Critical Care Bulletin - January 2022

 

Mechanical power in pediatric acute respiratory distress syndrome: a PARDIE study

 

by Anoopindar K. Bhalla, Margaret J. Klein, Vicent Modesto I Alapont, Guillaume Emeriaud, Martin C. J. Kneyber, Alberto Medina, Pablo Cruces, Franco Diaz, Muneyuki Takeuchi, Aline B. Maddux, Peter M. Mourani, Cristina Camilo, Benjamin R. White, Nadir Yehya, John Pappachan, Matteo Di Nardo

Critical Care volume 26, Article number: 2 (2022) Published: 03 January 2022

Background

Mechanical power is a composite variable for energy transmitted to the respiratory system over time that may better capture risk for ventilator-induced lung injury than individual ventilator management components. We sought to evaluate if mechanical ventilation management with a high mechanical power is associated with fewer ventilator-free days (VFD) in children with pediatric acute respiratory distress syndrome (PARDS).

Methods

Retrospective analysis of a prospective observational international cohort study.

Results

There were 306 children from 55 pediatric intensive care units included. High mechanical power was associated with younger age, higher oxygenation index, a comorbid condition of bronchopulmonary dysplasia, higher tidal volume, higher delta pressure (peak inspiratory pressure—positive end-expiratory pressure), and higher respiratory rate. Higher mechanical power was associated with fewer 28-day VFD after controlling for confounding variables (per 0.1 J·min−1·Kg−1 Subdistribution Hazard Ratio (SHR) 0.93 (0.87, 0.98), p = 0.013). Higher mechanical power was not associated with higher intensive care unit mortality in multivariable analysis in the entire cohort (per 0.1 J·min−1·Kg−1 OR 1.12 [0.94, 1.32], p = 0.20). But was associated with higher mortality when excluding children who died due to neurologic reasons (per 0.1 J·min−1·Kg−1 OR 1.22 [1.01, 1.46], p = 0.036). In subgroup analyses by age, the association between higher mechanical power and fewer 28-day VFD remained only in children < 2-years-old (per 0.1 J·min−1·Kg−1 SHR 0.89 (0.82, 0.96), p = 0.005). Younger children were managed with lower tidal volume, higher delta pressure, higher respiratory rate, lower positive end-expiratory pressure, and higher PCO2 than older children. No individual ventilator management component mediated the effect of mechanical power on 28-day VFD.

Conclusions

Higher mechanical power is associated with fewer 28-day VFDs in children with PARDS. This association is strongest in children < 2-years-old in whom there are notable differences in mechanical ventilation management. While further validation is needed, these data highlight that ventilator management is associated with outcome in children with PARDS, and there may be subgroups of children with higher potential benefit from strategies to improve lung-protective ventilation.

Take Home Message: Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome. This association is strongest in children <2-years-old in whom there are notable differences in mechanical ventilation management.

SARS-CoV-2 post-infective myocarditis: the tip of COVID-19 immune complications?

link to article: SARS-CoV-2 post-infective myocarditis: the tip of COVID-19 immune complications?

by Pierre Tissières and Jean-Louis Teboul 

Annals of Intensive Care volume 10, Article number: 98 (2020) 23 July 2020

Recent paediatric cases of acute myocarditis following a SARS-CoV-2 infection have raised the possibility of post-infective complications of COVID-19. This short editorial is reviewing current understanding of this new complication, its pathophysiology, diagnosis and therapeutic strategy.

COVID-19 post-infective acute myocarditis, an unrecognized complication?

Recent descriptions of a short outbreak of acute myocarditis in otherwise healthy children raise the hypothesis of additional critical complications of SARS-CoV-2 infection [1,2,3,4,5,6]. Grimaud et al. just reported in Annals of Intensive Care, a series of 20 critically ill children with shock admitted, during a 12-day period, in four pediatric intensive care units in the Paris urban area [1]. This outbreak occurred after 4–6 weeks of strict lockdown. All children had acute myocardial dysfunction requiring cardiovascular support. This study confirmed similar observations from United Kingdom, France and Switzerland [2,3,4,5,6]. In the Grimaud et al. study, 19 out of 20 children had either positive SARS-CoV-2 detection by quantitative PCR or positive serology. The remaining child had a typical SARS-CoV-2 chest tomography scan. Note that all children had abdominal symptoms [1].

Acute heart failure is clearly a dissonant clinical feature of COVID-19 infection in children that is known to be less frequent and less severe than in adults and with very low mortality [7, 8]. Besides its unusual nature, the main characteristic of COVID-19 acute myocarditis is its association with major multisystem inflammatory syndrome, mimicking a well-known pediatric entity, the Kawasaki disease. Currently three case definitions issued from the World Health Organization, the Centers for Disease Control and Prevention and the Royal College of Paediatrics and Child Health related to this emerging inflammatory condition during COVID-19 pandemic exist. Those definitions identify the multisystem inflammatory syndrome in children (MIS-C) or the Pediatric Inflammatory Multisystem Syndrome (PIMS) [4]. All three case definitions include either partial or full criteria for Kawasaki disease and evidence of COVID-19 diagnosis (clinical and/or biological—serology/PCR). Kawasaki disease’s, which affect mostly young children of less than 5 years of age, has typical clinical features including: (1) prolonged fever, (2) conjunctivitis, (3) dry cracked lips, ((4) cervical adenopathy (5) diffuse skin rash involving the trunk and extremities, subsequent desquamation of the tips of the toes and fingers, and 6) edema. In addition to classical manifestations of Kawasaki disease, MIS-C patients, who are much older, display digestive symptoms, shock and myocardial involvement more frequently [9]. Kawasaki disease pathophysiology refers to a systemic arteritis with the most severe complication being coronary aneurysm. Kawasaki disease can follow by a few days or weeks a wide range of infection involving numerous viruses such as EBV, MERS- and SARS-CoV-1, H1N1 influenza and other respiratory illnesses [10]… cont

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis*

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis*

by Abdelaal Ahmed Mahmoud M. Alkhatip, Ahmed; Younis, Mohamed; Jamshidi, Negar; Hussein, Hazem A; Farag, Ehab; Hamza, Mohamed K.; Bahr, Mahmoud H.; Goda Ahmed, Ahmed; Sallam, Amr M.; Mohamed, Hassan; Elayashy, Mohamed; Hosny, Hisham; Yassin, Hany M.; Abdelhaq, Mohamed; Elramely, Mohamed A.; Reeves, David; Mills, Kerry E.; Kamal, Ahmed M.; Zakaria, Dina

Critical Care Medicine: February 2020 - Volume 48 - Issue 2 - p 233-240

Objectives: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation.

 Data Sources: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching.

Study Selection: Studies in mechanically ventilated children that compared early with late tracheostomy were included.

Data Extraction: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark).

Data Synthesis: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis.

Conclusions: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.

Continuous Renal Replacement Therapy in Pediatric Severe Sepsis: A Propensity Score-Matched Prospective Multicenter Cohort Study in the PICU

Continuous Renal Replacement Therapy in Pediatric Severe Sepsis: A Propensity Score-Matched Prospective Multicenter Cohort Study in the PICU

by Miao, Huijie; Shi, Jingyi; Wang, Chunxia; Lu, Guoping; Zhu, Xiaodong; Wang, Ying; Cui, Yun; Zhang, Yucai 

Critical Care Medicine: October 2019 - Volume 47 - Issue 10 - p e806-e813

Objectives: Continuous renal replacement therapy becomes available utilization for pediatric critically ill, but the impact of mortality rate in severe sepsis remains no consistent conclusion. The aim of the study is to assess the effect of continuous renal replacement therapy in pediatric patients with severe sepsis and the impact this therapy may have on their mortality.

Design: Propensity score-matched cohort study analyzing data prospectively collected by the PICUs over 2 years (2016–2018).

Setting: Four PICUs of tertiary university children’s hospital in China. Patients: The consecutive patients with severe sepsis admitted to study PICUs were enrolled from July 2016 to June 2018. Interventions: The patients were divided into the continuous renal replacement therapy group and the conventional (noncontinuous renal replacement therapy) group.

Measurements and Main Results: A total of 324 patients with severe sepsis were enrolled. The hospital mortality rate was 35.6% (64/180) in the continuous renal replacement therapy group and 47.9% (69/144) in the noncontinuous renal replacement therapy group. After propensity score adjustment, the hospital mortality rate was 21.3% (29/136) in the continuous renal replacement therapy group and 32.4% (44/136) in the noncontinuous renal replacement therapy group. In subgroup analysis, the relative risk of dying was 0.447 (95% CI, 0.208–0.961) only in patients complicated by acute respiratory distress syndrome (p = 0.037), but not in patients with shock, acute kidney injury, acute liver dysfunction, encephalopathy, and fluid overload greater than 10%. The mean duration of continuous renal replacement therapy was 45 hours (26–83 hr) with an ultrafiltration rate of 50 mL/kg/hr. The level of interleukin-6 was decreased, and the percent of natural killer cells (%) was improved in the continuous renal replacement therapy group compared with the noncontinuous renal replacement therapy group. Furthermore, continuous renal replacement therapy was an independently significant risk factor for hospital mortality in pediatric patients with severe sepsis, and the interval between continuous renal replacement therapy initiation and PICU admission was an independent risk factor for hospital mortality in patients receiving continuous renal replacement therapy.

Conclusions: Continuous renal replacement therapy with an ultrafiltration rate of 50 mL/kg/hr decreases hospital mortality rate in pediatric severe sepsis, especially in patients with acute respiratory distress syndrome.

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children

by Faustino, Edward Vincent S et al: Critical Care Medicine: May 2019 - Volume 47 - Issue 5 - p 706–714

Objectives: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children.

Design: Nested case-control study.

Setting: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia.

Patients: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness.

Interventions: None.

Measurements and Main Results: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia.

Conclusions: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial*

Evaluation of Effect of Probiotics on Cytokine Levels in Critically Ill Children With Severe Sepsis: A Double-Blind, Placebo-Controlled Trial*

 by Angurana, Suresh K.; Bansal, Arun; Singhi, Sunit; Aggarwal, Ritu; Jayashree, Muralidharan; Salaria, Manila; Mangat, Navdeep K.  

Critical Care Medicine: October 2018 - Volume 46 - Issue 10 - p 1656–1664

Objectives: To evaluate the effect of probiotics on cytokines in children with severe sepsis.

Design: Randomized, double-blind, placebo-controlled trial. Setting: ICU of a tertiary care teaching hospital in North India.

Patients: Children 3 months to 12 years old with severe sepsis. Interventions: Enrolled children were randomized to probiotic (n = 50) and placebo (n = 50) groups. Probiotic group received VSL#3 (Danisco-Dupont USA, Madison, WI) (Lactobacillus paracasei, L. plantarum, L. acidophilus, L. delbrueckii, Bifidobacterium longum, B. infantis, B. breve, Streptococcus salivarius; maltose and silicon dioxide), and placebo group received maltose and silicon dioxide. Dose was 1 sachet twice daily for 7 days. Blood was collected on days 1 and 7 for estimation of interleukin-6, interleukin-12p70, interleukin-17, tumor necrosis factor-α, interleukin-10, and transforming growth factor -β1. “Primary outcome”: Change in cytokine levels in probiotic and placebo groups from day 1 to 7. “Secondary outcomes”: Sequential Organ Failure Assessment score, healthcare-associated infections, ICU stay, and mortality.

Measurements and Main Results: On day 7, probiotic group had significantly lower levels of proinflammatory cytokines (interleukin-6 [80 vs 186 pg/mL, p = 0.001]; interleukin-12p70 [44 vs 79 pg/mL, p = 0.001]; interleukin-17 [217 vs 293 pg/mL, p = 0.01]; and tumor necrosis factor-α [192 vs 348 pg/mL, p = 0.01]) and higher levels of antiinflammatory cytokines (interleukin-10 [320 vs 240 pg/mL, p = 0.02] and transforming growth factor-β1 [311 vs 221 ng/mL, p = 0.01]) than placebo group. From day 1 to 7, probiotic group showed significant decrease in proinflammatory cytokines (interleukin-6 [196–80 pg/mL, p = 0.001]; interleukin-12p70 [71–44 pg/mL, p = 0.01]; interleukin-17 [258–217 pg/mL, p = 0.01]; and tumor necrosis factor-α [347–192 pg/mL, p = 0.001]) and increase in antiinflammatory cytokines (interleukin-10 [198–320 pg/mL, p = 0.001] and transforming growth factor-β1 [216–311 ng/mL, p = 0.001]) as compared to placebo group. Sequential Organ Failure Assessment score on day 7 was significantly less in probiotic group (1 vs 3). There was a nonsignificant trend toward lower incidence of healthcare-associated infections (14% vs 20%) and duration of ICU stay (6.5 vs 9 d) in probiotic group. Mortality was similar in two groups.

Conclusions: Probiotics supplementation for 7 days resulted in significant decrease in proinflammatory and increase in antiinflammatory cytokines in children with severe sepsis.

Benzodiazepines and Development of Delirium in Critically Ill Children: Estimating the Causal Effect*

Benzodiazepines and Development of Delirium in Critically Ill Children: Estimating the Causal Effect*

by Mody, Kalgi; Kaur, Savneet; Mauer, Elizabeth A.; Gerber, Linda M.; Greenwald, Bruce M.; Silver, Gabrielle; Traube, Chani  

Critical Care Medicine: September 2018 - Volume 46 - Issue 9 - p 1486–1491

Objectives: Benzodiazepine use may be associated with delirium in critically ill children. However, benzodiazepines remain the first-line sedative choice in PICUs. Objectives were to determine the temporal relationship between administration of benzodiazepines and delirium development, control for time-varying covariates such as mechanical ventilation and opiates, and evaluate the association between dosage of benzodiazepines and subsequent delirium.

Design: Retrospective observational study. Setting: Academic tertiary care PICU. Patients: All consecutive admissions from January 2015 to June 2015. Interventions: Retrospective assessment of benzodiazepine exposure in a population that had been prospectively screened for delirium.

Measurements and Main Results: All subjects were prospectively screened for delirium throughout their stay, using the Cornell Assessment for Pediatric Delirium, with daily cognitive status assigned as follows: delirium, coma, or normal. Multivariable mixed effects modeling determined predictors of delirium overall, followed by subgroup analysis to assess effect of benzodiazepines on subsequent development of delirium. Marginal structural modeling was used to create a pseudorandomized sample and control for time-dependent variables, obtaining an unbiased estimate of the relationship between benzodiazepines and next day delirium. The cumulative daily dosage of benzodiazepines was calculated to test for a dose-response relationship. Benzodiazepines were strongly associated with transition from normal cognitive status to delirium, more than quadrupling delirium rates (odds ratio, 4.4; CI, 1.7–11.1; p < 0.002). Marginal structural modeling demonstrated odds ratio 3.3 (CI, 1.4–7.8), after controlling for time-dependent confounding of cognitive status, mechanical ventilation, and opiates. With every one log increase in benzodiazepine dosage administered, there was a 43% increase in risk for delirium development.

Conclusions: Benzodiazepines are an independent and modifiable risk factor for development of delirium in critically ill children, even after carefully controlling for time-dependent covariates, with a dose-response effect. This temporal relationship suggests causality between benzodiazepine exposure and pediatric delirium and supports limiting the use of benzodiazepines in critically ill children.

Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial

Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial

Penk, J et al

Critical Care Medicine: January 2018 - Volume 46 - Issue 1 - p 123–129

Objectives: Compare continuous infusions of morphine and midazolam in addition to intermittent doses with an intermittent only strategy for pain and sedation after pediatric cardiac surgery. Design: Randomized controlled trial. Setting: Advocate Children’s Hospital, Oak Lawn, IL. Patients: Sixty patients 3 months to 4 years old with early extubation after pediatric cardiac surgery. Interventions: Patients received a continuous infusion of morphine and midazolam or placebo for 24 hours. Both groups received intermittent morphine and midazolam doses as needed. Measurements and Main Results: Gender, age, bypass time, and surgical complexity were not different between groups. Scheduled ketorolac and acetaminophen were used in both groups and were not associated with adverse events. The mean, median, and maximum Faces, Legs, Activity, Cry, And Consolability score were not different between groups. There was no significant difference in number of intermittent doses received between groups. The total morphine dose was higher in the continuous/intermittent group (0.90 vs 0.23 mg/kg; p < 0.01). The total midazolam dose was also higher in the continuous/intermittent group (0.90 vs 0.18 mg/kg; p < 0.01). The hospital length of stay was longer in the continuous/intermittent group (8.4 vs 4.9 d; p = 0.04). Conclusions: Pain was not better controlled with the addition of continuous infusions of morphine and midazolam when compared with intermittent dosing only. Use of continuous infusions resulted in a significantly higher total dosage of these medications and a longer length of stay.

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

Davis, A et al

Critical Care Medicine: June 2017 - Volume 45 - Issue 6 - p 1061–1093

Objectives: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock.” 
Design: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006–2014). The PubMed/Medline/Embase literature (2006–14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. 
Measurements and Main Results: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. 
Conclusions: The major new recommendation in the 2014 update is consideration of institution—specific use of 1) a “recognition bundle” containing a trigger tool for rapid identification of patients with septic shock, 2) a “resuscitation and stabilization bundle” to help adherence to best practice principles, and 3) a “performance bundle” to identify and overcome perceived barriers to the pursuit of best practice principles.

Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium

Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium

Traube, C et al

Critical Care Medicine:  May 2017 - Volume 45 - Issue 5 - p 891–898

Objectives: Delirium occurs frequently in adults and is an independent predictor of mortality. However, the epidemiology and outcomes of pediatric delirium are not well-characterized. The primary objectives of this study were to describe the frequency of delirium in critically ill children, its duration, associated risk factors, and effect on in-hospital outcomes, including mortality. Secondary objectives included determination of delirium subtype, and effect of delirium on duration of mechanical ventilation, and length of hospital stay. 
Design: Prospective, longitudinal cohort study. Setting: Urban academic tertiary care PICU. Patients: All consecutive admissions from September 2014 through August 2015. Interventions: Children were screened for delirium twice daily throughout their ICU stay. Measurements and Main Results: Of 1,547 consecutive patients, delirium was diagnosed in 267 (17%) and lasted a median of 2 days (interquartile range, 1–5). Seventy-eight percent of children with delirium developed it within the first 3 PICU days. Most cases of delirium were of the hypoactive (46%) and mixed (45%) subtypes; only 8% of delirium episodes were characterized as hyperactive delirium. In multivariable analysis, independent predictors of delirium included age less than or equal to 2 years old, developmental delay, severity of illness, prior coma, mechanical ventilation, and receipt of benzodiazepines and anticholinergics. PICU length of stay was increased in children with delirium (adjusted relative length of stay, 2.3; CI = 2.1–2.5; p < 0.001), as was duration of mechanical ventilation (median, 4 vs 1 d; p < 0.001). Delirium was a strong and independent predictor of mortality (adjusted odds ratio, 4.39; CI = 1.96–9.99; p < 0.001). 
Conclusions: Delirium occurs frequently in critically ill children and is independently associated with mortality. Some in-hospital risk factors for delirium development are modifiable. Interventional studies are needed to determine best practices to limit delirium exposure in at-risk children.