The interest in pediatric anesthesia research has increased dramatically over the past 15–20 years especially on matters beyond anesthetic neurotoxicity [1–3]. This pediatric issue of Current Opinion in Anaesthesiology presents a collection of nine very interesting review articles on some of the current and hottest topics in pediatric anesthesia emphasizing these facts.
The need for properly conducted pharmacological studies in pediatric anesthesia has been recognized for many years. In the first review article, Afshari (pp. 327–333) describes and analyzes the current evidence for clonidine in children and includes a meta-analysis for its use in the prevention of emergence agitation. He concludes that clonidine is a well tolerated and beneficial drug with moderate to high-quality evidence supporting its use in pediatric anesthesia. He emphasizes that for some indications and populations (e.g. children < 12 months of age and those with hemodynamic instability), there is an urgent need for high-quality trials.
In the second review article, Schmidt et al. (pp. 334–342) describe the use of another α2 agonist – dexmedetomidine – in perioperative pediatric cardiac surgical setting. They conclude that because of its mix of favorable beneficial physiologic actions and limited adverse effect profile, the use of dexmedetomidine is well established in perioperative pediatric cardiac surgery. Evidence from high-quality randomized controlled trials on the effects of dexmedetomidine on meaningful patient outcomes (e.g. cardioprotection, neuroprotection or renoprotection), on the other hand, is still scarce.
In the third review article, Goobie and Faraoni (pp. 343–352) provide an update on the pharmacology of tranexamic acid (TXA) and its use in reducing bleeding in major pediatric surgeries (e.g. spinal fusions and craniofacial surgery). They conclude that prophylactic or therapeutic TXA administration is a safe and an effective strategy to reduce bleeding, decrease allogeneic blood product transfusion and improve pediatric patients’ outcomes. The authors recommend a dosing regimen of 10–30 mg/kg loading dose and 5–10 mg.kg–1.h-1 maintenance rate for pediatric trauma and surgery and highlight that maximal efficacy and minimal side-effects with this dosage regime will have to be determined in larger prospective trials including high-risk groups.
In the fourth review article, Anderson et al. (pp. 353–362) describe the use of pharmacokinetic/pharmacodynamic modeling in pediatric anesthetic research. They conclude that this analytic technique has improved our knowledge regarding variability in drug responses, dosing as well as optimizing sampling protocols for further studies. Although many of the models used for target controlled infusion pumps were developed in adults, translation for pediatric use has followed, including subgroups such as neonates and obese children. Models incorporating influential covariates that better describe a drug's pharmacokinetic/pharmacodynamic improve anesthetic treatments and safety in diverse populations. Their use in developing pediatric clinical studies improves trial conduct, often minimizing the number of individuals required for the study.
In the fifth review article, Marchesini and Disma (pp. 363–369) provide an overview of the recent literature on neuroprotection in relation to the preservation of neuronal structures and/or function against (potential) insults potentially caused by sedatives and/or anesthetics. Neuroprotective strategies include prevention of damage, such as postponing procedure, and counterbalance the damage. Mitigation of neurotoxicity can be obtained through pharmacological protection, reducing cumulative dose or promoting neuroplasticity. As surgery and pain can also interfere with normal neurodevelopment in children, treatment of pain plays a key role in preserving cortical activity and brain development. A variety of drugs have been investigated to preserve and reduce the damage caused by anesthetic agents in animal studies. At present, none of these are applicable clinically.
In the sixth review article, Davidson and Skowno (pp. 370–376) focus on the recent pediatric publications in two areas of neuromonitoring: measuring anesthesia effect and cerebral perfusion and oxygenation. They conclude that the impact of anesthesia on the electroencephalography of the small infants has some gross similarities to older children but that there are fundamental differences which mandate separate calibration of anesthesia depth monitors. The role of nociception monitors in children has yet to be defined. Although cerebral oxygenation monitoring during pediatric anesthesia improves our understanding of cerebral perfusion, evidence that its use improves outcome is not yet available.
In the seventh review article, Sommerfield and von Ungern-Sternberg (pp. 377–383) summarize the current evidence available to guide anesthetists along the decision-making process between inhalational and intravenous anesthetic induction in children. Intravenous induction is more beneficial in children when compared to inhalational induction with regard to respiratory adverse events, particularly in those with respiratory symptoms. It causes less postoperative behavioral disturbances but may be associated with more anxiety at induction. The anesthetists need to balance the clinical risks of respiratory adverse events, the ‘veins on offer’, the level of anxiety and previous experiences of the child and parents.
In the eighth review article, Sümpelman et al. (pp. 384–391) present recent developments and recommendations for perioperative fluid management in children. Optimized fasting times improve patient comfort as well as metabolic and hemodynamic condition after induction of anesthesia. Physiologically composed balanced isotonic electrolyte solutions are safer than hypotonic electrolyte solutions or isotonic saline 0.9% to protect young children against the risks of hyponatremia and hyperchloremic acidosis. For intraoperative maintenance infusion, addition of 1–2% glucose is sufficient to avoid hypoglycemia or hyperglycemia and lipolysis.
Finally, in the ninth review article, Hansen et al. (pp. 392–397) describe the various factors that have contributed to the substantial improvements in anesthesia-related outcomes in children during the years. They conclude that future improvements are still necessary in areas such as adverse-event reporting and long-term neurocognitive outcomes with much more focus on patient/family-centered outcomes. However, which outcome measures are important in pediatric anesthesia remains unknown.
There is an urgent need for clinical experts and stakeholders (not just small working groups) to meet and agree on a consensus to identify indicators that could act as outcome measures in future large-scale prospective observational studies and clinical trials. Such an approach will foster benchmarking and continuous quality assessment and improvement at individual, institutional, interinstitutional, regional, national and international levels and facilitate larger scale clinical research. It is encouraging to see that pediatric anesthetic researchers have realized that the most effective way to improve overall outcome is achieved by using a holistic approach of small steps. This accumulation of many relatively small but steady improvements (aggregation of marginal gains) will ultimately improve perioperative outcomes in children requiring anesthesia and surgery.
I would like to thank the contributing authors. As renowned experts on their respective fields, they have provided an excellent collection of insightful review papers. Additionally, I would like to thank the editorial staff at Current Opinion in Anaesthesiology for their fast and professional support and expertise in managing these articles in a timely fashion.
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1. Hansen TG. Use of anaesthetics in young children: consensus statement of the European Society of Anaesthesiology, the European Society for Paediatric Anaesthesiology, the European Association of Cardiothoracic Anaesthesiology and the European Safe Tots Research Initiative. Pediatr Anaesth 2017; 27:558–559.
2. Habre W, Disma N, Virag K, et al. APRICOT Group of the European Society of Anaesthesiology Clinical Trial Network. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicenter observational study in hospitals in Europe. Lancet Respir Med 2017; 5:412–425.
3. McCann ME, de Graaf JC, Doris L, et al. GAS Consortium. Neurodevelopmental outcome at 5 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicenter, randomized, controlled equivalence trial. Lancet 2019; 393:664–677.