Faculty Profile: Martin Keszler, MD

Martin Keszler, MD
Professor of Pediatrics
Pediatrics
Work: +1 401-274-1122-x-7490
Dr. Keszler's research focuses on advanced modes of conventional and high-frequency ventilation, prevention of lung injury and treatment of pulmonary hypertension. Current studies include a multinational study of lung volume recruitment at delivery (Co-PI), multicenter trial of high-frequency ventilation with a new device (PI), measurement of airway resistance in newborns (PI), and bench studies of volume-targeted ventilation. He is also Site PI for several Neonatal Research Network studies.

Biography

Dr. Keszler obtained his medical degree from McGill University and his Pediatric, and Neonatal training at Children's Hospital Medical Center of Akron, Ohio. In 2010, Dr. Keszler was recruited to Brown University from Georgetown University in Washington DC where he was Professor of Pediatrics, chair of the IRB, Medical Director of NICU and Director of ECMO. He served on the Advisory Board of the Maternal-Fetal Medicine Units Network of the NICHD and was Vice Chair of the Data Safety and Monitoring Board of the NICHD Neonatal Research Network (NRN), prior to becoming an NRN investigator upon joining Brown. He has published numerous original papers, review articles, book chapters and editorials, presented over 300 lectures at National and International conferences, moderated or conducted over 50 workshops or round-table discussions and was a Visiting Professor in over 20 medical institutions in the USA and abroad.

Research Description

Martin Keszler, MD. "Optimizing respiratory outcome in preterm infants through the use of novel respiratory support modalities" Advances in neonatal intensive care have improved survival of extremely low birth weight infants, but the immature lung is extremely vulnerable to injury due to a combination of mechanical injury (volutrauma), inflammatory response to biophysical forces and/or infection (biotrauma), and oxygen toxicity. As a consequence, chronic lung disease remains unacceptably high. The development of bronchopulmonary dysplasia (BPD) is influenced by a wide variety of factors, but there is mounting evidence that minimizing tidal volume, optimizing lung inflation (avoiding atelectasis) and reducing oxygen exposure are key factors in reducing the risk of chronic lung disease. Chronic lung disease adversely affects the infant's nutritional status, growth and neurodevelopment, in addition to predisposing to lower respiratory tract infections and reactive airway disease during infancy. Thus, reduction of this important complication of prematurity remains a high priority. In recent years, my clinical research has focused on investigation of volume-targeted ventilation as a means of reducing adverse consequences of mechanical ventilation and on the complex interactions between spontaneously breathing infants and the ventilator. Continuing work will examine the effectiveness of volume targeted ventilation in maintaining more stable gas exchange in a variety of clinical situations that perturb the stability of the system, for example, during suctioning and other manipulations. We have been working to define optimal tidal volume targets in a variety of clinical situations with different types of lung pathology that may influence physiologic dead space. My clinical and bench research has recently challenged the accepted dogma that anatomical dead space gas does not mix with fresh gas during the respiratory cycle; we showed both in the clinical setting and on the bench that it is possible to ventilate effectively with tidal volume below anatomical and instrumental dead space even at conventional ventilator rates. Currently, I am evaluating the capabilities of the newest state-of–the-art neonatal ventilator in relation to other available devices in a series of bench studies with a focus on how the devices react to a variety of simulated perturbations. A clinical trial of the high-frequency oscillation (HFO) feature of this device, which is unique in its ability to deliver volume-targeted HFO, is in the planning stages. The care of infants with chronic lung disease is made more difficult by the lack of suitable tools to evaluate the effects of interventions aimed at reducing airway resistance. Infants who are no longer mechanically ventilated, but still have significant lung disease typically have high airway resistance and are often treated with bronchodilators, diuretics and inhaled steroids. Currently, there is no suitable method to evaluate the efficacy of these therapies. I will be evaluating a simple, noninvasive device, called the Airflow perturbation device (APD) that is being modified for neonatal use. The device is capable of acquiring reproducible measurements in under 20 seconds in quietly breathing infants without any need for active cooperation. The initial phase will involve simple validation of the device, subsequently, we will compare the measurements obtained with the APD to the gold standard of body plethysmography in stable spontaneously breathing preterm infants. We will then examine the effectiveness of specific interventions on airway resistance in groups of infants with BPD using the APD to measure airway resistance before and after intervention. Other areas of clinical research interest include aerosolized surfactant therapy administered during CPAP support, inhaled nitric oxide and prediction of outcome in infants with congenital diaphragmatic hernia. Studies exploring the association of heart rate and respiratory rate variability with general degree of physiologic maturation in several specific subgroups of preterm infants and as predictor of extubation success are in the planning stages. (updated 6.13.13)

Grants and Awards

1981 Special Prize scientific paper presentation, Children's Hospital Medical Center of Akron, OH

1982 First Prize scientific paper presentation, Children's Hospital Medical Center of Akron, OH

1982 Special Teaching Award by house staff, Children's Hospital Medical Center of Akron, Akron, OH

1986 Young Investigator Award, Section of Perinatal Pediatrics, American Academy of Pediatrics

2000 Honorary Member, Czech Perinatal Society in recognition of 10 years of educational efforts in my country of origin

2008 Sponsor & Nominator, Monisha Bahri, MD, Recipient: Fellow Clinical Research Award, Pediatric Academic Societies Meeting, May 2008 (abstract, "A Randomized Controlled Trial to Determine the Lowest Effective Dose for Adequate Mydriasis in Preterm Infants" 4452.13

2009 Elected Member, American Pediatric Society

2013 Awarded Honorary Master of Arts ad eundem degree, Brown University

Affiliations

Member, American Pediatric Society
Member, Society for Pediatric Research
Member, Eastern Society for Pediatric Research
Fellow, American Academy of Pediatrics
Member, AAP Section of Perinatal Pediatrics
Charter Member of Steering Committee, Extracorporeal Life Support Organization
Member, American Association for Respiratory Care

Funded Research

GRANTS

1. Principal Investigator, Trustees of Akron Children's Hospital Research Foundation. "Clinical trial of high frequency jet ventilation in newborn infants", 02/28/1982 – 02/28/1983

2. Principal Investigator, IVAC Corporation equipment grant. "HFJV in an animal model of meconium aspiration". 09/1983

3. Principal Investigator, Basic Research Support Grant, Georgetown University. "High frequency jet ventilation in an animal model of meconium aspiration". 04/01/1983-04/30/1984

4. Principal Investigator, John Preston Marshall Foundation. "Extracorporeal Membrane Oxygenation". 01/01/1985-01/31/1987

5. Co - Sponsor of Awardee of Fellowship Grant. American Heart Association, Nation's Capital Affiliate. "Tidal flow veno-venous system for ECMO". 07/31/1986-06/30/1987

6. Principal Investigator, John Preston Marshall Foundation. "Extracorporeal Membrane Oxygenation". 06/01/1987–06/30/1989

7. Principal Investigator, American Heart Association, Nation's Capital Affiliate. "A tidal flow veno-venous system for ECMO: Long-term safety" 07/01/1988-06/30/1989 (extended till Sept 1990)

8. Site Principal Investigator, Pediatrix Medical Group. "Lung lavage with perfluorocarbons in an animal model of the meconium aspiration syndrome". 04/01/1993-06/30/1994

9. Site Principal Investigator, Abbot Laboratories/Ross Laboratories. "Evaluation of Survanta in term infants". 03/01/1994-12/31/1995

10. Site Principal Investigator I, Ohmeda Inc. "A double blind, placebo controlled dose response study of inhaled nitric oxide in the treatment of persistent pulmonary hypertension in the neonate". 07/01/1994-06/30/1996

11. Principal Investigator, Draeger Inc. "Validation and testing of new Babylog ventilator software". 05/01/1996-09/30/1996

12. Site Principal Investigator, Ohmeda Inc. "Multi-center trial of Nitric Oxide in near-term infants with hypoxemic respiratory failure". 04/01/1996-12/31/1998

13. Principal Investigator, Draeger Inc. "Clinical validation and testing of new Babylog ventilator software". 07/01/1997-03/31/1998

14. Site Principal Investigator, Acute Therapeutics Inc. (now Discovery Laboratories). "Multi-center randomized controlled trial of KL4 surfactant for treatment of MAS". 07/01/1997-07/31/1999

15. Site Principal Investigator, Discovery Laboratories. "Multi-center randomized controlled trial of Surfaxin for treatment of meconium aspiration syndrome". 05/01/2000-07/31/2001

16. Principal Investigator, Draeger Inc. "Randomized trial of the Volume Guarantee mode of ventilation in infants with periodic breathing. 12/01/2001-12/31/2003

17. Site Principal Investigator, Johnson and Johnson, Inc. "A Pharmacokinetic, Pharmacodynamic and Short-term Safety Study of Single and Multiple Day Doses of Rabeprazole Sodium in Neonates and Pre-term Infants with a Corrected Age of Less than 44 Weeks with a Presumptive Diagnosis of GERD". 12/01/2009-12/31/2010

18. Site Co- Principal Investigator Georgetown University, Canadian Institutes of Health Research MCT-80246 (Site CO-PI, Haresh Kirpalani, PI). "Nasal Intermittent Positive Pressure Ventilation in Premature Infants (NIPPV) Trial". 12/01/2009-12/31/2010

19. Alternate (Co)-Principal Investigator, Brown University/WIHRI site. NIH-NICHD U10 HD27904. "NICHD Cooperative Multicenter Neonatal Research Network, 04/01/2011-03/31/2016

20. Subcontract Principal Investigator, NIH Subcontract: R43 HL106366-01, J Vassoughi (PI) "Engineering and Scientific Research Associates". Responsive to RFA-HD-09-017 Safe and Effective Instruments and Devices for Use in the Neonatal Intensive Care Units (SBIR [R43]) "Neonatal APD, a Simple Noninvasive Diagnostic/Monitoring Device for Neonatal ICU". 07/01/2010-06/01/2014

21. Senior/Key Collaborator, Site Principal Investigator, Small Business Innovation Research Grant 1R44HL107000-01; PI, Segal, Robert, Discovery Laboratories. "Development and Utilization of a Novel Aerosol Generating Technology to Deliver Lucinactant, a KL4 Peptide-containing, Synthetic Surfactant for the Prevention of Neonatal Respiratory Distress Syndrome". 01/01/2011-06/01/2014

22. Overall Principal Investigator, Site PI at WIHRI, Draeger Medical, Inc. "Multicenter Clinical Trial of High-frequency Ventilation Using the Draeger VN500 Infant Ventilator in the Treatment of Respiratory Distress Syndrome in Premature Infants". 01/01/2011- 12/31/2015

23. Over all study Co – PI, Site PI at WIHRI. "The Delivery Room Recruit Trial." NIH grant 1U01HD072906-01A1. 09/01/13 to 09/01/18