Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats

Todd O. McKinley, Zhigang Lei, Yannik Kalbas, Fletcher White, Zhongshan Shi, Fan Wu, Zao C. Xu, Richard Rodgers

Research output: Contribution to journalArticle

Abstract

BACKGROUND Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. METHODS Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact to their brain and pressure-controlled HS. Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents, Monmouth Junction, NJ) that removed circulating molecules between 5 kDa and 60 kDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96 hours postinjury. RESULTS Hemoadsorption improved survival from 47% in sham-treated rats to 86% in HA-treated rats. There were no treatment-related changes in histologic appearance. Hemoadsorption affected biomarker concentrations both during the treatment and over the ensuing 4 days after injury. Distinct changes in biomarker concentrations were also measured in survivor and nonsurvivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. CONCLUSION Blood purification by nonselective HA is an effective intervention to prevent death in a combined TBI/HS rat model. Hemoadsorption changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. Hemoadsorption has been safely implemented in human patients with sepsis and may be a treatment option after injury.

Original languageEnglish (US)
Pages (from-to)1063-1071
Number of pages9
JournalJournal of Trauma and Acute Care Surgery
Volume85
Issue number6
DOIs
StatePublished - Dec 1 2018

Fingerprint

Hemorrhagic Shock
Wounds and Injuries
Biomarkers
Therapeutics
Survival
Inflammation
Blood Circulation
Traumatic Brain Injury
Sprague Dawley Rats
Survivors
Sepsis
Technology
Pressure
Mortality
Brain

Keywords

  • cytokines
  • Hemoadsorption
  • hemorrhagic shock
  • multiple injuries
  • traumatic brain injury

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats. / McKinley, Todd O.; Lei, Zhigang; Kalbas, Yannik; White, Fletcher; Shi, Zhongshan; Wu, Fan; Xu, Zao C.; Rodgers, Richard.

In: Journal of Trauma and Acute Care Surgery, Vol. 85, No. 6, 01.12.2018, p. 1063-1071.

Research output: Contribution to journalArticle

McKinley, Todd O. ; Lei, Zhigang ; Kalbas, Yannik ; White, Fletcher ; Shi, Zhongshan ; Wu, Fan ; Xu, Zao C. ; Rodgers, Richard. / Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats. In: Journal of Trauma and Acute Care Surgery. 2018 ; Vol. 85, No. 6. pp. 1063-1071.
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T1 - Blood purification by nonselective hemoadsorption prevents death after traumatic brain injury and hemorrhagic shock in rats

AU - McKinley, Todd O.

AU - Lei, Zhigang

AU - Kalbas, Yannik

AU - White, Fletcher

AU - Shi, Zhongshan

AU - Wu, Fan

AU - Xu, Zao C.

AU - Rodgers, Richard

PY - 2018/12/1

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N2 - BACKGROUND Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. METHODS Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact to their brain and pressure-controlled HS. Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents, Monmouth Junction, NJ) that removed circulating molecules between 5 kDa and 60 kDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96 hours postinjury. RESULTS Hemoadsorption improved survival from 47% in sham-treated rats to 86% in HA-treated rats. There were no treatment-related changes in histologic appearance. Hemoadsorption affected biomarker concentrations both during the treatment and over the ensuing 4 days after injury. Distinct changes in biomarker concentrations were also measured in survivor and nonsurvivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. CONCLUSION Blood purification by nonselective HA is an effective intervention to prevent death in a combined TBI/HS rat model. Hemoadsorption changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. Hemoadsorption has been safely implemented in human patients with sepsis and may be a treatment option after injury.

AB - BACKGROUND Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. METHODS Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact to their brain and pressure-controlled HS. Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents, Monmouth Junction, NJ) that removed circulating molecules between 5 kDa and 60 kDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96 hours postinjury. RESULTS Hemoadsorption improved survival from 47% in sham-treated rats to 86% in HA-treated rats. There were no treatment-related changes in histologic appearance. Hemoadsorption affected biomarker concentrations both during the treatment and over the ensuing 4 days after injury. Distinct changes in biomarker concentrations were also measured in survivor and nonsurvivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. CONCLUSION Blood purification by nonselective HA is an effective intervention to prevent death in a combined TBI/HS rat model. Hemoadsorption changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. Hemoadsorption has been safely implemented in human patients with sepsis and may be a treatment option after injury.

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KW - multiple injuries

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