Anesthetic and Analgesic Drug Products Advisory Committee Activity and Decisions in the Opioid-crisis Era.

The United States Food and Drug Administration is tasked with ensuring the efficacy and safety of medications marketed in the United States. One of their primary responsibilities is to approve the entry of new drugs into the marketplace, based on the drug's perceived benefit-risk relationship. The Anesthetic and Analgesic Drug Product Advisory Committee is composed of experts in anesthesiology, pain management, and biostatistics, as well as consumer and industry representatives, who meet several times annually to review new anesthetic-related drugs, those seeking new indications, and nearly every opioid-related application for approval. The following report describes noteworthy activities of this committee since 2017, as it has grappled, along with the Food and Drug Administration, to balance the benefit-risk relationships for individual patients along with the overarching public health implications of bringing additional opioids to market. All anesthesia advisory committee meetings since 2017 will be described, and six will be highlighted, each with representative considerations for potential new opioid formulations or local anesthetics.

Exhaled nitric oxide measurement before pediatric adenotonsillectomy: A feasibility study.

BACKGROUND: Exhaled nitric oxide (eNO) is a known biomarker for the diagnosis and monitoring of bronchial hyperreactivity in adults and children. AIMS: To investigate the potential role of eNO measurement for predicting perioperative respiratory adverse events in children, we sought to determine its feasibility and acceptability before adenotonsillectomy. METHODS: We attempted eNO testing in children, 4-12 years of age, immediately prior to admission for outpatient adenotonsillectomy. We used correlations between eNO levels and postoperative adverse respiratory events to make sample size predictions for future studies that address the predictability of the device. RESULTS: One hundred and three (53%) of 192 children were able to provide an eNO sample. The success rate increased with age from 23% (9%-38%) at age 4 to over 85% (54%-98%) after age 9. Using the eNO normal value (<20 ppb) as a cutoff, an expected sample size to detect a significant difference between children with and without adverse events is 868, assuming that respiratory adverse events occur in 29% of children. CONCLUSIONS: eNO testing on the day of surgery has limited feasibility in children younger than 7 years of age. The most common reason for failure was inadequate physical performance while interacting with the testing device. The role of this respiratory biomarker in the context of perioperative outcomes for pediatric adenotonsillectomy remains unknown and should be further studied with improved technologies.

Drug Diversion in the Anesthesia Profession: How Can Anesthesia Patient Safety Foundation Help Everyone Be Safe? Report of a Meeting Sponsored by the Anesthesia Patient Safety Foundation.

Diversion in the workplace can adversely impact the safety of healthcare professionals and patients. The Anesthesia Patient Safety Foundation (APSF) believes that substance use disorder, diversion in the workplace, and their potential adverse effects on patient safety need to be addressed through open discussion, education, research, policy, and possible other interventions. To make progress in this area, the APSF convened a conference entitled "Drug Diversion in the Anesthesia Profession: How Can APSF Help Everyone Be Safe?" in Phoenix, Arizona, on September 7, 2017 (Supplemental Digital Content, Document, http://links.lww.com/AA/C616). It was comoderated by the authors.

Consensus Statement of the Malignant Hyperthermia Association of the United States on Unresolved Clinical Questions Concerning the Management of Patients With Malignant Hyperthermia.

At a recent consensus conference, the Malignant Hyperthermia Association of the United States addressed 6 important and unresolved clinical questions concerning the optimal management of patients with malignant hyperthermia (MH) susceptibility or acute MH. They include: (1) How much dantrolene should be available in facilities where volatile agents are not available or administered, and succinylcholine is only stocked on site for emergency purposes? (2) What defines masseter muscle rigidity? What is its relationship to MH, and how should it be managed when it occurs? (3) What is the relationship between MH susceptibility and heat- or exercise-related rhabdomyolysis? (4) What evidence-based interventions should be recommended to alleviate hyperthermia associated with MH? (5) After treatment of acute MH, how much dantrolene should be administered and for how long? What criteria should be used to determine stopping treatment with dantrolene? (6) Can patients with a suspected personal or family history of MH be safely anesthetized before diagnostic testing? This report describes the consensus process and the outcomes for each of the foregoing unanswered clinical questions.

Trends in Postoperative Opioid Prescribing in Outpatient Pediatric Surgery.

OBJECTIVE: To determine trends in opioid prescribing for home use after pediatric outpatient surgery. DESIGN: Retrospective analysis of a de-identified database. SETTING: Multispecialty children's hospital and freestanding surgery centers. PATIENTS, PARTICIPANTS: A total of 65,190 encounters of pediatric outpatient surgeries from 2013 through 2017 for nine different surgical specialties. Patients in the cardiothoracic service and nonpainful procedures were excluded. MAIN: Outcome Measures. Incidence rate of prescribing, dose, number of doses available (i.e., duration of therapy), and maximum weight-based home opioid availability from 2013 to 2017. Additional independent variables included sex, age, weight, race/ethnicity, insurance type (private vs public), and surgical service. RESULTS: The incidence rate of receiving a take-home opioid prescription at discharge ranged from 18% to 21% between 2013 and 2017, with no clear directional trend. Among patients prescribed opioids, however, the maximum available take-home dose steadily declined from 2013 through 2017 (P < 0.001). This was due to both a decrease in the number of doses prescribed (i.e., duration of treatment) and, beginning in 2015, the amount per dose. Females were more likely to receive an opioid than males, and patients with public insurance were more likely to receive an opioid than those with private insurance. Opioid prescribing was more likely in patients who did not disclose their ethnicity and those of ethnic minority compared with white patients (all P < 0.0001). CONCLUSIONS: The rate of receiving a take-home opioid prescription and the dose prescribed remained stable from 2013 to 2017, but the duration of treatment steadily declined, and beginning in 2015, the amount per dose also decreased. Certain subgroups of patients were more likely to be prescribed opioids and will require further investigation and confirmation.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations.

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public-private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses.

Abuse-deterrent Opioid Formulations.

Abuse-deterrent opioid formulations have been suggested as one way to decrease the abuse, addiction, and overdose of orally prescribed opioids. Ten oral opioid formulations have received abuse-deterrent labeling by the U.S. Food and Drug Administration (FDA). Their properties consist of physical and/or chemical means by which the pills resist manipulation and create a barrier to unintended administration, such as chewing, nasal snorting, smoking, and intravenous injection. In this review, we describe the mechanisms of abuse-deterrent technology, the types of premarketing studies required for FDA approval, the pharmacology of the currently approved abuse-deterrent opioid formulations, and the evidence for and against their influence on opioid abuse. We conclude that there is currently insufficient evidence to indicate that the availability of abuse-deterrent opioid formulations has altered the trajectory of opioid overdose and addiction; however, postmarketing studies are in their infancy, and novel deterrent formulations are continually being developed and submitted for marketing approval.

New solutions to reduce wrong route medication errors.

Wrong route medication errors due to tubing misconnections are potentially life-threatening complications that have been made possible by the universal use of the Luer connector. The new International Organization of Standardization standards for small bore connectors, ISO 80369 series, have been developed to reduce the risk of these types of erroneous connections. Tubing connectors for different routes of clinical application will contain differently designed connectors that are physically incompatible. However, design and manufacturing standards have progressed slowly, and clinical roll-outs have been delayed, despite the implementation of California laws to promote their use. We are currently in a state of transition where new connectors for enteral and neuraxial use will be entering the clinical market in the next few years, and increasing use will identify additional patient safety concerns.

A limited evaluation of the association of race and anesthetic medication administration: A single-center experience with appendectomies.

BACKGROUND: Although it is known that a patient's race may influence their medical care, racial patterns of medication administration in pediatric anesthesia have not been well-studied. The aim of this study was to determine if differences exist between Black and White children with regard to administration of anesthetic and analgesic medications for a single procedure at our institution. METHODS: We conducted a retrospective review of medications administered to patients for emergency appendectomies at a large academic children's hospital from 2010 to 2015. We examined the association between patient race and administration of preoperative midazolam and intraoperative ondansetron, lidocaine, ketorolac, and weight-based doses of fentanyl and morphine. RESULTS: During the study period, 1680 patients (1329 White, 351 Black) underwent emergency appendectomy. There were no significant racial differences in administration of intraoperative anesthetic medications between Black and White children. In unadjusted analysis, Black children were less likely to receive preoperative midazolam than White children (OR=0.74 [95% CI, 0.58-0.94], P=.012). After adjusting for confounders, there was no evidence of racial differences in administration of preoperative or intraoperative medications. CONCLUSION: We did not find a significant difference in preoperative or intraoperative medication administration based on race when we adjusted for age, gender, and attending anesthesiologist practice patterns. We encourage all institutions to monitor their own practice patterns with regard to race.

Medication Errors in Pediatric Anesthesia: A Report From the Wake Up Safe Quality Improvement Initiative.

BACKGROUND: Wake Up Safe is a quality improvement initiative of the Society for Pediatric Anesthesia that contains a deidentified registry of serious adverse events occurring in pediatric anesthesia. The aim of this study was to describe and characterize reported medication errors to find common patterns amenable to preventative strategies. METHODS: In September 2016, we analyzed approximately 6 years' worth of medication error events reported to Wake Up Safe. Medication errors were classified by: (1) medication category; (2) error type by phase of administration: prescribing, preparation, or administration; (3) bolus or infusion error; (4) provider type and level of training; (5) harm as defined by the National Coordinating Council for Medication Error Reporting and Prevention; and (6) perceived preventability. RESULTS: From 2010 to the time of our data analysis in September 2016, 32 institutions had joined and submitted data on 2087 adverse events during 2,316,635 anesthetics. These reports contained details of 276 medication errors, which comprised the third highest category of events behind cardiac and respiratory related events. Medication errors most commonly involved opioids and sedative/hypnotics. When categorized by phase of handling, 30 events occurred during preparation, 67 during prescribing, and 179 during administration. The most common error type was accidental administration of the wrong dose (N = 84), followed by syringe swap (accidental administration of the wrong syringe, N = 49). Fifty-seven (21%) reported medication errors involved medications prepared as infusions as opposed to 1 time bolus administrations. Medication errors were committed by all types of anesthesia providers, most commonly by attendings. Over 80% of reported medication errors reached the patient and more than half of these events caused patient harm. Fifteen events (5%) required a life sustaining intervention. Nearly all cases (97%) were judged to be either likely or certainly preventable. CONCLUSIONS: Our findings characterize the most common types of medication errors in pediatric anesthesia practice and provide guidance on future preventative strategies. Many of these errors will be almost entirely preventable with the use of prefilled medication syringes to avoid accidental ampule swap, bar-coding at the point of medication administration to prevent syringe swap and to confirm the proper dose, and 2-person checking of medication infusions for accuracy.