Infant periodic breathing and apneic threshold.

A mathematical model was proposed to predict the role played by apneic threshold in periodic breathing in preterm infants. Prior models have mainly applied linear control theory which predicted instability but could not explain sustained periodic breathing. Apneic threshold to CO2 which has been postulated to play a major role in infant periodic breathing is a nonlinear effect and cannot be described by linear theory. Another previously unexplored nonlinear factor affecting instability is brain vascular volume change with CO2 which affects time delay to chemoreceptors. The current model explored the influences of apneic threshold, central and peripheral chemoreceptor gains, cardiac output, lung volume, and circulatory time delay on periodic breathing. Apneic threshold was found to play a major role in ventilatory responses to spontaneous sighs. Sighs led to apneic pauses followed by periods of periodic breathing with peripheral chemoreceptor CO2 gain, cardiac output, and lung volume were at reported normal levels. Apneic threshold when exceeded was observed to cause an asymmetry in the periodic breathing cycling and an increased periodic breathing frequency. Sighs in infants occur frequently enough to lead to repeated stimulation within the epoch duration of periodic breathing for a single sigh. Multiple sighs may then play a major role in promoting continuous periodic breathing in infants. Peripheral chemoreceptor gain estimated using endogenous CO2 led to validated predicted periodic breathing cycle duration as a function of age. Brain vascular volume increase with CO2 contributes to periodic breathing in very young (1-2 day old) preterm infants.

Determining an Optimal Oxygen Saturation Target Range Based on Neonatal Maturity: Demonstration of a Decision Tree Analytic.

The utility of decision tree machine learning in exploring the interactions among the SpO2 target range, neonatal maturity, and oxemic-risk is demonstrated. METHODS: This observational study used 3 years of paired age-SpO2-PaO2 data from a neonatal ICU. The CHAID decision tree method was used to explore the interaction of postmenstrual age (PMA) on the risk of extreme arterial oxygen levels at six different potential SpO2 target ranges (88-92%, 89-93%, 90-94%, 91-95%, 92-96% and 93-97%). Risk was calculated using a severity-weighted average of arterial oxygen outside the normal range for neonates (50-80 mmHg). RESULTS: In total, 7500 paired data points within the potential target range envelope were analyzed. The two lowest target ranges were associated with the highest risk, and the ranges of 91-95% and 92-96% were associated with the lowest risk. There were shifts in the risk associated with PMA. All the target ranges showed the lowest risk at ≥42 weeks PMA. The lowest risk for preterm infants was within a target range of 92-96% with a PMA of ≤34 weeks. CONCLUSIONS: This study demonstrates the utility of decision tree analytics. These results suggest that SpO2 target ranges that are different from typical range might reduce morbidity and mortality. Further research, including prospective randomized trials, is warranted.

Invasive Ventilatory Support in Patients With Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: To provide evidence for the Second Pediatric Acute Lung Injury Consensus Conference updated recommendations and consensus statements for clinical practice and future research on invasive mechanical ventilation support of patients with pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included clinical studies of critically ill patients undergoing invasive mechanical ventilation for PARDS, January 2013 to April 2022. In addition, meta-analyses and systematic reviews focused on the adult acute respiratory distress syndrome population were included to explore new relevant concepts (e.g., mechanical power, driving pressure, etc.) still underrepresented in the contemporary pediatric literature. DATA EXTRACTION: Title/abstract review, full text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations, good practice statements and research statements. We identified 26 pediatric studies for inclusion and 36 meta-analyses or systematic reviews in adults. We generated 12 recommendations, two research statements, and five good practice statements related to modes of ventilation, tidal volume, ventilation pressures, lung-protective ventilation bundles, driving pressure, mechanical power, recruitment maneuvers, prone positioning, and high-frequency ventilation. Only one recommendation, related to use of positive end-expiratory pressure, is classified as strong, with moderate certainty of evidence. CONCLUSIONS: Limited pediatric data exist to make definitive recommendations for the management of invasive mechanical ventilation for patients with PARDS. Ongoing research is needed to better understand how to guide best practices and improve outcomes for patients with PARDS requiring invasive mechanical ventilation.

A Network Meta-analysis of Dexamethasone for Preventing Postextubation Upper Airway Obstruction in Children.

Rationale: Periextubation corticosteroids are commonly used in children to prevent upper airway obstruction (UAO). However, the best timing and dose combination of corticosteroids is unknown. Objectives: To compare effectiveness of different corticosteroid regimens in preventing UAO and reintubation. Methods: MEDLINE, CINAHL, and Embase search identified randomized trials in children using corticosteroids to prevent UAO. All studies used dexamethasone. The studies were categorized based on timing of initiation of dexamethasone (early use: >12 h before extubation) and the dose (high dose: ⩾0.5 mg/kg/dose). We performed Bayesian network meta-analysis with studies grouped into four regimens: high dose, early use (HE); low dose, early use (LE); high dose, late use (HL); and low dose, late use. Results: Eight trials (n = 903) were included in the analysis. For preventing UAO (odds ratio; 95% credible interval), HE (0.13; 0.04-0.36), HL (0.39; 0.19-0.74), and LE (0.15; 0.04-0.58) regimens appear to be more effective than no dexamethasone (low certainty). HE and LE had the highest probability of being the top-ranked regimens for preventing UAO (surface under the cumulative ranking curve 0.901 and 0.808, respectively). For preventing reintubation, the effect estimate was imprecise for all four dexamethasone regimens compared with no dexamethasone (very low certainty). HE and LE were the top-ranked regimens (surface under the cumulative ranking curve 0.803 and 0.720, respectively) for preventing reintubation. Sensitivity analysis showed that regimens that started >12 hours before extubation were likely more effective than regimens started >6 hours before extubation. Conclusions: Periextubation dexamethasone can prevent postextubation UAO in children, but effectiveness is highly dependent on timing and dosing regimen. Early initiation (ideally >12 h before extubation) appears to be more important than the dose of dexamethasone. Ultimately, the specific steroid strategy should be personalized, considering the potential for adverse events associated with dexamethasone and the individual risk of UAO and reintubation.

The American Thoracic Society Guideline Methodology Training Program.

A new era in guideline creation began in 2011 with publication of the Institute of Medicine (now the National Academy of Medicine) Standards for Developing Trustworthy Clinical Practice Guidelines. The American Thoracic Society (ATS) was committed to developing guidelines in accordance with the new standards and decided that an experienced guideline methodologist would be required on ATS guideline projects to ensure correct implementation of the standards. The ATS Guideline Methodology Training Program was launched to increase the pool of trained methodologists. Each year, accepted trainees (methodology scholars) attend a workshop that introduces them to the terminology and process of guideline development and are given the option of participating in a guideline project. Scholars work with the mentorship of a lead methodologist to conduct and then present a systematic review to the guideline committee, discuss the evidence, and participate in the development of evidence-based graded recommendations. Scholars have participated in 22 ATS guidelines over the past 9 years, and most remain engaged in guideline development. For the past 2 years, the methodological aspects of all ATS guideline projects were led by graduates of the training program, and several scholars have accepted positions to lead guidelines for other professional societies. Guideline methodology is particularly suitable for clinician educators because the work is clinically oriented, and guidelines confer high academic capital. Those who elect not to continue in guideline development still acquire the skills to perform and publish systematic reviews, as well as to educate trainees in reading and reviewing literature.

Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity.

BACKGROUND: Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited. METHODS: This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50-80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels. RESULTS: Neonates were categorized by postmenstrual age: < 33 (n = 155), 33-36 (n = 192) and > 36 (n = 1031) weeks. From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24-28) n = 2603; 34 (33-35) n = 2501; and 38 (37-39) n = 21,058. The chance of normoxemia (65, 95%-CI 64-67%) was similar across the SpO2 range of 88-95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21-29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18-33%), for infants 33-36 weeks at 97% SpO2 (24, 95%-CI 14-25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17-22%). CONCLUSIONS: The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.

The Adverse Impact of Unplanned Extubation in a Cohort of Critically Ill Neonates.

BACKGROUND: We sought to describe adverse events associated with unplanned extubation (UE) and to explore risk factors for serious adverse events post-UE among infants who experienced UE. METHODS: Data were prospectively collected on all infants who had a UE event at a single institution over a 4-y period. Demographic information and information on outcomes were obtained retrospectively. We described the frequency of post-UE adverse events: success or failure of extubation trial if offered, rate of re-intubation, post-UE changes in ventilator settings, and serious adverse events post-UE (eg, need for cardiopulmonary resuscitation, clinical sepsis, and death or tracheostomy prior to discharge). We used a multivariate logistic regression model to identify the risk factors associated with serious adverse events. RESULTS: There were 134 documented UE events. Agitation was the most common known cause. After UE, 49% of the subjects were given a trial of extubation, and 65% of the trials were successful at 48 h. Cardiopulmonary resuscitation (CPR) was performed in 13% of cases. In subjects requiring immediate re-intubation, mean airway pressure (̄Paw) and oxygen requirement increased in 33% and 55% of the subjects, respectively. Post-UE clinical sepsis occurred in 17% of subjects. Higher pre-UE ̄Paw and difficult re-intubation were associated with a need for CPR. Subjects who received CPR had increased odds (3.7×) of developing clinical sepsis. CONCLUSION: UE can result in serious adverse events, including hemodynamic instability and possibly an increased risk for clinical sepsis. Difficult re-intubation was associated with a higher risk of needing CPR and, later, tracheostomy and death.

Hypoxemic and hyperoxemic likelihood in pulse oximetry ranges: NICU observational study.

OBJECTIVE: Describe the likelihood of hypoxemia and hyperoxemia across ranges of oxygen saturation (SpO2), during mechanical ventilation with supplemental oxygenation. DESIGN: Retrospective observational study. SETTING: University affiliated tertiary care neonatal intensive care unit. PATIENTS: Two groups of neonates based on postmenstrual age (PMA): <32 weeks (n=104) and >36 weeks (n=709). MAIN MEASURES: Hypoxemia was defined as a PaO2 <40 mm Hg, hyperoxemia as a PaO2 of >99 mm Hg and normoxemia as a PaO2 of 50-80 mm Hg. Twenty-five per cent was defined as marked likelihood of hypoxemia or hyperoxemia. RESULTS: From these infants, 18 034 SpO2-PaO2 pairs were evaluated of which 10% were preterm. The PMA (median and IQR) of the two groups were: 28 weeks (27-30) and 40 weeks (38-41). With SpO2 levels between 90% and 95%, the likelihoods of hypoxemia and hyperoxemia were low and balanced. With increasing levels of SpO2, the likelihood of hyperoxemia increased. It became marked in the preterm group when SpO2 was 99%-100% (95% CI 29% to 41%) and in the term group with SpO2 levels of 96%-98% (95% CI 29% to 32%). The likelihood of hypoxemia increased as SpO2 decreased. It became marked in both with SpO2 levels of 80%-85% (95% CI 20% to 31%, 24% to 28%, respectively). CONCLUSIONS: The likelihood of a PaO2 <40 mm Hg is marked with SpO2 below 86%. The likelihood of a PaO2 >99 mm Hg is marked in term infants with SpO2 above 95% and above 98% in preterm infants. SpO2 levels between 90% and 95% are appropriate targets for term and preterm infants.

Indwelling Pleural Catheter versus Pleurodesis for Malignant Pleural Effusions. A Systematic Review and Meta-Analysis.

RATIONALE: Several randomized trials have compared the efficacy of an indwelling pleural catheter (IPC) versus the more traditional chemical pleurodesis in the management of malignant pleural effusion (MPE). OBJECTIVES: As part of the American Thoracic Society's guidelines for management of MPE, we performed a systematic review and a meta-analysis to compare patient-centered outcomes with the use of a tunneled pleural catheter versus chemical pleurodesis for the first-line treatment of malignant pleural effusions. METHODS: We performed literature searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials comparing IPC and pleurodesis in adult patients with symptomatic MPE. Risk of bias was assessed with the Cochrane Risk of Bias tool recommended by the Cochrane Methods Bias Group. The meta-analysis was performed with Review Manager software, using a random effects model. We used risk ratios (RRs) with 95% confidence interval (CI) as the effect measure for dichotomous outcomes and mean differences for continuous outcomes. RESULTS: We identified five randomized trials, involving 545 patients, that compared IPC and pleurodesis. Lack of blinding and the inevitable attrition of patients due to death resulted in an overall high risk of bias among the studies. No differences in survival or measures of dyspnea were observed in any of the studies. Total hospital length of stay was shorter, and repeat pleural interventions were less common in the IPC group (RR, 0.32; 95% CI, 0.18-0.55). However, the risk of cellulitis was higher with IPC (RR, 5.83; 95% CI, 1.56-21.8). No differences were noted in other adverse events. CONCLUSIONS: Compared with chemical pleurodesis, IPC results in shorter hospital length of stay and fewer repeat pleural procedures but carries a higher risk of cellulitis. Careful assessment of individual patient preferences and costs should be considered when choosing between IPC and pleurodesis.

Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline.

BACKGROUND: This Guideline, a collaborative effort from the American Thoracic Society, Society of Thoracic Surgeons, and Society of Thoracic Radiology, aims to provide evidence-based recommendations to guide contemporary management of patients with a malignant pleural effusion (MPE). METHODS: A multidisciplinary panel developed seven questions using the PICO (Population, Intervention, Comparator, and Outcomes) format. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the Evidence to Decision framework was applied to each question. Recommendations were formulated, discussed, and approved by the entire panel. RESULTS: The panel made weak recommendations in favor of: 1) using ultrasound to guide pleural interventions; 2) not performing pleural interventions in asymptomatic patients with MPE; 3) using either an indwelling pleural catheter (IPC) or chemical pleurodesis in symptomatic patients with MPE and suspected expandable lung; 4) performing large-volume thoracentesis to assess symptomatic response and lung expansion; 5) using either talc poudrage or talc slurry for chemical pleurodesis; 6) using IPC instead of chemical pleurodesis in patients with nonexpandable lung or failed pleurodesis; and 7) treating IPC-associated infections with antibiotics and not removing the catheter. CONCLUSIONS: These recommendations, based on the best available evidence, can guide management of patients with MPE and improve patient outcomes.

Neural breathing pattern in newborn infants pre- and postextubation.

AIM: To describe the neural breathing pattern before and after extubation in newborn infants. METHODS: Prospective, observational study. In infants deemed ready for extubation, the diaphragm electrical activity (EAdi) was continuously recorded from 30 minute before to two hours after extubation. RESULTS: Total of 25 neonates underwent 29 extubations; 10 extubations resulted in re-intubation within 72 hours. Postextubation, there was an increase in peak EAdi (EAdi-max) and EAdi-delta (peak minus minimum EAdi) in both groups. The pre- to postextubation change in EAdi-max (8.9-11.1 µv) and EAdi-delta (6-8 µv) was less in the failure group in comparison with the change in EAdi-max (10.2-13.4 µv) and EAdi-delta (6.3-10.6 µv) in the success group, (p = 0.02 and 0.01, respectively). CONCLUSION: In our neonatal cohort, extubation failure was associated with a smaller increase in peak and delta EAdi after extubation. If confirmed, these findings indicate an important cause of extubation failure in preterm infants.

Respiratory severity score and extubation readiness in very low birth weight infants.

BACKGROUND: The respiratory severity score (RSS) is a byproduct of mean airway pressure (MAP) and fraction of inspired oxygen (FiO2). We sought to determine whether RSS could be used as a screening tool to predict extubation readiness in very low birth weight (VLBW) infants. METHODS: In a retrospective cohort study, medical records of all VLBW infants admitted to our unit (6/1/09-2/28/12) were reviewed for infants' demographics, prenatal characteristics, and medication use. Also, records were reviewed for unplanned vs. planned extubation, blood gas, ventilator parameters and signs of severe respiratory failure [RF, defined as partial pressure of carbon dioxide (pCO2) > 65, pH < 7.20, FiO2 > 50%, and MAP > 10 cm] on the day of extubation. RESULTS: During the study period 31% (45/147) failed extubation. Overall, infants who failed extubation had a lower birth weight (BW) and gestational age (GA), and on the day of extubation had a higher RSS and percentage of having one or more signs of severe RF. In a logistic regression model, adjusting for BW, GA, RSS and RF, RSS remained the only risk factor associated with extubation failure [adjusted OR 1.63 (95% CI: 1.10-2.40); p = 0.01]. RSS had a sensitivity of 0.86 (95% CI: 0.72-0.94) at a cutoff of 1.26 and a specificity of 0.88 (95% CI: 0.80-0.94) at a cutoff of 2.5. There was no difference in extubation failure between unplanned vs. planned extubation [41% (9/22) vs. 29% (36/125); p = 0.25]. CONCLUSION: An elevated RSS is associated with extubation failure. Successful unplanned extubation is common in VLBW infants.

Association Between High-Flow Nasal Cannula and End-Expiratory Esophageal Pressures in Premature Infants.

BACKGROUND: High-flow nasal cannula (HFNC) is commonly being used to provide noninvasive respiratory support in newborn infants. Continuous distending pressure generated by these devices in preterm infants has not been elucidated. The aim of this work was to determine the association between HFNC flow in L/min and end-expiratory esophageal pressure in cm H2O in premature infants. METHODS: In a prospective observational study, end-expiratory esophageal pressure measurements were conducted in clinically stable premature infants who required HFNC. The end-expiratory esophageal pressure generated by the HFNC was measured by a regular feeding tube overlying the lower esophagus and connected to a pressure transducer. Each infant had different end-expiratory esophageal pressure measurements at different high flows ranging from 2 to 8 L/min. RESULTS: Nineteen premature infants were studied. Their birthweight (mean ± SD) was 904 ± 574 g, and gestational age was 26.6 ± 3.1 weeks. Overall, 93 end-expiratory esophageal pressure measurements were conducted. At the time of the end-expiratory esophageal pressure measurements, infants were 1,458 ± 828 g and 7.2 ± 4.8 weeks old. At HFNC flows ranging from 2 to 8 L/min, the corresponding esophageal pressures ranged from 2 to 15 cm H2O. There was a statistically significant association between esophageal pressures and flows. In a linear regression model with the end-expiratory esophageal pressure as the dependent variable and HFNC flow as the independent variable, there was a significant correlation between the 2 variables: end-expiratory esophageal pressure (cm H2O) = 1.18 × HFNC (L/min) (r(2) = 0.95, P < .001). CONCLUSIONS: HFNC-associated end-expiratory esophageal pressure is measurable in premature infants. There is a significant association between flows and generated esophageal pressures. There is also variability in the amount of end-expiratory esophageal pressure generated. These observations should be kept in mind when using high HFNC flows in preterm infants.

Evaluation of a nasal cannula in noninvasive ventilation using a lung simulator.

BACKGROUND: Nasal noninvasive ventilation (NIV) is a common form of noninvasive respiratory mode used in newborn infants. A next-generation nasal cannula (Neotech RAM cannula) has recently been used to provide nasal NIV. The impact of the Neotech RAM cannula on the delivery of pressure needs to be studied. METHODS: In this ex vivo experimental design, a lung simulator (IngMar ASL 5000, version 3.4) was programmed to model a neonate (∼1-3 kg of body weight) with normal-to-moderately affected lungs. We used a Covidien PB840 ventilator with NIV software activated to compensate for leaks. Nasal NIV was set at peak airway pressures of 15, 20, and 25 cm H2O and PEEP of 5, 6, and 7 cm H2O. Three sizes of the Neotech RAM cannula were used (prong outer diameters of 3.0, 3.5, and 4.0 mm). The nose was designed to keep the leak of the nares by the prongs to 30%. We also created a worst case leak (58% leak) by using the largest simulated nostril diameter with the smallest diameter Neotech RAM cannula prong. The outcome measure was the difference in pressures, referred to as leak effect, measured by the lung simulator relative to the set peak airway pressure and PEEP on the ventilator. RESULTS: For the interface with 30% leak, leak effects of peak airway pressure during simulated nasal NIV were similar with all Neotech RAM cannula sizes, with 63-75% of peak airway pressure and 70-90% of PEEP being transmitted across the nasal interface. The worst case scenario produced a 92% leak effect in peak airway pressure and PEEP. CONCLUSIONS: When used with ≤ 30% leak, the Neotech RAM cannula interface results in clinically acceptable transmission of pressures. With > 50% leak, a clinically negligible amount of pressure is transmitted to the artificial lungs.

The use of extubation readiness parameters: a survey of pediatric critical care physicians.

BACKGROUND: The pediatric literature addressing extubation readiness parameters and strategies to wean from mechanical ventilation is limited. METHODS: We designed a survey to assess the use of extubation readiness parameters among pediatric critical care physicians at academic centers in the United States. RESULTS: The overall response rate was 44.1% (417/945). The majority of respondents check for air leak and the amount of tracheal secretions. Fewer respondents use sedation score, the rapid shallow breathing index, or the airway-occlusion pressure 0.1 s after the start of inspiratory flow prior to extubation. The majority perform a spontaneous breathing trial with pressure support. The majority consider 30 cm H2O as the upper limit of an air leak test, and the need for endotracheal suctioning once every 2-4 hours as acceptable for extubation. In preparation for termination of mechanical ventilation the majority daily wean the ventilator rate and/or the pressure support instead of conducting a spontaneous breathing trial. CONCLUSIONS: Most pediatric critical care physicians reported assessing extubation readiness by checking air leak and suctioning need, and less often consider or perform sedation score or the rapid shallow breathing index.