A Call to Action: A Specialty-Specific Course to Support the Next Generation of Clinician Scientists in Anesthesiology.

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns. A 2022 study examining National Institutes of Health (NIH) grant recipients associated with anesthesiology departments across 10 years (2011-2020) outlines total awarded funds at $1,676,482,440, with most of the funds awarded to only 10 departments in the United States. Of note, the total 1-year NIH funding in 2021 for academic internal medicine departments was 3 times higher than the 10-year funding of anesthesiology departments. Additionally, American Board of Anesthesiology (ABA) diplomats represent a minority (37%) of the anesthesiology researchers obtaining grant funding, with a small number of faculty members receiving a prevalence of monies. Overall, the number of publications per academic anesthesiologist across the United States remains modest as does the impact of the scholarly work. Improving environments in which academic anesthesiologists thrive may be paramount to successful academic productivity. In fact, adding to the lack of academic time is the limited bandwidth of senior academic physicians to mentor and support aspiring physician scientists. Given then the challenges for individual departments and notable successes of specialty-specific collaborative efforts (eg Foundation for Anesthesia Education and Research [FAER]), additional pooled-resource approaches may be necessary to successfully support and develop clinician scientists. It is in this spirit that the leadership of Anesthesia and Analgesia and the Journal of Education in Perioperative Medicine, unified with the Association of University Anesthesiologists, aim to sponsor the Introduction to Clinical Research for Academic Anesthesiologists (ICRAA) Course. Directed toward early career academic anesthesiologists who wish to gain competency specifically in the fundamentals of clinical research and receive mentorship to develop an investigative project, the yearlong course will provide participants with the skills necessary to design research initiatives, ethically direct research teams, successfully communicate ideas with data analysts, and write and submit scientific articles. Additionally, the course, articulated in a series of interactive lectures, mentored activities, and workshops, will teach participants to review articles submitted for publication to medical journals and to critically appraise evidence in published research. It is our hope that this initiative will be of interest to junior faculty of academic anesthesiology departments nationally and internationally.

A Call to Action: A Specialty-Specific Course to Support the Next Generation of Clinician Scientists in Anesthesiology.

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns. A 2022 study examining National Institutes of Health (NIH) grant recipients associated with anesthesiology departments across 10 years (2011-2020) outlines total awarded funds at $1,676,482,440, with most of the funds awarded to only 10 departments in the United States. Of note, the total 1-year NIH funding in 2021 for academic internal medicine departments was 3 times higher than the 10-year funding of anesthesiology departments. Additionally, American Board of Anesthesiology (ABA) diplomats represent a minority (37%) of the anesthesiology researchers obtaining grant funding, with a small number of faculty members receiving a prevalence of monies. Overall, the number of publications per academic anesthesiologist across the United States remains modest as does the impact of the scholarly work. Improving environments in which academic anesthesiologists thrive may be paramount to successful academic productivity. In fact, adding to the lack of academic time is the limited bandwidth of senior academic physicians to mentor and support aspiring physician scientists. Given then the challenges for individual departments and notable successes of specialty-specific collaborative efforts (eg, Foundation for Anesthesia Education and Research [FAER]), additional pooled-resource approaches may be necessary to successfully support and develop clinician scientists. It is in this spirit that the leadership of Anesthesia & Analgesia and The Journal of Education in Perioperative Medicine, unified with the Association of University Anesthesiologists, aim to sponsor the Introduction to Clinical Research for Academic Anesthesiologists (ICRAA) Course. Directed toward early career academic anesthesiologists who wish to gain competency specifically in the fundamentals of clinical research and receive mentorship to develop an investigative project, the yearlong course will provide participants with the skills necessary to design research initiatives, ethically direct research teams, successfully communicate ideas with data analysts, and write and submit scientific articles. Additionally, the course, articulated in a series of interactive lectures, mentored activities, and workshops, will teach participants to review articles submitted for publication to medical journals and to critically appraise evidence in published research. It is our hope that this initiative will be of interest to junior faculty of academic anesthesiology departments nationally and internationally.

Expert Consensus Statement on the Perioperative Management of Adult Patients Undergoing Head and Neck Surgery and Free Tissue Reconstruction From the Society for Head and Neck Anesthesia.

The perioperative care of adult patients undergoing free tissue transfer during head and neck surgical (microvascular) reconstruction is inconsistent across practitioners and institutions. The executive board of the Society for Head and Neck Anesthesia (SHANA) nominated specialized anesthesiologists and head and neck surgeons to an expert group, to develop expert consensus statements. The group conducted an extensive review of the literature to identify evidence and gaps and to prioritize quality improvement opportunities. This report of expert consensus statements aims to improve and standardize perioperative care in this setting. The Modified Delphi method was used to evaluate the degree of agreement with draft consensus statements. Additional discussion and collaboration was performed via video conference and electronic communication to refine expert opinions and to achieve consensus on key statements. Thirty-one statements were initially formulated, 14 statements met criteria for consensus, 9 were near consensus, and 8 did not reach criteria for consensus. The expert statements reaching consensus described considerations for preoperative assessment and optimization, airway management, perioperative monitoring, fluid management, blood management, tracheal extubation, and postoperative care. This group also examined the role for vasopressors, communication, and other quality improvement efforts. This report provides the priorities and perspectives of a group of clinical experts to help guide perioperative care and provides actionable guidance for and opportunities for improvement in the care of patients undergoing free tissue transfer for head and neck reconstruction. The lack of consensus for some areas likely reflects differing clinical experiences and a limited available evidence base.

Prolonged time to extubation after general anaesthesia is associated with early escalation of care: A retrospective observational study.

BACKGROUND: Prolonged time to extubation after general anaesthesia has been defined as a time from the end of surgery to airway extubation of at least 15 min. This occurrence can result in ineffective utilisation of operating rooms and delays in patient care. It is unknown if unanticipated delayed extubation is associated with escalation of care. OBJECTIVES: To assess the frequency of 'prolonged extubation' after general anaesthesia and its association with 'escalation of care before discharge from the postanaesthesia care unit', defined as administration of reversal agents for opioids and benzodiazepines, airway re-intubation and need for ventilatory support. In addition, we tried to identify independent factors associated with 'prolonged extubation'. DESIGN: Single-centre retrospective study of cases performed from 1 January 2010 to 31 December 2014. SETTING: A large US tertiary academic medical centre. PATIENTS: Adult general anaesthesia cases excluding cardiothoracic, otolaryngology and neurosurgery procedures, classified as: Group 1 - regular extubation (≤15 min); Group 2 - prolonged extubation (≥16 and ≤60 min); Group 3 - very prolonged extubation (≥61 min). MAIN OUTCOME MEASURES: First, cases with prolonged time to extubation; second, instances of escalation of care per extubation group; third, independent factors associated with prolonged time to extubation. RESULTS: A total of 86 123 cases were analysed. Prolonged extubation occurred in 8138 cases (9.5%) and very prolonged extubation in 357 cases (0.4%). In Groups 1, 2 and 3 respectively, naloxone was used in 0.4, 4.1 and 3.9% of cases, flumazenil in 0.03, 0.6 and 2% and respiratory support in 0.2, 0.7 and 2%, and immediate re-intubation occurred in 0.1, 0.3 and 2.8% of cases. Several patient-related, anaesthesia-related and procedure-related factors were independently associated with prolonged time to extubation. CONCLUSION: Prolonged time to extubation occurred in nearly 10% of cases and was associated with an increased incidence of escalation of care. Many independent factors associated with 'prolonged extubation' were nonmodifiable by anaesthetic management.

The metabotropic glutamate receptor 5 negative allosteric modulator fenobam: pharmacokinetics, side effects, and analgesic effects in healthy human subjects.

Metabotropic glutamate receptor 5 (mGlu5) has been shown to modulate nociception in animals, but no mGlu5 antagonists have been developed commercially as analgesics. The mGlu5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl)urea] was originally evaluated for development as a nonbenzodiazepine anxiolytic. Fenobam is analgesic in numerous mouse pain models, acting exclusively through mGlu5 blockade. Furthermore, fenobam showed no signs of analgesic tolerance with up to 2 weeks of daily dosing in mice. Analgesic effects of fenobam in humans have not been reported. The purpose of this investigation was to evaluate fenobam pharmacokinetics and analgesic effects in humans. We first evaluated single-dose oral fenobam disposition in a parallel-group dose-escalation study in healthy volunteers. A second investigation tested the analgesic effects of fenobam in an established experimental human pain model of cutaneous sensitization using capsaicin cream and heat, in a double-blind placebo-controlled study. The primary outcome measure was the area of hyperalgesia and allodynia around the area applied with heat/capsaicin. Secondary outcome measures included nociception, measured as pain rating on a visual analog scale, heat pain detection threshold, and effects on cognition and mood. Fenobam plasma exposures showed considerable interindividual variability and were not linear with dose. Fenobam reduced sensitization vs placebo at a single timepoint (peak plasma concentration); we found no other difference between fenobam and placebo. Our results suggest highly variable fenobam disposition and minimal analgesic effects at the dose tested. We suggest that future studies testing analgesic effects of mGlu5 blockade are warranted, but such studies should use molecules with improved pharmacokinetic profiles.

Modifiable and Nonmodifiable Factors Associated With Perioperative Failure of Extraglottic Airway Devices.

BACKGROUND: Extraglottic airway device (EGA) failure can be associated with severe complications and adverse patient outcomes. Prior research has identified patient- and procedure-related predictors of EGA failure. In this retrospective study, we assessed the incidence of perioperative EGA failure at our institution and identified modifiable factors associated with this complication that may be the target of preventative or mitigating interventions. METHODS: We performed a 5-year retrospective analysis of adult general anesthesia cases managed with EGAs in a single academic center. Univariable and multivariable logistic regressions were used to identify clinically modifiable and nonmodifiable factors significantly associated with 3 different types of perioperative EGA failure: (1) "EGA placement failure," (2) "EGA failure before procedure start," and (3) "EGA failure after procedure start." RESULTS: A total of 19,693 cases involving an EGA were included in the analysis dataset. EGA failure occurred in 383 (1.9%) of the cases. EGA placement failure occurred in 222 (1.13%) of the cases. EGA failure before procedure start occurred in 76 (0.39%) of the cases. EGA failure after procedure start occurred in 85 (0.43%) of the cases. Factors significantly associated with each type of failure and controllable by the anesthesia team were as follows: (1) EGA placement failure: use of desflurane (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.23-2.25) and EGA size 4 or 5 vs 2 or 3 (OR, 0.07; 95% CI, 0.05-0.10); (2) EGA failure before procedure start: use of desflurane (OR, 2.05; 95% CI, 1.23-3.40) and 3 or more placement attempts (OR, 4.69; 95% CI, 2.57-8.56); and (3) EGA failure after procedure start: 3 or more placement attempts (OR, 2.06; 95% CI, 1.02-4.16) and increasing anesthesia time (OR, 1.35; 95% CI, 1.17-1.55). CONCLUSIONS: The overall incidence of EGA failure was 1.9%, and EGA placement failure was the most common type of failure. We also found that use of desflurane and use of smaller EGA sizes in adult patients were factors under the direct control of anesthesia clinicians associated with EGA failure. An increasing number of attempts at EGA placement was associated with later device failures. Our findings also confirm the association of EGA failure with previously identified patient- and procedure-related factors such as increased body mass index, male sex, and position other than supine.

Bedside predictors of difficult intubation: a systematic review.

BACKGROUND: Unanticipated difficult intubation is associated with unwanted patient outcomes. The capability of predicting difficult airways may contribute to patient safety, efficient patient flow and rational use of limited resources. We evaluated current literature on performance of bedside airway tests in predicting difficult tracheal intubation. METHODS: Eligibility criteria were: prospective clinical studies; adult population of least 100 subjects; accepted definition of difficult intubation; direct laryngoscopy approach; true positive, false negative, false positive and true negative either reported or inferred. Medline and EMBASE database were searched for the following terms: "predictors", "prediction" and "risk factors" of "difficult intubation", "difficult laryngoscopy" and "difficult airway". The publication dates considered for the search were January 1st 2004 to March 31st 2014. Risk of bias was assessed according to QUADAS-2 criteria. RESULTS: Twenty-four studies involving 20,582 patients and consistent with eligibility criteria were included. Numerous airways screening tests were evaluated. The most frequently performed tests were: Mallampati Score, measurement of thyro-mental distance, upper lip bite test, inter-incisors gap, and sterno-mental distance. Assessed individual and combined tests are characterized by limited discriminative capacity, sensitivity, specificity, and positive likelihood ratio. CONCLUSION: Current bedside tests have limited and inconsistent capacity to discriminate between patients with difficult and easy airways. Most studies are characterized by high risk of bias and concerns of applicability. Reliable bedside criteria to predict difficult intubation remain elusive.

Prognosis and patterns of failure for the extubation of patients who remain intubated after head and neck surgery.

OBJECTIVE: This study aimed to analyze the rate of failure, patterns of failure, and prognostic factors for patients who remain intubated after head and neck surgery and then undergo delayed extubation. METHODS: Retrospective chart review of all otolaryngology patients who remained intubated after head and neck surgery and then underwent delayed extubation between 2006 and 2013. The incidence and patterns of extubation failure were analyzed. Univariable logistic regression analysis was performed to identify risk factors for postextubation failure. RESULTS: Fifteen of the 129 patients (12%) who remained intubated after head and neck surgery and underwent delayed extubation subsequently failed and required either repeat intubation or an emergency surgical airway. The most common reasons for failure were hemorrhage (47%) and upper airway edema (33%). Failure typically occurred within 6 hours of extubation. Twenty-seven percent of the patients who failed extubation (4/15) required an emergency surgical airway. On univariable logistic regression analysis, ligation of a major neck vessel predicted extubation failure (odds ratio=5.20; 95% confidence interval, 1.48-18.23). CONCLUSION: Postextubation failure in carefully selected patients undergoing delayed extubation after head and neck surgery is infrequent and most commonly due to postoperative bleeding. Prospective data are required to facilitate safe and quality care for these patients.

Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers.

INTRODUCTION: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm(2) versus 12.5-15.7 cm(2)). STUDY DESIGN AND METHODS: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A). In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF) filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B). RESULTS: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo. CONCLUSION: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of experimental pain models is critical to the advancement of translational pain research.

Review article: Extubation of the difficult airway and extubation failure.

Respiratory complications after tracheal extubation are associated with significant morbidity and mortality, suggesting that process improvements in this clinical area are needed. The decreased rate of respiratory adverse events occurring during tracheal intubation since the implementation of guidelines for difficult airway management supports the value of education and guidelines in advancing clinical practice. Accurate use of terms in defining concepts and describing distinct clinical conditions is paramount to facilitating understanding and fostering education in the treatment of tracheal extubation-related complications. As an example, understanding the distinction between extubation failure and weaning failure allows one to appreciate the need for pre-extubation tests that focus on assessing airway patency in addition to evaluating the ability to breathe spontaneously. Tracheal reintubation after planned extubation is a relatively rare event in the postoperative period of elective surgeries, with reported rates of reintubation in the operating room and postanesthesia care unit between 0.1% and 0.45%, but is a fairly common event in critically ill patients (0.4%-25%). Conditions such as obesity, obstructive sleep apnea, major head/neck and upper airway surgery, and obstetric and cervical spine procedures carry significantly increased risks of extubation failure and are frequently associated with difficult airway management. Extubation failure follows loss of upper airway patency. Edema, soft tissue collapse, and laryngospasm are among the most frequent mechanisms of upper airway obstruction. Planning for tracheal extubation is a critical component of a successful airway management strategy, particularly when dealing with situations at increased risk for extubation failure and in patients with difficult airways. Adequate planning requires identification of patients who have or may develop a difficult airway, recognition of situations at increased risk of postextubation airway compromise, and understanding the causes and underlying mechanisms of extubation failure. An effective strategy to minimize postextubation airway complications should include preemptive optimization of patients' conditions, careful timing of extubation, the presence of experienced personnel trained in advanced airway management, and the availability of the necessary equipment and appropriate postextubation monitoring.

Metabotropic glutamate receptor 5 antagonism with fenobam: examination of analgesic tolerance and side effect profile in mice.

BACKGROUND: The metabotropic glutamate receptor 5 noncompetitive antagonist fenobam is analgesic in rodents. Future development of fenobam as an analgesic in humans will require a favorable long-term treatment profile and a lack of significant deleterious side effects. This study aimed to determine whether tolerance to fenobam's analgesic effects developed over 14 days and to assess for side effects in mice. METHODS: Mouse models of pain, locomotor behavior, and coordination were used. Fenobam or vehicle (n = 8 or 11 per group) was administered for 14 days, and analgesic tolerance to fenobam was assessed using the formalin test. Histopathologic examination, hematology, and clinical chemistry analysis after 14-day fenobam administration were also assessed (n = 12 or 9). The effects of fenobam on locomotor activity were assessed in the open field and elevated zero maze (n = 8 or 7). Coordination was assessed using ledge crossing and vertical pole descent tasks (n = 11 or 10). RESULTS: Tolerance to fenobam's analgesic effect did not develop after 14 days. Chronic fenobam administration resulted in statistically significantly less weight gain compared with vehicle control subjects, but did not cause any physiologically or statistically significant hematologic abnormalities, altered organ function, or abnormal histopathology of the liver, brain, or testes. Fenobam administration resulted in a metabotropic glutamate receptor 5-dependent increase in exploratory behavior but does not impair motor coordination at analgesic doses. CONCLUSIONS: Analgesic tolerance to repeat fenobam dosing does not develop. Chronic dosing of up to 14 days is well tolerated. Fenobam represents a promising candidate for the treatment of human pain conditions.

Postoperative myocardial injury after major head and neck cancer surgery.

BACKGROUND: Patients with head and neck cancer often have multiple risk factors for coronary artery disease. Yet, little is known about the incidence of postoperative myocardial injury after major head and neck cancer surgery and its clinical relevance. The aim of this study was to determine the risk of postoperative myocardial injury in patients undergoing major head and neck cancer surgery. METHODS: This was a retrospective cohort study of all patients who underwent major head and neck cancer surgery (n = 378) at a single major academic center from April 2003 to July 2008. Peak postoperative troponin I (TnI) concentration was the primary outcome. RESULTS: Of 378 patients who underwent major head and neck cancer surgery, 57 patients (15%) had development of an elevated TnI; 90% of these occurred within the first 24 hours after surgery. Preexisting renal insufficiency (unadjusted OR [OR]: 4.60; 95% CI 1.53-13.82), coronary artery disease (OR: 2.33; 95% CI 1.21-4.50), peripheral vascular disease (OR: 2.83; 95% CI 1.31-6.14), hypertension (OR: 2.22; 95% CI 1.20-4.12), and previous combined chemotherapy and radiation (OR: 2.68; 95% CI 1.04-6.91) were associated with elevated postoperative TnI levels. Patients with elevated TnI levels had a significantly longer length of stay in the hospital (8.5 vs 10.1 days; p = .014) and ICU (3 vs 4.5 days; p = .001) and an 8-fold increased risk of death at 60 days after surgery (adjusted OR: 8.01, 95% CI 2.03-31.56). At 1 year, patients with an abnormal postoperative TnI level were twice as likely to die (OR 1.93; 95% CI 1.02-3.63). CONCLUSIONS: Patients who undergo major head and neck cancer surgery are at significant risk for postoperative myocardial injury, which is a strong predictor of 60-day mortality after surgery. Monitoring of myocardial injury during the first postoperative days, as well as optimizing preventive cardiac care, may be helpful to reduce postoperative mortality rates.

The metabotropic glutamate receptor subtype 5 antagonist fenobam is analgesic and has improved in vivo selectivity compared with the prototypical antagonist 2-methyl-6-(phenylethynyl)-pyridine.

Metabotropic glutamate receptor subtype 5 (mGlu5) has been demonstrated to play a role in the modulation of numerous nociceptive modalities. When administered via peripheral, intrathecal, or systemic routes, mGlu5 antagonists have analgesic properties in a variety of preclinical pain models. Despite a wealth of data supporting the use of mGlu5 antagonists to treat pain, studies have been limited to preclinical animal models due to a lack of mGlu5 antagonists that are approved for use in humans. It has been demonstrated previously that fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl)urea], an anxiolytic shown to be safe and effective in human trials, is a selective and potent noncompetitive antagonist of mGlu5 (J Pharmacol Exp Ther 315:711-721, 2005). Here, we report a series of studies aimed at testing whether fenobam, similar to the prototypical mGlu5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), has analgesic properties in mice. We show that fenobam reduces formalin-induced pain behaviors and relieves established inflammation-induced thermal hypersensitivity in mice. Similar results were seen with MPEP. Administration of fenobam resulted in an increase in locomotor activity in the open-field task but did not impair performance on the accelerating Rotarod. Analysis of brain and plasma fenobam levels indicated that fenobam is rapidly concentrated in brain after intraperitoneal administration in mice but is essentially cleared from circulation within 1 h after injection. Fenobam had no analgesic effect in mGlu5 knockout mice, whereas the prototypical antagonist MPEP retained significant analgesic efficacy in mGlu5 knockouts. These results demonstrate that fenobam is analgesic in mice and has an improved in vivo selectivity for mGlu5 over MPEP.