Pilot Findings of Pharmacogenomics in Perioperative Care: Initial Results From the First Phase of the ImPreSS Trial.

BACKGROUND: Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care. METHODS: The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers. RESULTS: Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P < .0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow. CONCLUSIONS: Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.

Anesthesia providers as stakeholders to adoption of pharmacogenomic information in perioperative care.

OBJECTIVES: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care. METHODS: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources and barriers. RESULTS: Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1-10 years of experience, and nearly two-thirds with 11+ years (P < 0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time and whether testing is worth financial costs. CONCLUSIONS: Anesthesiology, critical care and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on the use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes.

2022 American Society of Anesthesiologists Practice Guidelines for Management of the Difficult Airway.

The American Society of Anesthesiologists; All India Difficult Airway Association; European Airway Management Society; European Society of Anaesthesiology and Intensive Care; Italian Society of Anesthesiology, Analgesia, Resuscitation and Intensive Care; Learning, Teaching and Investigation Difficult Airway Group; Society for Airway Management; Society for Ambulatory Anesthesia; Society for Head and Neck Anesthesia; Society for Pediatric Anesthesia; Society of Critical Care Anesthesiologists; and the Trauma Anesthesiology Society present an updated report of the Practice Guidelines for Management of the Difficult Airway.

Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application.

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility.

Trends in Central Venous Catheter Insertions by Anesthesia Providers: An Analysis of the Medicare Physician Supplier Procedure Summary From 2007 to 2016.

BACKGROUND: Central line insertion is a core skill for anesthesiologists. Although recent technical advances have increased the safety of central line insertion and reduced the risk of central line-associated infection, noninvasive hemodynamic monitoring and improved intravenous access techniques have also reduced the need for perioperative central venous access. We hypothesized that the number of central lines inserted by anesthesiologists has decreased over the past decade. To test our hypothesis, we reviewed the Medicare Physician Supplier Procedure Summary (PSPS) database from 2007 to 2016. METHODS: Claims for central venous catheter placement were identified in the Medicare PSPS database for nontunneled and tunneled central lines. Pulmonary artery catheter insertion was included as a nontunneled line claim. We stratified line insertion claims by specialty for Anesthesiology (including Certified Registered Nurse Anesthetists and Anesthesiology Assistants), Surgery, Radiology, Pulmonary/Critical Care, Emergency Physicians, Internal Medicine, and practitioners who were not anesthesia providers such as Advanced Practice Nurses (APNs) and Physician Assistants (PAs). Utilization rates per 10,000 Medicare beneficiaries were then calculated by specialty and year. Time-based trends were analyzed using Joinpoint linear regression, and the Average Annual Percent Change (AAPC) was calculated. RESULTS: Between 2007 and 2016, total claims for central venous catheter insertions of all types decreased from 440.9 to 325.3 claims/10,000 beneficiaries (AAPC = -3.4, 95% confidence interval [CI], -3.6 to -3.2: P < .001). When analyzed by provider specialty and year, the number of nontunneled line insertion claims fell from 43.1 to 15.9 claims/10,000 (AAPC = -7.1; -7.3 to -7.0: P < .001) for surgeons, from 21.3 to 18.5 claims/10,000 (AAPC = -2.5; -2.8 to -2.1: P < .001) for radiologists, and from 117.4 to 72.7 claims/10,000 (AAPC = -5.2; 95% CI, -6.3 to -4.0: P < .001) for anesthesia providers. In contrast, line insertions increased from 18.2 to 26.0 claims/10,000 (AAPC = 3.2; 2.3-4.2: P < .001) for Emergency Physicians and from 3.2 to 9.3 claims/10,000 (AAPC = 6.0; 5.1-6.9: P < .001) for PAs and APNs who were not anesthesia providers. Among anesthesia providers, the share of line claims made by nurse anesthetists increased by 14.5% over the time period. CONCLUSIONS: We observed a 38.3% decrease in claims for nontunneled central lines placed by anesthesiologists from 2007 to 2016. These findings have implications for anesthesiology resident training and maintenance of competence among practicing clinicians. Further research is needed to clarify the effect of decreasing line insertion numbers on line insertion competence among anesthesiologists.

Pharmacogenomic considerations for medications in the perioperative setting.

Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks. Pharmacogenomic information is increasingly being utilized in certain areas of medicine. Despite this, routine preoperative genetic screening to inform medication risk is not yet standard practice. In this review, we assess the current readiness of pharmacogenomic information for clinical consideration for several common perioperative medications, including description of key pharmacogenes, pharmacokinetic implications and potential clinical outcomes. The goal is to highlight medications for which emerging or considerable pharmacogenomic information exists and identify areas for future potential research.

The American Society of Anesthesiologists Practice Parameter Methodology.

The methodology used during the development of American Society of Anesthesiologists evidence-based practice parameters, from conceptualization through final adoption of the documents, is described. Features of the methodology include the literature search, review and analysis, survey development and application, and consolidation of the full body of evidence used for preparing clinical practice recommendations. Anticipated risks of bias, validation of the process, and the importance of the documents for clinical use are discussed.

Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: There are currently no drugs clinically available to reverse general anesthesia. We previously reported that caffeine is able to accelerate emergence from anesthesia in rodents. This study was carried out to test the hypothesis that caffeine accelerates emergence from anesthesia in humans. METHODS: We conducted a single-center, randomized, double-blind crossover study with eight healthy males. Each subject was anesthetized twice with 1.2% isoflurane for 1 h. During the final 10 min of each session, participants received an IV infusion of either caffeine citrate (15 mg/kg, equivalent to 7.5 mg/kg of caffeine base) or saline placebo. The primary outcome was the average difference in time to emergence after isoflurane discontinuation between caffeine and saline sessions. Secondary outcomes included the end-tidal isoflurane concentration at emergence, vital signs, and Bispectral Index values measured throughout anesthesia and emergence. Additional endpoints related to data gathered from postanesthesia psychomotor testing. RESULTS: All randomized participants were included in the analysis. The mean time to emergence with saline was 16.5 ± 3.9 (SD) min compared to 9.6 ± 5.1 (SD) min with caffeine (P = 0.002), a difference of 6.9 min (99% CI, 1.8 to 12), a 42% reduction. Participants emerged at a higher expired isoflurane concentration, manifested more rapid return to baseline Bispectral Index values, and were able to participate in psychomotor testing sooner when receiving caffeine. There were no statistically significant differences in vital signs with caffeine administration and caffeine-related adverse events. CONCLUSIONS: Intravenous caffeine is able to accelerate emergence from isoflurane anesthesia in healthy males without any apparent adverse effects.

Local anesthetic systemic toxicity.

Local anesthetic systemic toxicity (LAST) is a rare yet devastating complication from the administration of local anesthesia. The ability to recognize and treat LAST is critical for clinicians who administer these drugs. The authors reviewed the literature on the mechanism, treatment, and prevention of LAST, with the goal of proposing a practical method for its management.