage, venous thromboembolism and progression of disease.(11,12) Outcomes vary depending on the etiology of the respiratory failure. Greater understanding of the pathophysiology of ARDS, use of lung-protective ventilation strategies, conservative fluid management and effective ventilator weaning protocols, paired with timely discontinuation of sedation and the increased use of noninvasive ventilation, are thought to be reasons behind improved outcomes for cancer patients with ARF.(13-18) However, patients who develop ARF requiring mechanical ventilation following hematopoietic stem cell transplantation (HSCT) and those patients presenting with metastatic cancer or multiorgan failure continue to have extremely high mortality rates.(3,19-21)

Patients with cancer have a three- to five-fold higher risk of severe sepsis compared to patients without cancer, often necessitating ICU care.(22-26) Neutropenic patients and those with hematologic malignancies requiring HSCT4,(27) are at particularly high risk for septic shock; mortality rates as high as 80% to 90% were reported before 2000.(7,9,28,29) Early recognition and aggressive treatment of severe sepsis, as recommended by the Surviving Sepsis Campaign,(30) are associated with improved survival independent of recent chemotherapy administration.(24,31-33) Adverse prognostic factors among cancer patients with sepsis include the need for mechanical ventilation and the development of multiorgan failure during the ICU stay.(2,5,20,22,34)

AKI in cancer patients may occur as a consequence of the cancer itself (e.g., myeloma kidney, urinary tract obstruction) or its treatment (acute tumor lysis syndrome, drug-induced nephropathy, or major surgical procedures) and associated severe complications (sepsis, hypercalcemia).(2,20,34,35) When the underlying process causing AKI is reversible (e.g., chemotherapy-induced AKI, tumor lysis syndrome), the mortality rate is lower than when the causative factor is related to severe sepsis.(2.20,31) Patients with hematological malignancies who develop AKI necessitating renal replacement therapy (RRT) have poor outcomes.(2,20,34) However, when adjusted for severity of disease on admission and length of ICU stay, the presence of malignancy by itself is not an indicator of higher mortality rates.(34) Thus, while the presence of AKI and need for RRT in cancer patients is associated with a poor prognosis, these individuals should not routinely be denied ICU admission.(34,35)

Favorable outcomes commonly are observed among cancer patients who are admitted to the ICU for postoperative care, administration of chemotherapy or immunomodulatory agents, and management of tumor lysis syndrome. These outcomes are mostly ascribable to early recognition and treatment of complications.(3,36)

Age
The effect of age on the outcomes of critically ill cancer patients is controversial, as early studies have suggested no impact on mortality rates.(5,23,37-39) However, none of these studies evaluate age as an independent prognostic factor in the ICU. More recent studies indicate a higher mortality rate in patients older than age 60 with severe comorbidities, poor functional status and multiorgan failure.(40)Such findings are not universal, and larger studies are required to explore further the effects of age in cancer patients requiring life support.

Type of Underlying Malignancy
Several studies in the early 1990s showed that patients with hematologic malignancies had worse outcomes in the ICU compared to those with solid tumors.(9,28,41) The high mortality rates were attributed to greater degrees of immunosuppression and neutropenia, the  increased incidence of sepsis and bleeding, and a history of HSCT.(9,23,28,41) The presence of a hematological malignancy is no longer considered an independent risk factor for poor prognosis on ICU admission.(3,4,27,34,41,42) Possible reasons for this include the availability of novel treatments for hematologic malignancies and neutropenia and advances in sepsis management.(4,22,23,42)

Hematopoietic Stem Cell Transplantation Status
Patients with HSCT may present with severe complications including ALI/ARDS, infectious pneumonia, chemical pneumonitis, graft versus-host disease (GVHD), veno-occlusive disease of the liver, gastrointestinal hemorrhage, neurological catastrophes and AKI. As many as 16% to 40% of HSCT recipients require ICU admission.(23) Critically ill HSCT patients with ARF have mortality rates ranging from 42% to 88%, with overall survival rates of only 10% to 15% in those receiving mechanical ventilation.(4,23,37,38,42,43) However, outcomes for these patients have improved slightly over time, a trend attributed to more widespread use of colony-stimulating factors for neutropenia and autologous and peripheral blood HSCT, as well as corticosteroids for respiratory failure due to diffuse alveolar hemorrhage and peri-engraftment respiratory distress syndrome, earlier application of noninvasive ventilation, and advances in sepsis therapies.(34-44) The presence of GVHD and multiorgan failure in an HSCT recipient admitted to the ICU continues to portend a grave prognosis.(37,38,42)

Stage of Malignancy and Performance Status
The stage of the malignancy has little or no impact on short-term survival of cancer patients admitted to the ICU.(5) However, as many as 60% of critically ill patients with advanced cancer admitted to the ICU are never discharged home; those who are have a median survival of only 33 days.(22,45) Furthermore, 55% to 75% of ICU cancer survivors report severe symptoms such as pain, discomfort, anxiety and sleep disorders.(22,46) Poor performance status also is shown to be a predictor of poor outcome.(3,19,22) Although aggressive treatment is not recommended for this group, ICU admission may be appropriate for the treatment of reversible conditions, such as cardiac tamponade, severe dehydration or respiratory insufficiency that can be managed with noninvasive ventilation.

The ICU Trial: A New Admission Policy for Cancer Patients
Requiring Mechanical Ventilation General severity-of-illness scores, such as the Acute Physiology and Chronic Health Evaluation(APACHE), Simplified Acute Physiology Score (SAPS) and Mortality Probability Models (MPM), have fared poorly in critically ill patients with cancer because of inadequate calibration and underestimation of mortality.(3,5,47) In addition, bedside evaluation by physicians has been deemed a poor tool for prognostication of outcome in ICU cancer patients.(48,49) Several investigators have demonstrated that the severity and number of organ failures occurring during the course of the ICU stay are better determinants of patient outcome than organ failures present at admission.(2,3,5,19)

In an effort to identify better those patients likely to benefit from ICU admission and those for whom prolonged ICU care would not be appropriate, Lecuyer and colleagues conducted the ICU Trial, a prospective study of 188 cancer patients on mechanical ventilation utilizing a broad admission policy.(19) Cancer patients with previously untreated malignancies, acute tumor lysis syndrome, bulky or infiltrating tumors at the earliest phase of treatment, and in complete remission were admitted to the ICU for five days for full-code treatment. Patients who were bedridden, refused admission, or who were receiving palliative care as their only cancer treatment option were excluded. The majority of the patients had acute leukemia or non-Hodgkin’s lymphoma. The mortality rate within the first four days of ICU admission was 47%. Among the 103 survivors on day five, none of the malignancy characteristics between those who died and those who survived were significantly different. There were no survivors among patients who required RRT, vasopressors or intubation after day three. After day five, an increasing number of organ failures were associated with poor outcomes. The authors recommended that treatment-limitation decisions should be considered only after five to six days of full-code ICU management.(19) After this trial period, if there is no improvement, the physician should contemplate transition to comfort or end-of-life care.

Summary
In general, cancer patients with poor performance status and no cancer treatment options should not be considered for ICU admission. To date, no specific severity-of-illness scoring system can predict the outcome of critically ill cancer patients consistently. The major determinants of mortality are the severity and number of organ failures. Additional prospective studies are needed to validate the results of the admission triage process used in the ICU Trial. Close collaboration among medical and surgical oncologists and intensivists will ensure the establishment of clear goals and approach to treatment for every patient with cancer who requires ICU admission.

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