Todd J. Kilbaugh
VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1997–2026
About
Todd J. Kilbaugh, MD, is a Professor of Anesthesiology and Critical Care at the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia. He serves as an Attending Anesthesiologist and Attending Physician in Pediatric Critical Care Medicine within the Department of Anesthesiology and Critical Care Medicine at the Children's Hospital of Philadelphia. Dr. Kilbaugh is a member of the Medical Staff at the Hospital of the University of Pennsylvania and holds multiple leadership roles, including Co-Director of Neurosurgical Critical Care, Medical Director of The ECMO Center, and Director of the Resuscitation Science Center of Emphasis at Children's Hospital of Philadelphia. He is also the Associate Chair for Research in the Department of Anesthesiology and Critical Care Medicine and participates in executive leadership at the Children's Hospital of Philadelphia, including roles in translational medicine, clinical innovation, and strategy. His research interests focus on resuscitation science, mitochondrial and epigenomic medicine, and pediatric critical care, with numerous publications in these areas. Dr. Kilbaugh holds a BS in Biology from Wake Forest University and an MD from the Medical University of South Carolina.
Research topics
- Medicine
- Anesthesia
- Internal medicine
- Cardiology
- Intensive care medicine
- Pathology
- Surgery
- Radiology
- Psychiatry
- Chemistry
- Biology
- Pediatrics
Selected publications
Metabolites · 2026-01-11
articleOpen accessBackground/Objectives: Mitochondrial dysfunction is a major cause of brain injury in patients with primary mitochondrial disease. New mitochondrial therapeutics and non-invasive tools for efficacy monitoring are urgently needed. To these ends, succinate prodrug NV354 (methyl 3-[(2-acetylaminoethylthio)carbonyl]propionate) and diffuse optical techniques are promising. In this proof-of-concept study, we characterize NV354’s effects on microdialysis metrics of cerebral metabolism in a swine model of mitochondrial dysfunction and assess the associations of diffuse optical metrics with mitochondrial dysfunction and metabolic improvement. Methods: One-month-old swine received a four-hour co-infusion of rotenone with either the succinate prodrug NV354 (n = 5) or placebo (n = 5). Rotenone is a mitochondrial complex I inhibitor. Before and during co-infusion, cerebral metabolism was probed with microdialysis and diffuse optics. Microdialysis acquired interstitial lactate and pyruvate levels invasively, while diffuse optics measured changes in oxygen extraction fraction (OEF) and oxidized cytochrome-c-oxidase concentration (oxCCO). Results: Interstitial lactate continually increased in the placebo group (p < 0.01), but lactate levels plateaued in the NV354 group (p = 0.90). oxCCO also increased in the placebo group (p = 0.05), but OEF remained constant (p = 0.80). In the NV354 group, oxCCO increased (p < 0.01) while OEF decreased (p < 0.01). Conclusions: Microdialysis results suggest that NV354 treatment can increase oxygen metabolism in large animals with mitochondrial dysfunction. The optical oxCCO metric was also sensitive to metabolic changes induced by rotenone and NV354 administration.
Circulation · 2025-11-03
articleBackground: Nitric oxide signaling can mediate ischemia-reperfusion injury by altering vascular resistance and inflammatory responses, including the production and degradation of reactive oxygen species (ROS). Excess ROS contributes to oxidative stress and can impair mitochondrial energy synthesis via oxidative phosphorylation (OxPhos). We previously demonstrated that ROS and mitochondrial respiration in the neonatal brain can be adversely affected following deep hypothermic circulatory arrest (DHCA). It is unknown if inhaled nitric oxide (iNO) alters cerebral ROS and OxPhos capacity post-DHCA. Research Question: Does intraoperative iNO therapy affect cerebral ROS, OxPhos capacity, and neurologic injury or recovery after DHCA? Methods: Ten neonatal swine underwent DHCA (90min, 18 o C) prior to reperfusion and rewarming, of which half were randomized and blinded to receive iNO (40ppm) intraoperatively (DHCA 90min+iNO , N=5) and half did not (DHCA 90min , N=5). Five additional piglets underwent sham procedures without bypass, DHCA, or iNO. Upon study completion, brain tissue was analyzed using high-resolution mitochondrial respirometry. Immunohistochemistry assessed microglia- and neuron-specific inflammation using antibodies for ionized calcium-binding adaptor molecule 1 (IBA-1) and beta-amyloid precursor protein (β-APP), respectively. Results: Following DHCA 90min+iNO , cerebral ROS production did not decline compared to DHCA 90min animals ( P =0.210, Figure ), and OxPhos capacity via mitochondrial complex I was reduced compared to both sham ( P =0.041 ) and DHCA 90min animals ( P =0.078, Figure ). Rare and frequent β-APP staining was more common after DHCA 90min and DHCA 90min+iNO compared to sham animals ( P =0.055), and IBA-1 staining in subcortical white matter increased following DHCA 90min+iNO compared to both sham ( P =0.001 ) and DHCA 90min animals ( P =0.013 , Figure ). Conclusions iNO does not attenuate cerebral ROS following DHCA, and may even increase microglial inflammation and post-operative white matter injury by impairing energy synthesis via mitochondrial complex I. Further studies are warranted to elucidate how regional changes in the cerebral microcirculation may affect the delivery, efficacy, and toxicity of targeted therapeutics following DHCA. Improved insights into how microglial inflammation and mitochondrial energy synthesis mediate neurologic injury and recovery post-DHCA might ultimately help improve neurocognitive outcomes in congenital cardiac surgery.
Circulation · 2025-11-03
articleIntroduction: Hemodynamic-directed cardiopulmonary resuscitation (HD-CPR) targets blood pressure (BP) goals during resuscitation and has shown improved outcomes compared to conventional algorithmic CPR. However, the relationship between specific BP targets and cerebral health remains poorly understood. Objective: Evaluate the association of intra- and post-arrest cerebral hemodynamics, assessed using non-invasive optical neuromonitoring, with CPR strategies that include higher and lower target HD-CPR and algorithmic CPR. Hypothesis: Higher target HD-CPR will result in increased crerebral oxygenation (StO 2 ) and relative blood flow (rCBF) and blood volume (rCBV) compared to lower target HD-CPR or algorithmic CPR. Methods: Invasive BP monitoring and non-invasive optical neuromonitoring were performed in a pediatric swine model of asphyxia-associated cardiac arrest. After baseline (5 min) and asphyxia (7 min), ventricular fibrillation was induced. Animals were randomized to 1) high target HD-CPR with a goal systolic BP of 110 and diastolic BP of 45 mmHg (n=15), 2) low target HD-CPR with a goal systolic BP of 80 and diastolic BP of 30 mmHg (n=15), or 3) algorithmic depth-directed CPR (n=15). During HD-CPR, vasopressor administration was titrated to BP goals versus protocolized administration every 4 min in algorithmic CPR. After 15 min of CPR, animals were eligible for defibrillation. Animals achieving return of spontaneous circulation (ROSC) were monitored for 4 hours post-ROSC. A Kruskal Wallis test compared cerebral hemodynamics between groups during baseline, asphyxia (7th min), CPR (15th min), and post-ROSC (10, 60, and 240th min). Since not all subjects achieved HD-CPR goals intra-arrest, a secondary analysis compared subjects where mean BP in the 10-15th min of CPR was at goal. Results: No intra- or post-arrest group differences were observed in StO 2 , rCBV, rCBF, and MAP (p>0.05; Fig. 1). In the secondary analysis of HD-CPR animals that achieved goal BP, StO 2 was higher in the high (n=8) vs. low (n=10) target BP groups (median [IQR]: 36.5 [32.9, 38.9] vs. 27.8 [20.1, 35.2], p=0.03). Discussion: In our primary intention-to-treat analysis, no differences were observed between CPR strategies. However, high BP target HD-CPR that achieved BP goals increased cerebral oxygenation. This reinforces the established association between BP and cerebral oxygenation. Future work is needed to optimize HD-CPR strategies to consistently achieve higher blood pressures.
Circulation · 2025-11-03
articleIntroduction: Excess lipolysis and dysregulated fatty acid oxidation can exacerbate neuroglial injury and impair neurodevelopment. Neurodevelopment is also regulated by histone deacetylation and methylation, which often repress gene transcription and can alter cerebral metabolism. It is unknown if fatty acid metabolism and histone modifications are altered in the neonatal brain following cardiopulmonary bypass (CPB). Research Question: This study sought to determine if histone modifications regulating chromatin accessibility and gene transcription are altered in the brain or associated with changes in cerebral metabolism at 12-24hrs post-CPB. Methods: Fifteen neonatal swine underwent 3hrs of CPB prior to decannulation and survival for 12hrs, 18hrs, or 24hrs (N=5 per cohort). Three additional piglets underwent similar sham procedures with 4hr survival. Cortical brain tissue was then analyzed with liquid chromatography-mass spectrometry using an untargeted approach to quantify 129 metabolites and 45 histone modifications in each sample. Histone modifications with a statistically significant fold-change (FC) post-CPB ( P <0.0001) were correlated with metabolites across all timepoints of analysis. Results: In total, 6/45 (13%) histone modifications were significantly altered in cortical brain tissue following CPB. The acetylation of histone H4 on lysine residue 16 (H4K16ac) was reduced at 12-24hrs post-CPB (FC=0.7-0.8, P <0.0001 ), while trimethylation was enriched on histone H4 at lysine residue 20 (H4K20me3: FC=1.5-2.4; Figure ). H4K20me3 enrichment directly correlated with intermediates of fatty acid metabolism, specifically polyunsaturated long-chain acylcarnitines ( Table ). Histone H3 variants had enriched mono-methylation on lysine 36 residues at 12hrs (H33K36me1: FC=6.9, P <0.0001 ) and 18hrs post-CPB (H31K36me1: FC=1.6, P <0.0001 ). Histone H3 mono-methylation was also enriched on lysine residue 23 (H3K23me1) at 18hrs post-CPB (FC=5.1, P <0.0001 ), and phosphorylation on serine residue 10 (H3S10ph) was enriched at 24hrs post-CPB (FC=6.2, P <0.0001 ). Conclusion: Dynamic changes in histone methylation and deacetylation post-CPB may impact metabolic homeostasis in the neonatal brain during critical periods of neurodevelopment. Further investigations are warranted to elucidate how alterations in lipolysis, fatty acid oxidation, chromatin accessibility, and gene transcription may affect myelination, neuroglial injury, and neurodevelopment in neonates requiring cardiac surgery.
Resuscitation · 2025-11-08 · 1 citations
articleOpen accessCirculation · 2025-11-03 · 1 citations
articleIntroduction: We have developed non-invasive optical devices for concurrent monitoring of cerebral and somatic hemodynamics using frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS). Objectives: In a pediatric swine model of asphyxia-associated cardiac arrest, compare cerebral and somatic hemodynamics during asphyxia and CPR and assess their association with return of spontaneous circulation (ROSC) in early (<15 min) and late CPR (15-25 min). Hypothesis: Cerebral hemodynamics will exceed somatic hemodynamics. Greater hemodynamics, and their temporal increase, during CPR will be associated with return of spontaneous circulation (ROSC). Methods: Optical cerebral and somatic monitoring was performed on the left forehead and left biceps femoris, respectively, in pediatric swine during asphyxia followed by ventricular fibrillation induction and CPR for a minimum of 15 min, up to 25 min. Animals were eligible for defibrillation at 15 min, and every 2 min thereafter. FD-DOS tissue oxygenation (StO2), total hemoglobin concentration (HbT), and DCS blood flow index (BFI) quantified oxygenation, blood volume (BV), and blood flow (BF), respectively. Wilcoxon signed-rank tests with Bonferroni correction compared cerebral versus somatic hemodynamics in 1-min intervals during asphyxia and CPR. Rank-based mixed-effects models assessed the associations of hemodynamics with ROSC in early and late CPR. For late CPR, only data from animals without ROSC at each respective timepoint were included. Results: Of 22 animals monitored, 10 achieved ROSC (5 after first defibrillation). Cerebral and somatic hemodynamics differed throughout, but cerebral was not consistently greater. Compared to somatic, cerebral StO2 was lower during asphyxia and the 1st min of CPR but did not differ after. Cerebral BV and BF were greater during asphyxia. Cerebral BV remained greater to the 10th min of CPR but did not differ after; unexpectedly, cerebral BF was lower throughout CPR (Fig. 1). Examining ROSC associations, increasing somatic BV (p<0.001), absolute cerebral StO2 (p<0.003), and increasing cerebral-somatic BF difference (p<0.05) were associated in both early and late CPR. Notably, increasing cerebral BV (p=0.002) was also strongly associated in late CPR. Conclusion: Advanced optical monitoring during asphyxia and CPR provided novel quantification of cerebral and somatic hemodynamics, their differences, and their associations with ROSC in early and late CPR.
Circulation · 2025-11-03
articleSenior authorBackground: Animal and recent clinical studies have identified differences in the hemodynamic response to epinephrine between survivors and non-survivors. We aimed to evaluate how sequential epinephrine responses during CPR relate to survival outcomes in an animal model of cardiac arrest with standard chest compression depth. Hypothesis: Hemodynamic responses to sequential epinephrine doses during CPR change over time and are associated with ROSC. Methods: We retrospectively analyzed hemodynamic data acquired in pediatric swine models ( Sus scrofa , 9-13kg) of asphyxia-associated cardiac arrest treated with CPR (n=69). Epinephrine (0.02mg/kg) was administered every 3-4min starting 2 minutes into CPR. Defibrillation was attempted after 10 or 15min of CPR based off the cohort. Manual or mechanical chest compressions were performed at a set depth and rate throughout CPR. Median and interquartile ranges were calculated for diastolic blood pressure (DBP), systolic blood pressure (SBP), end-tidal CO 2 (ETCO 2 ), pulse pressure (SBP-DBP), and right atrium pressure (RaP) for each 15-second epoch and the change between pre-epinephrine values and each 15-second value for the 3m post-epinephrine were determined. Wilcoxon rank-sum tests were used for sequential Epi dose to compare survivors and non-survivors at each epoch. Trends across Epi doses within both groups were compared using Kruskal-Wallis test with Bonferroni correction. Results: Sixty-nine animals (survivor 42, non-survivor 27) were included. Baseline characteristics were similar between groups. Comparisons between survivors and non-survivors for the first 3 Epi doses are show in in Figure 1. During the evaluation period, non-survivors had progressively diminished responses to Epi as noted by lower delta DBP and SBP. RaP showed no significant change. Non-survivors exhibited progressive decline in median pulse pressure with each subsequent dose (Figure 2), whereas survivors maintained stable pulse pressure with no significant change between the first and the third doses. Discussion: In an animal model of asphyxia-associated cardiac arrest, the response to successive epinephrine administration diverge between survivors and non-survivors. Although the two groups have comparable responses to the first Epi dose, non-survivors have lower blood pressures and a decreased response to subsequent Epi doses. Future studies should explore alternative resuscitation strategies for animals based off Epi responsiveness.
Critical Care Medicine · 2025-01-01
articleResuscitation Plus · 2025-03-14 · 1 citations
articleOpen accessMeasurement of coronary perfusion pressure (CoPP) and diastolic blood pressure (DBP) during cardiopulmonary resuscitation (CPR) is important for titration of physiologic-directed CPR. However, agreement between different calculation methods and their relative performance as outcome discriminators are not well established. Four calculation methods, differentiated by sampling technique, were retrospectively applied to pressure waveforms from piglet CPR: late diastole (CoPP 65 , DBP 65 ), mid-diastole (CoPP 50 , DBP 50 ), diastolic minimum (CoPP min , DBP min ), and diastolic mean (CoPP mean , DBP mean ). Intermethod agreement was assessed by Bland-Altman analysis and Cohen’s kappa statistic. Logistic regression was used to evaluate performance in discriminating return of spontaneous circulation (ROSC) and to identify optimal thresholds. Relative to CoPP 65 , measurements by CoPP 50 , CoPP min , and CoPP mean were within 5 mmHg limits of agreement (LOA) in 97%, 64%, and 99% of instances with kappa 0.88, 0.76, and 0.91, respectively. Relative to DBP 65 , measurements by DBP 50 , DBP min , and DBP mean were within 5 mmHg LOA in 98%, 71%, and 99% of instances with kappa 0.90, 0.80, and 0.91, respectively. The areas under the ROC curves (AUC) for CoPP 65 , CoPP 50 , CoPP min , and CoPP mean were 0.777, 0.792, 0.787, and 0.788, and optimal thresholds to discriminate ROSC were 15.3, 15.8, 12.3, and 14.7 mmHg, respectively. The AUCs for DBP 65 , DBP 50 , DBP min , and DBP mean were 0.813, 0.827, 0.833, and 0.826, and optimal thresholds to discriminate ROSC were 28.6, 27.3, 26.2, and 29.7 mmHg, respectively. During piglet CPR, measurements by late diastole, mid-diastole, and diastolic mean strongly agreed, whereas those at diastolic minimum were more discrepant. All methods performed similarly in discrimination of ROSC.
1756: SEVERE PEDIATRIC TBI AND TRANSPORT TO A QUATERNARY PEDIATRIC FACILITY: AN OUTCOME ANALYSIS
Critical Care Medicine · 2025-01-01
article
Recent grants
Mitochondrial Targeted Biofuels as Countermeasures Against Chemical Threats
NIH · $473k · 2017–2020
Improving Pediatric Cardiac Arrest Survival and Neurologic Outcome
NIH · $4.4M · 2019–2025
Frequent coauthors
- 229 shared
Robert A. Berg
University of Pennsylvania
- 204 shared
Ryan W. Morgan
University of Pennsylvania
- 191 shared
Vinay Nadkarni
Children's Hospital of Philadelphia
- 154 shared
Robert M. Sutton
Children's Hospital of Philadelphia
- 127 shared
Alexis A. Topjian
- 104 shared
Jimmy W. Huh
University of Pennsylvania
- 95 shared
Michael Karlsson
Rigshospitalet
- 89 shared
Tiffany S. Ko
University of Pennsylvania
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