Pediatric sedation: Still a hard long way to go

To allow a patient’s ventilation to be controlled while providing comfort during mechanical ventilation is the main purpose of sedation. Critical illness itself brings intrinsic issues such as hemodynamic instability, altered mental status, and altered pharmacodynamics and pharmacokinetics, making sedation of these patients a complex problem and an inexact procedure. Several drugs have been used to provide sedation and analgesia in pediatric intensive care unit (ICU) patients. Opioids, benzodiazepines, and barbiturates among others are administered alone or combined with the aim of achieving adequate sedation. Although these drugs have analgesic and/or sedative effects, it is very hard to achieve an equilibrium between analgesia and sedation. Additionally, many of these agents have important adverse effects limiting their clinical use. Due to its major analgesic, sedative, ansyolytic, and sympatholytic action, dexmedetomidine, a new α2-agonist, has a potential place in the pediatric ICU armamentarium and can possibly be used in various patients and procedures. Patients sedated with dexmedetomidine may be easily awakened when required, becoming more cooperative, which is a critical point in the pediatric patient. Another important feature is that dexmedetomidine may improve oxygenation and does not cause respiratory depression, not affecting the respiratory rate or carbon dioxide clearance (1). The major concern with dexmedetomidine may be the hemodynamic effects. Hypotension and bradycardia are the most frequently reported side effects and may be minimized by slow drug infusion (2, 3). Because of the complexity and uncertainty in the sedation of critically ill patients, particularly pediatric patients, problems related to sedation are frequent and not easy to deal with. Morbidity and mortality have been reported with sedative drugs that are safely used in the adult setting (4). That is why the indication and use of these drugs is an important issue. Sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting, administered by continuous infusion for ≤24 hrs, is the approved and labeled indication of dexmedetomidine in adults. Data have not been submitted to the Food and Drug Administration to support safe and effective administration of dexmedetomidine lasting >24 hrs outside the intensive care setting or in nonventilated adult patients; also, the and Drug Administration has not approved dexmedetomidine for the pediatric patient. All these would be considered “off-label” use in disagreement with the indications and usage, precautions, and dosage and administration sections of the label (5). Although new drugs and technologies are welcome, we should be careful in adopting them promptly. In this issue of the Pediatric Critical Care Medicine, Dr. Chrysostomou and colleagues (6) describe their experience with the use of dexmedetomidine in spontaneously breathing patients (n = 33) as well as in mechanically ventilated patients (n = 5) after congenital cardiac and thoracic surgery. Using their ICU sedation scale and two pain scales (Numeric Visual Analog Scale and Face, Legs, Activity, Cry, and Consolability), they demonstrated that the majority of the patients (93%) achieved mild to moderate sedation. Hypotension and bradycardia were the most concerning adverse events related to the drug infusion but were resolved by titration of the infused dose or discontinuing the infusion. No respiratory adverse events occurred. The authors noted that the drug seemed to be less effective in patients <1 yr old. Part of the complexity of sedation is evaluating the sedation level, which is mainly achieved using various scales that measure depth of sleep and/or loss of consciousness. An objective physiologic variable is not measured. These scales may be problematic to evaluate the “arousable sedation” provided by dexmedetomidine. Electroencephalography may be one way to objectively assess both quantity and quality of sleep in sedated patients (7). Although the patients presented in this study by Dr. Chrysostomou and colleagues (6) did not experience severe cardiovascular adverse events and the ones who had hypotension or bradycardia were managed simply by titration or discontinuation of the drug infusion, we should note that there are no available data, in children, about the effects of dexmedetomidine on cardiac output, ventricular function, and systemic and pulmonary vascular resistance. Preliminary data suggest that dosing of dexmedetomidine may be age dependent (8). These data enhance the need for pharmacokinetic studies in the pediatric population to determine more precisely the dose needed to provide appropriate sedation with less risk of adverse events. Up to now we only have a few published case report series of the pediatric use of dexmedetomidine (9–13) suggesting that this drug may be an effective sedative for the pediatric population and only two randomized trials (14, 15). Tobias and Berkenbosch (14) compared the α2-agonist with midazolam, showing that it is at least as effective as midazolam. Guler et al. (15) found that dexmedetomidine reduces agitation after sevoflurane anesthesia for adenotonsillectomy. The initial data regarding dexmedetomidine are promising, and the study by Dr. Chrysostomou and colleagues (6) along with all the others indicates that the investigation of this new drug in the pediatric ICU armamentarium should continue, with pharmacokinetic studies followed by more randomized controlled trials in different clinical scenarios. Werther Brunow de Carvalho, MD Marcelo Cunio Machado Fonseca MD Federal University of Sao Paolo Sao Paolo, Brazil