Low-Order Mechanistic Models for Volumetric and Temporal Capnography: Development, Validation, and Application.

OBJECTIVE: Develop low-order mechanistic models accounting quantitatively for, and identifiable from, the capnogram - the CO 2 concentration in exhaled breath, recorded over time (Tcap) or exhaled volume (Vcap). METHODS: The airflow model's single "alveolar" compartment has compliance and inertance, and feeds a resistive unperfused airway comprising a laminar-flow region followed by a turbulent-mixing region. The gas-mixing model tracks mixing-region CO 2 concentration, fitted breath-by-breath to the measured capnogram, yielding estimates of model parameters that characterize the capnogram. RESULTS: For the 17 examined records (310 breaths) of airflow, airway pressure and Tcap from ventilated adult patients, the models fit closely (mean rmse 1% of end-tidal CO 2 concentration on Vcap; 1.7% on Tcap). The associated parameters (4 for Vcap, 5 for Tcap) for each exhalation, and airflow parameters for the corresponding forced inhalation, are robustly estimated, and consonant with literature values. The models also allow, using Tcap alone, estimation of the entire exhaled airflow waveform to within a scaling. This suggests new Tcap-based tests, analogous to spirometry but with normal breathing, for discriminating chronic obstructive pulmonary disease (COPD) from congestive heart failure (CHF). A version trained on 15 exhalations from each of 24 COPD/24 CHF Tcap records from one hospital, then tested 100 times with 15 random exhalations from each of 27 COPD/31 CHF Tcap records at another, gave mean accuracy 80.6% (stdev 2.1%). Another version, tested on 29 COPD/32 CHF, yielded AUROC 0.84. CONCLUSION: Our mechanistic models closely fit Tcap and Vcap measurements, and yield subject-specific parameter estimates. SIGNIFICANCE: This can inform cardiorespiratory care.

Predictors of Laryngospasm During 276,832 Episodes of Pediatric Procedural Sedation.

STUDY OBJECTIVE: Laryngospasm is a rare but potentially life-threatening complication of sedation. The objective of this study was to perform a predictor analysis of biologically plausible predictors and the interventions and outcomes associated with laryngospasm. METHODS: Secondary analysis of prospectively collected data from consecutively sedated patients, less than or equal to 22 years of age, at multiple locations at 64 member institutions of the Pediatric Sedation Research Consortium. The primary outcome was laryngospasm. The independent variables in the multivariable model included American Society of Anesthesiologists category, age, sex, concurrent upper respiratory infection, medication regimen, hospital sedation location, whether the procedure was painful, and whether the procedure involved the airway. The analysis included adjusted odds ratios (aORs) and predicted probabilities. RESULTS: We analyzed 276,832 sedations with 913 reported events of laryngospasm (overall unadjusted prevalence 3.3:1,000). A younger age, a higher American Society of Anesthesiologists category, a concurrent upper respiratory infection (aOR 3.94, 2.57 to 6.03; predicted probability 12.2/1,000, 6.3/1,000 to 18.0/1,000), and airway procedures (aOR 3.73, 2.33 to 5.98; predicted probability 9.6/1,000, 5.2/1,000 to 13.9/1,000) were associated with increased risk. Compared with propofol alone, propofol combination regimens had increased risk (propofol+ketamine: aOR 2.52, 1.41 to 4.50; predicted probability 7.6/1,000, 3.1/1,000 to 12/1,000; and propofol+dexmedetomidine: aOR 2.10, 1.25 to 3.52; predicted probability 6.3/1,000, 3.7,/1,000 to 8.9/1,000). Among patients with laryngospasm, the resulting outcomes included desaturation less than 70% for more than 30 seconds (19.7%), procedure not completed (10.6%), emergency airway intervention (10.0%), endotracheal intubation (5.3%), unplanned admission/increase in level of care (2.3%), aspiration (1.1%), and cardiac arrest (0.2%). CONCLUSION: We found increased associations of laryngospasm in pediatric procedural sedation with multiple biologic factors, procedure types, and medication regimens. However, effect estimates showed that the laryngospasm prevalence remained low, and this should be taken into consideration in sedation decisionmaking.

Does Point-of-Care Gastric Ultrasound Correlate With Reported Fasting Time?

OBJECTIVE: Traditionally, patient-reported fasting time has been the primary objective presedation measure of aspiration risk. Recently, gastric ultrasound has been used to assess gastric volume for the determination of aspiration risk in patients undergoing anesthesia in the operative setting. We sought to determine the correlation of gastric volume estimated by point-of-care ultrasound (POCUS) to reported fasting time. METHODS: We included children 4 to 18 years of age who presented with an acute traumatic injury. Enrolled children underwent POCUS to calculate gastric volume, which was calculated using a validated formula: Volume (mL) = -7.8 + (3.5 × Cross-sectional Area [CSA]) + (0.127 × Age in months). The CSA was measured (CSA = (anterior-posterior diameter × craniocaudal diameter × π)/4). We analyzed the relationship between time since last reported oral intake and measured gastric volume using Spearman rank correlation (ρ). RESULTS: A total of 103 patients with a median age of 10.5 years (interquartile range, 7.3-13.7 years) were enrolled. The gastric antrum was identified and measured in 88 (85%) patients; air obstructing the posterior surface of the gastric antrum prevented measurement in 14 of the 15 remaining patients. We observed a weak inverse correlation between fasting time (either liquid or solid) and estimated gastric volume (ρ = -0.33), with no significant difference based on type of intake (solids, ρ = 0.28; liquids, ρ = 0.22). CONCLUSION: Gastric volume can be estimated by POCUS and is not strongly correlated with fasting time in children in the emergency department setting.

Unscheduled Procedural Sedation: A Multidisciplinary Consensus Practice Guideline.

The American College of Emergency Physicians (ACEP) organized a multidisciplinary effort to create a clinical practice guideline specific to unscheduled, time-sensitive procedural sedation, which differs in important ways from scheduled, elective procedural sedation. The purpose of this guideline is to serve as a resource for practitioners who perform unscheduled procedural sedation regardless of location or patient age. This document outlines the underlying background and rationale, and issues relating to staffing, practice, and quality improvement.

Clinical Practice Guideline for Emergency Department Procedural Sedation With Propofol: 2018 Update.

We update an evidence-based clinical practice guideline for the administration of propofol for emergency department procedural sedation. Both the unique considerations of using this drug in the pediatric population and the substantial new research warrant revision of the 2007 advisory. We discuss the indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, and adverse events for propofol sedation.

Prolonged central apnoea after intravenous morphine administration in a 12-year-old male with a UGT1A1 loss-of-function polymorphism.

ADVERSE EVENT: Repeated and prolonged episodes of central apnoea and hypoxia after receiving intravenous morphine for analgesia and ketamine for sedation. DRUG IMPLICATED: Intravenous morphine sulfate. THE PATIENT: Previously healthy 12-year-old male with no history of sleep apnoea who presented with distal tibia and fibula fracture. EVIDENCE THAT LINKS DRUG TO EVENT: Pharmacogenomic testing revealed that the patient was homozygous for the T allele at the rs887829 SNP in UGT1A1, an enzyme involved in the metabolism of morphine. This polymorphism is a loss-of-function variant, leading to impaired metabolism of morphine. MECHANISM: Morphine is metabolized by UDP-glucuronosyltransferase (UGT)-2B7 and UGT1A1 to form its major metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Our patient was a poor metabolizer through UGT1A1, likely leading to increased respiratory depression as morphine has greater respiratory depressant effects compared to its metabolites. IMPLICATIONS: When appropriate, physicians should enquire about prior receipt of opioids, in both the patient and family, to be better prepared for potential adverse reactions. In the patient with excessive sedation or respiratory depression to standard doses of morphine, genetic testing may be warranted, especially if there is a family or past history that supports a metabolic defect in morphine metabolism and/or excretion.

An Enhanced Mechanistic Model For Capnography, With Application To CHF-COPD Discrimination.

Capnography records CO2 partial pressure in exhaled breath as a function of time or exhaled volume. Time-based capnography, which is our focus, is a point-of-care, noninvasive, effort-independent and widely available clinical monitoring modality. The generated waveform, or capnogram, reflects the ventilation-perfusion dynamics of the lung, and thus has value in the diagnosis of respiratory conditions such as chronic obstructive pulmonary disease (COPD). Effective discrimination between normal respiration and obstructive lung disease can be performed using capnogram-derived estimates of respiratory parameters in a simple mechanistic model of CO2 exhalation. We propose an enhanced mechanistic model that can capture specific capnogram characteristics in congestive heart failure (CHF) by incorporating a representation of the inertance associated with fluid in the lungs. The 4 associated parameters are estimated on a breath-by-breath basis by fitting the model output to the exhalations in the measured capnogram. Estimated parameters from 40 exhalations of 7 CHF and 7 COPD patients were used as a training set to design a quadratic discriminator in the parameter space, aimed at distinguishing between CHF and COPD patients. The area under the ROC curve for the training set was 0.94, and the corresponding equal-error-rate value of approximately 0.1 suggests classification accuracies of the order of 90% are attainable. Applying this discriminator without modification to 40 exhalations from each CHF and COPD patient in a fresh test set, and deciding on a simple majority basis whether the patient has CHF or COPD, results in correctly labeling all 8 out of the 8 CHF patients and 6 out of the 8 COPD patients in the test set, corresponding to a classification accuracy of 87.5%.

Statistical analysis of the age dependence of the normal capnogram.

The age dependence of the time-based capnogram from normal, healthy subjects has not been quantitatively characterized. The existence of age dependence would impact the development and operation of automated quantitative capnographic tools. Here, we quantitatively assess the relationship between normal capnogram shape and age. Capnograms were collected from healthy subjects, and physiologically-based features (exhalation duration, end-tidal CO2 and time spent at this value, normalized time spent at end-tidal CO2, end-exhalation slope, and instantaneous respiratory rate) were computationally extracted. The mean values of the individual features over 30 exhalations were linearly regressed against subject age, accounting for inter-feature correlation. After data collection, 154 of 178 subjects were eligible for analysis, with an age range of 3-78 years (mean age 39, std. dev. 20 years). The Bonferroni-corrected joint 95% confidence intervals (CIs) of the regression line slopes contained the origin for five of six features (the remaining CI was only slightly offset from the origin). The associated individual r2 values for the regressions were all below 0.07. We conclude that age is not a significant explanatory factor in describing variations in the shape of the normal capnogram. This finding could be exploited in the design of automated methods for quantitative capnogram analysis across a range of ages.

Fever in Children: Pearls and Pitfalls.

Fever in children is a common concern for parents and one of the most frequent presenting complaints in emergency department visits, often involving non-pediatric emergency physicians. Although the incidence of serious infections has decreased after the introduction of conjugate vaccines, fever remains a major cause of laboratory investigation and hospital admissions. Furthermore, antipyretics are the most common medications administered to children. We review the epidemiology and measurement of fever, the meaning of fever and associated clinical signs in children of different ages and under special conditions, including fever in children with cognitive impairment, recurrent fevers, and fever of unknown origin. While the majority of febrile children have mild, self-resolving viral illness, a minority may be at risk of life-threatening infections. Clinical assessment differs markedly from adult patients. Hands-off evaluation is paramount for a correct evaluation of breathing, circulation and level of interaction. Laboratory markers and clinical prediction rules provide limited help in identifying children at risk for serious infections; however, clinical examination, prudent utilization of laboratory tests, and post-discharge guidance ("safety netting") remain the cornerstone of safe management of febrile children.

Model-Based Estimation of Respiratory Parameters from Capnography, With Application to Diagnosing Obstructive Lung Disease.

OBJECTIVE: We use a single-alveolar-compartment model to describe the partial pressure of carbon dioxide in exhaled breath, as recorded in time-based capnography. Respiratory parameters are estimated using this model, and then related to the clinical status of patients with obstructive lung disease. METHODS: Given appropriate assumptions, we derive an analytical solution of the model, describing the exhalation segment of the capnogram. This solution is parametrized by alveolar CO2 concentration, dead-space fraction, and the time constant associated with exhalation. These quantities are estimated from individual capnogram data on a breath-by-breath basis. The model is applied to analyzing datasets from normal (n = 24) and chronic obstructive pulmonary disease (COPD) (n = 22) subjects, as well as from patients undergoing methacholine challenge testing for asthma (n = 22). RESULTS: A classifier based on linear discriminant analysis in logarithmic coordinates, using estimated dead-space fraction and exhalation time constant as features, and trained on data from five normal and five COPD subjects, yielded an area under the receiver operating characteristic curve (AUC) of 0.99 in classifying the remaining 36 subjects as normal or COPD. Bootstrapping with 50 replicas yielded a 95% confidence interval of AUCs from 0.96 to 1.00. For patients undergoing methacholine challenge testing, qualitatively meaningful trends were observed in the parameter variations over the course of the test. SIGNIFICANCE: A simple mechanistic model allows estimation of underlying respiratory parameters from the capnogram, and may be applied to diagnosis and monitoring of chronic and reversible obstructive lung disease.

Characteristics of and Predictors for Apnea and Clinical Interventions During Procedural Sedation.

STUDY OBJECTIVE: We describe the characteristics of and predictors for apnea and clinical interventions during emergency department (ED) procedural sedation. METHODS: High-resolution data were collected prospectively, using a convenience sample of ED patients undergoing propofol or ketofol sedation. End tidal CO2 (etco2), respiratory rate, pulse rate, and SpO2 were electronically recorded in 1-second intervals. Procedure times, drug delivery, and interventions were electronically annotated. Kaplan-Meier curves were used to describe the onset of clinical interventions as a function of sedation time. The onset of apnea (15 consecutive seconds with carbon dioxide ≤10 mm Hg) and clinical interventions were estimated with a series of Cox proportional hazards survival models, with time to first apnea or clinical intervention as the dependent variable. Finally, we tested the association between apnea and clinical intervention. RESULTS: Three hundred twelve patients were analyzed (53% male patients). Apnea was preceded by etco2 less than 30 mm Hg or greater than 50 mm Hg at 30, 60, and 90 seconds before its onset. Clinical interventions were predicted by apnea, SpO2, and propofol use. Increasing age predicted both apnea and interventions. Apnea was not predicted by respiratory rate or SpO2. Apnea occurred in half of the patients and clinical interventions in a quarter of them. Clinical intervention was not predicted by abnormal respiratory rate or abnormal etco2 level. The majority of clinical interventions (85%) were minor, with no cases of assisted ventilation, intubation, or complications. CONCLUSION: Alterations in etco2 predicted apnea along a specific time course. Alterations in SpO2, apnea, and propofol use predicted clinical interventions. Increasing age predicted both apnea and clinical intervention.