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A New Standard of Care for Critically Ill Patients With CancerMechanical Ventilation in Patients With Cancer FREE TO VIEW

Elie Azoulay, MD, PhD on behalf of the Groupe de Recherche en Réanimation Onco-Hématologique (Grrr-OH)
Author and Funding Information

From the AP-HP, Hôpital Saint-Louis, Université Paris-Diderot, Sorbonne Paris-Cité.

CORRESPONDENCE TO: Elie Azoulay, MD, PhD, AP-HP, Hôpital Saint-Louis, Medical ICU, Université Paris-Diderot, Sorbonne Paris-Cité, Faculté de medicine, 1 avenue Claude Vellefaux, 75010 Paris, France; e-mail: elie.azoulay@sls.aphp.fr


FINANCIAL/NONFINANCIAL DISCLOSURES: The author has reported to CHEST the following conflicts: Dr Azoulay has received research grants from Pfizer, Inc and fees for lecturing from Gilead and MSD and is on the on board of Gilead.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(2):241-244. doi:10.1378/chest.14-0620
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Published online

Several million patients worldwide live with cancer.1,2 Possible outcomes are complete cancer eradication; cancer control using chemotherapy, targeted therapies, or both; and palliative treatments that may both prolong life and increase quality of life.3 All patients with cancer are at a high risk for pulmonary disease due to infections, infiltration by malignant cells, or treatment toxicities.4 Severe respiratory episodes, usually with acute respiratory failure, affect up to 40% of patients with cancer.5

Mechanical ventilation (MV), whether invasive or noninvasive ventilation (NIV), must be considered the standard of care for consenting patients who are not bedridden and who are receiving curative or palliative chemotherapy. This statement indicates a major change in the care of critically ill patients with cancer. It is based on substantial improvements achieved over the past decade in the survival of patients with cancer requiring MV.6,7 Previous survival rates, in contrast, were so low that MV was considered futile in this population.8,9 The improved survival is ascribable to advances in both cancer and ICU management8-10 as well as to better patient selection for ICU admission. Patients with cancer are increasingly admitted to the ICU,11,12 with a current hospital mortality rate of 40%. Full-code treatment is used for the first few days, and the response is then assessed to determine the best subsequent course of action.13

In this issue of CHEST (see page 257), Azevedo et al14 provide valuable information on survival in patients with cancer requiring mechanical ventilation. Their prospective multicenter study was performed in 28 ICUs in Brazil. Most of the patients had solid tumors, and 67% were admitted for medical reasons. The results should help to further erode the view still held by many intensivists that MV is not beneficial in patients with cancer. The ICU and hospital survival rates were 46% and 33%, respectively. Although lower than those in patients without cancer receiving MV,15 these survival rates are far higher than those reported in patients with cancer 2 decades ago.16 This study, together with more recently published data,7 argue for a broad policy of ICU admission of patients with cancer. It indicates a clear need for defining a standard of care (Table 1): At ICU admission, patients with cancer should not be deprived from potentially lifesaving interventions such as MV, renal replacement therapy, and vasopressor therapy.8 Moreover, survival is particularly high in patients requiring chemotherapy initiation in the ICU for newly diagnosed malignancies with specific organ dysfunctions, such as leukemic pulmonary infiltration, leukostasis, tumor lysis syndrome, or macrophage activation syndrome.17

Table Graphic Jump Location
Table 1  ] Features of the Standard of Care for Critically Ill Patients With Cancer

NIV = noninvasive ventilation.

This large prospective multicenter study of patients who received MV has several major strengths. Although the investigators are experts in the field, not all the study ICUs admitted large numbers of patients with cancer. The data collection method allows comparisons with previous studies. The results provide large-scale confirmation of earlier evidence that NIV failure and MV in patients with tumoral obstruction are associated with high mortality rates.18,19 Several caveats are in order, however. First, hematology patients accounted for only 14% of the population. Second, long-term outcomes were not available, and disease control 6 months after ICU discharge was not assessed. Similarly, quality-of-life data were not obtained, casting doubt on whether ICU management increased survival or merely prolonged the dying process. Third, as ICU mortality was probably very low in patients successfully managed with NIV, the 40% hospital mortality rate in these patients raises concerns about the goals of care after ICU discharge. Also, important information not provided in the article is how the treatment-limitation decisions taken for 21% of patients were made20 and the proportion of patients who received palliative NIV.21 Last, although this study supports recent findings encouraging the use of MV in patients with cancer, it also identifies a subset of patients who seem unlikely to benefit from MV (patients with poor performance status, extensive and uncontrolled disease, or nonpulmonary organ dysfunctions).

The study by Azevedo et al14 offers three major opportunities to further improve outcomes in this high-risk population (Fig 1). First, although the difference was not statistically significant, patients who died spent more time in wards before ICU admission than patients who survived (2 median [0–8 interquartile range] vs 4 [0–13] days, P = .11). Similarly, earlier studies showed that delayed ICU admission was associated with higher mortality.7,22-24 Interventional studies on optimal ICU admission timing are warranted, not only in the overall population of patients with cancer but also in patients receiving chemotherapy and having a single mild organ dysfunction. Better delineation of the criteria that should prompt oncologists and hematologists to consider ICU admission, and intensivists to admit patients with cancer, is urgently needed. The second opportunity for improvement identified in the study by Azevedo et al14 pertains to the high mortality after NIV failure. NIV was recommended for first-line ventilatory support in immunocompromised patients at a time when MV was associated with 90% mortality.25 However, since then, the marked decrease in mortality and the concerns raised about NIV in hypoxemic patients have challenged the wisdom of this approach.18,26 We believe that NIV should not be used in patients with ARDS. In immunocompromised patients with acute respiratory failure but no criteria for ARDS, the evidence has to be confirmed. Thus, a trial of NIV is warranted to appraise the findings that were reported 15 years ago. Last, the study by Azevedo et al14 suggests a need for clearly defining the standard of care for critically ill patients with cancer. For instance, the finding that only one-third of patients with cancer admitted to the participating ICUs received MV and that among patients given MV only one-third received vasopressors and only 7% renal replacement therapy casts doubt on whether appropriate intensity of care was provided. Along this line, all the deaths occurred after treatment-limitation decisions. The use of intensive care must change in patients with cancer. Studies must provide survival rates separately for patients who receive full-code management, an ICU trial, or palliative ICU management. In addition to hospital mortality, these studies must provide data on long-term overall survival, event-free and disease-free survival, quality of life, and other markers of post-ICU burden.

Figure Jump LinkFigure 1  Remaining questions and research agenda. MV = mechanical ventilation; NIV = noninvasive ventilation; RCT = randomized controlled trial.Grahic Jump Location

References

Verdecchia A, Francisci S, Brenner H, et al; EUROCARE-4 Working Group. Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol. 2007;8(9):784-796. [CrossRef] [PubMed]
 
Vogelzang NJ, Benowitz SI, Adams S, et al. Clinical cancer advances 2011: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2012;30(1):88-109. [CrossRef] [PubMed]
 
Smith TJ, Temin S, Alesi ER, et al. American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol. 2012;30(8):880-887. [CrossRef] [PubMed]
 
Azoulay E, Schlemmer B. Diagnostic strategy in cancer patients with acute respiratory failure. Intensive Care Med. 2006;32(6):808-822. [CrossRef] [PubMed]
 
Rabbat A, Chaoui D, Montani D, et al. Prognosis of patients with acute myeloid leukaemia admitted to intensive care. Br J Haematol. 2005;129(3):350-357. [CrossRef] [PubMed]
 
Groeger JS, White P Jr, Nierman DM, et al. Outcome for cancer patients requiring mechanical ventilation. J Clin Oncol. 1999;17(3):991-997. [PubMed]
 
Azoulay E, Mokart D, Pène F, et al. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol. 2013;31(22):2810-2818. [CrossRef] [PubMed]
 
Azoulay E, Afessa B. The intensive care support of patients with malignancy: do everything that can be done. Intensive Care Med. 2006;32(1):3-5. [CrossRef] [PubMed]
 
Azoulay E, Soares M, Darmon M, Benoit D, Pastores S, Afessa B. Intensive care of the cancer patient: recent achievements and remaining challenges. Ann Intensive Care. 2011;1(1):5. [CrossRef] [PubMed]
 
Dellinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228. [CrossRef] [PubMed]
 
Peigne V, Rusinová K, Karlin L, et al. Continued survival gains in recent years among critically ill myeloma patients. Intensive Care Med. 2009;35(3):512-518. [CrossRef] [PubMed]
 
Khassawneh BY, White P Jr, Anaissie EJ, Barlogie B, Hiller FC. Outcome from mechanical ventilation after autologous peripheral blood stem cell transplantation. Chest. 2002;121(1):185-188. [CrossRef] [PubMed]
 
Lecuyer L, Chevret S, Thiery G, Darmon M, Schlemmer B, Azoulay E. The ICU trial: a new admission policy for cancer patients requiring mechanical ventilation. Crit Care Med. 2007;35(3):808-814. [CrossRef] [PubMed]
 
Azevedo LCP, Caruso P, Silva UVA, et al. Outcomes for patients with cancer admitted to the ICU requiring ventilatory support: results from a prospective multicenter study. Chest. 2014;146(2):257-266.
 
Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188(2):220-230. [CrossRef] [PubMed]
 
Groeger JS, Lemeshow S, Price K, et al. Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model. J Clin Oncol. 1998;16(2):761-770. [PubMed]
 
Benoit DD, Depuydt PO, Vandewoude KH, et al. Outcome in severely ill patients with hematological malignancies who received intravenous chemotherapy in the intensive care unit. Intensive Care Med. 2006;32(1):93-99. [CrossRef] [PubMed]
 
Depuydt PO, Benoit DD, Vandewoude KH, Decruyenaere JM, Colardyn FA. Outcome in noninvasively and invasively ventilated hematologic patients with acute respiratory failure. Chest. 2004;126(4):1299-1306. [CrossRef] [PubMed]
 
Soares M, Darmon M, Salluh JI, et al. Prognosis of lung cancer patients with life-threatening complications. Chest. 2007;131(3):840-846. [CrossRef] [PubMed]
 
Azoulay E, Garrouste M, Goldgran-Toledano D, et al. Increased nonbeneficial care in patients spending their birthday in the ICU. Intensive Care Med. 2012;38(7):1169-1176. [CrossRef] [PubMed]
 
Azoulay E, Kouatchet A, Jaber S, et al. Noninvasive mechanical ventilation in patients having declined tracheal intubation. Intensive Care Med. 2013;39(2):292-301. [CrossRef] [PubMed]
 
de Montmollin E, Tandjaoui-Lambiotte Y, Legrand M, et al. Outcomes in critically ill cancer patients with septic shock of pulmonary origin. Shock. 2013;39(3):250-254. [CrossRef] [PubMed]
 
Mokart D, Lambert J, Schnell D, et al. Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure. Leuk Lymphoma. 2013;54(8):1724-1729. [CrossRef] [PubMed]
 
Lengliné E, Raffoux E, Lemiale V, et al. Intensive care unit management of patients with newly diagnosed acute myeloid leukemia with no organ failure. Leuk Lymphoma. 2012;53(7):1352-1359. [CrossRef] [PubMed]
 
Organized jointly by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française, and approved by ATS Board of Directors, December 2000. International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 2001;163(1):283-291. [CrossRef] [PubMed]
 
Azoulay E, Lemiale V. Non-invasive mechanical ventilation in hematology patients with hypoxemic acute respiratory failure: a false belief? Bone Marrow Transplant. 2012;47(4):469-472. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1  Remaining questions and research agenda. MV = mechanical ventilation; NIV = noninvasive ventilation; RCT = randomized controlled trial.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1  ] Features of the Standard of Care for Critically Ill Patients With Cancer

NIV = noninvasive ventilation.

References

Verdecchia A, Francisci S, Brenner H, et al; EUROCARE-4 Working Group. Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol. 2007;8(9):784-796. [CrossRef] [PubMed]
 
Vogelzang NJ, Benowitz SI, Adams S, et al. Clinical cancer advances 2011: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2012;30(1):88-109. [CrossRef] [PubMed]
 
Smith TJ, Temin S, Alesi ER, et al. American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. J Clin Oncol. 2012;30(8):880-887. [CrossRef] [PubMed]
 
Azoulay E, Schlemmer B. Diagnostic strategy in cancer patients with acute respiratory failure. Intensive Care Med. 2006;32(6):808-822. [CrossRef] [PubMed]
 
Rabbat A, Chaoui D, Montani D, et al. Prognosis of patients with acute myeloid leukaemia admitted to intensive care. Br J Haematol. 2005;129(3):350-357. [CrossRef] [PubMed]
 
Groeger JS, White P Jr, Nierman DM, et al. Outcome for cancer patients requiring mechanical ventilation. J Clin Oncol. 1999;17(3):991-997. [PubMed]
 
Azoulay E, Mokart D, Pène F, et al. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium—a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol. 2013;31(22):2810-2818. [CrossRef] [PubMed]
 
Azoulay E, Afessa B. The intensive care support of patients with malignancy: do everything that can be done. Intensive Care Med. 2006;32(1):3-5. [CrossRef] [PubMed]
 
Azoulay E, Soares M, Darmon M, Benoit D, Pastores S, Afessa B. Intensive care of the cancer patient: recent achievements and remaining challenges. Ann Intensive Care. 2011;1(1):5. [CrossRef] [PubMed]
 
Dellinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228. [CrossRef] [PubMed]
 
Peigne V, Rusinová K, Karlin L, et al. Continued survival gains in recent years among critically ill myeloma patients. Intensive Care Med. 2009;35(3):512-518. [CrossRef] [PubMed]
 
Khassawneh BY, White P Jr, Anaissie EJ, Barlogie B, Hiller FC. Outcome from mechanical ventilation after autologous peripheral blood stem cell transplantation. Chest. 2002;121(1):185-188. [CrossRef] [PubMed]
 
Lecuyer L, Chevret S, Thiery G, Darmon M, Schlemmer B, Azoulay E. The ICU trial: a new admission policy for cancer patients requiring mechanical ventilation. Crit Care Med. 2007;35(3):808-814. [CrossRef] [PubMed]
 
Azevedo LCP, Caruso P, Silva UVA, et al. Outcomes for patients with cancer admitted to the ICU requiring ventilatory support: results from a prospective multicenter study. Chest. 2014;146(2):257-266.
 
Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188(2):220-230. [CrossRef] [PubMed]
 
Groeger JS, Lemeshow S, Price K, et al. Multicenter outcome study of cancer patients admitted to the intensive care unit: a probability of mortality model. J Clin Oncol. 1998;16(2):761-770. [PubMed]
 
Benoit DD, Depuydt PO, Vandewoude KH, et al. Outcome in severely ill patients with hematological malignancies who received intravenous chemotherapy in the intensive care unit. Intensive Care Med. 2006;32(1):93-99. [CrossRef] [PubMed]
 
Depuydt PO, Benoit DD, Vandewoude KH, Decruyenaere JM, Colardyn FA. Outcome in noninvasively and invasively ventilated hematologic patients with acute respiratory failure. Chest. 2004;126(4):1299-1306. [CrossRef] [PubMed]
 
Soares M, Darmon M, Salluh JI, et al. Prognosis of lung cancer patients with life-threatening complications. Chest. 2007;131(3):840-846. [CrossRef] [PubMed]
 
Azoulay E, Garrouste M, Goldgran-Toledano D, et al. Increased nonbeneficial care in patients spending their birthday in the ICU. Intensive Care Med. 2012;38(7):1169-1176. [CrossRef] [PubMed]
 
Azoulay E, Kouatchet A, Jaber S, et al. Noninvasive mechanical ventilation in patients having declined tracheal intubation. Intensive Care Med. 2013;39(2):292-301. [CrossRef] [PubMed]
 
de Montmollin E, Tandjaoui-Lambiotte Y, Legrand M, et al. Outcomes in critically ill cancer patients with septic shock of pulmonary origin. Shock. 2013;39(3):250-254. [CrossRef] [PubMed]
 
Mokart D, Lambert J, Schnell D, et al. Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure. Leuk Lymphoma. 2013;54(8):1724-1729. [CrossRef] [PubMed]
 
Lengliné E, Raffoux E, Lemiale V, et al. Intensive care unit management of patients with newly diagnosed acute myeloid leukemia with no organ failure. Leuk Lymphoma. 2012;53(7):1352-1359. [CrossRef] [PubMed]
 
Organized jointly by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française, and approved by ATS Board of Directors, December 2000. International Consensus Conferences in Intensive Care Medicine: noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 2001;163(1):283-291. [CrossRef] [PubMed]
 
Azoulay E, Lemiale V. Non-invasive mechanical ventilation in hematology patients with hypoxemic acute respiratory failure: a false belief? Bone Marrow Transplant. 2012;47(4):469-472. [CrossRef] [PubMed]
 
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