Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis

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Research paper

Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis Miles Wilson, BPhty a, * Marc Nickels, BPhty a, b Brooke Wadsworth, BPhty a, c Peter Kruger, PhD, MBBS, BSc(hons), FCICM, FANZCA d, e Adam Semciw, PhD, B.Appl.Sci (Physio, Hons), G.Cert (Epidemiology) a, f, g, h a

Department of Physiotherapy, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia Queensland University of Technology, Australia c The Hopkins Centre, Menzies Health Institute Queensland, Griffith University, Logan Campus, Queensland, Australia d Intensive Care Unit, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia e School of Medicine, University of Queensland, Australia f Centre for Functioning and Health Research, Metro South Hospital and Health Service, Brisbane, Queensland, Australia g School of Health and Rehabilitation Sciences, The University of Queensland, Australia h La Trobe University, Australia b

article information

a b s t r a c t

Article history: Received 13 September 2018 Received in revised form 19 January 2019 Accepted 25 January 2019

Purpose: Respiratory complications are the most significant cause of morbidity and mortality in acute cervical spinal cord injury (CSCI). The prevalence of extubation failure (EF) and factors associated with it are unclear. This research aimed to systematically synthesise and pool literature describing EF and associated risk factors in acute CSCI. Methods: A systematic review was performed using medical literature analysis and retrieval system online, cummulative index of nursing and allied health literature, excerpta medica dataBASE, and Cochrane library. Articles were screened using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A proportion meta-analysis was conducted to pool rates of EF. Odds ratios and weighted mean differences were calculated to evaluate risk factors. The R statistical software package was used. Results: Of the 347 articles that were identified, six articles satisfied the inclusion criteria (387 participants). The pooled EF rate was 20.25% (10.13e36.38%). Type of CSCI was the only statistically significant risk factor. The odds of EF occurring were 2.76 [95% confidence interval (CI): 1.14; 6.70] times greater for complete CSCI than for incomplete CSCI. Conclusions: One in five patients with acute cervical SCI fails extubation. The odds of EF occurring are almost three times greater in complete CSCI. Future research should aim to improve standard data sets and prospective evaluation of adjuvant therapy in the peri-extubation period. © 2019 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Keywords: Spinal cord injury Extubation Ventilation Wean Airway

1. Introduction Spinal cord injury (SCI) is estimated to affect up to 32 people per million in Australia each year, with 38.4 per million suffering from traumatic SCI in North America.1,2 Respiratory complications are

* Corresponding author at: Physiotherapy Department, Princess Alexandra Hospital, 199, Ipswich Road, Woolloongabba. Queensland 4102, Australia. Tel.: þ3176 2120; fax: þ3176 5759. E-mail address: [email protected] (M. Wilson).

the most significant cause of morbidity and mortality for this population3 and significantly contribute to the hospital length of stay (LOS) and subsequent economic burden.4 These respiratory complications are multifactorial but are associated with denervation of muscles required for inspiration and secretion clearance as a consequence of the SCI.5 These impairments can lead to atelectasis, secretion retention, and, in many cases, pneumonia.5 The type and severity of complications are typically associated with the neurological level of injury.6 Intubation after acute cervical spinal cord injury (CSCI) is often necessary for both the management of respiratory deterioration

https://doi.org/10.1016/j.aucc.2019.01.007 1036-7314/© 2019 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007

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and when surgical intervention is required.7e9 In cases where high CSCI and diaphragmatic impairment exist, intubation and mechanical ventilation may be required more urgently.3,7,10,11 Once the patient is medically stable and deemed unlikely to be dependent on a ventilator to sustain life (such as complete injury at C1-2), a decision must be made whether or not to extubate. There is no clear consensus for best practice of airway management at this point in time. Some clinicians advocate for noninvasive mechanical ventilation instead of invasive tracheostomy,12 whereas others support early tracheostomy.13 Early tracheostomy is associated with reduced duration of mechanical ventilation and intensive care unit (ICU) LOS.14 Yet, other studies find that unnecessary tracheostomy is associated with a number of undesirable outcomes.10,15,16 Thus, the clinician is faced with considering the balance of these risks and benefits when deciding to extubate or perform a tracheostomy. Research has revealed factors that may be useful in this decisionmaking process. This includes level and classification of CSCI, associated injuries,13,17 respiratory factors,10,18e20 and changes on magnetic resonance imaging.21 Further to this, one systematic review concluded that a clinical pathway with a structured respiratory protocol that includes a combination of regular physiotherapy treatment techniques is effective in reducing respiratory complications and costs.8 Despite the valuable insights provided by previous research, some patients who meet clinical criteria for extubation go on to develop respiratory failure, subsequently requiring emergent reintubation. Extubation failure has been defined as the unplanned reintubation after the removal of an endotracheal tube.18,22 Although extubation failure has been investigated in a number of populations including postsurgical, medical, and neurocritical patients,23e25 research specifically examining this issue in SCI is scarce. Extubation failure rate in the SCI population has been reported to vary between 0% and 60% and can result from multiple causes involving the respiratory, cardiovascular, or neurological systems.15,26 Respiratory complications play an important role, being responsible for up to one-third of occurrences of extubation failure in the general ICU population16 and likely to be even higher in the SCI population. Potential consequences of extubation failure include hypoxia, pneumonia, cardiac arrest, and prolonged ICU LOS.3,27 Furthermore, Whiting et al.16 who studied a cohort of critically ill patients in an Australian ICU found that hospital mortality was significantly increased after extubation failure even after accounting for severity of illness. It was postulated that poor outcomes were related to the time spent in respiratory failure before reintubation or the subsequent prolonged mechanical ventilation and occurrence of pneumonia after reintubation.16 Although all extubation failures are typically considered an unplanned or adverse event, this can be debated in the clinical context of acute CSCI. For some patients deemed unlikely to be dependent on a ventilator after initial injury, a trial of extubation may be conducted as part of the weaning process. In some cases, extubation failure may be considered as a possible outcome of this process and appropriate contingencies are put in place for timely reintubation should that be required. Consequently, it is the patients who unexpectedly require intubation, who are of greatest interest. Determining the reasons for reintubation may inform and enable future evaluation of strategies that are targeted at minimising the incidence of unplanned extubation failure. The primary aim of this systematic review was to examine the rate of extubation failure in acute CSCI. The secondary aim is to identify factors associated with the occurrence of extubation failure. Pooling failure rates across studies may provide researchers and clinicians with a meaningful estimate of its occurrence and in

turn facilitate benchmarking of extubation failure rates within hospitals and healthcare settings. These findings may equip clinicians with further information when assessing patients for extubation and to identify areas to target future interventions. 2. Methods 2.1. Data sources and searches An electronic search was conducted in Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica database (EMBASE), and Cochrane Library from earliest possible date until October 21, 2017. The search strategy was modified according to the specifications of each database. Terms were searched under two concepts: 1) spinal cord injury and 2) extubation failure/ respiratory complications. Terms for the concept of SCI were adapted from a recent Cochrane review.28 Synonyms within each concept were mapped to medical subject headings where possible or searched under title or abstract. Terms within each concept were combined with the “or” Boolean operator. Terms from each concept were then combined with the “and” Boolean operator and exported to the EndNote reference management software (version X7; Thomson Reuters Corporation, New York, NY). Supplementary information regarding further details of the search methodology can be found in Appendix A. After removal of duplicates, the titles and abstracts of articles were screened for eligibility by two reviewers (M.W. and B.W. or M.N.). Differences in opinion were discussed and resolved by consensus with a third reviewer (B.W. or M.N.). Full texts of remaining articles were further screened for eligibility by two reviewers. Citation tracking and reference checking were completed by one reviewer using Google Scholar. The review was registered with PROSPERO-CRD42015027783. 2.2. Inclusion criteria (1) Participants sustained acute CSCI due to trauma or vascular compromise; (2) Required invasive mechanical ventilation; (3) Extubated to natural airway.

2.3. Exclusion criteria (1) Majority of participants younger than 18 years; (2) Participants not mechanically ventilated; (3) Extubation failure or success rate not recorded or could not be imputed; (4) Individual case studies or conference studies

2.4. Data extraction and quality appraisal Data were extracted by one reviewer and checked by a second. The following data were extracted: sample size, the number of patients who failed extubation, the number of patients extubated successfully, gender, age, level of injury, American Spinal Injury Association classification, injury severity score, Glasgow Coma Scale, forced vital capacity (FVC), associated health conditions (i.e. ventilator acquired pneumonia), and postextubation treatment. The quality of the included studies was assessed by two reviewers using a modified epidemiological appraisal instrument in which 10 items were included (Table 2).29 Quality was evaluated according to clarity and description of the aims, intervention,

Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007

Study, year Design

Participants n ¼ sample size Sex: Male; female Age: [mean (SD)] years ASIA: AeE VC: mL NLI: cervical, thoracic, lumbar FVC: mL GCS: [mean (SD)] arbitrary units ISS: [mean (SD)] arbitrary units

Protocol

Results

Proportion Berney et al., 2011 Prospective observational

Call et al., 2011 Retrospective chart review

Chendrasekhar, 2001 Prospective observational

Kim et al., 2017 Retrospective study

Kornblith et al., 2013 Retrospective observational

n ¼ 46 Sex: 41 male; 5 female Age: 31 (IQR, 22e50) ASIA: A 24; B 11; C6; D 5 VC: NR NLI: C4 10; C5 18; C6 5; C7 2; C8 2 FVC: 1600 mL GCS: NR ISS: NR n ¼ 24 Sex: 64 male; 16 femalea Age: 46.1 ± 19.6 ASIA: NR VC: NR NLI: cervical 37; thoracic 25; lumbar 18a FVC: NR GCS 12 ± 3.7a ISS 30.1 ± 12.5a n ¼ 20 Age: 25.4 (±6.4) Sex: 14 male; 6 female ASIA: NR VC ¼ 18.57 ml/kg NLI: C4eT1 GCS: NR ISS ¼ 22.45 (±2.16) n¼2 Age: 47.6 ± 15.8a Age: 47 (18e90)a Sex: 55 male, 7 femalea ASIA: A (49), B 13 VC: NLI: C0 (1), C1 (3), C2 (9), C3 (23), C4 (20), C5 (2), C6 (2), C7 (0), C8 (2)a FVC: 1012.4 ± 561.6a GCS: NR ISS: NR n ¼ 95 Age: 47 (18e90)a Sex: 175 male; 76 femalea ASIA: NR VC: NR NLI: 64.5% cervicala FVC: NR GCS: 14a ISS: NR

Risk factors for extubation failure or tracheostomy 75% of extubation failures attributed to sputum retention Discriminating variables for tracheostomy:  FVC  830 ml (11.9 ml/kg)  Suctioning required  hourly  PaO2/FiO2 188.8

 Patients transferred to specialised spinal centre in Australia between 2004 and 2009  Patients intubated during stay  Patients extubated or received tracheostomy

Extubation failure rate ¼ 8.7%

 Patients who were mechanically ventilated between 2003 and 2007 at San Francisco General Hospital  Extubation failure defined as unplanned reintubation within 96hrs of extubation  Extubation failure event reviewed and categorised independently by two attending physicians

Extubation failure rate ¼ 29.17% Extubation failure rate was significantly higher for cervical compared with lumbar (C spine 64%, L spine 10%, p ¼ 0.004)

Extubation failure attributed to  Pulmonary mechanical insufficiency  Inadequate pulmonary toilet

 Patients admitted to a rural university-based trauma centre over a two-year period  Extubation occurred after orthopaedic stabilisation  Respiratory measures obtained before extubation through endotracheal tube

Extubation failure rate of 60% Extubation failure occurred  5 days after extubation

FVC significantly lower for extubation failure group (no p value given) No difference in ISS, smoking hx, age, NIF, RR, and TV between extubation failure and success

 Patients with complete or sensory Cervical SCI referred to pulmonary rehabilitation centre at Gangnam Severance Hospital between 2003 and 2015  Patients either intubated or with tracheostomy given trial of decannulation or extubation  Criteria for decannulation/extubation followed based on alertness of respiratory status

Extubation failure rate ¼ 0%

NA

 Patients admitted to 14 trauma centres between 2005 and 2009 who required intubation and ventilation  Extubation failure defined as unplanned reintubation or tracheostomy at any point after initial removal of endotracheal tube

Extubation failure rate ¼ 15.79% Median time to extubation was 2 days

No differences in ventilator settings and arterial blood gas values between extubation failure and successa

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Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007

Table 1 Characteristics of included studies.

(continued on next page) 3

Extubation failure rate ¼ 10.5%  Patients admitted to the Oregon Health & Science University, a level-1 trauma centre, from 1998 to 2011.  Airway management and need for tracheostomy determined by spontaneous breathing trials  If shallow breathing index <110, adequate oxygenation in the airway, then extubated n ¼ 200 Age: 46 (IQR, 27, 60) Sex: 92 male; 64 female ASIA ¼ NR VC: NR NLI: C1eT3 FVC: NR GCS: NR ISS: NR McCully et al., 2014 Retrospective analysis

Results Protocol Participants n ¼ sample size Sex: Male; female Age: [mean (SD)] years ASIA: AeE VC: mL NLI: cervical, thoracic, lumbar FVC: mL GCS: [mean (SD)] arbitrary units ISS: [mean (SD)] arbitrary units Study, year Design

Table 1 (continued )

n ¼ number of participants; Age ¼ mean years (standard deviation); ASIA ¼ American Spinal Injury Association (AeE); VC ¼ vital capacity (mL); NLI ¼ neurological level of injury (C1eC7); FVC ¼ forced vital capacity (mL); GCS ¼ Glasgow Coma Scale (3e15); ISS ¼ Injury Severity Score (1e75); OR ¼ odds ratio. a data only available for entire cohort from study and not specifically for sub-cohort of Cervical SCI and extubation.

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Predictors of tracheostomy  Complete injury above C6 (OR: 6.4 (3.1e13.5); P ¼ 0.05)  GCS < 8 (OR: 8.4 (3.5e20.3); P ¼ 0.05

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outcomes, study design, and statistical analysis. A total of 10 items were assessed and scored. A trial with a score of 60% or more was considered to be of high quality.30 2.5. Statistical analysis The proportion of people who failed extubation within each study was summarised as a percent with 95% confidence interval (CI). A proportion meta-analysis was conducted to pool rates of extubation failure across studies, using a random-effects model to account for high levels of clinical and statistical heterogeneity between studies. Statistical heterogeneity across pooled studies was assessed using the Tau (t2) and I2 statistic. An I2 value of 25%, 50%, or 75% was considered a low, moderate, or high level of heterogeneity, respectively.31 Odds ratios (dichotomous variables) and weighted mean differences (continuous variables) were calculated with 95% confidence intervals to evaluate potential risk factors, which included the type of spinal cord injury (complete vs incomplete), age, and sex. Risk factors were pooled in separate meta-analyses where data from two or more studies were available. The ‘meta’ package, version 4.9-2, of the R statistical software package (version 3.3.1) was used for all statistical analyses (https://www.r-project.org/). The ManteleHaenszel method was used for pooling data for odds ratios, whereas for the weighted mean differences, the data were pooled using inverse variance weighting. 3. Results 3.1. Study selection A total of 347 articles were identified using the MEDLINE, CINAHL, EMBASE, and COCHRANE databases. Of these articles, 292 were excluded by the inclusion/exclusion criteria. The remaining 55 articles were retrieved for review by full text, with six studies finally included in the review after application of the eligibility criteria (Fig. 1). 3.2. Characteristics of the included studies The characteristics of the six included studies are detailed in Table 1. Four studies investigated a cohort that only included CSCI.10,26,32,33 Two studies included a cohort of patients of all levels of SCI, from which only data relating to CSCI patients were analysed.22,34 One study that primarily investigated decannulation included data relating to two patients who were extubated.33 All the studies were found to be of high quality based on the epidemiological appraisal instrument (Table 2).29 However, most studies lacked sufficient details with regards to methodology to allow the study to be repeated within another centre. One study was published in 2001, with the remaining four studies published between 2011 and 2017. The total number of participants was 387. The sample sizes in each study ranged from two to 200.32,33 One study contributed more than half of the overall cohort.32 The included studies were conducted in the United States of America,22,26,32,34 Australia,10 and Korea.33 Mean age ranged from 25.4 (± 6.4) to 47.6 (±15.8).26,33 There were more males in each cohort, ranging from 70% to 89%.26,33 Articles presented variable extubation protocols. One study described the use of spontaneous breathing trials before extubation.32 3.3. Extubation failure rate Only three studies provided a definition of extubation failure, which ranged from unplanned reintubation within 96 h of

Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007

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Table 2 Epidemiological appraisal instrument. Study

Berney, 2011 Call, 2011 Chendrasekhar, 2001 Kim, 2017 Kornblith, 2013 McCully, 2014

Item 1

2

3

4

5

6

8

14

15

16

2 2 2 2 2 2

2 2 2 2 2 2

2 1 2 2 2 2

2 2 2 2 2 2

2 2 2 2 2 2

2 0 1 1 1 2

2 2 2 2 2 2

2 2 2 2 2 2

2 2 2 2 2 2

2 2 1 0 2 2

Total

Total (%)

Quality

20 17 18 17 19 20

100 85 90 85 95 100

H H H H H H

0 ¼ no; 1 ¼ partial; 2 ¼ yes; H ¼ high; M ¼ medium; L ¼ Large; Items: (1) Is the hypothesis/aim/objective of the study clearly described? (2) Are all the exposure variables/ intervention(s) clearly described? (3) Are the main outcomes clearly described? (4) Is the study design clearly described? (5) Is the source of subject population (including sampling frame) clearly described? (6) Are the eligibility criteria for subject selection clearly described? (8) Are the characteristics of study participants described? (14) Are the main findings of the study clearly described? (15) Does the study provide estimates of the random variability in the data for the main outcomes or exposures (i.e. confidence intervals and standard deviations)? (16) Does the study provide estimates of the statistical parameters (e.g. regression coefficients or parameter estimates such as odds ratio)?

endotracheal tube removal22 to unplanned reintubation or tracheostomy at any point after initial removal of the endotracheal tube.34 Despite differences in definition of extubation failure, the rates of extubation failure from each study were pooled for the purposes of the meta-analysis. Other specific factors relating to local extubation protocol were not detailed. Extubation failure across the six studies ranged from 0% (0.00e84.19%) to 60% (36.05e80.88%).26,33 However, as discussed, one of these articles included only two eligible participants.33 When data were pooled in a meta-analysis, the proportion of people who failed extubation was 20.25% (10.13e36.38%) (Fig. 2). Only three articles reported on factors that were attributed as influencing extubation outcome.10,22,26 These factors included sputum retention and pulmonary insufficiency. 3.4. Risk factors 3.4.1. Complete vs incomplete Of the six included studies, only two studies could be analysed with respect to the type of SCI [complete or incomplete as defined by the American spinal injury association impairment scale)].10,32 Sample size of these studies ranged from 46 to 200, with a total of 246. Males made up the majority of each sample, ranging from 75% to 89%. Median age of participants ranged from 31 (interquartile range, 22e50) to 46 (27e60) years. The proportion of complete injuries ranged from 20% to 52%. When data were pooled in a meta-analysis across the two studies, the odds of failing extubation was 2.76 (1.14e6.70) times greater for complete CSCI than for incomplete injury (Fig. 3). 3.4.2. Age Only two studies provided information with respect to the age of participants with CSCI who failed extubation.10,26 The mean/ median age of participants was 25.4 (±6.4) or 31 (interquartile range, 22e50) years. Males made up the majority of each sample, ranging from 70% to 89%. When data were pooled in a metaanalysis across the two studies, no relationship was found between age and extubation failure with a weighted mean difference of 1.29 (6.75; 4.17) (Fig. 4). 3.4.3. Sex Only two studies presented data with respect to sex and extubation failure.10,26 These two studies are the same as those included for analysis with respect to age. When data were pooled in a metaanalysis across the two studies, no relationship was found between sex and extubation failure with an odds ratio of 0.63 (0.47; 1.32) (Fig. 5).

4. Discussion The aim of this systematic review and meta-analysis was to examine the rate and factors associated with extubation failure in acute CSCI. It was determined that the rate of extubation failure in acute CSCI is one in five (20%). Furthermore, it was found that the odds of extubation failure for a patient with a complete CSCI were almost three times that of a patient with an incomplete injury based on two studies. In addition, it was found that no relationship existed between extubation failure and age or sex. Extubation failure has been investigated in a number of other populations including postsurgical, medical, and neurocritical patients, with failure rates ranging from 4% to 11%.23e25 A recent article by Burns et al.35 found that the rate of extubation failure varied from 12 to 20% in patients weaning from mechanical ventilation. The rate of extubation failure in people with acute CSCI may not vary significantly from that of other cohorts, whereas the combination of physiological processes that drive its occurrence may do so. These factors can be considered in terms of those related to ventilation impairment, increased sputum load, and impairment of secretion clearance.36 The primary muscles involved in ventilation and secretion clearance are innervated by nerves that arise in or below the cervical spinal cord. Subsequently, injury to the cervical spinal cord impairs these functions.6 Effective inspiration, and in turn ventilation, is also impaired by the period of spinal shock that follows the initial injury. Spinal shock may last from days to months after injury.37 During the initial phases of spinal shock, the musculature below the level of lesion is rendered flaccid. This flaccidity increases thoracic and abdominal compliance, which further impairs respiratory mechanics and the effectiveness of the diaphragm to generate negative inspiratory pressure required for ventilation.38,39 Secretion clearance is dependent on the coupling of inspiration and forceful expiration to effectively generate sufficient peak cough flows.9,40 Acute CSCI is accompanied by a period of mucous hypersecretion. It is thought that this is due to unopposed vagal stimulation due to impairment of normal parasympathetic function.38 The resulting combination of these factors leaves the individual with suboptimal capacity to self-ventilate, increased sputum load, and impaired ability to expectorate secretions. The intersection of these respiratory impairments is unique to the individual with CSCI and may contribute to the rate of extubation failure seen in this review. 4.1. Risk factors For any given neurological level, an SCI classified as “complete” (AIS A) has the greatest neurological injury. A complete injury

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Fig. 1. Selection process of included studies.

Fig. 2. Forest plot meta-analysis of pooled extubation failure rate. CI, confidence interval.

Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007

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Fig. 3. Meta-analysis of extubation failure in complete vs. incomplete spinal cord injury. CI, confidence interval; OR, odds ratio.

occurring in the cervical spine is therefore likely to have the greatest respiratory impairments and highest risk factor for extubation failure. The findings in the present review support the rationale that individuals with a complete CSCI are at greater risk of extubation failure than individuals with an incomplete CSCI.3 Sex was not found to be a risk factor for extubation failure. This may be attributed to the heavily skewed population. This could also be a reflection of physiological mechanisms. Healthy males and females have previously been found to have differences in FVC due to anatomical differences, yet differences in peak flow are minimal.41 As peak cough flow is vital for airway clearance after acute CSCI, it is possible that the similarity that exists between males and females in this respiratory measure explains the similar extubation failure rate. Despite this, further research with greater methodological uniformity and larger sample size is needed to confirm these findings. Age was not found to be a risk factor for extubation failure. Again, the skewed nature of the data makes this finding difficult to interpret. The younger age of our cohort likely reflects the demographics with SCI, consistent with previous research that suggests an increased likelihood of patients sustaining an acute CSCI when younger than 30 years of age.42 Several alternative but less likely explanations may also contribute to this finding. It is understood that a number of detrimental changes in respiratory function occur with age.43 As most participants included in our systematic review were of younger age, it is possible that we did not see a relationship between extubation failure and age as patients were too young for age-related respiratory changes to have clinical significance. The young age of our cohort may also be explained by the increased mortality of older individuals with CSCI or by the fact that older patients are less likely to be extubated.44e47 Consequently, the relationship between age and extubation failure after CSCI is an area that requires further research.

4.2. Clinical implications Screening patients for risk factors associated with poor outcomes may assist in the clinical decision-making process for the treating clinician. Berney et al.10 have explored this in the Australian SCI population with a classification and regression tree model. Patients found to have these risk factors may benefit from more aggressive respiratory management after extubation with the use of support measures advocated by Bach et al.15 Alternatively, should the potential risks be too great, it may be most appropriate for a tracheostomy to be performed to prevent almost certain extubation failure and the associated negative outcomes. The challenge for the clinician is as Brown et al. aptly comment, “… neither 0% or 100% (extubation failure rate) would be appropriate, it is currently unclear and undefined what the ideal extubation failure rate should be.”18 Excessively conservative or aggressive extubation practices would yield such outcomes. This review has identified an extubation failure rate of 20% for people with CSCI. The quantification of extubation failure in CSCI provides specialist centres in SCI management with provisional evidence upon which to benchmark and compare standards with the opportunity to optimise care. However, this figure needs to be investigated in a prospective large cohort with the incidence of extubation failure clearly defined. 4.3. Limitations of the review Although this present review was able to achieve its primary aim, there were limitations regarding the ability to identify factors associated with extubation failure. Although all the included studies investigated CSCI, there was limited uniformity in the reporting of specific patient factors, respiratory measures, and associated comorbidities. The definition of extubation failure varied across studies, with respect to time of reintubation. Comparing extubation failure rates in this patient population therefore

Fig. 4. Meta-analysis representing weighted mean difference of mean age in those who failed extubation vs. those who were successfully extubated. CI, confidence interval; SD, standard deviation.

Fig. 5. Meta-analysis representing odds ratio of extubation failure in males and females. CI, confidence interval; OR, odds ratio.

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remains difficult. These factors limit the ability to draw definitive conclusions from the data. Furthermore, the high degree of statistical heterogeneity suggests a high degree of variability between the included studies. A random-effects model was therefore used to provide a more conservative estimate of the overall pooled effect. Furthermore, the study appraisal instrument suggests that the included studies were of a high quality. However, the tool does not have the fidelity to rate the consistency of definitions or similarity of populations or treatments across the study populations. Although the present meta-analysis identified an extubation failure rate, it is difficult to provide recommendations on what rate is acceptable.18 Several patient factors, such as respiratory history, mechanism of injury (i.e. involving drowning), concomitant injuries, and even patient resolve in the context of significant lifealtering injury, may contribute to extubation failure.3 Local factors relating to the healthcare facility practices and clinician knowledge of and experience with SCI respiratory dysfunction may also affect extubation failure rates. These factors include differences in the local extubation criteria, nurse-to-patient ratios, and the readiness of a clinician to reintubate. Centres with liberal or aggressive extubation protocol are likely to experience more failure, whereas those with very conservative protocols are likely to experience less extubation failure, yet may potentially provide unnecessary tracheostomies. None of the included studies detailed postextubation management. Given the ability of certain treatment modalities such as mechanical insufflation/exsufflation (MIE) to assist in the liberation of patients from mechanical ventilation, postextubation management is likely to have affected the variable rate of success/ failure seen in each study.12 4.4. Further research Future research is needed to explore the wide range of risk factors that could influence extubation risk in this patient group. Standardised data collection using the recently revised international spinal cord injury data set will help clinical investigators use standardised data collection techniques as they design and conduct new clinical studies.48 Important respiratory measures, mechanism of injury, cocommitment injuries, levels of consciousness, neurological level of injury, and classification of SCI would all provide further insights. Established methods for performing these assessments already exist; however, a variety of methods were used across the included studies. Past medical history including smoking status and the development of complications such as respiratory aspiration or pneumonia would also provide valuable data for analysis. Postextubation treatment, including the use of intensive physiotherapy, manual cough assistance, MIE, positioning, and the use of non-invasive ventilation (NIV), should be clearly reported. Information regarding risk factors for extubation failure may also guide future evaluations of the effectiveness of postextubation management considerations. The combination of all these data could better inform clinical decisions about airway management with respect to extubation and tracheostomy. Although the success of extubation after mechanical ventilation depends on multiple factors, there are some unique considerations in the SCI patient group. As previously discussed, respiratory mechanics are impaired after CSCI. Subsequently, FVC is higher in supine than sitting.49e53 This is the opposite for the healthy population and may seem counterintuitive.50 Patient positioning after extubation therefore needs careful consideration after SCI for patients without functioning abdominal musculature. To date, no studies have reported on patient positioning after extubation. Obstructive sleep apnoea (OSA) has a prevalence of 40e83% after CSCI.54e58 Whether a person with CSCI had preinjury or postinjury OSA, central sleep apnoea or other form of sleep-

disordered breathing needs to be acknowledged and screened for as this may further compound postextubation fatigue and hypoxia. Potential lack of early OSA identification and interventions to address OSA may result in some cases of preventable extubation failure. Bach et al.15 advocate liberation from mechanical ventilation through the proactive use of airway clearance using MIE of ventilator-dependent patients with chronic CSCI. Noninvasive ventilation via a mouthpiece has been used to successfully liberate individuals from mechanical ventilation with other types of neuromuscular disease.15,20,59 This form of mouthpiece ventilatory support delivering intermittent positive pressure breathing is currently utilised as part of standard physiotherapy management after extubation from mechanical ventilation, however usually only for the duration of the physiotherapy intervention. The provision of patient-controlled mouthpiece noninvasive ventilation may provide the tetraplegic patient with necessary ventilatory support to allow an alternate or complementary option to bilevel positive airway pressure delivered via a facemask or nasal interface. Further investigation into the effectiveness of increased respiratory support after extubation with established and novel techniques such as noninvasive ventilation, cuirass, and physiotherapy could be investigated further in a prospective study to establish the role of adjuvant therapy in this setting.60 5. Conclusion Across the included studies, this review found a pooled extubation failure rate in acute CSCI of 20%. The odds of a patient with a complete CSCI injury failing extubation are nearly three times that of a patient with an incomplete CSCI. These results provide provisional data for benchmarking extubation failure rates for future studies in patients with an acute CSCI. Future research should be directed towards improved standard data sets and prospective evaluation of adjuvant therapy in the peri-extubation period.

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Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007

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Please cite this article as: Wilson M et al., Acute cervical spinal cord injury and extubation failure: A systematic review and meta-analysis, Australian Critical Care, https://doi.org/10.1016/j.aucc.2019.01.007