Predictors of Failed Extubation in Mechanically Ventilated Children: Single Center Experience

Document Type : Original Research

Authors

Department of Pediatrics, Faculty of Medicine, Cairo University, Egypt

Abstract

Background: Extubation failure is failure to maintain normal spontaneous breathing after a period of mechanical ventilation with the need for reintubation within 24–72 hours. It has multiple risk factors such as deconditioned muscles, upper airway edema and others.
Aim of the Work: To study the frequency and causes of extubation failure in mechanically ventilated children.
Patients and Methods: This is an observational prospective study that included all admitted children in Pediatric Intensive Care Unit (PICU), Cairo University Children Hospital who underwent mechanical ventilation (MV) through ETT for more than 48 hours (145 child) with Glasgow coma scale above 8. They were subdivided into successfully extubated (78 children) and failed extubation (67 children). 
Results: The mean ± SD age of the cohort was 13.5 ± 15.15 months (range1.3-48, median= 8 months). Of them  80 (55.17%) were males, and 65 (44.8%) were females. The commonest underlying diagnosis was pneumonia in 38 (26.2%),  bronchial asthma in 32 (22%), encephalopathy in 32 (22%), and aspiration in 11 (7.58%). Failed extubation was encountered in 67 (46.2%) children. The encountered risk factors of extubation failure were: sedation in 12 (16.7%) (p=0.001), excessive tracheal secretion of more than 200 ml /24 h in 14 (18.7%) (p=0.03), accidental extubation in  27 (40.3%) (p=0.01) and the need for higher setting on MV in all 67 children with failed extubation. Among failed extubated patients, the mean± SD for PIP, PEEP, and FiO2 were 14.5± 1.8 /cm H2O, 5.5± 0.5/cm H2O, and 27.5± 6.1% respectively. While, PIP, PEEP, and FiO2 in the successfully extubated group were  12.8± 1.6 /cm H2O, 4.1± 0.4/cm H2O, and 24.8± 5.3%, (p= 0.01, p=0.001 and p= 0.001) respectively. Patients who underwent gradual withdrawal of ventilatory support had a higher frequency of successful extubation than those extubated accidentally (p= 0.01). Sensitivity, and specificity of above mentioned indices for successful extubation were 53.79%, and 28.72% respectively.
Conclusion: Causes of extubation failure are the need for long duration of sedation, excessive tracheal secretion, and need for high setting on MV. Furthermore, gradual weaning decreases the frequency of extubation failure. There is a need for a more sensitive and specific comprehensive objective indicator(s) for successful timely extubation. 

Keywords


Introduction

Almost 24-60% of admitted patients to pediatric intensive care (PICUs) need mechanical ventilation (MV) (2).  Liberation from MV is called the weaning process, in which reduction of respiratory support should be made gradually and steadily over a duration almost 40-50% of the total duration of MV to allow the patient to take his spontaneous breath independently (35). At removal of the endotracheal tube i.e. extubation, the patient must be assessed carefully to determine whether he can breathe spontaneously. Specific measures for successful extubation are mandatory, including the ability to protect the airway and the management of secretions (6). Extubation failure (EF) represents a specific condition at which reintubation and MV must be restored and usually occur within the first 24–72 h after endotracheal tube removal  (7). Many factors may influence extubation failure, such as deconditioned muscles, upper airway edema, inability to clear secretions, and decreased consciousness level due to persistent effects of sedatives and analgesics (8). Extubation failure has been independently associated with increased mortality and prolonged hospitalization (9). Therefore, identifying risk factors associated with extubation failure may help reduce the duration of mechanical ventilation and improve outcomes. Several criteria, such as maximum inspiratory pressure (MIP), minute ventilation (VE), rapid shallow breathing index, and tidal volume (VT), respiratory rate (810) are often used as indicators for extubation. Other parameters may also aid in making the decision of extubation, such as: occlusion pressure (P 0.1), work of breathing, esophageal pressure, transdiaphragmatic pressure, electro-myographic activity of diaphragm, and physiological dead space (11).

 We aimed to study the frequency and causes of extubation failure in mechanically ventilated children in our unit.

Subjects and Methods 

This observational prospective study was carried out in the PICU in Cairo University Children Hospital over a period of 6 months. The research was approved by the Faculty of Medicine, Cairo University Health Ethics Review Board  (IRB Approval Number: MS371-2019). The study conforms with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans (12).

Participants

This study included consecutive 145 critically ill patients admitted to PICU with acute hypoxemic respiratory failure who were ventilated for more than 48 hours. Only those with a Glasgow Coma Scale of> 8 were included. Of those with neurological disease only acute cases of Guillain-Barre syndrome were  included,  while we excluded others who were previously diagnosed with chronic neuromuscular disorder in need of more than 21 days of mechanical ventilation, as spinal muscle atrophy.

Methods

Data were collected 24 hours prior to spontaneous breathing trials. All children underwent spontaneous breathing trial (SBT) for 48 hours prior to extubation. For all cases, demographic data were analyzed, including age, gender, detailed medical history, and examination findings. In addition, diagnosis on admission, cause of ventilation, duration of ventilation, modes and settings of MV before extubation, number of extubation trials, level of consciousness, inotropic support if present, tracheal secretion volume, and fluid balance (calculated as fluid input minus output over 24 hours). Pulmonary indices (oxygen saturation index (OSI) were calculated for all patients and recorded using the following equation MAP x FiO2  x 100/SpO2 (13). Calculated OSI for mild, moderate, and severe ARDS are 5->7.5, 7.5-12.3 respectively. 

The SBT was based upon achievement of the following parameters: respiratory rate (RR) according to age (20-60 breath per minute (bpm) < 6 months; 15-45 < 2 years; 15-40 < 5 years; 10-35 > 5 years);  tidal volume (VT of 6-8ml/kg); the assessments of vital signs (with goals of age related heart rate, respiratory rate, and systolic blood pressure);  ventilator criteria (PEEP ≤ 5 cmH2O, pressure support ≤ 10 cmH2O and FiO2 ≤ 40%); and calculated OSI

The data collected post-extubation were the frequency of extubation failure, and causes of extubation failure. Extubation failure was considered if their was inability to maintain spontaneous breathing after a period of mechanical ventilation and the need arises for reintubation within 24–72 h [4]. Chest X-ray findings and laboratory investigations (blood gases and serum levels of K and PO4) before and after extubation were collected.

Statistical Analysis             

The data were analyzed using Microsoft Excel 2016 and the Statistical Package for Social Sciences (SPSS) version 26 (IBM Corp., Armonk, N.Y., USA). The mean ± standard deviation (SD) was used to demonstrate the continuous, normally distributed variables. Moreover, the median with 25% and 75% was used to represent the non-normal variables, and the frequencies and percentages were used for categorical variables. A p-value < or = 0.05 was considered statistically significant. The Student’s t-test was performed to compare the means of normally distributed variables between groups, and the Mann-Whitney U test was used for non-normal variables. The Chi-squared test or Fisher’s exact test were used to determine the significance of categorical variables between groups. The diagnostic power of ventilatory setting in croup and other causes with failed extubation was evaluated by the receiver operating characteristic (ROC) curve.

Results 

Demographics and clinical characteristics of the studied group:

The study included 145 patients whose age mean ± SD was 13.5 ± 15.15 and was (range1.3-48, median 8 months). Of them 80 (55.17%) were males, and 65 (44.8%) were females.  The commonest underlying diagnosis was pneumonia in 38 (26.2%) cases, bronchial asthma in 32 (22%), encephalopathy (with GCS>8) in 32 (22%), and aspiration in 11 (7.58%). Only 25 (17.2%) patients were  on assisted control mode while 120 (82.7%) were on synchronized intermittent mandatory ventilation. The mean ± SD duration of mechanical ventilation was 4.8±4.7 days (range=0.5-30, median= 3 days), and of the duration of weaning from mechanical ventilation was 2.4± 2.3 days (range=0.5-15, median= 1 day). Failed extubation was encountered in 67 (46.2%) children. Clinical characteristics of the studied group are shown in tables 1 and 2. The successfully extubated group had a mean ± SD age of 12.3 ±17.5 months (range= 1.3-36, median= 9.5months), of them 33 (42%) were females, and 45 (57.7%) were males. The failed extubation group had a mean ± SD age of 12.8 ±12.4 months (range= 1.3-48, median= 7.5 months), of them 32 (47.7%) were females, and 35 (52.2%) were males. There was no significant difference in age and gender distribution between both groups (p=0.2) and (p= 0.5) respectively.  (Table 1).

 

Table 1. Demographics  and clinical characteristics of the studied group of 145 mechanically ventilated children. 

 

Cohort

N=145

Successfully extubated

N=78

Failed extubation

N=67

P-value

Age (months)

     

 

       Range

1.3-48

1.3-36

1.3-48

 

       Mean

13.6

14.3

12.8

0.2

       SD

15.15

17.5

12.4

       Median

8

9.5

7.5

 

Duration on MV (days)

4.8±4.7

4.8 ± 6.3

4.6 ± 2.6

0.4

MV weaning duration of (days)

2.4± 2.3

2.4 ±3.2

2.3±1.3

 0.4

         

 

Number

%

Number

%

Number

%

 

Gender 

 

        Males

80

55.1

45

57.7

35

52.2

0.5 

        Females

65

44

33

42.3

32

47.7

0.5 

Diagnosis 

           

 

        Pneumonia 

38

26.2

18

23.1

20

29.8

0.2 

        DCL (GCS>8)

32

22

15

19.5

17

25 .3

0.2 

        Bronchial asthma

32

22

15

15.4

17

25.3

 0.2

        Aspiration 

11

7.58

9

11.5

2

2.9

0.05 

        ARF

3

2

3

3.8

0

0.00

0.1 

        GBS

6

4

6

7.7

0

0.0

 0.8

        DKA

3

2

3

3.8

0

0.0

 0.1

        Others*

20

14

12

15.4

8

11.9

0.4 

MV mode

 

 

 

 

 

 

 

        A/C mode

25

17.2

12

15.4

12

18

0.6

        SIMV mode

120

82.7

66

84.6

55

82

*Others includes: Fallot tetralogy with cyanotic spell, hydrocephalus, Post Kasai biliary atresia, metabolic acidosis, and foreign body aspiration.  A/c mode: Assisted control mode; ARF: Acute renal failure;  DCL: disturbed conscious level; DKA: Diabetic ketoacidosis; GBS: Guillain barre syndrome; GCS: Glasco coma scale; MV: mechanical ventilation; SIMV mode: synchronized intermittent mandatory ventilation.

The successfully extubated group had a mean ± SD age of 12.3 ±17.5 months (range= 1.3-36, median= 9.5months), of them 33 (42%) were females, and 45 (57.7%) were males. The failed extubation group had a mean ± SD age of 12.8 ±12.4 months (range= 1.3-48, median= 7.5 months), of them 32 (47.7%) were females, and 35 (52.2%) were males. Foreign body aspiration had a highly successful extubation rate (p= 0.05), where 9 (11.5%) patients were successfully extubated compared with 2 (2.5%) patients whose extubation failed. (Table 1).

Patients who presented with pneumonia, encephalopathy, bronchial asthma, acute renal failure and Guillain Barre syndrome showed no significant difference as regards the failure rate of extubation (p=0.2), (p=0.2), (p=0.2), (p=0.8) and (p=0.1) respectively. (Table 1).

 

Risk factors for extubation failure:

Many risk factors contributed to failed extubation; continuous sedation in 12(16.7%) (p=0.001), excessive tracheal secretion >200ml in 30 (23%) (p=0.03), accidental extubation in 27(40.3%) (p=0.01) and higher ventilatory setting in 67(100%), namely: the mean± SD for PIP, PEEP, and FiO2were 14.5± 1.8 /cm H2O, 5.5± 0.5/cm H2O, and 27.5± 6.1%, respectively (p=0.01), (p=0.001), and (p=0.001) respectively. On the other hand, PIP, PEEP, and FiO2 in successfully extubated patients were 12.8± 1.6 cm H2O, 4.1± 0.4cm H2O, and 24.9± 5.3% respectively (p=0.01), (p=0.001), and (p=0.001) respectively. (Figure 1).

The 12(16.7%) on continuous sedation on MV and the 30 (23%)  with the excessive tracheal secretion of more than 200 ml/24 hours had a high extubation failure rate (p=0.001) and (p=0.03) respectively. (Table 2). No significant difference was found between both groups as regards the serum electrolytes (p=0.2), ABG before (p=0.1),  or after extubation (p=0.4), or fluid balance (p=0.6).  A shorter duration of length of stay on MV was associated with more successful extubation (p=0.05).  (Table 2). 

 

Table 2.  Risk factors for failed extubation in our studied cohort.

 

Successful extubation

Failed 

extubation

P value

Length of stay on MV(<7)days

69 (88.5%)

57 (77.6%)

0.05

Length of stay on MV>7days

9 (11.5%)

15 (20.8%)

0.05

PIP (cmH2O)

12.8±1.6

14.5±1.8

0.01

PEEP (cmH2O)

4.1±0.4

5.5±0.5

0.001

FiO2%

24.9±5.3

27.8±6.1

0.001

OSI

2.5±1.8

3.3±1.8

0.01

Conscious

75 (96.2%)

60 (83%)

0.01

Continuous sedation

3 (3.8%)

12 (16.7%)

0.001

Tracheal secretion ml/24hr

50.0 (20.0- 100.0)

70.0 (30.0- 200)

0.03

Fluid balance over 24hr

-90.0 (-140.0- 130.0)

-57.0 (-125.0- 119.0)

0.6

Serum K(mmol\L)

3.9±0.5

4.0±0.4

0.2

Serum PO4 (mg\dl)

4.4 (4.1- 4.7)

4.2 (4.0- 4.8)

0.2

Inotropic support

yes

3 (3.8%)

3 (4.2%)

0.6

no

75 (96.2%)

69 (95.8%)

0.6

ABG before extubation

 

 

 

PH (mmHg)

7.4±0.1

7.4±0.1

0.1

PCO2 (mmHg)

44.6±5.8

43.8±8.1

0.5

HCO3 (mmHg)

24.0 (20.9- 26.0)

21.8 (20.0- 23.6)

0.06

ABG after extubation

 

 

 

PH (mmHg)

7.4±0.1

7.3±0.1

0.4

PCO2 (mmHg)

44.0±5.5

44.2±9.7

0.8

HCO3 (mmHg)

23.0 (22.0- 27.2)

18.9 (17.6- 24.0)

0.1

ABG: Arterial blood gases; FIO2: fraction of oxygen; MV :mechanical ventilation; OSI: oxygen saturation index; PIP: peak inspiratory pressure; PEEP: positive end expiratory pressure.

 

 

Figure 1.  Associations of extubation outcome in our studied cohort.

 

Cut off value for ventilator settings for the failed extubation group:

The sensitivity and specificity of relying on PIP of > 13 cmH2O as a cut off to predict failure of extubation were 58.6%and 62.1%, respectively, PEEP of > 5.5 cmH2O were 58.6% and 100%, respectively and FiO2 of > 25.5% were 69% and 93.1%, respectively (Table 3).

 

Table3.  Cut off value for ventilator settings for the failed extubation group.

 

Cut off point

The area under the curve

95 % confidence interval

Sensitivity

Specificity

PIP (cmH2O)

13

.603

.456- .750

58.6%

62.1%

PEEP (cmH2O)

5.5

.793

.672-.915

58.6%

100%

FiO2%

25.50

.820

.706- .934

69%

93.1%

FIO2: fraction of oxygen; PIP: peak inspiratory pressure; PEEP: positive end expiratory pressure

 

 

Causes of reintubation:

The most frequent causes of reintubation encountered in this study were laryngeal edema among 31(46.3%) patients, followed by encephalopathy 13 (19.4%), then excessive secretion 12 (17.9%), and hemodynamic instability in 11 (16.4%) (Table 4).

The present study revealed that patients who underwent gradual weaning 63 (80.7%) according to extubation protocol, had a highly successful extubation rate (p = 0.01), and those with accidental and unplanned extubation 27(40.3%) had a significantly high extubation failure rate (p value = 0.01). (Figure 2).

 

 

Figure 2.  Accidental extubation outcome in our studied cohort. 

                                         

Rate of extubation failure trial:

In this study, the first time of extubation failed in 42 (62.6%) patients, then the second time for re-intubation failed 19 (28.4%)patients, and the third time trial failed 6 (8.2%) patients. Sensitivity and specificity of our protocol in extubation were 53.79% and 28.72% respectively. 

 

Table 4. Causes of reintubation among our studied cohort.

Causes of extubation failure

 (Total number= 67)

Number   %

Laryngeal edema

31

46.3

Encephalopathy

13

19.4

Excessive chest secretions

12

17.9

Hemodynamic instability

11

16.4

Encephalopathy causes: hypertensive encephalopathy, hepatic encephalopathy, neurological insult.

 Discussion

Indicators for mechanical ventilation weaning and extubation aim to achieve successful extubation (7). Many risk factors contributed to failed extubation in our current study; as continuous sedation, excessive tracheal secretion, accidental extubation and higher ventilatory settings.

Our single center study results indicate high extubation failure rate. We rely upon respiratory rate (RR);  tidal volume, the assessments of vital signs,  ventilator criteria (PEEP ≤ 5 cmH2O, pressure support ≤ 10 cmH2O and FiO2 ≤ 40%); and calculated OSI

The preventable commonest cause of failed extubation was accidental extubation.  Our study showed that the patients who underwent gradual weaning had a highly successful extubation rate compared to those who extubated accidentally. There are many contributing factors for accidental extubation e.g. patient agitation, inappropriate handling of patients during performance of procedures and inappropriate positioning and fixation of endotracheal tube. All are potentially preventable risk factors, and in turn lead to high extubation failure rate. 

Strict measures should be taken to lower the frequency of accidental extubation as much as possible to lower the rate of extubation failure. In addition, proper assessment of the patients who accidentally extubate. Reintubation as early as possible should be taken into consideration if the patients do not fulfill the criteria for extubation. The only benefit for successfully tolerated unplanned extubation is unintentional decrease in the duration of weaning trials, as it has no other measurable beneficial impact on outcome (14).

 The prolonged use of sedation was another risk factor of failed extubation in our study. The prolonged use of sedation seems possible to control, or fine tune to achieve more successful smooth extubation. Especially that evidence supports that comfort during MV can be achieved with no or very light sedation, and this is associated with lower incidences of delirium, and shorter length of stay (15), and there is no difference between deeply sedated patients and those not deeply sedated regarding extubation success (16). More research is needed to assess the minimum effective dose, duration, methods of administration whether continuous or interrupted and decrease its empirical unnecessary  use as in encephalopathic patients, as it  may be of value  to decrease the frequency of extubation failure.

Chest care and toilette is an essential component in MV care, which include session of nebulizer followed by percussion  and  vibration then suction after flushing the endotracheal tube with normal saline and its implementation to address the amount of secretions more than 200cc/24 hours seems to be an important factor to reduce the failed extubation. No proof that a semi-quantitative airway care score (ACS) comprising six parts: spontaneous cough, gag, sputum quantity, sputum viscosity, suctioning frequency and sputum character in brain injured patients was found effective in prevention of failure of extubation (17). Hence, more research is needed to define an effective chest toilette that achieves successful extubation. 

Assessment of the hydration status of the patients is necessary as dehydration is known to increase the viscidity of secretions, decrease ciliary movement, that increase duration of weaning (18). Control of cough reflex and amount of tracheal secretion is important to decrease the reintubation.

High ventilatory setting i.e. high-pressure support (PIP and PEEP) with a high pulmonary index (e.g. OSI) may lead to a volutrauma in which ultra-structural lung injury is occurring because of using high pressure support. Our study supports close follow-up of ventilatory settings to avoid complications and decrease the extubation failure rate (19).

Duration of mechanical ventilation is very much related to the indication and rate of improvement of the ventilated child (20). Antibiotics, fluids and management of other system affection are all crucial factors in reducing the MV duration and procuring the better extubation. We did not study the effect of nutritional status on the success of extubation, but it is logical to consider that a healthier child would improve in a shorter duration.  

Further research is needed to create a new extubation scoring system based on more individualized and non-invasive objective predictors. We have not assessed sensitivity and specificity of other extubation readiness scores (20), yet, every effort should be made to introduce effective MV strategies.  Neurally adjusted ventilatory assist (NANA) might prove helpful in gradual weaning of patients with a well-trained respiratory therapist (21).

Our study had its limitations, we did not study the effect of nutritional status of the patients, their BMI, their enteral feeding cardiac dysfunction, deconditioned muscle effect and the medications prior to extubation. 

Conclusions

The most common causes of extubation failure are continuous sedation, excessive tracheal secretion, high ventilatory settings on MV and accidental extubation. Furthermore, research is needed to create a new extubation scoring system based on more individualized and non-invasive objective predictors.

Author Contributions: All authors searched medical literature, databases, conceptualized, conducted the case review and reviewed the finalmanuscript. All authors have read and agreed to the published version of the manuscript.

 

FUNDING 

Authors declare there was no extramural funding provided for this study. 

CONFLICT OF INTEREST

The authors declare no conflict of interest in connection with the reported study. Authors declare veracity of information.

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