Anoopindar K. Bhalla

Alveolar Dead Space Fraction Discriminates Mortality in Pediatric Acute Respiratory Distress Syndrome.

Objectives: Physiologic dead space is associated with mortality in acute respiratory distress syndrome, but its measurement is cumbersome. Alveolar dead space fraction relies on the difference between arterial and end-tidal carbon dioxide (alveolar dead space fraction = (PaCO2 – PetCO2) / PaCO2). We aimed to assess the relationship between alveolar dead space fraction and mortality in a cohort of children meeting criteria for acute respiratory distress syndrome (both the Berlin 2012 and the American-European Consensus Conference 1994 acute lung injury) and pediatric acute respiratory distress syndrome (as defined by the Pediatric Acute Lung Injury Consensus Conference in 2015). Design: Secondary analysis of a prospective, observational cohort. Setting: Tertiary care, university affiliated PICU. Patients: Invasively ventilated children with pediatric acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Of the 283 children with pediatric acute respiratory distress syndrome, 266 had available PetCO2. Alveolar dead space fraction was lower in survivors (median 0.13; interquartile range, 0.06–0.23) than nonsurvivors (0.31; 0.19–0.42; p < 0.001) at pediatric acute respiratory distress syndrome onset, but not 24 hours after (survivors 0.12 [0.06–0.18], nonsurvivors 0.14 [0.06–0.25], p = 0.430). Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminated mortality with an area under receiver operating characteristic curve of 0.76 (95% CI, 0.66–0.85; p < 0.001), better than either initial oxygenation index or PaO2/FIO2. In multivariate analysis, alveolar dead space fraction at pediatric acute respiratory distress syndrome onset was independently associated with mortality, after adjustment for severity of illness, immunocompromised status, and organ failures. Conclusions: Alveolar dead space fraction at pediatric acute respiratory distress syndrome onset discriminates mortality and is independently associated with nonsurvival. Alveolar dead space fraction represents a single, useful, readily obtained clinical biomarker reflective of pulmonary and nonpulmonary variables associated with mortality.

Higher Dead Space Is Associated With Increased Mortality in Critically Ill Children.

Objective: Elevated dead space has been consistently associated with increased mortality in adults with respiratory failure. In children, the evidence for this association is more limited. We sought to investigate the association between dead space and mortality in mechanically ventilated children. Design: Single-center retrospective review. Setting: Tertiary care pediatric critical care unit. Patients: Seven hundred twelve mechanically ventilated children with an arterial catheter. Interventions: None. Measurements and Main Results: The end-tidal alveolar dead space fraction ((PaCO2 – PETCO2)/PaCO2), a dead space marker, was calculated with each arterial blood gas. The initial end-tidal alveolar dead space fraction (first arterial blood gas after intubation) (per 0.1 unit increase: odds ratio, 1.59; 95% CI, 1.40–1.81) and day 1 mean end-tidal alveolar dead space fraction (odds ratio, 1.95; 95% CI, 1.66–2.30) were associated with mortality. The relationship between both initial and day 1 mean end-tidal alveolar dead space fraction and mortality held in multivariate modeling after controlling for any of the following individually: PaO2/FIO2, oxygenation index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III (all p < 0.01), although end-tidal alveolar dead space fraction was no longer significant after controlling for the combination of oxygenation index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III. In 217 children with acute hypoxemic respiratory failure, initial end-tidal alveolar dead space fraction (per 0.1 unit increase odds ratio, 1.38; 95% CI, 1.14–1.67) and day 1 mean end-tidal alveolar dead space fraction (per 0.1 unit increase odds ratio, 1.60; 95% CI, 1.27–2.0) were associated with mortality. Day 1 mean end-tidal alveolar dead space fraction remained associated with mortality after controlling individually for any of the following in multivariate models: PaO2/FIO2, oxygenation index, and 24-hour maximal inotrope score (p ⩽ 0.02), although end-tidal alveolar dead space fraction was no longer significant after controlling for the combination of oxygenation index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III. Conclusions: Increased dead space is associated with higher mortality in critically ill children, although it is no longer independently associated with mortality after controlling for severity of oxygenation defect, inotrope use, and severity of illness. However, because end-tidal alveolar dead space fraction is easy to calculate at the bedside, it may be useful for risk stratification and severity-of-illness scores.

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.

Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality

&NA; Rationale: The ARDS Network (ARDSNet) used a positive end‐expiratory pressure (PEEP)/FiO2 model in many studies. In general, pediatric intensivists use less PEEP and higher FiO2 than this model. Objectives: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/FiO2 model had higher mortality. Methods: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/FiO2 protocol. Four distinct datasets were combined for analysis. We extracted time‐matched PEEP/FiO2 values, calculating the difference between PEEP level and the ARDSNet‐recommended PEEP level for a given FiO2. We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP. Measurements and Main Results: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of FiO2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32‐3.17). Findings were similar after propensity‐based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24‐3.22). Conclusions: Patients with PARDS managed with lower PEEP relative to FiO2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.

Recruitment Maneuvers to the Extreme

Alveolar collapse is a common problem in mechanically ventilated children, particularly those with significant lung disease, such as ARDS. Many different methods are used by clinicians to recruit collapsed alveoli, including sustained inflation or incremental increases in PEEP until recruitment is

Elevated Positive End-Expiratory Pressure Decreases Cardiac Index in a Rhesus Monkey Model

Rationale: Clinicians are often concerned that higher positive end-expiratory pressure (PEEP) will decrease cardiac index (CI). PEEP affects CI through multiple inter-related mechanisms. The adult Rhesus monkey is an excellent model to study cardiopulmonary interaction due to similar pulmonary and chest wall compliances to human infants. Objective: Our goal was to examine the impact of increasing PEEP on CI in Rhesus monkeys as a model for critically ill children. Methods: Prospective, experimental animal study. Nine healthy anesthetized, intubated Rhesus monkeys were allowed to breathe spontaneously at a PEEP of 0, 5, 10, and 15 cm H2O while CI was measured with an ultrasonic Doppler (USCOM). Measurements and main results: Cardiac index decreased between PEEP levels of 5 and 15 cm H2O. The mean decrease in CI for the entire cohort of monkeys was 18% (p < 0.01) with a range of −11 to 49%. Stroke volume and oxygen delivery also decreased between PEEP levels of 5 and 15 cm H2O (p < 0.01). Conclusion: Between PEEP levels of 5 and 15 cm H2O, there was a decrease in CI, stroke volume, and oxygen delivery in intubated Rhesus monkeys. A plausible mechanism is that over-distention of normally compliant lungs at increased PEEP resulted in decreased preload to the right ventricle, outweighing the potentially beneficial decrease in left ventricular afterload or pulmonary vascular resistance. Further investigation is warranted, particularly in children with lung injury, who have historically benefited from increased PEEP levels without over-distention.

Accuracy of Transcutaneous Carbon Dioxide Levels in Comparison to Arterial Carbon Dioxide Levels in Critically Ill Children

BACKGROUND: Widespread use of transcutaneous PCO2 (PtcCO2) monitoring is currently limited by concerns many practitioners have regarding accuracy. We compared the accuracy of PtcCO2 with that of PaCO2 measurements in critically ill children, and we investigated whether clinical conditions associated with low cardiac output or increased subcutaneous tissue affect this accuracy. METHODS: We performed a single-center prospective study of critically ill children placed on transcutaneous monitoring. RESULTS: There were 184 children enrolled with paired PaCO2 and PtcCO2 values. Subjects had a median age of 31.8 mo (interquartile range 3.5–123.3 mo). Most children were mechanically ventilated (n = 161, 87.5%), and many had cardiac disease (n = 76, 41.3%). The median PaCO2 was 44 mm Hg (interquartile range 39–51 mm Hg). The mean bias between PaCO2 and PtcCO2 was 0.6 mm Hg with 95% limits of agreement from −13.6 to 14.7 mm Hg. The PtcCO2 and PaCO2 were within ±5 mm Hg in 126 (68.5%) measurements. In multivariable modeling, cyanotic heart disease (odds ratio 3.5, 95% CI 1.2–10, P = .02) and monitor number 2 (odds ratio 3.8 95% CI 1.3–10.5, P = .01) remained associated with PtcCO2 ≥ 5 mm Hg higher than PaCO2. Serum lactate, fluid balance, renal failure, obesity, vasoactive-inotrope score, and acyanotic heart disease were not associated with high or low PtcCO2 values. In 130 children with a second paired PtcCO2 and PaCO2 measurement, predicting the second measured PaCO2 by subtracting the initial observed difference between the PtcCO2 and PaCO2 from the subsequent measured PtcCO2 decreased the mean bias between observed and predicted PaCO2 to 0.2 mm Hg and the 95% limits of agreement to −9.4 to 9.7 mm Hg. CONCLUSIONS: PtcCO2 provides an acceptable estimate of PaCO2 in many critically ill children, including those with clinical conditions that may be associated with low cardiac output or increased subcutaneous tissue, although it does not perform as well in children with cyanotic heart disease. PtcCO2 may be a useful adjunct monitoring method, but it cannot reliably replace PaCO2 measurement.

942: THE ASSOCIATION OF INHALED NITRIC OXIDE WITH OUTCOMES IN CHILDREN WITH ARDS.

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) HSR⁄DEX group, 6.36 ± 2.29 vs 5.01 ± 1.85, n = 5 per group) The mRNA levels of TNF-alpha and iNOS were significantly decreased in the HSR⁄DEX group compared with HSR⁄vehicle group. Conclusions: We found that Dexmedetomidine could have a protective role against hemorrhagic shock and resuscitation induced lung injury, and that Dexmedetomidine suppresses inflammatory gene expression on lung.