Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain.

BACKGROUND: Moderate-to-severe acute pain is prevalent in many healthcare settings and associated with adverse outcomes. Peripheral nerve blockade using traditional needle-based and local anesthetic-based techniques improves pain outcomes for some patient populations but has shortcomings limiting use. These limitations include its invasiveness, potential for local anesthetic systemic toxicity, risk of infection with an indwelling catheter, and relatively short duration of blockade compared with the period of pain after major injuries. Focused ultrasound is capable of inhibiting the peripheral nervous system and has potential as a pain management tool. However, investigations of its effect on peripheral nerve nociceptive fibers in animal models of acute pain are lacking. In an in vivo acute pain model, we investigated focused ultrasound's effects on behavior and peripheral nerve structure. METHODS: Focused ultrasound was applied directly to the sciatic nerve of rats just prior to a hindpaw incision; three control groups (focused ultrasound sham only, hindpaw incision only, focused ultrasound sham+hindpaw incision) were also included. For all four groups (intervention and controls), behavioral testing (thermal and mechanical hyperalgesia, hindpaw extension and flexion) took place for 4 weeks. Structural changes to peripheral nerves of non-focused ultrasound controls and after focused ultrasound application were assessed on days 0 and 14 using light microscopy and transmission electron microscopy. RESULTS: Compared with controls, after focused ultrasound application, animals had (1) increased mechanical nociceptive thresholds for 2 weeks; (2) sustained increase in thermal nociceptive thresholds for ≥4 weeks; (3) a decrease in hindpaw motor response for 0.5 weeks; and (4) a decrease in hindpaw plantar sensation for 2 weeks. At 14 days after focused ultrasound application, alterations to myelin sheaths and nerve fiber ultrastructure were observed both by light and electron microscopy. DISCUSSION: Focused ultrasound, using a distinct parameter set, reversibly inhibits A-delta peripheral nerve nociceptive, motor, and non-nociceptive sensory fiber-mediated behaviors, has a prolonged effect on C nociceptive fiber-mediated behavior, and alters nerve structure. Focused ultrasound may have potential as a peripheral nerve blockade technique for acute pain management. However, further investigation is required to determine C fiber inhibition duration and the significance of nerve structural changes.

Association of Common Pediatric Surgeries With New Onset Chronic Pain in Patients 0-21 Years of Age in the United States.

Chronic pain (CP) is a major public health issue. While new onset CP is known to occur frequently after some pediatric surgeries, its incidence after the most common pediatric surgeries is unknown. This retrospective cohort study used insurance claims data from 2002 to 2017 for patients 0 to 21 years of age. The primary outcome was CP 90 to 365 days after each of the 20 most frequent surgeries in 5 age categories (identified using CP ICD codes). Multivariable logistic regression identified surgeries and risk factors associated with CP after surgery. A total of 424,590 surgical patients aged 0 to 21 were included, 22,361 of whom developed CP in the 90 to 365 days after surgery. The incidences of CP after surgery were: 1.1% in age group 0 to 1 years; 3.0% in 2 to 5 years; 5.6% in 6 to 11 years; 10.1% in 12 to 18 years; 9.9% in 19 to 21 years. Some surgeries and patient variables were associated with CP. Approximately 1 in 10 adolescents who underwent the most common surgeries developed CP, as did a striking percentage of children in other age groups. Given the long-term consequences of CP, resources should be allocated toward identification of high-risk pediatric patients and strategies to prevent CP after surgery. PERSPECTIVE: This study identifies the incidences of and risk factors for chronic pain after common surgeries in patients 0 to 21 years of age. Our findings suggest that resources should be allocated toward the identification of high-risk pediatric patients and strategies to prevent CP after surgery.

Visualizing Opioid-Use Variation in a Pediatric Perioperative Dashboard.

BACKGROUND: Anesthesiologists integrate numerous variables to determine an opioid dose that manages patient nociception and pain while minimizing adverse effects. Clinical dashboards that enable physicians to compare themselves to their peers can reduce unnecessary variation in patient care and improve outcomes. However, due to the complexity of anesthetic dosing decisions, comparative visualizations of opioid-use patterns are complicated by case-mix differences between providers. OBJECTIVES: This single-institution case study describes the development of a pediatric anesthesia dashboard and demonstrates how advanced computational techniques can facilitate nuanced normalization techniques, enabling meaningful comparisons of complex clinical data. METHODS: We engaged perioperative-care stakeholders at a tertiary care pediatric hospital to determine patient and surgical variables relevant to anesthesia decision-making and to identify end-user requirements for an opioid-use visualization tool. Case data were extracted, aggregated, and standardized. We performed multivariable machine learning to identify and understand key variables. We integrated interview findings and computational algorithms into an interactive dashboard with normalized comparisons, followed by an iterative process of improvement and implementation. RESULTS: The dashboard design process identified two mechanisms-interactive data filtration and machine-learning-based normalization-that enable rigorous monitoring of opioid utilization with meaningful case-mix adjustment. When deployed with real data encompassing 24,332 surgical cases, our dashboard identified both high and low opioid-use outliers with associated clinical outcomes data. CONCLUSION: A tool that gives anesthesiologists timely data on their practice patterns while adjusting for case-mix differences empowers physicians to track changes and variation in opioid administration over time. Such a tool can successfully trigger conversation amongst stakeholders in support of continuous improvement efforts. Clinical analytics dashboards can enable physicians to better understand their practice and provide motivation to change behavior, ultimately addressing unnecessary variation in high impact medication use and minimizing adverse effects.

Dose-dependent effects of high intensity focused ultrasound on compound action potentials in an ex vivo rodent peripheral nerve model: comparison to local anesthetics.

BACKGROUND: In animal models, focused ultrasound can reversibly or permanently inhibit nerve conduction, suggesting a potential role in managing pain. We hypothesized focused ultrasound's effects on action potential parameters may be similar to those of local anesthetics. METHODS: In an ex vivo rat sciatic nerve model, action potential amplitude, area under the curve, latency to 10% peak, latency to 100% peak, rate of rise, and half peak width changes were assessed after separately applying increasing focused ultrasound pressures or concentrations of bupivacaine and ropivacaine. Focused ultrasound's effects on nerve structure were examined histologically. RESULTS: Increasing focused ultrasound pressures decreased action potential amplitude, area under the curve, and rate of rise, increased latency to 10% peak, and did not change latency to 100% peak or half peak width. Increasing local anesthetic concentrations decreased action potential amplitude, area under the curve, and rate of rise and increased latency to 10% peak, latency to 100% peak, and half peak width. At the highest focused ultrasound pressures, nerve architecture was altered compared with controls. DISCUSSION: While some action potential parameters were altered comparably by focused ultrasound and local anesthetics, there were small but notable differences. It is not evident if these differences may lead to differences in clinical pain effects when focused ultrasound is applied in vivo or if focused ultrasound pressures that result in clinically relevant changes damage nerve structures. Given the potential advantages of a non-invasive technique for managing pain conditions, further investigation may be warranted in an in vivo pain model.

Publication misrepresentation among pediatric anesthesiology fellowship applicants: A retrospective single-center cohort study.

BACKGROUND: Many medical specialties have found publication misrepresentation in residency and fellowship applications, but pediatric anesthesia fellowship application data is lacking. AIMS: We sought to determine the prevalence of publication misrepresentation among pediatric anesthesia fellowship applications. METHODS: In this retrospective cohort study, fellowship applications to Stanford University's pediatric anesthesiology fellowship program from 2009 to 2019 were reviewed. Only peer-reviewed journal articles listed as accepted or published were included. Nine additional variables were collected: applicant age, gender, citizenship status, American vs. international medical school, public vs. private medical school, allopathic doctor versus osteopathic doctor, number of years between college and medical school, additional degrees, and application year. The primary outcome was the rate of publication misrepresentation, defined as peer-reviewed journal citations listed on the application that could not be verified or on which the applicant was not listed as an author. Secondary outcomes were the associations between publication misrepresentation and the additional collected variables. RESULTS: 1280 peer-reviewed journal publications from 877 applicants were reviewed. 3.4% of all citations listed as peer-reviewed journal articles were misrepresented and 9.0% of all applicants with at least 1 publication had ≥1 misrepresented publications. 30.2% of publications labelled "misrepresented" were located in our search of databases but did not have the applicant as an author, and 69.8% could not be located using the search databases. Only one of the 9 collected variables (public vs private medical school) was significantly associated with publication misrepresentation. CONCLUSIONS: In this single-center retrospective study, publication misrepresentation was found to occur in one out of 11 pediatric anesthesia fellowship applications with at least one publication. Since residency and fellowship applicant publications may be heavily weighted during the application process, programs may want to include additional inquiries into the accuracy of applicant publications.

Ex Vivo Whole Nerve Electrophysiology Setup, Action Potential Recording, and Data Analyses in a Rodent Model.

Ex vivo rodent whole nerves provide a model for assessing the effects of interventions on nerve impulse transmission and consequent sensory and/or motor function. Nerve impulse transmission can be measured through sciatic nerve compound action potential (CAP) recordings. However, de novo development and implementation of an ex vivo whole nerve resection protocol and an electrophysiology setup that retains nerve viability, that produces low noise CAP signals, and that allows for data analysis is challenging. Additionally, some of the existing literature lacks detail and accuracy and may be out of date. This article describes detailed protocols for rodent ex vivo sciatic nerve dissection and handling; importance of an optimal physiologic solution; computer-aided designs for 3D printing of readily adaptable ex vivo rodent whole nerve electrophysiology chambers; construction of low-cost, effective suction electrodes; setup and use of nerve stimulators and amplifiers; acquisition of low noise, small voltage CAP data and digital conversion; use of software for data analyses of CAP components; and tips for troubleshooting. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Electrophysiology wiring and hardware setup Support Protocol 1: 3D printing an electrophysiology chamber Support Protocol 2: Building suction electrodes Basic Protocol 2: Sciatic nerve dissection and compound action potential recording Basic Protocol 3: Data export and analysis Support Protocol 3: Preparation of HEPES-buffered physiologic solution.

Cardiac Output Measurements Based on the Pulse Wave Transit Time and Thoracic Impedance Exhibit Limited Agreement With Thermodilution Method During Orthotopic Liver Transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is characterized by significant intraoperative hemodynamic variability. Accurate and real-time cardiac output (CO) monitoring aids clinical decision making during OLT. The purpose of this study is to compare accuracy, precision, and trending ability of CO estimation obtained noninvasively using pulse wave transit time (estimated continuous cardiac output [esCCO; Nihon Kohden, Tokyo, Japan]) or thoracic bioimpedance (ICON; Osypka Medical GmbH, Berlin, Germany) to thermodilution cardiac output (TDCO) measured with a pulmonary artery catheter. METHODS: Nineteen patients undergoing OLT were enrolled. CO measurements were collected with esCCO, ICON, and thermodilution at 5 time points: (T1) pulmonary artery catheter insertion; (T2) surgical incision; (T3) portal reperfusion; (T4) hepatic arterial reperfusion; and (T5) abdominal closure. The results were analyzed with Bland-Altman plot, percentage error (the percentage of the difference between the CO estimated with the noninvasive monitoring device and CO measured with the thermodilution technique), 4-quadrant plot with concordance rate (the percentage of the total number of points in the I and III quadrant of the 4-quadrant plot), and concordance correlation coefficient (a measure of how well the pairs of observations deviate from the 45-degree line of perfect agreement). RESULTS: Although TDCO increased at T3-T5, both esCCO and ICON failed to track the changes of CO with sufficient accuracy and precision. The mean bias of esCCO and ICON compared to TDCO were -2.0 L/min (SD, ±2.7 L/min) and -3.3 L/min (SD, ±2.8 L/min), respectively. The percentage error was 69% for esCCO and 77% for ICON. The concordance correlation coefficient was 0.653 (95% confidence interval [CI], 0.283-0.853) for esCCO and 0.310 (95% CI, -0.167 to 0.669) for ICON. Nonetheless, esCCO and ICON exhibited reasonable trending ability of TDCO (concordance rate: 95% [95% CI, 88-100] and 100% [95% CI, 93-100]), respectively. The mean bias was correlated with systemic vascular resistance (SVR) and arterial elastance (Ea) for esCCO (SVR, r = 0.610, 95% CI, 0.216-0.833, P < .0001; Ea, r = 0.692, 95% CI, 0.347-0.872; P < .0001) and ICON (SVR, r = 0.573, 95% CI, 0.161-0.815, P < .0001; Ea, r = 0.612, 95% CI, 0.219-0.834, P < .0001). CONCLUSIONS: The noninvasive CO estimation with esCCO and ICON exhibited limited accuracy and precision, despite with reasonable trending ability, when compared to TDCO, during OLT. The inaccuracy of esCCO and ICON is especially large when SVR and Ea were decreased during the neohepatic phase. Further refinement of the technology is desirable before noninvasive techniques can replace TDCO during OLT.

Heart rate variability: implications for perioperative anesthesia care.

PURPOSE OF REVIEW: Heart rate variability (HRV) is a measure of the balance between both the parasympathetic and sympathetic nervous system and may provide useful information for anesthesia care providers. HRV may offer predictive information about critically ill and operative patients. Further, HRV collection provides real-time information of patient autonomic nervous system status and may allow tailoring of the analgesia for patients in the ICU and operating room. RECENT FINDINGS: Reduced and abnormal resting HRV predict sudden and nonsudden cardiac death. Recent evidence shows that decreased HRV correlates with worsened outcomes in both trauma patients and patients with sepsis, as well as the risk of developing hypotension after induction of general anesthesia and placement of intrathecal local anesthesia. In addition, HRV appears to provide an accurate assessment of the nociception-analgesia balance in deeply sedated ICU patients and those under general anesthesia. SUMMARY: No study has assessed the prognostic value of preoperative HRV in patients presenting for surgery. Use of HRV for patient risk stratification and intraoperative analgesia management may allow tailored perioperative care and improved outcomes. If intraoperative HRV data leads to decreased perioperative opioid use, opioid-related adverse events, a serious perioperative issue, may be decreased. CLINICAL TRIALS REGISTRATION: Not applicable.

The effectiveness of nasal mask vs face mask ventilation in anesthetized, apneic pediatric subjects over 2 years of age: a randomized controlled trial.

BACKGROUND: We hypothesized that anesthetized, apneic children could be ventilated equivalently or more efficiently by nasal mask ventilation (NMV) than face mask ventilation (FMV). The aim of this randomized controlled study was to test this hypothesis by comparing the expiratory tidal volume (Vte) between NMV and FMV. METHODS: After the induction of anesthesia, 41 subjects, 3-17 years of age without anticipated difficult mask ventilation, were randomly assigned to receive either NMV or FMV with neck extension. Both groups were ventilated with pressure control ventilation (PCV) at 20 cmH2 O of peak inspiratory pressure (PIP) with positive end-expiratory pressure (PEEP) levels of 0, 5, and 10 cmH2 O. An additional mouth closing maneuver (MCM) was applied for the NMV group. RESULTS: The Vte was higher in the FMV group compared with the NMV group (median difference [95% CI]: 8.4 [5.5-11.6] ml·kg(-1) ; P < 0.001) when MCM was not applied. NMV achieved less PEEP than FMV (median difference [95% CI]: 5.0 [4.3-5.3] cmH2 O at 10 cmH2 O; P < 0.001) though both groups achieved the set PIP level. In the NMV group, MCM markedly increased Vte (median increase [95% CI]: 5.9 [2.5-9.0] ml·kg(-1) ; P < 0.005) and PEEP (median increase [95% CI]: 5.0 [0.6-8.6] cmH2 O at 10 cmH2 O; P < 0.005); however, PEEP was highly variable and lower than that of FMV (median difference [95% CI]: 2.5 [0.8-8.5] cmH2 O at 10 cmH2 O; P < 0.05). CONCLUSIONS: In anesthetized, apneic children greater than 2 years of age ventilated with an anesthesia ventilator and neck extension, FMV established a greater Vte than NMV regardless of mouth status. NMV could not maintain the set PEEP level due to an air leak from the mouth. The MCM increased the Vte and PEEP.

Volatile anesthetics for status asthmaticus in pediatric patients: a comprehensive review and case series.

Status asthmaticus is an acute, intractable asthma attack refractory to standard interventions that can lead to progressive respiratory failure. Successful management requires a fundamental understanding of the disease process, its clinical presentation, and proper evaluation. Treatment must be instituted early and is aimed at reversing the airway inflammation, bronchoconstriction, and hyper-reactivity that often lead to lower airway obstruction, impaired ventilation, and oxygenation. Most patients are effectively treated with standard therapy including beta2-adrenergic agonists and corticosteroids. Others necessitate adjunctive therapies and escalation to noninvasive ventilation or intubation. We will review the pathophysiology, evaluation, and treatment options for pediatric patients presenting with status asthmaticus with a particular focus on refractory status asthmaticus treated with volatile anesthetics. In addition, we include a proven approach to the management of these patients in the critical care setting, which requires close coordination between critical care and anesthesia providers. We present a case series of three patients, two of which have the longest reported cases of continuous isoflurane use in status asthmaticus. This series was obtained from a retrospective chart review and highlights the efficacy of the volatile anesthetic, isoflurane, in three pediatric patients with refractory life-threatening status asthmaticus.

Continuous noninvasive cardiac output in children: is this the next generation of operating room monitors? Initial experience in 402 pediatric patients.

BACKGROUND: Electrical Cardiometry(™) (EC) estimates cardiac parameters by measuring changes in thoracic electrical bioimpedance during the cardiac cycle. The ICON(®), using four electrocardiogram electrodes (EKG), estimates the maximum rate of change of impedance to peak aortic blood acceleration (based on the premise that red blood cells change from random orientation during diastole (high impedance) to an aligned state during systole (low impedance)). OBJECTIVE: To determine whether continuous cardiac output (CO) data provide additional information to current anesthesia monitors that is useful to practitioners. METHODS: After IRB approval and verbal consent, 402 children were enrolled. Data were uploaded to our anesthesia record at one-minute intervals. Ten-second measurements (averaged over the previous 20 heart beats) were downloaded to separate files for later comparison with routine OR monitors. RESULTS: Data from 374 were in the final cohort (loss of signal or improper lead placement); 292,012 measurements during 58,049 min of anesthesia were made in these children (1 day to 19 years and 1 to 107 kg). Four events had a ≥25% reduction in cardiac index at least 1 min before a clinically important change in other monitored parameters; 18 events in 14 children confirmed manifestations of other hemodynamic measures; eight events may have represented artifacts because the observed measurements did not seem to fit the clinical parameters of the other monitors; three other events documented decreased stroke index with extreme tachycardia. CONCLUSIONS: Electrical cardiometry provides real-time cardiovascular information regarding developing hemodynamic events and successfully tracked the rapid response to interventions in children of all sizes. Intervention decisions must be based on the combined data from all monitors and the clinical situation. Our experience suggests that this type of monitor may be an important addition to real-time hemodynamic monitoring.

Anesthetic considerations in Sheldon-Hall syndrome.

Arthrogryposis is characterized by multiple, nonprogressive joint contractures which may be caused by maternal disorders such as oligohydramnios as well as fetal akinesia resulting from primary disorders of muscle, connective tissue, or neurologic tissue. Its prevalence is about 1 : 3000. Distal arthrogryposis (DA) is a heterogenous group of genetic disorders with a characteristic flexion of the joints of the hands and feet divided into different types with additional features. Sheldon-Hall Syndrome (SHS), also known as distal arthrogryposis type 2A (DA2A), has some nonorthopedic features of specific importance to anesthetic care.