Early tracheotomy versus prolonged endotracheal
intubation in unselected severely ill ICU patients
(Electronic Supplementary Material)
François Blot, Thomas Similowski, Jean-Louis Trouillet, Patrick Chardon, JeanMichel Korach, Marie-Alyette Costa, Didier Journois, Guillaume Thiéry, Muriel
Fartoukh, Isabelle Pipien, Nicolas Bruder, David Orlikowski, Frédéric Tankere,
Isabelle
Durand-Zaleski,
Christian
Auboyer,
Gérard
Holzapfel, Alain Tenaillon, Jean Chastre, Agnès Laplanche
F. Blot (), Institut Gustave Roussy, Intensive Care Unit, Villejuif
1
Nitenberg,
Laurent
Patients and methods
Exclusion criteria:
Patients were excluded if they 1. had previously been enrolled in the trial; 2. had been
or were already tracheotomised; 3. had a major risk of bleeding (platelet count <50 000/mm3,
prothrombin time >1.5 times,...); 4. had a soft tissue infection of the neck; 5. had an
anatomical deformity of the neck; 6. had undergone a sternotomy <15 days; 7. were suffering
from well established chronic obstructive or restrictive respiratory insufficiency; 8. had an
irreversible neurological disease; 9. had post-trauma intra-cranial hypertension (intracranial
pressure > 20 cm H2O and/or cerebral oedema on head CT scan); 10. had a poor chance of
survival, as defined by a Simplified Acute Physiology Score (SAPS II [12]) of more than 80
points and/or a number of organ failures (OSF [13]) exceeding 4; or 11. if a decision had
been reached to limit care.
Ventilation, weaning and sedation protocol
In both groups, weaning off MV was conducted according to a strict study protocol.
Weaning criteria were defined as follows: improvement in or resolution of the underlying
cause of acute respiratory failure; SaO2>90% with a fraction of inspired oxygen (FiO2) <40%
and a positive end-expiratory pressure of <5 cm of water; a core temperature below 38°5C;
correction of electrolytic disorders; a good level of consciousness; and no further need for
high doses of vasoactive and sedative agents. Patients fulfilling these criteria underwent a
trial of spontaneous breathing lasting up to two hours, and were finally extubated (PI group)
or placed on a tracheotomy collar (ET group, or secondarily tracheotomised). If they met
poor tolerance criteria (respiratory rate > 35 per minute or increased by 50%, use of
accessory respiratory muscles, diaphoresis, heart rate or blood pressure increased by >20%
or alteration of consciousness), assist-control ventilation was first reinstituted and two
weaning strategies were proposed : daily T-piece trials or pressure support ventilation (PSV),
as recommended [14]. When weaning criteria were obtained, the patients were extubated or
2
placed on a tracheotomy collar. Even if there were no signs of distress by the end of this trial,
extubation could be postponed for a maximum of 24 hours if the primary physician felt a
patient might not be able to evacuate secretions or protect the airway against aspiration.
Weaning was considered to have failed if reintubation was necessary within 48 hours after
extubation, and a single episode of MV was recorded.
End-points and follow-up
The primary end-point was death at 28 days. Secondary end-points included d-28
incidence of ICU-acquired pneumonia, the duration of MV during the first 28 days, the day-60
mortality rate, hospital mortality rate, the total duration of MV, infectious complications (other
than pneumonia) during the first 28 days, early laryngeal and tracheal complications,
sedation requirements during the first 28 days and comfort of patients.
ICU-acquired pneumonia
Respiratory secretion samples were obtained at the attending physician’s request
when a new episode of ICU-acquired pneumonia was clinically suspected. Clinical suspicion
of pneumonia was based on classic criteria [19] (chest radiograph, fever, leukocytosis,
purulent tracheal secretions or gas exchange alterations ). The diagnosis of pneumonia was
established when clinical criteria were confirmed by positive quantitative cultures of
pulmonary secretion samples, obtained within 24 h of clinical suspicion : depending on the
investigator’s habits, bronchoalveolar lavage (significant threshold
104 colony-forming
units/mL) [20], protected specimen brush or catheter ( 103 colony-forming units/mL) [21, 22]
and quantitative tracheal aspirate ( 106 colony-forming units/mL) [23] were allowed. In
patients who could not provide pulmonary samples (e.g. unstable respiratory condition after
extubation or removal of the cannula), any introduction of antibiotics for 48 hrs or more for
suspicion of pneumonia (without another remote focus of infection) was considered as
possible pneumonia.
Infectious complications (other than pneumonia)
3
Episodes of bloodstream infections were recorded during the first 28 days. One
positive blood culture was required for the diagnosis of significant bacteraemia, except for
coagulase negative Staphylococci and other skin contaminants (for which two positive blood
cultures were required).
Stomal complications were recorded for patients who underwent an early or late
tracheotomy : local inflammation, significant infection at the stomal site, antibiotic
requirements, as well as haemorrhagic complications requiring blood transfusion or surgery.
Results
Outcome measures
Mechanical ventilation, endotracheal prosthesis: reintubation, secondary tracheotomy
and type of procedure
Tracheotomy offers the benefit of reconnecting the ventilator after spontaneous
breathing trial (SBT) failure. The number of reintubations was 15 in the PI group : 5 after
accidental extubation, 10 after a successful SBT, one half of which were secondarily
converted to tracheotomy.
Sixteen patients in the PI group were finally tracheotomised, three-fourths of them
after d14 as stipulated in the protocol (median [range] delay of 15 [5-32 days]). The
incidence of complications (pneumonia, maxillary sinusitis and bloodstream infections) was
compared between these patients and the 46 patients who did not undergo tracheotomy.
There was an increased incidence of each complication, but none was statistically
significant.
The number of complications was also examined between open and percutaneous
tracheotomy procedures. In the ET group, 19 had a percutaneous procedure and 41 a
surgical procedure (1 patient died before tracheotomy). The incidence of complications was
similar in these 2 subgroups.
4
Figure 3. Percentages of patients on mechanical ventilation during the first 28
days
100%
Tracheotomy
Intubation
80%
60%
40%
logrank, p = 0.54
20%
Days from randomisation
0%
At risk
at risk
0
4
8
61
62
57
59
50
53
12
36
41
16
29
33
5
20
23
25
24
18
21
28
15
16
Figure 4. Cumulative incidence of ICU-acquired pneumonia during the first 28
days
100%
80%
60%
40%
Tracheotomy
Intubation
20%
logrank, p = 0.94
Days from randomisation
0%
0
4
8
61
62
48
51
41
38
12
16
20
24
28
9
8
6
7
At risk
30
25
19
20
6
12
14
Figure 5. Random effects meta-analysis of relative risk (95% confidence interval) of mortality with early tracheotomy compared with
prolonged intubation.
Study
Bouderka et al 2004
Rodriguez et al 1990
Rumbak et al 2004
Saffle et al 2002
Blot et al 2008
Early tracheostomy
n/N
Late tracheostomy
n/N
12/31
9/51
19/60
4/21
21/61
7/31
13/55
37/60
6/23
20/62
224
Total (95% CI)
Total events: 65 (Early tracheostomy), 83 (Late tracheostomy)
Test for heterogeneity: Chi² = 9.17, df = 4 (P = 0.06), I² = 56.4%
Test for overall effect: Z = 0.73 (P = 0.47)
RR (random)
95% CI
17.26
17.95
28.14
11.14
25.52
231
100.00
0.1
0.2
0.5
Favours early
7
Weight
%
1
2
5
Favours late
10
RR (random)
95% CI
1.71
0.75
0.51
0.73
1.07
[0.78,
[0.35,
[0.34,
[0.24,
[0.65,
3.77]
1.60]
0.78]
2.23]
1.76]
0.85 [0.54, 1.32]
Figure 6. Random effects meta-analysis of relative risk (95% confidence interval) of hospital-acquired pneumonia with early tracheotomy
compared with prolonged intubation.
Study
Bouderka et al 2004
Dunham et al 1984
Rodriguez et al 1990
Rumbak et al 2004
Saffle et al 2002
Blot et al 2008
Early tracheostomy
n/N
Late tracheostomy
n/N
18/31
20/34
40/51
3/60
21/21
30/61
19/31
20/40
53/55
15/60
22/23
31/62
RR (random)
95% CI
Weight
%
14.88
14.59
24.30
3.43
26.10
16.70
258
271
Total (95% CI)
Total events: 132 (Early tracheostomy), 160 (Late tracheostomy)
Test for heterogeneity: Chi² = 24.58, df = 5 (P = 0.0002), I² = 79.7%
Test for overall effect: Z = 0.67 (P = 0.50)
100.00
0.1
0.2
0.5
Favours early
8
1
2
5
Favours late
10
RR (random)
95% CI
0.95
1.18
0.81
0.20
1.05
0.98
[0.63,
[0.77,
[0.70,
[0.06,
[0.96,
[0.69,
1.43]
1.79]
0.95]
0.66]
1.14]
1.40]
0.92 [0.73, 1.17]
Figure 7. Random effects meta-analysis of relative risk (95% confidence interval) of duration of mechanical ventilation in days, with early
tracheotomy compared with prolonged intubation.
Study
N
Bouderka et al 2004
Rodriguez et al 1990
Rumbak et al 2004
Saffle et al 2002
Blot et al 2008
31
51
60
21
61
Early tracheostomy
Mean (SD)
14.50(7.30)
12.00(7.14)
7.60(4.00)
35.50(20.62)
16.00(9.00)
224
Total (95% CI)
Test for heterogeneity: Chi² = 53.28, df = 4 (P < 0.00001), I² = 92.5%
Test for overall effect: Z = 1.96 (P = 0.05)
N
31
55
60
23
62
Late tracheostomy
Mean (SD)
WMD (random)
95% CI
17.50(10.60)
32.00(22.25)
17.40(5.30)
31.40(24.94)
16.00(8.00)
21.63
19.79
23.82
11.77
23.00
231
100.00
-100
-50
Favours early
9
Weight
%
0
50
Favours late
100
WMD (random)
95% CI
-3.00
-20.00
-9.80
4.10
0.00
[-7.53, 1.53]
[-26.20, -13.80]
[-11.48, -8.12]
[-9.38, 17.58]
[-3.01, 3.01]
-6.46 [-12.91, 0.00]
Table 5. Characteristics of Mechanical Ventilation and Organ System Failures at the time of
randomisation, n (%)
Previous episode of MV:
invasive / noninvasive MV
Causes of MV :
Respiratory failure
- ARDS
- Pneumonia
- Cardiogenic pulm.oedema
- COPD
- thoracic trauma
- other
Haemodynamic failure
Neurological Failure
Cardiac arrest
Intubation route :
oral / nasal route
Radiological score
PaO2/FiO2 *
PaCO2 (mmHg) *
PEEP cmH20 *
Antibiotic or antifungal therapy
Duration* of MV at the time of
randomisation (days) :
Number of organ failures
1
2
3
4
Type of organ failures
- respiratory
- circulatory
- neurological
- renal
- haematological
- hepatic
SAPS II*
* median (range)
10
Early
tracheotomy
(n=61)
11 (18)
6 /6
49 (80)
13
9
2
4
9
12
27 (44)
27 (44)
0
58 / 3
4
208
38
6
46
(95 / 5)
(0-10)
(47-660)
(24-73)
(2-12)
(75)
2 (0-4)
Prolonged
intubation
(n=62)
10 (16)
6 /5
51
11
14
0
4
8
14
24
27
3
57 / 5
5
184
41
6
50
(82)
(39)
(44)
(5)
(92 / 8)
(0-12)
(63-465)
(23-72)
(2-16)
(81)
2 (0-4)
10
31
13
7
(16)
(51)
(21)
(11)
12
31
17
2
(19)
(50)
(27)
(3)
61
31
26
14
4
3
47
(100)
(51)
(43)
(23)
(7)
(5)
(19-76)
62
29
23
13
2
4
43
(100)
(47)
(37)
(21)
(3)
(6)
(19-80)
Table 6 : Tracheotomy characteristics of patients with early tracheotomy or prolonged
intubation, n (%)
Early
tracheotomy
(n=61)
60 (98)
Prolonged
intubation
(n=62)
16 (26)
Tracheotomy 1
Time between randomisation and
tracheotomy (days) *
0 (0-6)
15 (5-32)
0-2
58
0
3-6
22
2
7 - 28
0
10
29 - 60
4
Cause of tracheotomy
Randomisation arm
60 (100)
Extubation failure
3 (19)
Prolonged MV
11 (69)
Other
2 (12)
Procedure performed in the:
Intensive care unit
52 (87)
13 (81)
Operating room
8 (13)
3 (19)
Operator
Intensivist
37 (62)
11 (69)
Surgeon / ENT
23 (38)
5 (31)
Technique
Surgical
41 (68)
9 (56)
Percutaneous
19 (32)
7 (44)
* median (range)
1
Early tracheotomy group: 1 death before tracheotomy
Intubation group: 16 delayed tracheotomies (12 within the first 28 days, 4 between d28
and d60)
2
One patient was successfully tracheotomised on d6 (2nd attempt)
11
Table 7 (3-bis). Late airway assessment of patients with early tracheotomy or prolonged
intubation
Early tracheotomy
(n=61)
Late assessment (two months) : alive pts
Late assessment performed
At least one symptom *
- Swallowing troubles
- Dysphonia
- Laryngeal dyspnea
- Tracheal dyspnea
Laryngeal examination performed
At least one sign
- Abnormal arytenoid mobility
- Abnormal vocal cord mobility
- Laryngeal oedema
- Post-intubation laryngeal granuloma
- Post-intubation vocal cord ulceration
Tracheal examination performed
At least 1 sign (stenosis and granuloma)
* Chi-2 : NS
** (n): severe complications;
12
43
13
1
0
1
0
0
13
3
1
1
2
0
1
5
1
(30%)
(8%)
(30%)
(25%)
(12%)
(20%)
Prolonged
intubation
(n=62)
43
12
7
2
5
0
0
12
3
0
0
2
1
0
2
0
(28%)
(58%)
(1) **
(28%)
(25%)
(1) **
(5%)
(0%)