Differently from inside the operating room, anesthesiological management cannot be based only on patient status and on the procedure, but it should be decided also on the actual environment.

Flexibility is a key factor in the good outcome of NORA. Most of the procedures are scheduled in remote locations, which often do not guarantee a wide space of action and cannot allow the use of some drugs or equipment. Anesthesiologists have to tailor an anesthesia service to the particular requirements imposed by the actual context. For example, procedures performed directly in neonatal intensive care unit often do not allow the use of halogenated vapors for the absence of adequate anesthesia machines, vaporizers, and scavenger systems so that only intravenous drugs can be utilized; MRI and many radiologic exams do not allow to remain close to the patient, reducing the direct control on his ventilation and other vital signs; dentistry and endoscopy oblige the anesthesiologist to share airways with the co-workers (more challenging when outside the operating room); some electrophysiological retinal exams require a dark room without possibility to look at the child, etc. In these challenges, a right choice of drugs and an efficient and reliable monitoring is essential for a safe outcome.

Although respiratory adverse events are the most common [2, 22], a basic hemodynamic monitoring (EKG, NiBP) is recommended in every patient, independent from procedure, location, and clinical status. If deep sedation is performed, or if a patient has significant underlying illness, vital signs should be measured at least every 5 min.

Experience and evidence suggest that respiratory complications are the most reported and are likely to occur within 5–10 min after administration of intravenous medications and immediately after the procedure when the painful stimuli are removed.

Provided that continuous visual observation of the face, mouth, and chest wall movements is not reliable, adequate respiratory monitoring is recommended throughout the procedure [23, 24]. The use of SaO₂ is mandatory but does not give a value in real time. EtCO₂ monitoring, on the contrary, better by Microstream Sensor particularly in neonates, is strongly recommended [25]. Microstream monitors have a sampling chamber of 15 mcl and work well even with low flow of 50 ml.

EtCO₂ monitoring is increasingly available in many settings for non-intubated patients and may be helpful to assess ventilation during sedation and analgesia. Increases in EtCO₂ may be detected in children undergoing respiratory depression before hypoxemia is noted, particularly in those who are receiving supplemental oxygen. Different approaches to preoxygenation and to the use of continuous supplemental oxygen during procedural sedation are reported in literature [26]. A FiO₂ higher than 0.21 can allow to maximize O₂ lung storage [27] and a longer maintenance of a good level of PaO₂ during occurrence of apnea. However, continuous supplemental oxygen can delay desaturation and apnea detection unless capnographic monitoring is available [28]. Furthermore, there is no evidence that preoxygenation or increasing FiO₂ is associated with improved safety in NORA [29].

An additional monitoring is represented by the cerebral activity monitoring. The most utilized technology is the bispectral index (BIS). It is able to quantify the level of consciousness ranging from 0 (no brain activity) to 100 (alert), obtained by continuous EEG monitoring through probes placed on the forehead. It has shown good sensitivity in children older than 6 months, and it can be useful to guide adequate drug administration and to avoid overdosage [30] that could delay awakening. It should be considered that BIS index is not sensitive to drugs that have site effect out of the cerebral cortex, as ketamine, dexmedetomidine, remifentanil, and N₂O [31].

Other brain activity monitoring devices, as entropy [32] and cerebral state index [33], are under validation for pediatric age, but results are even controversial.

Various drugs and techniques can be chosen: clinicians who administer sedation must understand the pharmacology of the drugs used. Because sedation is a continuum in which responses to medications vary greatly upon developmental, behavioral, and clinical status, type of procedure, need to cover painful maneuvers or only immobility, clinicians must identify the appropriate level of sedation/analgesia for the single child (Table 6.4). Careful titration of the chosen medication is often necessary to safely achieve the desired depth of sedation. A wide range of short-acting sedative-hypnotic and analgesic medications are available [24, 34, 35], and many of these agents have multiple routes of administration (Table 6.5). Procedures that are not painful and require only immobility can usually be performed with sedation alone. Children undergoing painful procedures require also analgesia. It has to be underlined that every performer must be able to deal with possible complications, and competence in emergency airway management is mandatory [5, 24, 36].

Historically, children have been anesthetized in operating rooms by halogenated vapors. The increasing demand of procedures in NORA has transferred this technique even outside of the operating room. The recent attention to the environmental pollution and to the occupational safety has restricted the use of inhalation anesthesia inside the locations equipped by specific scavenger systems.

The most used vapor in this field is sevoflurane that guarantees a safe profile for maintenance of spontaneous breathing and stabile hemodynamic. It is also advantageous for its rapid onset and the possibility to find a venous access in not cooperating children. It can be used trough facial mask or even by nasal probes, very useful in procedures performed on the eyes or on the face where the mask could result cumbersome.

Other halogenated (as desflurane or isoflurane) are not indicated for this use, due to their irritating effect on the tracheobronchial system, when used in spontaneous ventilation.

Nitrous oxide (N₂O) is an old gas which recently has been proposed again, in a new formulation. It is commercialized as a mixture with O₂ 50 % in portable tanks. It is delivered through a demand valve mask or continuous flow system [37]. Because the demand valve mask requires cooperation and may be difficult to be activated by smaller children, N₂O is used primarily in patients older than 4 years of age. To prevent excessive exposure, dedicated facial masks connected with a scavenger system can be utilized. A continuous delivery system (a mask strapped over the nose and/or mouth) has been used in younger children with variable success. This system indeed is more frequently associated with emesis [38, 39]. N₂O provides good analgesia, sedation, amnesia, and anxiolysis [40, 41], and it is a widely used analgesic for acute, short-term pain relief in a diverse range of clinical situations. Contraindications to nitrous oxide include nausea and vomiting and trapped gas within body cavities (e.g., bowel obstruction, pneumothorax, middle ear infection). Deeper sedation than anticipated can occur with prolonged inhalation and when N₂O is combined with opioids or benzodiazepines [42]. It is reported that fasting is not mandatory using 50 % N₂O/O₂ mixture [43]. In the absence of a clear evidence, every physician should identify the best choice according to his experience or skill.

Children are usually afraid of needles, and often in NORA, there is no possibility to use inhalation induction, so the cooperation of the child for finding a venous access is important. Application of anesthetic transdermic cream 45 min earlier can be very useful, in association with administration of midazolam 0.4–0.5 mg/kg (for a maximum of 15 mg) by mouth or better through the more rapid nasal route, thanks to the high mucosal vascularization [44].

Over the last decade, intravenous techniques are developed even in pediatrics with successful outcome. The marketing of new short-acting drugs and the safer profile of pharmacodynamics allows to calibrate anesthesia in real time with respect to the procedure.

The development of pediatric pharmacokinetic models for target-controlled infusion (TCI), Paedfusor and Kataria, has been a further boost to better utilize propofol in children.

TCI technique is particularly advantageous in NORA, allowing to perform sedation in spontaneous breathing assuring a constant propofol plasma concentration [45]. When compared with manual controlled infusion or intermittent bolus, TCI provides reduced apnoeic events and shorter awakening time [46].

For these reasons, propofol currently is the commonest intravenous agent (alone or in combination) administered in NORA. Safety profile is very comfortable even in smaller children [47], despite propofol infusion syndrome has been described after longer or high-dose infusion [48]. However, high doses administered by mistake for short procedures have not shown fatal outcome, despite a transient alteration in the metabolic pattern [49].

Remifentanil shows a pharmacokinetic profile even more advantageous in general anesthesia due to the efficacy of plasmatic esterases, which seems already mature even in premature babies [50]. Among opiates, remifentanil is the most indicated for a rapid recovery and discharge, even if the apnoeic effect requires a strict capnographic monitoring when spontaneous breathing is performed.

Outside the operating room, other opioids have proven useful. Alfentanil has been utilized by bolus in association with propofol or midazolam in short painful procedures as bone marrow aspiration or lumbar puncture [51]. Opioids with longer half-life are less recommended, as unique sedation agent, due to the increased interindividual variability and difficult titration. Recently sufentanil has been experimented successfully in a preliminary study by nasal route in dentistry [52], but this technique still needs major validation.

Ketamine, which came back to our attention in the last years, provides sedation, analgesia, and immobilization while usually preserving upper airway muscle tone and spontaneous breathing [53–55]. Its use in small doses in association with hypnotic agents is common, particularly for the possibility of administration by several routes.

Dexmedetomidine can be considered the future of sedation also in NORA. It causes minimal respiratory depression and, in healthy children, has been found generally safe and effective for nonpainful procedures [56], and in some sedation service, it is already the preferred agent for diagnostic imaging [57, 58].