Amnesia and analgesia are important to our patients. Without an “amnesia” monitor, we tend to target a deep level of sedation in order to minimize the risk of recall. The deeper the level of sedation achieved during procedural sedation, however, the higher the rate of respiratory depression, and therefore the higher the risk of adverse events [2]. Ideally, the optimal sedation encounter would ensure amnesia and analgesia with minimal risk of respiratory depression and other adverse events.

To date, there is no means of ensuring amnesia during sedation [29]. Currently, a patient’s level of sedation is mainly determined through interactive, subjective assessments, which integrate the physiological vital signs with a patient’s response to verbal or painful stimulation. Factors such as eye opening, response to voice, and response to pain are often used to extrapolate depth of sedation and likelihood of amnesia. These factors, although likely to be associated with the progression toward deeper levels of sedation and associated adverse events, do not predict recall or analgesia. Patients who appear alert may actually have no recall following a painful procedure with propofol [28], and patients who appear to have a much decreased level of consciousness may have recall of a procedure with an opioid [30]. As we advance our knowledge of sedation, it will be important to determine the presence of procedural amnesia in order to guide us in our titration of sedation while minimizing the risk of adverse outcome.

The future of sedation would benefit from a physiological monitor that accurately follows “depth” of sedation and likelihood of amnesia. The Bispectral Index (BIS) is a monitor that was originally introduced to monitor the depth of anesthesia. It is a noninvasive monitor that monitors electroencephalogram (EEG) activity from adhesive leads that are placed on the forehead. Using a 1–100 analog score, BIS denotes a number that is intended to reflect brain activity and provide an objective monitor of depth of anesthesia [2, 3, 28, 31]. Although initially hoped to be a monitor that could follow depth of sedation and provide a surrogate marker for risk of patient recall, BIS is neither accurate nor reliable for most sedation [31–33]. It often defaults to high values in sedated patients when there is motion artifact, limiting its utility for pediatric sedation. Currently, its practical application as a monitor for depth of sedation is controversial, and its use remains investigational. Mid-latency auditory-evoked potentials (MLAEPs) have also been described as demonstrating the depth of sedation in a dose-dependent fashion and may also represent a potential depth of sedation measurement [34]. The development of an objective monitor that would quantify the level of consciousness and improve the precision in achieving adequate sedation and amnesia without progressing to a deeper level of sedation will be an important step forward in the advancement of procedural sedation [2].

The urgency of the patient’s requirement for procedural sedation and the patient’s current medical condition play an important role in determining the level of risk for adverse events that can be accepted for a procedure. A common tool used to assess the severity of a patient’s underlying illness is the American Society of Anesthesiologists (ASA) physical status classification system [51]. Most research in the area of pediatric sedation outside of the operating room has focused on physical status class 1 and 2 patients, and the risk of an adverse event in these patients is well known. The risk of adverse effects of procedural sedation is likely higher in patients who have physical status scores of 3 or 4 [52]. The urgency of a patient’s need for the procedure for which one is being sedated is based on the nature of the problem that requires sedation. Emergent indications for procedures may include cardioversion for life-threatening arrhythmias, reduction of fractures or dislocations with soft tissue or vascular compromise, or intractable pain or suffering. Not all procedures are emergent, however, and the remainder must be triaged to urgent, semiurgent, or elective/nonurgent. The degree of urgency often guides the acceptable level of risk for adverse events for procedural sedation. Patients with an emergent need for sedation are unlikely to benefit from a delay in the procedure if they have eaten food prior to the procedure [53], whereas a patient with a nonurgent need for sedation is much more likely to benefit from such a delay.

Other than the ASA physical status score, the patient’s current medical condition, NPO status, and the assessment of the patient’s airway and respiratory status, there has not been a great deal of investigation into the risk factors for adverse events that can be identified before the procedure has begun. As our knowledge of procedural sedation increases, the risk of adverse events subsequent to specific procedures and in patients with a variety of medical conditions needs to be established. Once these data are available, this information, along with the risk of adverse events associated with various depths of sedation, can be used to decide on the best level and timing for procedural sedation for each given procedure and can allow us to better tailor sedation to a given circumstance for a patient’s specific medical situation and sedation needs.

Patients who present in pain would benefit from analgesics prior to initiating the sedation. The combination of sedatives and analgesics, however, may increase the likelihood of adverse outcomes [6, 54–57]. The optimal method to treat procedural pain during sedation, and the degree to which it should be relieved, has not been determined. It is likely that patients who receive more preprocedural analgesia are more prone to respiratory depression during the sedation [48]. Recent work has demonstrated that during brief procedures, the physiologic stress of respiratory depression may be more pronounced than the stress of unrecalled pain [57].

The determination of the optimal balance between pain management and safety is difficult and requires close assessment of the patient’s ongoing pain. Future work should focus on improving our ability to provide analgesia without increasing the risk of adverse events. In those situations in which the procedure is successfully completed albeit with some pain, it will be important to determine whether the inability to recall this painful experience, because of the amnestic effects of the medication, could have enduring, subversive, psychological effects.

Since pain is a subjective experience, our knowledge of a child’s pain is achieved by patient report. Due to the limitations of communication with children, especially in younger children, the assessment of pain is often done simply by observation, and many methods of assessing exist [58–67]. Numerous studies have found that healthcare providers consistently underestimate a child’s pain, as do the child’s parents (although the parents are usually closer to the child’s rating than the healthcare providers) [68]. Furthermore, it has been recently shown that sedatives may increase pain perception, at least in terms of how it is reported [69]. It is often difficult to distinguish a child’s pain and agitation from distress due to the situation surrounding the pain.

The physiologic measurement of pain remains beyond current capabilities, and there is no blood test or physical sign that can accurately predict how much pain a patient experiences, leaving the situation more difficult in children than it is in adults. In the setting of repeated painful experiences, children will begin to recognize the activities of the event and develop conditioned behaviors related to upcoming painful events. The determination of which aspects of the pain response are most associated with changes in future pain behavior will guide us in modifying our sedation technique to reduce the risk of sensitizing the child to future painful procedures.

Most of the data on procedural sedation are drawn from large academic centers with high sedation volumes. Sedation data from lower volume settings suggest that their outcomes are similar to that of busy nonacademic centers [70], but it is difficult to make conclusive comparisons regarding these two settings. Since many aspects of safe and effective procedural sedation rely on the interactive monitoring, experience, and the judgment of the operator, such as the ability to accurately recognize the depth of sedation and adequacy of ventilatory effort, it seems likely that less experienced providers would experience a comparatively higher rate of adverse events. There is likely a minimal amount of experience required in order to bring a provider to the point where he can balance the sedation depth with the adverse event risk effectively. Determining the point at which a provider can safely perform these tasks will be important in the determination of appropriate training for procedural sedation. At a national, state, and professional society level, there has been evolving interest and commitment to setting guidelines and standards for sedation delivery among healthcare professionals.

At a national level, the Joint Commission does not mandate specific credentialing for moderate sedation, but leaves it to the organizations to determine the necessary training and skills. In an update on July 7, 2010, the Joint Commission reiterated that “the individuals who are ‘permitted’ to administer sedation are able to rescue patients at whatever level of sedation or anesthesia is achieved either intentionally or unintentionally, e.g., when the patient slips from moderate into deep sedation or from deep sedation into full anesthesia. Each organization is free to define how it will determine that the individuals are able to perform the required types of rescue. Acceptable examples include, but are not limited to, ACLS certification, a satisfactory score on a written examination developed in concert with the department of anesthesiology, or a mock rescue exercise evaluated by an anesthesiologist” [71].

In the United States, some specialty organizations such as the American Dental Association (ADA) have released policy statements that put the onus of credentialing on the dental boards of each state. In their October 2007 Policy Statement on the Use of Sedation and General Anesthesia by Dentists, the ADA leaves the responsibility for credentialing in the hands of the individual states: “Appropriate permitting of dentists utilizing moderate sedation, deep sedation and general anesthesia is highly recommended. State dental boards have the responsibility to ensure that only qualified dentists use sedation and general anesthesia. State boards set acceptable standards for safe and appropriate delivery of sedation and anesthesia care, as outlined in this policy and in the ADA Guidelines for the Use of Sedation and General Anesthesia by Dentists” [23]. (Refer to Chap. 20.) The ASA has been much more specific in making recommendations for training and credentialing. They issued a Statement on “Granting Privileges For Deep Sedation To Non-Anesthesiologist Sedation Practitioners” on October 20, 2010 [22]. It recommends that the nonanesthesiologist be able to bag-valve-mask ventilate, insert an oro/pharyngeal airway and laryngeal mask airway, and perform an endotracheal intubation. This should include a minimum of 35 patients, inclusive of simulator experience. Practitioners should also be familiar with the use and interpretation of capnography. Deep sedation of children requires PALS and ACLS certification as well as separate education training and credentialing [72]. The ASA statement recommends that nonanesthesiologists be proficient in advanced airway management for rescue when they deliver deep sedation. This proficiency and competency would be determined by the Director of Anesthesia Services of the facility in which the sedation is delivered [17, 22]. In addition, the ASA specified that performance evaluation and a performance improvement program would be required for privileging—both of which would be developed with and reviewed by the Director of Anesthesia Services [22].

The topic of training, credentialing, and privileging process of nonanesthesia specialists has become an area of debate. In response to the aforementioned ASA statement, in July 2011 the American College of Emergency Physicians released a policy statement entitled “Procedural Sedation and Analgesia in the Emergency Department: Recommendations for Physician Credentialing, Privileging, and Practice” [72]. This policy iterated that the chief of the Emergency Medicine Service at each institution will be responsible for establishing criteria for credentialing and recommending emergency physicians for sedation privileges. Sedation training should “focus on the unique ED environment.” (Refer to Chaps. 2, 6 and 19.)

The federal government has also issued guidelines via the Center for Medicaid and Medicare Services (CMS), and as recently as May 2010 and February 2011, updated the Hospital Anesthesia Services Condition of Participation 42 CFR 482.52 (a) [24]. The ASA recognizes the Center for Medicare and Medicaid Services (CMS) as defining those qualified to administer deep sedation. The 2010 CMS guidelines limited deep sedation to be delivered only by an anesthesiologist, nonanesthesiologist MD or DO, dentist, oral surgeon, podiatrist, Certified Registered Nurse Anesthetist (CRNA), or Anesthesia Assistant (AA) [24]. These CMS guidelines toward nonanesthesia providers of sedation were revised in January 2011 in the PUB 100–07 State Operations Provider Certification, which revises Appendix A for various provisions of 42 CFR 482.52 concerning anesthesia services [24]. (Refer to Chap. 12.) These revisions were made in response to feedback from practitioners and allow the individual hospitals to establish their own policies and procedures with respect to the qualifications of analgesia providers and the clinical situations that distinguish anesthesia from analgesia. The policies must follow nationally recognized guidelines and can include guidelines of one or more specialty societies.

In response to the January 2011 update to the CMS guidelines [24], the American College of Emergency Physicians used their policy statement of July 2011, entitled “Procedural Sedation and Analgesia in the Emergency Department: Recommendations for Physician Credentialing, Privileging, and Practice” to delineate who would be appropriate to deliver deep sedation [72]. (Refer to Chap. 2.) The emergency medicine physicians, physician assistants, and nurse practitioners could be credentialed to deliver sedation. Furthermore, the policy acknowledges that the emergency medicine physician may commonly administer general anesthesia for specific situations in the emergency department (intubation, postintubation, procedures on intubated patients). It expands the role of the emergency physicians as well as emergency medicine nurses by condoning the capability of qualified ED nurses to “administer propofol, ketamine, and other sedatives under the direct supervision of a privileged emergency physician.” The policy also recognizes that there may be occasions whereby the emergency medicine environment may not lend itself to having a separate physician administer the sedative and another to perform the procedure: For these situations, the policy states “Deep sedation may be accomplished by the same emergency physician both administering sedation and performing the procedure” [72].

California has taken the initiative to credential sedation care providers. Specifically, the California Board of Medicine recently sponsored and passed legislation (AB2637.Eng, Chap. 499) allowing the dental board to issue a dental sedation assistant permit after a minimum of 12 months of work experience. The permit allows the assistant to monitor conscious sedation or general anesthesia from noninvasive instrumentation. They may also add drugs, medications, and fluids to intravenous lines using a syringe [73].

At a state level, the New York State Department of Health has already recognized the importance of safe delivery of sedation in the office-based setting. In 2007, the state required that office-based surgery (OBS) be performed in an accredited setting. Expounding on this, on July 14, 2009, the state became more specific: any physician performing “office-based surgery” (OBS) must do so either in an Article 28 licensed hospital, ambulatory surgery center, diagnostic and treatment center, or in a private physician’s office that is accredited [74]. Accreditation may come from one of three organizations: The Joint Commission, Accreditation Association for Ambulatory Health Care (AAAHC), or American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF).

In the future, it is very likely that other states will follow New York’s lead and increase the vigilance and scrutiny of OBS, which requires moderate to deep sedation. We anticipate that there will be increased requirements for accrediting outpatient facilities to perform moderate or deep sedation and to credential practitioners in those settings. Outpatient clinics and providers will likely be held to the same standards as hospital-based centers. This will further increase the need for standardized and effective practitioner training and assessment.

In general, all sedation care providers agree that sedation training, credentialing, and privileging are important. There is a lack of consensus among the different specialties as to who should be responsible for developing the sedation training programs as well as for credentialing the provider. One skill set required for the safe delivery of sedation, however, remains universally accepted: the ability to recognize and manage a compromised airway. This skill set will remain a critical and integral component of the training and credentialing process and would benefit from a standardized approach among all providers.

A possible approach to facilitate and standardize the credentialing process would be to develop simulation training as an added tool to the didactic and hands-on experience. (Refer to Chap. 35.) These simulators could develop scenarios that are specific for the specialty, patient population, and type of facility (office versus hospital-based setting). They could also be used as a research tool to evaluate adverse events: By artificially creating an adverse event model, one could develop techniques to identify the contributing factors as well as ways in which to monitor, detect, and manage these occurrences. Such a model was recently described by Tobin et al., who developed a sedation simulation course, and found participants preferred it to standard didactic training [75]. Further research in the impact of such training and the validity of such models for determining sedation competency are needed, but the goal of developing sedation simulation for training appears at hand. A recent study of pediatric residents described a sedation simulation model that was able to differentiate the skills and identify the educational needs of residents, highlighting the potential use of simulation as an assessment and credentialing tool [76]. This model of training has long been in existence in the airline industry. Flight simulation dates back to before World War I and has been used to train pilots and subsequently crew and air traffic controllers [77]. The roots of Crew Resource Management training in the United States are usually traced back to a workshop, Resource Management on the Flight Deck, sponsored by the National Aeronautics and Space Administration (NASA) in 1979. This conference was the outgrowth of NASA research into the causes of air transport accidents. The research presented at this meeting identified human error aspects of the majority of air crashes as failures of interpersonal communications, decision making, and leadership. At this meeting, the label Cockpit Resource Management (CRM) was applied to the process of training crews to reduce “pilot error” by making better use of the human resources on the flight deck [78].

The Federal Aviation Authority (FAA) as well as NASA have incorporated and mandated simulation training for credentialing, licensing, and continued education. The enactment of incidences that occur with low incidence, potentially so low that a pilot may never actually even experience the real-life scenario, offers the pilot the advantage to rehearse for such an occasion. These “rehearsals” could be as important to ensuring the safety of the passengers on an airplane as they are to the children that we sedate. Simulation models and training have already been implemented throughout the specialties for training purposes [79–82]. The importance of adopting sedation-directed simulation scenarios into the training and credentialing process has been recently explored by Babl et al., who found an improvement in sedation safety 3 years after the implementation of a simulation-based sedation training curriculum [83].

With recent publicity over the sedation-related deaths of celebrities (Anna Nicole Smith, Heath Ledger, Michael Jackson), the public awareness of sedation, the sedation agents (propofol, in particular), and the risk of mixing multiple sedatives is in the spotlight. (Refer to Chap. 36.) The National Institute of Health has even published a three-page patient education brochure entitled “Conscious (Moderate) Sedation for Adults” [84] in order to educate the layperson. In New York, as of 14 July 2009, patients can refer to www.​nyhealth.​gov to determine whether the OBS center that is using more than minimal sedation to perform a surgical or invasive procedure is accredited. Any practices that perform such procedures with more than minimal sedation and no accreditation are hence guilty of professional misconduct and disciplinary action. Patient awareness and scrutiny of sedation practice, including the agents, qualifications, and experience of providers, emergency preparedness, and outcome data should drive the field of pediatric sedation forward.

Establishing a “safe culture” around sedation practice is important. (Refer to Chap. 30.) Credentialing, standardizing the definition of adverse events, improving sedation delivery methods and techniques, introducing new sedatives, incorporating simulation into provider training, and using more objective means of identifying the depth of sedation and associated risks are all important first steps. There are also new methods that could be adopted. Once again, the airline industry has been on the forefront of adopting and exploring new methods at ensuring safety. The industry has adopted the use of checklists. The airline industry, National Aeronautics and Space Administration (NASA), and FAA have been developing checklists since before World War II. Checklists have begun to be adopted in the medical community as a means to foster active discussions and teamwork [85–88]. In 2009, a multi-institutional, international group of eight hospitals published prospectively collected data on a total of 7,688 consecutive patients, before and after the adoption of a 19-item Surgical Safety Checklist. This was an initiative of the World Health Organization’s (WHO) Safe Surgery Saves Lives Program. The mortality rate (at 30 days) decreased from 1.5 to 0.8 % following implementation [88]. A global commitment by the sedation community to develop checklists to foster teamwork and the “safety culture” may ultimately improve patient outcomes [86, 89].

A method of increasing procedural safety may also be the use of computerized provider order entry (CPOE). A recent study of the effect on error reduction in hospitals that have introduced CPOE shows a moderate improvement [90]. It is likely the CPOE will improve sedation safety, especially in terms of dosing errors and adjuvant medications. Electronic systems have the added benefit of the potential to facilitate the use of safety checklists before, during, and after the procedure.

As described previously, the works of the Pediatric Sedation Research Consortium and the ketamine individual patient data meta-analysis are important first steps toward generating the data required to carefully assess sedation practice in children outside the OR. Recently, the World Society of Intravenous Anesthesia (World SIVA) established an International Sedation Task Force (ISTF) represented by 26 members from multispecialties, both adult and pediatric, from 11 countries. The ISTF has proposed an Adverse Event Reporting Tool designed to standardize the collection of sedation outcome data worldwide [91]. This tool is an open-access web-based tool, available to providers globally.¹ The data collected will be available to individual and institutional users and will, in addition, populate the global ISTF sedation database. (Refer to Chap. 28.) The collection of large data from multispecialists globally will be an important first step to identify and carefully evaluate the range of variables that effect sedation-related adverse event rates. Such studies must be broad reaching in scope yet flexible enough to consider new developments in sedation techniques and monitoring as well as the use of the ever-emerging new sedation drugs that become available.

Compiling standardized data sets allowing for the aggregation of data will only be possible through the rigorous adherence to the use of standardized adverse events definitions and reporting structures such as described in the Quebec Guidelines and by the ISTF. Such an advancement will allow for the meaningful comparison of studies and the analysis of uncommon but important adverse events such as the need for endotracheal intubation [92]. National and international multispecialty collaboration will be required to develop such databases with sufficient patient numbers and the clinical data required to develop and evaluate sedation practice based on patient populations and providers, procedures performed, and drugs administered. The feasibility of such a collaborative endeavor requires not only cooperation of multiple specialties using cutting-edge data collection technology, but also a level of funding that to date has not been realized.

The ideal agent for procedural sedation would provide analgesia, anxiolysis, amnesia, and somnolence rapidly and predictably with no adverse effects. Ideally, this drug would be devoid of respiratory side effects and ensure hemodynamic stability. To date, such a drug does not exist. Currently, there are still a limited number of sedatives with pediatric labeling and Food and Drug Administration (FDA) approval. Labeling with pediatric information is in less than 50 % of drug products [93]. The Best Pharmaceuticals for Children Act of 2002 and the Pediatric Research Equity Act of 2003 advocated for expanding the number of drugs with pediatric labeling [94, 95]. In March, 2014 the American Academy of Pediatrics and its Committee on Drugs published a policy statement on off-label drugs in children. The policy concluded that “evidence, not label indication, remains the gold standard from which practitioners should draw when making therapeutic decisions for their patients.” The statement made recommendations for off-label drug administration and the advocating of off-label drug research and publication. Finally, the policy statement recommended, “institutions and payers should not use labeling status as the sole criterion that determines the availability on formulary or reimbursement status for medications in children. Similarly, less expensive therapeutic alternatives considered appropriate for adults should not automatically be considered appropriate first-line treatment in children. Finally, off-label uses of drugs should be considered when addressing various drug-related concerns, such as drug shortages.” [96] (Refer to Chap. 26.)