Shahzad Shaefi, M.B.,B.S.
Associate Professor of Anaesthesia
Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center
330 Brookline Ave
Boston MA 02215
|Harvard T.H. Chan School of Public Health||MPH||2017||Clinical Effectiveness|
|University College London||MD||2001||Medicine|
The Shaefi lab research program is focused on translational and clinical research surrounding the protective effects of different admixtures of oxygen administered perioperatively, as well as prevention and treatment of Perioperative Neurocognitive Disorders following cardiac surgery. His laboratory and clinical focus include the following areas of interest
Preclinical Effects of Protective Hypoxia in Sepsis and Critical Illness Models
The Shaefi lab is investigating whether hypoxia could be beneficial and perhaps even necessary for attenuation of the inflammatory response in various disease states. Murine models of sepsis, trauma, subsequent critical illness and cardiac arrest are currently being utilized. A study of the effects of differing concentrations of oxygen and use of other gasotransmitters in a porcine cardiopulmonary bypass model is also underway.
Clinical Trials Regarding Titration of Oxygen and Use of Low Dose Carbon Monoxide
Dr. Shaefi has completed a randomized clinical trial examining the effect of different intraoperative oxygen concentrations and the effect on postoperative neurocognition in cardiac surgery. Additionally, Dr. Shaefi is involved in a clinical study in which he is assessing clinical outcome and changes in inflammatory signatures with administration of conservative vs conventional oxygen levels delivered to patients in the ICU. Furthermore, he is embarking upon work associated with the administration low-dose carbon monoxide. Carbon monoxide exerts its effects in part by binding to the same hemoproteins as oxygen, largely in the mitochondria. There is significant preclinical data that has been amassed regarding the anti-inflammatory, anti-apoptotic and antimicrobial effects of carbon monoxide. The lab is performing exploratory studies in healthy human volunteers with carbon monoxide exposure as a prelude to larger clinical trials in various surgical and critical illness settings. The demonstration of salutary effects of carbon monoxide in the perioperative space has far reaching and significant implications for the care of our patients.
Biomarker Discovery of Delirium in Cardiac Surgery
Dr. Shaefi has a long-standing interest in post-cardiac surgical delirium. His laboratory is examining proteomic signatures of patients exhibiting delirium after cardiac surgery. This proteomic analysis, together with advanced bioinformatics, has led to the potential identification of various candidate biomarker proteins of delirium after cardiac surgery. Ongoing prospective work will further examine and validate these biomarkers and assess the potential of regulating upstream and downstream signaling of pathways that involve these proteins.
Available: 04/05/22, Expires: 06/01/23
The Shaefi Lab, housed within the Department of Anesthesia, Critical Care and Pain Medicine at Beth Israel Deaconess Medical Center, focuses on translational and clinical areas of research that investigate the most appropriate perioperative administration and titration of oxygen. The use of oxygen is ubiquitous in clinical practice representing the most widely prescribed drug in the modern in-hospital setting. It is estimated that 15% patient admitted to the hospital and 95% of patients entering an intensive care unit or undergoing surgery receive supplemental oxygen. Overall 50 million people or one sixth of the United States population receives oxygen in these settings every year. Traditionally, anesthesiologists, critical care physicians and other clinicians have almost universally administered oxygen at higher than required levels in order to avoid potentially injurious levels of hypoxemia in their patients. There is mounting evidence that this stance of liberal administration and relative lack of titration of oxygen may not be as benign as first thought. Further, the clinical weight of evidence persuasively supports the finding that high levels of administered oxygen (hyperoxia) without endpoint titration confer more risk than benefit. Compelling preclinical evidence exists for the protective and regenerative aspects of low levels of oxygen (hypoxia) in specific settings. Significant efforts in the Shaefi lab are geared towards an understanding of the mechanisms of this protective hypoxia, especially in the setting of inflammation and sepsis through the use of preclinical models. Further work examining the beneficial role of hypoxia with human subjects in the clinical sphere are ongoing within the Shaefi lab. Admittedly, the concept of titrating hypoxic admixtures in acutely ill patients is fought with challenges. It would be ideal to impart the protective effects of hypoxic cellular exposure while avoiding the unforgiving repercussions of administering hypoxic admissions. Therefore, much of the work within the lab focuses on interventions to up regulate protective hypoxic properties under normoxic conditions, termed pseudo-hypoxia. Both small and large animal preclinical models are focused on developing this very palatable option for treatment, feasibility, safety and efficacy before moving this into human clinical interventional trials. There are various cytoprotective mechanisms activated during cellular stress. Heme Oxygenase-1 is one such mechanism, and is highly upregulated in periods of tissue hypoxia and sepsis. This stress response gene, regulated in part by hypoxia inducible factor, can metabolize heme to its metabolites biliverdin, iron and carbon monoxide. Although some of the mechanisms are unclear, the anti-inflammatory, antimicrobial and overall salutary effects of carbon monoxide have been well characterized in preclinical models. The translational aspect of investigations in the Shaefi lab aim to further delineate aspects of the mechanisms underlying the benefit observed with the administration of low dose exogenous carbon monoxide. Once these effects have been more fully elucidated in preclinical models, stepwise clinical observational and interventional studies will be performed in healthy subjects, patients undergoing major cardiac and noncardiac surgery as well as our vulnerable critically ill patient population
The research activities and funding listed below are automatically derived from
NIH ExPORTER and other sources, which might result in incorrect or missing items.
to make corrections and additions.
(LEAF, DAVID EVAN)
Jul 15, 2022 - Jul 14, 2027
Hepcidin-Ferroportin-Iron Axis in Cardiac Surgery-associated Acute Kidney Injury
(LEAF, DAVID EVAN)
Sep 1, 2020 - Jun 30, 2025
Deferoxamine for the Prevention of Acute Kidney Injury
Aug 1, 2019 - Jul 31, 2023
Sepsis and the benefits of permissive hypoxia
Role: Principal Investigator
Aug 1, 2018 - Apr 30, 2021
Proteomic Analysis of Postoperative Delirium from a randomized trial in Older Patients undergoing Cardiac Surgery exposed to Intraoperative Normoxia versus Hyperoxia: A Nested Case-Control Study
Role: Principal Investigator
Jan 1, 2016 - Dec 31, 2020
DAMP-Mediated Innate Immune Failure and Pneumonia after Trauma
Role Description: The goal of this Program Project Grant is to provide greater immunobiological understanding of the cellular and molecular mechanisms predisposing to infection
FAER Mentored Research Grant
Jan 1, 2016 - Dec 31, 2017
Foundation of Anesthesia Education and Research (FAER)
The relationship between administered oxygen levels and arterial partial oxygen pressure to neurocognition in cardiac surgical patients.
Jul 1, 2015 - Dec 31, 2018
BIDMC Chief Academic Officer
The relationship of administered oxygen levels and arterial partial oxygen pressure to kidney injury following cardiac surgery
John Hedley Whyte Research Award
Jul 1, 2014
Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine, Harvard Medical School
Oxygen and Neurocognition in Cardiac Surgery
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