Surgical Critical Care Articles of Interest

Introduction

The APSA Surgical Critical Care Committee has identified the following articles to help identify best practice and appropriate standards for clinical management of pediatric surgical disease.

Articles

Evaluation of Bivalirudin As an Alternative to Heparin for Systemic Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation [1], Hamzah et al Pediatr Crit Care Med 2020 Sept; 21(9): 827-834.

Heparin is the universal anticoagulant for patients supported on extracorporeal life support. Heparin has some advantages but also has inherent limitations. These limitations include that heparin requires the cofactor antithrombin III for efficacy, causes platelet activation and dysfunction, inhibits free thrombin only and does not affect clot bound thrombin. In addition, heparin is highly antigenic and may trigger an immune-mediated response, HIT. Bivalirudin binds directly to thrombin (no need for antithrombin III) and inhibits both free-and clot-bound thrombin. Bivalirudin is being used by more ECMO centers for anticoagulation.
The study demonstrates that both heparin and bivalirudin systemic anticoagulation results in similar recovery and ECMO decannulation results. But the study demonstrates several advantages to bivalirudin anticoagulation. These include shorter time to reach therapeutic anticoagulation levels, fewer bleeding events and fewer blood product transfusions. They also demonstrated no difference in thrombotic events between both heparin and bivalirudin. Bivalirudin is known to be more expensive than heparin but when reviewing the comprehensive cost analysis of the medication, blood draws, transfusions and all related costs, bivalirudin anticoagulation therapy is significantly less than heparin. Bivalirudin is a safe and potentially superior alternative to heparin anticoagulation therapy in pediatric ECMO.

Lung ultrasound completely replaced chest X-ray for diagnosing neonatal lung diseases: a 3-year clinical practice report from a neonatal intensive care unit in China [2], Gao et al J Matern Fetal Neonatal Med 2020 Oct;1–9.

The current use of lung ultrasound to diagnosis of neonatal lung disease is becoming more common. Lung ultrasound has been shown to have higher accuracy and reliability than traditional chest radiograph (CXR) in diagnosing neonatal lung disease.

This study demonstrates that lung ultrasound could completely replace CXR for the diagnosis and differential diagnosis of neonatal lung disease. This single institution completely replaced CXRs in their neonatal intensive care unit with lung ultrasound and reported their three-year clinical practice experience. In the study, the authors demonstrated that CXRs often lead to misdiagnosis (greater than 20%) and missed diagnosis (greater than five percent). The authors also note that up to 36% of bronchopulmonary dysplasia cases diagnosed by traditional criteria are incorrect and lung ultrasound more accurately diagnoses the presence of other lung pathological changes. These include atelectasis, pneumonia, severe pulmonary edema and pulmonary edema with focal lung consolidation. With the improved accuracy of neonatal lung disease, their NICU was able more accurately treat the neonates and thereby minimize or completely resolve their oxygen needs. The authors report no bronchopulmonary dysplasia in 931 preterm infants treated in their NICU. Lung ultrasound should be considered in our management of neonates and has the potential to decrease radiation exposure while improving our diagnosis of neonatal lung diseases.

Dexmedetomidine Sedation in Mechanically Ventilated Critically Ill Children: A Pilot Randomized Controlled Trial [3], Erickson et al Pediatr Crit Care Med 2020 Sept; 21(9): e731-e739.

Optimal sedation is an integral component in treating critically ill children and provides anxiolysis, amnesia and facilitates mechanical ventilation. However, there is no universally accepted approach (lack of quality evidence) to the sedation of mechanically ventilated children. Over sedation may result in prolonged mechanical ventilation, delirium and drug tolerance and withdrawal; while under sedation may lead to loss or displacement of intravenous access and drains, unplanned extubation and emotional distress. Midazolam is still widely used as a primary sedative in children but has been linked to neurotoxicity, delirium and significant drug withdrawal. Dexmedetomidine, a selective α2-adrenoreceptor agonist, provides sedation, anxiolysis and analgesia and has not been linked to neurotoxicity.

The Baby SPICE Investigators and the Australian and New Zealand Intensive Care Society Paediatric Study Group (ANZICS-PSG) demonstrate that a sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation and reduced midazolam requirements. The dexmetomidine group achieved the goal of light sedation quicker in the first 24 hours and maintained that goal over the first 48 hours significantly more often than usual care arm. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm. There were more episodes of hypotension and bradycardia with dexmedetomidine but no difference in vasopressor requirements. In light of growing concerns with long term effects of our usual sedation practices this study demonstrates the safety of the alternative sedation strategies with dexmedetomidine.

Bacterial and Fungal Etiology of Sepsis in Children in the United States: Reconsidering Empiric Therapy [4], Prout et al Crit Care Med 2019 Nov 27

Bleeding Assessment Scale in Critically Ill Children (BASIC): Physician-Driven Diagnostic Criteria for Bleeding Severity [5], Nellis et al Crit Care Med 2019 Dec;47(12)1766-1772

Effect of Gastric Residual Evaluation on Enteral Intake in Extremely Preterm Infants: A Randomized Clinical Trial [6], Parker et al JAMA Pediatr 2019 Jun 1;173(6):534-543.

This was a single center randomized clinical trial comparing the omission of gastric residual evaluation with prefeed gastric residual evaluation. The authors found that among extremely preterm infants, the omission of gastric residual evaluation increased the delivery of enteral nutrition as well as improved weight gain, especially at week five and six after birth and led to earlier hospital discharge. When controlled for gestational age, infants in the no residual group were discharged on average eight days earlier. In addition, the no residual group was not found to have an increased incidence of necrotizing enterocolitis or ventilator associated pneumonia.

gastric residuals
Descriptive text is not available for this image

Visual abstract courtesy of David Darcy

Mortality of Critically Ill Children Requiring Continuous Renal Replacement Therapy: Effect of Fluid Overload, Underlying Disease, and Timing of Initiation [7], Cortina et al Pediatr Crit Care Med 2019 Apr;20(4):314-322.

Extracorporeal Cardiopulmonary Resuscitation: One-Year Survival and Neurobehavioral Outcome Among Infants and Children With In-Hospital Cardiac Arrest [8], Meert et al Crit Care Med 2019 Mar;47(3):393-402.

Neurologic Outcomes After Extracorporeal Membrane Oxygenation: A Systematic Review [9], Boyle et al Pediatr Crit Care Med 2018 Aug;19(8):760-766.

A wide range of disabilities were identified on a systematic review of neurologic outcomes after extracorporeal life support in children including behavior problems (16 to 46%) and severe motor impairment (12%). The quality of life, evaluated at school age or adolescence, was more than one standard deviation below the population mean at their respective groups. The study highlights a need for consistent, long term follow-up in pediatric patients after ECMO and counseling of expectations for parents and families.

neurologic outcome after ECMO
Descriptive text is not available for this image

Visual abstract courtesy of Francois Luks

The Rate of PD Catheter Complication does not Increase with Simultaneous Abdominal Surgery [10], Miyata J Pediatr Surg 2018 Aug;53(8):1499-1503.

Cardiac Index Changes With Fluid Bolus Therapy in Children With Sepsis – An Observational Study [11], Long Pediatr Crit Care Med. 2018 Jun;19(6):513-518.

Short-term Neurodevelopmental Outcome in Congenital Diaphragmatic Hernia: The Impact of Extracorporeal Membrane Oxygenation and Timing of Repair [12], Danzer et al Pediatr Crit Care Med 2018 Jan;19(1):64-74.

This retrospective study assessed neurodevelopmental outcomes at a median age of 22 months. The authors found that the need for extracorporeal membrane oxygenation in patients with congenital diaphragmatic hernias is associated with worse neurocognitive and neuromotor outcomes. They also found that the need for congenital diaphragmatic hernia repair while on extracorporeal support is associated with worse cognitive and motor scores. Twenty percent of congenital diaphragmatic hernia survivors repaired on extracorporeal membrane oxygenation (ECMO) support scored within the average range for all composite domains. Based on this analysis it may be that children who can be successfully weaned off ECMO support and undergo a delayed CDH repair have improved outcomes with decreased mortality and neurodevelopmental sequelae.

Initiating Nutritional Support Before 72 Hours is Associated with Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia [13], Meinert et al. Pediatr Crit Care Med 2018 Apr;19(4):345-352.

Renal Replacement Therapy in the Critically Ill Child [14], Westrope et al Pediatr Crit Care Med 2018 Mar;19(3):210-217.

Vascular Access in Critically Ill Pediatric Patients With Obesity [15], Halvorson et al Pediatr Crit Care Med 2018 Jan;19(1):1-8.

Are children with obesity more likely to require vascular device insertion and do they develop more complications associated with that access?
120,272 patients were admitted to the pediatric intensive care unit (PICU) in 94 United States hospitals. 73,964 vascular devices were placed in 45,409 patients (38% of total cohort). Placement of vascular access devices decreased with increasing body mass index (BMI). Overall, there were more device complications associated with class 3 obesity and more mechanical and bleeding complications associated with all classes of obesity.
Vascular access devices may be more difficult to place in obese patients and may be one of the contributing factors to the reduced number of devices. Patients with obesity, especially those in increased BMI categories, although less likely to have a more permanent device placed, were more likely to keep those devices in place upon discharge. This may be due to concerns about being able to regain access should the patient return to the PICU. Obese patients may also have had increased complications because their total device time was also longer.

Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation [16], Delaplain et al J Pediatr Surg. 2017 Dec;52(12):2018-2025.

Do infants with CDH requiring ECMO with either a birth weight (BW) of less than 2 kg or a gestational age at birth of less than 34 weeks have an increased risk of death?
In the ELSO registry between 1988 and 2015, 7564 neonates with CDH were treated with ECMO, 100 of which had a BW less than 2 kg. Patients with birth weight less than 2 kg had an increased risk of death but did not have an increased risk of neurologic complications. However, those patients with gestational age at birth of less than 34 weeks did have an increased risk of neurologic complications.
Birth weight of less than 2 kg and a gestational age of less than 34 weeks are typically listed as cutoffs for use of ECMO in the management of CDH. This study suggests that given improved strategies for anticoagulation and ventilator management, ECMO may be safe to offer in this population, however it may lead to increased neurologic complications. Additionally, long term neurodevelopmental outcomes were not evaluated.

Dexmedetomidine for Sedation During Noninvasive Ventilation in Pediatric Patients [17], Venkatraman et al Pediatr Crit Care Med 2017 Sep;18(9):831-837.

Over the past 10 years the use of dexmedetomidine has become progressively more widespread. In many centers it is now routinely used as the first line agent for sedation in the pediatric intensive care unit. In addition, because of its safety profile when it comes to hypotension and respiratory depression, many have begun to use dexmedetomidine with weaning protocols, postextubation and with noninvasive ventilation. However, very little data has been collected and published in children for these uses.

This study is a single center retrospective report collecting data on the use of dexmedetomidine, specifically in children while receiving noninvasive ventilation. The results demonstrate a reasonable safety profile and to some extent validates a practice that is an evolving trend in many institutions.

The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: Executive Summary [18], Davis et al Pediatr Crit Care Med 2017; Sep;18(9):884-890.

Guidelines for the care of septic shock in pediatrics were developed in 2002, updated in 2007 and have become standards throughout the country. The American College of Critical Care Medicine has now finalized the next update and provided an executive summary of the key points of these guidelines. The new recommendations advocate hospital specific guidelines that address three key issues: recognition of sepsis, resuscitation and stabilization and performance. Practical examples of potential bundles to address each of these issues are provided in the summary.

Functional Outcome After Intracranial Pressure Monitoring for Children With Severe Traumatic Brain Injury [19], Bennett et al JAMA Pediatr 2017 Oct 1;171(10):965-971.

The widespread use of intracranial pressure (ICP) monitors for severe traumatic brain injury in children has been a passionately debated topic over the past several years with conflicting expert opinion and low likelihood of a true randomized controlled trial to settle the questions. This study collected data from two large national databases and used sophisticated statistical analysis on cohorts of patients to look at outcome measures with and without the use of ICP monitoring. They concluded there was no association between ICP monitor use and functional survival.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition [20], Mehta et al Pediatr Crit Care Med 2017 Jul;18(7):675-715.

Neurodevelopmental outcomes in infants undergoing general anesthesia [21], Nestor et al J Pediatr Surg. 2017 Jun;52(6):895-900.

Centrifugal pumps and hemolysis in pediatric extracorporeal membrane oxygenation (ECMO) patients: An analysis of Extracorporeal Life Support Organization (ELSO) registry data [22], O’Brien et al
J Pediatr Surg 2017 Jun;52(6):975-978.

Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants [23], Slaughter et al JAMA Pediatr 2017 Mar 6;171(3):e164354.

Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors [24], Unegbu et al Pediatrics 2017 Mar;139(3).

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children [25], Moler et al N Engl J Med 2017 Jan 26;376(4):318-329.

Effect of Inhaled Nitric Oxide on Outcomes in Children with Acute Lung Injury: Propensity Matched Analysis From a Linked Database [26], Gupta et al Crit Care Med 2016 Oct; 44(10): 1901-9.

Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults [27], Kaddourah et al N Engl J Med. 2017 Jan;376(1):11-20.

New Medical and Surgical Insights into Neonatal Necrotizing Enterocolitis: A Review [28], Frost et al JAMA Pediatr 2017 Jan; 171(1): 83-88.

Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome [29], Ward et al Crit Care Med 2016 Nov;44(11):2052-2059.

Prediction of Catheter-Associated Thrombosis in Critically Ill Children [30], Marquez et al Pediatr Crit Care Med 2016 Sep 22.

Persistent Challenges in Pediatric Pulmonary Hypertension [31], Hopper et al Chest 2016 Jul;150(1):226-36.

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial [32], Wu et al Pediatrics. 2016 Jun;137(6).

Evaluation of the “Early” Use of Albumin in Children with Extensive Burns: A Randomized Controlled Trial [33], Müller Dittrich et al Pediatr Crit Care Med 2016 Jun;17(6):e280-6.

Recommendations for the Use of Inhaled Nitric Oxide Therapy in Premature Newborns with Severe Pulmonary Hypertension [34], Kinsella et al J Pediatr 2016 Mar;170:312-4.

New Modes in Non-invasive Ventilation [35], Rabec C, et al Paediatr Respir Rev 2016 Mar;18:73-84.

Obesity and Mortality Risk in Critically Ill Children [36], Ross et al Pediatrics 2016 Mar;137(3):1-8.

Mortality Among Injured Children Treated at Different Trauma Center Types [37], Sathya et al JAMA Surg 2015 Sep;150(9):874-81.

Maintenance Intravenous Fluids in Acutely Ill Patients [38], Moritz et al N Engl J Med. 2016 Jan 21;374(3):290-1.

Ventilatory support in children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference [39], Rimensberger et al Pediatr Crit Care Med 2015 Jun;16(5 Suppl 1):S51-60.

References

  1. Hamzah M, Jarden AM, Ezetendu C, et al. Evaluation of Bivalirudin As an Alternative to Heparin for Systemic Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2020;21(9):827-834.  [PMID:32404633]
  2. Gao YQ, Qiu RX, Liu J, et al. Lung ultrasound completely replaced chest X-ray for diagnosing neonatal lung diseases: a 3-year clinical practice report from a neonatal intensive care unit in China. J Matern Fetal Neonatal Med. 2020.  [PMID:33032479]
  3. Erickson SJ, Millar J, Anderson BJ, et al. Dexmedetomidine Sedation in Mechanically Ventilated Critically Ill Children: A Pilot Randomized Controlled Trial. Pediatr Crit Care Med. 2020;21(9):e731-e739.  [PMID:32740192]
  4. Prout AJ, Talisa VB, Carcillo JA, et al. Bacterial and Fungal Etiology of Sepsis in Children in the United States: Reconsidering Empiric Therapy. Crit Care Med. 2020;48(3):e192-e199.  [PMID:31789702]
  5. Nellis ME, Tucci M, Lacroix J, et al. Bleeding Assessment Scale in Critically Ill Children (BASIC): Physician-Driven Diagnostic Criteria for Bleeding Severity. Crit Care Med. 2019;47(12):1766-1772.  [PMID:31567407]
  6. Parker LA, Weaver M, Murgas Torrazza RJ, et al. Effect of Gastric Residual Evaluation on Enteral Intake in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2019;173(6):534-543.  [PMID:31034045]
  7. Cortina G, McRae R, Hoq M, et al. Mortality of Critically Ill Children Requiring Continuous Renal Replacement Therapy: Effect of Fluid Overload, Underlying Disease, and Timing of Initiation. Pediatr Crit Care Med. 2019;20(4):314-322.  [PMID:30431556]
  8. Meert KL, Guerguerian AM, Barbaro R, et al. Extracorporeal Cardiopulmonary Resuscitation: One-Year Survival and Neurobehavioral Outcome Among Infants and Children With In-Hospital Cardiac Arrest. Crit Care Med. 2019;47(3):393-402.  [PMID:30422861]
  9. Boyle K, Felling R, Yiu A, et al. Neurologic Outcomes After Extracorporeal Membrane Oxygenation: A Systematic Review. Pediatr Crit Care Med. 2018;19(8):760-766.  [PMID:29894448]
  10. Miyata S, Golden J, Lebedevskiy O, et al. The rate of PD catheter complication does not increase with simultaneous abdominal surgery. J Pediatr Surg. 2018;53(8):1499-1503.  [PMID:29249456]
  11. Long E, Babl FE, Oakley E, et al. Cardiac Index Changes With Fluid Bolus Therapy in Children With Sepsis-An Observational Study. Pediatr Crit Care Med. 2018;19(6):513-518.  [PMID:29533353]
  12. Danzer E, Hoffman C, D'Agostino JA, et al. Short-Term Neurodevelopmental Outcome in Congenital Diaphragmatic Hernia: The Impact of Extracorporeal Membrane Oxygenation and Timing of Repair. Pediatr Crit Care Med. 2018;19(1):64-74.  [PMID:29303891]
  13. Meinert E, Bell MJ, Buttram S, et al. Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia. Pediatr Crit Care Med. 2018;19(4):345-352.  [PMID:29370008]
  14. Westrope CA, Fleming S, Kapetanstrataki M, et al. Renal Replacement Therapy in the Critically Ill Child. Pediatr Crit Care Med. 2018;19(3):210-217.  [PMID:29315136]
  15. Halvorson EE, Case D, Skelton JA, et al. Vascular Access in Critically Ill Pediatric Patients With Obesity. Pediatr Crit Care Med. 2018;19(1):1-8.  [PMID:29117059]
  16. Delaplain PT, Zhang L, Chen Y, et al. Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation. J Pediatr Surg. 2017;52(12):2018-2025.  [PMID:28941930]
  17. Venkatraman R, Hungerford JL, Hall MW, et al. Dexmedetomidine for Sedation During Noninvasive Ventilation in Pediatric Patients. Pediatr Crit Care Med. 2017;18(9):831-837.  [PMID:28598946]
  18. Davis AL, Carcillo JA, Aneja RK, et al. The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: Executive Summary. Pediatr Crit Care Med. 2017;18(9):884-890.  [PMID:28723883]
  19. Bennett TD, DeWitt PE, Greene TH, et al. Functional Outcome After Intracranial Pressure Monitoring for Children With Severe Traumatic Brain Injury. JAMA Pediatr. 2017;171(10):965-971.  [PMID:28846763]
  20. Mehta NM, Skillman HE, Irving SY, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Pediatr Crit Care Med. 2017;18(7):675-715.  [PMID:28691958]
  21. Nestor KA, Zeidan M, Boncore E, et al. Neurodevelopmental outcomes in infants undergoing general anesthesia. J Pediatr Surg. 2017;52(6):895-900.  [PMID:28342581]
  22. O'Brien C, Monteagudo J, Schad C, et al. Centrifugal pumps and hemolysis in pediatric extracorporeal membrane oxygenation (ECMO) patients: An analysis of Extracorporeal Life Support Organization (ELSO) registry data. J Pediatr Surg. 2017;52(6):975-978.  [PMID:28359588]
  23. Slaughter JL, Reagan PB, Newman TB, et al. Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants. JAMA Pediatr. 2017;171(3):e164354.  [PMID:28046188]
  24. Unegbu C, Noje C, Coulson JD, et al. Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors. Pediatrics. 2017;139(3).  [PMID:28235796]
  25. Moler FW, Silverstein FS, Holubkov R, et al. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N Engl J Med. 2017;376(4):318-329.  [PMID:28118559]
  26. Gupta P, Richardson T, Hall M, et al. Effect of Inhaled Nitric Oxide on Outcomes in Children With Acute Lung Injury: Propensity Matched Analysis From a Linked Database. Crit Care Med. 2016;44(10):1901-9.  [PMID:27163193]
  27. Kaddourah A, Basu RK, Bagshaw SM, et al. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med. 2017;376(1):11-20.  [PMID:27959707]
  28. Frost BL, Modi BP, Jaksic T, et al. New Medical and Surgical Insights Into Neonatal Necrotizing Enterocolitis: A Review. JAMA Pediatr. 2017;171(1):83-88.  [PMID:27893069]
  29. Ward SL, Gildengorin V, Valentine SL, et al. Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome. Crit Care Med. 2016;44(11):2052-2059.  [PMID:27355525]
  30. Marquez A, Shabanova V, Faustino EV, et al. Prediction of Catheter-Associated Thrombosis in Critically Ill Children. Pediatr Crit Care Med. 2016;17(11):e521-e528.  [PMID:27662566]
  31. Hopper RK, Abman SH, Ivy DD. Persistent Challenges in Pediatric Pulmonary Hypertension. Chest. 2016;150(1):226-36.  [PMID:26836930]
  32. Wu YW, Mathur AM, Chang T, et al. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. Pediatrics. 2016;137(6).  [PMID:27244862]
  33. Müller Dittrich MH, Brunow de Carvalho W, Lopes Lavado E. Evaluation of the "Early" Use of Albumin in Children with Extensive Burns: A Randomized Controlled Trial. Pediatr Crit Care Med. 2016;17(6):e280-6.  [PMID:27077832]
  34. Kinsella JP, Steinhorn RH, Krishnan US, et al. Recommendations for the Use of Inhaled Nitric Oxide Therapy in Premature Newborns with Severe Pulmonary Hypertension. J Pediatr. 2016;170:312-4.  [PMID:26703869]
  35. Rabec C, Emeriaud G, Amadeo A, et al. New modes in non-invasive ventilation. Paediatr Respir Rev. 2016;18:73-84.  [PMID:26688194]
  36. Ross PA, Newth CJ, Leung D, et al. Obesity and Mortality Risk in Critically Ill Children. Pediatrics. 2016;137(3):e20152035.  [PMID:26908670]
  37. Sathya C, Alali AS, Wales PW, et al. Mortality Among Injured Children Treated at Different Trauma Center Types. JAMA Surg. 2015;150(9):874-81.  [PMID:26106848]
  38. Moritz ML, Ayus JC. Maintenance Intravenous Fluids in Acutely Ill Patients. N Engl J Med. 2016;374(3):290-1.  [PMID:26789888]
  39. Rimensberger PC, Cheifetz IM, Pediatric Acute Lung Injury Consensus Conference Group. Ventilatory support in children with pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015;16(5 Suppl 1):S51-60.  [PMID:26035364]