Benjamin E Zusman1,2,3, Patrick M Kochanek3,4,5,6,7,8, Zachary S Bailey9, Lai Yee Leung9,10, Vincent A Vagni7,8, David O Okonkwo11, Ava M Puccio11, Lori A Shutter7, Keri L Janesko-Feldman7,8, Janice S Gilsdorf9, Deborah A Shear9, Ruchira M Jha12,13,14,15,16. 1. University of Pittsburgh School of Medicine, Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA. 2. Institute for Clinical Research Education, University of Pittsburgh, Pittsburgh, PA, USA. 3. Clinical and Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 4. Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 5. Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 6. UPMC Children's Hospital of Pittsburgh, UPMC, Pittsburgh, PA, USA. 7. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 8. Safar Center for Resuscitation Research, John G. Rangos Research Center, Pittsburgh, PA, USA. 9. Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USA. 10. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 11. Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 12. Clinical and Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ruchirajha@gmail.com. 13. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ruchirajha@gmail.com. 14. Safar Center for Resuscitation Research, John G. Rangos Research Center, Pittsburgh, PA, USA. ruchirajha@gmail.com. 15. Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ruchirajha@gmail.com. 16. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. ruchirajha@gmail.com.
Abstract
BACKGROUND: Despite increasing use in hemorrhagic shock (HS), whole blood (WB) resuscitation for polytrauma with traumatic brain injury (TBI) is largely unexplored. Current TBI guidelines recommend crystalloid for prehospital resuscitation. Although WB outperforms lactated Ringer's (LR) in increasing mean arterial pressure (MAP) in TBI + HS models, effects on brain tissue oxygenation (PbtO2), and optimal MAP remain undefined. METHODS: C57BL/6 mice (n = 72) underwent controlled cortical impact followed by HS (MAP = 25-27 mmHg). Ipsilateral hippocampal PbtO2 (n = 40) was measured by microelectrode. Mice were assigned to four groups (n = 18/group) for "prehospital" resuscitation (90 min) with LR or autologous WB, and target MAPs of 60 or 70 mmHg (LR60, WB60, LR70, WB70). Additional LR (10 ml/kg) was bolused every 5 min for MAP below target. RESULTS: LR requirements in WB60 (7.2 ± 5.0 mL/kg) and WB70 (28.3 ± 9.6 mL/kg) were markedly lower than in LR60 (132.8 ± 5.8 mL/kg) or LR70 (152.2 ± 4.8 mL/kg; all p < 0.001). WB70 MAP (72.5 ± 2.9 mmHg) was higher than LR70 (59.8 ± 4.0 mmHg, p < 0.001). WB60 MAP (68.7 ± 4.6 mmHg) was higher than LR60 (53.5 ± 3.2 mmHg, p < 0.001). PbtO2 was higher in WB60 (43.8 ± 11.6 mmHg) vs either LR60 (25.9 ± 13.0 mmHg, p = 0.04) or LR70 (24.1 ± 8.1 mmHg, p = 0.001). PbtO2 in WB70 (40.7 ± 8.8 mmHg) was higher than in LR70 (p = 0.007). Despite higher MAP in WB70 vs WB60 (p = .002), PbtO2 was similar. CONCLUSION: WB resuscitation after TBI + HS results in robust improvements in brain oxygenation while minimizing fluid volume when compared to standard LR resuscitation. WB resuscitation may allow for a lower prehospital MAP without compromising brain oxygenation when compared to LR resuscitation. Further studies evaluating the effects of these physiologic benefits on outcome after TBI with HS are warranted, to eventually inform clinical trials.
BACKGROUND: Despite increasing use in hemorrhagic shock (HS), whole blood (WB) resuscitation for polytrauma with traumatic brain injury (TBI) is largely unexplored. Current TBI guidelines recommend crystalloid for prehospital resuscitation. Although WB outperforms lactated Ringer's (LR) in increasing mean arterial pressure (MAP) in TBI + HS models, effects on brain tissue oxygenation (PbtO2), and optimal MAP remain undefined. METHODS: C57BL/6 mice (n = 72) underwent controlled cortical impact followed by HS (MAP = 25-27 mmHg). Ipsilateral hippocampal PbtO2 (n = 40) was measured by microelectrode. Mice were assigned to four groups (n = 18/group) for "prehospital" resuscitation (90 min) with LR or autologous WB, and target MAPs of 60 or 70 mmHg (LR60, WB60, LR70, WB70). Additional LR (10 ml/kg) was bolused every 5 min for MAP below target. RESULTS: LR requirements in WB60 (7.2 ± 5.0 mL/kg) and WB70 (28.3 ± 9.6 mL/kg) were markedly lower than in LR60 (132.8 ± 5.8 mL/kg) or LR70 (152.2 ± 4.8 mL/kg; all p < 0.001). WB70 MAP (72.5 ± 2.9 mmHg) was higher than LR70 (59.8 ± 4.0 mmHg, p < 0.001). WB60 MAP (68.7 ± 4.6 mmHg) was higher than LR60 (53.5 ± 3.2 mmHg, p < 0.001). PbtO2 was higher in WB60 (43.8 ± 11.6 mmHg) vs either LR60 (25.9 ± 13.0 mmHg, p = 0.04) or LR70 (24.1 ± 8.1 mmHg, p = 0.001). PbtO2 in WB70 (40.7 ± 8.8 mmHg) was higher than in LR70 (p = 0.007). Despite higher MAP in WB70 vs WB60 (p = .002), PbtO2 was similar. CONCLUSION: WB resuscitation after TBI + HS results in robust improvements in brain oxygenation while minimizing fluid volume when compared to standard LR resuscitation. WB resuscitation may allow for a lower prehospital MAP without compromising brain oxygenation when compared to LR resuscitation. Further studies evaluating the effects of these physiologic benefits on outcome after TBI with HS are warranted, to eventually inform clinical trials.
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