Determinants of Limiting Life-Sustaining Treatment in Critically Ill COVID-19 Patients: A Multicenter Study in Korean Intensive Care Units

Article information

Tuberc Respir Dis. 2025;88(3):557-565

Publication date (electronic) : 2025 April 28

doi : https://doi.org/10.4046/trd.2024.0137

I Re Heo¹, Tae Hoon Kim¹, Won Jai Jung², Gil Myeong Seong³, Sun Jung Kwon⁴, Jae Young Moon⁵, Song-I Lee⁶, Do Sik Moon⁷, Tae-Ok Kim⁸, Chul Park⁹, Eun Young Choi¹⁰, Jung-Wan Yoo¹¹, Sunghoon Park¹², Ae Rin Baek¹³, Sung Yoon Lim¹⁴, Jung Soo Kim¹⁵, Jongmin Lee¹⁶, Chi Ryang Chung¹⁷, Sang-Min Lee¹⁸, Su Hwan Lee¹⁹, Moon Seong Baek²⁰, Jin Won Huh²¹, Woo Hyun Cho²², Ho Cheol Kim^,1

¹Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Changwon, Republic of Korea

²Division of Pulmonary, Allergy, and Critical Care Medicine, Korea University Anam Hospital, Seoul, Republic of Korea

³Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea

⁴Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea

⁵Department of Internal Medicine, Chungnam National University Sejong Hospital, Chungnam National University College of Medicine, Sejong, Republic of Korea

⁶Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Republic of Korea

⁷Department of Pulmonology and Critical Care Medicine, Chosun University Hospital, Gwangju, Republic of Korea

⁸Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea

⁹Division of Pulmonology and Critical Care Medicine, Wonkwang University Hospital, Iksan, Republic of Korea

¹⁰Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University College of Medicine and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea

¹¹Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea

¹²Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea

¹³Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea

¹⁴Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

¹⁵Division of Critical Care Medicine, Department of Hospital Medicine, Inha University College of Medicine, Incheon, Republic of Korea

¹⁶Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

¹⁷Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

¹⁸Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

¹⁹Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

²⁰Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea

²¹Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

²²Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Internal Medicine, Transplant Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea

Address for correspondence Ho Cheol Kim Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, 11 Samjeongja-ro, Seongsan-gu, Changwon 51472, Republic of Korea Phone 82-55-214-3730 Fax 82-55-214-8618 E-mail hochkim@gnu.ac.kr

Received 2024 September 20; Revised 2025 January 5; Accepted 2025 March 31.

Abstract

Introduction

The coronavirus disease 2019 (COVID-19) pandemic has significantly affected healthcare systems worldwide, particularly intensive care units (ICUs). Physicians in ICUs face numerous challenges in treating severely ill patients with COVID-19 who require more aggressive treatment strategies, such as renal replacement therapy (RRT), invasive mechanical ventilation (MV), vasopressor support, and extracorporeal membrane oxygenation (ECMO) [1,2]. Although these treatments are crucial for patient survival, they raise complex ethical and medical explorations regarding limiting life-sustaining treatment (LST), which involves complicated decision-making processes that balance potential benefits, risks, and ethical considerations. Thus, determining LST in critically ill patients depends on various factors that include patient age, comorbid illness, severity of the illness, and overall probabilities of recovery. General guidelines suggest that LST decisions should involve comprehensive evaluation of the patient’s prognosis, potential benefits from continuous treatment, and the wishes of the patient or their family [3-6].

Substantial research of the factors influencing LST decisions in the general ICU population is available. However, deeper understanding regarding these decisions is required, especially for patients with COVID-19 [7-9], since the global COVID-19 pandemic, along with the significant strain on ICU resources and higher mortality rates among older patients, has increased the complexity of these decisions [10]. The highly contagious airborne transmission of COVID-19, which requires negative-pressure isolation, further complicates LST decisions. From this standpoint, further research on the factors influencing the decision to use LST in patients with COVID-19 is warranted, particularly in ICUs in Korea.

In consequence, this study sought to address this research gap by analyzing data from a nationwide, multicenter, retrospective study of COVID-19 patients admitted to ICUs. The primary aim was to identify the key factors affecting decisions regarding LST in critically ill COVID-19 patients. This study also aimed to compare the clinical outcomes between patients who received LST, and those who did not.

Materials and Methods

Results

1. Demographic and baseline clinical characteristics

Figure 1 shows a flowchart of the selection of 1,081 patients with COVID-19 with acute respiratory failure admitted to the ICUs across 22 hospitals. Of these, 207 (19.2%) made decisions regarding LST, whereas 874 (80.8%) did not (Figure 1). The median age of the LST group was higher (76 years) than that of the non-LST group (67 years) (p=0.001). More patients in the LST group had comorbidities (85.5% vs. 70.4%, p<0.001) such as cardiovascular disease (17.9% vs. 10.4%, p=0.003) and chronic lung disease (13.5% vs. 7.0%, p=0.002), than did those in the non-LST group. Laboratory results showed higher BUN levels (25 mg/dL vs. 18 mg/dL, p=0.025), lower albumin levels (3.1 g/dL vs. 3.3 g/dL, p<0.001), and higher D-dimer levels (1.56 μg/mL vs. 0.98 μg/mL, p<0.001) in the LST group, than that in the non-LST group (Table 1).

Fig. 1.

Flowchart of patient inclusion and decisions regarding limiting life-sustaining treatment among intensive care unit (ICU)-admitted coronavirus disease 2019 (COVID-19) patients with acute respiratory failure.

Table 1.

Baseline characteristics of enrolled patients

2. ICU intervention and clinical outcomes

The data on ICU interventions and clinical outcomes revealed significant differences between the LST and non-LST groups. The use of HFNC was lower in the LST group than that in the non-LST group at 74.4% vs. 83.9%, respectively (p=0.001). Conversely, MV use was higher in the LST group than that in the non-LST group at 82.6% vs. 50.9%, respectively (p<0.001). Similarly, the use of ECMO at 18.8% vs. 9.8%, respectively (p<0.001), and use of CRRT at 26.6% vs. 7.8%, respectively (p<0.001), were more common in the LST group, compared to those in the non-LST group. These interventions indicated the higher level of critical care required by patients in the LST group. The median ICU stay was longer in the LST group than that in the non-LST group at 19.5 days vs. 15 days, respectively (p=0.001). Mortality rates were significantly different between the groups, with ICU mortality being greater in the LST group than in the non-LST group at 82.6% vs. 8.9%, respectively (p<0.001); and hospital mortality was greater for the LST group than for the non-LST group at 94.2% vs. 9.3%, respectively (p<0.001) (Table 2). Kaplan-Meier survival curves showed significant differences in survival probabilities between patients with and without LST (log-rank p<0.001) (Figure 2).

Table 2.

ICU intervention and clinical outcomes

Fig. 2.

Kaplan-Meier survival curves comparing the probability of survival between patients with and without limiting life-sustaining treatment.

3. Factors influencing LST decision

The results of both univariate and multivariate logistic regression analyses identified significant factors associated with LST. In the multivariate model, the predictors included age (OR, 1.054; 95% CI, 1.026 to 1.083; p<0.001), with each additional year increasing the odds of LST by 5.4%. The use of MV (OR, 2.789; 95% CI, 1.446 to 5.378; p=0.002) and ECMO (OR, 3.580; 95% CI, 1.604 to 7.990; p=0.002) were also significant predictors, indicating a higher likelihood of LST in patients requiring these interventions (Table 3).

Table 3.

Univariate and multivariate logistic regression for LST

Discussion

The COVID-19 pandemic has led to a significant increase in the number of critically ill patients requiring ICU admission. Despite aggressive treatment, several patients deteriorate, necessitating decisions regarding LST because of poor prognosis and impending death. This study aimed to identify the factors influencing these decisions, and compare the outcomes between patients who received LST, and those who did not. Our findings revealed that age, comorbidities, and severity of illness significantly influenced LST decisions. Older patients and those with multiple comorbidities were more likely to undergo LST. Clinical indicators, such as the need for invasive MV, ECMO, and vasopressor support, were also significant in determining LST. These treatments indicate the presence of severe illness, and often result in poor prognosis, making them crucial to these decision-making processes.

In the present study, the proportion of patients with LST was approximately 20%. However, the proportion of ICU patients with LST varies widely globally, with some studies reporting rates ranging 4.8% to 27.2% [3,13,14]. This variability is because of the complexity of decisions regarding LST in critically ill patients, which vary significantly across countries and communities, reflecting diverse ethical, social, and medical perspectives. For example, northern European countries make LST decisions more frequently than do southern European countries. In North America, parents are often the primary decision-makers regarding LST, whereas in Europe and South America, doctors play a more dominant role in determining LST in critically ill pediatric patients [14,15]. Moreover, physicians in the United States are more likely to accommodate requests to continue LST [16], while LST is more common in high-income countries, and less frequent in religious or lower-income regions [17]. Significant differences in LST practices are also observed in East Asia. A study comparing LST in ICUs across China, Korea, and Japan found that Chinese physicians were the least likely to apply do-not-resuscitate (DNR) orders. In contrast, Japanese physicians were most likely to practice DNR in terminally ill patients during cardiac arrest, even without prior orders. Korean physicians’ attitudes regarding the withdrawal of treatments, such as total parenteral nutrition, antibiotics, dialysis, and suctioning, were intermediate [18]. Thus, decisions regarding LST are often influenced by the specific ICU and medical specialty services involved, including oncology and heart failure units [19]. In addition, there is a trend towards increasing LST over time, reflecting changing attitudes towards aggressive end-of-life care decisions [3].

The ‘Act on hospice and palliative care and decisions on life-sustaining treatment for patients at the end of life,’ enacted in Korea in February 2018 [20], has shaped LST decision-making processes in hospitals, including ICUs. The law provides clear guidelines to ensure ethical and transparent LST decisions, while respecting the wishes of patients or their families. Recent studies in South Korea indicate an increasing trend in LST decisions, influenced by older age, frequent ICU readmissions, and specific diseases like cancer. Most LST decisions were made by family members, highlighting the need for improved communication and support for families [21].

To enhance ICU management and decision-making in future pandemics, several strategies are recommended. Developing flexible systems to fairly distribute ICU beds, ventilators, and staff, along with implementing centralized tools to monitor and allocate resources in real-time, can help address regional disparities and ensure equitable care [22]. Establishing clear and culturally sensitive guidelines for LST decision-making that aligns with ethical standards is critical, as is providing regular training for ICU teams on ethical considerations and transparent decision-making processes during crises [22]. Improving communication with families is equally important. Families should receive clear and consistent information about patients’ conditions, treatment options, and prognoses. Dedicated support, such as social workers or palliative care teams, can help provide emotional and psychological support during these challenging times [23]. Promoting multicenter research collaborations to evaluate LST practices and patient outcomes is vital to improve policies and clinical guidelines. Establishing data-sharing platforms will enable real-time insights into ICU capacity and treatment outcomes, allowing healthcare systems to respond more effectively during crises [24].

This study had several strengths. First, the nationwide sample from diverse ICUs across Korea enhances the generalizability of the findings. Second, the extended study period allowed the pandemic’s evolving nature and its impact on ICU practices to be captured. Third, the extensive dataset thoroughly examined factors influencing LST decisions. However, the study’s retrospective design may have introduced biases in data collection, and limited its applicability outside Korea. Incomplete data and missing information may also have affected the results. Additionally, variability in endof-life care policies across hospitals and reliance on medical records may have led to the underreporting or misclassifying of some variables.

In conclusion, this study highlighted the complexity of LST decisions for critically ill patients with COVID-19. Our results emphasize that identifying the key factors and ethical considerations provides a foundation to improve clinical guidelines and decision-making processes during future pandemics and similar healthcare crises.

Article information Continued