The authors have declared that no competing interests exist.
Conceived and designed the experiments: HH JL. Performed the experiments: JL YL. Analyzed the data: HH YL. Contributed reagents/materials/analysis tools: XC RH FA. Wrote the paper: HH YL XC JL.
To compare important outcomes between early tracheostomy (ET) and late tracheostomy (LT) or prolonged intubation (PI) for critically ill patients receiving long-term ventilation during their treatment.
We performed computerized searches for relevant articles on PubMed, EMBASE, and the Cochrane register of controlled trials (up to July 2013). We contacted international experts and manufacturers. We included in the study randomized controlled trials (RCTs) that compared ET (performed within 10 days after initiation of laryngeal intubation) and LT (after 10 days of laryngeal intubation) or PI in critically ill adult patients admitted to intensive care units (ICUs). Two investigators evaluated the articles; divergent opinions were resolved by consensus.
A meta-analysis was evaluated from nine randomized clinical trials with 2,072 participants. Compared to LT/PI, ET did not significantly reduce short-term mortality [relative risks (RR) = 0.91; 95% confidence intervals (CIs) = 0.81–1.03; p = 0.14] or long-term mortality (RR = 0.90; 95% CI = 0.76–1.08; p = 0.27). Additionally, ET was not associated with a markedly reduced length of ICU stay [weighted mean difference (WMD) = −4.41 days; 95% CI = −13.44–4.63 days; p = 0.34], ventilator-associated pneumonia (VAP) (RR = 0.88; 95% CI = 0.71–1.10; p = 0.27) or duration of mechanical ventilation (MV) (WMD = − 2.91 days; 95% CI = −7.21–1.40 days; p = 0.19).
Among the patients requiring prolonged MV, ET showed no significant difference in clinical outcomes compared to that of the LT/PI group. But more rigorously designed and adequately powered RCTs are required to confirm it in future.
Tracheostomy is customarily performed when ICU patients require long-term ventilation and fail to remove the tracheal intubation in the near future. This procedure has become more widespread, because of the extensive application of percutaneous dilatational tracheostomy (PDT) performed at the patients’ bedside
Tracheostomy is an invasive procedure that is associated with complications such as bleeding, infection, subcutaneous emphysema, pneumothorax and tracheal stenosis
Three meta-analyses have been published regarding the effect of the timing of tracheostomy on the prognosis of prolonged mechanically ventilated patients
An extensive computer search of the literature was conducted, including PubMed, EMBASE and the Cochrane Library (up to July 2013). Manual searches of journals and reference lists were also performed. Authors of papers were contacted when the results were unclear or when relevant data were not reported. Searches were performed using multiple terms, including “tracheotomy” or “tracheostomy” and “ill patients” or “critical care” or “intensive care”. The search was limited to human subjects and RCTs. No language restriction was imposed. Finally, the websites of the international network were searched to ensure that all suitable trials were included.
Studies were eligible for inclusion in the present analysis if they met the following criteria: (1) research design: RCTs; (2) population: critically ill adult patients who were admitted to ICUs, and required prolonged MV; (3) intervention: patients were assigned to either an ET group or a late tracheostomy (LT)/PI group, regardless of the tracheotomy technique used such as surgical technique (ST) or PDT. We defined ET as a tracheostomy conducted within 10 days after the initiation of translaryngeal intubation, whereas LT was performed more than 10 days after the initiation of translaryngeal intubation; (4) studies should contain data for at least one of the following outcomes: mortality, duration of MV, length of ICU stay and VAP.
Studies were excluded for following reasons: (1) the studies were quasi-randomized clinical trials; (2) ET was performed more than 10 days after the initiation of translaryngeal intubation or LT was conducted within 10 days after the initiation of translaryngeal intubation; (3) the data were missing or incomplete or the study authors were unreachable or did not reply if additional information from their trials was required.
Full-text versions of all eligible studies were obtained for quality assessment and the following data were independently extracted by two authors (HH and YL): first author, publication year, tracheostomy approach (PDT or ST), previously mentioned important clinical outcome data in our analysis, definition of VAP and methodological quality of the study. The extracted data were entered using Microsoft Excel 2010 and were checked by a third author (XC). Disagreement or doubt was resolved in pairs by consensus.
The methodological quality of the included studies was evaluated by two authors (HH and YL) using the Jadad 5-point scale, which consists of three items describing (1) randomization, (2) blinding, and (3) drop-outs and withdrawals in the report of a RCT. We assigned 2 points if the method of item was described and was appropriate; 1 point if the corresponding information of item was of insufficient detail and 0 point if the information was inappropriate. The quality scale ranged from 0 to 5 points. The studies were regarded to be of high quality if the Jadad score was ≥3 points and low quality if the score was ≤2 points
The quality of studies was additionally examined using the method recommended by a Cochrane Collaboration tool for assessing risk of bias in the included RCTs. We assigned a value of ‘high’, ‘unclear’, or ‘low’ to the following items: (1) selection bias (Was there adequate generation of the randomization sequence?); (2) selection bias (Was allocation concealment satisfactory?); (3) performance and detection bias (Was there blinding of participants, personnel and outcome assessors?); (4) attrition bias (Were incomplete outcome data sufficiently assessed and dealt with?); (5) reporting bias (Was there evidence of selective outcome reporting?); and (6) other bias (Were any other sources of bias identified?)
The primary outcomes were short-term mortality and long-term mortality, and the secondary outcomes included duration of MV, length of ICU stay (defined as the time from admission to discharge from the ICU) and VAP. To facilitate comparisons with the previous meta-analysis
The results from all of the relative studies were combined to estimate the relative risks (RRs) and associated 95% confidence intervals (CIs) for dichotomous outcomes such as incidence of mortality and VAP. With respect to the continuous outcomes of the duration of MV and ICU stay, weighted mean differences (WMDs) and 95% CI were estimated as the effect results. Heterogeneity was tested by using the I2 statistic, and studies were considered to have low (I2 = 25–49%), moderate (I2 = 50–74%) or high (I2≥75%) heterogeneity
The initial search yielded 187 potentially relevant studies, of which 35 were excluded as duplicate studies and 139 were excluded based on the titles and abstracts. Thus, the full texts of fourteen studies were read for further evaluation, and five studies were excluded because two were quasi-randomized controlled trials
Study/yearpublished | Ref.No. | ICUsetting | Surgicalapproach | ET group | LT/PI group | Outcome pre-state/Jadad score | VAP definition |
Young 2013 | 11 | 70 adult general and 2cardiothoracic CCU | PDT/ST | Within 4 days (n = 451) | After 10 days if still indicated(n = 448) | Mortality, length of ICU stay/3 | Not reported |
Zheng 2012 | 9 | Surgical patients | PDT | Day 3 of MV (n = 58) | Day 15 of MV (n = 61) | Mortality, duration of MV, length ofICU stay, VAP/5 | Using the modified CPIS. |
Trouillet2011 | 13 | Postcardiac surgeryICU | PDT | Before 5 days after surgery(n = 109) | 15 d after initiation of MV(n = 107) | Mortality, duration of MV, length ofICU stay, VAP/4 | Clinical features with positiveBAL cultures |
Terragni 2010 | 25 | 12 ICUs | PDT | After 6–8 days of laryngealintubation (n = 209) | After 13–15 days of laryngealintubation (n = 210) | Mortality, duration of MV, length ofICU stay, VAP/4 | Using the modified CPIS. |
Bolt 2008 | 12 | 25 Medical or surgicalICUs | PDT/ST | Within 4 days (n = 61) | Prolonged endotrachealintubation (n = 62) | Mortality, duration of MV, length ofICU stay, VAP/3 | Clinical features with positiveBAL cultures |
Barquist 2006 | 26 | Trauma center | ST | Before day 8 (n = 29) | After day 28 (n = 31) | Mortality, duration of MV, length ofICU stay, VAP/4 | CDC criteria |
Rumbak 2004 | 7 | 3 Medical ICUs | PDT | Within 48 hr (n = 60) | Days 14–16 of MV (n = 60) | Mortality, duration of MV, length ofICU stay, VAP/4 | Clinical features with positiveBAL cultures |
Bouderk2004 | 8 | Units for head injurypatients | PDT | 5–6 days after ICUadmission (n = 31) | Prolonged endotracheal intubation(n = 31) | Mortality, length of ICU stay/3 | CDC criteria |
Saffle 2002 | 24 | Burn ICU. | ST | 4 days after burn Injury(n = 21) | 14 days after burn injury(n = 23) | Mortality, duration of MV, length ofICU stay, VAP/3 | CDC criteria |
ICU, intensive care unit; MV, mechanical ventilation; VAP, ventilator-associated pneumonia; CPIS, Clinical Pulmonary Infection Score; CDC, Centers for Disease Control and Prevention; ET, early tracheotomy; LT late tracheotomy; PI, prolonged intubation; PDT, percutaneous dilatational tracheostomy; ST, surgery technique; BAL, bronchoalveolar lavage.
The Jadad scores of the studies (range, 3–5) are described in
All of the nine studies
Subgroupanalysis | ET≤10 days andLT≥10 days | ET≤7 days andLT≥10 days | ET≤4 days andLT≥10 days | ||||||
Trials,number | Patients,number | RR/WMD(95% CI), p | Trialsnumber | Patientsnumber | RR/WMD(95% CI), p | Trialsnumber | Patientsnumber | RR/WMD(95% CI), p | |
Short-termmortality | 9 | 2,023 | 0.91 [0.81, 1.03], p = 0.14 | 7 | 1,544 | 0.93 [0.83, 1.04], p = 0.19 | 4 | 1,222 | 0.84 [0.61, 1.15], p = 0.28 |
Long-termmortality | 3 | 994 | 0.93 [0.81, 1.07], p = 0.32 | 2 | 702 | 0.97 [0.81, 1.07], p = 0.79 | 1 | 551 | – |
Duration ofMV | 6 | 621 | −2.91 [−7.21, 1.40], p = 0.19 | 5 | 521 | −3.57 [−8.28, 1.13], p = 0.14 | 2 | 239 | −6.03 [−13.48, 1.42], p = 0.11 |
ICU stay | 3 | 396 | −4.41 [−13.44, 4.63], p = 0.34 | 2 | 336 | −6.93 [−16.50, 2.63], p = 0.16 | 1 | 120 | – |
VAP | 8 | 1,163 | 0.88 [0.71, 1.10], p = 0.27 | 6 | 684 | 0.87 [0.65, 1.15], p = 0.31 | 2 | 239 | 0.39 [0.13, 1.16], p = 0.09 |
ICU, intensive care unit; MV, mechanical ventilation; VAP, ventilator-associated pneumonia; ET, early tracheotomy; LT, late tracheotomy; PI, prolonged intubation; RR, relative risks; WMD, weighted mean difference.
Data that identified MV duration were available in the nine studies
Six studies included ICU stay as an outcome of interest
Eight studies
When only studies with ET performed within four or seven days were included to assess the effectiveness of the secondary outcomes, no significant differences were noted between the ET group and the control group (all p≥0.09) (
We performed sensitivity analyses to explore the potential sources of heterogeneity. Exclusion of the study by Rumbak et al.
We investigated the influence of important clinical outcomes in critically ill adult patients who received an ET or LT during their treatment. Our meta-analysis showed that ET did not significantly reduce short-term or long-term mortality. Additionally, ET was not associated with a markedly reduced duration of MV, length of ICU stay and VAP.
Despite the acknowledged or controversial advantages, tracheostomy, either PDT or ST, had been extensively adopted for decades by many clinicians in their routine clinical practice. However, uncertainty exists with regard to the optimal timing and potential benefits of the tracheotomy in critically ill patients requiring prolonged ventilation. Thus, there is no consistency about specific timing of the tracheotomy either early or late. In fact, the timing of the tracheostomy varied. A survey conducted by Blot et al
To the best of our knowledge, three meta-analyses of ET performed in critically ill patients have been published
To provide a better characterization of the evidence base for ET for critically ill patients, we pre-stated rigorous inclusion criteria and included only RCTs that provided specific clinical outcomes. Therefore larger sample sizes were included, and nine RCTs comprising 2,072 participants were enrolled, thus giving greater statistical power to evaluate this effect.
Our meta-analysis indicated that tracheotomy performed at an early stage within 10 days did not significantly decrease the short-term mortality, which was consistent with previous meta-analyses. Exclusion of any single study (excluding each in turn) and sensitivity analyses based on various criteria did not significantly change the pooled results and may demonstrate sufficient robustness in our findings. Significant heterogeneity was observed among these studies. Our sensitivity analyses found that one study by Rumbak et al. likely contributed to this heterogeneity
The absence of a significant effect on the duration of MV and the length of ICU stay in this meta-analysis is contrary to the results of an earlier meta-analysis by Griffiths et al.
However, our findings require additional consideration because significant heterogeneity was presented. In our sensitivity analyses, we noted that this heterogeneity was likely attributed to one trial conducted by Rumbak et al.
Although advances have been made in the diagnosis, prevention and treatment strategies of VAP in recent years, VAP remains a serious problem in ICU patients, with reported incidence rates of 10% to 65%
The strength of our meta-analysis is that we had defined rigorous inclusion criteria and incorporated original studies that enrolled large samples of patients in a randomized controlled design. We conducted additional analyses and noted the invalidity of ET performed in an earlier stage within 4 or 7 days. Nevertheless, several limitations of our meta-analysis should be considered. First, all of the RCTs included in our study were published in English; several trials
Although our results showed no statistically significant difference, there is insufficient evidence to support or refute claims of clinical benefit of ET in critically ill patients due to significant heterogeneity and inconsistent definitions of the studies included. In addition, the questions that remain to be evaluated in more rigorously designed and adequately powered RCTs of ET performed in critically ill patients include the tracheotomy approach, type of patients, safety and complications.
In summary, based on the available data, our meta-analysis suggested that ET as an intervention in critically ill adult patients did not reduce short-term or long-term mortality compared to LT/PI; moreover, incidence of VAP and duration of MV and ICU stay were also unaffected. Future RCTs are needed to define which subgroups of critically ill adult patients are most likely to benefit from this intervention.
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