Abstract
Aetiology of acquired laryngotracheal stenosis (ALTS) is complex and heterogenous. The aim of this study is to discuss the role of primary aetiology of intubation in the development and outcomes of Post intubation Laryngo tracheal stenosis (PILTS). A retrospective review of patients diagnosed and managed as PILTS from May 2008 to January 2017 was conducted. Demography, primary aetiology of intubation, grade of stenosis, length of the stenotic segment, treatment and outcomes of these patients were recorded and analysed. Based on aetiology of intubation, patients were divided into Poisoning (I), Neurogenic (II) and Rest of aetiologies (III) group respectively. Group I had 28/52 patients (53.8%) followed by group II, 15/52(28.8%) and group III, 9/52(17.3%) respectively. Organophosphorus compound poisoning (OPP) (44.2%) was the commonest cause overall followed by Brain injury (23.1%) and Acute Respiratory Distress Syndrome (ARDS) (11.5%). Trachea (46.15%) was the commonest subsite involved in this study. 24/28(85.7%) of patients had advanced (either grade 3 or 4) subglottic stenosis. The average length of stenotic segment in the study was 18.5 ± 9.2 mm (7–34 mm). 39/52(74.9%) of patients underwent open surgical approaches like cricotracheal resection and anastomosis, Laryngotracheal reconstruction or Shian-Yan Lee technique. 48/52(92.3%) patients were decannulated successfully. There was no significant association between primary etiology of intubation and outcomes. We conclude that OPP and neurological disease patients are more susceptible to airway injury. The authors emphasize that clinicians should be aware of these facts and manage these susceptible patients accordingly.
Keywords: Acquired Laryngotracheal stenosis, Primary etiology of intubation, Poisoning, Neurological, Outcomes
Introduction
Aetiology of acquired laryngotracheal stenosis (ALTS) is complex and heterogenous. Based on the aetiology, ALTS can be grouped into iatrogenic, idiopathic, autoimmune and traumatic. Identifying the primary aetiology of intubation helps in characterization of the disease, comparison and prognostication of treatment outcome.
Iatrogenic aetiology is the most common cause for ALTS in Indian subcontinent. Securing and maintaining airway either by intubation or tracheostomy are the major causative factors for iatrogenic ALTS. The etiopathogenesis following intubation is due to the development of ischemia, leading to necrosis of the laryngotracheal mucosa, submucosa and cartilage, ultimately leading to scarring, fibrosis and stenosis [1]. Many risk factors have been identified and discussed in literature. Prolonged intubation, increased cuff pressure, intubation trauma, increased number of attempts during intubation, inexperienced handling of the airway by the clinician, disproportionately larger tube size, superadded infection, irritability of synthetic material in airway etc. are important risk factors that have been identified to cause post intubation laryngotracheal stenosis (PILTS) [2–5]. In spite of addressing these risk factors, few patients develop PILTS leading to prolonged hospital stay and significant morbidity. The incidence of PILTS in intensive care unit is 11–16% [6]. Researchers in the past have evaluated the role of systemic factors which affect the airway mucosa indirectly. Knowledge of these systemic risk factors helps in better understanding of pathogenesis of PILTS. Primary aetiology of intubation is often neglected and its role in development of PILTS is poorly understood. The purpose of this study is to evaluate the association of primary aetiology of intubation and outcomes in PILTS.
Methods
A retrospective review of patients diagnosed and managed as PILTS from May 2008 to January 2017 was conducted. Data were retrieved from the medical records section of hospital. Institutional Ethical committee approval was obtained. Consent obtained from patients to participate in the study. Patients who developed ALTS following autoimmune disease, direct trauma, tumour and idiopathic aetiology, congenital airway stenosis, patients with associated supraglottic stenosis, glottic stenosis and vocal cord paralysis and patients who were lost to follow up were excluded from the study.
All PILTS patients were managed by Intensive Care Unit (ICU) team affiliated to the institution. All patients were intubated either in Emergency Department or ICU. Patients were managed by ICU protocol designed by the institution. Appropriately sized poly vinyl chloride (PVC) endotracheal tubes were used in all patients. The cuff pressure was constantly monitored and kept < 30 mmHg. Patients who required prolonged ventilation underwent elective tracheostomy. Tracheostomy was managed by a dedicated team of doctors and nurses. The first tube change was done after 10–14 days. Stomal site infections were appropriately managed. Decannulation was decided based on patient’s general condition. Fibreoptic laryngoscopy (FOL) was done in all patients before decannulation and findings recorded. LTS was diagnosed during FOL and confirmed patients underwent computed Tomography of Neck and thorax.
Demography, primary aetiology of intubation, grade of stenosis, length of the stenotic segment, treatment and outcomes of these patients were recorded and analysed. Based on aetiology of intubation, patients were divided into Poisoning (I), Neurogenic (II) and Rest of aetiologies (III) group respectively.
Statistical Analysis
The collected data was entered and analysed using Statistical Package for the social sciences (SPSS, SPSS Inc., Chicago, IL, US) software, version 17.0. The quantitative data was expressed as mean and standard deviation while qualitative data was expressed as percentages. Multiple logistic regression was used to analyse the association between primary aetiology and severity of stenosis, treatment and outcomes. P < 0.05 was considered statistically significant.
Results
A total of 71 patients were treated for ALTS during the study period. 52 patients who satisfied the inclusion criteria and didn’t satisfy the exclusion criteria were included in the study. Mean age of patients in the study was 29.5 ± 12.9 years (3–67 years). There was female preponderance with female: male ratio of 1.26(29: 23). The average duration of intubation was 9.08 ± 4.35 days (3–34 days).
Organophosphorus compound poisoning (OPP), snake bite and drug overdose were the causes in Group I. Brain injury (BI) following stroke/head injury/encephalitis and Guillain Barre syndrome (GBS) were the neurological causes in Group II. Adult Respiratory Distress syndrome (ARDS) and Myocardial infarction (MI) were causes in Group III.
Aetiology
Group I had 28/52 patients (53.8%) followed by group II, 15/52(28.8%) and group III, 9/52(17.3%) respectively. Regarding the primary aetiology of intubation, OPP (44.2%) was the commonest cause overall followed by BI (23.1%) and ARDS (11.5%) (Table 1).
Table 1.
Primary aetiology of intubation
| Groups based on aetiology | Actual aetiology | Frequency | Percent |
|---|---|---|---|
| I | OPP | 23 | 44.2 |
| Snake bite | 4 | 7.7 | |
| Drug overdose | 1 | 1.9 | |
| II | Brain Injury | 12 | 23.1 |
| GBS | 3 | 5.8 | |
| III | ARDS | 6 | 11.5 |
| MI | 3 | 5.8 | |
| Total | 52 | 100.0 |
Subsite of Stenosis
Trachea was the commonest subsite involved followed by subglottis and cricotracheal stenosis (Fig. 1).
Fig. 1.
Pie chart showing the involved subsites of stenosis
Grade of Stenosis
Cotton Meyer classification was used to grade the subglottic stenosis. Out of 52 patients, 28(53.8%) had subglottic involvement. The frequency distribution of these patients according to Cotton-Meyer grading is shown in Table 2. Overall, irrespective of aetiology 24/28(85.7%) of patients had either advanced (grade 3 or 4) stenosis. There was no significant association between the aetiology and grade of stenosis (P = 0.180).
Table 2.
Distribution of patients according to Cotton Meyer classification
| Groups | Cotton Meyer grade of stenosis | Total | |||
|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 1 | |
| I |
1 (100%) |
2 (66.7%) |
5 (33.3%) |
4 (44.4%) |
12 (42.9%) |
| II |
0 (0%) |
1 (33.3%) |
6 (40%) |
2 (22.2%) |
9 (32.1%) |
| III |
0 (0%) |
0 (0%) |
4 (26.7%) |
3 (33.3%) |
7 (25%) |
| Total |
1 (100%) |
3 (100%) |
15 (100%) |
9 (100%) |
28 (100%) |
Length of Stenosis
The length of the stenotic segments was measured using CT scan of neck and recorded. The average length of stenotic segment in this study was 18.5 ± 9.2 mm (7–34 mm). 14/52(26.9%) had length of ≤ 10 mm, 30/52(57.6%) had length of 10–30 mm and 8/52(15.6%) had > 30 mm stenotic segments.
Management
All these patients were managed depending on the grade of stenosis, length of stenotic segments, age and associated co-morbidities (Table 3). Grade 1 and 2 stenosis mostly underwent endoscopic dilatation with or without LASER assistance. Grade 3 and 4 underwent open surgeries like Cricotracheal Resection and Anastomosis (CTR), Laryngotracheal Reconstruction (LTR) using costal cartilage graft or Shian-Yan Lee technique. Patients who were unfit for any procedure were managed conservatively by keeping them tracheostomised. There was no significant association between etiology and surgical treatment (P = 0.05).
Table 3.
Distribution of patients based on treatment
| Treatment | Frequency | Percent |
|---|---|---|
| CTR | 28 | 53.8 |
| LTR | 9 | 17.3 |
| Endoscopic dilatation ± LASER | 11 | 21.2 |
| Shian-Yan Lee technique | 2 | 3.8 |
| Conservative | 2 | 3.8 |
| Total | 52 | 100.0 |
Outcomes
25/28(89.3%) were decannulated successfully in group I, while 14/15(93.3%) in group II and 9/9(100%) in group III. (Table 4). There was no significant association between etiology and overall outcomes (P = 0.441).
Table 4.
Distribution of patients based on outcome
| Groups | Outcome | Total | |
|---|---|---|---|
| Decannulated | Failed | ||
| I |
25 (89.3%) |
3 (10.7%) |
28 (100%) |
| II |
14 (93.3%) |
1 (6.7%) |
15 (100%) |
| III |
9 (100%) |
0 (0%) |
9 (100%) |
| Total |
48 (92.3%) |
4 (7.7%) |
52 (100%) |
Discussion
The incidence of ALTS is difficult to assess due to its rarity and heterogeneity. Some of the prospective studies that have evaluated the incidence of post intubation laryngotracheal injuries (LTI) have documented variable incidence for acute and chronic sequelae. Shinn et al. in a prospective cohort study observed that 57% of patients had evidence of acute laryngotracheal injury (ALTI) in patients who were intubated for more than 12 h in an ICU setting [7]. Tadié et al. had reported 73% ALTI following intubation for more than 3 days [8]. Kastanos et al. in a prospective study noted that 6/19 (31%) of patients had evidence of ring shaped tracheitis of which 2/29(10%) had progressed to develop PILTS [9]. Rangachari et al. have reported temporary LTI of 80% and 20% having permanent sequelae in ICU patient intubated for 24 h [10]. A systematic review of database for laryngotracheal injuries following endotracheal intubation among mechanically ventilated patients in the ICU, found nine studies and 775 patients that fulfilled the criteria. They observed that the mean duration of intubation of 8.2 days. PILTI was observed in 83%, moderate to severe injury was observed in 13–31% of patients [11].
Intubation trauma and its sequelae are widely regarded as the main predisposing factors for ALTS. Most studies in literature, have focussed on local causes for PILTS while ignoring the systemic causes. This was probably due to the difficulty in planning and executing a study design in PILTS. The role of primary aetiology of intubation in the development of ALTS could not be evaluated for this reason. Megarbane et al. prospectively evaluated intubation related laryngeal complication in poisoning and concluded that though duration of intubation adversely affected the laryngeal injuries, poisoning patients had a high risk of initial laryngeal injuries despite the short duration of intubation [12]. However, this study had its own limitations in regards to specifying the type of chemical poisoning and the follow up laryngoscopies that was difficult and not done.
Basoglu et al. re-evaluated PILTS patients and observed that 9 (31.03%) out of 29 patients who were intubated for OPP developed LTS [13]. They concluded that the primary cause of intubation and the medical therapy received could have had an effect in PILTS.
In this study, it has been observed that patients who were intubated or tracheotomised for poisoning were the most common who developed PILTS. In this study, poisoning accounted for 53.8% of the cases, with OPP as the most common cause of primary intubation accounting for 44.2% of cases. Snake bite and drug overdose were the other causes in poisoning group contributing 7.7% and 1.9% respectively. Previous studies that have evaluated PILTS based on the primary cause for intubation is summarized in Table 5. It is noted that the most common reason for intubation in PILTS has been OPC poisoning, followed by neurological disease. All the patients had suicidal intention behind consumption of organophosphorus compound. It is used as a pesticide and is widely available in Indian subcontinent.
Table 5.
Table showing various studies conducted in Indian subcontinent
| Study | Total number of cases of PILTS | Poisoning | Neurological disease | Rest of causes (ARDS, MI) |
||
|---|---|---|---|---|---|---|
| No of cases with OPP | Other poisoning | Brain injury following stroke/encephalitis | Guillain Barre syndrome/ encephalitis/ CNS lesion, others | |||
| Kelkar et al. [23] | 18 | 7 (38.8%) | – | 316.6%) | – | – |
| Kandakure et al. [24] | 13 | 6 (54%) | – | 1 (8%) | – | – |
| Gupta et al. [25] | 32 | 22 (69%) | Snake bite -4 (13%) | 3 (9%) | – | – |
| Nair et al. [17] | 20 | 4 | – | 9 |
2-CNS disorders 2-CNS tumours |
– |
| Kumar A et al. [18] | 18 | 2 (11.11%) | – | 7 (38.8%) |
3-Cerebrovascular accident 1-Guillain barre syndrome |
Pneumonia-2 Tetanus-1 |
| Our study | 52 | 23 (44.2%) | 5 (9.6%) | 12 (23.1%) | 3 (5.8%) | 9 (17.7%) |
The second most common cause associated with PILTS in this study was a neurological cause (28.8%). Brain injury (diffuse axonal injury) due to stroke was the most common cause accounting to 23.1% of patients. Brain injury patients present to emergency department with variable cognitive and hemodynamic status. Most of patients present with hemodynamic instability potentially leading to tissue hypoxia. Woo et al. had observed 13/50 (26%) patients managed for neurological cause developed airway stenosis [14]. Richard et al. had reported an incidence of 20% of airway stenosis following orotracheal intubation and tracheostomy in patients suffering from neurological disease [15]. They also mentioned that the laryngotracheal stenosis is observed in patients having more severe brain injury along with hypotonia. Nowak et al. reported the various airway complications in patients presented with closed head injuries [16]. According to their study, tracheitis and glottic web are early complications of intubation while laryngotracheal stenosis, vocal cord palsy and tracheomalacia are the late complications respectively. The hemodynamic instability along with intubation related trauma in an emergency setting may lead to airway complications in such patients. Nair et al. have reported 9/20 patients managed for LTS had history of head injury along with polytrauma [17].
Guillain Barre syndrome a neurological disease resulting in acute demyelinating polyneuropathy which causes ascending paralysis of body resulting in respiratory paralysis was also noted to be a cause for primary intubation in some patients. Guillain Barre syndrome as primary aetiology of intubation in PILTS has been rarely described in literature [18].
Di silvo et al. conducted a study and analysed the outcomes and complications of patients with ARDS [19]. According to their study, tissue hypoxia resulting from ARDS along with intubation trauma contributes to development of LTS in approximately 5% of patients. In our study, ARDS 6/52(11.5%) was the cause of patients.
Similarly, Myocardial infarction can cause tissue hypoxia indirectly and increase the odds of developing ALTS. The tissue hypoxia resulting from cardiac failure and intubation trauma together may lead to mucosal injury, ischemia and stenosis [20].
The authors had evaluated the degree of stenosis and treatment outcomes with respect to each aetiology in this study. In case of subglottic stenosis, 24/28(85.7%) patients had advanced (grade 3 or 4) stenosis in this study. 37/52(71.1%) patients required open procedures as a treatment option.
Most published literature in the recent past have discussed the management of established PILTS, very few articles have revisited the etiopathogenesis of LTS. The authors have made an effort to highlight the importance of conducting an audit so as to identify the risk factors and reduce the occurrence of PILTS. Farzanegan et al. have emphasized that studies aimed at preventive aspects, identifying risk factors is the need of the hour especially when dealing with iatrogenic PILTS [21]. This would reduce the burden of disease on the health care system and further reduce the morbidity and mortality related to this iatrogenic aetiology. They have also emphasised that each country should identify the local risk factors and establish an evidence based protocols to reduce incidence of LTS [22]. This requires integrated multi-institutional effort from all like-minded individuals who are interested and are dealing with LTS to come together on a common platform to create a database to identify important issues, conduct prospective research in this field and help in creating a health care policy so as to provide a definitive direction to prevent PILTS from occurring.
The aetiology of LTS is multifactorial. Hence a single risk factor cannot be concluded as an isolated factor responsible for development of LTS. This study and existing data suggest that the primary cause for establishing airway has a significant role in PILTI. This study also identifies the risk groups based on the primary aetiology for intubation. This data would help in stratifying these groups of patients and providing them with additional care when handling the airway. However, the authors have identified few limitations in this study. This study lacks adequate statistical evidence to prove a direct correlation between the PILTS and primary cause for intubation. Small sample size and lack of a control group makes this evaluation difficult and provide enough proof for the causal relationship. A prospective multicentric case control study comparing the outcomes of intubated patient with various aetiology is recommended for analysis. A prospective /RCT would be always better; However, matching the confounding factors in a multifactorial aetiology would be a difficult task.
Conclusion
The cause of PILTS is multifactorial. Though local trauma to airway mucosa play an important role, other systemic physical factors like primary aetiology of intubation also cause tissue hypoxia indirectly. OPP and neurological disease patients may be more susceptible for airway injury during establishing and maintaining airway. The authors emphasize that clinicians should be aware of the increased risks involved in these patients and plan initial airway management so as to reduce the incidence of PILTS.
Funding
None.
Compliance with Ethical Standards
Conflicts of interest
The authors declare that there is no conflict of interest.
Ethical approval
Institutional ethical committee approval obtained.
Footnotes
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