Supplemental Digital Content Title: Effect of early versus late tracheostomy or prolonged intubation in critically ill patients with acute brain injury: A systematic review and meta-analysis Authors: Victoria A. McCredie, MBChB 1 ; Aziz S. Alali, MD, PhD 2 ; Damon C. Scales, MD, PhD 1,2 ; Neill K. J. Adhikari, MDCM, MSc 1,2 ; Gordon D. Rubenfeld, MD, MSc 1,2 ; Brian H. Cuthbertson, MBChB, MD 1,2,3 ; Avery B. Nathens, MD, PhD 2,4 Supplemental Digital Content – Search strategy Supplemental Digital Content – Data extraction sheet Supplemental Digital Content –Table 1. Summary of characteristics of excluded studies from meta-analysis Supplemental Digital Content –Table 2. List of authors contacted Supplemental Digital Content –Table 3. Ongoing trials for timing of tracheostomy in Neurocritically ill patients Supplemental Digital Content – Table 4. Patient characteristics of included studies Supplemental Digital Content –Table 5. Definitions Supplemental Digital Content – Table 6. Risk of bias table Supplemental Digital Content – Fig. 1. Risk of bias summary Supplemental Digital Content – Table 7. Summary of Results Supplemental Digital Content – Fig. 2. Short-term mortality Supplemental Digital Content – Fig. 3. Hospital mortality
Transcript
Supplemental Digital Content
Title: Effect of early versus late tracheostomy or prolonged intubation in critically ill patients with acute brain injury: A systematic review and meta-analysis
Authors: Victoria A. McCredie, MBChB1; Aziz S. Alali, MD, PhD2; Damon C. Scales, MD, PhD1,2; Neill K. J. Adhikari, MDCM, MSc1,2; Gordon D. Rubenfeld, MD, MSc1,2; Brian H. Cuthbertson, MBChB, MD1,2,3; Avery B. Nathens, MD, PhD2,4
Supplemental Digital Content – Search strategy
Supplemental Digital Content – Data extraction sheet
Supplemental Digital Content –Table 1. Summary of characteristics of excluded studies from meta-analysis
Supplemental Digital Content –Table 2. List of authors contacted
Supplemental Digital Content –Table 3. Ongoing trials for timing of tracheostomy in Neurocritically ill patients
Supplemental Digital Content – Table 4. Patient characteristics of included studies
Supplemental Digital Content –Table 5. Definitions
Supplemental Digital Content – Table 6. Risk of bias table
Supplemental Digital Content – Fig. 1. Risk of bias summary
Supplemental Digital Content – Table 7. Summary of Results
Supplemental Digital Content – Fig. 2. Short-term mortality
Supplemental Digital Content – Fig. 3. Hospital mortality
Supplemental Digital Content- Fig. 4. ICU mortality
Supplemental Digital Content- Fig. 5. Number of tracheostomy procedures performed
Supplemental Digital Content- Fig. 6. Laryngotracheal complications
Supplemental Digital Content- Fig. 7. Duration of mechanical ventilation
Supplemental Digital Content – Fig. 8. ICU length of stay
Supplemental Digital Content – Fig. 9. Ventilator-associated pneumonia
Supplemental Digital Content- References
Supplemental Digital Content – Search strategyThe following tables record the search strategies and terms used in each of the databases. Search results were limited to randomized and quasi-randomized controlled trials to include articles indexed from the inception of each of the databases to the third week of April 2015.
MedlineSet
History Results Comments
1 randomized controlled trial.pt. or randomized.mp. or placebo.mp.
606500 Haynes BMJ 2005 top optimizing sensitivity and specificity filter used. Also tried Cochrane HSS 2008 strategy (less articles), and Haynes highest sensitivity filter (resulted in articles up to 4600 rather than 466). Gap analysis reveals this search strategy with optimization, rather than Haynes highest sensitivity filter search, doesn’t miss any known RCTs, also tried AND NOT Boolean term- no difference
2 exp Tracheostomy/ or tracheo?tom*.af.
19672 Tracheostomy term with wild card and explosion and truncation. Tried longer versions, again no difference in sensitivity with this short line.
Base clinical set3 1 and 2 468 FINAL Results
EMBASE Set
History Results Comments
1 tracheo?tom*.af. 34450 Tracheostomy with truncation and wild card, search all fields
Base Clinical set2 random:.tw. or placebo:.mp. or
double-blind:.tw. 1188127
RCTs with Wong 2006 filter
3 1 and 2 1083 Final results
CENTRALSet
History Results Comments
1 tracheo?tom* in Trials (Word variations have been searched)
346 Tracheostomy with truncation and wild card, search all fields
Base Clinical set2 MeSH descriptor: [Tracheostomy]
explode all trees177 Trach MESH term
3 1 and 2 346 Final results
Web of ScienceSet
History Results Comments
1 TI=(tracheostom* OR tracheotom*) 4,705 Tracheostomy with truncation, search TITLE only
Base Clinical set2 TS=(random* OR clinical trial* OR
"health care quality" OR "healthcare quality")
1,401,478
RCTs, search all text
3 1 and 2 246 Final resultsIndexes=SCI-EXPANDED, CPCI-S Timespan=All years
SCI-EXPANDED =Science Citation IndexCPCI-S = Conference Proceedings Citation Index
CINAHLSet
History Results Comments
1 TX tracheostomy Tracheostomy text anywhere
2 TX tracheostomies Tracheostomies text anywhere
3 TX randomized controlled trial RCT text anywhere4 TX clinical trial* Clinical trial text anywhere5 S1 OR S2 Base Clinical set6 S3 OR S4 Base study design7 S5 AND S6 132 Final resultsTX= text anywhere*= truncation
Supplemental Digital Content – Data extraction sheet
StudyDate of study yearCountryJournal published inReviewerAuthor (last name)Author’s contact details:
Action: contact author for-Multi-Center Single-CenterPARTICIPANTS (ABI= acute brain injury)ICU setting/ patient populationBrain injury types:e.g. traumatic brain injury, aneurysmal subarachnoid hemorrhage, ischemic stroke, spontaneous intracranial hemorrhage, post-craniotomy, global cerebral anoxia, status epilepticus, meningitis, encephalitis, or cerebral abscessN (%) Total ABI Early LateAge Mean (SD) Total ABI Early LateGender (female %) Total ABI Early LateType of tracheostomy n/N (%)
Percutaneous Surgical
Any statistical differences at baseline between groups?
INTERVENTIONSEarly tracheostomy timing (state whether day 0 or 1= intubation or ICU admission)Actual time of trach placement in EarlyMean (SD)/Median (IQR)Late tracheostomy timing (state whether day 0 or 1= intubation or ICU admission)Actual time of trach placement in LateMean (SD)/Median (IQR)
OUTCOMESSTUDY’s primary outcome: STUDY’s secondary outcome:Primary outcome for this systematic review Long-term mortality Early N (%) Late N (%)
Number of patients providing relevant dataTiming:Hospital discharge 6 months1 year Other______________
(Tick below)
Secondary outcomes 1. ICU mortality Early N (%) Late N (%)
Number of patients providing relevant data2. Hospital mortality Early N (%) Late N (%)
Number of patients providing relevant data3. Duration of MV (days) Early Median (IQR) Late Median (IQR)
Number of patients providing relevant data
4. Actual number of patients receiving tracheostomy
Early N (%) Late N (%)
Number of patients providing relevant data5. Duration of sedation (days) Early Median (IQR) Late Median (IQR)
Number of patients providing relevant data6. Length of stay in ICU (days) Early Median (IQR) Late Median (IQR)
Number of patients providing relevant data7. Length of stay in hospital (days) Early Median (IQR) Late Median (IQR)
Number of patients providing relevant data8. Hospital-associated pneumonia at any time point
Early N (%) Late N (%)
Number of patients providing relevant data9. Total tracheostomy complications Early N (%) Late N (%)
Number of patients providing relevant data10. Tracheostomy bleeding at any time point
Early N (%) Late N (%)
Number of patients providing relevant data11. Laryngotracheal injury at any time point (Epiglottis, vocal cords, larynx, subglottic
Early N (%) Late N (%)
ulceration, inflammation)
Number of patients providing relevant data
METHODOLOGICAL QUALITY OF STUDY (Higgins BMJ 2011)
RISK OF SELECTION BIAS (Low risk of bias of both random sequence generation and allocation concealment necessary to categorize trial as low risk of selection bias)Random sequence generationWas the random allocation sequence adequately generated?
Supplemental Digital Content –Table 2. List of authors contacted
Author’s name Reason for contact Response
Blot(13) Requested subgroup data Supplied subgroup dataTerragni(14) Requested subgroup data Supplied subgroup dataYoung(15) Requested subgroup data Supplied subgroup dataKoch(6) Requested subgroup data Replied, but no data suppliedRodriguez(11) Requested subgroup data Replied, but no data suppliedZheng(5) Requested subgroup data No reply
Bösel (16) Requested further details on continuous outcomes for meta-analysis
Supplied means and standard deviations for continuous data
Fayed(17) Requested further details (abstract only available) Provided provisional unpublished manuscript
Barquist(18) Requested further details on severity and number of TBI patients included, timing of mortality outcome (ICU, hospital or longer-term)
No reply
Bouderka(19) Requested further details on timing of mortality outcome (ICU, hospital or longer-term)
No reply
Mohamed(20) Requested further details to assess risk of bias No replyPriyamvadha(7)
Requested further details (abstract only available) No reply
Sabouri(3) Requested further details on mortality outcomes (no mortality outcomes reported in abstract)
No reply
Sugerman(21) Requested additional information on TBI subgroup, timing of mortality outcome (ICU, hospital or longer-term)
Replied, but not in possession of the primary data
Shaded rows indicate where authors supplied data.
Supplemental Digital Content –Table 3. Ongoing trials for timing of tracheostomy in neurocritically ill patients
Principal investigator
Year trial started
Title of trial Current status
Dr. Julian Bösel
2015 Early Tracheostomy in Ventilated Stroke Patients 2 (SETPOINT2) (NCT02377167)
This study is currently recruiting participants. Estimated completion year 2018.
Dr. Juliet Nalwoga
2015 Early Tracheostomy Versus Standard of Care in Patients With Severe Head Injury (E-Trac) (NCT02442154)
This study is not yet open for participant recruitment.
Dr. Hagen B Huttner
2010 WEANING-Study: "Weaning by Early Versus lAte Tracheostomy iN supratentorIal iNtracerebral Bleedings” (NCT01176214)
Terminated in 2014 (slow recruitment of patients)
Dr. Russel Daumire
2006 A Prospective, Randomized Trial of Early Versus Late Tracheostomy in Trauma Patients With Severe Brain Injury (NCT00292097)
Terminated in 2008 (Difficulty obtaining enrollment)
Supplemental Digital Content – Table 4. Patient characteristics of included studies
aDue to a slow accrual rate of appropriate patients, the study was terminated early.bDemographics for all patients in early tracheostomy group (n=20), five patients had renal failure (n=3) or respiratory failure (n=2).cDemographics for all patients in the late tracheostomy group (n=20), eight patients had renal failure (n=3), respiratory failure (n=4) or tetanus (n=1).dPatients were included in the study if APACHE II ≥15.eAfter an independent Data Monitoring and Ethics Committee reviewed unblinded data from an interim analysis using the Haybittle-Peto boundary rule (the study would continue unless the primary outcome was different between the groups at P < .001 at interim analysis), the trial was terminated early due to study fatigue indicated by a
Study Type of T,N (%)
Age in years,mean (SD) or median (IQR)
Female, (%) Disease severity,mean (SD) or median (IQR)
decreasing average-per-center recruitment rate. The a priori planned sample size was not achieved; the final sample of 899 patients available for analysis of the primary outcome had the power to detect an 8.3% absolute change in 30-day mortality from the “late” group value of 31.5% with 80% power.fData only available for entire study cohort, rather than acutely brain-injured patients only.gData extracted from the published abstract and provisional unpublished manuscript supplied by the corresponding author. Data was taken from Group II (20 patients to where percutaneous endoscopic gastrostomy was placed within 24 hours and patients remained intubated via translaryngeal route) and Group III (20 patients where tracheostomy and percutaneous endoscopic gastrostomy were placed within 24 hours of endotracheal intubation).hThe study was halted after the first interim analysis as no significant difference was found between groups in any of the outcome parameters. iData not reported for actual proportions for tracheostomy types.jNo statistically significant difference between the compared groups according to the authors of this trial.APACHE, Acute Physiology and Chronic Health Evaluation; GCS, Glasgow Coma Scale; IGS, Indice de Gravité Simplifié; ITT, intention-to-treat; IQR, inter-quartile range; ISS, injury severity score; ET, early tracheostomy; LT, late tracheostomy; N, number of patients; NR, not reported; PI, prolonged intubation; PT, percutaneous tracheostomy; SAPS, Simplified Acute Physiology Score; SD, standard deviation; ST, surgical tracheostomy; T, tracheostomy.
Supplemental Digital Content –Table 5. Definitions
Term DefinitionAcutely brain injured patient Adults with traumatic brain injury, aneurysmal subarachnoid
hemorrhage, ischemic stroke, spontaneous intracranial hemorrhage, post-craniotomy, global cerebral anoxia, status epilepticus, meningitis, encephalitis, or cerebral abscess cared for in the critical care unit.
Critically ill patient Adults cared for in the critical care unit, with a disease or in a state in which death is possible or imminent.
Duration of mechanical ventilation
Total duration of mechanical ventilation (i.e., both before and after tracheostomy).
Percutaneous tracheostomy Tracheostomy without direct surgical visualization of the trachea based on: 1) needle-guide wire airway access followed by serial dilations with sequentially larger dilators; 2) guide wire dilating forceps.
Surgical tracheostomy Tracheostomy performed by surgeons in the operating room using an open technique.
Tracheostomy-related complications
Refers to both intraoperative (bleeding, tube dislocation, hypoxemia, arrhythmia, and cardiac arrest) and postoperative (bleeding, stoma infection, stoma inflammation, pneumothorax, subcutaneous emphysema, tracheal stenosis, tracheoesophageal fistula and cannula displacement) complications. Not all the patients in each trial were analyzed for this outcome, only those who actually underwent tracheostomy. For trials that did not report on the number of patients who actually underwent tracheostomy, we considered that all included patients received a tracheostomy.
Tracheostomy-related bleeding
It refers to both intraoperative and postoperative bleeding and can be either minor (i.e., not requiring blood transfusion) or major (i.e., requiring transfusion of at least 1 unit of packed red cells). Not all the patients in each trial were analyzed for this outcome, only those who actually underwent tracheostomy. For trials that did not report on the number of patients who actually underwent tracheostomy, we considered that all included patients received a tracheostomy.
Ventilator-associated pneumonia
Barquist(18)CDC criteria were used for the diagnosis of pneumonia including:(23)
Elevated white blood cells (WBC), fevers CXR infiltrate Broncho-Alveolar Lavage (BAL) culture with greater than
10,000 colony-forming units per milliliter (CFU/mL)
Blot(13) Respiratory samples were obtained when a new episode of ICU-acquired pneumonia was clinically suspected. The diagnosis of pneumonia was established by positive quantitative cultures of pulmonary secretion samples obtained within 24 hours of clinical suspicion.(24) Either BAL (significant threshold 104 colony-forming
units/mL), protected specimen brush or catheter (103 colony-forming units/mL), and quantitative tracheal aspirate (106 colony-forming units/mL) were allowed.
Bourderka(19)The diagnosis of pneumonia was by CDC criteria.(23)
Dunham(22) Not explicitly referenced, pneumonia diagnosis aligned with CDC criteria. Patients were assessed daily for a CXR infiltrate (new, persistent, or progressive), abnormal WBC (<4,000 or >11000, or immature neutrophils >=10%), abnormal temp (> 101.2 or <97.6), and P/FO2<240. Ventilator-associated pneumonia (VAP) was suspected if the following criteria were met:
CXR infiltrate or P/FO2 <240 Purulent tracheal secretions or abnormal WBC or abnormal
temp.When suspicion for VAP was present, a BAL was performed and empiric antimicrobial therapy was initiated. The patient was considered to have VAP if the lavage result demonstrated bacteria with ≥ 104 colony-forming units per mL.
Fayed(17)VAP was diagnosed if a new and persistent infiltrate developed on the chest X-ray and at least two of the following criteria were fulfilled:(25)
Fever, an increase of > 1°C or core temperature > 38.3 °C Leukocytosis, 25% increase in leukocytic count from baseline
and an absolute count of >10,000 mm3 or leucopenia, 25% decrease in leukocytic count from baseline and an absolute count<4,000 mm3
Purulent tracheal aspirate, >25 neutrophils per high power field on gram stain.
Sugerman(21)Not explicitly referenced, pneumonia diagnosis aligned with CDC criteria. The diagnosis of pneumonia required all of the following:
WBC count > 11,000 or > 30% band (or more immature) forms regardless of WBC count
Temperature > 101°F New or worsening consolidation on chest radiograph Positive sputum culture for pathogens
Supplemental Digital Content – Table 6. Risk of bias tableSelection bias Detection bias Attrition bias Reporting bias
Dunham 2014(22) Unclear riskInsufficient information to permit judgment of 'low risk'.
Unclear riskInsufficient information to permit judgment of 'low risk'.
High riskAuthors excluded patients who violated the protocol from the study (from outcome reporting and analysis).
Low risk
Mohamed 2014(20)
Unclear riskCan't adequately assess, authors did not mention how random sequence was generated. Authors don’t mention if/how allocation was concealed.
Unclear riskCan't adequately assess, authors did not mention whether assessors were blinded to intervention allocation.
Unclear riskNot clear how much missing data was there and how they dealt with it.
Unclear riskNot clear if there was missing data and not clear how they defined certain outcomes like VAP.
Insufficient information to permit judgment of 'low risk'.
Unclear riskInsufficient information to permit judgment of 'low risk'.
Unclear riskMortality was recorded for patients until hospital discharge or death, whichever came first, for a maximum of 6 months. No data on follow-up for patients discharged before 6 months or death after discharge.
Authors mentioned envelopes but do not specify whether they were opaque and where envelopes were kept.
Unclear riskUnclear from study details.
Unclear riskNot enough information provided to assess properly.
Unclear riskMortality was not well defined; unclear if ICU or hospital mortality, or longer term mortality.
Bouderka 2004(19)
Unclear riskUnclear from study details.
Unclear riskUnclear from study details.
Unclear riskInsufficient reporting of attrition/exclusions to permit judgment of ‘low risk’ or ‘high risk’.
Low risk
Sugarman 1997(21)
Unclear riskUnclear if envelopes were unsealed, non-opaque, or sequentially numbered.
Unclear riskInsufficient information to permit judgment of ‘low risk’.
High riskAuthors reported that 29 patients out of 155 (19%) had missing outcome data.
High riskAuthors mentioned in the discussion that some centers entered the study and enrolled patients but failed to send completed data forms for unknown reasons.
Lori Lynn L Reinstrom, 2016-08-24,
“or” death after discharge ???
Blinding of participants and personnel was not feasible in any trial. In six trials, no information was provided on whether the data collectors
were blinded to allocation (17-22). However, we considered trials to have an overall low risk of detection bias since mortality is an objective
outcome and unlikely to be influenced by lack of blinding (26). Two studies were considered to have a high risk of attrition bias due to the
amount, nature, or handling of incomplete outcome data (21, 22). In one trial, the authors excluded patients if the study protocol was violated
(2/30 patients randomized in the intervention group and 5/30 in the control group) (22). The other trial reported missing outcome data in 19%
of patients (29/155), where a number of centers entered patients but failed to send the completed data forms (21). The authors comment there
could have been bias in withholding data or forms of patients who failed to do well in either arm of the study, and so we assigned this study a
high risk of reporting bias.
Supplemental Digital Content – Fig. 1. Risk of bias summary
Supplemental Digital – Table 7. Summary of results
Study
Actual number that received T, n/N (%)
Short-term mortality, n
(%)
ICU mortality,
n (%)
Hospital mortality,
n (%)
Long-term mortality, n
(%)
Ventilator- associated
pneumonia,n (%)
Duration of MV, mean days
(SD)
Duration of sedation,
median days (IQR)
ICU LOS, mean days
(SD)
Laryngotracheal
complications,n (%)
ET LT/PI ET LT/PI ET LT/PI ET LT/PI ET LT/PI ET LT/PI ET LT/PI ET LT/PI ET LT/PI ET LT/PI
Dunhama
2014(22) 17/17 (100%)
11/14 (79%)
0/17 (0%
)b
1/14 (7%)b
7/15 (47%)b
4/9(44%)b
14.1 (5.7)b
17(5.4)b
Mohamed2014(20) NR NR 7/15
(47%)c4/9
(44%)c
Böseld
2013(16) 30 /30 (100%)
18/30e
(60%)3/30
(10%)14/30 (47%)
8/30 (27%
)f
18/30 (60%
)f
14.9 (5.1)g
15.5 (8.9)g
42% of ICU stay
62% of ICU stay
17.6 (7.4)g
18.6 (17.1
)g
1/30 (3%)
2/30 (6%)
Youngh
2013(15) 19/21 (90%)
6/14 (43%)
3/21 (14%)
3/14 (21%)
7/21 (33%)
5/14 (36%)
9/21 (43%)i
7/14 (50%)i
6.2 (4.8)
14.4 (15.4) 3 (1-7) 4
(2-5)12.9 (7.7)
16.5 (10.5)
Fayedj 2012(17) 20/20
(100%) NAk 3/20 (15%)l
7/20 (35%)l
3/20 (15%
)
8/20 (40)
5.4 (4.5)**
10.6 (5.8)**
13.2 (3.6)**
17.7 (8.5)**
16/20m
(80%)
0 /20 (0%)
Terragni2010(14) 33/48
(69%)33/54 (61%)
9/48 (19%)n
17/54 (31%)n
9/48 (19%)n
17/54 (31%)n
10.2 (7.5)
12.6 (7.5)
17.2 (9.6)
18 (8.8)
Blot2008(13) 9/9
(100%)3/13
(23%)5/9
(56%)o 0/13 (0%)o 5/9 (56%)o
0/13 (0%)o
3/9(33%)
9/13(69%)
14.3 (8.4) 16.3 (10) 64 (99) 38
(30.8)
Barquistp
2006(18) 27/29 (93%)
11/31(36%)
2/29 (7%)q
5/31 (16%)q
28/29 (97%) 28/31
(90%)
8.6 (7.9)r,s
8.8(9)r,s
1/29t
(3%)0/31t
(0%)
Bouderka 2004(19) 31/31
(100%) NAk12/31 (39%
)q
7/31 (23%)q
18/31(58%
)u
19/31(61%
)u
14.5 (7.3)v
17.5(10.6)v
8/31(26%)w
5/31(16%)x
Sugarman 1997(21) 35/35
(100%)25/32 (78%)
5/35 (14%
)q
1/32 (3%)q
17/35 (49%)
17/32(53%)
16(5.9)s
19(11.3
)s
aDue to a slow accrual rate of appropriate patients, the study was terminated early.bAuthors excluded patients from analysis and outcome reporting who violated the study protocol, leaving 15 patients in the early group (1 patient didn’t follow protocol and received no bronchoalveolar lavage [BAL] for pneumonia diagnosis, and 1 patient had a C2 fracture needing early tracheostomy) and 9 patients analyzed in late group (2 patients didn’t follow the protocol to receive a BAL, and 3 patients did not receive the intervention [tracheostomy] as 1 expired prior to intervention and 2 improved
Lori Lynn L Reinstrom, 08/24/16,
Data is difficult to read because font is so small
and did not require a tracheostomy). For our primary mortality analysis in our review, we used ITT principle with 0/17 in the early group and 1/14 in the late group. For the VAP analysis, we used PP with 7/15 in the early group and 4/9 in the late group. The proportion of missing outcomes in the late group compared with the early group may be enough to induce clinically relevant bias in intervention effect estimate.cAuthors did not provide outcome data for all of the acutely brain injured patients (Table 2 in the manuscript states there were 15 patients in the early group and 12 patients in the late group.) Two patients are missing in the early group and 4 patients from the late group in Table 4b, reporting the mortality for the multivariate analysis for mortality, tracheostomy timing & diagnosis on ICU admission. For our primary mortality analysis, we used ITT principle with 7/15 in the early group and 4/9 in the late group.dICU death was predominantly related to refractory brain injury complications such as rebleeding, vasospasms, or secondary infarctions, eventually leading to intractable increases in intracranial pressure (ICP) and herniation.eTwelve patients in the late tracheostomy/prolonged intubation group died before tracheostomy (not included for analysis of time to tracheostomy and decannulation).fMortality at 6 months. Two patients in each group were lost to follow-up.gThe mean and standard deviation were calculated from the original data via personal communication with the main author, Dr Julian Bösel (data not published in original article).hDue to study fatigue the planned sample size was not achieved.iMortality at 1 year.jData extracted from the published abstract and provisional unpublished manuscript supplied by the corresponding author.kNo mention in manuscript whether any of the prolonged intubation patients received a late tracheostomy.lMortality was recorded for patients after the first 3 weeks until hospital discharge or death, whichever came first, for a maximum of six months. No mention of follow-up for patients discharged before 6 months for death after discharge.mTwenty-four total laryngotracheal complications occurred in the 20 patients in the early group, including tracheostomy infection (n=16), pneumothorax (n=3), and tracheoesophageal fistula (n=5). We used a conservative estimate of 16, assuming multiple complications could occur in any one patient.nMortality at 28 days.oMortality at day 60.pThe study was halted after the first interim analysis as no significant difference was found between groups in any of the outcome parameters. qPresumed short-term mortality.rVentilator- free days at 30 days, no mention of how patients that die in ICU are censored.sAuthors reported standard error of the mean; this was converted to standard deviations using the standard formula (SD=SEM x √n).tNumber of patients providing relevant data not specified.uNosocomial pneumonia.vPresumed standard deviation, not formally identified in study.wTwo stomal bleeds, 5 stomal infections, and 1 tracheal stenosis treated surgically.xFive inflammatory granulomas, treated with steroids.** Presumed study reported standard errors of the mean. We calculated the standard deviations and used these values in the pooled analysis. Duration of MV (mean days) in early vs late group: 5.4 (SEM 1) vs 10.6 (SEM 1.3) = 5.4 (SD 4.5) vs 10.6 (SD 5.8). ICU LOS (mean days) in early vs late group: 13.2 (SEM 0.8) vs 17.7 (SEM1.9) = 13.2 (SD 3.6) vs 17.7 (SD 8.5).
N, number of patients; T, tracheostomy; ET, early tracheostomy; LT, late tracheostomy; PI, prolonged intubation; NR, not reported; NA, non-applicable; MV, mechanical ventilation; ICU, intensive care unit; LOS, length of stay; SD, standard deviation; IQR, interquartile range.
Supplemental Digital Content – Fig. 2. Short-term mortality Random-effects meta-analysis of early tracheostomy versus late tracheostomy or prolonged intubation on short-term, expressed as the risk ratio (RR), with values more than 1 indicating increased mortality with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s RR. The diamond signifies the pooled RR for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall RR. Young et al. measured mortality at 1 year, Bösel et al. measured at 6 months, and Fayed et al. recorded mortality until hospital discharge or death (whichever came first) for a maximum of 6 months. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Supplemental Digital Content – Fig 3. Hospital MortalityRandom-effects meta-analysis of early tracheostomy versus late tracheostomy or prolonged intubation on in-hospital mortality, expressed as the risk ratio (RR), with values more than 1 indicating increased mortality with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s RR. The diamond signifies the pooled RR for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall RR. Blot, mortality at 60 days. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 3.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 2?Change “Favours” to “Favors”? (Depends upon if this is a reprint w/ permission.) This holds true for all figures.
Lori Lynn L Reinstrom, 08/24/16,
Move to top of page if material above is Fig. 2.
Supplemental Digital Content – Fig. 4. ICU mortalityRandom-effects meta-analysis of early tracheostomy versus late tracheostomy or prolonged intubation on ICU mortality, expressed as the risk ratio (RR), with values more than 1 indicating increased mortality with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s RR. The diamond signifies the pooled RR for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall RR. ICU mortality was a composite of ICU mortality or 28-day mortality. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Supplemental Digital Content – Fig. 5. Number of tracheostomy procedures performedEffect of early tracheostomy versus late tracheostomy or prolonged intubation on the proportion of patients undergoing the procedure, expressed as the risk ratio (RR), with values more than 1 indicating a higher proportion of tracheostomies performed with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s RR. The diamond signifies the pooled RR for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall RR. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Lori Lynn L Reinstrom, 2016-08-24,
Is this correct?
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 5.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 4?
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 4.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 3?
Supplemental Digital Content – Fig. 6. Laryngotracheal complicationsEffect of early tracheostomy versus late tracheostomy or prolonged intubation on laryngotracheal complications, expressed as the risk ratio (RR), with values more than 1 indicating increased laryngotracheal complications with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s RR. The diamond signifies the pooled RR for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall RR. Fayed et al. trial reported a total of 24 laryngotracheal complications in the early tracheostomy group (20 patients) including tracheostomy infection (16 patients), pneumothorax (3 patients), and tracheoesophageal fistula (5 patients), but we were unable to ascertain the total number of patients with any complication in the early group. We used a conservative estimate of 16, assuming multiple complications could occur in any one patient (17). ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Supplemental Digital Content – Fig. 7. Duration of mechanical ventilation
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 7.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 6?
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 6.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 5?
Random-effects meta-analysis of early tracheostomy versus late tracheostomy or prolonged intubation on duration of mechanical ventilation, expressed as the mean difference (MD) in days, with values more than 0 indicating increased duration with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s MD. The diamond signifies the pooled MD for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall MD. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Supplemental Digital Content – Fig. 8. ICU length of stayRandom-effects meta-analysis of early tracheostomy versus late tracheostomy or prolonged intubation on length of stay in ICU, expressed as the mean difference (MD) in days, with values more than 0 indicating increased length of stay with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s MD. The diamond signifies the pooled MD for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall MD. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 8?
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 8.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 7?
Supplemental Digital Content – Fig. 9. Ventilator-associated pneumoniaRandom-effects meta-analysis of early tracheostomy versus late tracheostomy or prolonged intubation on ventilator-associated pneumonia, expressed as the risk ratio (RR), with values more than 1 indicating increased ventilator-associated pneumonia with early tracheostomy. Each black square and horizontal line denotes the point estimate and 95% CI for each trial’s RR. The diamond signifies the pooled RR for all trials with the center denoting the point estimate and the width the 95% CI. Weight is the contribution of each study to the overall RR. ET, early tracheostomy group; LT/PI, late tracheostomy or prolonged intubation; I2, percentage of total variation across studies from between-study heterogeneity rather than chance; CI, confidence interval.
Lori Lynn L Reinstrom, 08/24/16,
Is this Fig. 9?
Lori Lynn L Reinstrom, 08/24/16,
Move to top of figure if material above is Fig. 9.
Supplemental Digital Content- References
1. Dunham CM, LaMonica C. Prolonged tracheal intubation in the trauma patient. J Trauma. 1984;24(2):120-124.
2. Bylappa K, Mohiyudin A, Silvia CR WD, et al. A Comparative Study of Early and Late Tracheostomy in Patients Requiring Prolonged Tracheal Intubation. World Articles in Ear, Nose and Throat 2011;4(2).
3. Sabouri Masih ETM, Hosseini Benham. The Effects of Early Tracheostomy on Outcomes of Patients with Severe Head Injury. Journal of Isfahan Medical School (IUMS) 2009;27(95):211-216.
4. Diaz-Prieto A, Mateu A, Gorriz M, et al. A randomized clinical trial for the timing of tracheotomy in critically ill patients: factors precluding inclusion in a single center study. Critical care (London, England) 2014;18(5):585.
5. Zheng Y, Sui F, Chen XK, et al. Early versus late percutaneous dilational tracheostomy in critically ill patients anticipated requiring prolonged mechanical ventilation. In: Chinese medical journal; 2012. p. 1925-1930.
6. Koch T, Hecker B, Hecker A, et al. Early tracheostomy decreases ventilation time but has no impact on mortality of intensive care patients: a randomized study. Langenbecks Archives of Surgery 2012;397(6):1001-1008.
7. Priyamvadha K, Rao S, Bundela Y, et al. Early versus late tracheostomy in critical brain injury: A prospective randomized study priyamvadha K, Rao S, Bundela Y, Gupta V, Dua S, Singh AK department of neurosciences, fortis hospitals, Noida, Delhi NCR, India. Brain Injury 2012;26 (4-5):504.
8. Trouillet JL, Luyt CE, Guiguet M, et al. Early percutaneous tracheotomy versus prolonged intubation of mechanically ventilated patients after cardiac surgery: a randomized trial.[Summary for patients in Ann Intern Med. 2011 Mar 15;154(6):I-38; PMID: 21403060]. Annals of Internal Medicine 2011;154(6):373-383.
9. Rumbak MJ, Newton M, Truncale T, et al. A prospective, randomized, study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation (delayed tracheotomy) in critically ill medical patients.[Erratum appears in Crit Care Med. 2004 Dec;32(12):2566]. Critical Care Medicine 2004;32(8):1689-1694.
10. Saffle JR, Morris SE, Edelman L. Early tracheostomy does not improve outcome in burn patients. In: Journal of burn care & rehabilitation; 2002. p. 431-438.
11. Rodriguez JL, Steinberg SM, Luchetti FA, et al. Early tracheostomy for primary airway management in the surgical critical care setting. Surgery 1990;108(4):655-659.
12. El-Naggar M, Sadagopan S, Levine H, et al. Factors influencing choice between tracheostomy and prolonged translaryngeal intubation in acute respiratory failure: a prospective study. Anesthesia & Analgesia 1976;55(2):195-201.
13. Blot F, Similowski T, Trouillet JL, et al. Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients. In: Intensive care medicine; 2008. p. 1779-1787.
14. Terragni PP, Antonelli M, Fumagalli R, et al. Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: A randomized controlled trial. JAMA - Journal of the American Medical Association 2010;303(15):1483-1489.
15. Young D, Harrison DA, Cuthbertson BH, et al. Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial. In: Jama; 2013. p. 2121-2129.
Lori Lynn L Reinstrom, 08/24/16,
Be consistent w/ journal name, volume, issue, page #’s.
16. Bösel J, Schiller P, Hook Y, et al. Stroke-related Early Tracheostomy versus Prolonged Orotracheal Intubation in Neurocritical Care Trial (SETPOINT): a randomized pilot trial. In: Stroke; a journal of cerebral circulation; 2013. p. 21-28.
17. Fayed AM, Elbadawy TH, Gamal MA, et al. Early gastrostomy and tracheostomy prevent ventilator associated pneumonia in traumatic brain injured patients. Intensive Care Medicine 2012;38:S123.
18. Barquist ES, Amortegui J, Hallal A, et al. Tracheostomy in ventilator dependent trauma patients: A prospective, randomized intention-to-treat study. Journal of Trauma - Injury, Infection and Critical Care 2006;60(1):91-97.
19. Bouderka MA, Fakhir B, Bouaggad A, et al. Early tracheostomy versus prolonged endotracheal intubation in severe head injury. In: Journal of trauma; 2004. p. 251-254.
20. Mohamed KAE, Mousa AY, ElSawy AS, et al. Early versus late percutaneous tracheostomy in critically ill adult mechanically ventilated patients. Egyptian Journal of Chest Diseases and Tuberculosis 2014;63(2):443-448.
21. Sugerman HJ, Wolfe L, Pasquale MD, et al. Multicenter, randomized, prospective trial of early tracheostomy. In: Journal of trauma; 1997. p. 741-747.
22. Dunham CM, Cutrona AF, Gruber BS, et al. Early tracheostomy in severe traumatic brain injury: evidence for decreased mechanical ventilation and increased hospital mortality. Int J Burns Trauma 2014;4(1):14-24.
23. Garner JS, Jarvis WR, Emori TG, et al. CDC definitions for nosocomial infections, 1988. American journal of infection control 1988;16(3):128-140.
24. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. American journal of respiratory and critical care medicine 1996;153(5):1711-1725.
25. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. American journal of respiratory and critical care medicine 2005;171(4):388-416.
26. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions: Wiley; 2011.
