Laryngoscope Investigative Otolaryngology

© 2019 The Authors. Laryngoscope Investigative Otolaryngology

published by Wiley Periodicals, Inc. on behalf of The Triological Society.

Effect of Early Tracheostomy in Mechanically Ventilated Patients

Hirotomo Dochi, MD ; Masanori Nojima, MD, MPH; Michiya Matsumura, MD, PhD;
Ivor Cammack, MBChB; Yasushi Furuta, MD, PhD

Objective: To investigate the effect of the timing of tracheostomy in patients who required prolonged mechanical ventila-
tion using two methods: analysis of early versus late tracheostomy and landmark analysis.
Study Design: Retrospective cohort study.
Methods: Patients who were emergently intubated and admitted into the intensive care unit or high dependency unit
between January 2011 and August 2016, with or without tracheostomy, were included. In the early and late tracheostomy
analysis, all patients were divided into early (≤10 days, n = 88) and late (>10 days, n = 132) groups. In the landmark analysis,
198 patients requiring ventilation for more than 10 days were divided into early tracheostomy (≤10 days, n = 57) and nonearly
tracheostomy (>10 days, n = 141) groups. We compared 60-day ventilation withdrawal rate and 60-day mortality.
Results: Early tracheostomy was a significant factor for early ventilation withdrawal, as shown by log-rank test results
(early and late tracheostomy: P = .001, landmark: P = .021). Multivariable analysis showed that the early group was also associ-
ated with a higher chance of ventilation withdrawal in each analysis (early and late tracheostomy: adjusted hazard ratio
[aHR] = 1.69, 95% confidence interval [CI] = 1.20–2.39, P = .003; landmark: aHR = 1.61, 95% CI = 1.06–2.38, P = .027). Early
tracheostomy, however, was not associated with improved 60-day mortality (early and late tracheostomy: aHR = 0.88, 95%
CI = 0.46–1.69, P = .71; landmark: aHR = 1.46; 95% CI = 0.58–3.66; P = .42).
Conclusion: For patients requiring ventilation, performing tracheostomy within 10 days of admission was independently
associated with shortened duration of mechanical ventilation; 60-day mortality was not associated with the timing of
tracheostomy.
Key Words: Early tracheostomy, mechanical ventilation, withdrawal, landmark analysis.
Level of Evidence: 2b

INTRODUCTION recommendation or guideline that has been based on

Tracheostomy is a well-established procedure for objective evidence.
critically ill patients requiring prolonged mechanical ven- Recently, the potential advantage of early tracheos-
tilation. This procedure is invasive and carries some risk; tomy has attracted considerable attention; several retro-
however, it also has advantages, including decreased tube spective and prospective studies have suggested a clinical
dead space and breathing effort compared with endotra- benefit of early tracheostomy on patients requiring pro-
cheal intubation. Clinicians are required to consider the longed mechanical ventilation.2–11 However, the design of
risk-benefit profile for each patient; however, the ideal these trials is insufficient to investigate the effect of early
timing for performing tracheostomy remains unclear. In tracheostomy. For example, in retrospective studies, it is
1989, the National Association of Medical Directors of difficult to match patients because there are no consistent
Respiratory Care recommended, based on expert opinion indication criteria for tracheostomy.
The timing of tracheostomy is affected by various
alone, that translaryngeal intubation should be reserved
factors, including illness severity, clinical physician pref-
for patients requiring <10 days of mechanical ventilation.
erence, patient and family requests, and hospital
Furthermore, they recommended that tracheostomy
resources. For example, in patients with a favorable prog-
should be performed in patients requiring intubation
nosis, clinicians might be more likely to perform early
beyond 21 days.1 However, to date, there is no tracheostomy, causing selection bias. Furthermore, as
tracheostomy timing is variable, one must consider
This is an open access article under the terms of the Creative immortal time bias: patients undergoing tracheostomy
Commons Attribution-NonCommercial-NoDerivs License, which permits must be alive before the surgery is performed. Therefore,
use and distribution in any medium, provided the original work is prop-
erly cited, the use is non-commercial and no modifications or adaptations the time-to-event for patients undergoing late tracheos-
are made. tomy is necessarily longer than that for patients undergo-
From the Department of Otolaryngology-Head and Neck Surgery ing early tracheostomy, even if the timing does not affect
(H.D., M.M., Y.F.), Teine-Keijinkai Hospital, Sapporo, Japan; Center for
Translational Research (M.N.), The Institute of Medical Science Hospital, the event. In addition, patients undergoing late tracheos-
The University of Tokyo, Tokyo, Japan; Clinical Residency Department tomy appear to have a longer duration of ventilation
(I.C.), Teine-Keijinkai Hospital, Sapporo, Japan
Conflict of Interest: We have no conflicts of interest to disclose.
dependence. Randomized prospective trials could elimi-
Send correspondence to Hirotomo Dochi, MD, Department of nate the risk of such selection and immortal time biases;
Otolaryngology-Head and Neck Surgery, Teine-Keijinkai Hospital, 1-12 however, no criteria or tools are currently available to
Maeda, Teine-ku, Sapporo 006-8555, Japan. Email: [email protected]
predict accurately upon admission which of the patients
DOI: 10.1002/lio2.265 might require prolonged ventilation support, and there is

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a risk of over-treatment with tracheostomy. Such criteria Of these, 110 were chosen at random using a computer
are crucial for safe prospective trials of early tracheos- algorithm and reviewed retrospectively. A group size of
tomy; therefore, they are recommended targets for future 110 was chosen for the control group because it was half
research. the size of the tracheostomy group, which is suitable for sta-
Evidence-based guidance for tracheostomy timing is tistical analysis.
long overdue; however, establishing this evidence remains
difficult. To address this, we have constructed a double-
analysis approach: first, we compared patients undergoing Study Analysis
early and late tracheostomy; and second, we performed a This study consisted of two separate analyses: an
landmark analysis using a tertiary referral center cohort early and late tracheostomy analysis and a landmark
of ventilation-dependent critically ill patients. In the tra- analysis. We selected patients for each analysis from the
cheostomy analysis, we divided the patients into early tracheostomy and nontracheostomy groups. Study enroll-
(≤10 days) and late (>10 days) tracheostomy groups, and ment is detailed in Figure 1.
compared the duration of ventilation dependence from In the early and late tracheostomy analysis, all the
time of tracheostomy to withdrawal or death. The land- patients in the tracheostomy group were assigned to the
mark analysis included ventilated patients who had not early (tracheostomy performed ≤10 days after admission) or
undergone tracheostomy, and we evaluated the effect of late (>10 days after admission) groups, and we compared the
early tracheostomy on patients with prolonged mechanical outcomes between the groups. However, using this analysis,
ventilation use (>10 days). Our objective was to determine we were not able to evaluate the patients who required ven-
the benefits of early tracheostomy using these methods. tilation for a long duration because there was a considerable
difference in the median (95% confidence interval [CI]) day
of ventilation withdrawal or death from intubation of the
METHODS patients in our cohort undergoing early (median = 7 days;
This retrospective cohort study was conducted in range = 2–18 days) and late (median = 14 days; range = 5–-
accordance with the Declaration of Helsinki and approved 32 days) tracheostomy. Furthermore, to evaluate effective-
by the institutional review board of Teine-Keijinkai Hos- ness of the tracheostomy, it was important to include
pital, Sapporo, Japan. patients who were withdrawn from ventilation without tra-
cheostomy (nontracheostomy group) in our analysis. The
nontracheostomy group also showed early ventilation with-
drawal or death (median = 3 days; range = 2–7 days).
Patient Selection
To avoid any selection bias due to a higher chance of
Between January 2011 and August 2016, the follow-
ventilation withdrawal or death among the early trache-
ing patients were included in the study: 1) Tracheostomy
ostomy and nontracheostomy groups compared with late
group: patients emergently intubated in the emergency
tracheostomy group (which had a longer time-to-outcome,
room (ER) and admitted to an intensive care unit (ICU)
which is a type of immortal time bias), we performed a
or high dependency unit (HDU) who subsequently under-
landmark analysis by excluding patients in the tracheos-
went tracheostomy; and 2) Nontracheostomy group:
tomy and nontracheostomy groups who died or were with-
patients emergently intubated in the ER who were admit-
drawn from ventilation before the landmark, which was
ted to ICU/HDU without tracheostomy.
set at day 10 from endotracheal intubation. This type of
TRACHEOSTOMY GROUP. All medical records of analysis was introduced by Anderson et al. to match the
the 337 patients who were intubated in the ER because of conditions within each group.12,13 In this analysis,
emergent respiratory distress, and admitted to ICU/HDU patients who underwent tracheostomy within 10 days of
and underwent tracheostomy due to prolonged mechani- admission were categorized into the early-tracheostomy
cal ventilation, were reviewed retrospectively. The exclu- (ET) group, while patients who underwent tracheostomy
sion criteria were as follows: age <20 years, ventilation more than 10 days after admission (from the tracheos-
withdrawal before undergoing tracheostomy, tracheos- tomy group), or were withdrawn from ventilation or died
tomy due to control of suctioning, and upper airway after 10 days without tracheostomy (from the non-
obstruction (deep neck infection, neck trauma, or diffi- tracheostomy group) were categorized into non-ET group.
culty with laryngeal intubation). After application of the We used day 10 as the landmark point and for defin-
above exclusion criteria, the remaining 220 patients were ing early tracheostomy for the following reasons: previous
reviewed retrospectively. trials14,15 have defined early tracheostomy as that per-
formed within 7, 10, or 14 days of admission; the median
NONTRACHEOSTOMY GROUP. A total of duration from intubation to tracheostomy in our study
946 patients were identified who had been intubated in the was 12 days, and we sought to investigate the effect of
ER because of emergent respiratory distress, admitted to tracheostomy at days earlier than our current average.
ICU/HDU, and were withdrawn from ventilation or died There are currently no set criteria for the timing of
without undergoing tracheostomy. The exclusion criteria tracheostomy; however, the attending physician evaluated
were as follows: death within 24 hours of intubation; whether patients could be weaned from ventilation daily,
age <20 years; and intubation due to upper airway obstruc- and tracheostomy was considered via clinical evaluation.
tion or for other investigations, such as bronchoscopy. After Written informed consent for tracheostomy was obtained
application of the exclusion criteria, 563 patients remained. from the patients or their family. Open tracheostomy was

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293
Fig. 1. Flowchart of enrolling patients in the study cohort.

the most common procedure, but percutaneous dilatational timing was not thought to be associated with the cases
tracheostomy was also performed in selected patients. requiring mechanical ventilation for more than 60 days.
The secondary outcome was 60-day survival. In both ana-
lyses, we evaluated the primary and secondary outcomes.
Variables
We collected the following data from the patients:
demographic and clinical data; number of ventilation- Statistical Analysis
dependent days; time to tracheostomy (if performed); Time-to-event data of primary and secondary out-
number of days with use of intravenous medication, such comes were estimated using the Kaplan-Meier method,
as opioid analgesics, sedatives, or antibiotics; total and group comparisons were performed using a log-rank
ICU/HDU and overall hospital stay; Acute Physiology test. In the early and late tracheostomy analysis, the out-
and Chronic Health Evaluation16 (APACHE II) score in comes were not measured as time postintubation, but as
the first 24 hours of ICU/HDU admission, which esti- time post-tracheostomy.
mates severity of disease and risk of death; and Charlson In the landmark analysis, the outcomes were mea-
Comorbidity Index17 (CCI) score, which estimates the risk sured as time postintubation because the timing of tra-
of death due to a selection of comorbid conditions. cheostomy did not interfere with duration of events. For
the primary outcome (60-day ventilation withdrawal)
measurement, the patients who were lost to follow-up or
Outcome Measures died within 60 days were censored at the date of last
The primary outcome was mechanical ventilation follow-up. For the secondary outcome (60-day survival),
withdrawal by day 60. Ventilation withdrawal was defined only the patients who were lost to follow-up were cen-
as maintaining spontaneous breathing for at least 2 days. sored at the date of last follow-up. The patients who were
Day 60 was chosen because of a high withdrawal rate by withdrawn from mechanical ventilation or died after
60 days from intubation, and effectiveness of tracheostomy 60 days were also censored at day 60.

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 TABLE I.
Baseline Characteristics of the Patients Included in the Early and Late Tracheostomy and Landmark Analyses.
Early and Late Trach Analysis Landmark Analysis
Characteristics Early Trach (n = 88) Late Trach (n = 132) P Value ET Group (n = 57) Non-ET Group (n = 141) P Value

Age
Mean (SD), years 71 (16) 71 (13) .69 71 (14) 71 (13) .85
Sex: number (%)
Male 62 (70) 89 (67) .74 39 (68) 93 (66) .87
Female 26 (30) 43 (33) 18 (32) 48 (34)
APACHE-II score, mean (SD) 22.3 (6.7) 22.1 (7.5) .86 21.3 (6.8) 22.0 (7.4) .45
CCI, mean (SD) 2.0 (1.8) 2.2 (1.8) .47 2.2 (1.7) 2.2 (1.7) .61
Main reason for admission: number (%)
Hypoxic encephalopathy 23 (26) 20 (15) .06 8 (14) 20 (14) .53
Head trauma and stroke 23 (26) 31 (23) 13 (23) 34 (24)
Cardiovascular disease 5 (6) 28 (21) 18 (32) 32 (23)
Respiratory disease 22 (25) 34 (26) 14 (25) 35 (25)
Infectious disease 15 (17) 19 (14) 4 (7) 20 (14)
Admission type*
Medical 56 (64) 86 (65) .93 32 (56) 94 (67) .17
Surgical 32 (36) 46 (35) 25 (44) 47 (33)

*Patients were assigned to the surgical group if they needed surgical procedures, except tracheostomy.
APACHE-II = acute physiology and chronic health evaluation; CCI = Charlson comorbidity index; ET = early tracheostomy; Trach = tracheostomy.

For each analysis, univariate and multivariate characteristics of both groups were similar in both analyses
Cox proportional hazard regression analyses were con- (Table I).
structed. In the multivariate analyses, the hazard
ratio (HR) was adjusted for age, sex, APACHE-II score,
CCI score, admission diagnosis, hypoxic encephalopa- 60-Day Ventilation Withdrawal
thy, head trauma and stroke, cardiovascular disease, In the early and late tracheostomy analysis, median
respiratory disease (infection or chronic obstructive ventilation-dependent time by day 60 was 9 days (95%
pulmonary disease), and nonrespiratory infectious CI = 5–13) in the early tracheostomy group, which was
diseases. significantly higher than that in the late tracheostomy
We compared categorical parameters using Fisher’s group (median = 20 days; 95% CI = 14–40; P = .001;
exact test, and continuous parameters using unpaired t test Fig. 2a). Multivariate analysis showed that performing
or Mann-Whitney U test, where appropriate. Data analysis tracheostomy within 10 days of admission was associated
was performed using EZR, which is a graphical user inter- with a significantly higher chance of mechanical ventila-
face for R (The R Foundation for Statistical Computing, tion withdrawal (adjusted hazard ratio [aHR] = 1.69; 95%
Vienna, Austria). This modified version of R commander is CI = 1.20–2.39; P = .003; Table II).
designed to add statistical functions frequently used in bio- In the landmark analysis, median ventilation-
statistics.18 A significance level of P < .05 was used. dependent time by day 60 was 27 days (95% CI = 20–36)
in the ET group and 37 days (95% CI = 31–55) in the non-
ET group, which was significantly different (P = .021,
Fig. 2b). After adjusting for covariates, early tracheostomy
RESULTS
within 10 days remained a significant positive factor for
Baseline Patient Characteristics ventilation withdrawal (aHR = 1.61; 95% CI = 1.06–2.38;
In the early and late tracheostomy analysis, a total P = .027; Table II). In the multivariate analysis of early
of 220 patients in the tracheostomy group were included and late tracheostomy, the presence of respiratory disease,
and divided into early (≤10 days, n = 88) and late including pneumonia and chronic obstructive pulmonary
(>10 days, n = 132) tracheostomy groups. disease, significantly increased ventilation dependence
The landmark analysis included patients requiring (aHR = 0.48; 95% CI = 0.27–0.85; P = .012); however, there
ventilation support for at least 10 days. Patients who were was no significant difference in the landmark analysis
weaned off the ventilator or died before day 10 were (aHR = 0.90; 95% CI = 0.45–1.79; P = .75; Table II).
excluded from the tracheostomy and nontracheostomy
groups. We excluded 132 patients; therefore, the landmark
analysis cohort included 198 patients (Fig. 1). In the 60-Day Survival
landmark group, 57 and 141 patients were categorized into The Kaplan-Meier curve of 60-day survival of the early
the ET and non-ET groups, respectively. The baseline and late tracheostomy groups, and landmark analyses

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Fig. 2. Kaplan-Meier estimates of ventilation withdrawal according to timing of tracheostomy for patients in the early and late tracheostomy
groups, and landmark analysis results. (a) In the early and late tracheostomy analysis, median ventilation-dependent time by day 60 was
9 days (95% confidence interval [CI] = 5–13) in the early tracheostomy group, which was significantly higher than that in the late tracheostomy
group (median = 20 days; 95% CI = 14–40; P = .001). (b) In the landmark analysis, median ventilation-dependent time by day 60 was 27 days
(95% CI = 20–36) in the early-tracheostomy group, which was significantly higher than that in the nonearly tracheostomy group
(median = 37 days; 95% CI = 31–55; P = .021).

showed no significant difference in mean (standard devia- aHR = 0.88, 95% CI = 0.46–1.69, P = .71; landmark:
tion) 60-day survival time (early and late tracheostomy: aHR = 1.46, 95% CI = 0.58–3.66; P = .42; Table III).
39 [21.2] vs. 44 [19.1] days, P = .56; landmark: 45 [16.8]
vs. 50 [14.3] days; P = .097, figures not shown). Multivariate
analysis showed that performing tracheostomy within Other Clinical Outcomes
10 days was not associated with an improvement in 60-day In the early and late tracheostomy analysis, the
survival in either analysis (early and late tracheostomy: early tracheostomy group had significantly shorter

TABLE II.
Univariate and Multivariate Analyses of 60-Day Ventilation Withdrawal.
Early and Late Trach Analysis Landmark Analysis
HR (95% CI) P Value HR (95% CI) P Value

Univariate analysis
Early trach within day 10 1.70 (1.22–2.37) .002 1.59 (1.06–2.38) .024
Multivariate analysis
Early trach within day 10 1.69 (1.20–2.39) .003 1.61 (1.06–2.46) .027
Age 0.99 (0.98–1.00) .086 0.99 (0.97–1.00) .05
Sex 1.11 (0.76–1.60) .59 0.96 (0.63–1.45) .84
APACHE-II score 0.99 (0.97–1.02) .64 1.00 (0.97–1.04) .82
CCI 0.96 (0.87–1.06) .43 0.94 (0.84–1.05) .26
Main reason for ICU/HDU admission
Hypoxic encephalopathy 1 (reference) NA 1 (reference) NA
Head trauma and stroke 0.74 (0.44–1.24) .25 1.17 (0.60–2.30) .65
Cardiovascular disease 0.79 (0.38–1.64) .53 1.30 (0.55–3.09) .55
Respiratory disease 0.48 (0.27–0.85) .012 0.90 (0.45–1.79) .75
Infectious disease 0.79 (0.45–1.40) .42 1.36 (0.67–2.74) .39

APACHE-II = acute physiology and chronic health evaluation; CCI = Charlson comorbidity index; CI = confidence interval; HDU = high dependency unit;
HR = hazard ratio; ICU = intensive care unit; Trach = tracheostomy.

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 TABLE III.
Univariate and Multivariate Analyses of 60-Day Survival.
Early and Late Trach Analysis Landmark Analysis
HR (95% CI) P Value HR (95% CI) P Value

Univariate analysis
Early trach within day 10 0.83 (0.45–1.55) .56 0.89 (0.45–1.73) .71
Multivariate analysis
Early trach within day 10 0.88 (0.46–1.69) .71 0.88 (0.44–1.76) .72
Age 1.03 (1.00–1.06) .047 1.03 (1.00–1.05) .056
Sex 0.98 (0.52–1.87) .96 0.88 (0.47–1.64) .69
APACHE-II score 0.98 (0.94–1.03) .50 0.98 (0.94–1.02) .38
CCI 1.09 (0.95–1.26) .22 1.15 (1.00–1.32) .043
Main reason for ICU/HDU admission
Hypoxic encephalopathy 1 (reference) NA 1 (reference) NA
Head trauma and stroke 0.41 (0.11–1.50) .18 0.43 (0.10–1.76) .24
Cardiovascular disease 1.30 (0.37–4.54) .68 1.31 (0.35–4.96) .69
Respiratory disease 1.27 (0.45–3.60) .65 1.35 (0.42–4.34) .62
Infectious disease 1.77 (0.65–4.84) .27 1.58 (0.50–5.01) .44

APACHE-II = acute physiology and chronic health evaluation; CCI = Charlson comorbidity index; CI = confidence interval; HDU = high dependency unit;
HR = hazard ratio; ICU = intensive care unit; Trach = tracheostomy.

ICU/HDU and overall hospital admission durations, and surgery. Although our study reported no life-threatening
less medication use than the late tracheostomy group complications of tracheostomy, avoiding unnecessary
(Table IV). treatment is important in clinical practice.
In the landmark analysis, the ET group tended to Our approach is unique in that it uses two comple-
have better clinical outcomes, such as shorter hospital mentary analyses to reduce selection and immortal-time
admission duration, and less antibiotic use than the non- biases. In the early and late tracheostomy analysis, we
ET group; however, these differences did not reach statis- defined the time-to-event as the time from tracheostomy
tical significance. Patients in the ET group tended to have to the event, which reduced immortal-time bias. However,
fewer complications. No deaths were directly attributed this analysis did not include patients who did not
to complications arising from tracheostomy. undergo tracheostomy. To assess this, we sought to com-
pare the clinical outcomes among patients who were
intubated with or without tracheostomy. Therefore, we
DISCUSSION added the landmark analysis. Comparing outcomes
Several previous trials have evaluated the clinical between tracheostomy and nontracheostomy groups can
effect of early tracheostomy; however, the best timing for introduce selection bias for different factors from each
tracheostomy in patients requiring prolonged ventilation group; therefore, we included only the patients who
remains to be elucidated. Our analyses revealed that required ventilation until the landmark of day 10.
early tracheostomy within 10 days significantly decreased Patients who were successfully extubated or died soon
the degree of ventilation dependence at 60 days; however, after early tracheostomy were excluded. This reduced any
it did not improve 60-day survival. Our findings are con- biases caused by the time-dependent variable: the timing
sistent with previous reports. Furthermore, we argue that of tracheostomy. To the best of our knowledge, this is the
our analysis is less susceptible to bias, and therefore, first report to apply landmark analysis to investigate the
makes a significant contribution to the literature. effect of early tracheostomy. Furthermore, the primary
Prospective trials are hindered by uncertainty outcome of early tracheostomy was consistent in both
regarding inclusion criteria and lack of guidelines. In the analyses.
TracMan prospective trial, almost half of the patients In our analysis, early tracheostomy did not improve
assigned to the late tracheostomy (≥10 days) group were 60-day survival, which is consistent with the findings of
withdrawn from ventilation without tracheostomy.15 two RCTs and a meta-analysis.7,20,21 In contrast, another
Based on this result, if the groups were comparable, tra- RCT and two meta-analyses have shown a mortality ben-
cheostomy could have been avoided for half of the efit with early tracheostomy.6,14,19 Thus, the association
patients undergoing early tracheostomy (≤4 days). Simi- between early tracheostomy and improved survival
larly, a meta-analysis of 12 randomized controlled trials remains controversial.
(RCTs) showed a much higher tracheostomy rate in In the early and late analysis performed in the pre-
patients undergoing early tracheostomy (87% vs. 53%).19 sent study, early tracheostomy was significantly associ-
In these trials, the patients may have been excessively ated with shorter ICU/HDU and overall hospital stays,
treated and exposed to the complications related to this and reduced medication use. We expected that early

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 TABLE IV.
Clinical Outcomes of the Early and Late Tracheostomy and Landmark Analyses.
Early and Late Trach Analysis Landmark Analysis
Early Late ET Non-ET P
Variable Trach (n = 88) Trach (n = 132) P Value Group (n = 57) Group (n = 141) Value

Duration of trach, days, median (IQR) 7 (5–8) 15 (13–17) 7 (6–9) 15 (13–19)

Procedure
Open trach: number (%) 80 (91) 128 (97) .10 54 (95) 128 (91) .068
PDT: number (%) 8 (9) 4 (3) 3 (5) 4 (3)
VAP: number (%)† 11 (13) 23 (17) .36* 6 (11) 23 (16) .32*
ICU/HDU length of stay, days, median (95% CI) 13 (11–16) 20 (17–23) .01* 15 (12–19) 19 (17–21) .31*
Hospital length of stay, days, median (95% CI) 49 (42–58) 70 (62–78) .002* 58 (46–63) 70 (62–78) .07*
ICU/HDU mortality: number (%) 6 (7) 15 (11) .84* 4 (7) 17 (12) .43*
Hospital mortality: number (%) 16 (18) 36 (27) .74* 12 (21) 42 (30) .67*
Transferred to other hospital: number (%) 66 (75) 85 (65) .13 40 (70) 88 (62) .38
Discharged to home: number (%) 6 (7) 11 (8) .88 5 (9) 11 (8) 1
Days free of medication, 60-day, median (95% CI)
Sedatives‡ 53 (52–55) 45 (44–47) <.00001* 52 (50–53) 45 (44–47) .21
Opioidsk 56 (54–58) 51 (48–54) .008* 54 (53–55) 51 (48–54) .37
Antibiotics§ 47 (45–49) 41 (39–44) .009* 49 (43–NA) 44 (40–48) .068
All complications with trach: number (%) 7 (8) 22 (11) .13 7 (12) 24 (17) .80
Early complications with trach: number (%) 4 (4) 15 (11) .18 4 (7) 17 (10) .61
Infection 3 (3) 3 (2) 3 (5) 3 (2)
Minor necrosis 0 5 (4) 0 5 (4)
Minor bleeding 0 4 (3) 0 3 (2)
Major bleeding 1 (1) 3 (2) 1 (2) 3 (2)
Late complications with trach: number (%) 3 (3) 7 (6) .74 3 (5) 7 (5) 1
Granulation tissue 1 (1) 5 (4) 1 (2) 5 (4)
Ulceration 2 (2) 2 (2) 2 (3) 2 (1)

*P value was calculated using Kaplan-Meier curve and log-rank methods.

†
VAP was diagnosed clinically, not based on VAP criteria.
‡
Sedative medication included propofol, midazolam, and dexmedetomidine.
§
Opioid medication included fentanyl and ketamine.
k
Included antibiotics used for main disease.
CI = confidence interval; ET = early tracheostomy; HDU = high dependency unit; ICU = intensive care unit; IQR = interquartile range; PDT = percutaneous
dilational tracheostomy; Trach = tracheostomy; VAP = ventilation associated pneumonia.

tracheostomy would be associated with these outcomes in developed. In the present study, 28 of the 88 patients who
the landmark analysis also; however, the results were not underwent early tracheostomy were withdrawn from ven-
statistically significant. We hypothesize that the non-ET tilation within 10 days of intubation. We hypothesize that
patients in the landmark analysis who were ventilated the effectiveness of early tracheostomy in these patients
for a longer period required intensive care and medication may be limited. To avoid unnecessary early tracheostomy,
unrelated to early tracheostomy intervention. This sug- it is crucial to analyze the indicators for predicting longer
gests that the clinical benefits of early tracheostomy could ventilation requirements at the time of endotracheal intu-
not be demonstrated in the landmark analysis. Further- bation. By applying such tools prospectively, the effect of
more, in both analyses, the ET group tended to have early tracheostomy might be assessed more accurately.
fewer complications than late tracheostomy or the non- Our study has several limitations. First, we did not
ET group; however, these differences did not reach statis- adjust the tracheostomy timing HR for variables such as
tical significance. These outcomes might contribute to level of consciousness; ventilator status, such as ventila-
improvements in cost-effectiveness and quality of life. tor settings; and PaO2/FiO2 ratio in our multivariable
Further studies with validated outcome measures for analysis. We adjusted for APACHE-II score in our multi-
cost-effectiveness, quality of life, and tracheostomy com- variable analysis, which contained PaO2 and Glasgow
plications would be useful to evaluate the potential bene- Coma Scale parameters; however, we may have under-
fits of early tracheostomy. estimated the contribution of these or other variables.
Our findings demonstrated the effectiveness of early Second, the retrospective nature of this study may have
tracheostomy for critically ill patients who required pro- led to selection bias. We performed the landmark analysis
longed ventilation. However, a tool to prospectively pre- to avoid immortal-time bias; however, the analysis itself
dict the need for prolonged ventilation is yet to be is limited because patients were excluded to correct for

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Effect of early vs late tracheostomy placement on survival in patients
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