Abstract
Extubation failure (EF) following neonatal cardiac surgery is associated with increased mortality. Neonates who experienced EF twice or more (recurrent EF) may have worse outcomes than those who have a single EF or no-EF. The aims of this study are to investigate the in hospital mortality for neonates with recurrent EF compared to those with single or no-EF, and determine factors associated with recurrent EF. Neonates’ ≤ 28 days who underwent cardiac surgery from January 2008 to December 2019 were included. EF was defined as unplanned reintubation within 72 h after a planned extubation. 1187 (18 recurrent EF, 84 single EF and 1085 no-EF) neonates were included. Recurrent EF occurred in 18 (17.6%) of 102 neonates undergoing a second extubation. The median time (IQR) to reintubation after the first and second extubations were similar, being 20.9 (3.3–45.2) versus 19.4 (5.5–47) h. The reason for a second-time EF was respiratory in 39% and cardiovascular in 33%. Recurrent EF and single EF was associated with increased mortality (odds ratio, 95% confidence interval (CI) 23.5, 6.9–79.9) and (odds ratio, 95% CI 5.2, 2.3–12.0) compared to no-EF. Based on the final model with risk adjustment, predicted mortality was 29.0% in recurrent EF, 6.5% in single EF, and 1.2% in no-EF. First-time EF due to cardiovascular compromise was associated with recurrent EF (odds ratio, 95% CI 3.1, 1.0–9.7). This study confirmed that patients with recurrent EF have a high morality. Neonates with a cardiovascular reason for first-time EF are more likely to have a recurrent EF than those with other causes.
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
Background
Previous studies have demonstrated that extubation failure (EF) occurs in 12–18% of neonates after cardiac surgery and is associated with increased mortality (8–30%), prolonged length of stay in the pediatric intensive care unit (PICU) and hospital [1,2,3,4]. Several reports have shown that the etiology of EF was diverse including residual cardiac issues, respiratory or tracheal pathology, upper airway obstruction, diaphragmatic palsy, sepsis, or bleeding [4,5,6]. Some causes are amenable to simple treatments which will increase the likelihood of subsequent successful extubation, whilst other causes are more complex and may involve further surgery or be associated with complex congenital malformations [7].
We hypothesized that neonates experiencing EF twice or more (recurrent EF) may have a higher mortality than neonates experiencing EF once (single EF) or those experiencing no EF (non-EF). It was unclear as to the likely causes of each type of EF and whether this was important to ultimate outcome. Hence this study was done with the primary aim of investigating the hospital mortality among recurrent EF, single EF and non-EF. Secondary aims were to explore the reason of second-time EF, and the association between first EF due to cardiovascular compromise and outcomes.
Methods
Study Design and Participants
This is a single-center retrospective cohort study. The paediatric intensive care unit at the Royal Children’s Hospital Melbourne is a 30-bed combined medical-surgical PICU. All patients after cardiac surgery are admitted to the cardiac pod in the PICU except premature neonates after patent ductus arteriosus ligation. We included all neonates who were 28 days or younger at cardiac operation and admitted to the PICU from January 1, 2008 to December 31, 2019. This study included only the first cardiac surgery for each neonate during the study period. Exclusion criteria included unplanned extubation, no extubation attempt, withdrawal prior to the extubation attempt and tracheostomy.
Definitions and Data Collection
EF was defined as unplanned reintubation within 72 h after planned extubation. The recurrent EF was defined as those who underwent EF twice or more after cardiac surgery. The single EF was defined as those who had EF once. Non-EF was defined as those who had no EF. The following data were retrospectively collected from the medical chart; patient characteristics and preoperative data (sex, gestation, weight, date of birth, date of surgery, date of PICU admission, cardiac diagnosis, comorbidities), operative data (risk adjustment in congenital heart surgery-1 (RACHS-1) category, cardiopulmonary bypass (CPB) time), peri-extubation data (the date and timing of extubation and reintubation, respiratory support post extubation), and outcomes (hospital death, PICU and hospital length of stay). RACHS-1 category was classified as low, medium, high RACHS-1 category based on the mortality in previous literatures. The cause of EF was chosen from a preset table of the etiology of EF by an investigator (S.M.) using information from the medical chart, laboratory result, radiology, echocardiography and other imaging, and conference report. If there are two or more etiologies, the primary one was decided in discussions among study investigators. In cases where there was any uncertainty as to the cause of EF, the cause was ascertained by another investigator (S.P.N.) until two investigators reached an agreement. Among deceased patients without extubation attempt, they were considered to have treatment withdrawal if associated words such as palliation or treatment withdrawn due to fertility were documented in medical records.
Statistical Analysis
Collected data were presented as a number with the percentage for dichotomous variables and median with interquartile range (IQR) for continuous variables. For the analysis for hospital mortality among recurrent EF, single EF and non-EF, a multivariable logistic regression model was developed by adjusting with preset study covariates (age, sex, gestation, chromosomal abnormality, CPB time, preoperative PICU admission, and RACHS-1 category). The predicted risk for hospital mortality by category of EF for the neonate after cardiac surgery was estimated from the final logistic model with covariates adjusted at the mean of observed values. Among 102 neonates who experienced EF once or more, the outcome was compared by the reason of reintubation (cardiovascular or the others) using a logistic regression model after adjusting with same study covariates. Two-tailed p values less than 0.05 were considered significant. STATA 14 (Stata Corp LLC, College Station, TX, USA) was used for all statistical analyses.
Results
During the study period, 1253 neonates underwent cardiac surgery. After excluding 56 neonates who met the exclusion criteria prior to the first extubation, 1197 underwent extubation. 9.4% (112 out of 1197) neonates failed (Fig. 1). Ten of 112 reintubated neonates were excluded from the analysis prior to the second extubation attempt. 17.6% (18 out of 102) experienced recurrent EF. 1187 neonates (18 recurrent EF, 84 single EF, 1085 non-EF) were included for the analysis. The characteristics of included patients are described in the Table 1. The overall hospital mortality was 3.3%. Among the excluded 13 neonates who had an unplanned extubation, 11 were successful (non-EF), 1 failed and extubated successfully the next time and 1 died after 46 days in the PICU.
The crude mortality in recurrent EF, single EF, and non-EF were 33.3% (6 out of 18), 13.1% (11 out of 84), and 2.0% (22 out of 1085) (Fig. 2a). A logistic regression model showed higher hospital mortality in recurrent EF (odds ratio 23.5, 95% confidence interval (CI) 6.9–79.9, p < 0.001) and single EF (odds ratio 5.2, 95% CI 2.3–12.0, p < 0.001) compared to non-EF after adjusting for study covariates. The predicted risk of hospital mortality by EF categories after adjustment of the study covariates are shown in the Fig. 2b, providing the predicted mortality of 29.0% in recurrent EF, 6.5% in single EF, and 1.2% in non-EF. Recurrent EF was associated with prolonged length of stay in PICU and hospital (Table 2). The Hosmer–Lemeshow goodness of fit test showed p value of 0.30. When recurrent EF was compared to single EF among 102 neonate who experienced EF once or more, neonates with recurrent EF nearly had a fivefold increased odds of death (odds ratio 4.8 (95% CI 1.2–19.2), p = 0.02).
The proposed reason for recurrent EF was respiratory (39%), cardiovascular (33%), upper airway obstruction (6%), and others (22%) (Appendix Table 4). Characteristics of first-time and second-time EF is described in the Table 3. The median (IQR) time to reintubation after second extubation attempt was 19.4 (5.5–47) h. Thirteen of eighteen neonates with recurrent EF were placed on continuous positive airway pressure (CPAP) immediately after second extubation while 119 of 1085 children with non-EF were extubated to CPAP. 39% (7 out of 18) of recurrent EF experienced second EF due to the same etiology as at first EF; ventricle dysfunction 2, aortic valve regurgitation 1, sepsis 2, tracheomalacia 1, tracheostenosis 1.
Neonates who failed first extubation due to cardiovascular reasons had a higher odds of recurrent EF (odds ratio 3.1 (95% CI 1.0–9.7), p = 0.048) and higher hospital mortality (odds ratio 3.7 (95% CI 1.1–12.4), p = 0.036) compared to the other reasons for first EF after adjusting for study covariates.
The duration of mechanical ventilation in 102 neonates following first reintubation was 89 (68–134) h. The duration of mechanical ventilation from reintubation to second extubation attempt was associated with a hospital mortality of 13% in < 24 h, 6% in 24–48 h, 5% in 48–72 h, 7% in 72–96 h, and 36% in > 96 h. Mechanical ventilation > 96 h was associated with increased mortality (odds ratio 14.9 (95% CI 1.7–128.6.7), p = 0.01). 30% (31 out of 102) had surgical interventions before second extubation attempt; open heart surgery (n = 3), regulation of the Blalock–Taussig shunt flow (n = 4), patent ductus arteriosus ligation (n = 1), hemostasis (n = 3), diaphragm plication (n = 4), aortopexy (n = 1), abdominal surgery (n = 3), chest washout (n = 7), exploration of heart (n = 2), and permanent pacemaker insertion (n = 3). The timing of surgical interventions following EF was on the same calendar day in 16, 1–2 days later in 5; 3–4 days later in 5, ≥ 5 days in 5.
Discussion
The main findings of this study are: (1) recurrent EF occurred in 18% of neonates who had a first EF, (2) hospital mortality incrementally increased as neonates experienced EF, and (3) first EF due to cardiovascular reasons was associated with an increased risk of recurrent EF and mortality.
The association between recurrent EF and increased morality could be multi-factorial including patient-factors and ICU system-factors. Regarding patient-factors, we found that approximately 40% of neonates with recurrent EF failed their second extubation for the same reason, which was mainly structural or functional issues in the heart or airway. Previous studies also reported these are common reasons of EF in neonates after cardiac surgery although only first the EF was reviewed [4]. In relation to ICU system-factors, neonates with congenital cardiac disease receiving multiple-periods of mechanical ventilation have an increased risk of nosocomial infection (sepsis, ventilator-associated pneumonia), lung injury secondary to prolonged positive pressure ventilation, deconditioning and weakness with respiratory muscle [8]. Frutos-Vivar et al. reported that among reintubated patients evolving infections after EF was associated with increased mortality [9]. Consequently, one neonate could be affected by multi-factors, especially considering the fact that mortality is often caused by multiple factors including both patient-factors and ICU system-factors.
Importantly, the cause of first-time EF can be a useful indicator to identify the high-risk cohort in neonates following cardiac surgery. In this study, cardiovascular reason for first EF was associated with recurrent EF and increased mortality. Thus, the ventilation plan tailored to neonates with the cause of EF is essential to avoid further ICU-related complications and recurrent EF, which eventually increase the risk of morality. As an example, neonates experiencing EF with advanced heart failure may subsequently need further therapy including surgical interventions, long-term positive pressure support and nutrition plan for weeks or even months until the heart failure recovers. Some units are increasingly using the inotrope rotation therapy with long-term positive pressure support for heart failure [10]. The timing of surgical interventions following EF is also important point to consider since the timely interventions are associated with improved outcome compared to later operation if residual lesions are modifiable [11, 12]. By contrast, the timely ventilator weaning and extubation following stabilization of causes of EF may be the priority in neonates experiencing EF due to other causes (e.g., medically modifiable causes), especially considering the fact that prolonged mechanical ventilation after cardiac surgery is associated with a poor outcome and similarly in our study neonates who were ventilated 96 h or more after reintubation had a high mortality [1, 13]. For smoothing ventilation weaning, intensivists should be aware of latent issues deferring ventilator weaning, i.e., some respiratory and cardiovascular compromises could be difficult to recognize during ventilator support but would manifest at the weaning process, including diastolic dysfunction, hyperinflation associated with obstructive airway, reduced lung compliance compensated by baseline respiratory effort, and diaphragmatic dysfunction [8, 14,15,16,17,18]. There are a number of potentially useful tools to assess extubation-readiness during Spontaneous Breathing Trial (SBT) in high-risk patients including monitoring mixed venous oxygen saturation [19], B-type natriuretic peptide [20], respiratory workload [21], echocardiography [22], and ultrasound for diaphragm thickening and/or excursion [23].
Another important point to be studied is the setting of SBT in the second extubation. Thille et al. advocated that the risk of reintubation in high-risk population may become unacceptably high if they were assessed in the same way as unselected low-risk patients [16]. For example, SBT with pressure support may have better ability to pick up patients ready for extubation than SBT with T-piece alone in unselected patients while SBT with pressure support may overestimate the extubation-readiness in high-risk patients, which randomized controlled trials could not have showed due to small cohort size of high-risk patients [16]. Among patients with difficult weaning, Cabello et al. demonstrated greater respiratory and cardiac workload in SBT with T-piece than SBT with pressure support [23]. Compared to commonly-used pressure support of 6–10 cmH2O during SBT at PICU [24, 25], Takeuchi et al. alarmed the possible overestimation of extubation-readiness by SBT with pressure support by demonstrating that SBT with the pressure support of 4 cmH2O could replicate work of breathing post-extubation [21]. We need further evidence with regard to the setting of SBT prior to extubation in re-intubated neonates after cardiac surgery.
There are several challenges for acquiring future evidence, as this cohort is characterized as a special population by following reasons. First, although tracheostomy is a common approach to smooth liberation from respiratory support and avoid complications by reducing sedation requirement and promoting rehabilitation among adults receiving prolonged ventilation, neonates after cardiac surgery may not as good candidates for tracheostomy because of the risk of surgical site infection and long-term airway complications. Second, the efficacy of post-extubation respiratory support could be different from other age groups; bi-level positive airway pressure is rarely feasible in this age as a nature of neonates breathing fast with small tidal volume; positive pressure of non-invasive respiratory support may not be delivered due to open mouth which is common in crying babies. Third, the etiology of EF and comorbidities varies from elder age group post cardiac surgery [26, 27]. Thus, these facts also highlight the importance of future studies in neonates suffering EF.
There are limitations in this study. First, it was a single-center study, limiting the generalizability of our findings to other centers as the mortality in recurrent EF can be influenced by patient-, surgery-, and intensive care-associated factors. Second, the setting of respiratory support pre and post extubation was not reviewed in this study, which could influence the outcome. Third, some potential cause of EF may be missed as some possible causes of EF (delirium, withdrawal, diaphragm muscle weakness, etc.) were difficult to detect in a neonatal study and may have been substituted by other causes like secretion or atelectasis. Forth, mortality is likely to be underestimated by excluding palliated neonates without extubation attempt. The decision of the palliation may vary depending on institutions. Lastly, as this study included twelve years of data, the chronological change in the use of non-invasive respiratory support (CPAP, and humidified high-flow nasal cannula therapy) may have influenced the study result.
Conclusions
Recurrent EF occurred in approximately 18% following first EF in neonatal cardiac surgery and it was associated with an even higher mortality than single EF. This study showed that recurrent EF is an important patient group in terms of high mortality. Neonates with a cardiovascular reason for first time EF are more likely to have a recurrent EF.
References
Benneyworth BD, Mastropietro CW, Graham EM et al (2017) Variation in extubation failure rates after neonatal congenital heart surgery across Pediatric Cardiac Critical Care Consortium hospitals. J Thorac Cardiovasc Surg 153:1519–1526. https://doi.org/10.1016/j.jtcvs.2016.12.042
Mastropietro CW, Cashen K, Grimaldi LM et al (2017) Extubation failure after neonatal cardiac surgery: a multicenter analysis. J Pediatr 182:190–196. https://doi.org/10.1016/j.jpeds.2016.12.028
Scodellaro T, McKenzie JM, D’Udekem Y et al (2017) Extubation failure is associated with increased mortality following first stage single ventricle reconstruction operation. Pediatr Crit Care Med 18:1136–1144. https://doi.org/10.1097/PCC.0000000000001334
Miura S, Hamamoto N, Osaki M et al (2017) Extubation failure in neonates after cardiac surgery: prevalence, etiology, and risk factors. Ann Thorac Surg 103:1293–1298. https://doi.org/10.1016/j.athoracsur.2016.08.001
Laudato N, Gupta P, Walters HL et al (2015) Risk factors for extubation failure following neonatal cardiac surgery. Pediatr Crit Care Med 16:859–867. https://doi.org/10.1097/PCC.0000000000000512
Gupta P, McDonald R, Gossett JM et al (2012) A single-center experience of extubation failure in infants undergoing the norwood operation. Ann Thorac Surg 94:1262–1268. https://doi.org/10.1016/j.athoracsur.2012.05.033
Epstein SK, Ciubotaru RL (1998) Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med 158:489–493
Thille AW, Cortés-Puch I, Esteban A (2013) Weaning from the ventilator and extubation in ICU. Curr Opin Crit Care 19:57–64. https://doi.org/10.1097/MCC.0b013e32835c5095
Frutos-Vivar F, Esteban A, Apezteguia C et al (2011) Outcome of reintubated patients after scheduled extubation. J Crit Care 26:502–509. https://doi.org/10.1016/j.jcrc.2010.12.015
Ryerson LM, Alexander PMA, Butt WW et al (2011) Rotating inotrope therapy in a pediatric population with decompensated heart failure. Pediatr Crit Care Med 12:57–60. https://doi.org/10.1097/PCC.0b013e3181e2a437
Agarwal HS, Hardison DC, Saville BR et al (2014) Residual lesions in postoperative pediatric cardiac surgery patients receiving extracorporeal membrane oxygenation support. J Thorac Cardiovasc Surg 147:434–441. https://doi.org/10.1016/j.jtcvs.2013.03.021
Nathan M, Gauvreau K, Liu H et al (2014) Outcomes differ in patients who undergo immediate intraoperative revision versus patients with delayed postoperative revision of residual lesions in congenital heart operations. J Thorac Cardiovasc Surg 148:2540–2547. https://doi.org/10.1016/j.jtcvs.2014.07.073
Peñuelas O, Frutos-Vivar F, Fernández C et al (2011) Characteristics and outcomes of ventilated patients according to time to liberation from mechanical ventilation. Am J Respir Crit Care Med 184:430–437. https://doi.org/10.1164/rccm.201011-1887OC
Brodsky JB (1988) Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology 69:171–179
Buda AJ, Pinsky MR, Ingels NBJ et al (1979) Effect of intrathoracic pressure on left ventricular performance. N Engl J Med 301:453–459. https://doi.org/10.1056/NEJM197908303010901
Thille AW, Richard JCM, Brochard L (2013) The decision to extubate in the intensive care unit. Am J Respir Crit Care Med 187:1294–1302. https://doi.org/10.1164/rccm.201208-1523CI
Papanikolaou J, Makris D, Saranteas T et al (2011) New insights into weaning from mechanical ventilation: left ventricular diastolic dysfunction is a key player. Intensive Care Med 37:1976–1985. https://doi.org/10.1007/s00134-011-2368-0
Khemani RG, Sekayan T, Hotz J, Flink RC, Rafferty GF, Narayan Iyer CJLN (2017) Risk factors for pediatric extubation failure: the importance of respiratory muscle strength. Crit Care Med 45:e798–e805. https://doi.org/10.1097/CCM.0000000000002433
Jubran A, Mathru M, Dries D, Tobin MJ (1998) Continuous recordings of mixed venous oxygen saturation during weaning from mechanical ventilation and the ramifications thereof. Am J Respir Crit Care Med 158:1763–1769. https://doi.org/10.1164/ajrccm.158.6.9804056
Mekontso-Dessap A, De Prost N, Girou E et al (2006) B-type natriuretic peptide and weaning from mechanical ventilation. Intensive Care Med 32:1529–1536. https://doi.org/10.1007/s00134-006-0339-7
Takeuchi M, Imanaka H, Miyano H, Kumon K (2000) Effect of patient-triggered ventilation on respiratory workload in infants after cardiac surgery. Anesthesiology 93:1238–1244. https://doi.org/10.1097/00000542-200011000-00017
Lamia B, Maizel J, Ochagavia A et al (2009) Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation. Crit Care Med 37:1696–1701. https://doi.org/10.1097/CCM.0b013e31819f13d0
Llamas-Álvarez AM, Tenza-Lozano EM, Latour-Pérez J (2017) Diaphragm and lung ultrasound to predict weaning outcome: systematic review and meta-analysis. Chest 152:1140–1150. https://doi.org/10.1016/j.chest.2017.08.028
Newth CJL, Venkataraman S, Willson DF et al (2009) Weaning and extubation readiness in pediatric patients. Pediatr Crit Care Med 10:1–11. https://doi.org/10.1097/PCC.0b013e318193724d
Randolph AG, Wypij D, Venkataraman ST et al (2002) Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children: a randomized controlled trial. J Am Med Assoc 288:2561–2568. https://doi.org/10.1001/jama.288.20.2561
Gupta P, Rettiganti M, Gossett JM et al (2016) Risk factors for mechanical ventilation and reintubation after pediatric heart surgery. J Thorac Cardiovasc Surg 151:451-458.e3. https://doi.org/10.1016/j.jtcvs.2015.09.080
Gaies M, Tabbutt S, Schwartz SM et al (2015) Clinical epidemiology of extubation failure in the pediatric cardiac icu: a report from the pediatric cardiac critical care consortium. Pediatr Crit Care Med 16:837–845. https://doi.org/10.1097/PCC.0000000000000498
Acknowledgements
We thank doctors Andrew Girgis and Peter Jardim for helping with data collection. Dr. S P Namachivayam is supported by a health professional research scholarship (award number 101003) from the National Heart Foundation of Australia.
Author information
Authors and Affiliations
Contributions
All authors provided concept/idea/research design. SM provided data collection/data analysis/writing. JT provided and managed patient data. JT, SPN and WB revised and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The Authors declare that there is no conflict of interest.
Ethical approval
This study was approved by the Royal Children’s Hospital Melbourne Human Research Ethics Committee (reference no; 38300), and the need for informed consent was waived.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Miura, S., Butt, W., Thompson, J. et al. Recurrent Extubation Failure Following Neonatal Cardiac Surgery Is Associated with Increased Mortality. Pediatr Cardiol 42, 1149–1156 (2021). https://doi.org/10.1007/s00246-021-02593-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00246-021-02593-2