Loma Linda University

The Department of Anesthesiology and Loma Linda University Medical Center has a very active research division with many ongoing clinical and basic science projects. Reach within the department is geared with a single purpose in mind, to improve patient outcomes. Many opportunities for neuroscience research are available in the Zhang Neuroscience Laboratory, which is housed in the Anesthesiology Department. The Zhang lab has NIH P01 program grant funding to study hemorrhagic stroke, and many R01 grants for studies of methods to improve outcome following ischemic stroke, global cerebral ischemia including hypoxia-ischemia, neonatal hypoxia, surgical brain injury (edema and bleeding) and cardiac arrest. Many of these projects have translation components that are actively being implemented. In addition the department works closely with the Center for Perinatal Biology on topic of vascular reactivity.

Clinical research focuses on: the utility of ultrasound in medicine, medical technology development, hemodynamic monitoring, coagulation disorders, innovation in laboratory testing, medical education, perioperative medicine and care coordination development. Clinical research is focused not only improving perioperative care but also demonstrating the utility of collaboration across multiple patient care settings. The department has also developed a perioperative hospitalist service that strives to educate residents on the continuum of perioperative care and facilitate medical management and coordination of care of postsurgical patients.

For 2016, the clinical faculty produced over 30 publications and the basic research division produced over 40 publications. An overview of recent topics are below:

Medical Ultrasound:

• Point-of-Care Ultrasound: Novel Technology to Routine Perioperative Assessment Tool. Ramsingh D, Gudzenko V, Martin RD. Anesthesia and Analgesia. Mar 2017.

• Clinical Impact of a Perioperative Point of Care Ultrasound Service: A Quality Improvement Initiative – Western Anesthesia Residents Conference -2017.
• Intraoperative point-of-care ultrasound for identification of endotracheal tube position in the pediatric population. – Western Anesthesia Residents Conference -2017.
• Left ventricular endocardial and epicardial strain changes with apical myocardial ischemia in an open-chest porcine model. McCabe M, Howard-Quijano K, Cheng A, Zhou W, Yamakawa K, Mazor E, Scovotti JC, Mahajan A. Physiological Reports. Dec 2016.
• Auscultation versus Point-of-Care Ultrasound to Determine Endotracheal versus Bronchial Intubation: A Diagnostic Accuracy Study. Ramsingh D, Frank E, Haughton R, Schilling J, Gimenez KM, Banh E, Rinehart J, Cannesson M. Anesthesiology. May 2016.
• Ramsingh D, Singh S, Ross M, Williams W, Cannesson M, Review of Point of Care (POC) Ultrasound for the 21st Century Perioperative Physician. Current Anesthesiology Reports. December 2015, Volume 5, Issue 4, pp 452–464
• Ramsingh D, Rinehart J, Kain Z, Strom S, Canales C, Alexander B, Capatina A, Ma M, Le KV, Cannesson M: Impact Assessment of Perioperative Point-of-Care Ultrasound Training on Anesthesiology Residents. Anesthesiology 2015; 123: 670-82

Hemodynamic Monitoring:

• Evaluation of Clinical Impact of Non-Invasive Hemodynamic Monitoring to Optimize Perioperative Care in Moderate to High Risk Patients with Poor Functional Status – Western Anesthesia Residents Conference -2017.
• Utilization of Non-Invasive Hemodynamic Monitoring to Optimize Preventative Care of Heart Failure Patients Western Anesthesia Residents Conference -2017.
• Cannesson M, Ramsingh D, Rinehart J, Demirjian A, Vu T, Vakharia S, Imagawa D, Yu Z, Greenfield S, Kain Z: Perioperative goal directed therapy and postoperative outcomes in patients undergoing high-risk abdominal surgery: a historical-prospective, comparative effectiveness study. Crit Care 2015; 19: 261.
• Applegate II R, Ramsingh DS, Dorrota I, Sanghvi C, Blood AB. Evaluation of Multiple Modes of Oximetry Monitoring as an Index of Splanchnic Blood Flow in a Newborn Lamb Model of Hypoxic, Ischemic, and Hemorrhagic stress. Shock. 2013 Jun;39(6):501-6.
• Ramsingh, Davinder, Brenton Alexander, and Maxime Cannesson. "Clinical review: Does it matter which hemodynamic monitoring system is used?." Crit Care. 2013 Mar 5;17(2):208.
• Ramsingh DS, Sanghvi C, Gamboa J, Cannesson M, Applegate RL 2nd. Outcome impact of goal directed fluid therapy during high risk abdominal surgery in low to moderate risk patients: a randomized controlled trial. J Clin Monit Comput. 2012 Dec 22. PMID: 23264068.

Blood Disorders and Coagulation:

• Extreme Plasma Dilution Decreases Heparin and Protamine Cardiopulmonary Bypass Requirements: A Case Report on a Jehovah's Witness Patient. Gatling JW, Bode S, Herrmann PC, Bull BS, Applegate RL 2nd. A & A Case Reports. March 15, 2017.
• The Relationship Between Oxygen Reserve Index and Arterial Partial Pressure of Oxygen During Surgery. Applegate Rl 2nd, Wells B, Juma D, Applegate PM. Anesthesia and Analgesia. September, 2016.
• Crotalus atroc venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury. Kim CH, McBride DW, Sherchan P, Hay KL, Gren EC, Kelln W, Lekic T, Hayes WK, Bull BS, Applegate R, Tang J, Zhang JH. Scientific Reports January 19, 2017.

Pediatric Anesthesia Research:

• Intraoperative Red Blood Cell Transfusion in Infant Heart Transplant Patients Is Not Associated with Worsened Outcomes. Lau C, Juma D, Wells B, Applegate RL 2nd. Anesthesia and Analgesia. May 2016.
• Intraoperative point-of-care ultrasound for identification of endotracheal tube position in the pediatric population. – Western Anesthesia Residents Conference -2017.
• A Comparison of Midazolam and Zolpidem as Oral Premedication in Children, a Randomized Control Trial. – Western Anesthesia Residents Conference -2017.
• Comparison of the GlideScope Cobalt and Storz DCI video laryngoscopes in children younger than two years of age during manual in-line stabilization: A randomized trainee evaluation study. Ghazal E, Applegate R, Roddy K, Um M, Neiheisel A. Pediatr Emerg Care. 2016.
• Continuous Non-Invasive Hemodynamic Monitoring in an Infant with Tetra-Amelia. Ayodeji A Applegate R. Anesth & Analg. 2016.
• Analgesia following surgery in children can be challenging. A team of LLU researchers investigated the impact of acetaminophen following cleft palate repair, finding a decrease in opioid use (Nour C, Ratsiu J, Singh N, Mason L, Ray A, Martin M, Hassanian M, Uhler J, Applegate II RL: Analgesic Effectiveness of Acetaminophen for Primary Cleft Palate Repair in Young Children: A Randomized Placebo Controlled Trial. Pediatric Anesthesia 2014; 24:574-58)
• Finding optimum methods to control pain in pediatric urologic surgery patients is being studied by a team led by Dr. Shannon Mulder: Preemptive analgesia in children using caudal epidural ropivacaine: A prospective, randomized, controlled study NCT01494272.

Educational Research:

• Evaluation of an Online Training Website for Perioperative Point of Care Ultrasound and the Clinical Impact of a Perioperative Point of Care Ultrasound Service – Western Anesthesia Residents Conference -2017.
• Current Practice Strategies in the Acute Care Setting and the Utilization of Point of Care Ultrasound: A Survey Study Across all Acute Care Specialties – Western Anesthesia Residents Conference -2017.
• Staying Alive: Active Shooter Simulation in the Operating Room. Cristall J Czynki A Layel V Denmark TK. J Investig Med. 2016.
• Comparison of web-based and face-to-face interviews for application to an anesthesiology training program: a pilot study. Vadi MG, Malkin MR, Lenart J, Stier GR, Applegate RL 2nd. International Journal of Medical Education. April 2016.
• Decision making in critical events was reported on by a collaborative group that includes Dr. Marissa Vadi: Vadi MG, Patel N, Stiegler Anesthesiology 2014; 120 (4):987-96.
• Use of video interviews for resident selection is being studied by a group that includes Dr. Robert Martin, Dr. Marissa Vadi, Dr. Mathew Malkin, Dr. Gary Stier, Dr. John Lenart, Dr. Jason Gatling and Dr. Richard Applegate. An abstract based on preliminary analysis of this work has been submitted to the 2015 ASA Annual Meeting.

Perioperative Medicine and Coordinated Patient Care:

• Anesthesiologists as Perioperative Hospitalists and Outcomes in Patients Undergoing Major Urologic Surgery: a historical-prospective, comparative effectiveness study – Western Anesthesia Residents Conference -2017.
• Quality Improvement Initiative to Develop a Data Architecture and Process Flow Map for Physicians at an Academic Medical Center - Western Anesthesia Residents Conference -2017.
• Evaluating Factors Resulting in Delayed Labor Epidural Placement: A Quality Improvement Study - Western Anesthesia Residents Conference -2017.
• Current Anesthesia and Post-procedure Management Techniques for Transfemoral Aortic Valve Replacement (TAVR) in the United Sates: A Survey of TAVR Centers - Western Anesthesia Residents Conference -2017.
• Opportunities for improvement in care among women with severe maternal morbidity. Ozimek JA, Eddins RM, Greene N, Pak S, Wong M, Zakowski M, Kilpatrick SJ. American Journal of Obstetrics and Gynecology. October 2016.
• Management of Complex Cardiac Issues in the Pregnant Patient. Pasca, I Critical Care Clinics. January 2016.
• Advanced Monitoring Is Associated with Fewer Alarm Events During Planned Moderate Procedure-Related Sedation: A 2-Part Pilot Trial. Applegate RL 2nd, Lenart J, Meineke MN, Qoshlli S, Neumann M, Jacobson JP, Kruger A, Ching J, Hassanian M, Um M. Anesthesia and Analgesia. Feb 2016.

Neuroscience:

Snake venom pretreatment to prevent surgical brain injury: The potential benefit of pretreatment with a variety of snake venoms in studies of surgical bleeding and post-surgery edema is promising. A number of projects are underway that involve department members and trainees. These projects are supported by an R01 NIH Grant (“Crotalus Snake Venom Preconditioning to Prevent Surgical Brain Injury”).

Neurologic function after cardiac arrest: Interventions to improve neurologic outcome following cardiac arrest are being studied using a rat model of sudden cardiac arrest and resuscitation by researcher Dr. Lei Helen Huang. Working with other members of the Zhang lab this study of post-resuscitation interventions could provide treatments to improve outcome after cardiac arrest. This work is partially supported by a $25,000 grant from the Floyd S. Brauer Anesthesiology.

Research Endowment:

• Vasovagal syncope: The potential benefit provided by remote ischemic pre-conditioning for vasovagal syncope is being studied by a team led by Dr. Jiping Tang. This work is partially supported by a $75,000 Grant to Promote Translational and Collaborative Research (GCAT) from Loma Linda University School of Medicine.
• Presentations and Publications:
• Pharmacological Management Options to Prevent and Reduce Ischemic Hemorrhagic Transformation. Ho WM, Reis C, Akyol O, Akyol GY, Applegate 2nd R, Martin R, Zhang JH. Current Drug Targets. August 18, 2016.
• Remote Ischemic Preconditioning in Aneurysmal Subarachnoid Hemorrhage – Western Anesthesia Residents Conference -2017.
• Thrombin Preconditioning in Surgical Brain injury in Rats. Chen H, Applegate RL 2nd, Zhang J. Acta Neurochirurgica. Supplement 2016.
• Propofol Pretreatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model. Pakkianathan C, Khatibi NH, Chen H, Marcantonio S, Applegate R 2nd, Tang J, Zhang J. Acta Neurochirurgica. Supplement 2016.
• Beta Blockade and Clinical Outcomes in Aneurysmal Subarachnoid Hemorrhage. Raval RN, Southerland JJ, Adewumi DA, Bahiri KA, Samuel RK, Woods RO, Ajayi RO, Lee BS, Hsu FP, Applegate li RL, Dorotta IR. The Open Neurology Journal. Dec 2016.
• IARS Annual Meeting 2014 Barnhart M, Raval R, Applegate R, Zhang J: Identification Of Potential Target Proteins Leading To Reduced Surgical Bleeding From Pretreatment Of Sprague Dawley Rats With C. Atrox Venom S-142.
• ASA Annual Meeting 2013 Raval R, Kim C, Hay K, Zhang J, Bull B, Applegate II RL: Decreased Surgical Bleeding in Sprague Dawley Rats Pretreated With Crotalus Atrox Venom, A1047.
• Soliman S, McBride D, Tang J, Applegate II R: Remote Ischemic Pre-Conditioning Can Modulate the Systemic Response to VVS and Decreases Syncopal Episodes. S-482.
• Drunalini Perera PN, Hu Q, Tang J, Li L, Barnhart M, Doycheva DM, Zhang JH, Tang J:Â Delayed remote ischemic postconditioning improves long term sensory motor deficits in a neonatal hypoxic ischemic rat model. PLoS One. 2014 28;9(2):e90258.
• Doycheva DM, Hadley T, Li L, Applegate II RL, Zhang JH, Tang J: Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by decreasing neutrophil mobilization in hypoxic ischemic neonatal rat model. Neurobiol Dis. 2014 Sep;69:192-9.
• Manaenko A, Lekic T, Barnhart M, Hartman R, Zhang JH: Inhibition of Transforming Growth Factor-β Attenuates Brain Injury and Neurological Deficits in a Rat Model of Germinal Matrix Hemorrhage. Stroke. 2014;45(3):828-34.
• Fujii M, Sherchan P, Krafft PR, Rolland WB, Soejima Y, Zhang JH. Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats. Journal of the Neurological Sciences 2014;342:101-6.
• Fujii M, Sherchan P, Soejima Y, Hasegawa Y, Flores J, Doycheva D, Zhang JH. Cannabinoid receptor type 2 agonist attenuates apoptosis by activation of phosphorylated CREB-Bcl-2 pathway after subarachnoid hemorrhage in rats. Clinical and Experimental Neurology 2014;261:396-403.
• Benggon M, Chen H, Applegate R, Zhang JH: Thrombin preconditioning in surgical brain injury in rats. IARS Annual Meeting 2014 Resident Oral Abstract Competition; Benggon M, Chen H, Applegate II RL, Zhang JH: Thrombin preconditioning in surgical brain injury in rats. Acta Neurochirurgica Supplement 2015.
• Komanapalli ES, Sherchan P, Rolland II W, Khatibi N, Applegate II RL, Martin RD, Tang J, Zhang JH: Epsilon Aminocaproic Acid Pre-Treatment Provides Neuroprotection Following Surgically Induced Brain Injury In A Rat Model. Acta Neurochirurgica Supplement 2015.
• Huang L, Woo W, Sherchan P, Khatibi NH, Krafft P, Rolland II W, Applegate II RL, Martin RD, Zhang JH: Valproic acid pretreatment reduces brain edema in a rat model of surgical brain injury. Acta Neurochirurgica Supplement 2015.
• Pakkianathan C, Benggon M, Khatibi NH, Chen H, Marcantonio S, Applegate II RL, Tang J, Zhang JH: Propofol Pre-Treatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model. Acta Neurochirurgica Supplement 2015.
• Meineke M, Applegate II RL, Rasmussen T, Anderson D, Azer S, Mehdizadeh A, Kim A, Allard M.: Cognitive dysfunction following desflurane versus sevoflurane general anesthesia in elderly patients: a randomized controlled trial. Â Medical Gas Research 2014; 4:6.

Program Project Grant:

Program Project Grant to establish the Center for Brain Hemorrhage Research: $7.7 million NIH award to the Zhang Neuroscience Laboratories. We anticipate a number of important findings to come from this Center. It is our hope that based on results from basic science projects we will be able to carry out translational research on interventions that show promise to improve outcomes after hemorrhagic stroke.