Practice what you teach: An approach to integrate airway education for experienced anesthesia clinicians.

BACKGROUND: The COVID-19 pandemic has disrupted clinician education. To address this challenge, our divisional difficult airway program (AirEquip) designed and implemented small-group educational workshops for experienced clinicians. Our primary aim was to test the feasibility and acceptability of a small-group, flexible-curriculum skills workshop conducted during the clinical workday. Secondary objectives were to evaluate whether our workshop increased confidence in performing relevant skills and to assess the work-effort required for the new program. METHODS: We implemented a 1:1 and 2:1 (participant to facilitator ratio) airway skills workshop for experienced clinicians during the workday. A member of the AirEquip team temporarily relieved the attendee of clinical duties to facilitate participation. Attendance was encouraged but not required. Feasibility was assessed by clinician attendance, and acceptability was assessed using three Likert scale questions and derived from free-response feedback. Participants completed pre and postworkshop surveys to assess familiarity and comfort with various aspects of airway management. A work-effort analysis was conducted and compared to the effort to run a previously held larger-format difficult airway conference. RESULTS: Fifteen workshops were conducted over 7 weeks; members of AirEquip were able to temporarily assume participants' clinical duties. Forty-seven attending anesthesiologists and 17 CRNAs attended the workshops, compared with six attending anesthesiologists and five CRNAs who attended the most recent larger-format conference. There was no change in confidence after workshop participation, but participants overwhelmingly expressed enthusiasm and satisfaction with the workshops. The number of facilitator person-hours required to operate the workshops (105 h) was similar to that required to run a single all-day larger-format conference (104.5 h). CONCLUSION: It is feasible and acceptable to incorporate expert-led skills training into the clinical workday. Alongside conferences and large-format instruction, this modality enhances the way we are able to share knowledge with our colleagues. This concept can likely be applied to other skills in various clinical settings.

Imaging sedation and anesthesia practice patterns in pediatric radiology departments - a survey of the Society of Chiefs of Radiology at Children's Hospitals (SCORCH).

BACKGROUND: There are few data describing practice patterns related to the use of sedation/anesthesia for diagnostic imaging in pediatric radiology departments. OBJECTIVE: To understand current practice patterns related to imaging with sedation/anesthesia in pediatric radiology departments based on a survey of the Society of Chiefs of Radiology at Children's Hospitals (SCORCH) in conjunction with the American College of Radiology's Pediatric Imaging Sedation and Anesthesia Committee. MATERIALS AND METHODS: A multi-question survey related to imaging with sedation/anesthesia in pediatric radiology departments was distributed to SCORCH member institutions in January 2019. A single reminder email was sent. Descriptive statistical analyses were performed. RESULTS: Of the 84 pediatric radiology departments, 23 (27%) completed the survey. Fifty-seven percent of the respondents self-identified as academic/university-affiliated and 13% as a division/section in an adult radiology department. Imaging sedation (excluding general anesthesia) is commonly performed by pediatric anesthesiologists (76%) and intensive care unit physicians (intensivists, 48%); only 14% of departments expect their pediatric radiologists to supervise imaging sedation. Ninety-six percent of departments use child life specialists for patient preparation. Seventy percent of departments have preparatory resources available on a website, including simulation videos (26%) and audio clips (17%). Nearly half (48%) of the departments have a mock scanner to aid in patient preparation. Imaging sedation/anesthesia is most often scheduled at the request of ordering clinicians (65%), while 57% of departments allow schedulers to place patients into imaging sedation/anesthesia slots based on specified criteria. CONCLUSION: Imaging sedation/anesthesia practice patterns vary among pediatric radiology departments, and understanding current approaches can help with standardization and practice improvement.

Guide to the statistical analysis plan.

Biomedical research has been struck with the problem of study findings that are not reproducible. With the advent of large databases and powerful statistical software, it has become easier to find associations and form conclusions from data without forming an a-priori hypothesis. This approach may yield associations without clinical relevance, false positive findings, or biased results due to "fishing" for the desired results. To improve reproducibility, transparency, and validity among clinical trials, the National Institute of Health recently updated its grant application requirements, which mandates registration of clinical trials and submission of the original statistical analysis plan (SAP) along with the research protocol. Many leading journals also require the SAP as part of the submission package. The goal of this article and the companion article detailing the SAP of an actual research study is to provide a practical guide on writing an effective SAP. We describe the what, why, when, where, and who of a SAP, and highlight the key contents of the SAP.

An International, Multicenter, Observational Study of Cerebral Oxygenation during Infant and Neonatal Anesthesia.

BACKGROUND: General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia-ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants. METHODS: This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline); for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg); and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%). RESULTS: The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation; American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze. CONCLUSIONS: Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.

Absence of Neuropathology With Prolonged Isoflurane Sedation in Healthy Adult Rats.

BACKGROUND: The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long-term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation. METHODS: Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with α-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7. RESULTS: Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged. CONCLUSIONS: No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology.

Optimal Timing of Surgical Procedures in Pediatric Patients.

The Pediatric Anesthesia Neuro Development Assessment (PANDA) team at the Anesthesiology Department at Columbia University Medical Center held its fifth biennial symposium to discuss issues regarding potential neurotoxicity of anesthetic agents in pediatric patients. Overall optimal surgical timing as well as a "critical window" for surgery on a specialty specific basis are areas of focus for the American Academy of Pediatrics Surgical Advisory Panel. An ad hoc panel of pediatric surgical experts representing general surgery, urology, neurosurgery, and ophthalmology was assembled for this meeting and provided a dialogue focused on the benefits of early intervention versus potential anesthetic risk, addressing parental concerns, and the need for continued interdisciplinary collaboration in this area.

Neurocognitive Adverse Effects of Anesthesia in Adults and Children: Gaps in Knowledge.

Numerous preclinical and clinical studies investigating the neurodevelopmental and neurocognitive effects of exposure to anesthesia and the combination of anesthesia and surgery have demonstrated histopathological and both temporary and long-term cognitive and behavioral effects at the extremes of the human age spectrum. Increasing coverage in the lay press for both our youngest and oldest patient populations has led to heightened concerns regarding the potential harmful side effects of almost all commonly used anesthetic drug regimens. Although the majority of information regarding anesthetic risks in the developing brain derives from preclinical work in rodents, research involving the aged brain has identified a well-defined postoperative cognitive phenotype in humans. While preclinical and clinical data appear to support some association between anesthesia and surgery and the development of detrimental cognitive changes in both the developing and the aged brain, correlation between anesthesia and surgery and poor neurological outcomes does not imply causation. Given this information, no single anesthetic or group of anesthetics can be recommended over any other in terms of causing or preventing negative neurocognitive outcomes in either population. This review summarizes the growing body of preclinical and clinical literature dedicated to the detrimental effects of anesthesia on both the developing and the aging brain.

Neurotoxicity, general anesthesia in young children, and a survey of current pediatric anesthesia practice at US teaching institutions.

BACKGROUND: Recent articles in both scholarly journals and the lay press about the topic of anesthetic related neurotoxicity have increased the awareness and discussion of this topic with parents and other pediatric medical specialties (i.e., surgeons, radiologists, and pediatricians). AIM: The purpose of the present study was to survey how a subset of pediatric anesthesia departments in the US have responded to the issue of anesthetic related neurotoxicity in terms of clinical practice, training and communication with other medical specialties, and the frequency and timing of discussions with families. METHODS: A survey consisting of 22 questions was sent to PALC (Pediatric Anesthesia Leadership Council) & PAPDA (Pediatric Anesthesia Program Directors Association) via SurveyMonkey. The survey was divided into sections on Anesthesia Faculty/Trainees, Parents and Non-Anesthesia Providers. Responses to the survey were solicited via email to PALC and PAPDA, and then followed up with reminders to individual emails using the mailing lists of both organizations. RESULTS: The results of this survey demonstrate that pediatric anesthesia programs around the US do not have a consistent approach in managing the topic of anesthesia-related neurotoxicity with pediatric anesthesiologists, anesthesiology residents, pediatric anesthesiology fellows and their non-anesthesia medical and surgical colleagues, as well as the discussion of this topic with parents. CONCLUSION: A significant need exists to provide information to other pediatric professionals and parents. A consistent message from all providers that includes what is known, and indeed more importantly what is not known may be a useful approach.

Characterization and quantification of isoflurane-induced developmental apoptotic cell death in mouse cerebral cortex.

BACKGROUND: Accumulating evidence indicates that isoflurane and other, similarly acting anesthetics exert neurotoxic effects in neonatal animals. However, neither the identity of dying cortical cells nor the extent of cortical cell loss has been sufficiently characterized. We conducted the present study to immunohistochemically identify the dying cells and to quantify the fraction of cells undergoing apoptotic death in neonatal mouse cortex, a substantially affected brain region. METHODS: Seven-day-old littermates (n = 36) were randomly assigned to a 6-hour exposure to either 1.5% isoflurane or fasting in room air. Animals were euthanized immediately after exposure and brain sections were double-stained for activated caspase 3 and one of the following cellular markers: Neuronal Nuclei (NeuN) for neurons, glutamic acid decarboxylase (GAD)65 and GAD67 for GABAergic cells, as well as GFAP (glial fibrillary acidic protein) and S100ß for astrocytes. RESULTS: In 7-day-old mice, isoflurane exposure led to widespread increases in apoptotic cell death relative to controls, as measured by activated caspase 3 immunolabeling. Confocal analyses of caspase 3-labeled cells in cortical layers II and III revealed that the overwhelming majority of cells were postmitotic neurons, but some were astrocytes. We then quantified isoflurane-induced neuronal apoptosis in visual cortex, an area of substantial injury. In unanesthetized control animals, 0.08% ± 0.001% of NeuN-positive layer II/III cortical neurons were immunoreactive for caspase 3. By contrast, the rate of apoptotic NeuN-positive neurons increased at least 11-fold (lower end of the 95% confidence interval [CI]) to 2.0% ± 0.004% of neurons immediately after isoflurane exposure (P = 0.0017 isoflurane versus control). In isoflurane-treated animals, 2.9% ± 0.02% of all caspase 3-positive neurons in superficial cortex also coexpressed GAD67, indicating that inhibitory neurons may also be affected. Analysis of GABAergic neurons, however, proved unexpectedly complex. In addition to inducing apoptosis among some GAD67-immunoreactive neurons, anesthesia also coincided with a dramatic decrease in both GAD67 (0.98 vs 1.84 ng/mg protein, P < 0.00001, anesthesia versus control) and GAD65 (2.25 ± 0.74 vs 23.03 ± 8.47 ng/mg protein, P = 0.0008, anesthesia versus control) protein levels. CONCLUSIONS: Prolonged exposure to isoflurane increased neuronal apoptotic cell death in 7-day-old mice, eliminating approximately 2% of cortical neurons, of which some were identified as GABAergic interneurons. Moreover, isoflurane exposure interfered with the inhibitory nervous system by downregulating the central enzymes GAD65 and GAD67. Conversely, at this age, only a minority of degenerating cells were identified as astrocytes. The clinical relevance of these findings in animals remains to be determined.

Cell age-specific vulnerability of neurons to anesthetic toxicity.

OBJECTIVE: Anesthetics have been linked to widespread neuronal cell death in neonatal animals. Epidemiological human studies have associated early childhood anesthesia with long-term neurobehavioral abnormalities, raising substantial concerns that anesthetics may cause similar cell death in young children. However, key aspects of the phenomenon remain unclear, such as why certain neurons die, whereas immediately adjacent neurons are seemingly unaffected, and why the immature brain is exquisitely vulnerable, whereas the mature brain seems resistant. Elucidating these questions is critical for assessing the phenomenon's applicability to humans, defining the susceptible age, predicting vulnerable neuronal populations, and devising mitigating strategies. METHODS: This study examines the effects of anesthetic exposure on late- and adult-generated neurons in newborn, juvenile, and adult mice, and characterizes vulnerable cells using birth-dating and immunohistochemical techniques. RESULTS: We identify a critical period of cellular developmental during which neurons are susceptible to anesthesia-induced apoptosis. Importantly, we demonstrate that anesthetic neurotoxicity can extend into adulthood in brain regions with ongoing neurogenesis, such as dentate gyrus and olfactory bulb. INTERPRETATION: Our findings suggest that anesthetic vulnerability reflects the age of the neuron, not the age of the organism, and therefore may potentially not only be relevant to children but also to adults undergoing anesthesia. This observation further predicts differential heightened regional vulnerability to anesthetic neuroapoptosis to closely follow the distinct regional peaks in neurogenesis. This knowledge may help guide neurocognitive testing of specific neurological domains in humans following exposure to anesthesia, dependent on the individual's age during exposure.

Anesthetics and sedatives: toxic or protective for the developing brain?

Despite our insufficient understanding of the exact molecular mechanisms of general anesthetics and sedatives, every year millions of children are treated with these drugs in a seemingly safe manner. However, increasing evidence particularly from animal studies has suggested the possibility for deleterious effects in pediatric patients. All currently clinically utilized anesthetic drugs have been found to induce neuronal cell death in the developing brain and to potentially cause long-term neurological impairment. Conversely, painful stimuli without analgesia and anesthesia have also been shown to initiate a harmful stress response in young children and to trigger neurotoxic effects in the developing brain, which can be blunted by anesthetics. Moreover, anesthetic drugs may also confer neurological protection during hypoxic and ischemic insults. The mechanisms and human applicability of anesthetic neurotoxicity and neuroprotection remain under intense investigation and this Perspectives article summarizes the current state of research.

The impact of the perioperative period on neurocognitive development, with a focus on pharmacological concerns.

Mounting evidence from animal studies has implicated that all commonly used anaesthetics and sedatives may induce widespread neuronal cell death and result in long-term neurological abnormalities. These findings have led to serious questions regarding the safe use of these drugs in young children. In humans, recent findings from retrospective, epidemiological studies do not exclude the possibility of an association between surgery with anaesthesia early in life and subsequent learning abnormalities. These results have sparked discussions regarding the appropriate timing of paediatric surgery and the safe management of paediatric anaesthesia. However, important questions need to be addressed before findings from laboratory studies and retrospective clinical surveys can be used to guide clinical practice. This article summarises the currently available preclinical and clinical information regarding the impact of anaesthetics, sedatives, opioids, pain and stress, inflammation, hypoxia-ischaemia, co-morbidities and genetic predisposition on brain structure and long-term neurological function. Moreover, this article outlines the putative mechanisms of anaesthetic neurotoxicity, and the phenomenon's implications for clinical practice in this rapidly emerging field.