Dr. Paul Pepe, an internationally-recognized scientist in resuscitation medicine and emergency medical services delivery, has a quarter century track record in designing and successfully conducting major clinical trials that have achieved significant notoriety. He has even published state of the art papers on how to conduct trials in the out-of-hospital setting (eg, Pepe, et al: Crit Care Med Jan 2009) and he has continued to help shape the national agenda in resuscitation research priorities. Many of his research initiatives have not only led to change in medical practice worldwide, but they have also pioneered new approaches to resuscitation and avenues of investigation. His first publication (Pepe and Marini: Occult positive end expiratory pressure in mechanically ventilated patients with airflow obstruction: The Auto-PEEP Effect. Am Rev Resp Dis, 1982; 126:166-170) spawned a critical new area of research and is considered a landmark paper that showed how to detect and measure this important physiological parameter and often unrecognized complication of assisted ventilation. The same year, he published (Pepe, et al: Am J Surgery, 1982; 144:124 130) the first prospective study of risk factors for Adult Respiratory Distress Syndrome (ARDS). This study paved the way for a widely-quoted major clinical trial examining the early application of PEEP in patients at risk for ARDS (Pepe, et al: N Engl J Med 1984; 311:281 286). Simultaneously, in the laboratory, he directly measured the relationship between oxygen delivery and actual oxygen consumption (Pepe and Culver: Am Rev Resp Disease 1985;132:788 792) and better defined the tipping point for total body oxygen consumption impairment in very low flow states. This work set the stage for Dr. Pepe’s subsequent innovative work on better matching ventilation to cardiac output when providing ventilatory support. Based on these very early research experiences with ventilation and flow, he subsequently went on to demonstrate the detrimental effects of overzealous ventilation in severe hemorrhagic states (Pepe, et al: J Trauma 2003;54:1048-1057) and he was also one of the first scientists to encourage elimination of assisted ventilation in the first few minutes after sudden cardiac arrest in adults (Becker LB, Berg RA, Pepe PE, et al: A reappraisal of mouth to mouth ventilation during bystander initiated cardiopulmonary resuscitation. Resuscitation November 1997;35:189-201). During the 1980s, he began to pioneer clinical trials of trauma (eg, Bickell, Pepe, et al: Randomized trial of pneumatic antishock garments in the prehospital management of penetrating abdominal injury. Ann Emerg Med 1987;16:653-658; and Bickell, Wall, Pepe, et al: Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injury. N Engl J Med 1994;331:1105-1109). Adding to his portfolio, he then began to establish major advances in adult and pediatric cardiac arrest research (eg, Pepe PE, et al: Crit Care Med December 1993;21:1838-1843; Bonnin, Pepe, et al: JAMA 1993;270:1457-462; and Sirbaugh PE, Pepe PE, et al: A prospective, population-based study of the demographics, epidemiology, management and outcome of out-of-hospital pediatric cardiopulmonary arrest. Ann Emerg Med 1999; 33:174-184). Simultaneously, he conducted several other major clinical trials for cardiac arrest and trauma (eg, Brown, Martin, Pepe, et al: N Engl J Med 1992;327:1051-1055; and Ann Surgery 1991;213:482-491) and he also developed improved ways of delivering prehospital (EMS system) care and even demonstrated life-saving effects and quality of care improvements (Pepe, et al: The effect of full time-specialized physician supervision on the success of a large urban emergency medical services system. Crit Care Med 1993;21:1279-1286; and Curka, Pepe, et al: Emergency medical services priority dispatch. Ann Emerg Med 1993;22:1688-1695). Many of the factors involved were later detailed in a conceptual treatise called the Chain of Survival (Cummins, Ornato, Thies and Pepe for the American Heart Association: Improving survival from sudden cardiac arrest- the chain of survival concept. Circulation 1991; 83:1832-1847). This metaphorical Chain is now cited either symbolically or in writing in almost every CPR publication worldwide. Since then he has helped to develop similar concepts for the National Institutes of Health (NIH) in the area of stroke intervention (eg, Pepe: Initial links in the chain of recovery for brain attack. In: National Institute of Neurological Disorders and Stroke [NINDS] - Setting New Directions for Stroke Care; an NIH publication, Marler, Jones, Emr [eds], August, 1997; Bethesda, MD, pp. 17-28; and Pepe PE: Executive Summary: NINDS Symposium - Improving the Chain of Recovery for Acute Stroke in Your Community - publication of the NIH NINDS, September 2003; pp. vi-vii). He has now provided similar discourses for global drowning investigations (eg, Pepe and Bierens: Consensus and recommendations - Task Force on Resuscitation - The Handbook on Drowning, the Final Report of the World Congress on Drowning, Bierens[ed], Springer-Lager, Heidelberg, 2006 pp. 314-323; and Idris, et al, including Pepe [corresponding author and committee chair] for the International Liaison Committee on Resuscitation: Recommended guidelines for uniform reporting of data from drowning - the Utstein style. Resuscitation 2003;59:45-57). More recently, he and his team at UT Southwestern have been advancing research in: 1) public access to defibrillation (Caffrey, Willoughby, Pepe, Becker: Public use of automated defibrillators. N Engl J Med 2002, 347(16):1242-1247); 2) CPR instructions by dispatchers (Roppolo, Westfall, Pepe, Idris: Assessment of agonal breathing improves detection of cardiac arrest. Circulation 2004;110 (17) suppl III-456; and Roppolo, Pepe, et al. Modified CPR instruction protocols for emergency medical dispatchers - rationale and recommendations. Resuscitation May 2005; 65:203-210); 3) mass CPR training (eg, Roppolo, Pepe, et al: Prospective, randomized trial of the effectiveness and retention of 30-minute layperson training for cardiopulmonary resuscitation and automated external defibrillators. Resuscitation August 2007;74:276-285); and 4)the influence of sex hormones in both cardiac and trauma resuscitation (eg, Wigginton, Pepe, et al: Sex-related differences in the presentation and outcome of out-of-hospital cardiopulmonary arrest - a multi-year, prospective population-based study. Crit Care Med 2002;30[4]Supplement:S1-6). He has also undertaken miscellaneous clinical research projects in acute heart failure (clinical trial of nesiritide), acute coronary syndromes (the Immediate Trial), ultrasound medicine (ruling out gallstones at the bedside), disaster management (eg, Klein, Pepe et al: The evolving need for alternative triage-management protocols in public health emergencies. Disaster Med Public Health Prep; 2008); and tactical medicine (Eastman, Metzger, Pepe, et al: Conductive electrical weapons - a prospective, population-based study of the medical safety of law enforcement use. J Trauma June 2008;64:1567-1572). Most notably, his academic unit (UT Southwestern Emergency Medicine) and its affiliated 16 partner cities in the Dallas EMS System have also been designated jointly as an NIH Center for Resuscitation Research. For this purpose, he and his team are scheduled to conduct ten or more federally-funded clinical trials in cardiac arrest and trauma resuscitation over the next 5 to 10 years.
RESEARCH INTERESTS
Clinical Trials of Interventions for Cardiac Arrest Resuscitation
Clinical Trials of Interventions for Trauma Resuscitation
Therapeutic Hypothermia for Pediatric Head Injury
Optimization of Ventilatory Techniques in Severe Hemorrhage and Cardiac Arrest
Interventions for Coronary Artery Syndromes
RECENT PUBLICATIONS
Pepe PE, "Defending the rights of all individuals to have access to potential life-saving therapies and resuscitation studies - Food and Drug Administration public hearing on the conduct of emergency clinical research: testimony of Dr. Pepe:" Academic Emergency Medicine [www.aemj.org], 14:e51-e56, April 2007
Roppolo LP, Pepe PE, Campbell L, et al, "Prospective, randomized trial of the effectiveness and retention of 30-minute layperson training for cardiopulmonary resuscitation and automated external defibrillators" Resuscitation, 67:276-285, August 2007
Eastman AL, Metzger JC, Pepe PE, et al, "Conductive electrical weapons: A prospective, population-based study of the medical safety of law enforcement use." Journal of Trauma, 64:1567-1572, June 2008
Klein KR, Pepe PE, Burkle FM, Nagle NE, Swienton RE, "The evolving need for alternative triage-management protocols in public health emergencies." Disaster Med Public Health Prep, 2 (Special Supplement):S40-44, Fall 2008
Miller AH, Nazeer S, Pepe PE, Estes B, Gorman A, Yancy C., "Acutely decompensated heart failure in a county emergency department: a double-blind, randomized, controlled comparison of nesiritide vs. placebo treatment." Ann Emeg Med, 51:580-582, May 2008
SIGNIFICANT PUBLICATIONS
Pepe PE and Marini JJ, "Occult positive end expiratory pressure in mechanically ventilated patients with airflow obstruction The AUTO PEEP Effect." American Review Resp Disease, 126:166-170, July 1982
Pepe PE, Hudson LD, Carrico CJ, "Early application of positive end expiratory pressure in patients at risk for the adult respiratory distress syndrome." N Engl J Med, 311:281-286, August 1984
Bickell WH, Wall MJ, Pepe PE, et al, "Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injury." N Engl J Med, 331:1105-1109, October 1994
Becker LB, Berg RA, Pepe PE, et al, "A reappraisal of mouth to mouth ventilation during bystander initiated cardiopulmonary resuscitation." Resuscitation, 35:189-201, November 1997
Caffrey SL, Willoughby PJ, Pepe, PE, Becker LB, "Public use of automated defibrillators." New England Journal of Medicine, 347 (16):1242-1247, October 2002
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