Clinical Outcomes of Acute Respiratory Failure Associated With Noninvasive and Invasive Ventilation in a Pediatric ICU.

BACKGROUND: It remains unknown if pediatric patients failing initial noninvasive ventilation (NIV) experience worse clinical outcomes than those successfully treated with NIV or those primarily intubated. METHODS: This was a single-center, retrospective review of patients admitted with acute respiratory failure to the University of Michigan pediatric intensive care or cardiothoracic ICUs and receiving NIV or invasive mechanical ventilation as first-line therapy. RESULTS: One hundred seventy subjects met inclusion criteria and were enrolled: 65 NIV success, 55 NIV failure, and 50 invasive mechanical ventilation alone. Of those failing NIV, median time to intubation was 1.8 (interquartile range [IQR] < 1-7) h. On multivariable regression, ICU-free days were significantly different between groups (NIV success: 22.9 ± 6.9 d; NIV failure: 13.0 ± 6.6 d; invasive ventilation: 12.5 ± 6.9 d; P < .001 across all groups). Multivariable regression revealed no difference in ventilator-free days between NIV failure and invasive ventilation groups (15.4 ± 10.1 d vs 15.9 ± 9.7 d, P = .71). Of 64 subjects (37.6%) meeting Pediatric Acute Lung Injury Consensus Conference pediatric ARDS criteria, only 14% were successfully treated with NIV. Ventilator-free days were similar between the NIV failure and invasive ventilation groups (11.6 vs 13.2 d, P = .47). On multivariable analysis, ICU-free days were significantly different across pediatric ARDS groups (P < .001): NIV success: 20.8 + 31.7 d; NIV failure: 8.3 + 23.8 d; invasive alone: 8.9 + 23.9 d, yet no significant difference in ventilator-free days between those with NIV failure versus invasive alone (11.6 vs 13.2 d, P = .47). CONCLUSIONS: We demonstrated that critically ill pediatric subjects unsuccessfully trialed on NIV did not experience increased ICU length of stay or fewer ventilator-free days when compared to those on invasive mechanical ventilation alone, including in the pediatric ARDS subgroup. Our findings are predicated on a median time to intubation of < 2 h in the NIV failure group and the provision of adequate monitoring while on NIV.

Brainstem hypoxic-ischemic lesions on MRI in infants treated with therapeutic cooling: effects on the length of stay and mortality.

OBJECTIVE: To test the hypothesis that brainstem hypoxic-ischemic injury on magnetic resonance imaging (MRI) would be independently associated with short-term outcomes in cooled asphyxiated infants. METHODS: A total of 90 consecutively cooled asphyxiated infants who survived to have brain MRI were reviewed. A neuroradiologist who was masked to outcomes evaluated MRI images for brainstem involvement. Outcomes were mortality and length of stay. RESULTS: Brainstem lesions were present on post-cooling brain MRI in 20 of the 90 infants (22%). Overall, four infants died before discharge, and all four had brainstem involvement. The infants with brainstem involvement had longer hospital stay (29 days, IQR 20-47 versus 16 days, IQR 10-26; P = 0.0001), compared to infants without brainstem lesions (n = 70); and upon multivariate analysis, brainstem involvement remained independently associated with prolonged hospital stay (ß = 12.4, P = 0.001). CONCLUSION: This study demonstrates the importance of recognizing brainstem injury for the prediction of short-term outcomes in cooled asphyxiated infants.

Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique.

BACKGROUND: Several indirect calorimetry (IC) instruments are commercially available, but comparative validity and reliability data are lacking. Existing data are limited by inconsistencies in protocols, subject characteristics, or single-instrument validation comparisons. The aim of this study was to compare accuracy and reliability of metabolic carts using methanol combustion as the cross-laboratory criterion. METHODS: Eight 20-minute methanol burn trials were completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O2 and CO2 recovery were calculated. RESULTS: For accuracy, 1 Omnical, Cosmed Quark CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3 variables within 2% of the true value; both DeltaTracs and the Vmax Encore System (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking best (coefficient of variation [CV] < 1.26%). Both Cosmeds, Parvos, DeltaTracs, 1 Jaeger Oxycon Pro (Oxycon), Max-II Metabolic Systems (Max-II), and Vmax were reliable for at least 1 variable (CV ≤ 3%). For multiple regression, humidity and amount of combusted methanol were significant predictors of RER (R2 = 0.33, P < .001). Temperature and amount of burned methanol were significant predictors of O2 recovery (R2 = 0.18, P < .001); only humidity was a predictor for CO2 recovery (R2 = 0.15, P < .001). CONCLUSIONS: Omnical, Parvo, Cosmed, and DeltaTrac had greater accuracy and reliability. The small number of instruments tested and expected differences in gas calibration variability limits the generalizability of conclusions. Finally, humidity and temperature could be modified in the laboratory to optimize IC conditions.

Predicting the need for home gavage or g-tube feeds in asphyxiated neonates treated with therapeutic hypothermia.

BACKGROUND: Asphyxiated infants treated with therapeutic cooling can have persistent oral feeding difficulty because of involvement of neural pathways in the brainstem, cortex, and basal ganglia. The goal is to predict the composite adverse outcome of death or persistent oral feeding difficulty using precooling/cooling attributes, and the severity and distribution of hypoxic-ischemic lesions, especially brainstem lesions on post-cooling brain magnetic resonance imaging (MRI). METHODS: Retrospective review of 86 asphyxiated infants cooled from January 2006 to August 2014. Persistent feeding difficulty was defined as needing feeding support (gastrostomy tube (g-tube) or home gavage feeds) after discharge. Clinical and laboratory risk factors, and the brain MRI abnormalities including the presence of brainstem lesions were compared between infants with and without adverse outcome using univariate analysis. Significant variables were then analyzed in a stepwise logistic regression (LR) model. RESULTS: Infants with adverse outcome (n = 31, 4 died pre-discharge) had longer hospital stay (26 days, interquartile range (IQR) 19-43 vs. 13 days, IQR 9-20; p < 0.01) and reached goal enteral feeds (oral/gavage) later (11 days vs. 8 days, p < 0.01) compared to 55 infants discharged on full oral feeds. The former infants were more likely to have cord pH ≤ 7.15, severely abnormal neurological examination, bleeding diathesis, continued need for ventilation, and positive MRI findings including brainstem lesions. In LR analysis, brainstem lesions on MRI (p = 0.00, odds ratio 19, 95% confidence interval 4-85) was independently associated with the adverse outcome. CONCLUSIONS: Brainstem involvement on post-cooling brain MRI was predictive of adverse outcome. Early identification of these infants may facilitate discussion of home feeding plans between clinicians and parents earlier, thereby potentially reducing the length of hospital stay.

Assessment of association between rapid fluctuations in serum sodium and intraventricular hemorrhage in hypernatremic preterm infants.

AIM: This study aims to determine the association between the rapid fluctuations in serum sodium and intraventricular hemorrhage (IVH) or death in hypernatremic preterm infants. STUDY DESIGN: Single center observational study including 216 infants < 1,000 g birth weight and <29 weeks gestational age, who had serum sodium levels monitored at least every 12 hours. Logistic regression analyses were used to identify which of the commonly cited risk factors for IVH, including the rapid (to the extent of ≥10 and ≥15 mmol/L/d) rise or fall in serum sodium, was associated with the primary outcome of any IVH, or the secondary composite outcome of severe IVH or death during the first 10 days of life in hypernatremic infants. RESULTS: Of 216 infants, 126 (58%) studied developed hypernatremia (serum sodium ≥ 150 mmol/L). IVH was more frequent in hypernatremic infants (p = 0.01). Presence of hypernatremia was an independent risk factor for IVH on logistic regression analysis (p = 0.022, odds ratio 2.0, 95% confidence interval: 1.1-3.8). Rapid (≥ 10 and ≥ 15 mmol/L/d) rise or fall in serum sodium in hypernatremic infants was not associated with the outcomes. CONCLUSION: Hypernatremia per se, but not the rapid fluctuations (not exceeding 10-15 mmol/L/d) in serum sodium was independently associated with IVH.

Validation of the V(max) metabolic cart in a simulated pediatric model.

BACKGROUND: The ability to accurately measure resting energy expenditure (REE) using indirect calorimetry, often referred to as the "gold standard" in nutrition needs assessment, is important given the well-established positive correlation between patient outcome and proportion of the nutrition goal met. While many studies have been done to compare various metabolic carts with one another, the literature lacks a large simulator-based validation of any metabolic cart system. MATERIALS AND METHODS: In the present study, 8 specifically trained staff members independently conducted 10 simulation trials each using the V(max) Encore metabolic analyzer in conjunction with a metabolic calibration system, which simulates patient metabolic activity, to validate the accuracy of the V(max) Encore across a wide range of simulated metabolic conditions. Testing conditions consisted of incremental adjustments in calibrated gas infusion with a consistently set tidal volume and respiratory rate. RESULTS: There was a strong, statistically significant correlation between the predicted and actual VO2 and VCO2 data (VO2, R (2) = 0.998; VCO2, R (2) = 0.997). In addition, we observed no significant difference between individuals performing these trials (VO2, P = 1.000, F = 0.021, df = 79; VCO2, P = 1.000, F = 0.030, df = 79). CONCLUSIONS: This study is the first to report on such a wide spectrum of metabolic activity (50-2000 kcal REE) using a calibrated bench model and validates the accuracy, reproducibility, and use of the V(max) Encore metabolic cart.

Evaluation of the oxygenation index in adult respiratory failure.

BACKGROUND: The oxygenation index (mean airway pressure × FIO2 divided by PaO2) was originally devised to measure severity of illness and predict outcome in neonatal respiratory failure. We evaluated the discrimination of a modified oxygenation index (modified with age) for predicting 28-day mortality in adults with respiratory failure (adult respiratory distress syndrome [ARDS]) using the ALVEOLI section of the ARDSNet database and validated the results in the full ARDSNet database. METHODS: We compared age-adjusted oxygenation index (AOI) on ventilator Days 1 to 4 with 28-day mortality. RESULTS: AOI correlated positively with mortality (area under the receiver operating characteristic curve, 0.70-0.74, for ARDS Days 1-4). Following initial development, AOI related to mortality was validated in two other ARDSNet databases producing similar results (area under the receiver operating characteristic curve, 0.70-0.78). CONCLUSION: The observed sensitivity and specificity analysis demonstrated that AOI is equivalent to or better than other mortality prediction systems used for ARDS. LEVEL OF EVIDENCE: Prognostic, level III.

Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia.

BACKGROUND: We hypothesized that acute kidney injury (AKI) in asphyxiated neonates treated with therapeutic hypothermia would be associated with hypoxic-ischemic lesions on brain magnetic resonance imaging (MRI). METHODS: Medical records of 88 cooled neonates who had had brain MRI were reviewed. All neonates had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h through cooling; and then on day 5 or 7 of life. A neonatal modification of the Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI. MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of interest was abnormal brain MRI at 7-10 d of life. RESULTS: AKI was found in 34 (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and 3, respectively. Brain MRI abnormalities related to hypoxia-ischemia were present in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.3-8.2). Multivariate analysis identified AKI (OR = 2.9; 95% CI = 1.1-7.6) to be independently associated with the primary outcome. CONCLUSION: AKI is independently associated with the presence of hypoxic-ischemic lesions on postcooling brain MRI.

Esophageal and rectal temperatures as estimates of core temperature during therapeutic whole-body hypothermia.

We monitored whole-body cooling concurrently by both esophageal and rectal probes. Esophageal temperature was significantly higher compared with simultaneous rectal temperature during cooling, with a temperature gradient ranging from 0.46 to 1.03°C (median, 0.8°C; IQR, 0.6-0.8°C). During rewarming, this temperature difference disappeared.

Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia.

OBJECTIVE: To test the hypothesis that acute kidney injury (AKI) would be independently associated with increased morbidity and mortality. STUDY DESIGN: A total of 96 consecutively cooled infants were reviewed retrospectively. Modified Acute Kidney Injury Network criteria were used to classify AKI based on absolute rise in serum creatinine (SCr) level from a previous trough (stage I, rise in SCr of 0.3 mg/dL or SCr 150-<200%; stage II, rise in SCr of 200-<300%; stage III, rise in SCr of ≥300%, SCr 2.5 mg/dL, or dialysis). Outcomes were mortality, duration of neonatal intensive care unit (NICU) stay, and duration of mechanical ventilation. RESULTS: AKI occurred in 36 of 96 infants (38%). Overall mortality was 7% and was higher for those with AKI, with the difference approaching statistical significance (14% vs 3% in those without AKI; P = .099). Patients with AKI stayed longer in the NICU (mean, 15.4 ± 9.3 days vs 11 ± 5.9 days; P = .014) and required prolonged mechanical ventilation (mean, 9.7 ± 5.9 days vs 4.8 ± 3.7 days; P < .001). On multivariate analysis, AKI remained predictive of prolonged duration of mechanical ventilation and prolonged NICU stay. CONCLUSION: We used the Acute Kidney Injury Network definition for AKI in asphyxiated newborns undergoing therapeutic hypothermia to demonstrate that the incidence of AKI remains high, but lower than rates published before the advent of therapeutic hypothermia. We highlight the importance of recognizing AKI in asphyxiated newborns undergoing therapeutic hypothermia, along with the potential benefits of early recognition.

Current knowledge of acute lung injury and acute respiratory distress syndrome.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) continues to be a major cause of mortality in adult and pediatric critical care medicine. This article discusses the pulmonary sequelae associated with ALI and ARDS, the support of ARDS with mechanical ventilation, available adjunctive therapies, and experimental therapies currently being tested. It is hoped that further understanding of the fundamental biology, improved identification of the patient's inflammatory state, and application of therapies directed at multiple sites of action may ultimately prove beneficial for patients suffering from ALI/ARDS.

The effect of late preterm birth on mortality of infants with hypoplastic left heart syndrome.

OBJECTIVES: We evaluated the effect of late preterm (34 to 36 weeks' gestation) delivery on hospital mortality of infants with hypoplastic left heart syndrome (HLHS). STUDY DESIGN: Retrospective review of records of infants born at or after 34 weeks with no other lethal anomalies, cared for in a single tertiary perinatal center between 2002 and 2009. Factors associated with death prior to discharge from the hospital were ascertained using univariate and multivariate analyses. RESULTS: Of the 243 infants with HLHS, 35 were late preterm and 208 were ≥37 weeks (term). Using logistic regression analysis, late preterm delivery (odds ratio [OR] 2.95; 95% confidence interval [CI] 1.35 to 6.45), the presence of other major cardiac defects (OR 3.76; 95% CI 1.31 to 10.81), and the presence of noncardiac congenital anomalies (OR 6.13; 95% CI 1.43 to 26.22) were independently associated with hospital death. CONCLUSION: Late preterm birth of infants with HLHS was independently associated with an increased risk of hospital death compared with those delivered at term.

A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury.

RATIONALE: Despite recent advances in critical care and ventilator management, acute lung injury and acute respiratory distress syndrome continue to cause significant morbidity and mortality. Granulocyte-macrophage colony stimulating factor may be beneficial for patients with acute respiratory distress syndrome. OBJECTIVES: To determine whether intravenous infusion of granulocyte-macrophage colony stimulating factor would improve clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome. DESIGN: A randomized, double-blind, placebo-controlled clinical trial of human recombinant granulocyte-macrophage colony stimulating factor vs. placebo. The primary outcome was days alive and breathing without mechanical ventilatory support within the first 28 days after randomization. Secondary outcomes included mortality and organ failure-free days. SETTING: Medical and surgical intensive care units at three academic medical centers. PATIENTS: One hundred thirty individuals with acute lung injury of at least 3 days duration were enrolled, out of a planned cohort of 200 subjects. INTERVENTIONS: Patients were randomized to receive human recombinant granulocyte-macrophage colony stimulating factor (64 subjects, 250 µg/M) or placebo (66 subjects) by intravenous infusion daily for 14 days. Patients received mechanical ventilation using a lung-protective protocol. MEASUREMENTS AND MAIN RESULTS: There was no difference in ventilator-free days between groups (10.7 ± 10.3 days placebo vs. 10.8 ± 10.5 days granulocyte-macrophage colony stimulating factor, p = .82). Differences in 28-day mortality (23% in placebo vs. 17% in patients receiving granulocyte-macrophage colony stimulating factor (p = .31) and organ failure-free days (12.8 ± 11.3 days placebo vs. 15.7 ± 11.9 days granulocyte-macrophage colony stimulating factor, p = .16) were not statistically significant. There were similar numbers of serious adverse events in each group. CONCLUSIONS: In a randomized phase II trial, granulocyte-macrophage colony stimulating factor treatment did not increase the number of ventilator-free days in patients with acute lung injury/acute respiratory distress syndrome. A larger trial would be required to determine whether treatment with granulocyte-macrophage colony stimulating factor might alter important clinical outcomes, such as mortality or multiorgan failure. (ClinicalTrials.gov number, NCT00201409 [ClinicalTrials.gov]).

Rebound in ventilator-associated pneumonia rates during a prevention checklist washout period.

OBJECTIVE To describe the washout effect after stopping a prevention checklist for ventilator-associated pneumonia (VAP). METHODS VAP rates were prospectively monitored for special cause variation over 42 months in a paediatric intensive care unit. A VAP prevention bundle was implemented, consisting of head of bed elevation, oral care, suctioning device management, ventilator tubing care, and standard infection control precautions. Key practices of the bundle were implemented with a checklist and subsequently incorporated into the nursing and respiratory care bedside flow sheets to achieve long-term sustainability. Compliance with the VAP bundle was monitored throughout. The timeline for the project was retrospectively categorised into the benchmark phase, the checklist phase (implementation), the checklist washout phase, and the flowsheet phase (cues in the flowsheet). RESULTS During the checklist phase (12 months), VAP bundle compliance rose from <50% to >75% and the VAP rate fell from 4.2 to 0.7 infections per 1000 ventilator days (p<0.059). Unsolicited qualitative feedback from frontline staff described overburdensome documentation requirements, form fatigue, and checklist burnout. During the checklist washout phase (4 months), VAP rates rose to 4.8 infections per 1000 ventilator days (p<0.042). In the flowsheet phase, the VAP rate dropped to 0.8 infections per 1000 ventilator days (p<0.047). CONCLUSIONS Salient cues to drive provider behaviour towards best practice are helpful to sustain process improvement, and cessation of such cues should be approached warily. Initial education, year-long habit formation, and effective early implementation demonstrated no appreciable effect on the VAP rate during the checklist washout period.

Nutrition in critical care.

Critical care has evolved from a prolonged recovery room stay for cardiac surgery patients to a full medical and nursing specialty in the last 5 decades. The ability to feed patients who cannot eat has evolved from impossible to routine clinical practice in the last 4 decades. Nutrition in critically ill patients based on measurement of metabolism has evolved from a research activity to clinical practice in the last 3 decades. The authors have been involved in this evolution and this article discusses past, present, and likely future practices in nutrition in critically ill patients.

The relationship between clinically identifiable intrapartum sentinel events and short-term outcome after therapeutic hypothermia.

OBJECTIVE: To determine the impact of intrapartum sentinel events on short-term outcome post-hypothermia. STUDY DESIGN: Records of 77 infants of 36 weeks' gestation or more, who received therapeutic hypothermia, were reviewed. Some were delivered after a clinically identifiable intrapartum sentinel event (IISE). All survivors had brain magnetic resonance imaging (MRI) at 7 to 10 days of life. The primary outcome of neonatal death related to hypoxic-ischemic encephalopathy was compared in infants born with (n = 39) or without an IISE (n = 38). MRI abnormalities were also compared. Logistic regression analysis was used to determine the variables predicting the primary outcome. RESULTS: The two groups had similar Apgar scores, initial blood pHs, and early neurologic examinations. Base deficit was more severe in the IISE group. Neonatal death and hypoxic-ischemic injury was shown on brain MRI with basal nuclei, cortical, and subcortical white matter lesions extending beyond the watershed areas in infants surviving beyond the neonatal period were more common in the IISE group (P = .014; OR 11.1; 95% CI 1.3-92.6; and P = .034; OR 4.1; 95% CI 1.1-14.9, respectively). Multivariate analysis identified IISE (P = .023; OR 12.2; 95% CI 1.4-105.8) to be independently associated with neonatal death. CONCLUSIONS: IISEs are associated with neonatal death and severe injury as shown in brain MRI, even after hypothermia.

Predicting death despite therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy.

OBJECTIVE: To determine precooling attributes possibly predicting death in infants with hypoxic-ischaemic encephalopathy (HIE) despite therapeutic cooling. METHODS: Eighty-five consecutive infants of ≥36 weeks' gestation who received cooling for HIE were reviewed. Logistic regression analysis was performed using precooling clinical and laboratory variables with death related to HIE during the first 9 months of life as the primary outcome. RESULTS: Thirteen (15%) of the 85 infants died during 9-18 months of follow-up despite cooling. 27 of the 85 were asystolic at birth but only 12 had Apgar scores of zero at both 5 and 10 min. Univariate analysis identified Apgar scores of zero at 5 and 10 min, pH <6.7, base deficit >22 mmol/l, and absent spontaneous movement as significantly associated with death during the first 9 months despite cooling. On multivariate analysis, only the Apgar score of zero at 10 min (p<0.001, OR 51.7, 95% CI 9.9 to 269.5) remained significantly associated with the primary outcome of death from HIE. Of the 12 infants who were asystolic at and beyond 10 min of life, nine died from HIE, two had spastic quadriparesis and global delay at 18-24 months, and one had extensive encephalomalacia on brain MRI during follow-up. CONCLUSIONS: Of the selected precooling variables, only the 10 min Apgar score is independently associated with death despite therapeutic cooling in infants with HIE. Infants who remain asystolic at 10 min and beyond are unlikely to survive despite cooling, and the rare survivor is likely to have severe disability.