Traqueostomía temprana versus tardía para pacientes graves
Resumen
Antecedentes
La asistencia respiratoria mecánica a largo plazo es la situación más común en que se indica la traqueostomía para los pacientes en unidades de cuidados intensivos (UCI). Las traqueostomías “temprana” y “tardía” son dos categorías relacionadas con el momento adecuado del procedimiento. Las pruebas sobre las ventajas atribuidas a la traqueostomía temprana sobre la tardía son algo conflictivas aunque incluyen estancias hospitalarias más breves y tasas de mortalidad más bajas.
Objetivos
Evaluar la efectividad y la seguridad de la traqueostomía temprana (≤ 10 días después de la intubación traqueal) versus tardía (> 10 días después de la intubación traqueal) en pacientes adultos graves con diferentes trastornos clínicos en los que se prevé la implementación de asistencia respiratoria mecánica prolongada.
Métodos de búsqueda
Ésta es una actualización de una revisión publicada por última vez en 2012 (número 3, The Cochrane Library) con búsquedas anteriores realizadas en diciembre 2010. En esta versión, se hicieron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL) (2013, número 8); MEDLINE (vía PubMed) (1966 hasta agosto 2013); EMBASE (vía Ovid) (1974 hasta agosto 2013); LILACS (1986 hasta agosto 2013); PEDro (Physiotherapy Evidence Database) en www.pedro.fhs.usyd.edu.au (1999 hasta agosto 2013) y en CINAHL (1982 hasta agosto 2013). Se repitió la búsqueda en octubre de 2014 y se considerarán los estudios de interés cuando se actualice la revisión.
Criterios de selección
Se incluyeron todos los ensayos controlados aleatorios (ECA) o cuasialeatorios que compararon la traqueostomía temprana (dos a 10 días después de la intubación) versus traqueostomía tardía (> 10 días después de la intubación) en pacientes adultos graves en los que se prevé la implementación de asistencia respiratoria mecánica prolongada.
Obtención y análisis de los datos
Dos autores de la revisión extrajeron los datos y realizaron una evaluación de la calidad. Se realizaron metanálisis con modelos de efectos aleatorios para la mortalidad, el tiempo de asistencia respiratoria mecánica y el tiempo en la UCI.
Resultados principales
Se incluyeron ocho ECA (N = 1977 participantes). En el seguimiento a más largo plazo disponible en estos estudios, las pruebas de calidad moderada de siete ECA (n = 1903) mostraron tasas de mortalidad inferiores en el grupo de traqueostomía temprana en comparación con el de traqueostomía tardía (cociente de riesgos [CR] 0,83; intervalo de confianza [IC] del 95%: 0,70 a 0,98; valor de P 0,03; número necesario a tratar para un resultado beneficioso adicional [NNTB] de 11). Se informaron resultados divergentes en el tiempo de asistencia respiratoria mecánica y no se observaron diferencias para la neumonía, aunque la probabilidad de alta de la UCI fue mayor a los 28 días en el grupo de traqueostomía temprana (CR 1,29; IC del 95%: 1,08 a 1,55; valor de p 0,006; NNTB = 8).
Conclusiones de los autores
Todos los hallazgos de esta revisión sistemática no son más que evocadores de la superioridad de la traqueostomía temprana sobre la tardía, porque no hay información de alta calidad disponible para subgrupos específicos con características particulares.
PICO
Resumen en términos sencillos
Momento adecuado de la traqueostomía para pacientes graves en los que se prevé la implementación de asistencia respiratoria mecánica a largo plazo
Pregunta de la revisión: Se revisaron las pruebas disponibles sobre los efectos de la traqueostomía temprana (≤ 10 días después de la intubación traqueal) en comparación con la traqueostomía tardía (> 10 días después de la intubación traqueal) en cuanto a la mortalidad en pacientes graves en que se prevé la implementación de respiración artificial a largo plazo.
Antecedentes: La traqueostomía es un procedimiento quirúrgico en que se crea una abertura artificial externa en la tráquea. La asistencia respiratoria mecánica a largo plazo (en la que se utiliza una máquina para ayudar mecánicamente a la respiración) es la situación más común en que se indica la traqueostomía para los pacientes en las unidades de cuidados intensivos (UCI). Pueden llevarse a cabo traqueostomías "temprana" y "tardía".
Características de los estudios: Las pruebas están actualizadas hasta agosto de 2013. Se incluyeron ocho estudios con un total de 1977 pacientes asignados a la traqueostomía temprana o tardía. Cuatro estudios recibieron apoyo económico de diferentes instituciones que no participaron en el estudio ni en la preparación del contenido de las publicaciones finales. La búsqueda se repitió en octubre de 2014. Cuando se actualice la revisión se analizará cualquier estudio de interés.
Resultados clave: Los pacientes sometidos a traqueostomía temprana tuvieron un riesgo menor de mortalidad en el momento del seguimiento a más largo plazo disponible en siete estudios que midieron la mortalidad (un intervalo de entre 28 días y dos años de seguimiento), en comparación con pacientes sometidos a una traqueostomía tardía. Sin embargo, las pruebas disponibles deben considerarse con cuidado debido a que la información es insuficiente con respecto a cualquier subgrupo o característica individual potencialmente asociada con las mejores indicaciones para la traqueostomía temprana o tardía. Según los resultados disponibles, aproximadamente 11 pacientes necesitarían ser tratados con una traqueostomía temprana en lugar de tardía para evitar una muerte. Los resultados en cuanto al tiempo de asistencia respiratoria mecánica no son definitivos, aunque indican beneficios asociados con la traqueostomía temprana. Dos estudios revelan una probabilidad significativamente mayor de alta de la UCI a los 28 días de seguimiento en el grupo de traqueostomía temprana y ninguna diferencia significativa para la neumonía. Las diferencias posibles entre la traqueostomía temprana y tardía aún deben investigarse de forma adecuada en estudios de alta calidad debido a que no hay información disponible sobre la mejor indicación para la traqueostomía temprana o tardía en pacientes con características específicas.
Calidad de la evidencia: La calidad de las pruebas varió de acuerdo a qué resultado se analizó. Las pruebas se consideraron de calidad moderada para la mortalidad y el tiempo de asistencia respiratoria mecánica; de alta calidad para el alta de la UCI a los 28 días; y de calidad muy baja y baja para la neumonía y la infección de la herida esternal, respectivamente. La heterogeneidad clínica y metodológica entre los estudios fueron los principales factores determinantes de la disminución de la calidad de las pruebas disponibles.
Authors' conclusions
Summary of findings
| Early vs late tracheostomy for critically ill patients | ||||||
| Patient or population: critically ill patients | ||||||
| Outcomes | Illustrative comparative risksa (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Early vs late tracheostomy | |||||
| Mortality at longest follow‐up time available in the studies | Study population | RR 0.83 | 1903 | ⊕⊕⊕⊝ | ||
| 532 per 1000 | 442 per 1000 | |||||
| Moderate | ||||||
| 537 per 1000 | 446 per 1000 | |||||
| Ventilator‐free days during 1 to 28 days | Mean ventilator‐free days during 1 to 28 days in the intervention groups was | 335 | ⊕⊕⊕⊝ | |||
| Days of MV during 1 to 60 days | See comment | See comment | Not estimable | 336 | ⊕⊝⊝⊝ | |
| Length of ICU stay | See comment | See comment | Not estimable | 336 | ⊕⊝⊝⊝ | |
| ICU discharge (at day 28 after randomization) | Study population | RR 1.29 | 538 | ⊕⊕⊕⊕ | ||
| 410 per 1000 | 528 per 1000 | |||||
| Moderate | ||||||
| 433 per 1000 | 559 per 1000 | |||||
| Pneumonia | See comment | See comment | Not estimable | 948 | ⊕⊝⊝⊝ | |
| aThe basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| See 'Risk of bias' table found in the Characteristics of included studies table and in Figure 1 and Figure 2. | ||||||
Flow diagram of studies from studies recovered by the sensitive search strategy for inclusion in the systematic review.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Background
Description of the condition
Long‐term mechanical ventilation is the most common situation for which tracheostomy is indicated for patients in intensive care units (ICUs) (Heffner 2001). Although the definition of prolonged ventilation can include periods as short as 24 hours (Criner 1994; Griffiths 2005), only patients who are foreseen to be on artificial ventilation for approximately 10 days or longer (Armstrong 1998; Plummer 1989) are generally subjected to elective tracheostomy. In this circumstance, tracheostomy is offered as a strategy to reduce respiratory injury and other undesired consequences of prolonged translaryngeal intubation. These include ventilator‐associated pneumonia (Ranes 2006), sinusitis (Holzapfel 1993) and tracheal stenosis (Cavaliere 2007). Predictive systems have been used to predict the duration of mechanical ventilation in various patient settings (Agle 2006; Gajic 2007; Légaré 2001; Sellers 1997), but many of these systems are not appropriately validated. Several other factors have also been shown, in studies, to provide indications for tracheostomy: neuromuscular disease, trauma, age, injury severity score, damage control laparotomy and others (Frutos‐Vivar 2005; Goettler 2006). Some researchers have proposed that the decision to perform tracheostomy should be based on objective measures obtained from spontaneous breathing trials or from trials on weaning from mechanical ventilation (Freeman 2008). Thus, the development of predictive methods that can be tailored for each clinical condition would be a major advance in patient care.
Description of the intervention
Tracheostomy is a surgical procedure whereby an external artificial opening is made in the trachea (Stedman 1995). Several techniques are used to perform tracheostomy, including the classical standard surgical procedure completed in a surgical room and the percutaneous method performed at the patient's bedside (Friedman 2006; Gullo 2007; Pappas 2011; Schultz 2007). Surgical and percutaneous procedures are usually performed by different surgical specialists such as general; thoracic; ear, nose and throat (ENT); or maxillofacial surgeons, but percutaneous procedures are usually but not exclusively performed by surgeons and intensivists (Pappas 2011; Plummer 1989). A diversity of materials (equipment and designs) are used in performing tracheostomy (Björling 2007; Crimlisk 2006; Hess 2005). These can be associated with complications such as tracheal ulceration, distortion of soft tracheal tissue and airway obstruction (Tibballs 2006).
Plummer 1989 used the translaryngeal route for patients expected to be on mechanical ventilation for up to 10 days and tracheostomy for those on artificial ventilation for longer than 21 days; however, tracheostomy is usually performed between the 10th and 14th days of intubation (Armstrong 1998). Nowadays, opinions regarding the best time to perform tracheostomy are conflicting (Heffner 2003). Relevant studies vary in design and in the clinical condition examined (Ahmed 2007; Barquist 2006). To circumvent this, the literature offers two categories of 'early' and 'late' for the timing of tracheostomy. Unfortunately these categories are not precisely defined, and study authors may characterize different times as 'early' and 'late,' resulting in some overlap between the categories (Aissaoui 2007; Barquist 2006; Dunham 2006; Lesnik 1992). Conflicting evidence is available on the advantages of early over late tracheostomy. For example, some comparative studies have reported shorter hospital stays, lower mortality rates and other benefits with the use of early as compared with late tracheostomy (Arabi 2004; Rodriguez 1990). Conversely, Clec'h 2007 observed no differences in mortality in the ICU between patients undergoing early versus late tracheostomy.
How the intervention might work
Potential benefits of tracheostomy include lower airway resistance, easier and safer tracheal suction, greater patient comfort, better communication, improved oral feeding, faster weaning from the ventilator and lower rates of ventilator‐associated pneumonia (Heffner 2001; Plummer 1989). On the other hand, some of the disadvantages of tracheostomy include dislodgement or obstruction, wound infection, scarring, a false passage, haemorrhage and subglottic and tracheal stenosis (Bartels 1998; Dollner 2002; Higgins 2007; Norwood 2000).
Why it is important to do this review
The present review is intended to systematically map available evidence on the timing of tracheostomy (early vs late) in mechanically ventilated, critically ill patients.
Objectives
To evaluate the effectiveness and safety of early (≤ 10 days after tracheal intubation) versus late tracheostomy (> 10 days after tracheal intubation) in critically ill adults predicted to be on prolonged mechanical ventilation with different clinical conditions.
Methods
Criteria for considering studies for this review
Types of studies
We included all randomized (RCTs) and quasi‐randomized controlled trials (QRCTs) published in any language. We included studies published in abstract form if sufficient information regarding their methods and results was provided. We approached the principal authors for additional information when necessary.
Types of participants
Inclusion criteria
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Critically ill patients (for whom death is possible or imminent).
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Patients expected to be on prolonged mechanical ventilation.
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Adults (≥ 18 years).
We defined prolonged mechanical ventilation as ventilation provided for 24 hours to 21 consecutive days, six or more hours per day (Divo 2010; Shirzad 2010).
Exclusion criteria
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Anatomical anomalies of the neck that would impair the tracheostomy procedure.
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Previous tracheostomy.
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Coagulation disturbances (e.g. thrombocytopenia).
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Soft tissue infection of the neck.
Types of interventions
We considered the following comparison arms.
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Early tracheostomy, if no serious attempt was made to wean the patient from the ventilator (tracheostomy based only on clinical or laboratory results and performed from two days to 10 days after intubation).
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Late tracheostomy, if weaning had not been successful; performed later than 10 days after intubation.
Types of outcome measures
We considered all outcome measures reported in the primary studies. For each outcome, we accepted the definition used by the study authors. We discussed when necessary limitations such as use of non‐validated instruments for evaluation or a divergence of definitions.
Primary outcomes
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Mortality (time to mortality or frequency of deaths at any time point: in hospital, in ICU, or after discharge).
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Duration of artificial ventilation.
Secondary outcomes
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Length of stay in ICU (or frequency of tracheostomy at any time point).
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Ventilator‐associated pneumonia at any time point.
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Laryngotracheal lesions at any time point (in epiglottis, vocal cord, larynx; subglottic ulceration and inflammation; stenosis).
For details about definitions, see Appendix 1 (Glossary of terms).
Search methods for identification of studies
Electronic searches
In this updated review, we searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 8); MEDLINE (via Ovid) (1966 to August 2013); EMBASE (via Ovid) (1974 to August 2013); LILACS (1986 to August 2013); PEDro (Physiotherapy Evidence Database) at http://www.pedro.fhs.usyd.edu.au) (1999 to August 2013) and CINHAL (via EBSCO host, 1982 to August 2013). We reran the search in October 2014. We will deal with any studies of interest when we update the review.
The original search was run in December 2010 (Gomes Silva 2012).
The search strategy for MEDLINE included terms for clinical conditions and interventions as well as their synonyms (Appendix 2). This strategy was modified as required for other databases (Appendix 3 (CENTRAL); Appendix 4 (EMBASE); Appendix 5 (LILACS); Appendix 6 (Current Controlled trials); Appendix 7 (PEDro); and Appendix 8 (CINAHL)). We used a highly sensitive search filter for randomized controlled trials in databases for which this was necessary (MEDLINE, EMBASE and LILACS) to optimize the search process (Higgins 2011b).
We imposed no language restrictions.
Searching other resources
We handsearched the references of relevant articles including narrative reviews and non‐randomized controlled studies on mechanical ventilation.
We searched for ongoing randomized controlled trials in the Current Controlled Trials database at http://www.controlled‐trials.com/.
Data collection and analysis
Selection of studies
Two review authors (HS and BNGA) independently analysed the titles and abstracts of publications obtained through the search strategy. We (RA and BNGA) acquired full‐text versions of all studies that met our inclusion criteria.
Data extraction and management
We (RA and BNGA) extracted data using a specially designed data extraction sheet (Appendix 9) that contained information about methods (study design), participants, interventions (e.g. surgical procedures, materials) and results. We resolved all disagreements by consensus. We contacted the authors of the primary studies to request further information about methodology and participants, when necessary. Two review authors (RA and BNGA) abstracted the data and entered all into Review Manager (RevMan 5.1). A third review author (HS) rechecked all entries.
Assessment of risk of bias in included studies
Two review authors (RA and BNGA) assessed all included studies for methodological quality based on the criteria put forth in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a).
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Was the random allocation sequence adequately generated?
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Was allocation adequately concealed?
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Was knowledge of the allocated interventions adequately prevented for data collectors, or were data collectors independent of the researchers who planned the study (blinding)?
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Were incomplete outcome data adequately addressed?
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Are reports of the study free of the suggestion of selective reporting?
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Was the study apparently free of other bias?
We classified each of the items as low risk of bias, high risk of bias or unclear risk of bias.
Because of the nature of the interventions of interest for this systematic review, we considered item 3 (blinding) only at the data collection level.
Measures of treatment effect
For comparable studies, we expressed dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) using the random‐effects model (Deeks 2001a). We calculated the number needed to treat for an additional beneficial outcome (NNTB) when risk differences were statistically significant (Christensen 2006). For continuous data, we calculated the mean difference using the random‐effects model. We planned to calculate the standardized mean difference when trials assessed the same outcome but used different instruments or scales (Deeks 2001b).
Unit of analysis issues
We based the unit of analysis on the individual participant (unit to be randomly assigned to interventions to be compared) (Higgins 2011a). We did not expect to find cross‐over study designs because of the characteristics of the interventions.
Dealing with missing data
Irrespective of the type of data obtained, we planned to report dropout rates in the Characteristics of included studies table and to perform intention‐to‐treat (ITT) analyses only for dichotomous data (Deeks 2005).
Assessment of heterogeneity
We presented data using a random‐effects model (DerSimonian 1986). We quantified inconsistency among pooled estimates by using the Chi2 statistic; for heterogeneity we used the I2 statistic (where I2 = [(Q ‐ df)/Q] × 100%; Q is the Chi2 statistic and df is its degrees of freedom). This illustrates the percentage of variability in effect estimates resulting from heterogeneity rather than from sampling error (Higgins 2002; Higgins 2003). We decided that we would not combine studies in a meta‐analysis when they presented considerable statistical heterogeneity as indicated by the I2 statistic, according to the following thresholds.
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0% to 40%: may not be important.
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30% to 60%: may represent moderate heterogeneity.
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50% to 90%: may represent substantial heterogeneity.
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75% to 100%: shows considerable heterogeneity.
Assessment of reporting biases
We planned to assess publication bias or a systematic difference between smaller and larger studies (small‐study effects) by preparing a funnel plot (trial effect vs trial size) when sufficient numbers of studies were available (Copas 2000).
Data synthesis
We synthesized qualitative information relative to methods, risk of bias, description of participants and outcomes measures and presented them in the Characteristics of included studies table. For quantitative data, we planned to use the random‐effects model in the meta‐analysis because of substantial clinical and methodological heterogeneity between studies, which by themselves could generate substantial statistical heterogeneity. When data from primary studies were not parametric (e.g. effects were reported as medians, quartiles, etc) or were reported without sufficient statistical information (e.g. standard deviations, numbers of participants, etc), we planned to insert them into an 'Appendix.' Additionally, each clinically relevant estimate of effect was presented in summary of findings Table for the main comparison (Schünemann 2009).
Subgroup analysis and investigation of heterogeneity
We planned to stratify our analysis by using the following independent variables, which are expected to be associated with heterogeneity.
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Clinical condition (e.g. trauma, preexisting neurological and lung diseases).
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Different timing of 'early' and 'late' tracheostomies.
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Type of tracheostomy, such as percutaneous or surgical tracheostomy.
We planned to conduct these analyses only if data were available in the report or were obtained by contacting the main authors of the studies. In spite of the number of defined subgroup analyses, the eventual statistical heterogeneity observed across subgroups would not be assumed to show a true causal relationship between dependent and independent variables, but only to generate a hypothesis to be tested in future trials.
Sensitivity analysis
If an adequate number of studies were identified, we planned to perform a sensitivity analysis to explore the causes of heterogeneity and the robustness of study results. We planned to consider the following factors when performing the sensitivity analysis: quality of allocation concealment (adequate or unclear or inadequate); blinding (adequate or unclear or inadequate or not performed); analysis using both random‐effects and fixed‐effect models; intention‐to‐treat analysis and available case analysis (only for dichotomous data). Inclusion of studies with different timing for early and late tracheostomies than was presented in our inclusion criteria was considered in a sensitivity analysis.
We did not plan to present the results obtained from subgroup and sensitivity analyses as conclusions. We intended that they would be used for generation of hypotheses that would be tested in future adequately designed studies.
Results
Description of studies
Results of the search
The search resulted in retrieval of 1433 studies in the first version of this systematic review (Gomes Silva 2012). In this updated version, the search yielded 2006 citations across all electronic databases. We excluded duplicate references and thus retrieved 1466 unique citations. Of these citations, we excluded a further 1359 on the basis of title and abstract, because they were not specifically related to the 'timing of tracheostomy.' From the remaining 107 studies, we excluded a further 84 because of their study design. Thus, 23 studies had the potential to be included in the review (Figure 1). Of those 23 studies, four were ongoing RCTs and one has been awaiting assessment. We contacted the main authors of one of the remaining 18 studies to request further information on the comparison groups (Blot 2008). This study was later excluded for reasons outlined in the Characteristics of excluded studies table.
We reran the search in October 2014 and retrieved 204 new citations, with 18 studies referring to timing of tracheostomy. Of those studies, two RCTs were of interest and are awaiting assessment (Dunham 2014; Mohamed 2014) (see Characteristics of studies awaiting classification). We will deal with them in the next update of this review.
At the title and abstract stage of selection, the Kappa coefficients (Kc) used to evaluate concordances between the two observers (RA and BNGA) were calculated in databases with at least one discordance (Latour 1997). At the first study selection, concordance levels were considered excellent for three databases—Kc = 0.91 (CENTRAL), Kc = 0.85 (EMBASE), Kc = 0.94 (MEDLINE)—and good for CINAHL (Kc = 0.63). For the other databases as well, and in the updated version of this review, no discordance between observers was noted.
Included studies
In the first version (Gomes Silva 2012), we included four studies (Barquist 2006; Dunham 1984; Rumbak 2004; Terragni 2010). In this updated version, we included eight studies (Barquist 2006; Bösel 2013; Dunham 1984; Rumbak 2004; Terragni 2010; Trouillet 2011; Young 2013; Zheng 2012), with a total of 1977 participants randomly assigned to early or late tracheostomy. The authors of four of the RCTs revealed that they had received support from different institutions that did not participate in preparing the content of the final publications, including design, conduct, analysis, interpretation and writing of the studies (Terragni 2010; Trouillet 2011; Young 2013; Zheng 2012). These studies were diverse with respect to their inclusion criteria, methods of tracheostomy and outcome measures (see Characteristics of included studies).
Excluded studies
We excluded seven studies because they compared early tracheostomy versus prolonged endotracheal intubation (Blot 2008; Bouderka 2004; El‐Naggar 1976; Fayed 2012; Saffle 2002; Stauffer 1981; Sugerman 1997). In one quasi‐randomized study, late tracheostomy was performed eight days after admission (< 10 days), thus breaching the selection criteria (> 10 days after intubation) for this review (Rodriguez 1990). Another study performed late tracheostomy ≥ 6 days after intubation (before 10 days) (Koch 2012). For further details, see the Characteristics of excluded studies table.
Risk of bias in included studies
We paid special attention to descriptions of randomization and allocation concealment, as the absence of adequate methodological aspects is associated with biased estimated effects (Schulz 1995). A synthesis of the assessment of all items of methodological quality described below is presented in Figure 2 and Figure 3.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Allocation
Randomization
Five studies (Barquist 2006; Bösel 2013; Terragni 2010; Trouillet 2011; Zheng 2012) reported computer‐generated randomization or automated 24‐hour telephone service (Young 2013), which we considered to possess low risk of bias. Neither study found significant differences between comparison groups in terms of baseline characteristics.
Dunham 1984 referred to randomization based upon the last digit of the patient's hospital number—a method that we deemed indicative of resulting in high risk of bias (quasi‐randomized study).
Rumbak 2004 did not explicitly report the method of randomization; thus the study was considered to reflect moderate risk of bias.
Allocation concealment
Four studies (Barquist 2006; Bösel 2013; Rumbak 2004; Zheng 2012) utilized envelopes to conceal the allocation of participants. Terragni 2010 and Trouillet 2011 clearly reported a centralized process of randomization. Young 2013 used an automated 24‐hour telephone service based on an algorithm that minimized the imbalance between groups.These seven studies were therefore considered to have low risk of bias. However, Dunham 1984, a quasi‐randomized study, was considered to possess high risk of bias associated with allocation concealment.
Blinding
In six studies (Barquist 2006; Dunham 1984; Rumbak 2004; Trouillet 2011; Young 2013; Zheng 2012), investigators clearly did not blind participants or therapists, or no information was given as to whether the data collectors were independent from the researchers who designed the study, or whether they were blinded to the allocations. However, these studies were considered to have low risk of bias associated with potential knowledge about the allocated interventions (blinding) because all primary outcomes analysed in this systematic review were considered objective, as suggested in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). Additionally, Bösel 2013 and Terragni 2010 used blinded or independent data collectors. Consequently, these studies were also deemed as possessing low risk of bias associated with blinding.
Incomplete outcome data
Six studies (Barquist 2006; Bösel 2013; Rumbak 2004; Trouillet 2011; Young 2013; Zheng 2012) were considered to have low risk of bias associated with incomplete outcome data resulting from low dropout rates, use of intention‐to‐treat (ITT) analysis and clear participant flows. At the first version of this systematic review, we considered that the numbers of participants from randomization to analysis of each outcome were not clearly reported for each of the comparison groups in Terragni 2010. Therefore this study was considered to have high risk of bias. However, we could now identify that ITT analysis was properly performed by the study authors. Withdrawals at one year of follow‐up consisted of the following: n = 10 (4.78%) in the early tracheostomy group, and n = 4 (1.9%) in the late tracheostomy group.
Dunham 1984 was considered to possess high risk of bias as, after randomization, only participants who were intubated for at least seven days were included in the study. The study authors did not indicate the percentages or numbers of participants not considered for analysis after randomization.
Selective reporting
Seven studies were considered to have low risk of bias based on the relevant outcomes considered for evaluation and the absence of suspected selective outcome reporting (Barquist 2006; Bösel 2013; Rumbak 2004; Terragni 2010; Trouillet 2011; Young 2013; Zheng 2012). Dunham 1984 was deemed to be a study with high risk of systematic error resulting from the absence of clinically relevant outcomes (such as mortality rates).
Other potential sources of bias
Dunham 1984 evaluated 50% of participants at four to six months after extubation. The remaining participants were interviewed 12 months after extubation, but the exact number of participants per comparison group was not specified. No indication was given of the absence of substantial differences between comparison groups at baseline (comparable groups).
Seven studies showed no other suspected potential for bias (Barquist 2006; Bösel 2013; Rumbak 2004; Terragni 2010; Trouillet 2011; Young 2013; Zheng 2012).
Effects of interventions
See: Summary of findings for the main comparison Early vs late tracheostomy for critically ill patients
Primary outcomes
Mortality
Evidence of moderate quality demonstrates that mortality rate at the longest follow‐up time available in seven studies combined was lower in the group given early tracheostomy (47.1%; 448/950) than in the group given late tracheostomy (53.2%; 507/953), with a statistically significant risk ratio (RR) of 0.83 (95% confidence interval (CI) 0.70 to 0.98; P value 0.03; number needed to treat for an additional beneficial outcome (NNTB) ≅11; Analysis 1.1) (Barquist 2006; Bösel 2013; Rumbak 2004; Terragni 2010; Trouillet 2011; Young 2013; Zheng 2012).
With regard to mortality at 30 days of follow‐up, the review authors have opted to present results from individual studies because the inconsistency test may represent substantial statistical heterogeneity between studies (I2 = 77%). Thus, Rumbak 2004 is the only study that demonstrated a significant difference between groups, with a lower mortality rate in the early tracheostomy group (RR 0.51, 95% CI 0.34 to 0.78; P value 0.002; NNTB = 3.33); Young 2013 and Zheng 2012 did not demonstrate significant differences between groups (Analysis 1.3 and Table 1, lines 1.1.1 to 1.1.3). At 180 days of follow‐up, Bösel 2013 reported a lower percentage of mortality in the early tracheostomy group (RR 0.44, 95% CI 0.23 to 0.85; P value 0.01; NNTB = 2.8) (Table 1, line 1.1.5). The same study author reported a statistically significant difference, with a lower mortality rate until ICU discharge, in the early tracheostomy group (RR 0.21, 95% CI 0.07 to 0.67; P value 0.008; NNTB = 2.7), but Young 2013 found no significant differences between groups (RR 0.98, 95% CI 0.81 to 1.19; P value 0.83) (Analysis 1.6 and Table 1, lines 1.1.7 and 1.1.8). The two studies were not combined in a meta‐analysis because the inconsistency test (I2 = 85%) may represent substantial heterogeneity between studies (Bösel 2013; Young 2013).
| 1. Primary outcomes | n | Estimate effect (MD or RR, 95% CI, P, NNTB, 95% CI for NNTB) | Favoured group | Study |
| 1.1. Mortality | ||||
| 1.1.1. Mortality at 30 days | 120 | RR 0.51 (0.34 to 0.78, P value 0.002, NNTB = 3.3) | Early tracheostomy | |
| 1.1.2. Mortality at 30 days | 909 | RR 0.97 (0.80 to 1.17, P value 0.76) | Early tracheostomy | |
| 1.1.3. Mortality at 30 days | 119 | RR 1.50 (0.61 to 3.68, P value 0.37) | Late tracheostomy | |
| 1.1.4. Mortality at 90 days | 216 | RR 1.01 (0.67 to 1.52, P value 0.95) | Late tracheostomy | |
| 1.1.5. Mortality at 180 days | 60 | RR 0.44 (0.23 to 0.85, P value 0.01, NNTB = 2.8) | Early tracheostomy | |
| 1.1.6. Mortality at 2 years | 909 | RR 0.94 (0.83 to 1.06, P value 0.33) | Early tracheostomy | |
| 1.1.7. Mortality until ICU discharge | 60 | RR 0.21 (0.07 to 0.67, P value 0.008, NNTB = 2.7) | Early tracheostomy | |
| 1.1.8. Mortality until ICU discharge | 909 | RR 0.98 (0.81 to 1.19, P value 0.83) | Early tracheostomy | |
| 1.1.9. Mortality until hospital discharge | 909 | 0.96 (0.82 to 1.12, P value 0.58) | Early tracheostomy | |
| 1.2. Duration of artificial ventilation | ||||
| 1.2.1. Days of mechanical ventilation 1 to 60 days | 120 | MD ‐9.80 (‐11.48 to ‐8.12, P value < 0.001) | Early tracheostomy | |
| 1.2.2. Days of mechanical ventilation 1 to 60 days | 216 | MD ‐1.40 (‐5.65 to 2.85, P value 0.52) | Early tracheostomy | |
| 1.2.3. Ventilator‐free days during 1 to 60 days | 216 | MD 2.10 (‐4.05 to 8.25, P value 0.50) | Early tracheostomy | |
| 1.2.4. Ventilator‐free days during 1 to 90 days | 216 | MD 1.80 (‐7.94 to 11.54, P value 0.72) | Early tracheostomy | |
| 1.2.5. Intubation for longer than 21 days | 74 | RR 0.85 (0.53 to 1.36, P value 0.49) | Late tracheostomy | |
| 2. Secondary outcomes | n | Estimate effect (MD or RR, 95% CI, P, NNTH, 95% CI for NNTH) | Favoured group | Study |
| 2.1. Length of stay in ICU | ||||
| 2.1.1. Time spent on ICU (days) | 120 | MD ‐11.40 (‐12.42 to ‐10.38, P value < 0.001) | Early tracheostomy | |
| 2.1.2. Time spent on ICU (days) | 419 | ‐1.40 (‐5.65 to 2.85, P value 0.52) | Early tracheostomy | |
| 2.2. Ventilator‐associated pneumonia | ||||
| 2.2.1. Ventilator‐associated pneumonia | 74 | RR 1.18 (0.77 to 1.79, P value 0.45) | Late tracheostomy | |
| 2.2.2. Ventilator‐associated pneumonia | 120 | RR 0.20 (0.06 to 0.66, P value 0.008, NNTB = 1.66) | Early tracheostomy | |
| 2.2.3. Ventilator‐associated pneumonia | 419 | RR 0.69 (0.45 to 1.05, P value 0.08) | Early tracheostomy | |
| 2.2.4. Ventilator‐associated pneumonia | 216 | RR 1.04 (0.78 to 1.40, P value 0.77) | Late tracheostomy | |
| 2.2.5. Ventilator‐associated pneumonia | 119 | RR 0.60 (0.37 to 0.96, P value 0.03, NNTB = 5) | Early tracheostomy | |
| 2.3. Laryngotracheal lesions | ||||
| 2.3.1. Stoma inflammation | 264 | RR 1.00 (0.57 to 1.78, P value 0.99) | Late tracheostomy | |
| 2.3.2. Stoma infection | 264 | RR 1.06 (0.41 to 2.75, P value 0.91) | Late tracheostomy | |
| 2.3.3. Postoperative minor bleeding | 264 | RR 1.09 (0.39 to 3.07, P value 0.86) | Late tracheostomy | |
| 2.3.4. Postoperative major bleeding | 264 | RR 0.82 (0.17 to 3.99, P value 0.81) | Early tracheostomy | |
| 2.3.5. Postoperative bleeding | 60 | RR 0.03 (0.00 to 0.55, P value 0.02, NNTB = 2.12) | Early tracheostomy | |
| 2.3.6. Intraoperative minor bleeding | 264 | RR 0.55 (0.09 to 3.22, P value 0.50) | Early tracheostomy | |
| 2.3.7. Intraoperative significant bleeding | 264 | No event in both groups | ‐ | |
| 2.3.8. Tracheo‐oesophageal fistula | 264 | RR 2.47 (0.10 to 59.98, P value 0.58) | Late tracheostomy | |
| 2.3.9. Significant laryngotracheal pathology | 74 | RR 1.41 (0.47 to 4.22, P value 0.54) | Late tracheostomy | |
| 2.3.10. Tracheal stenosis (%) 0 to 20 (in‐hospital) | 120 | RR 1.27 (1.04 to 1.55, P value 0.02, NNTH=10) | Late tracheostomy | |
| 2.3.11. Tracheal stenosis (%) 21 to 50 (in‐hospital) | 120 | RR 0.50 (0.20 to 1.25, P value 0.14) | Early tracheostomy | |
| 2.3.12. Tracheal stenosis (%) > 50 (in‐hospital) | 120 | RR 0.40 (0.08 to 1.98, P value 0.26) | Early tracheostomy | |
| 2.3.13. Tracheal stenosis irrespective of severity (in‐hospital) | 120 | RR 1.03 (0.98 to 1.09, P value 0.24) | Late tracheostomy | |
| 2.3.14. Tracheal stenosis (%) 0 to 20 (10‐week post intubation) | 120 | RR 2.00 (1.14 to 3.51, P value 0.02, NNTH = 4.54) | Late tracheostomy | |
| 2.3.15. Tracheal stenosis (%) 21 to 50 (10‐week post intubation) | 120 | RR 1.67 (0.65 to 4.30, P value 0.29) | Late tracheostomy | |
| 2.3.16. Tracheal stenosis (%) > 50 (10‐week post intubation) | 120 | RR 1.25 (0.35 to 4.43, P value 0.73) | Late tracheostomy | |
| 2.3.17. Tracheal stenosis irrespective of severity (10‐week post intubation) | 120 | RR 1.78 (1.24 to 2.57, P value 0.002, NNTH = 3.33) | Late tracheostomy | |
NNTB: number needed to treat for an additional beneficial outcome
NNTH: number needed to treat for an additional harmful outcome
Studies did not demonstrate significant differences between early and late tracheostomy groups for mortality at 28 days (Analysis 1.2), 60 days (Analysis 1.4), 90 days (Table 1, line 1.1.4) and one and two years of follow‐up (Analysis 1.5 and Table 1, line 1.1.6, respectively), nor until the time of ICU or hospital discharge (Table 1, lines 1.1.8. and 1.1.9, respectively).
Duration of artificial ventilation
Trouillet 2011 and Zheng 2012 evaluated mean ventilator‐free days until 28 days of follow‐up, but the meta‐analysis resulted in no statistically significant estimated effect (mean difference (MD) 1.62, 95% CI −0.01 to 3.25; P value 0.05; I2 = 0%; Analysis 1.7). Rumbak 2004 and Trouillet 2011 measured mean days of mechanical ventilation, but their results cannot be combined in a meta‐analysis because substantial statistical heterogeneity has been observed between them (I2 = 92%) (Analysis 1.8). Rumbak 2004 reported a statistically significant mean reduction of 9.8 days of mechanical ventilation (95% CI ‐11.48 to ‐8.12; P value < 0.00001) in the early tracheostomy group (Table 1, line 1.2.1), and Trouillet 2011 found a statistically insignificant reduction of ‐1.40 days (95% CI ‐5.65 to 2.85; P value 0.52), also in the early group (Table 1, line 1.2.2). No statistically significant differences between comparison groups were noted in other ways of measuring duration of artificial ventilation, as reported by Trouillet 2011 (ventilator‐free days during one to 60 days, Table 1, line 1.2.3; ventilator‐free days during one to 90 days, Table 1, line 1.2.4) and Dunham 1984 (intubation for longer than 21 days, Table 1, line 1.2.5). Terragni 2010 found a statistically significant difference in ventilator‐free days (at day 28) in the early tracheostomy group (median of 11 days, interquartile range zero to 21) as compared with the late tracheostomy group (median of six days, interquartile range zero to 17) (P value 0.02) (Table 2, line 1). Although Bösel 2013 found a median reduction of three days of ventilation time in the early tracheostomy group, the difference was not statistically significant (P value 0.23) (Table 2, line 2).
| Study ID | Comparison groups | Median | Interquartile range | P value |
| 1. Primary outcome: ventilator free‐days (at day 28) | ||||
| Early tracheostomy | 11 | 0to 21 | 0.02 | |
| Late tracheostomy | 6 | 0 to 17 | ||
| 2. Primary outcome: ventilation time (days) | ||||
| Early tracheostomy | 15 | 10 to 17 | 0.23 | |
| Late tracheostomy | 12 | 8 to 16 | ||
| 3. Secondary outcome: intensive care unit‐free days (at day 28) | ||||
| Early tracheostomy | 0 | 0 to 13 | 0.02 | |
| Late tracheostomy | 0 | 0 to 8 | ||
| 4. Secondary outcome: intensive care unit length of stay (days) | ||||
| Early tracheostomy | 17 | 13 to 22 | 0.38 | |
| Late tracheostomy | 18 | 16 to 28 | ||
| 5. Secondary outcome: intensive care unit‐free days (at day 28) | ||||
| Early tracheostomy | 8.0 | 5 to 12 | 0.048 | |
| Late tracheostomy | 3.0 | 0 to 12 | ||
Statistical test referred to in Terragni 2010; Zheng 2012; Bösel 2013: Wilcoxon signed rank test.
Secondary outcomes
Length of ICU stay
Two studies measured the mean number of days in the ICU. Their findings could not be combined in a meta‐analysis, however, because substantial heterogeneity between them was observed (Analysis 1.9). Thus, Rumbak 2004 showed a clinically and statistically relevant lower mean number of days in the ICU in the early tracheostomy group than in the late tracheostomy group (MD ‐11.40 days, 95% CI ‐12.42 to ‐10.38; P value < 0.00001; Table 1, line 2.1.1). Otherwise, Trouillet 2011 found a slightly lower mean number of ICU days in the early tracheostomy group but no statistically significant differences between groups (MD ‐1.60 days, 95% CI ‐7.40 to 4.20; P value 0.59; Table 1, line 2.1.2). Two other studies combined in a meta‐analysis showed a significantly higher probability of discharge from ICU at 28 days of follow‐up in the early tracheostomy group (140/267; 52.4%) than in the late tracheostomy group (111/271; 40.9%), with an RR of 1.29 (95% CI 1.08 to 1.55; P value 0.006; NNTB = 8.3) (Analysis 1.10). Additionally, Terragni 2010 and Bösel 2013 found no differences between comparison groups that were clinically or statistically relevant (Table 2, lines 3 and 4), but Zheng 2012 observed a clinically and statistically significant difference in ICU‐free days at day 28 between the early tracheostomy group (median 8.0 days, interquartile range five to 12 days) and the late tracheostomy group (median 3.0 days, interquartile range zero to 12 days) (P value 0.048) (Table 2, line 5).
Pneumonia
The combination of all studies measuring pneumonia rates in a meta‐analysis (Dunham 1984; Rumbak 2004; Terragni 2010; Trouillet 2011; Zheng 2012) yielded substantial statistical heterogeneity (I2 = 71%). By consensus, we have decided to present the data on pneumonia in a forest plot with isolated estimated effects from the studies, excluding a meta‐analysis (Analysis 1.11). The combined percentage of pneumonia events in the early tracheostomy group is 25.5%, versus 32.6% in the late tracheostomy group. Rumbak 2004 and Zheng 2012 showed a significantly lower probability of pneumonia in study participants allocated to the early tracheostomy group, with estimated effects of RR 0.20 (95% CI 0.06 to 0.66; P value 0.008; NNTB = 5; Table 1, line 2.2.2) and RR 0.60 (95% CI 0.37 to 0.96; P value 0.03; NNTB = 5; Table 1, line 2.2.5), respectively. Terragni 2010, which did not include patients with pneumonia at study entry, reported an RR of 0.69 in favour of the early tracheostomy group but without statistical significance (95% CI 0.45 to 1.05; P value 0.08). Two studies (Dunham 1984; Trouillet 2011) found higher percentages of participants with pneumonia in the early tracheostomy group but without statistical significance, as observed in the following estimations of RR 1.18 (95% CI 0.77 to 1.79; P value 0.45) (Table 1, line 2.2.1) and RR 1.04 (95% CI 0.78 to 1.40; P value 0.77) (Table 1, line 2.2.4), respectively.
Laryngotracheal lesions at any time point (in epiglottis, vocal cord, larynx; subglottic ulceration and inflammation; stenosis)
The studies included in this systematic review found no clinically or statistically relevant differences between early and late tracheostomies in occurrence of the following postoperative adverse events: stoma inflammation; postoperative and intraoperative minor and major bleeding; pneumothorax; subcutaneous emphysema; tracheo‐oesophageal fistula and cannula displacement or need for replacement (Terragni 2010); significant laryngotracheal pathology; respiratory sepsis; major complications; complications (Dunham 1984); percentage of tracheal stenosis, irrespective of severity (in‐hospital); tracheal stenosis > 50 (10 weeks post intubation) (Rumbak 2004); self‐extubation (Rumbak 2004) and sternal wound or stoma infection (Terragni 2010; Trouillet 2011). For details on the estimated effects, please refer to Table 1 (lines 2.3.1 to 2.3.4; 2.3.6 to 2.3.9; and 2.3.12 to 2.3.16) and Analysis 1.12.
The following events occurred significantly more often in the early tracheostomy group: tracheal stenosis with a severity score from zero to 20 in hospital and 10 weeks after intubation; and tracheal stenosis, irrespective of severity, 10 weeks after intubation (Rumbak 2004, Table 1, lines 2.3.10, 2.3.14 and 2.3.17). Bösel 2013, however, found a significantly lower proportion of participants with postoperative bleeding in early tracheostomy (Table 1, line 2.3.5).
Other potentially relevant outcomes not planned in the protocol of this systematic review
Of the 43 outcomes with potential clinical relevance that were not previously planned in this systematic review, 18 outcomes showed statistically significant estimated effects in favour of early tracheostomy. These outcomes included recannulation, reintubation, nursing evaluation, nutrition, self‐extubation, successful weaning, bed‐to‐chair transfer, cannula displacement and need for replacement as aspects relative to duration of sedation, as shown in Appendix 10 (lines 15 to 24; 26 to 29; 33, 35 and 36) and Appendix 11 (lines 9 and 11).
Sensitivity analysis
Because of the relative paucity of included studies, we performed a sensitivity analysis just for mortality at the longest follow‐up time available in the studies. This analysis was performed by including one RCT and one quasi‐RCT that had been excluded from this systematic review (Koch 2012; Rodriguez 1990, respectively). These studies were excluded because late tracheostomies (< 10 days) did not meet our inclusion criteria. This sensitivity analysis showed very similar estimate effects upon their exclusion (please refer to Analysis 1.1) with an RR of 0.84 (95% CI 0.73 to 0.98; P value 0.02; I2 = 40%; NNTB = 12.5; n = 206 participants).
Discussion
Summary of main results
Primary outcomes
At the longest follow‐up time available in the studies, moderate‐quality evidence from seven randomized controlled trials showed a significant mortality rate in the early tracheostomy group as compared with the late tracheostomy group (Barquist 2006; Bösel 2013; Rumbak 2004; Terragni 2010; Trouillet 2011; Young 2013; Zheng 2012); it was necessary to treat for an additional beneficial outcome (NNTB) approximately 11 critically ill patients with early tracheostomy to prevent one death. The review authors paid special attention to the sensitivity analysis that tested the effects of studies excluded because their times of tracheostomy did not meet our inclusion criteria. This sensitivity analysis was done for mortality at the longest follow‐up time available in the studies. Although the results of this sensitivity analysis (please see Effects of interventions at sensitivity analysis) may not be considered in our conclusions, they were very similar to the findings of the meta‐analysis of included studies, in spite of the inclusion of two additional excluded randomized controlled trials (RCTs) (Analysis 1.1). At 30 days of follow‐up, only one study (Rumbak 2004) out of three (Rumbak 2004; Young 2013; Zheng 2012) demonstrated a significant difference between groups, with a lower mortality rate in the early tracheostomy group; thus, it was necessary to treat approximately three critically ill participants with early tracheostomy to prevent one death. Additionally, significant differences favouring the early tracheostomy group were reported by Bösel 2013 at 180 days and until ICU discharge; it was necessary to treat approximately three participants with early tracheostomy to prevent one death at both times of follow‐up. No study demonstrated significant differences between early and late tracheostomy groups for mortality at 28, 60 and 90 days, and at one and two years of follow‐up, nor until both ICU and hospital discharge.
Two studies combined in a meta‐analysis contributed to the moderate‐quality evidence found to support the absence of differences between comparison groups for mean ventilator‐free days until 28 days of follow‐up (Trouillet 2011; Zheng 2012). Individual studies, however, showed significantly less mean time spent in mechanical ventilation in the early tracheostomy group, with a mean reduction of 9.8 days in Rumbak 2004 and, in Terragni 2010, a longer median time in the early tracheostomy group of five ventilator‐free days at 28 days of follow‐up. Other individual studies showed non‐significantly less time on mechanical ventilation in the early tracheostomy group (Bösel 2013; Dunham 1984; Trouillet 2011). In addition, Terragni 2010 demonstrated that early tracheostomy is significantly associated with a higher rate of successful weaning—an outcome related closely to time spent on mechanical ventilation.
Secondary outcomes
With respect to secondary outcomes, two studies combined in a meta‐analysis showed a significantly higher probability of discharge from the ICU at 28 days of follow‐up in the early tracheostomy group; it was necessary to offer the early tracheostomy to approximately eight participants to account for one discharge from ICU at day 28 (Terragni 2010; Zheng 2012). One study showed a relevant mean reduction of approximately 11 days in the ICU in the early as opposed to the late tracheostomy group (Rumbak 2004). Another important difference of a median of five ICU‐free days was observed by Zheng 2012 in the early tracheostomy group. Bösel 2013, Terragni 2010 and Trouillet 2011, however, found insignificant differences in the time spent in the ICU: approximately one day.
No definitive evidence demonstrated that any one treatment is associated with lower probability of pneumonia, possibly because of the large heterogeneity between studies (Dunham 1984; Rumbak 2004; Terragni 2010; Trouillet 2011; Zheng 2012). Terragni 2010, in fact, unlike the other studies, excluded patients with chronic obstructive pulmonary disease and pneumonia at study entry.
Laryngotracheal lesions were observed significantly more frequently in participants who had undergone early tracheostomy as measured by tracheal stenosis (Rumbak 2004), but Bösel 2013 found a significantly lower probability of postoperative bleeding in participants who had undergone early tracheostomy.
Overall completeness and applicability of evidence
The whole findings of this systematic review are no more than suggestive of the superiority of early over late tracheostomy, because no information is available on high quality for specific subgroups with particular characteristics. Thus, our results suggest, but not definitively, that it would be necessary to treat (NNTB) approximately 11 patients to prevent one death (Barquist 2006; Bösel 2013; Rumbak 2004; Terragni 2010; Trouillet 2011; Zheng 2012). It is important to consider that available studies showed significant (Rumbak 2004; Terragni 2010) to little benefit (Bösel 2013; Dunham 1984; Trouillet 2011; Zheng 2012) of early tracheostomy for time spent on mechanical ventilation, and one study demonstrated that early tracheostomy was significantly associated with a higher rate of successful weaning—an outcome related closely to time spent on mechanical ventilation (Terragni 2010). Four studies suggested a possible but not definitive benefit of early tracheostomy for time spent in the ICU (Bösel 2013; Rumbak 2004; Terragni 2010; Zheng 2012). Thus, such results would outweigh the possibly higher risk of tracheal stenosis in the early tracheostomy group, which was reported only by Rumbak 2004.
Quality of the evidence
According to summary of findings Table for the main comparison, the quality of the evidence was considered moderate for mortality at the longest follow‐up time available in the studies. Besides clinical heterogeneity, which is a condition naturally present among critically ill patients, the main suspected reason to downgrade the quality of evidence was the influence of three larger trials with more modest and statistically non‐significant effect estimates (Terragni 2010; Trouillet 2011; Young 2013). Although small trials are prone to stronger estimate effects (Pereira 2012), it is far from assumed that they are inherently flawed (Batterham 2013). Moreover, Ioannidis 1998 considered that there exist more divergences between meta‐analyses and large trials published in the more persuasive scientific journals, and that the latter tend to be preferred over meta‐analyses. Additionally, some study authors have indicated that when results from individual studies are fundamentally in the same direction (consistency across studies), the meta‐analysis merits greater confidence, and they criticize those who look for strict "black and white" conclusions in scientific research (Cook 1995; Hill 1965; McCormack 2013).
As yet we have not included sufficient studies to enable us to explore publication bias. This bias can be considered a possibility because, in virtually all areas of knowledge, some investigators do not make their studies available, particularly those studies that show no effect (Song 2010). Apart from mortality, It was possible, however, to detect distinct qualities of evidence for the same outcomes as measured in different ways. For example, the quality of evidence of the specific outcome of ventilator‐free days at 28 days of follow‐up was graded as moderate, and the outcome of mean days of mechanical ventilation until 60 days of follow‐up was considered to be of very low quality. Such a large divergence in the definitions of outcomes has been crucial in downgrading the quality of available evidence on this research question.
Potential biases in the review process
A high‐sensitivity search strategy was used in this systematic review so as to avoid missing any randomized controlled trials that compared early versus late tracheostomy in critically ill patients. We prevented language bias by not imposing language restrictions upon the search. Other studies have been conducted but have not yet been published (Dumire 2008; Huttner 2010; Kluge 2009; Ranieri 2009), and their results may improve the evidence in this area. Such ongoing studies will probably be included in future versions of this review once their results have been made available.
Agreements and disagreements with other studies or reviews
The findings of our previous systematic review and of the reviews by Dunham 2006 and Griffiths 2005 did not consistently support either early or late tracheostomy for reducing mortality. Newly available studies, however, have helped prove, although still not definitively, the potential benefits of early tracheostomy as compared with late tracheostomy for mortality. Another systematic review carried out by Shan 2013 clearly supports the choice of early tracheostomy for reducing length of ICU stay, duration of mechanical ventilation and mortality, but the results apparently have been overestimated as a result of the inclusion of observational studies. In this sense, Scales 2008, in a large observational study involving more than 10,000 participants, showed that early tracheostomy is associated with significant advantages over late tracheostomy in terms of mortality for critically ill patients. Previous systematic reviews, as well as other observational studies and non‐randomized controlled trials with lower methodological rigour, have also showed decreased time spent on ventilatory support (Arabi 2004; Arabi 2009; Blot 1995; Dunham 2006; Gandía‐Martínez 2010; Griffiths 2005; Lesnik 1992; Zagli 2010), decreased time in the ICU (Arabi 2004; Arabi 2009, Gandía‐Martínez 2010; Griffiths 2005; Lesnik 1992; Zagli 2010) and at the hospital (Arabi 2004; Arabi 2009; Blot 1995) and lower probabilities of pneumonia (Gandía‐Martínez 2010; Lesnik 1992) and extubation (El‐Naggar 1976) with early tracheostomy than with late tracheostomy. All of these results have been observed in the face of large clinical, regional, methodological and chronological diversity among studies.
Flow diagram of studies from studies recovered by the sensitive search strategy for inclusion in the systematic review.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Comparison 1 Early vs late tracheostomy, Outcome 1 Mortality at longest follow‐up time available in studies.
Comparison 1 Early vs late tracheostomy, Outcome 2 Mortality at 28 days.
Comparison 1 Early vs late tracheostomy, Outcome 3 Mortality at 30 days.
Comparison 1 Early vs late tracheostomy, Outcome 4 Mortality at 60 days.
Comparison 1 Early vs late tracheostomy, Outcome 5 Mortality at 1 year.
Comparison 1 Early vs late tracheostomy, Outcome 6 Mortality until ICU discharge.
Comparison 1 Early vs late tracheostomy, Outcome 7 Ventilator‐free days during 1 to 28 days.
Comparison 1 Early vs late tracheostomy, Outcome 8 Days of MV during 1 to 60 days.
Comparison 1 Early vs late tracheostomy, Outcome 9 Length of ICU stay.
Comparison 1 Early vs late tracheostomy, Outcome 10 ICU discharge (at day 28 after randomization).
Comparison 1 Early vs late tracheostomy, Outcome 11 Pneumonia.
Comparison 1 Early vs late tracheostomy, Outcome 12
Sternal wound infection.
| Early vs late tracheostomy for critically ill patients | ||||||
| Patient or population: critically ill patients | ||||||
| Outcomes | Illustrative comparative risksa (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Early vs late tracheostomy | |||||
| Mortality at longest follow‐up time available in the studies | Study population | RR 0.83 | 1903 | ⊕⊕⊕⊝ | ||
| 532 per 1000 | 442 per 1000 | |||||
| Moderate | ||||||
| 537 per 1000 | 446 per 1000 | |||||
| Ventilator‐free days during 1 to 28 days | Mean ventilator‐free days during 1 to 28 days in the intervention groups was | 335 | ⊕⊕⊕⊝ | |||
| Days of MV during 1 to 60 days | See comment | See comment | Not estimable | 336 | ⊕⊝⊝⊝ | |
| Length of ICU stay | See comment | See comment | Not estimable | 336 | ⊕⊝⊝⊝ | |
| ICU discharge (at day 28 after randomization) | Study population | RR 1.29 | 538 | ⊕⊕⊕⊕ | ||
| 410 per 1000 | 528 per 1000 | |||||
| Moderate | ||||||
| 433 per 1000 | 559 per 1000 | |||||
| Pneumonia | See comment | See comment | Not estimable | 948 | ⊕⊝⊝⊝ | |
| aThe basis for the assumed risk (e.g. median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence. | ||||||
| See 'Risk of bias' table found in the Characteristics of included studies table and in Figure 1 and Figure 2. | ||||||
| 1. Primary outcomes | n | Estimate effect (MD or RR, 95% CI, P, NNTB, 95% CI for NNTB) | Favoured group | Study |
| 1.1. Mortality | ||||
| 1.1.1. Mortality at 30 days | 120 | RR 0.51 (0.34 to 0.78, P value 0.002, NNTB = 3.3) | Early tracheostomy | |
| 1.1.2. Mortality at 30 days | 909 | RR 0.97 (0.80 to 1.17, P value 0.76) | Early tracheostomy | |
| 1.1.3. Mortality at 30 days | 119 | RR 1.50 (0.61 to 3.68, P value 0.37) | Late tracheostomy | |
| 1.1.4. Mortality at 90 days | 216 | RR 1.01 (0.67 to 1.52, P value 0.95) | Late tracheostomy | |
| 1.1.5. Mortality at 180 days | 60 | RR 0.44 (0.23 to 0.85, P value 0.01, NNTB = 2.8) | Early tracheostomy | |
| 1.1.6. Mortality at 2 years | 909 | RR 0.94 (0.83 to 1.06, P value 0.33) | Early tracheostomy | |
| 1.1.7. Mortality until ICU discharge | 60 | RR 0.21 (0.07 to 0.67, P value 0.008, NNTB = 2.7) | Early tracheostomy | |
| 1.1.8. Mortality until ICU discharge | 909 | RR 0.98 (0.81 to 1.19, P value 0.83) | Early tracheostomy | |
| 1.1.9. Mortality until hospital discharge | 909 | 0.96 (0.82 to 1.12, P value 0.58) | Early tracheostomy | |
| 1.2. Duration of artificial ventilation | ||||
| 1.2.1. Days of mechanical ventilation 1 to 60 days | 120 | MD ‐9.80 (‐11.48 to ‐8.12, P value < 0.001) | Early tracheostomy | |
| 1.2.2. Days of mechanical ventilation 1 to 60 days | 216 | MD ‐1.40 (‐5.65 to 2.85, P value 0.52) | Early tracheostomy | |
| 1.2.3. Ventilator‐free days during 1 to 60 days | 216 | MD 2.10 (‐4.05 to 8.25, P value 0.50) | Early tracheostomy | |
| 1.2.4. Ventilator‐free days during 1 to 90 days | 216 | MD 1.80 (‐7.94 to 11.54, P value 0.72) | Early tracheostomy | |
| 1.2.5. Intubation for longer than 21 days | 74 | RR 0.85 (0.53 to 1.36, P value 0.49) | Late tracheostomy | |
| 2. Secondary outcomes | n | Estimate effect (MD or RR, 95% CI, P, NNTH, 95% CI for NNTH) | Favoured group | Study |
| 2.1. Length of stay in ICU | ||||
| 2.1.1. Time spent on ICU (days) | 120 | MD ‐11.40 (‐12.42 to ‐10.38, P value < 0.001) | Early tracheostomy | |
| 2.1.2. Time spent on ICU (days) | 419 | ‐1.40 (‐5.65 to 2.85, P value 0.52) | Early tracheostomy | |
| 2.2. Ventilator‐associated pneumonia | ||||
| 2.2.1. Ventilator‐associated pneumonia | 74 | RR 1.18 (0.77 to 1.79, P value 0.45) | Late tracheostomy | |
| 2.2.2. Ventilator‐associated pneumonia | 120 | RR 0.20 (0.06 to 0.66, P value 0.008, NNTB = 1.66) | Early tracheostomy | |
| 2.2.3. Ventilator‐associated pneumonia | 419 | RR 0.69 (0.45 to 1.05, P value 0.08) | Early tracheostomy | |
| 2.2.4. Ventilator‐associated pneumonia | 216 | RR 1.04 (0.78 to 1.40, P value 0.77) | Late tracheostomy | |
| 2.2.5. Ventilator‐associated pneumonia | 119 | RR 0.60 (0.37 to 0.96, P value 0.03, NNTB = 5) | Early tracheostomy | |
| 2.3. Laryngotracheal lesions | ||||
| 2.3.1. Stoma inflammation | 264 | RR 1.00 (0.57 to 1.78, P value 0.99) | Late tracheostomy | |
| 2.3.2. Stoma infection | 264 | RR 1.06 (0.41 to 2.75, P value 0.91) | Late tracheostomy | |
| 2.3.3. Postoperative minor bleeding | 264 | RR 1.09 (0.39 to 3.07, P value 0.86) | Late tracheostomy | |
| 2.3.4. Postoperative major bleeding | 264 | RR 0.82 (0.17 to 3.99, P value 0.81) | Early tracheostomy | |
| 2.3.5. Postoperative bleeding | 60 | RR 0.03 (0.00 to 0.55, P value 0.02, NNTB = 2.12) | Early tracheostomy | |
| 2.3.6. Intraoperative minor bleeding | 264 | RR 0.55 (0.09 to 3.22, P value 0.50) | Early tracheostomy | |
| 2.3.7. Intraoperative significant bleeding | 264 | No event in both groups | ‐ | |
| 2.3.8. Tracheo‐oesophageal fistula | 264 | RR 2.47 (0.10 to 59.98, P value 0.58) | Late tracheostomy | |
| 2.3.9. Significant laryngotracheal pathology | 74 | RR 1.41 (0.47 to 4.22, P value 0.54) | Late tracheostomy | |
| 2.3.10. Tracheal stenosis (%) 0 to 20 (in‐hospital) | 120 | RR 1.27 (1.04 to 1.55, P value 0.02, NNTH=10) | Late tracheostomy | |
| 2.3.11. Tracheal stenosis (%) 21 to 50 (in‐hospital) | 120 | RR 0.50 (0.20 to 1.25, P value 0.14) | Early tracheostomy | |
| 2.3.12. Tracheal stenosis (%) > 50 (in‐hospital) | 120 | RR 0.40 (0.08 to 1.98, P value 0.26) | Early tracheostomy | |
| 2.3.13. Tracheal stenosis irrespective of severity (in‐hospital) | 120 | RR 1.03 (0.98 to 1.09, P value 0.24) | Late tracheostomy | |
| 2.3.14. Tracheal stenosis (%) 0 to 20 (10‐week post intubation) | 120 | RR 2.00 (1.14 to 3.51, P value 0.02, NNTH = 4.54) | Late tracheostomy | |
| 2.3.15. Tracheal stenosis (%) 21 to 50 (10‐week post intubation) | 120 | RR 1.67 (0.65 to 4.30, P value 0.29) | Late tracheostomy | |
| 2.3.16. Tracheal stenosis (%) > 50 (10‐week post intubation) | 120 | RR 1.25 (0.35 to 4.43, P value 0.73) | Late tracheostomy | |
| 2.3.17. Tracheal stenosis irrespective of severity (10‐week post intubation) | 120 | RR 1.78 (1.24 to 2.57, P value 0.002, NNTH = 3.33) | Late tracheostomy | |
| NNTB: number needed to treat for an additional beneficial outcome NNTH: number needed to treat for an additional harmful outcome | ||||
| Study ID | Comparison groups | Median | Interquartile range | P value |
| 1. Primary outcome: ventilator free‐days (at day 28) | ||||
| Early tracheostomy | 11 | 0to 21 | 0.02 | |
| Late tracheostomy | 6 | 0 to 17 | ||
| 2. Primary outcome: ventilation time (days) | ||||
| Early tracheostomy | 15 | 10 to 17 | 0.23 | |
| Late tracheostomy | 12 | 8 to 16 | ||
| 3. Secondary outcome: intensive care unit‐free days (at day 28) | ||||
| Early tracheostomy | 0 | 0 to 13 | 0.02 | |
| Late tracheostomy | 0 | 0 to 8 | ||
| 4. Secondary outcome: intensive care unit length of stay (days) | ||||
| Early tracheostomy | 17 | 13 to 22 | 0.38 | |
| Late tracheostomy | 18 | 16 to 28 | ||
| 5. Secondary outcome: intensive care unit‐free days (at day 28) | ||||
| Early tracheostomy | 8.0 | 5 to 12 | 0.048 | |
| Late tracheostomy | 3.0 | 0 to 12 | ||
| Statistical test referred to in Terragni 2010; Zheng 2012; Bösel 2013: Wilcoxon signed rank test. | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mortality at longest follow‐up time available in studies Show forest plot | 7 | 1903 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.70, 0.98] |
| 2 Mortality at 28 days Show forest plot | 3 | 744 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.64, 1.08] |
| 3 Mortality at 30 days Show forest plot | 3 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 4 Mortality at 60 days Show forest plot | 2 | 335 | Risk Ratio (M‐H, Random, 95% CI) | 0.93 [0.65, 1.35] |
| 5 Mortality at 1 year Show forest plot | 2 | 1318 | Risk Ratio (M‐H, Random, 95% CI) | 0.91 [0.82, 0.99] |
| 6 Mortality until ICU discharge Show forest plot | 2 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 7 Ventilator‐free days during 1 to 28 days Show forest plot | 2 | 335 | Mean Difference (IV, Random, 95% CI) | 1.62 [‐0.01, 3.25] |
| 8 Days of MV during 1 to 60 days Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 9 Length of ICU stay Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 10 ICU discharge (at day 28 after randomization) Show forest plot | 2 | 538 | Risk Ratio (M‐H, Random, 95% CI) | 1.29 [1.08, 1.55] |
| 11 Pneumonia Show forest plot | 5 | Risk Ratio (M‐H, Random, 95% CI) | Totals not selected | |
| 12 | 2 | 480 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.57, 1.76] |
