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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 2  |  Page : 67-73

Clinico-etiological profile of children who had unplanned extubation and subsequent re-intubation in level-4 pediatric intensive care unit


Department of Pediatric Intensive Care Unit, Rainbow Children's Hospital, Banjara Hills, Hyderabad, Telangana, India

Date of Submission29-Sep-2020
Date of Decision16-Dec-2020
Date of Acceptance31-Dec-2020
Date of Web Publication10-Mar-2021

Correspondence Address:
Dr. Vishnu Vardhan Kodicherla
Rainbow Children Hospital, Banjara Hills, Hyderabad
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_143_20

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  Abstract 


Background: There are few studies on unplanned extubation (UE) in pediatric intensive care units (PICU). This study is to identify factors associated with UE in PICUs.
Subjects and Methods: In this observational study, the data of UE from January 1, 2013, to May 31, 2019, in a level-4 PICU were analyzed with an objective to study the etiology of UE and its impact on therapeutic outcomes.
Results: Of 7079 patients hospitalized in PICU, 1721 were invasively ventilated (mean ventilator days 4.33 days). UE occurred in 39 patients (2.26% of intubated patients) at 0.52 UE events per 100 ventilation days. The median age was 14 months. The most common cause of UE was inadequate sedation (n = 24, 61.53%), endotracheal tube suctioning (n = 05, 20.8%), one during adjusting ET tube (4.1%), one during central venous line insertion (4.1%), and one during Foley's catheter insertion (4.1%) and 7 unexplained (29.1%). As long as the appropriate nurse: patient ratio was maintained, the incidence of UE was un-affected by day versus night shift or high versus low bed occupancy rates. Re-intubation rate in UE cohort was higher (74.35%) than planned-extubation cohort 0.11% (P < 0.001). All re-intubations were within 2 h of UE. Most common cause of re-intubation following UE was respiratory distress (72.41%), stridor (17.24%), and apnea (10.34%). Re-intubations following UE showed higher incidence of ventilator-associated pneumonia but statistically not significant (P = 0.54).
Conclusion: UE is associated with a significantly high incidence of re-intubations and associated complications arising from re-intubations. Maintaining a pool of skilled nurses in adequate nurse-to-patient ratio may play an important role in preventing UE. UE can be minimized by optimizing sedation and monitoring during common ICU procedures. Multicentric studies are warranted to design a uniform standard of care of ventilated patients aimed at reducing the incidence of UE.

Keywords: Pediatric intensive care unit, re-intubation, unplanned extubation, ventilator-associated pneumonia


How to cite this article:
Kodicherla VV, Shaikh F, Duvvana PK, Yerra A, Reddy Y, Dekate P, Sachane K, Chirla DK. Clinico-etiological profile of children who had unplanned extubation and subsequent re-intubation in level-4 pediatric intensive care unit. J Pediatr Crit Care 2021;8:67-73

How to cite this URL:
Kodicherla VV, Shaikh F, Duvvana PK, Yerra A, Reddy Y, Dekate P, Sachane K, Chirla DK. Clinico-etiological profile of children who had unplanned extubation and subsequent re-intubation in level-4 pediatric intensive care unit. J Pediatr Crit Care [serial online] 2021 [cited 2021 Apr 20];8:67-73. Available from: http://www.jpcc.org.in/text.asp?2021/8/2/67/311049




  Introduction Top


Unplanned extubation (UE) one of the frequent occurrences in the pediatric intensive care unit (PICU) is defined as the displacement of endotracheal tube (ETT) that occurs at any time other than the time chosen for planned extubation.[1],[2] Despite having a high incidence of 3%–16% in mechanically ventilated patients,[3] it is a less focused area, particularly in developing countries. It is associated with fatal adverse events such as hypoventilation, hypoxia, and even death.[4],[5] The re-intubation rate in these patients is also high (46.1%).[6] Cardiorespiratory complications are the most common causes for re-intubation. The hospital mortality rate of patients who had UE ranges from 10% to 25% and higher for patients who require re-intubation.[7],[8],[9]

Inadequate sedation, agitation, inadequate nursing supervision, workload of nursing staff, high nurse:-to-patient ratio, and inadequate fixation of the ETT predispose to accidental extubations in the ICU.[10]

Understanding the etiology, clinical scenarios of UE help in minimizing the chance of occurrence. There are insufficient data from the developing countries on UE, we intend to share the results of UE from a level 4 PICU and compare it with the available international literature.


  Subjects and Methods Top


This was a retrospective and prospective observational study. Our department of quality and patient safety has been involved in regular audits and maintaining databank of various quality indicators (including rates of UEs in PICU) over the past decade.

We decided to take patients who had UE in the past 4 years (January 1, 2013, to December 31, 2016) from this databank to be included in our “retrospective cohort.” The “prospective” data of patients who had UE were collected from January 1, 2017, to May 31, 2019.

The primary aim of the study was to describe the clinico-etiological profile of the children who had UE. We observed incidence of re-intubation rates in children with UE and the clinical implications following UE and re-intubation in the form of mortality and morbidity (hypoxia, need for re-intubation, and incidence of ventilator-associated pneumonia (VAP)). We also tried to analyze whether the time of extubation (day vs. night) and the patient load in PICU (season with high bed occupancy rate vs. season with lower bed occupancy rates) had any impact on the incidence of UE.

All children aged 1 month to 18 years who were mechanically ventilated and encountered UE from January 1, 2013, to June 31, 2019, were included. Children who were extubated in a planned manner for some procedure (e.g., bronchoscopy, microdirect laryngoscopy, and bronchoscopy etc.) and later re-intubated were excluded.

Sedation policy during ventilation and extubations

Standard hospital policy was utilized for sedation, mechanical ventilation, and extubation.

As per our unit policy, if a child is sick and unstable after intubation, we sedate them with continuous infusion of sedatives such as midazolam, fentanyl, ketamine, dexmedetomidine, or morphine. Those children who were intubated for short ventilation and are stable hemodynamically with minimal ventilator support and an expectation of extubation within 1 or 2 days are managed by an intermittent bolus of sedatives and analgesics (midazolam plus fentanyl) and background infusion of intravenous (IV) dexmedetomidine.

In both the scenarios, the target was to achieve Ramsay Sedation Scale of 3–4. Very deep sedation and paralysis, in general, were avoided. After the acute phase was over, and the FiO2 requirement was below 60% with moderate ventilator settings, early morning “sedation holiday” was given by stopping IV sedation infusions in morning. “Spontaneous breathing trial (SBT)” was given, once the FiO2 requirement is below 40% with minimal ventilator settings and the patient is on “assisted mode” of ventilation (e.g., synchronized intermittent mandatory ventilation with pressure support) and sensorium is good with good spontaneous breathing efforts.

If a patient passes SBT, he/she is generally considered “safe” for extubation, a good chest physiotherapy was carried out followed by oral and endotracheal suctioning, and then, the patient was extubated. In stable patients, further management by oxygen is delivered through a face mask or nonrebreather mask. In postextubation stridor, 3% saline nebulization and/or adrenaline nebulization were administered.

Decision of using high-frequency nasal canula (HFNC) or continuous positive airway pressure (CPAP) in the postextubation period was made depending on the patient's breathing efforts, oxygenation, and hemodynamic status.

In the presence of signs of breathing difficulty (poor respiratory efforts or signs of respiratory distress), hypoxia, hemodynamic instability (hypotension, tachycardia, or bradycardia), or poor sensorium with an inability to handle secretions or airway, re-intubation was considered.

Endotracheal tube size and policy on endotracheal tube cuff pressures

All the patients in our PICU are intubated with cuffed ETT (cuffed = age [years]/4 + 3.5).

The decision of inflating the ETT cuff was made depending on the leak around the ETT and patient's ventilator requirement; a leak of 10%–15% not affecting patients' ventilation and oxygenation was considered acceptable and the cuff was not inflated. If there was a requirement for high ventilator settings (acute respiratory distress syndrome, pulmonary edema, etc), even a 10% leak around the ETT was considered not acceptable and the ETT cuff was inflated.

Depth from the lip (in cm) = age (years)/2 + 12

Oral intubation was performed as a standard protocol, and the ETT was fixed with double Dynaplast tape.

Nurse:Patient ratio

The nurse-to-patient ratio recommended by the Indian Nurse Council and some Indian resources[11] is:

For very sick patient (ventilated patients on high ventilator settings, multiple inotropes, high-frequency oscillation ventilation, continuous renal replacement therapy, or extracorporeal membrane oxygenation etc.), 1 patient: 2 nurses; for sick patients (ventilated on moderate settings, those on CPAP/HFNC with severe distress, and on multiple inotropes), 1 patient: 1 nurse; for moderately sick patients (on CPAP/HFNC but stable, hemodynamically stable, etc.), 2 patients: 1 nurse; and for stable patients (on low flow oxygen or room air, feeding on NG, or direct oral feeds,), 3 patients: 1 nurse.

The shift in-charge nurse documents the nurse-to-patient ratio in the nursing register every midnight and takes the signature of the night on-call consultant/fellow. We audited the nurse–patient register during the study period and found that this procedure was diligently followed and documented in the register.

Statistical analysis

The data were captured on Microsoft Excel (2013) for further analysis after checking the completeness and consistency of the data. The results were expressed as mean, standard deviation or median, and interquartile range for the continuous variables. The categorical variables were expressed as percentage (%) and frequency distribution.

Appropriate tests of significance such as Student's t test, Chi-square test, and Fisher's exact test were applied as applicable. Odds ratios were computed to assess the risk factors for UE and planned extubation. The analysis was carried out by using Statistical Package for the Social Sciences v20. P < 0.05 with two-tailed test was considered as statistically significant.


  Results Top


Of 7079 patients hospitalized in PICU, 1721 (21.31%) were invasively ventilated, of whom 39 (2.27%) had UE. There were 1682 patients (97.73%) who did not have UE and were either discharged subsequently or died or went LAMA and they were not studied further as they were not part of our study population [Figure 1].
Figure 1: Unplanned extubation study flowchart

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The median age of the children who had UE was 14 months; 28 (71.79%) children were aged <2 years. Of those who had PE, 850 (49.39%) were aged <2 years. There was no statistically significant (P = 0.14) difference between the age distribution between the two groups.

There was a male preponderance (n = 30, 76.92%) in the UE cohort compared to the PE cohort (n = 987, 57.35%).

Respiratory (n = 19 48.7%) and neurological causes (n = 9.23%) were the common indications for mechanical ventilation in the UE cohort [Figure 2].
Figure 2: Indications for intubation in the unplanned extubation cohort

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Of 39, UE occurred due to inadequate sedation (Ramsay score <2) (n = 24, 61.53%), during ET suctioning (n = 05, 12.82%), and other procedure (n = 02, 5.12%; during central vascular line insertion and removal of Foley's catheter) and 8 were unexplained.

Modes of ventilation

Of 39 children who had UE, 31 (79%) were on full ventilatory support in “Control Mode” (of whom pressure regulated volume control [n = 14, 35%], pressure Control mode [n = 15, 38%], and high-frequency oscillation (n = 02, 5%)]. Eight (21%) patients were on “weaning” mode (SIMV (n = 06, 15%) and CPAP-PS mode (n = 02, 5%).

Sedation used during the episode of unplanned extubation

At the time of occurrence of UE, most children were on morphine infusion [Table 1].
Table 1: Sedatives at the time of unplanned extubation

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Among children who underwent UE, the mean Ramsay sedation score was 2.44 [Figure 3].
Figure 3: Ramsay sedation score at the time of unplanned extubation

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Associated mortality

Of 39 patients with UE, 29 (74.35%) recovered and discharged; there were six (15.38%) deaths and four (10.25%) were DAMA. All in the cohort of UE who did not require re-intubation survived and discharged.

Re-intubation

Of 39 UEs, 29 (74.35%) patients were re-intubated, rate of re-intubation was higher compared to those with planned extubations (n = 191/1682, 11.36%), and was statistically significant (P < 0.001). Of 29 re-intubated patients, 23 (79.31%) were re-intubated immediately following UE due to desaturation or respiratory failure; six (20.69%) of them were relatively stable, received a trial of noninvasive ventilation but failed later, and were re-intubated within 2 h of UE.

Increased work of breathing/hypoxia (n = 21, 72.41%) patients, severe stridor (n = 05, 17.24%), and apnea (n = 03, 10.34%) were the reasons for re-intubations.

Of 23 re-intubated patients, 21 (81.48%) were extubated in the next 48 h and two (7.40%) required ventilator support for >96 h. Those who did not get re-intubated (10/39) after the event of UE were managed by high-flow oxygen therapy either via nonrebreathing mask (n = 07) or heated humidified high-flow oxygen therapy via nasal canula (n = 03).

Ventilator-associated pneumonia

VAP rate in this study was 8.72/1000 ventilator days. In those, who underwent re-intubation (n = 29), VAP was seen in one child with a VAP rate of 11.36/1000 ventilator days. There was an increased incidence of VAP rate in those who were re-intubated post-UE than the total VAP rate in PICU, but this was not statistically significant (P = 0.54).

Timing during unplanned extubation

We had 20 patients encountering UE between 7 am and 7 pm time duration, while there were 19 patients with UE between 7 pm and 7 am time period. Thus, there was not much difference in theincidence of UE based on time of the day.

Unplanned extubation rates based on bed occupancy rate

We analysed the association of bed occupancy during first half and the second half of the years in last 3 years (2016, 2017 and 2018) [Table 2].
Table 2: Unplanned extubation rates based on bed occupancy rate

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In the past 3 years, we had significantly higher bed occupancy (P = 0.0037) during the second half of the year (July to December period) as compared to the first half of the year (January to June). This is mainly due to the increased number of PICU admissions for dengue illness, scrub typhus, and viral flu in the second half of the year [Table 3].
Table 3: Baseline characteristics of our study

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We found that the rate of UE was not significantly different in the first half or the second half of the years (P = 0.3389).


  Discussion Top


There are very few studies published internationally on UE s in the pediatric population. Our study is an observational study of children who had UE and is not a comparative study between children who had UE and children who had planned extubations.

In this retrospective and prospective study, we noted that the rate of UE was 0.52 per 100 ventilation days. In the published literature, the rate of UE is ranging widely from 0.1 to 4.2/100 intubation days. Our UE rate of 0.52 per 100 intubation days is in sync with the internationally published data.[12],[13] The most common reason was inadequate sedation and the re-intubation rate among UE was higher than those with planned extubation (74.35% vs. 11.36%).

In the multicenter analysis of the factors associated with UE in the PICU, Fitzgerald et al.[14] observed that there were conflicting and inconclusive study results about the association of age with UE, with several findings that younger age groups are at higher risk for UE. In our study, the median age group of the children who underwent UE s is 14 months.

Among the children who underwent UE, maximum number of extubations occurred in children <2 years (71.79%), supporting the observation that the association of age below 2 years to be associated with a higher incidence of UE though it was not statistically significant (P = 0.14) in our study. Menon et al.[15] have reported UE to be more common among those aged <1 year (66.6%).

We had anticipated that UE would occur during the “weaning phase” when we reduce sedation and allow more spontaneous breathing. We had UE in 79% of children who were on full ventilatory support in “control mode” and only 20.5% were on weaning mode. Our findings are consistent with those reported by other authors.[7],[16]

The rate of re-intubation in patients with UE in published literature ranged from 14% to 65%,[16],[17] while in our study, we had 74.35% of children who got reintubated following the event of UE. UE had an adverse clinical impact on our patients by having significantly higher rates (P < 0.001) of re-intubation (74.35%) as compared to the re-intubation rates following planned extubation (11.36%).

ETT fixation method and the materials used were not part of this study; however, Fitzgerald et al.[14] in their study observed that simply being consistent with taping method within a unit and all the members adhering to the standard unit practice leads to less UE.

Cuffed ETT was associated with a decreased rate of UE compared with uncuffed ETT in some studies.[18] In our unit, all the patients are intubated with cuffed ETT; hence, we could not a comparative data to confirm whether cuffed ETT indeed reduces the risk of UE.

Inadequate sedation is clearly a risk factor for UE in many studies.[18],[19] In our study too, in 24 patients out of 39 UEs, inadequate sedation was the main cause for UE. In our study, the mean Ramsay sedation score was 2.44 which is a little less than our unit standard targeting score of 3–4 for all intubated patients on control mode of ventilation. All the intubated patients in our study were on continuous sedation infusion with an intermittent bolus dose of sedative to maintain an optimum sedation score of 3–4 and if required, bolus dose of neuromuscular blocking agent (rocuronium or pancuronium).

There was an increased incidence of VAP rate in the subgroup of children who were re-intubated post-UE compared to patients who were ventilated and extubated without any event of UE; however, this was not statistically significant (P = 0.54). However, we could not find studies with similar findings to compare.

Our study supports the finding of two previous single-center pediatric studies, showing no difference in the rate of UE by the time of day[16],[20] when split by a 12-h shift model and an 7-h shift model. In our study, we had similar number of UEs in day (n = 20) and night (n = 19) shifts.

We found that the rate of UE was not significantly different in the first half or the second half of the years (P = 0.3389). This was similar to the findings of the study done by Censoplano et al. and Klugman et al. who found low rates of UEs even during high admission rates as long as the quality- and patient safety-related processes are firmly in place.[21],[22] As discussed already in methodology, our shift in-charge nurse maintains nurse-to-patient ratio as per the recommendation from the National Accreditation Board for Hospitals and health-care providers, Indian nursing council guidelines, and as part of our unit policy. The rate of UE in our study is 2.26%. Maintaining adequate nurse patient ratio and their appropriate training and education could have been one possible reason for low rates of UE in our unit and the reason for same rates of UE during periods of high bed occupancy and during night shifts.

We believe that maintaining well trained nurses with sufficient work experience may have played a crucial role in preventing UEs during periods of high bed occupancies and during night shifts. Hickey et al.[5] studied on impact of critical care nursing on patient outcomes reinforcing the importance of organization-wide mentoring strategies for new nurses, consistent nurse staffing, and retention strategies for experienced nurses. Their study demonstrated that higher levels of nursing education and experience were significantly associated with fewer complications and reduced mortality in the pediatric cardiac intensive care unit.

Strengths and limitations of the study

In our study, we have analyzed various factors which can cause UE including the impact of day versus night shifts and seasonal variation of patient load in the unit.

We have also analyzed the impact of UE on adverse clinical outcomes like re-intubation rates.

As this is a retrospective and prospective observational study from a single center, it has its inherent limitation in applying it on larger populations.


  Conclusion Top


UE is associated with a significantly high incidence of re-intubations and associated complications arising from re-intubations. Maintaining a pool of skilled nurses in adequate nurse-to-patient ratio may play an important role in preventing UE.

UE can be minimized by optimizing sedation and monitoring during common ICU procedures. Multicentric studies are warranted to design a uniform standard of care of ventilated patients aimed at reducing the incidence of UE.[22]

Recommendations

  • We recommend standardization of sedation policy and regular training and education of the doctors and nurses to reduce the incidence of UEs
  • Standardizing unit practices of intubation techniques and technique of ETT fixation also are useful interventions in preventing UE
  • Maintaining optimum nurse-to-patient ratio based on the sickness level of the patients can be an important step toward reducing incidents of UEs.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Frank BS, Lewis RJ. Experience with intubated patients does not affect the accidental extubation rate in pediatric intensive care units and intensive care nurseries. Pediatr Pulmonol 1997;23:424-8.  Back to cited text no. 1
    
2.
Popernack ML, Thomas NJ, Lucking SE. Decreasing unplanned extubations: Utilization of the Penn State Children's Hospital Sedation Algorithm. Pediatr Crit Care Med 2004;5:58-62.  Back to cited text no. 2
    
3.
American Academy of Pediatrics Steering Committee on Quality Improvement and Management. Classifying recommendations for clinical practice guidelines. Pediatrics 2004;114:874-7.  Back to cited text no. 3
    
4.
Kapadia FN, Bajan KB, Raje KV. Airway accidents in intubated intensive care unit patients: An epidemiological study. Crit Care Med 2000;28:659-64.  Back to cited text no. 4
    
5.
Hickey PA, Pasquali SK, Gaynor JW, He X, Hill KD, Connor JA, et al. Critical care nursing's impact on pediatric patient outcomes. Ann Thorac Surg 2016;102:1375-80.  Back to cited text no. 5
    
6.
Chao CM, Sung MI, Cheng KC, Lai CC, Chan KS, Cheng AC, et al. Prognostic factors and outcomes of unplanned extubation. Sci Rep 2017;7:8636.  Back to cited text no. 6
    
7.
de Groot RI, Dekkers OM, Herold IH, de Jonge E, Arbous MS. Risk factors and outcomes after unplanned extubations on the ICU: A case-control study. Crit Care 2011;15:R19.  Back to cited text no. 7
    
8.
Krinsley JS, Barone JE. The drive to survive: Unplanned extubation in the ICU. Chest 2005;128:560-6.  Back to cited text no. 8
    
9.
Phoa LL, Pek WY, Syap W, Johan A. Unplanned extubation: A local experience. Singapore Med J 2002;43:504-8.  Back to cited text no. 9
    
10.
Chatterjee A, Islam S, Divatia JV. Airway accidents in a surgical ICU. Indian J Crit Care Med 2004;8:36-9.  Back to cited text no. 10
  [Full text]  
11.
Ream RS, Mackey K, Leet T, Green MC, Andreone TL, Loftis LL, et al. Association of nursing workload and unplanned extubations in a pediatric intensive care unit. Pediatr Crit Care Med 2007;8:366-71.  Back to cited text no. 11
    
12.
Da Silva PS, Fonseca MC. Unplanned endotracheal extubations in the intensive care unit: Systematic review, critical appraisal, and evidence-based recommendations. Anesth Analg 2012;114:1003-14.  Back to cited text no. 12
    
13.
Al-Abdwani R, Williams CB, Dunn C, Macartney J, Wollny K, Frndova H, et al. Incidence, outcomes and outcome prediction of unplanned extubation in critically ill children: An 11 year experience. J Crit Care 2018;44:368-75.  Back to cited text no. 13
    
14.
Fitzgerald RK, Davis AT, Hanson SJ. Multicenter analysis of the factors associated with unplanned extubation in the PICU. Pediatr Crit Care Med 2015;16:e217-23.  Back to cited text no. 14
    
15.
Menon K, Dundon B, Twolan BL, AlShammari S. Approach to unplanned extubations in a pediatric intensive care unit. Can J Crit Care Nurs 2015;26:25-9.  Back to cited text no. 15
    
16.
da Silva PS, de Aguiar VE, Neto1 HM, de Carvalho WB. Unplanned extubation in a paediatric intensive care unit: Impact of a quality improvement programme. Anaesthesia 2008;63:1209-16.  Back to cited text no. 16
    
17.
Kurachek SC, Newth CJ, Quasney MW, Rice T, Sachdeva RC, Patel NR, et al. Extubation failure in pediatric intensive care: A multiple-center study of risk factors and outcomes. Crit Care Med 2003;31:2657-64.  Back to cited text no. 17
    
18.
Meregalli CN, Jorro Barón FA, D'Alessandro MA, Danzi EP, Debaisi GE. Impact of a quality improvement intervention on the incidence of unplanned extubations in a pediatric intensive care unit. Arch Argent Pediatr 2013;111:391-7.  Back to cited text no. 18
    
19.
Menon K, Dundon B, Twolan BL, AlShammari S. Approach to unplanned extubations in a pediatric intensive care unit. Can J Crit Care Nurs 2015;26:25-9. PMID: 26562971.  Back to cited text no. 19
    
20.
Sadowski R. Continuous quality improvement: Reducing unplanned extubations in a pediatric intensive care unit. Pediatrics 2004;114:628-32.  Back to cited text no. 20
    
21.
Censoplano NM, Barrett CS, Ing RJ, Reichert K, Rannie M, Kaufman J. Achieving sustainability in reducing unplanned extubations in a pediatric cardiac ICU. Pediatr Crit Care Med 2020;21:350-6.  Back to cited text no. 21
    
22.
Klugman D, Melton K, Maynord PO, Dawson A, Madhavan G, Montgomery VL, et al. Assessment of an unplanned extubation bundle to reduce unplanned extubations in critically ill neonates, infants, and children. JAMA Pediatr 2020;174:e200268.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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