Ketamine Clinical Use on the Pediatric Critically Ill Infant: A Global Bibliometric and Critical Review of Literature

The developing central nervous system is vulnerable to several stimuli, especially psychotropic drugs. Sedation procedures during the developmental period are frequent in pediatric intensive care units (PICUs), in which the use of the sedative agent is still a challenge for the PICU team. Ketamine has been indicated for sedation in critically ill children with hemodynamic and ventilatory instabilities, but the possible neurobehavioral consequences related to this use are still uncertain. Here, we performed a bibliometric analysis with conventional metrics and a critical review of clinical findings to reveal a gap in the literature that deserves further investigation. We revealed that only 56 articles corresponded to the inclusion criteria of the study. The United States of America emerges as the main country within the scope of this review. In addition, professional clinical societies play a key role in the publications of scientific clinical findings through the specialist journals, which encourages the sharing of research work. The co-occurrence of keywords evidenced that the terms “sedation”, “ketamine”, and “pediatric” were the most frequent. Case series and review articles were the most prevalent study design. In the critical evaluation, the scarce studies highlight the need of use and post-use monitoring, which reinforces the importance of additional robust clinical studies to characterize the possible adverse effects resulting from ketamine anesthetic protocol in critically ill children.

[1]  J. López-Herce Cid,et al.  Prospective observational study on the use of continuous intravenous ketamine and propofol infusion for prolonged sedation in critical care. , 2023, Anales de pediatria.

[2]  R. R. Lima,et al.  Global Trends and Future Research Directions for Temporomandibular Disorders and Stem Cells , 2023, Journal of functional biomaterials.

[3]  L. Paranhos,et al.  Dental Caries and Salivary Oxidative Stress: Global Scientific Research Landscape , 2023, Antioxidants.

[4]  A. Pettenazzo,et al.  Is ketamine infusion effective and safe as an adjuvant of sedation in the PICU? Results from the Ketamine Infusion Sedation Study (KISS) , 2022, Pharmacotherapy.

[5]  R. R. Lima,et al.  “K-Powder” Exposure during Adolescence Elicits Psychiatric Disturbances Associated with Oxidative Stress in Female Rats , 2022, Pharmaceuticals.

[6]  P. Martins‐Júnior,et al.  Global research trends on maternal exposure to methylmercury and offspring health outcomes , 2022, Frontiers in Pharmacology.

[7]  Christopher M. Horvat,et al.  Patient-Specific Factors Associated with Dexmedetomidine Dose Requirements in Critically Ill Children , 2022, Journal of Pediatric Intensive Care.

[8]  C. Honey,et al.  Deep brain stimulation as a rescue for pediatric dystonic storm. Case reports and literature review , 2022, Interdisciplinary Neurosurgery.

[9]  Raj Kumar,et al.  Clinical Uses of Ketamine in Children: A Narrative Review , 2022, Cureus.

[10]  Peter N. Johnson,et al.  Efficacy and Safety of Prolonged Magnesium Sulfate Infusions in Children With Refractory Status Asthmaticus , 2022, Frontiers in Pediatrics.

[11]  Peter N. Johnson,et al.  2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility , 2022, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[12]  M. Qorbani,et al.  The effects of nebulized ketamine and intravenous magnesium sulfate on corticosteroid resistant asthma exacerbation; a randomized clinical trial , 2021, Asthma Research and Practice.

[13]  W. Hakmeh,et al.  Resolution of status epilepticus after ketamine administration. , 2021, The American journal of emergency medicine.

[14]  Weng Marc Lim,et al.  How to conduct a bibliometric analysis: An overview and guidelines , 2021 .

[15]  Z. Karakaya,et al.  Emergency application of extracorporeal membrane oxygenation in a pediatric case of sudden airway collapse due to anterior mediastinal mass: A case report and review of literature , 2021, Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES.

[16]  D. Tibboel,et al.  Towards Evidence-Based Weaning: a Mechanism-Based Pharmacometric Model to Characterize Iatrogenic Withdrawal Syndrome in Critically Ill Children , 2021, The AAPS Journal.

[17]  Annette Marinkovic,et al.  Low-Dose Ketamine Infusion as Adjuvant Therapy during an Acute Pain Crisis in Pediatric Patients , 2021, Journal of pain & palliative care pharmacotherapy.

[18]  C. Maia,et al.  Long-lasting neurocognitive disorders: a case report of previously undescribed adverse effects after ketamine sedation and analgesia in a pediatric patient , 2021, Annals of translational medicine.

[19]  A. Amigoni,et al.  Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis. , 2021, The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG.

[20]  R. S. Watson,et al.  Sleep Architecture in Mechanically Ventilated Pediatric ICU Patients Receiving Goal-Directed, Dexmedetomidine- and Opioid-based Sedation , 2020, Journal of Pediatric Intensive Care.

[21]  D. Yıldızdaş,et al.  Sedation and Analgesia Practices in Pediatric Intensive Care Units: A Survey of 27 Centers from Turkey , 2020, Journal of Pediatric Intensive Care.

[22]  Zikai Zhou,et al.  Neonatal exposure to ketamine disrupts developmental synapse unsilencing and predisposes adult mice for stressor-evoked anxiety , 2020, Neuropharmacology.

[23]  Y. Sertdemir,et al.  Effects of Sedation and/or Sedation/Analgesic Drugs Administered during Central Venous Catheterization on the Level of End-tidal Carbon Dioxide Measured by Nasal Cannula in Our PICU , 2020, Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine.

[24]  Peter N. Johnson,et al.  Extended Duration Ketamine Infusions in Critically Ill Children: A Case Report and Review of the Literature , 2020, Journal of Pediatric Intensive Care.

[25]  V. Nadkarni,et al.  Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events , 2020, Critical care medicine.

[26]  A. Amigoni,et al.  Efficacy and Safety of Dexmedetomidine for Prolonged Sedation in the PICU: A Prospective Multicenter Study (PROSDEX)* , 2020, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[27]  Helena Blažun Vošner,et al.  Application of bibliometrics in medicine: a historical bibliometrics analysis. , 2020, Health information and libraries journal.

[28]  Peter H. Chang,et al.  Enhanced Recovery and Early Extubation after Pediatric Cardiac Surgery Using Single-Dose Intravenous Methadone , 2020, Annals of cardiac anaesthesia.

[29]  De-xiang Liu,et al.  Chronic sub-anesthetic ketamine induces permanent hypolocomotion and impairment of hippocampus in adolescent cynomolgus monkeys , 2019, Neuroscience Letters.

[30]  Sojin Park,et al.  Effects of continuous ketamine infusion on hemodynamics and mortality in critically ill children , 2019, PloS one.

[31]  K. A. Trujillo,et al.  Long-lasting effects of repeated ketamine administration in adult and adolescent rats , 2019, Behavioural Brain Research.

[32]  De-xiang Liu,et al.  The effects of sub-anesthetic ketamine plus ethanol on behaviors and apoptosis in the prefrontal cortex and hippocampus of adolescent rats , 2019, Pharmacology Biochemistry and Behavior.

[33]  M. J. Solana,et al.  Sedative and Analgesic Drug Rotation Protocol in Critically Ill Children With Prolonged Sedation. Evaluation of Implementation and Efficacy to Reduce Withdrawal Syndrome. , 2019, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[34]  R. Prediger,et al.  “Special K” Drug on Adolescent Rats: Oxidative Damage and Neurobehavioral Impairments , 2019, Oxidative medicine and cellular longevity.

[35]  D. Yew,et al.  Effects of Perinatal Exposure to Ketamine on the Developing Brain , 2019, Front. Neurosci..

[36]  Christine M. Groth,et al.  Current practices and safety of medication use during rapid sequence intubation , 2018, Journal of critical care.

[37]  A. Bos,et al.  Pharmacokinetics of S‐ketamine during prolonged sedation at the pediatric intensive care unit , 2017, Paediatric anaesthesia.

[38]  T. Palmieri,et al.  Considerations for pediatric burn sedation and analgesia , 2017, Burns & Trauma.

[39]  Nader Ale Ebrahim,et al.  A bibliometric approach to tracking big data research trends , 2017, Journal of Big Data.

[40]  D. Tibboel,et al.  Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities , 2017, Child's Nervous System.

[41]  Kelli L. Crowley,et al.  Case Study of High-Dose Ketamine for Treatment of Complex Regional Pain Syndrome in the Pediatric Intensive Care Unit. , 2017, Critical care nursing clinics of North America.

[42]  Kyle J. Rehder Adjunct Therapies for Refractory Status Asthmaticus in Children , 2017, Respiratory Care.

[43]  T. Patterson,et al.  Relationship between ketamine-induced developmental neurotoxicity and NMDA receptor-mediated calcium influx in neural stem cell-derived neurons. , 2017, Neurotoxicology.

[44]  M. Hofbeck,et al.  Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study , 2017, Pediatric Drugs.

[45]  F. Vigevano,et al.  From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus. , 2016, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[46]  D. Nelson,et al.  Delayed sequence intubation with ketamine in 2 critically ill children. , 2016, The American journal of emergency medicine.

[47]  D. Ma,et al.  Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat , 2016, Scientific Reports.

[48]  D. Tibboel,et al.  Clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children: an ESPNIC position statement for healthcare professionals , 2016, Intensive Care Medicine.

[49]  M. Berkovitch,et al.  Propofol Use in Israeli PICUs* , 2016, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[50]  Peter N. Johnson,et al.  Ketamine Continuous Infusions in Critically Ill Infants and Children , 2016, The Annals of pharmacotherapy.

[51]  U. Celik,et al.  Cerebral salt wasting in pediatric critical care; not just a neurosurgical disorder anymore. , 2015, Neuro endocrinology letters.

[52]  V. Nadkarni,et al.  Current Medication Practice and Tracheal Intubation Safety Outcomes From a Prospective Multicenter Observational Cohort Study* , 2015, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[53]  Kiran B. Hebbar,et al.  Pediatric Critical Care Physician-Administered Procedural Sedation Using Propofol: A Report From the Pediatric Sedation Research Consortium Database* , 2015, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[54]  K. Engelhard,et al.  General anaesthetics and the developing brain: an overview , 2014, Anaesthesia.

[55]  Kyle J. Rehder,et al.  A review of the use of adjunctive therapies in severe acute asthma exacerbation in critically ill children , 2014, Expert review of respiratory medicine.

[56]  V. Nadkarni,et al.  Site-Level Variance for Adverse Tracheal Intubation–Associated Events Across 15 North American PICUs: A Report From the National Emergency Airway Registry for Children* , 2014, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[57]  M. Clifford,et al.  How does the introduction of a pain and sedation management guideline in the paediatric intensive care impact on clinical practice? A comparison of audits pre and post guideline introduction. , 2013, Australian critical care : official journal of the Confederation of Australian Critical Care Nurses.

[58]  P. Pandharipande,et al.  Pediatric Critical Care Perceptions on Analgesia, Sedation, and Delirium , 2013, Seminars in Respiratory and Critical Care Medicine.

[59]  Chris B Del Mar,et al.  Does Bradford's Law of Scattering predict the size of the literature in Cochrane Reviews? , 2012, Journal of the Medical Library Association : JMLA.

[60]  Z. Bosnjak,et al.  Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway. , 2012, Current drug safety.

[61]  J. López‐Herce,et al.  [Sedative, analgesic and muscle relaxant management in Spanish paediatric intensive care units]. , 2011, Anales de pediatria.

[62]  S. Haynes,et al.  General Anesthesia for Children With Severe Heart Failure , 2011, Pediatric Cardiology.

[63]  M. Weigand,et al.  Analgesia and sedation for painful interventions in children and adolescents. , 2010, Deutsches Arzteblatt international.

[64]  A. Loepke Developmental neurotoxicity of sedatives and anesthetics: A concern for neonatal and pediatric critical care medicine?* , 2010, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[65]  J. Guilburd,et al.  Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. , 2009, Journal of neurosurgery. Pediatrics.

[66]  A. Bhutta Ketamine: a controversial drug for neonates. , 2007, Seminars in perinatology.

[67]  W. Brunow de Carvalho,et al.  Procedural sedation for insertion of central venous catheters in children: comparison of midazolam/fentanyl with midazolam/ketamine , 2007, Paediatric anaesthesia.

[68]  W. Fendler,et al.  Hyperkalemia and cardiac arrest following succinylcholine administration in a 16-year-old boy with acute nonlymphoblastic leukemia and sepsis , 2007, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[69]  Fulton Crews,et al.  Adolescent cortical development: A critical period of vulnerability for addiction , 2007, Pharmacology Biochemistry and Behavior.

[70]  N. Morton,et al.  Sedation Analgesia and Neuromuscular Blockade Working Group Consensus guidelines on sedation and analgesia in critically ill children , 2006 .

[71]  Miou Zhou,et al.  Developmental Changes in NMDA Neurotoxicity Reflect Developmental Changes in Subunit Composition of NMDA Receptors , 2006, The Journal of Neuroscience.

[72]  Barry Bozeman,et al.  The Impact of Research Collaboration on Scientific Productivity , 2005 .

[73]  M. Cunliffe,et al.  Managing sedation withdrawal in children who undergo prolonged PICU admission after discharge to the ward , 2004, Paediatric anaesthesia.

[74]  A. Vardi,et al.  Is propofol safe for procedural sedation in children? A prospective evaluation of propofol versus ketamine in pediatric critical care* , 2002, Critical care medicine.

[75]  S. Rothrock,et al.  Ketamine sedation for pediatric critical care procedures , 2001, Pediatric emergency care.

[76]  F. Crews,et al.  Binge ethanol consumption causes differential brain damage in young adolescent rats compared with adult rats. , 2000, Alcoholism, clinical and experimental research.

[77]  Joseph D. Tobias Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit , 2000, Critical care medicine.

[78]  L. Lowrie,et al.  The pediatric sedation unit: a mechanism for pediatric sedation. , 1998, Pediatrics.

[79]  M. Sagy,et al.  Continuous infusion of ketamine in mechanically ventilated children with refractory bronchospasm , 1996, Intensive Care Medicine.

[80]  J. Tobias,et al.  Pain management and sedation in the pediatric intensive care unit. , 1994, Pediatric clinics of North America.

[81]  D. Hatch,et al.  Mechanisms of the relaxant action of ketamine on isolated porcine trachealis muscle. , 1993, British journal of anaesthesia.

[82]  R. Wetzel,et al.  Ketamine by continuous infusion for sedation in the pediatric intensive care unit. , 1990, Critical care medicine.

[83]  B. Brookes,et al.  Bradford's Law and the Bibliography of Science , 1969, Nature.

[84]  S. Kudchadkar,et al.  Pain and Sedation Management: 2018 Update for the Rogers’ Textbook of Pediatric Intensive Care , 2019, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[85]  C. Guerri,et al.  Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. , 2010, Alcohol.

[86]  Dinçer Yldzdaş,et al.  The value of capnography during sedation or sedation/analgesia in pediatric minor procedures. , 2004, Pediatric emergency care.