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Keywords:

  • cuff-leak test;
  • postextubation airway complications;
  • accuracy;
  • GRADE;
  • systematic review

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Background and objective: Postextubation problems such as laryngeal edema and reintubation are common complications after tracheal intubation. The cuff-leak test has been proposed as a method of identifying those patients at high risk in clinical practice, but its efficacy remains controversial.

Methods: We searched electronic databases including PubMed, the Cochrane Controlled Trials Register, Web of Science, Ovid, and Embase. Studies were included if they were concerned with accuracy of the cuff-leak test and the effect of cuff-leak test screening on patient-important outcomes. Two reviewers independently assessed study quality with the QUADAS tool and extracted data. We compiled diagnostic two by two tables and pooled estimates of sensitivity and specificity, but refrained from pooling when there was considerable clinical or statistical heterogeneity.

Results: Sixteen diagnostic tests with 3172 participants and six clinical trials with 2500 patients were identified. The median diagnostic odds ratios for predicting postextubation laryngeal edema and reintubation were 18.16 (range, 3.54 to 356.00) and 10.80 (2.74 to 1665.00), respectively. The accuracy of the cuff-leak test varied with different methods, duration of intubation, and study population. An indirect comparison found significant differences in post-extubation incidence of laryngeal edema (OR = 2.09, 95% CI, 1.28 to 2.89) but not reintubation (OR = 0.94, 95% CI, 0.32 to 1.57) if using cuff-leak test screening.

Conclusions: Our results suggest the cuff-leak test accurately predicts which adult patients are at high risk of postextubation airway complications, but randomized controlled trials are needed to further assess this diagnostic strategy.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Translaryngeal intubation is a potentially life-saving procedure for patients in respiratory distress, but it sometimes generates local complications (1). Our recent study showed that prophylactic administration of steroids in multidose regimens before planned extubation reduces the incidence of laryngeal edema after extubation and consequent reintubation for adults (2), but Young et al. suggest that corticosteroids should be given only to patients at high risk (3). However, pretreating patients with corticosteroids assumes postextubation airway complications are predictable events (4).

As the presence of an endotracheal tube precludes direct visualization of the upper airway prior to extubation, a cuff-leak test, which shows whether there is a leak around the endotracheal tube with the cuff deflated, was first proposed in 1988 as a simple method of predicting the occurrence of postextubation airway complications (5). This test consists of deflating the balloon cuff of the endotracheal tube in order to assess the air leak around the tube, which permits an indirect evaluation of upper airway patency (6).

A considerable number of studies on the cuff-leak test have been published, but their results remain controversial (7–9), leaving physicians to make difficult decisions regarding extubation. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance on grading the quality of underlying evidence and the strength of recommendations in health care. According to the GRADE system, the best way to assess any diagnostic strategy is a randomized controlled trial in which investigators randomize patients to experimental or control diagnostic approaches and measure mortality, morbidity, symptoms, and quality of life (10). Although a meta-analysis on the cuff-leak test's accuracy was undertaken recently (11), the test accuracy is at best a surrogate for patient-important outcomes. Furthermore, that study lacked subgroup or comparative analyses, and did not link evidence on diagnosis test accuracy to clinical practice. We performed the present systematic review to establish the overall accuracy of the cuff-leak test for predicting postextubation airway complications, which should trigger a clinical decision to initiate treatment.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Ethical review

This study was designed as a systematic review, so it did not require ethical approval, but we extracted any ethical review information from included studies.

Search strategy and selection criteria

We searched electronic databases including PubMed (1980 to Jan 2011), CENTRAL (Cochrane Controlled Trials Register, issue 1, 2011), Web of Science (1994 to Jan 2011), Ovid (1994 to Jan 2011), and Embase (1984 to Jan 2011). Using “cuff leak test”(13) as our only search term, we searched for all clinical trials on the cuff-leak test, and scanned the reference lists of review articles and included studies to identify other potentially eligible studies. There was no limitation on language, year of publication, or publication status. Trials were included if they involved diagnostic tests in adults and had adequately reported data for calculating sensitivity and specificity. After excluding duplicates, two reviewers (T.Z. and W.W.C.) reviewed the full text of all pieces with titles and abstracts that seemed to fit the criteria for inclusion.

Data extraction

From each included article we extracted details on authors, year of publication, study population, gender of subjects, sample size, duration of intubation, test methods, diagnostic cutoff points, true and false positive (TP and FP) and false and true negative (FN and TN) subjects, and methodological quality.

The two reviewers independently assessed the quality of each study and extracted data. Disagreements were resolved by consensus or by consulting a third reviewer (G.W.). If information was not reported adequately, we requested details from the authors. If the authors did not respond to our letters, the “unknown” items were treated as “no.” Each reviewer extracted the data to construct a 2 × 2 table for every cutoff point that was published in each study.

Reference standards and patient-important outcomes

After extubation, stridor or dyspnea, an audible high pitched inspiratory wheeze caused by turbulent airflow through narrowed airways, is generally accepted as a clinical indication of laryngeal edema (2). Major laryngeal edema necessitates postextubation reintubation. Therefore, reference standards for postextubation airway complications included laryngeal edema and reintubation secondary to upper airway obstruction. In this study, our primary patient-important outcome was laryngeal edema after extubation, with subsequent reintubation necessitated by laryngeal edema as the secondary patient-important outcome.

Quality assessment

We assessed the methodological quality of studies using guidelines in the quality assessment for studies of diagnostic accuracy (QUADAS) tool (maximum score, 14) (14). Quality scoring in QUADAS was undertaken, in which a score of 1 was given when a criterion was fulfilled, 0 if a criterion was unclear, and −1 if the criterion was not achieved. Test accuracy studies with design deficiencies can produce biased results (15). Accordingly, the following characteristics in study design, which encompass some of the more important forms of bias, were evaluated (13, 16): (1) cross-sectional design; (2) sample size calculation; (3) consecutive or random sampling subjects; (4) blinding; (5) prospective data collection.

Effect of cuff-leak test screening on patient-important outcomes

According to the GRADE system and using methods detailed in a previous review (2), we evaluated whether there was an effect of cuff-leak test screening—followed, when indicated, by prophylactic administration of steroids—on incidence of postextubation airway complications such as laryngeal edema and reintubation secondary to upper airway obstruction.

Statistical analysis

For each study, the sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and diagnostic odds ratio (DOR) were calculated. The DerSimonian Laird method (random effects model) was used to incorporate variation among studies when pooling sensitivity, specificity, PLR, NLR, and DOR. Furthermore, a summary receiver operator characteristic (sROC) curve of all the studies was created, as this is a better summary of the study results than is a single jointed summary estimate of sensitivity and specificity. The area under the sROC curve (AUC) was used to judge the degree of accuracy of the tests according to published guidelines (excellent: ≥0.97; very good: 0.93–0.96; good: 0.75–0.92; poor: 0.50–0.75) (17).

I2 or Q tests, though commonly used in meta-analysis, are not recommended for assessing statistical homogeneity in diagnostic reviews because they do not take into account the association between sensitivity and specificity. Statistical heterogeneity was defined as an overlapping 95% confidence interval (CI) of both sensitivity and specificity and differences in point estimates among the studies of less than 20% (18, 19). In cases of statistical or clinical heterogeneity (in terms of characteristics of populations and test characteristics), we refrained from pooling and presented median values and ranges instead. We carried out subgroup and comparative analyses to assess the effects of different methods of the cuff-leak test, as well as the effects of risk factors for postextubation airway complications (e.g., duration of intubation, gender, and reason for admission) (20) on the accuracy of the cuff-leak test, when each subgroup included data of at least four diagnostic studies. Furthermore, to assess the effects of QUADAS scores and other covariates (i.e., important study design characteristics) on the diagnostic ability of the cuff-leak test, we included them as covariates in univariate meta-regression analysis.

Investigating publication bias for diagnostic tests is problematic (21). Funnel plot-based tests used to detect publication bias in reviews of randomized controlled trials have proven misleading for diagnostic studies (22). Therefore, we did not assess publication bias in this systematic review.

The threshold of significance was set at P < 0.05. All statistical analyses were performed using Stata version 8.0 (Stata Corp LP, College Station, Texas) and MetaDiSc version 1.1.1 (Zamora J, Muriel A, Abraira V, Madrid, Spain).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Studies included

Our search strategy initially yielded 118 citations (Figure 1). Of these, 16 unique studies on predicting postextubation airway complications were included in our review; the included studies involved a total of 3172 participants (3218 extubations) (1, 7, 8, 23–35). In addition, six clinical trials (2500 total patients) on prophylactic administration of steroids (with or without cuff-leak test screening) for preventing postextubation airway complications were identified (20, 24, 25, 36–38), as described in our previous review (2).

image

Figure 1. Flow chart of study identification, inclusion, and exclusion

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Study characteristics and quality of reporting

The adult subjects of the included studies varied from the medical care population to trauma or surgical patients, and were thus somewhat heterogenous (Table 1). The average sample size of the included studies was 201, with a range of 49–543. We found that the sample size was not consistent with the number of extubations in four studies (27, 28, 32, 33), suggesting that at least two cuff-leak tests were performed in the same subject. Participants were tracheally intubated via the oral or nasal route for a length of time ranging from less than 24 hours to several days, and were monitored for about 24 or 48 hours after extubation.

Table 1.  Characteristics of included studies
StudyStudy populationn (% female)Extubations No.Age (y)Duration of intubationSuction of secretionsIntubated routeVentilation modeTidal volumeTime constraint (h)
  1. ICU = intensive care unit; NA = Not applicable; AC = assistant and control model, VC = volume control model. Time constraints are for investigation after extubation.

Fisher 1992 (35)Trauma or surgical patients 62 (NA)62NA23.9 hNANANANANA
Marik 1996 (34)Respiratory failure and postoperative100 (39.0)10057 ± 9 3.8 ± 3.2 dUnclearOral and nasalACNA24
Miller 1996 (33)Mechanically ventilated adult patients 88 (NA)10063 ± 175.8 ± 0.5 dUnclearOral and nasalACNA24
Engoren 1999 (32)Cardiac surgery population524 (33.0)53165 ± 1012.9 (10.5 to 21.2) hYNAAC10–12 mL/KgNA
Sandhu 2000 (31)Trauma patients110 (27.3)110NA2.6 ± 2.6 d (n = 97);YNAACNA24
     5.9 ± 5.0 d (n = 7);     
     6.5 ± 1.9 d (n = 6)     
De Bast 2002 (30)General adult population 76 (NA)7667 (51–76)Low leak: 3 (1 to 5) d; high leak: 1 (1 to 5) dUnclearNAACNA24
Jaber 2003 (29)ICU patients112 (30.4)112Absence of stridor: 59 ± 16; Presence of stridor: 61 ± 19Absence of stridor: 5.5 ± 6.3 d; Presence of stridor: 10.9 ± 7.0 dYNAAC10–12 mL/KgNA
Maury 2004 (28)ICU patients 99 (47.5)11560 ± 193.5 ± 3.4 dYOral and nasalNANA24
Erginel 2005 (27)Patients suffering from a variety of respiratory disease 56 (NA)6763.6 ± 12.15.6 ± 4.6 d (>24 h)YNAAC7 mL/KgNA
Kriner 2005 (26)Medical and surgical patients462 (46.8)46261 ± 175 ± 4 d (>24 h)YOral and nasalACNA24
Chung 2006 (1)Acute respiratory failure due to various medical causes 95 (33.7)9571.3 ± 13.628.1 ± 17.6 dYNAAC10 mL/KgNA
Cheng 2006 (25)Medical and surgical patients321 (NA)321>18>24 hNANAAC8 mL/Kg48
Lee 2007 (24)Medical care population365 (NA)365>18>48 hUnclearNAVC10 mL/Kg48
Wang 2007 (8)ICU patients110 (52.7)11071 ± 1313 ± 14 (1 to 65) dYoralAC10 mL/KgNA
Shin 2008 (7)Trauma patients 49 (32.7)49Cuff-leak present: 36.5; absent: 38.1Cuff-leak present: 87.1 h; absent: 36.6 hNANAAC10 mL/KgNA
Sukhupanvarak 2008 (23)ICU patients543 (41.1)543Presence of stridor: 67 ± 16; Absence of stridor: 60 ± 18Presence of stridor: 5.3 ± 3.2 d; Absence of stridor: 3.9 ± 3.8 dYNANANA24

All included diagnostic tests were cross-sectional studies (Table 2). Four of 16 trials were approved by Institutional Review Board (IRB), and only one study was registered in public service platform of trial registration (24). No sample size calculations were applied in any included study. Subjects who participated in the cuff-leak test were chosen consecutively or at random in 14 of the included studies. Blinding was used in 12 studies. The average QUADAS score of the methodological quality of studies was 8.2 whose QUADAS assessment was presented in Figure 2.

Table 2.  Quality assessment of included studies
StudyStudy registrationEthical reviewCross-sectional DesignSample size calculationConsecutive or randomBlindnessProspectiveInter-investigator agreementSubgroup analysisQUADAS
Fisher 1992 (35)NoNoYesNoUnclearNoYesNoNo 5
Marik 1996 (34)NoYesYesNoConsecutiveYesYesNoNo12
Miller 1996 (33)NoNoYesNoConsecutiveYesYesNoNo 7
Engoren 1999 (32)NoNoYesNoConsecutiveYesYesNoNo 7
Sandhu 2000 (31)NoNoYesNoConsecutiveUnclearYesNoNo 9
De Bast 2002 (30)NoYesYesNoConsecutiveYesYesNoNo10
Jaber 2003 (29)NoYesYesNoConsecutiveYesYesNoNo10
Maury 2004 (28)NoYesYesNoConsecutiveYesYesNoYes 9
Erginel 2005 (27)NoYesYesNoConsecutiveYesYesNoYes 7
Kriner 2005 (26)NoYesYesNoConsecutiveUnclearYesNoNo 6
Chung 2006 (1)NoYesYesNoConsecutiveYesYesNoNo10
Cheng 2006 (25)NoYesYesNoConsecutiveYesYesNoNo 4
Lee 2007 (24)YesYesYesNoRandomYesYesNoNo11
Wang 2007 (8)NoYesYesNoConsecutiveYesYesNoNo10
Shin 2008 (7)NoYesYesNoNoUnclearNoNoNo 5
Sukhupanvarak 2008 (23)NoYesYesNoRandomYesYesNoNo 9
image

Figure 2. Quality assessment in 16 diagnostic tests according to QUADAS items, presented as the proportion of included studies

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The cuff-leak test and the threshold effect

The included studies used two kinds of methods for the cuff-leak test, qualitative (presence or absence of leak around the tube) and quantitative. The quantitative method, Miller's test, was proposed by Miller et al. in 1996 (33), and can be further subdivided into an absolute measure (measured in milliliter volume) and a relative measure (quantified as percent volume). The cutoff value of the cuff-leak test in the quantitative method varied from 88–283 ml or 10–57% in included studies. Regression analysis of the diagnostic threshold found no threshold effect in this systematic review (all P > 0.05 for both Spearman correlation coefficient and beta coefficient in Moses’ model) (Data not shown).

Outcomes for systematic review and subgroup analyses

The total incidence of postextubation laryngeal edema was 6.79% (95% CI 5.94–7.73%) with a range of 0.60–36.8%, while the incidence for reintubation secondary to laryngeal edema was 3.52% (95% CI 2.79–4.36%) with a range of 0.0–10.53% (Table 3). The incidence of postextubation laryngeal edema was 0.57% for less than 24 hours of intubation, 4.61% for between 24 hours and 5 days, and 16.70% for more than 5 days.

Table 3.  Results of the cuff-leak test in included studies for identifying adult patients at high risk of postextubation airway complications
StudyCuff-leak test typeCutoffEstimates of optimal cutoffsLaryngeal edemaSubsequent reintubation of laryngeal edema
Incidence (%)TPFPFNTNIncidence (%)TPFPFNTN
  1. CLT = the cuff-leak test; NA = not applicable; TP = true positive; FP = false positive; FN = false negative; TN = true negative.

Fisher 1992 (35)Qualitative methodPresence or absence of leakNANANANANANANA70055
Marik 1996 (34)One methodPresence or absence of leakNA2.0/10024094NANANANANA
Miller 1996 (33)Miller's CLT110 mlDetermined by visual inspection of ROC curve5.3/954118960.023189
Engoren 1999 (32)Miller's CLT110 mlDetermined by visual inspection of ROC curve0.6/5310203508NANANANANA
Sandhu 2000 (31)Miller's CLT10%Determined by sub-group analysis11.8/1107269546.236398
De Bast 2002 (30)Miller's CLT15.5%Determined by visual inspection of ROC curve13.2/76NANANANA80.0619249
Jaber 2003 (29)Miller's CLT130 mlDetermined by visual inspection of ROC curve11.6/112115294NANANANANA
Maury 2004 (28)The qualitative methodPresence or absence of leakNA3.5/11542208925.0125089
Erginel 2005 (27)Miller's CLT283 mlDetermined by visual inspection of ROC curve10.4/67614146NANANANANA
  57%Determined by visual inspection of ROC curve 614146NANANANANA
Kriner 2005 (26)Miller's CLT110 mlRefer to Miller 19964.3/46210721037035.03794376
  15.50%Refer to De Bast 2002 74113401 2465409
Chung 2006 (1)Miller's CLT140 mlDetermined by visual inspection of ROC curve36.8/95316454NANANANANA
Cheng 2006 (25)Miller's CLT24%Determined by visual inspection of ROC curve8.10/32121107518857.70131152191
Lee 2007 (24)Miller's CLT110 mlRefer to Miller 19967.95/36515651427124.13774281
Wang 2007 (8)Miller's CLT88 mlThe best Youden index18.2/110121088055.0814385
  18%The best Youden index 1110980 NANANANA
Shin 2008 (7)Miller's CLT10%Defined by authors2.0/49170410.008041
Sukhupanyarak 2008 (23)The qualitative methodPresence or absence of leakNA4.8/5434242249380.8NANANANA

The subgroup and comparative analyses were based on the different methods of the cuff-leak test, durations of intubation, and study populations (Table 4). The heterogeneity was across Se, Sp, PLR NLR, and DOR. There were increased medians of specificity, DOR, and AUC for identifying patients at high risk of postextubation laryngeal edema in the qualitative method and the absolute volume compared with the relative volume cuff-leak test, but the sensitivity of the qualitative method, at 1.00, had a broader range (Figure 3A). All three methods of the cuff-leak test had similar specificities for predicting postextubation reintubation, about 0.85 (Figure 3B).

Table 4.  Outcomes of systematic review and subgroup and comparative analyses
Study characteristicNo. of studiesSensitivitySpecificityPositive LRNegative LRDiagnostic ORAUC
  1. LR = likelihood ratio; OR = odds ratio; AUC = area under curve. With medians and ranges in case of heterogeneity.

Laryngeal edema140.80 (0, 1.00)0.90 (0.64, 0.99)4.69 (2.23, 72.00)0.30 (0.13, 0.91)18.16 (3.54, 356.00)0.89 ± 0.04
 Mean duration of intubation       
   ≤5 days 51.00 (0, 1.00)0.85 (0.80, 0.96)4.48 (3.07, 18.33)0.30 (0.13, 0.91)16.6 (3.54, 105.00)0.87 ± 0.06
   >5 days 50.85 (0.60, 0.89)0.90 (0.77, 0.99)8.86 (3.67, 72.00)0.19 (0.13, 0.45)69.75 (12.00, 356.00)0.92 ± 0.05
 Study population       
   Surgical 30.54 (0.0, 1.00)0.96 (0.85, 0.98)4.90 (3.23, 26.12)0.47 (0.30, 0.91)16.60 (3.54, 55.42)0.92 ± 0.13
   Medical 30.86 (0.52, 0.89)0.81 (0.77, 0.90)3.67 (2.67, 8.86)0.19 (0.13, 0.60)19.71 (4.47, 69.75)0.91 ± 0.06
   Surgical and medical 80.80 (0.15, 1.00)0.92 (0.64, 0.99)4.94 (2.23, 72.00)0.25 (0.13, 0.89)23.9 (0.13, 356.00)0.89 ± 0.05
 Qualitative cuff-leak test method 31.00 (0.15, 1.00)0.95 (0.80, 0.96)4.48 (3.31, 18.33)0.17 (0.13, 0.89)35.80 (3.73, 105.00)0.94 ± 0.05
 Quantitative cuff-leak test methods       
   Absolute volume in cuff-leak 80.70 (0.00, 0.89)0.89 (0.77, 0.99)4.54 (2.67, 72.00)0.33 (0.13, 0.91)31.71 (3.54, 356.00)0.90 ± 0.05
   Relative volume in cuff-leak 60.68 (0.35, 1.00)0.87 (0.64, 0.98)4.34 (2.23, 26.12)0.39 (0.19, 0.72)13.19 (5.27, 55.42)0.82 ± 0.05
Reintubation100.67 (0.43, 1.00)0.83 (0.62, 1.00)3.38 (1.99, 105.00)0.34 (0.06, 0.73)10.80 (2.74, 1665.00)0.82 ± 0.05
 Mean duration of intubation       
   ≤5 days 50.88 (0.43, 1.00)0.81 (0.72, 1.00)3.03 (2.47, 105.00)0.34 (0.06, 0.69)9.14 (3.57, 1665.00)0.80 ± 0.21
   >5 days 20.70 (0.67, 0.73)0.92 (0.86, 0.97)12.79 (5.41, 9.42)0.33 (0.32, 0.34)37.76 (16.19, 59.33)
 Study population       
   Surgical 30.50 (0.50, 0.93)0.94 (0.84, 0.99)8.67 (3.06, 103.60)0.53 (0.07, 0.60)16.33 (5.13, 1540.00)0.94 ± 0.48
   Medical 10.43 (0.10, 0.82)0.78 (0.74, 0.83)1.99 (0.83, 4.79)0.73 (0.38, 1.39)2.74 (0.60, 12.49)
   Surgical and medical 60.74 (0.43, 1.00)0.81 (0.62, 0.97)3.03 (2.31, 20.44)0.33 (0.21, 0.69)10.67 (3.57, 59.33)*0.83 ± 0.04
 Qualitative cuff-leak test method 21.00 (1.00, 1.00)0.89 (0.78, 1.00)54.19 (3.38, 105.00)0.19 (0.06, 0.32)114.97 (10.53, 1665.00)
 Quantitative cuff-leak test methods       
   Absolute volume in cuff-leak 40.55 (0.43, 0.73)0.84 (0.78, 0.97)3.81 (1.99, 20.44)0.59 (0.32, 0.73)9.88 (2.74, 59.33)0.71 ± 0.30
   Relative volume in cuff-leak 50.50 (0.29, 0.87)0.84 (0.62, 0.94)2.83 (2.31, 8.67)0.53 (0.21, 0.79)7.74 (3.56, 16.33)0.81 ± 0.04
image

Figure 3. Symmetric ROC curves for the cuff-leak test in predicting postextubation laryngeal edema (A) and reintubation (B). inline image= each study in the meta-analysis (the size of each study is indicated by the size of the solid circle); SROC curves summarize the overall diagnostic accuracy

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The accuracy of the cuff-leak test varied with different durations of intubation. There was a higher median specificity of 0.90, DOR of 69.75, and AUC of 0.92 in predicting postextubation laryngeal edema in subjects with more than 5 days mean duration of intubation compared with those with less than 5 days. Furthermore, there was a higher median specificity of 0.92 and DOR of 37.76 for predicting postextubation reintubation in patients with more than 5 days of mean duration of intubation.

Multiple regression analysis

QUADAS scores, other quality factors of diagnostic tests, duration of intubation, and study populations were imported into a meta-regression analysis to assess the effect of study quality on the DOR of the cuff-leak test for identifying high-risk patients. The analysis found that variations of QUADAS, cross-sectional design, consecutive or random, blinding, prospective design, duration of intubation, and study population did not contribute to the heterogeneity of ratio of DOR (rDOR) (all P > 0.05) (Table 5).

Table 5.  Weighted meta-regression of the effects of methodological quality, duration of intubation, and study population on diagnostic precision of the cuff-leak test
CovariatesCoefficientrDOR (95%CI)P value
Laryngeal edema   
 QUADAS−0.0860.92 (0.30, 2.82)0.858
 Cross-sectional design 0.081.08 (0.11, 11.05)0.940
 Consecutive or random 0.081.08 (0.11, 11.05)0.940
 Blinding 0.2441.28 (0.03, 57.16)0.880
 Prospective 0.2921.34 (0.00, 854.09)0.915
 Duration of intubation 0.0771.08 (0.88,1.33)0.404
 Study population−0.8640.42 (0.02, 7.41)0.488
Reintubation   
 QUADAS−0.2040.82 (0.51, 1.31)0.336
 Cross-sectional design
 Consecutive or random−5.2390.01 (0.00, 0.98)0.057
 Blinding−0.8330.43 (0.06, 3.08)0.338
 Prospective
 Duration of intubation 0.0171.02 (0.76, 1.35)0.892
 Study population 0.5261.69 (0.40, 7.16)0.406

Effect of cuff-leak test screening with prophylactic administration of steroids on postextubation airway complications

We found no clinical trials in which investigators randomized subjects to either take or not take the cuff-leak test. In six of the studies, patients were divided into three groups who were treated with either the cuff-leak test screening following by prophylactic administration of steroids in the case of positive results (the CLT group, n = 686), or steroids or placebo without cuff-leak test screening (the steroids group, n = 905 and the placebo group, n = 909). In the CLT group, only 208 patients (30.3%) had positive cuff-leak test results [the CLT (positive) group)] and received prophylactic administration of steroids. There was no significant difference in the incidence of postextubation laryngeal edema between the CLT group and the steroids group (OR = 1.39, 95% CI 0.79–2.24, P = 0.070). However, the incidence of postextubation reintubation in the CLT group was similar to that in the placebo group (OR = 0.94, 95% CI 0.32 to 1.57, P = 0.860) (Table 6). According to inference analysis, the mean dose of equivalent methylprednisolone in the CLT group was much more decreased than that with the steroids group (34.23 ± 2.20 mg vs 74.23 ± 1.38 mg, P < 0.001).

Table 6.  Effect of the cuff-leak test on incidence of postextubation airway complications
GroupsNo. of studiesLaryngeal edemaReintubation
EventsOdds ratio (95%CI)NNTPEventsOdds ratio (95%CI)NNTP
  1. CLT = cuff-leak test; NNT = number needed to treat; CI = confidence interval. avs Steroids; bvs Placebo; cvs CLT.

CLT238/6861.39 (0.79, 2.24) 530.070a16/6864.34 (1.59 to11.82) 570.002a
 CLT (negative) 19/4781.09 (0.74, 1.44)3050.760a6/4782.27 (0.00, 4.97)1430.162a
 CLT (positive) followed by steroids 19/2080.79 (0.38, 1.20) 420.317b10/2082.24 (0.51, 3.98) 390.306b
Steroids433/9050.32 (0.19, 0.44) 130.000b5/9050.25 (0.01, 0.50) 610.003b
Placebo4105/9092.09 (1.28, 2.89) 140.000c20/9090.94 (0.32, 1.57)7060.860c

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Postextubation problems such as laryngeal edema and reintubation prolong the need for mechanical ventilation and increase morbidity in intensive care unit patients. In our study, the incidence of laryngeal edema varied from 0.6–36.8%, and the reintubation rates secondary to laryngeal edema from 0–80.0%, possibly because of different study populations, severity of diseases, and durations of intubation. We found that the cuff-leak test accurately identifies adult patients at high risk of postextubation airway complications, and cuff-leak test screening reduces the incidence of postextubation laryngeal edema but not of reintubation in indirect comparison analysis. We also found that the incidence of postextubation laryngeal edema increased when intubation was prolonged.

Systematic reviews of interventions sometimes find very similar estimates of the effects of competing interventions in different studies, with differences in effects small enough to be explicable by chance. However, in test accuracy reviews large differences are commonly noted among studies, differences too large to be explained by chance, indicating that actual test accuracy varies among studies, or that there is heterogeneity in test accuracy. Substantial heterogeneity was found to be present in our study, so we refrained from pooling and presented median values and ranges instead (37). We then explored the reasons for the heterogeneity with meta-regression techniques, but found no clinical heterogeneity. This indicates that the study design, duration of intubation, and study population did not substantially affect the diagnostic accuracy.

The cuff-leak test, a simple method for predicting postextubation airway complications, includes three methods, one qualitative and two quantitative. Pettignano et al. (40) demonstrated that the qualitative cuff-leak test is reproducible and reliable. We posited that the cuff-leak test quantified in percent volume would have the highest accuracy among the three approaches because height, weight, gender, and other factors would be adjusted for by this method. However, there were no reasonable explanations for this finding. The accuracy of the cuff-leak test for predicting postextubation airway complications varied among the three different methods. Therefore, the qualitative method should be used in combination with the quantitative method in clinical practice.

The best way to evaluate a diagnostic test is to understand the expected clinical benefits and harms attributable to its use. Integration of systematic reviews of diagnostic test accuracy and decision making is an emerging area of active research (12, 41). We need to consider the range of potential “threshold probabilities” that should trigger a clinical decision to initiate treatment (42). Ideally, patients at high risk of developing postextubation airway complications should be identified as early as possible. Treatments such as prophylactic administration of steroids to reduce postextubation airway complications should then be started (3). The best way to assess any diagnostic strategy is a randomized controlled trial in which investigators randomize patients to experimental or control diagnostic approaches and measure patient-important outcomes (43). There are no trials using random allocation of the cuff-leak test, but six trials were identified in which the diagnostic strategies of the cuff-leak test with prophylactic administration of steroids were compared indirectly. Our previous study suggests that patients with positive cuff-leak test results, or at high risk, would realize much more benefit from prophylactic steroid administration (2). Furthermore, a recently published study (44) and another abstract (45) show that the efficacy of steroids in preventing stridor and reintubation was only observed in a high-risk population as identified by the cuff-leak test, which strengthens the effect of the cuff-leak test on predicting postextubation airway complications. Using the GRADE system, we found evidence that cuff-leak test screening would reduce the incidence of postextubation laryngeal edema but not reintubation. However, this pattern was weaker for trials in which the comparisons were indirect (46).

Limitations

Our study has some limitations. First, three different methods of the cuff-leak test, and prophylactic administration of steroids with or without the cuff-leak test screening, were compared indirectly but not head-to-head, which would decrease the reliability and generalizability of the results. Second, substantial heterogeneity was found in our study, so we did not conduct pooled estimates. Third, only one therapeutic strategy (prophylactic administration of steroids) was used following a positive cuff-leak test in the included studies. Fourth, postextubation airway complications such as laryngeal edema and reintubation secondary to upper airway obstruction, which were taken as reference standards, were also patient-important outcomes. What's more, there is a time interval between cuff-leak test screening and the occurrence of patient-important outcomes or reference standards.

In conclusion, our systematic review suggests that the cuff-leak test accurately identifies patients at high risk of postextubation airway complications, and treating patients with positive test results with prophylactic steroids seems to reduce the incidence of postextubation laryngeal edema but not postextubation reintubation. Further randomized controlled trials, in which investigators randomize patients to the cuff-leak test or a sham test with prophylactic administration of steroids and measure postextubation airway complications, are needed to assess this diagnostic strategy.

Funding:

This research was supported by the National Natural Science Foundation of China (No. 30971326), the Sichuan Youth Science and Technology Foundation (No. 2010JQ0008), and the Funding Doctoral Fund of the Ministry of Education of China (No. 20070610155).

Conflicts of Interest:

Dr. Gang Wang is supported by the National Natural Science Foundation of China (No. 30971326), the Sichuan Youth Science and Technology Foundation (No. 2010JQ0008), Youth Science Funding of Sichuan University (2011SCU04B17) and the Funding Doctoral Fund of the Ministry of Education of China (No. 20070610155). Dr. Lei Wang is supported by the National Natural Science Foundation of China (No. 30901907).

Authorship:

Dr. Gang Wang contributed substantially to the conception and design of the study; collection, extraction and interpretation of the data; drafting of the manuscript; and statistical analysis. Drs. Ting Zhou, Hong-ping Zhang, Tao Fan, Juan-juan Fu, and Wei-wei Chen were responsible for collection, extraction, and interpretation of the data. Dr. Ze-yu Xiong was responsible for interpretation of the data and critical revision of the manuscript. Dr. Lei Wang provided insight into the statistical methods.

Ethics:

This study was designed as a systematic review, so it did not require ethical approval, but we extracted any ethical review information from included studies.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

We are grateful to Ding LW and De Bast Y who sent additional information on their original studies. We also thank Profs. Gibson PG. (University of Newcastle, Australia), Van der Windt DA (Keele University, UK), de Vet HC (VU University, Amsterdam). Liu GJ (Chinese Cochrane Center, China) for their statistics suggestions, and Ms. Ruan R for her help in preparing this manuscript.

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  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
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