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ORIGINAL
Prognosis of frail older patients treated with intubation andartificial ventilation for respiratory failure
Kazuhisa Nakashima, Ken Yoshihara, Kento Kono, Mika Horie, Seiko Tanaka, Keita Kawakado, Misato Kobayashi,
Yohei Shiratsuki, Takae Okuno, Mika Nakao, Yoshihiro Amano, Takamasa Hotta, Megumi Hamaguchi,
Shunichi Hamaguchi, Yukari Tsubata, Taishi Nagao, Noriaki Kurimoto, and Takeshi Isobe
Department of Internal Medicine, Division of Medical Oncology & Respiratory Medicine, Shimane University Faculty of Medicine, Shimane,Japan

Abstract : Background : Older patients with severe respiratory failure have higher mortality rates and are more
likely to experience impairments in activities of daily living (ADL). Methods : We retrospectively reviewed patients (≥ 75 years) who received intubation and artificial ventilation for respiratory failure at Shimane University
Hospital between November 2014 and December 2020. We compared the outcomes of frail patients with those of
self-sufficient patients. Results : Thirty-two patients were included. ADL ability before respiratory failure was
rated self-sufficient in 18 patients (self-sufficient group) and not self-sufficient in 14 patients (frail group). Noneof the patients in either group underwent advanced care planning prior to the onset of respiratory failure. In
the self-sufficient and frail groups, the in-hospital mortality rates were 33% and 50%, and the incidence of bedridden patients at discharge was 6% and 43%, respectively. Most patients in the frail group (93%) died or were
bedridden. The median hospitalization cost was JPY 2,984,000 for the self-sufficient group and JPY 3,008,000 for
the frail group. Conclusion : The overall prognosis of frail older patients who underwent intubation and artificial
ventilation was poor. When providing intensive care to such patients, it is important to carefully consider theirsuitability for the treatment. J. Med. Invest. 70 : 494-498, August, 2023
Keywords : artificial ventilation, frail, intubation, older patients, respiratory failure

INTRODUCTION
In Japan, societal aging has been progressing rapidly (1), andthe incidence of death due to respiratory diseases such as pneumonitis is increasing in older people (2). Although intubation
and artificial ventilation are indicated for patients with severe
respiratory failure, older patients have a high mortality rate andare more likely to have impaired physical function and activities
of daily living (ADL) (3-6). The intensive care required for treatment is associated with high medical costs (3, 4) ; however, no
studies to date have investigated this issue in Japan. Moreover,advanced-care planning (ACP) plays a significant role in protecting individual dignity (7), but it is not yet prevalent in Japan (8,9), Few previous reports have discussed whether the intensive
care provided was compliant with the wishes of older Japanesepatients with respiratory failure and their families.
Intensive treatment of respiratory failure can be a heavy
burden on the patient owing to its invasiveness and high cost.
In older patients, correct judgement about the necessity of suchtreatment is important in order to avoid excessive treatment,
which may result in poorer quality of life and functional prognosis in frail patients. Therefore, this retrospective study aimed
to compare the prognosis, ADL after treatment, and medical
cost incurred, of frail older patients who received intubation andartificial ventilation for severe respiratory failure with those of
self-sufficient patients.

Received for publication March 16, 2023 ; accepted August 28, 2023.
Address correspondence and reprint requests to Yukari Tsubata, MD,
PhD, Department of Internal Medicine, Division of Medical Oncology& Respiratory Medicine, Shimane University Faculty of Medicine,89-1 Enya-cho, Izumo, Shimane 693-8501, Japan and Fax : +81-85320-2581. E-mail : ytsubata@med.shimane-u.ac.jp

PATIENTS AND METHODSPatients

We retrospectively reviewed older patients who received intubation and artificial ventilation as treatment for respiratory
failure at Shimane University Hospital between November 2014and December 2020. In Japan, an institution with 600 beds
is considered a general hospital. The eligible patients included
cases in which the respiratory status of inpatients worsened andpatients presented to the emergency room with severe respiratory failure. When non-invasive oxygen therapy failed to maintainadequate oxygenation, intubation and artificial ventilation wereconsidered. Specifically, “older” patients were defined as those
aged ≥ 75 years based on the Japan Gerontological Society and
the Japan Geriatrics Society recommendations (10). We excluded
cases of cardiopulmonary arrest of uncertain etiology.

Assessment and statistical analysis
We retrospectively collected patients’ clinical information fromtheir medical records. We assessed the patient characteristics,
treatments, outcomes, survival time, and costs of intubation
and artificial ventilation treatment in older patients with severe
respiratory failure. Medical costs were the total hospitalization
costs at our institution, calculated by the medical affairs division
staff. Patient characteristics included age, sex, baseline ADL
ability, Charlson Comorbidity Index, presence or absence of ACP
before respiratory failure onset, and the cause of respiratory
failure. We decided that ACP was not conducted if there was norecord about the willingness of the patient for invasive treatment
or resuscitative efforts in worsening condition, or discussion ofend of life. Treatments included the period of artificial ventilation use, intensive care unit (ICU) stay duration, hospital stay
duration, and the presence or absence of physical rehabilitation.

The Journal of Medical Investigation Vol. 70 2023

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The Journal of Medical Investigation Vol. 70 August 2023
The ICU discharge criteria involved confirming respiratory
stability after extubation, or in cases where extubation was difficult, ensuring stable management of artificial ventilation aftertracheostomy. The discharge criteria included the completion of
acute-phase treatment. Outcomes included discharge destination and ADL ability at discharge.
Baseline ADL were not sufficiently assessed with well-established tools, such as the Barthel Index or Lawton Instrumental
ADLs (11, 12), because most patients presented to the emergency room with rapid-onset disease. Therefore, in this study,
we broadly classified ADL as “self-sufficient,” “requiring someassistance or care,” or “bedridden.” “Self-sufficient” is more orless equal to Clinical Frailty Scale (CFS : a tool to classify thecondition of older people to 9 levels) 1-3, “requiring some assistance or care” is more or less equal to CFS 4-6, and “bedridden”
is more or less equal to CFS 7-9 (13). We defined patients of “requiring some assistance or care” and “bedridden” as frail group.
We compared the outcomes of baseline frailty patients with thoseof self-sufficient patients.
Fisher’s exact test was used to compare the mortality andbedridden rates. Overall survival (OS) after intubation was
evaluated using the Kaplan-Meier method. Analyses were performed using JMP software (version 10.0 ; SAS Institute, Cary,
NC, USA).

Ethics
The retrospective study protocol was approved by our institutional review board (approval number : 5413 ; approvaldate : April 14, 2021), who waived the requirement of informed
consent.

are shown in Table 1. The self-sufficient group included 18
patients, and the frail group included 14 patients (10 patients required some assistance or care, and 4 patients were bedridden).
Most patients (72%) underwent intubation at the visit to theemergency room. Bacterial pneumonitis was the most common
cause of respiratory failure (N = 11). Aspiration pneumonitis was
also more common in the frail group. None of the patients underwent ACP before the onset of respiratory failure.

Treatments and outcomes
Treatments and outcomes are shown in Table 2. The medianperiod of artificial ventilation use, duration of ICU stay, and hospital stay were longer in the frail group than in the self-sufficientgroup. The in-hospital mortality rates were 41% (n = 13) in all
patients, 33% (n = 6) in the self-sufficient group, and 50% (n = 7)in the frail group (p = 0.47). Although most patients underwent
physical rehabilitation at the hospital, none of the patients ineither group was completely self-sufficient at discharge (Figure1). In the self-sufficient group, only 39% of patients died or were
bedridden ; however, in the frail group, most of the patients(93%) died or were bedridden (p = 0.0028).
The outcome subgroup analysis by age (75-84 years old vs > 85
years old) is shown in Table 3. Among 75-84 years old patients,ten (56%) died and four (22%) were bedridden. In contrast,
among patients aged ≥ 85 years old, three (21%) died, and three(21%) were bedridden.
The median overall survival was 1299 days in the self-sufficientgroup and 96 days in the frail group (Figure 2). We could not conduct a follow-up of the eight patients who were discharged.

Medical cost
The median hospitalization costs were JPY 2,984,000 (22,800
USD) in the self-sufficient group and JPY 3,008,000 in frailgroup (23,000 USD).

RESULTS

Patient characteristics
Thirty-two older patients (age range : 77–95 years ; 23 men
and 9 women) were enrolled in this study. Patient characteristics

Table 1. Patient characteristics
All
N = 32

Self-sufficient group
N = 18Frail group
N = 14

Median age (range)

84(77-95)84(79-95)

84(77-92)

Male

23 (72%)14 (78%)9 (64%)

Female9 (28%)

4 (22%)

5 (36%)

Self-sufficient

18 (56%)18 (100%)

0

Requiring some assistance or care

10 (31%)0 (0%)

10 (71%)

Bedridden

4 (13%)

0 (0%)

4 (29%)ADL before respiratory failure :Cause of respiratory failure
Bacterial pneumonitis

11 (34%)5 (28%)

6 (43%)

Aspiration pneumonitis

6 (19%)

1 (6%)

5 (36%)

Hemoptysis

4 (13%)

4 (22%)

0 (0%)

COPD

3 (9%)

1 (6%)

2 (14%)

Interstitial pneumonia

3 (9%)

3 (17%)

0 (0%)Other

5 (16%)

4 (22%)

1 (7%)Median CCI

6

6

6

ADL, activities of daily living ; CCI, Charlson Comorbidity Index ; COPD, chronic obstructive pulmonary
disease ; CFS, Clinical Frailty Scale.

K. Nakashima, et al. Frail patients with respiratory failure

496

Table 2. Patient treatments and outcomesAll
N = 32

Self-sufficient group
N = 18Frail group
N = 14

Median period of artificial ventilation use

9 days

7.5 days

13.5 days

Median ICU stay duration

11 days10.5 days

16.5 days

Median hospital time

36 days33.5 days

50 days

Patients who received rehabilitation

26 (81%)17 (94%)9 (64%)Death

13 (41%)

6 (33%)

7 (50%)

Transferred to another hospital

13 (41%)

7 (39%)

6 (43%)

Discharged to home

5 (16%)

4 (22%)

1 (7%)

Transferred to a nursing care facility

1 (3%)

1 (6%)

0 (0%)p

Outcome :0.47*

ADL ability at discharge :Self-sufficient

0 (0%)

0 (0%)

0 (0%)

Requiring some assistance or care

12 (38%)11 (61%)

1 (7%)

Bedridden

7 (22%)

1 (6%)

6 (43%)

0.027**ICU, intensive care unit ; ADL, activities of daily living ; CFS, Clinical Frailty Scale.
*The p-value pertains to the mortality rate. **The p-value pertains to the bedridden rate.

Table 3. Subgroup analysisAll
N = 32

Self-Sufficientgroup
N = 18Frail group
N = 1475-84 years
n = 1885+ yearsn = 14

Mortality

41%

33%

50%

56%

21%

Bedridden at discharge

22%

6%

43%

22%

21%

Total (death or bedridden)

63%

39%

93%

78%

p = 0.0028*

43%
p = 0.068**The p-value pertains to the total rate (death or bedridden).

Self-sufficient

Requiring someassistance or care

100

Self-sufficient group
Frail group

Overall survival probability (%)

80

Bedridden

Death

ADL ability before
respiratory failure

ADL ability
at discharge

Figure 1. Changes in activities of daily living (ADL) among
discharged survivors. The self-sufficient group is shown by a solidline, and the frail group is shown by a dotted line. “Self-sufficient” isapproximately equal to Clinical Frailty Scale (CFS) of 1-3, “requiring
some assistance or care” is approximately equal to CFS of 4-6, and“bedridden” is approximately equal to CFS of 7-9.

60

40

20

0
0

500

1000

1500

2000

2500

Days

Figure 2. Kaplan-Meier curve of the overall survival (OS) of
patients. The median OS was 1299 days in self-sufficient group, and96 days in frail group (p = 0.95).

The Journal of Medical Investigation Vol. 70 August 2023
DISCUSSION
This retrospective study evaluated the prognosis following
the use of intubation and artificial ventilation in the treatmentof frail elderly patients with severe respiratory failure. In a prospective cohort study, Dardaine et al. reported that in patients
aged ≥ 70 years who were admitted to the ICU and treated withmechanical ventilation, the mortality rates in the ICU and 6
months after discharge were 31% and 52%, respectively (5). The
mortality rate of all patients at discharge in our study was high(41%), similar to that in previous reports (3-6). In the self-sufficient and frail groups, the in-hospital mortality rates were 33%
and 50%, and the percentage of patients who were bedridden atdischarge was 6% and 43%, respectively. Most of the patients inthe frail group (93%) died or were bedridden. Low baseline ADL
ability was a poorer prognostic factor than age ≥ 85 years (Themore favorable prognosis among those aged ≥ 85 years might
have been influenced by the relatively low proportion of bedridden patients at baseline [75-84 years : 17%, and ≥ 85 years : 7%]).
Therefore, intubation and artificial ventilation should be avoided in frail older patients. In contrast, the life prognosis in the
self-sufficient group was favorable (median overall survival,
1299 days). Intubation and artificial ventilation should be considered for self-sufficient patients with severe respiratory failure.
The median hospitalization costs were similar in bothgroups : JPY 2,984,000 in the self-sufficient group and JPY
3,008,000 in the frail group. There was no cost disadvantage forthe frail group compared to the self-sufficient group. However,very high medical costs were incurred on intensive treatment.
Although balancing cost with human life is difficult, this treatment for frail patients may not be clinically or economicallyjustifiable.
ACP is important for protecting the dignity of individuals(7). None of the patients in this retrospective study underwent
ACP before respiratory failure. Similar to previous reports (8,9), our results reinforce the fact that ACP is not yet widespreadin Japan. This may be because of the Japanese cultural norms
that value sociality (their loved ones’ preferences) over the wishesof an individual (14). In addition, Japanese tend to believe thatthe unawareness of death is important for a good death (15).
Although we obtained informed consent from the patient or family members for performing intubation in this study, there may
not always be enough time and emotional leeway to make calm
judgments in emergency situations. Excessive treatment might
be avoided by ACP. Therefore, medical doctors and staff in Japan
should encourage the use of ACP.
This study had several limitations. First, it was a retrospective study performed at a single center with a small sample size.
Although we initially defined the “frail group” on the basis of
Clinical Frailty Scale of 4-9, it may have been more appropriate
to define it on the basis of Clinical Frailty Scale of 7-9. Unfortunately, our analysis using the Clinical Frailty Scale 7-9 range
was limited due to the inclusion of only four cases in this category. Second, the older patients comprised a heterogeneous population with age-related changes and comorbidities. The causesof respiratory failure varied. Third, ADL was assessed using arough scale because most patients presented to the emergency
room with rapid-onset disease. Fourth, follow-up after discharge
was not performed for some patients. Dardaine et al. reported
that most older patients (aged ≥ 70 years) requiring ventilatory
support in the ICU had a similar or improved functional statuscompared to the pre-admission status (5). In some patients, ADL
may be improved by long-term rehabilitation. Although thisstudy included these limitations, the results are useful for deciding whether intubation should be performed in older patientswith respiratory failure because performing a prospective study

497

on this topic is comparatively difficult. Further retrospective
studies with larger sample sizes and comparisons are warranted. Moreover, a tool to distinguish patients with a good prognosis
from those with a poor prognosis is needed.

CONCLUSION
The life and functional prognoses of frail older patients who
underwent intubation and artificial ventilation were poor. Hospitalization costs were high. When providing intensive care tosuch patients, it is important to carefully consider their suitability for the treatment.

FUNDING
This study did not receive any specific grants from funding
agencies in the public, commercial, or non-profit sectors.

CONFLICTS OF INTEREST
There are no conflicts of interest to declare.

ACKNOWLEDGMENTS
We would like to thank Mr. Takaaki Sonoyama of the Medical
Affairs Division staff at Shimane University Hospital for his
instructions regarding medical costs and Editage (www.editage.
com) for English language editing.

REFERENCES
1.

2.

3.

4.

5.

6.
7.

8.

Statistics Bureau of Japan : Result of the population estimates, https://www.stat.go.jp/index.html. [accessed 12
March 2023].
Ministry of Health, Labour and Welfare : Vital statistics,
https://www.mhlw.go.jp/english/index.html. [accessed 12
March 2023].
Hamel MB, Phillips RS, Davis RB, Teno J, Connors AF,
Desbiens N, Lynn J, Dawson NV, Fulkerson W, Tsevat
J : Outcomes and cost-effectiveness of ventilator support
and aggressive care for patients with acute respiratory
failure due to pneumonia or acute respiratory distress syndrome. A Am J Med 109 : 614-620, 2000
Hamel MB, Phillips RS, Davis RB, Teno J, Desbiens N,
Lynn J, Tsevat J : Are aggressive treatment strategies lesscost-effective for older patients? The case of ventilator support and aggressive care for patients with acute respiratory
failure. J Am Geriatr Soc 49 : 382-390, 2001
Dardaine V, Dequin PF, Ripault H, Constans T, Giniès
G : Outcome of older patients requiring ventilatory support
in intensive care : impact of nutritional status. J Am Geriatr
Soc 49 : 564-570, 2001
El Solh AA, Bhat A, Gunen H, Berbary E : Extubation failure in the elderly. Respir Med 98 : 661-668, 2004
Detering KM, Hancock AD, Reade MC, Silvester W : The
impact of advance care planning on end of life care in elderly patients : randomised controlled trial. BMJ 340 : c1345,
2010
Cheng SY, Lin CP, Chan HY, Martina D, Mori M, Kim SH,
Ng R : Advance care planning in Asian culture. Jpn J Clin
Oncol 50 : 976-989, 2020

498
9.

K. Nakashima, et al. Frail patients with respiratory failure

Takazono T, Imamura Y, Kawakami K, Yamasaki N,
Shimizu H, Usuki K, Kiyohara M, Hirayama T, Tashiro M,
Hosogaya N, Saijo T, Yamamoto K, Miyazaki T, Yanagihara
K, Izumikawa K, Mukae H : Discrepancies in preferences
regarding the care of terminal-phase pneumonia in elderly
patients among patients, families, and doctors : A multicenter questionnaire survey in nagasaki, Japan. Respir
Investig 58 : 488-494, 2020
10. The Japan geriatrics Society : The definition of “old”, https://www.jpn-geriat-soc.or.jp/proposal/pdf/definition_01.pdf.
[accessed 12 March 2023].
11. Mahoney FI, Barthel DW : Functional evaluation : theBarthel index. Md State Med J 14 : 61-65, 1965

12. Lawton MP, Brody EM : Assessment of older people : self-maintaining and instrumental activities of dailyliving. Gerontologist 9 : 179-186, 1969
13. Clinical Frailty Scale 2005-2020 Rockwood, Version 2.0(JA), https://www.dal.ca/sites/gmr.html [accessed 12 March
2023]
14. Bito S, Wenger NS, Ohki M, Fukuhara S : Japanese attitude toward advance care planning for end-of-life decisions.
Gen Med : 3-10, 2001
15. Miyashita M, Sanjo M, Morita T, Hirai K, Uchitomi Y : Good
death in cancer care : a nationwide quantitative study. Ann
Oncol 18 : 1090-1097, 2007