Present address: Department of Pulmonary, Allergy and Critical Care Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Republic of Korea
The aim of this study was to evaluate the long-term (5-year) clinical outcomes of patients who received intensive care unit (ICU) treatment using Korean nationwide data.
All patients aged >18 years with ICU admission according to Korean claims data from January 2008 to December 2010 were enrolled. These enrolled patients were followed up until December 2015. The primary outcome was ICU mortality.
Among all critically ill patients admitted to the ICU (n=323,765), patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p<0.001). However, there was no significant difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer (lung cancer or hematologic malignancies) (14.3%). Compared to patients without cancer, hazard ratios of those with cancer for ICU mortality at 5 years were: 1.90 (1.87–1.94) for lung cancer; 1.44 (1.43–1.46) for other solid cancers; and 3.05 (2.95–3.16) for hematologic malignancies.
This study showed that the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients. However, short term outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for those with lung cancer or hematologic malignancies.
The incidence rate of cancer is increasing as the elderly population increases. The National Institutes of Health (Bethesda, MD, USA) [
Numerous recent studies [
Thus, the aim of this study was to investigate long-term outcomes depending on the type of cancer. This population-based cohort study compared 5-year mortality rates of critically ill patients with and without cancer to investigate differences in the long-term outcome of each type of cancer.
This was a retrospective observational cohort study using claims data from the Health Insurance Review and Assessment Service (HIRA) between January 1, 2007 and December 31, 2015. In Korea, all individuals are covered by the National Health Insurance or Medical Aid Program. The claims data contain information regarding patients’ diagnoses, treatments, procedures, surgical history, and use of prescription drugs.
The study population included all patients aged >18 years who were examined by chest computed tomography for any reasons from January 2007 to December 2012. Enrolled patients were followed up until March 31, 2016. We identified the first ICU admissions with codes of ICU services (modified version of the International Classification of Diseases 10th revision [ICD-10] codes: AJ001-AJ590900). Patients with ICU admission were divided into two groups based on the presence or absence of cancer since January 2008. Exclusion criteria were as follows: (1) patients aged >100 years; (2) ICU admission prior to the diagnosis of cancer; and (3) any claims related to cancer prior to January 2008. Cancer was categorized into lung cancer (code C34 of the ICD-10), hematologic malignancy (codes C81–C86, C88, and C90–C95 of the ICD-10), and other solid cancers.
Comorbidities were recognized if claims data existed 6 months before the index of admission to the ICU. Comorbidity diagnoses were reached using ICD-10 codes. Concomitant medical therapy was defined by the procedure code of the Korean National Health Insurance or Korean drug and anatomical therapeutic chemical codes.
This study was approved by the HIRA. Ethical approval for this study was exempted by the Kangwon National University Hospital Institutional Review Board (B-2018-02-002) because the authors only accessed de-identified, previously collected data.
The study endpoint was all-cause mortality in the ICU. Variables are presented as numbers (percentages) or means (standard deviations). Between-group comparisons were performed using χ2 tests for categorical data and Student’s t-tests for continuous data. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for in-hospital mortality associated with patient characteristics. The value obtained by subtracting the cancer-related score from the Charlson Comorbidity Index (CCI) system was used to avoid overcorrection of cancer disease. Probabilities <0.05 were considered statistically significant. All analyses were performed using R v3.4.4 with packages of survival and ggplot2 function in R to obtain an appropriate updated citation.
During the study period, 323,765 patients were admitted to the ICU at least once. Of all critically ill patients admitted to the ICU, the proportion of patients with cancer continued to increase from 21.5% in 2008 to 27.8% in 2010. Critically ill patients with cancer showed significant male predominance (67.5%, p<0.001) and higher CCI (5.5±3.1 vs. 2.2±2.0, p<0.001) than patients without cancer (
Of 78,736 patients with cancer, except for 9,200 patients (10.5%) with multiple primaries, 5.8% had hematologic malignancies. The proportion of patients with a hematologic malignancy among critically ill patients with cancer increased from 5.4% in 2008 to 6.6% in 2010. These patients were predominantly females, younger, and had lower CCI versus those with solid cancer (
Lung cancer accounted for 28.2% of critically ill patients with solid cancer. Patients with lung cancer had a higher percentage of males (72.4% vs. 65.8%, p<0.001) than those with other solid cancers. Patients with lung cancer were admitted sooner to the ICU following diagnosis than patients with other solid cancers (205.1±409.5 days vs. 357.1±571.0 days, p<0.001). Patients with lung cancer had a shorter length of stay in the ICU than those with other solid cancers (16.1±12.9 days vs. 18.8±14.6 days, p<0.001). In addition, they required more ventilator support than others (31.0% vs. 27.6%, p<0.01). ICU mortality was higher in patients with lung cancer than in those with other solid cancer (25.5% vs. 14.4%, p<0.01). Compared with patients without cancer, the HRs of 28-day and 5-year survival were 1.93 (95% CI, 1.87–1.99) and 1.90 (95% CI, 1.87–1.94) in patients with lung cancer and 1.07 (95% CI, 1.04–1.10) and 1.44 (95% CI, 1.43–1.46) in patients with other solid cancers, respectively (
This study comprehensively presented short-term and long-term outcomes of critically ill patients over 5 years with relatively representative data. In the short term, outcomes of critically ill patients with cancer were not significantly different from those of general patients except for those with lung cancer or hematologic malignancies. After 60 days, the survival rate of patients with cancer was significantly worse than that of general critically ill patients. Although critical care had a limited effect on the overall course of cancer, it could be beneficial to patients with cancer in terms of overcoming the acute crisis in the ICU. However, patient selection for ICU admission is necessary for those with lung or hematologic malignancy who require intensive care to overcome an acute crisis.
Between 1987 and 1992, the 5-year survival rate of the Finnish mixed ICU was 59.9% [
Similar to the Finnish data [
Our study followed up critically ill patients for a long period of 5 years. However, a few limitations should be considered when interpreting our data. Firstly, this study used claims data designed for reimbursement purposes. It was not possible to present these data with standard scoring such as the Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology Score. Alternatively, the condition of organ failure was assessed based on medical resources used for organ failure. There was no information on the performance status before admission to the ICU. This study might have included both low-severity patients and futile cases. Although it is difficult to identify accurate predictors for survival in this study, it is important to realistically assess the demand for ICU in a society where the number of patients with cancer increases. This is because it is difficult for physicians to actually deny admission to the ICU for patients with acute problems [
The policy of admission to the ICU for patients with cancer remains unclear. This is because most previous studies have reported predictors for survival based on short-term outcomes of less-representative populations rather than all patients with cancer. Our study of a relatively representative population can assist physicians in developing a comprehensive understanding of the relatively long-term prognosis of 5 years. In the future, more comprehensive research and interdisciplinary discussions are warranted. Communication and collaboration between the ICU team and oncologists and palliative care specialists should pre-describe clearer ICU admission criteria for patients with cancer and assist in making informed decisions.
Conceptualization: Hong Y, Hong JY, Park J. Methodology: Hong Y, Hong JY, Park J. Formal analysis: Hong Y, Hong JY, Park J. Data curation: Hong Y, Hong JY, Park J. Software: Park J. Investigation: Hong Y, Hong JY, Park J. Writing - original draft preparation: Hong Y, Park J. Writing - review and editing: Hong Y, Kim WJ, Jeong Y, Hong JY, Park J. Approval of final manuscript: all authors.
No potential conflict of interest relevant to this article was reported.
This study was supported by a grant (NRF 2020R1A2C 1011455) of the National Research Foundation (NRF) funded by the Korean Government and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI21C1074).
Kaplan-Meier curves of risk for all-cause death in intensive care unit (ICU) (A) and at 5 years of each group (B) compared with that of critically ill patients without cancer. HMO: hematology and medical oncology.
Cox regression proportional hazard model analysis of all-cause mortality in comparison with critically ill patients without cancer. Adjusted hazard ratios (solid circles) and 95% confidence intervals (horizontal lines) for death are shown. Hazard ratios were adjusted for age, sex, year of admission to the intensive care unit, and use of life support system (such as ventilator, continuous renal replacement therapy, and vasopressor). CI: confidence interval; HMO: hematology and medical oncology.
Characteristics and outcomes of critically ill patients
Characteristic | Total (n=323,765) | With cancer (n=87,936) | Without cancer (n=235,829) | p-value |
---|---|---|---|---|
Female sex | 128,471 (39.7) | 28,611 (32.5) | 99,860 (42.3) | <0.001 |
Age, yr | 66.2±14.4 | 66.0±12.3 | 66.3±15.1 | <0.001 |
Charlson Comorbidity Index | 3.1±2.8 | 5.5±3.1 | 2.2±2.0 | <0.001 |
Overall follow-up, day | 1,074.7±988.6 | 843.6±908.9 | 1,160.9±1,003.2 | <0.001 |
LOS in ICU, day | 16.2±14.3 | 18.2±14.5 | 15.4±14.2 | <0.001 |
Use of mechanical ventilator | 104,444 (32.3) | 26,222 (29.8) | 78,222 (33.2) | <0.001 |
Renal replacement therapy | 21,261 (6.0) | 4,903 (5.6) | 16,358 (6.9) | <0.001 |
CRRT | 11,974 (3.7) | 3,305 (3.8) | 8,669 (3.7) | 0.273 |
Vasopressor | 100,836 (31.1) | 26,996 (30.7) | 73,840 (31.3) | 0.001 |
Overall mortality | 176,202 (54.4) | 55,388 (63.0) | 120,814 (51.2) | <0.001 |
ICU mortality | 47,459 (14.7) | 16,388 (18.6) | 341,071 (13.2) | <0.001 |
ICU mortality at day 28 | 50,069 (15.5) | 15,959 (18.1) | 34,110 (14.5) | <0.001 |
ICU mortality at day 60 | 68,747 (21.2) | 23,008 (26.2) | 45,739 (19.4) | <0.001 |
ICU mortality at day 90 | 77,585 (24.0) | 26,164 (29.8) | 51,421 (21.8) | <0.001 |
ICU mortality at 6 months | 92,314 (28.5) | 31,349 (35.6) | 60,965 (25.9) | <0.001 |
ICU mortality at 1 year | 109,618 (33.9) | 37,526 (42.7) | 72,093 (30.6) | <0.001 |
ICU mortality at 2 years | 130,656 (40.4) | 44,654 (50.8) | 86,002 (36.5) | <0.001 |
ICU mortality at 3 years | 145,106 (44.8) | 48,662 (55.3) | 96,444 (40.9) | <0.001 |
ICU mortality at 5 years | 166,595 (51.5) | 53,585 (60.9) | 113,010 (47.9) | <0.001 |
Values are presented as number (%) or mean±SD.
LOS: length of stay; ICU: intensive care unit; CRRT: continuous renal replacement therapy; SD: standard deviation.
Characteristics and outcomes of critically ill patients according to cancer type except for multiple primaries
Characteristic | Solid cancer |
Hematologic malignancies (n=4,552) | p-value | |
---|---|---|---|---|
Lung cancer (n=20,902) | Other solid cancers (n=53,282) | |||
Female sex | 5,770 (27.6) | 18,247 (34.2) | 1,879 (41.3) | <0.001 |
Age, yr | 67.3±10.8 | 66.0±12.5 | 60.4±15.3 | <0.001 |
Charlson Comorbidity Index | 5.5±3.1 | 5.5±3.1 | 4.3±2.6 | <0.001 |
Interval from diagnosis to ICU | 205.1±409.5 | 357.1±571.0 | 320.7±514.4 | <0.001 |
Overall follow-up | 796.2±946.9 | 887±896.4 | 383.1±693.2 | <0.001 |
LOS in ICU | 16.1±12.9 | 18.8±14.7 | 22.7±17.3 | <0.001 |
Use of mechanical ventilator | 6,490 (31.0) | 14,715 (27.6) | 2,483 (54.5) | <0.001 |
Renal replacement therapy | 660 (3.2) | 2,878 (5.4) | 1,002 (22.0) | <0.001 |
CRRT | 450 (2.2) | 1,793 (3.4) | 792 (17.4) | 0.273 |
Vasopressor | 6,017 (28.8) | 15,799 (29.7) | 2,693 (59.2) | 0.001 |
Overall mortality | 13,976 (66.9) | 31,831 (59.7) | 3,736 (82.1) | <0.001 |
ICU mortality | 5,322 (25.5) | 7,676 (14.4) | 1,997 (43.9) | <0.001 |
ICU mortality at day 28 | 5,291 (25.3) | 7,609 (14.3) | 1,638 (36.0) | <0.001 |
ICU mortality at day 60 | 7,363 (35.2) | 11,136 (20.9) | 2,454 (53.9) | <0.001 |
ICU mortality at day 90 | 8,145 (39.0) | 12,928 (24.3) | 2,722 (59.8) | <0.001 |
ICU mortality at 6 months | 9,347 (44.7) | 16,053 (30.3) | 3,051 (67.0) | <0.001 |
ICU mortality at 1 year | 10,551 (50.5) | 20,125 (37.8) | 3,311 (72.7) | <0.001 |
ICU mortality at 2 years | 11,796 (56.4) | 24,951 (46.8) | 3,522 (77.4) | <0.001 |
ICU mortality at 3 years | 12,548 (60.0) | 27,599 (51.8) | 3,602 (79.1) | <0.001 |
ICU mortality at 5 years | 13,568 (64.9) | 30,710 (57.6) | 3,699 (81.3) | <0.001 |
Values are presented as number (%) or mean±SD.
ICU: intensive care unit; LOS: length of stay; CRRT: continuous renal replacement therapy; SD: standard deviation.