Patrick A. Ross

Comparison of SpO2 to PaO2 based markers of lung disease severity for children with acute lung injury.

Objective:Given pulse oximetry is increasingly substituting for arterial blood gas monitoring, noninvasive surrogate markers for lung disease severity are needed to stratify pediatric risk. We sought to validate prospectively the comparability of SpO2/Fio2 to PaO2/Fio2 and oxygen saturation index to oxygenation index in children. We also sought to derive a noninvasive lung injury score. Design:Prospective, multicentered observational study in six pediatric intensive care units. Patients:One hundred thirty-seven mechanically ventilated children with SpO2 80% to 97% and an indwelling arterial catheter. Interventions:Simultaneous blood gas, pulse oximetry, and ventilator settings were collected. Derivation and validation data sets were generated, and linear mixed modeling was used to derive predictive equations. Model performance and fit were evaluated using the validation data set. Measurements and Main Results:One thousand one hundred ninety blood gas, SpO2, and ventilator settings from 137 patients were included. Oxygen saturation index had a strong linear association with oxygenation index in both derivation and validation data sets, given by the equation oxygen saturation index = 2.76 1 0.547*oxygenation index (derivation). 1/SpO2/Fio2 had a strong linear association with 1/PaO2/Fio2 in both derivation and validation data sets given by the equation 1/SpO2/Fio2 = 0.00232 1 0.443/PaO2/Fio2 (derivation). SpO2/Fio2 criteria for acute respiratory distress syndrome and acute lung injury were 221 (95% confidence interval 215–226) and 264 (95% confidence interval 259–269). Multivariate models demonstrated that oxygenation index, serum pH, and Paco2 were associated with oxygen saturation index (p < .05); and 1/PaO2/Fio2, mean airway pressure, serum pH, and Paco2 were associated with 1/SpO2/Fio2 (p < .05). There was strong concordance between the derived noninvasive lung injury score and the original pediatric modification of lung injury score with a mean difference of 20.0361 &agr;0.264 sd. Conclusions:Lung injury severity markers, which use SpO2, are adequate surrogate markers for those that use PaO2 in children with respiratory failure for SpO2 between 80% and 97%. They should be used in clinical practice to characterize risk, to increase enrollment in clinical trials, and to determine disease prevalence. (Crit Care Med 2012; 40:–1316)

Effort of breathing in children receiving high-flow nasal cannula.

Objective: High-flow humidified nasal cannula is often used to provide noninvasive respiratory support in children. The effect of high-flow humidified nasal cannula on effort of breathing in children has not been objectively studied, and the mechanism by which respiratory support is provided remains unclear. This study uses an objective measure of effort of breathing (Pressure. Rate Product) to evaluate high-flow humidified nasal cannula in critically ill children. Design: Prospective cohort study. Setting: Quaternary care free-standing academic children’s hospital. Patients: ICU patients younger than 18 years receiving high-flow humidified nasal cannula or whom the medical team planned to extubate to high-flow humidified nasal cannula within 72 hours of enrollment. Interventions: An esophageal pressure monitoring catheter was placed to measure pleural pressures via a Bicore CP-100 pulmonary mechanics monitor. Change in pleural pressure (&Dgr;Pes) and respiratory rate were measured on high-flow humidified nasal cannula at 2, 5, and 8 L/min. &Dgr;Pes and respiratory rate were multiplied to generate the Pressure.Rate Product, a well-established objective measure of effort of breathing. Baseline Pes, defined as pleural pressure at end exhalation during tidal breathing, reflected the positive pressure generated on each level of respiratory support. Measurements and Main Results: Twenty-five patients had measurements on high-flow humidified nasal cannula. Median age was 6.5 months (interquartile range, 1.3–15.5 mo). Median Pressure,Rate Product was lower on high-flow humidified nasal cannula 8 L/min (median, 329 cm H2O·min; interquartile range, 195–402) compared with high-flow humidified nasal cannula 5 L/min (median, 341; interquartile range, 232–475; p = 0.007) or high-flow humidified nasal cannula 2 L/min (median, 421; interquartile range, 233–621; p < 0.0001) and was lower on high-flow humidified nasal cannula 5 L/min compared with high-flow humidified nasal cannula 2 L/min (p = 0.01). Baseline Pes was higher on high-flow humidified nasal cannula 8 L/min than on high-flow humidified nasal cannula 2 L/min (p = 0.03). Conclusions: Increasing flow rates of high-flow humidified nasal cannula decreased effort of breathing in children, with the most significant impact seen from high-flow humidified nasal cannula 2 to 8 L/min. There are likely multiple mechanisms for this clinical effect, including generation of positive pressure and washout of airway dead space.

Accuracy of Pulse Oximetry in Children

OBJECTIVE: For children with cyanotic congenital heart disease or acute hypoxemic respiratory failure, providers frequently make decisions based on pulse oximetry, in the absence of an arterial blood gas. The study objective was to measure the accuracy of pulse oximetry in the saturations from pulse oximetry (SpO2) range of 65% to 97%. METHODS: This institutional review board–approved prospective, multicenter observational study in 5 PICUs included 225 mechanically ventilated children with an arterial catheter. With each arterial blood gas sample, SpO2 from pulse oximetry and arterial oxygen saturations from CO-oximetry (SaO2) were simultaneously obtained if the SpO2 was ≤97%. RESULTS: The lowest SpO2 obtained in the study was 65%. In the range of SpO2 65% to 97%, 1980 simultaneous values for SpO2 and SaO2 were obtained. The bias (SpO2 – SaO2) varied through the range of SpO2 values. The bias was greatest in the SpO2 range 81% to 85% (336 samples, median 6%, mean 6.6%, accuracy root mean squared 9.1%). SpO2 measurements were close to SaO2 in the SpO2 range 91% to 97% (901 samples, median 1%, mean 1.5%, accuracy root mean squared 4.2%). CONCLUSIONS: Previous studies on pulse oximeter accuracy in children present a single number for bias. This study identified that the accuracy of pulse oximetry varies significantly as a function of the SpO2 range. Saturations measured by pulse oximetry on average overestimate SaO2 from CO-oximetry in the SpO2 range of 76% to 90%. Better pulse oximetry algorithms are needed for accurate assessment of children with saturations in the hypoxemic range.

Obesity and Mortality Risk in Critically Ill Children

BACKGROUND AND OBJECTIVES: Childhood obesity is epidemic and may be associated with PICU mortality. Using a large multicenter PICU database, we investigated the association between obesity and PICU mortality, adjusting for initial severity of illness. We further investigated whether height- and weight-based classifications of obesity compared with a weight-based classification alone alter the mortality distribution. METHODS: This retrospective analysis used prospectively collected data from the Virtual PICU Systems database. Height, weight, age, and gender were used to calculate z score groups based on Centers for Disease Control and Prevention and World Health Organization growth curves. A random effects mixed logistic regression model was used to evaluate the association between obesity and PICU mortality, controlling for hospital, initial severity of illness, and comorbidities. RESULTS: A total of 127 607 patients were included; the mortality rate was 2.48%. Being overweight was independently associated with increased PICU mortality after controlling for severity of illness with the Pediatric Index of Mortality 2 score and preexisting comorbidities. Mortality had a U-shaped distribution when classified according to weight-for-age or weight-for-height/BMI. When classifying patients using weight-for-age without respect to height, the nadir of the mortality curve was shifted, potentially falsely implying a benefit to mild obesity. CONCLUSIONS: Risk-adjusted PICU mortality significantly increases as weight-for-height/BMI increases into the overweight and obese ranges. We believe that height data are necessary to correctly classify body habitus; without such information, a protective benefit from mild obesity may be incorrectly concluded.

Continuous infusion of bupivacaine reduces postoperative morphine use in adolescent idiopathic scoliosis after posterior spine fusion.

Study Design. Retrospective analysis. Objective. To determine if an infusion of bupivacaine will reduce the need for intravenous opioids following posterior spine fusion. Summary of Background Data. Adolescent idiopathic scoliosis is estimated to occur with a frequency of 1% to 3% among the at-risk age group of 10 to 18 years. A small percentage of these patients will require surgical intervention. Data are limited regarding continuous infusion of local anesthetic after posterior spine fusion for pain control. Methods. Retrospective review of children 10 to 18 years with idiopathic scoliosis admitted to a tertiary care, 20-bed pediatric intensive care unit (P pediatric intensive care unit), following posterior spine fusion. The primary outcome was postoperative opioid use stratified by the presence of a catheter for continuous bupivacaine. Secondary outcomes included pain scores, side effect management, depth of catheter placement, and fluid resuscitation. Results. Two hundred and forty-four children were eligible, 129 received a catheter for continuous bupivacaine, 115 did not. There were no differences in demographics. Significantly fewer patients receiving bupivacaine required a continuous basal infusion of morphine (32.6% vs. 85.2%, P < 0.001) resulting in an overall reduction opioid use on postoperative day 1 (18.9 vs. 26.4 mg, P < 0.001). Overall, pain scores were low in both groups. Limiting the analysis to only those with a bupivacaine catheter, the depth of catheter placement did not impact postoperative opioid use (P > 0.15). Conclusion. The use of a continuous infusion of bupivacaine provided good analgesia with low pain scores. The significant reduction in basal morphine use may reflect a replacement by bupivacaine, although this is limited by potential treatment bias. Multivariate analysis was required to control for ongoing changes in anesthesia practice over the many years of the study. The optimal depth of catheter placement is unclear from this analysis and should be studied prospectively.

Evaluating Risk Factors for Pediatric Post-extubation Upper Airway Obstruction Using a Physiology-based Tool

RATIONALE Subglottic edema is the most common cause of pediatric extubation failure, but few studies have confirmed risk factors or prevention strategies. This may be due to subjective assessment of stridor or inability to differentiate supraglottic from subglottic disease. OBJECTIVES Objective 1 was to assess the utility of calibrated respiratory inductance plethysmography (RIP) and esophageal manometry to identify clinically significant post-extubation upper airway obstruction (UAO) and differentiate subglottic from supraglottic UAO. Objective 2 was to identify risk factors for subglottic UAO, stratified by cuffed versus uncuffed endotracheal tubes (ETTs). METHODS We conducted a single-center prospective study of children receiving mechanical ventilation. UAO was defined by inspiratory flow limitation (measured by RIP and esophageal manometry) and classified as subglottic or supraglottic based on airway maneuver response. Clinicians performed simultaneous blinded clinical UAO assessment at the bedside. MEASUREMENTS AND MAIN RESULTS A total of 409 children were included, 98 of whom had post-extubation UAO and 49 (12%) of whom were subglottic. The reintubation rate was 34 (8.3%) of 409, with 14 (41%) of these 34 attributable to subglottic UAO. Five minutes after extubation, RIP and esophageal manometry better identified patients who subsequently received UAO treatment than clinical UAO assessment (P < 0.006). Risk factors independently associated with subglottic UAO included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO. CONCLUSIONS RIP and esophageal manometry can objectively identify subglottic UAO after extubation. Using this technique, preextubation leak pressures or cuff leak volumes predict subglottic UAO in children, but only if the ETT is cuffed.

An Examination of Multivariate Time Series Hashing with Applications to Health Care

As large-scale multivariate time series data become increasingly common in application domains, such as health care and traffic analysis, researchers are challenged to build efficient tools to analyze it and provide useful insights. Similarity search, as a basic operator for many machine learning and data mining algorithms, has been extensively studied before, leading to several efficient solutions. However, similarity search for multivariate time series data is intrinsically challenging because (1) there is no conclusive agreement on what is a good similarity metric for multivariate time series data and (2) calculating similarity scores between two time series is often computationally expensive. In this paper, we address this problem by applying a generalized hashing framework, namely kernelized locality sensitive hashing, to accelerate time series similarity search with a series of representative similarity metrics. Experiment results on three large-scale clinical data sets demonstrate the effectiveness of the proposed approach.

Monitoring Dead Space in Mechanically Ventilated Children: Volumetric Capnography Versus Time-Based Capnography

BACKGROUND: Volumetric capnography dead-space measurements (physiologic dead-space-to-tidal-volume ratio [VD/VT] and alveolar VD/VT) are considered more accurate than the more readily available time-based capnography dead-space measurement (end-tidal alveolar dead-space fraction [AVDSF]). We sought to investigate the correlation between volumetric capnography and time-based capnography dead-space measurements. METHODS: This was a single-center prospective cohort study of 65 mechanically ventilated children with arterial lines. Physiologic VD/VT, alveolar VD/VT, and AVDSF were calculated with each arterial blood gas using capnography data. RESULTS: We analyzed 534 arterial blood gases from 65 children (median age 4.9 y, interquartile range 1.7–12.8). The correlation between physiologic VD/VT and AVDSF (r = 0.66, 95% CI 0.59–0.72) was weaker than the correlation between alveolar VD/VT and AVDSF (r = 0.8, 95% CI 0.76–0.85). The correlation between physiologic VD/VT and AVDSF was weaker in children with low PaO2/FIO2 (< 200 mm Hg), low exhaled VT (< 100 mL), a pulmonary reason for mechanical ventilation, or large airway VD (> 3 mL/kg). All 3 dead-space measurements were highly correlated (r > 0.7) in children without hypoxemia (PaO2/FIO2 > 300 mm Hg), mechanically ventilated for a neurologic or cardiac reason, or on significant inotropes or vasopressors. CONCLUSIONS: In mechanically ventilated children without significant hypoxemia or with cardiac output-related dead-space changes, physiologic VD/VT was highly correlated with AVDSF and alveolar VD/VT. In children with significant hypoxemia, physiologic VD/VT was poorly correlated with AVDSF. Alveolar VD/VT and AVDSF correlated well in most tested circumstances. Therefore, AVDSF may be useful in most children for alveolar dead-space monitoring.

Algorithms to Estimate PaCO2 and pH Using Noninvasive Parameters for Children with Hypoxemic Respiratory Failure

BACKGROUND: Ventilator management for children with hypoxemic respiratory failure may benefit from ventilator protocols, which rely on blood gases. Accurate noninvasive estimates for pH or PaCO2 could allow frequent ventilator changes to optimize lung-protective ventilation strategies. If these models are highly accurate, they can facilitate the development of closed-loop ventilator systems. We sought to develop and test algorithms for estimating pH and PaCO2 from measures of ventilator support, pulse oximetry, and end-tidal carbon dioxide pressure (PETCO2). We also sought to determine whether surrogates for changes in dead space can improve prediction. METHODS: Algorithms were developed and tested using 2 data sets from previously published investigations. A baseline model estimated pH and PaCO2 from PETCO2 using the previously observed relationship between PETCO2 and PaCO2 or pH (using the Henderson-Hasselbalch equation). We developed a multivariate gaussian process (MGP) model incorporating other available noninvasive measurements. RESULTS: The training data set had 2,386 observations from 274 children, and the testing data set had 658 observations from 83 children. The baseline model predicted PaCO2 within ± 7 mm Hg of the observed PaCO2 80% of the time. The MGP model improved this to ± 6 mm Hg. When the MGP model predicted PaCO2 between 35 and 60 mm Hg, the 80% prediction interval narrowed to ± 5 mm Hg. The baseline model predicted pH within ± 0.07 of the observed pH 80% of the time. The MGP model improved this to ± 0.05. CONCLUSIONS: We have demonstrated a conceptual first step for predictive models that estimate pH and PaCO2 to facilitate clinical decision making for children with lung injury. These models may have some applicability when incorporated in ventilator protocols to encourage practitioners to maintain permissive hypercapnia when using high ventilator support. Refinement with additional data may improve model accuracy.

The Relationship between High Flow Nasal Cannula Flow Rate and Effort of Breathing in Children

Objective To use an objective metric of effort of breathing to determine optimal high flow nasal cannula (HFNC) flow rates in children <3 years of age. Study design Single‐center prospective trial in a 24‐bed pediatric intensive care unit of children <3 years of age on HFNC. We measured the percent change in pressure•rate product (PRP) (an objective measure of effort of breathing) as a function of weight‐indexed flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/minute. For a subgroup of patients, 2 different HFNC delivery systems (Fisher & Paykel [Auckland, New Zealand] and Vapotherm [Exeter, New Hampshire]) were compared. Results Twenty‐one patients (49 titration episodes) were studied. The most common diagnoses were bronchiolitis and pneumonia. Overall, there was a significant difference in the percent change in PRP from baseline (of 0.5 L/kg/minute) with increasing flow rates for the entire cohort (P < .001) with largest change at 2.0 L/kg/min (−21%). Subgroup analyses showed no significant difference in percent change in PRP from baseline when comparing the 2 different HFNC delivery systems (P = .12). Patients ≤8 kg experienced a larger percent change in PRP as HFNC flow rates were increased (P = .001) than patients >8 kg. Conclusions The optimal HFNC flow rate to reduce effort of breathing in infants and young children is approximately 1.5–2.0 L/kg/minute with more benefit seen in children ≤8 kg.