Michael Chen

All Publications

• Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Holubar, M., Subramanian, A., Purington, N., Hedlin, H., Bunning, B., Walter, K. S., Bonilla, H., Boumis, A., Chen, M., Clinton, K., Dewhurst, L., Epstein, C., Jagannathan, P., Kaszynski, R. H., Panu, L., Parsonnet, J., Ponder, E. L., Quintero, O., Sefton, E., Singh, U., Soberanis, L., Truong, H., Andrews, J. R., Desai, M., Khosla, C., Maldonado, Y. 2022

  Abstract

  Favipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.We conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1: 1 to receive placebo or favipiravir (1800mg BID Day 1, 800 mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis.From July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48-1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54-1.29; sustained: HR 0.87, 95% CI 0.52-1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.Our data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.

  View details for DOI 10.1093/cid/ciac312

  View details for PubMedID 35446944

• A Pilot Quality Improvement Project to Reduce Intraoperative MRI Hypothermia in Neurosurgical Patients. Pediatric quality & safety Wong, B. J., Rama, A., Caruso, T. J., Lee, C. K., Wang, E., Chen, M. 2022; 7 (2): e531

  Abstract

  Intraoperative hypothermia increases patient morbidity, including bleeding and infection risk. Neurosurgical intraoperative magnetic resonance imaging (iMRI) can lead to hypothermia from patient exposure and low ambient temperature in the MRI suite. This quality improvement project aimed to reduce the risk of hypothermia during pediatric neurosurgery laser ablation procedures with iMRI. The primary aim was to increase the mean lowest core temperature in pediatric patients with epilepsy during iMRI procedures by 1 °C from a baseline mean lowest core temperature of 34.2 ± 1.2 °C within 10 months and sustain for 10 months.Methods: This report is a single-institution quality improvement project from March 2019 to June 2021, with 21 patients treated at a pediatric hospital. After identifying key drivers, temperature-warming interventions were instituted to decrease hypothermia among patients undergoing iMRI during neurosurgery procedures. A multidisciplinary team of physicians, nurses, and MRI technologists convened for huddles before each case. Interventions included prewarmed operating rooms (ORs), blanket coverings, MRI table and room; forced-air blanket warming, temperature monitoring in the OR and iMRI environments; and the MRI fan turned off.Results: Data were analyzed for five patients before and nine patients after the institution of the temperature-warming elements. The sustainment period included 15 patients. The mean lowest intraoperative temperature rose from 34.2 ± 1.3 °C in the preintervention period to 35.5 ± 0.6 °C in sustainment (P = 0.004).Conclusion: Hybrid OR and MRI procedures increase hypothermia risk, which increases patient morbidity. Implementation of a multidisciplinary, multi-item strategy for patient warming mitigates the risk.

  View details for DOI 10.1097/pq9.0000000000000531

  View details for PubMedID 35369418

• Anesthesia for the Pediatric Patient With Epilepsy and Minimally Invasive Surgery for Epilepsy CURRENT ANESTHESIOLOGY REPORTS Wong, B. J., Agarwal, R., Chen, M. I. 2021

  View details for DOI 10.1007/s40140-021-00457-2

  View details for Web of Science ID 000686464700001

• Near Miss in Intraoperative Magnetic Resonance Imaging: A Case for In Situ Simulation. Pediatric quality & safety Rama, A., Knight, L. J., Berg, M., Chen, M., Gonzales, R., Delhagen, T., Copperman, L., Caruso, T. J. 2019; 4 (6): e222

  Abstract

  Pediatric patients in intraoperative magnetic resonance imaging (iMRI) settings are at high risk for morbidity should an adverse event occur. We describe an experience in the iMRI scanner where no harm occurred, yet revealed an opportunity to improve the safety of patients utilizing the iMRI. The perioperative quality improvement team, resuscitation team, and radiology nurse leadership collaborated to understand the process better through in situ simulation.Methods: After a problem analysis, the team planned an in situ, high-fidelity simulation with predefined learning objectives to identify previously overlooked opportunities for improvement. The iMRI simulation had unique considerations, including the use of a magnetic resonance imaging (MRI)-compatible mannequin and ensuring participants' safety. Audiovisual equipment was placed in strategic locations to record the MRI and operating room (OR) segments of the simulation, and trained health-care simulation experts provided debriefing.Results: After completion of the iMRI simulation, the quality improvement team solicited feedback from participants and reviewed the video-recorded simulation. Several opportunities for improvement surrounding staff responsibilities and unique aspects of the iMRI environment were identified.Conclusions: iMRI in situ simulation has not been previously described. It presents unique challenges given the integration of personnel from OR and radiology environments, anesthetized patients, and risks from the high-powered MRI magnet. Other institutions utilizing hybrid ORs with iMRI may consider conducting in situ simulations using the described methods.

  View details for DOI 10.1097/pq9.0000000000000222

  View details for PubMedID 32010849

• Operating Room Codes Redefined: A Highly Reliable Model Integrating the Core Hospital Code Team. Pediatric quality & safety Caruso, T. J., Rama, A. n., Knight, L. J., Gonzales, R. n., Munshey, F. n., Darling, C. n., Chen, M. n., Sharek, P. J. 2019; 4 (3): e172

  Abstract

  Typically, multidisciplinary teams manage cardiac arrests occurring outside of the operating room (OR). This approach results in reduced morbidity. However, arrests that occur in the OR are usually managed by OR personnel alone, missing the benefits of out-of-OR hospital code teams. At our institution, there were multiple pathways to activate codes, each having different respondents, depending on time and day of the week. This improvement initiative aimed to create a reliable intraoperative emergency response system with standardized respondents and predefined roles.A multidisciplinary improvement team led this project at an academic pediatric hospital in California. After simulations performed in the OR (in situ), the team identified a valuable key driver-a consistent activation process that initiated standard respondents, 24 hours a day, 7 days a week. By utilizing core hospital code members routinely available outside of the OR during days, nights, and weekends, respondents were identified to augment OR personnel. Code roles were preassigned. After education, we conducted in situ simulations that included the perioperative and out-of-OR code team members. We administered a knowledge assessment to perioperative staff.The knowledge assessment for perioperative staff (n = 52) had an average score of 96%. Review of subsequent OR codes reflects an improved initiation process and management.The process for activating the emergency response system and roles for intraoperative code respondents were standardized to ensure a predictable code response, regardless of time or day of the week. Ongoing simulations with perioperative personnel continue to optimize the process.

  View details for DOI 10.1097/pq9.0000000000000172

  View details for PubMedID 31579871

  View details for PubMedCentralID PMC6594783

• Small-Volume Injections: Evaluation of Volume Administration Deviation From Intended Injection Volumes. Anesthesia and analgesia Muffly, M. K., Chen, M. I., Claure, R. E., Drover, D. R., Efron, B., Fitch, W. L., Hammer, G. B. 2017

  Abstract

  In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase.Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025 mL, 0.05 mL, 0.1 mL, 0.25 mL, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence. To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear regression model. Analysis of variance was used to determine whether the absolute log proportional error differed by the intended injection volume. Interindividual and intraindividual deviation from the intended injection volume was also characterized.As the intended injection volumes decreased, the absolute log proportional injection volume error increased (analysis of variance, P < .0018). The exploratory analysis revealed no significant difference in the standard deviations of the log proportional errors for injection volumes between physicians and pediatric PACU nurses; however, the difference in absolute bias was significantly higher for nurses with a 2-sided significance of P = .03.Clinically significant dose variation occurs when injecting volumes ≤0.5 mL. Administering small volumes of medications may result in unintended medication administration errors.

  View details for DOI 10.1213/ANE.0000000000001976

  View details for PubMedID 28338490

• Small-Volume Injections: Evaluation of Volume Administration Deviation From Intended Injection Volumes. Anesthesia and analgesia Muffly, M. K., Chen, M. I., Claure, R. E., Drover, D. R., Efron, B., Fitch, W. L., Hammer, G. B. 2017

  Abstract

  In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase.Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025 mL, 0.05 mL, 0.1 mL, 0.25 mL, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence. To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear regression model. Analysis of variance was used to determine whether the absolute log proportional error differed by the intended injection volume. Interindividual and intraindividual deviation from the intended injection volume was also characterized.As the intended injection volumes decreased, the absolute log proportional injection volume error increased (analysis of variance, P < .0018). The exploratory analysis revealed no significant difference in the standard deviations of the log proportional errors for injection volumes between physicians and pediatric PACU nurses; however, the difference in absolute bias was significantly higher for nurses with a 2-sided significance of P = .03.Clinically significant dose variation occurs when injecting volumes ≤0.5 mL. Administering small volumes of medications may result in unintended medication administration errors.

  View details for DOI 10.1213/ANE.0000000000001976

  View details for PubMedID 28338490

• Affordable Simulation for Small-Scale Training and Assessment SIMULATION IN HEALTHCARE Edler, A. A., Chen, M., Honkanen, A., Hackel, A., Golianu, B. 2010; 5 (2): 112-115

  Abstract

  High-fidelity patient simulation is increasingly recognized as an effective means of team training, acquisition and maintenance of technical and professional skills, and reliable performance assessment; however, finding a cost effective solution to providing such instruction can be difficult. This report describes the rationale, design, and appropriateness of a portable simulation model and example of its successful use at national meetings.The Stanford Simulation Group, in association with several other centers, developed a portable Pediatric Simulation Training and Assessment Program (Pediatric Anesthesia in-Situ Simulation) and presented it at two national meetings. The technical challenges and costs of development are outlined, and a satisfaction survey was conducted at the completion of the program.All respondents (100%) either agreed or strongly agreed that the course was useful, met expectations, was enjoyable, and that the scenarios were realistic.The Portable Simulation Training and Assessment Program (Pediatric Anesthesia in-Situ Simulation) presents innovative educational and financial opportunities to assist in both training and assessment of critical emergency response skills at smaller institutions and allows specialized instruction in an in situ setting.

  View details for DOI 10.1097/SIH.0b013e3181c76332

  View details for PubMedID 20661010

• Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children PEDIATRIC ANESTHESIA Hammer, G. B., Sam, W. J., Chen, M. I., Golianu, B., Drover, D. R. 2009; 19 (2): 138-144

  Abstract

  Propofol is a sedative-hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration-response relationship during EGD in children. This study aimed to investigate the pharmacodynamic interaction of propofol and dexmedetomidine when used in combination for children undergoing EGD.A total of 24 children undergoing EGD, ages 3-10 years, were enrolled in this study. Twelve children received dexmedetomidine 1 microg x kg(-1) given over 10 min as well as a continuous infusion of propofol delivered by a computer-assisted target-controlled infusion (TCI) system with target plasma concentrations ranging from 2.8 to 4.0 microg x ml(-1) (DEX group). Another group of 12 children undergoing EGD also received propofol administered by TCI targeting comparable plasma concentrations without dexmedetomidine (control group). We used logistic regression to predict plasma propofol concentrations at which 50% of the patients exhibited minimal response to stimuli (EC50 for anesthesia).The EC50 +/- SE values in the control and DEX groups were 3.7 +/- 0.4 microg x ml(-1) and 3.5 +/- 0.2 microg x ml(-1), respectively. There was no significant shift in the propofol concentration-response curve in the presence of dexmedetomidine.The EC50 of propofol required to produce adequate anesthesia for EGD in children was unaffected by a concomitant infusion of dexmedetomidine 1 microg x kg(-1) given over 10 min.

  View details for DOI 10.1111/j.1460-9592.2008.02823.x

  View details for PubMedID 19207899

• Patient simulation: a literary synthesis of assessment tools in anesthesiology. Journal of educational evaluation for health professions Edler, A. A., Fanning, R. G., Chen, M. I., Claure, R., Almazan, D., Struyk, B., Seiden, S. C. 2009; 6: 3-?

  Abstract

  High-fidelity patient simulation (HFPS) has been hypothesized as a modality for assessing competency of knowledge and skill in patient simulation, but uniform methods for HFPS performance assessment (PA) have not yet been completely achieved. Anesthesiology as a field founded the HFPS discipline and also leads in its PA. This project reviews the types, quality, and designated purpose of HFPS PA tools in anesthesiology. We used the systematic review method and systematically reviewed anesthesiology literature referenced in PubMed to assess the quality and reliability of available PA tools in HFPS. Of 412 articles identified, 50 met our inclusion criteria. Seventy seven percent of studies have been published since 2000; more recent studies demonstrated higher quality. Investigators reported a variety of test construction and validation methods. The most commonly reported test construction methods included "modified Delphi Techniques" for item selection, reliability measurement using inter-rater agreement, and intra-class correlations between test items or subtests. Modern test theory, in particular generalizability theory, was used in nine (18%) of studies. Test score validity has been addressed in multiple investigations and shown a significant improvement in reporting accuracy. However the assessment of predicative has been low across the majority of studies. Usability and practicality of testing occasions and tools was only anecdotally reported. To more completely comply with the gold standards for PA design, both shared experience of experts and recognition of test construction standards, including reliability and validity measurements, instrument piloting, rater training, and explicit identification of the purpose and proposed use of the assessment tool, are required.

  View details for DOI 10.3352/jeehp.2009.6.3

  View details for PubMedID 20046456

  View details for PubMedCentralID PMC2796725

• Scenario and checklist for airway rescue during pediatric sedation. Simulation in healthcare Chen, M. I., Edler, A., Wald, S., Dubois, J., Huang, Y. M. 2007; 2 (3): 194-198

  View details for DOI 10.1097/SIH.0b013e3181461b60

  View details for PubMedID 19088623

• Flexor tendon suture methods: A quantitative analysis of suture material within the repair site ORTHOPEDICS Norris, S. R., Ellis, F. D., Chen, M. I., Seller, J. C. 1999; 22 (4): 413-416

  Abstract

  This study compared the cross-sectional area and volume occupied by suture material at the repair site in three common methods of flexor tendon repair. A total of 51 human cadaveric tendons were studied. Zone II flexor digitorum profundus tendon lacerations were created and then repaired using the techniques described by Kessler, Tajima, and Savage. Quantitative cross-sectional area and volumetric measurements of suture material within each repair site were determined using a digital image analysis system. The Tajima repair occupied 27% of the tendon area at the repair site, while the Savage and Kessler repairs occupied 18% and 2%, respectively.

  View details for Web of Science ID 000079967600010

  View details for PubMedID 10220056

• 1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor for lumbar spinal fusion. Part I: Biology of spinal fusion. Spine Boden, S. D., Schimandle, J. H., Hutton, W. C., Chen, M. I. 1995; 20 (24): 2626-2632

  Abstract

  The histology of lumbar intertransverse process spinal fusion was studied in an experimental model in rabbits.To qualitatively and quantitatively analyze the sequential histology of spinal fusion using a previously validated animal model.Few previous studies have described the sequential histology during the posterolateral spinal fusion healing process using autogenous bone, and a basic understanding of the biology of this repair process is lacking.Fourteen adult New Zealand white rabbits underwent single-level posterolateral lumbar intertransverse process arthrodesis with autogenous iliac bone graft. Animals were killed 1-10 weeks after surgery, and the fusion masses were analyzed histologically and quantitated using a semiautomated image analysis system.Three distinct phases of healing were identified (inflammatory, reparative, and remodeling) and occurred in sequence but in a delayed fashion in the central zone of the fusion mass compared with the outer transverse process zones. Membraneous bone formation, evident first at the ends of the fusion eminating from the decorticated transverse processes, was the predominant mechanism of healing. The central zone was somewhat different in that there was a period of endochondral bone formation during weeks 3 and 4 in this zone where cartilage formed and was converted to bone. Remodeling in the central zone had equilibrated with the transverse process zones by 10 weeks.Lumbar intertransverse process spinal fusion is a complex process from a spatial and temporal standpoint. When autogenous bone is used as the graft material, this process critically depends on a variety of factors from the decorticated host bone and exposed marrow. The persistence of a central cartilage zone may be related to some types of nonunions and deserves future investigation. This enhanced understanding of the biology of spinal fusion with autogenous bone graft will provide a foundation for optimizing the use of osteoinductive bone growth factors in this healing process.

  View details for PubMedID 8747240