Authored by Masoud Rasha*
Abstract
Objective: Study the predictors of extubation trial failure, for very low birth weight infant.
Methods:
Results: 0.30, and high PCO2 level above 55 mmhg post extubation, Ground glass appearance on chest XR at trial, large PDA, low and advanced grades IVH. Success associates FIO2 level <(0.25) before extubation, post extubation PEEP level (6-7) cm water.
GA (27- 29+6) weeks, failure associates FIO2 level >0.30, and low PH level (6.9 - 7.24) post extubation, advanced grade IVH. Success associates single antenatal steroid dose, FIO2 level (0.21) before extubation, post extubation PEEP level range (6-7) cm.
GA (30- 32) weeks, failure associates FIO2 level >0.30, low PH level (6.9 - 7.24), and low PO2 (20-40) mmhg post extubation, large PDA. Success associates mother’s Pre-labor rupture of membranes, adequately sized, waiting until FIO2 requirement level is < (0.25), and IT >0.38 sec before extubation.
Surfactant dose not determine extubation trial results for GA (21+4- 23+6). Success associates 2 doses for GA (24- 26+6) weeks, single dose for GA (27- 29+6) weeks, and all 1st, 2nd and 3rd doses for GA (30-32) weeks.
Low phosphorus level associate’s failure for GA (24- 26+6, 27- 29+6).
Conclusion: Predictors of extubation trial failure vary among GA groups, and may guide physician to predict the result of extubation trial and reduce exposure to failure. Optimizing documentation and follow up research studies on larger sample size, are recommended to analyze secondary predictors.
Keywords: ELBW; Extubation failure; Risk factor; Bronchopulmonary dysplasia; Ventilation; NAVA
Background
Antenatal steroids and early use of nasal continuous positive airway pressure (NCPAP) have significantly improved outcomes of very low birth weight infants with respiratory distress syndrome [1,2], but intubation with ventilator support is still required and the optimal timing of extubation remains unclear. Nearly two thirds of premature born at less than 29 week gestation require mechanical ventilation during NICU stay [3]. Acute complications, and bronchopulmonary dysplasia (BPD), adverse neurodevelopmental outcomes, related to mechanical ventilation and endotracheal intubation in extreme preterm infants [4,5] are encouraging physicians to extubate infants as early as possible. Short-term (less than 7 days) mechanical ventilation itself is known to be a cause of rapid diaphragmatic dysfunction, and long-term ventilation (more than 12 days) is also associated with failure of normal pulmonary growth and maturation [6]. But still 40% of mechanically ventilated ELBW infants require re-intubation following extubation [7]. Failure of extubation has been associated with higher mortality rates, increased length of hospital stays, and longer ventilation days [8,9].
Mode of ventilation that converts electrical activity of diaphragm into proportionally assisted and synchronized breath is known as neutrally adjusted ventilatory assist (NAVA) [6]. Infants inform the neonatologist of what support they need, directing both the timing and depth of their breath pattern [10]. NIV NAVA can provide synchronized post extubation ventilatory support as measured by decreased PCO2 in premature infant [11].
NAVA appears to work well in neonates, but if NAVA makes a difference in outcomes in this population, has not been established so far [10].
Methods
Research proposal was reviewed and approved by Tawam Human Research Ethics Committee-Abu Dhabi Health service company UAE. The purpose of the study is to evaluate the rate and predictors of extubation failure in VLBW, especially the post extubation ventilation set to establish a local protocol to avoid extubation failure, improve the outcome of VLBW infants, and decrease the rate of chronic lung disease. Hospital ID number was de-identified and masked to secure confidentiality and no consent was required, the study was in compliance with the Declaration of Helsinki. The study work starts by a pharmacy list of 1580 shot of surfactant 2011- 2018, given to 761 neonates admitted to NICU, as some patients require 1st, 2nd, 3rd or 4th doses of surfactant. Retrospectively we collect Data from records of 457 neonates who fit criteria of <32 weeks GA, or < 1500g BWT. 11 neonates are excluded for congenital anomaly.
We evaluate 446 VLBW admitted to neonatal intensive care unit (NICU) –Tawam Hospital and intubated from Jan 2011 till Jan 2018. Risk factors, ventilation parameters, blood gas results prior and 2 hours post extubation trial are analyzed. Definition of extubation failure is re-intubation within 5 days due to attending physician assessment of clinical status and blood gas. Over years of the study some of NICU team turned over (Guide for extubation is the aim of the study), causing bias that could not be handled retrospectively. Tool of statistical analysis is IBM SPSS Statistics version 20. We use non-parametric tests for non-normally distributed Data. Categorical variables analysis is loglinear and 3way Pearson’s Chi square X2. The test analyzes association between extubation trial result and each predictor for each GA group GA (21+4- 23+6, 24- 26+6, 27-29+6, 30-32), but have not allow for analysis of all predictors at once. At some steps analysis we must merge GA groups (21+4- 23+6, 24- 26+6) for small sample size of GA group (21+4- 23+6).
Extubation results are 1- success, 2- fail, 3- (not fit for extubation till end of 14 days of life). As not fit for extubation and failing it share the case of VLBW undue for extubation, We have merge 2 and 3 for part of predictors, while used (Success, Fail) for ventilation predictors. Goodness of fit tests and cramer’s V determines the strength of association. We run several steps analyses for some predictors to extract cut off significance or compare several variables in pairs. Prenatal Steroid is grouped (No steroid given or unknown, Steroid given) then subgrouped into (1 dose, 2 doses). Timing of each dose is not recorded. Size for GA groups (small for GA- below 10th centile on Fenton growth chart, Adequate for GA, Large for GAabove 90th centile on Fenton growth chart). Gender groups (Male, Female). Number of surfactant doses is determined by physician’s opinion and clinical requirement. Patients who died at 1st day of life are excluded from surfactant analysis. The test is performed on 4 levels to test the cut off statistically significant dose for each GA. Gestational diabetic status GDM groups (No GDM or unknown, GDM). Mother’s chorioamnionitis status before delivery is defined by gynecologist clinical assessment only and follow up histologic chorioamnionitis is not recorded. Chorioamnionitis groups (No chorioamnionitis or unknown, chorioamnionitis). Pre-labor ruptured membrane mother’s status groups (No PROM or unknown, PROM >18hours). Caffeine treatment groups (no Caffeine, Caffeine). Phosphorous level at 2nd week of life groups (less than 1.8 mmol/L, above 1.8 mmol/L). Day of life at 1st intubation (Intubated 1 in delivery room, any time later). Ventilation Mode before extubation trial groups (NAVA, Conventional ventilation +/- Volume targeted ventilation, PSV). Ventilation parameters before extubation are set by attending physician. Peak Inspiratory Pressure (PIP) level between (8-28) cm H2O, Median 18.8 cm H2O, Mode 20 cm H2O. Positive end-expiratory pressure (PEEP) level between (5-8) cm H2O. PEEP groups(<6, >6) cm H2O. Ventilation Rate 20-60/min, “mode 40/min”. Rate groups (20-40, 41-60)/ min.
Fraction of inspired oxygen FIO2 Mode is 0.21. Inspiratory time (IT) range (0.20-0.86) sec. Mode 0.38 sec. IT groups (0.20-0.33, 0.33-0.37, 0.38-0.4, 0.4-0.86) sec. Patient’s respiratory rate before extubation (RR) range (20-99)/min, Mode 50/min. RR groups (20- 40, 40-70, 70-99)/min. . Blood gases are capillary and arterial samples and we set groups following acid-base homeostasis range of arterial blood gas of VLBW. PH mean 7.33 (7.0-7.57), PH groups (7- 7.24, 7.25-7.34, 7.35-7.57).
PCO2 mean 41 (9.2-69) mmhg, PCO2 groups into (9-34, 35-54, 55-70) mmhg. PO2 mean 49.4 (21.5-144), PO2 level groups (20-40, 41-70, 71-145) mmhg. HCO3 mean 21.38 (9.7-34), groups (9.2-18, 18.1-25, 25.1-36). BE mean - 3.98 (-15.3 to +6), BE groups (-16 to -8, -7.9 to 6). HB mean 14.5 (7.3-24) g/dl. Post extubation ventilation mode and set are chosen by attending physician. Ventilation mode groups (Continuous positive airway pressure CPAP, Noninvasive NAVA ventilation “NIV NAVA”, non-invasive ventilation). PIP level mode 8 cm H2O. PIP groups (5-8, 9-30) cm H2O. FIO2 level mode 0.21, groups (0.21-0.30, 0.31-0.90). PEEP level (<6, 6-7, 8-10) cm H2O. Ventilation rate (15-30, 31-60)/min. Edi max mean 7 (2.8- 12) μV. Edi max mean 1.4 (0.2-5) μV. PH level mode 7.3, groups (6.9- 7.24, 7.25-7.34, 7.35-7.55). PCO2 level mode 42 mmhg, PCO2 groups (19-34, 35-54, 55-86) mmhg. PO2 level mode 40 (18-127) mmHG, groups (20-40, 41-70, 71-145) mmHG. HCO3 level groups (10-18, 18.1-25, 25.1-36) mEq/L. Each VLBW fails extubation and re-intubated has CXR to check ETT tip position. The major finding for all GA groups is ground glass appearance 60%, 51.6%, 87.5% for GA group (21+4- 26+6, 27- 29+6, 30-32). CXR at failure groups (nonground glass appearance, significant ground glass appearance). Times of extubation (1st, 2nd, 3rd). Extubation day (within 2days of life, within 7days of life, later). Air leak groups (No air leak, air leak syndrome till 14 days of life). Air leak syndrome include [PIE, Tension pneumothorax]. PDA (Tiny PDA and no treatment needed, Large significant PDA requiring treatment). IVH grade (No IVH, low grade 1&2, advanced grade 3&4). Continuous variables analysis is Mean and One-way ANOVA. We don’t have a non-parametric test that analyzes the effects of all predictors at once.
Results
The study evaluates 446 neonates <32 weeks GA, or < 1500g BWT. 132/446 are not fit for extubation trial till the end of 14 days of life.
1st trial extubation (till 14 days of life)
314/446 infant 1st extubated after assessment of clinical stability by attending physician. (before completing 14 days of life).
222/314 (70.7%) infant succeed at 1st trial extubation (success is defined by passing 5 days without re-intubation).
92/314 (29.29%) infant fail at 1st trial extubation (need re-intubation within 5 days post extubation).
2nd trial extubation (included only within 7 days of life to observe patients over the next 5 days)
We exclude 34/92 trial post 1st week.
15/92 infant are not fit for extubation till 14 days of life.
43/92 infant, 2nd trial extubation (within 7 days of life).
29/43 infant succeed 2nd trial extubation.
14/43 infant fail 2nd trial of extubation.
3rd trial extubation (only within 7 days to observe patients over the next 5 days)
We exclude 12 patients are not fit for extubation within the first 7 days of life.
3 infants, 3rd trial extubation within 1st week.
2 infants succeed 3rd trial extubation.
1 infant fails 3rd trial extubation.
Discussion
Our study is enlighted by the paper of Shih-Hsin Wang and his colleagues 2015, the only predictor that their study proved to be related to extubation failure is poor acid - base homeostasis 2 hours after extubation (pH < 7.3 and HCO3 < 18 mM/L) regardless of premature GA [12]. Our study is unique for the sample size and the analysis of subgroups GA. The following is discussion of results in Tables 1,2,3.
One dose of antenatal steroid is enough to statistically predict extubation success for GA (27- 29+6) weeks, and 2nd dose not add to the significance. Unrecorded cases may underestimate the effect of steroid (bias).
Adequately sized GA group (30-32) weeks, have moderate association with extubation success than small for GA. Male gender of GA (21+4-26+6) weeks is related to extubation failure, and no association for other GA groups.
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