Traumatic-brain-injury-in-companion-animals-Pathophysiology-and-treatment

Prévia do material em texto

Review Article
Traumatic brain injury in companion animals: Pathophysiology 
and treatment
Molly Wart a,*, Thomas H. Edwards a,b,*, Julie A. Rizzo c, Geoffrey W. Peitz c, Armi Pigott d, 
Jonathan M. Levine a, Nicholas D. Jeffery a
a School of Veterinary Medicine, Texas A&M University, College Station, TX
b US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX
c Brooke Army Medical Center, JBSA Fort Sam Houston, TX
d College of Veterinary Medicine, Cornell University, Ithaca, NY
A R T I C L E I N F O
Keywords:
Traumatic brain injury
TBI
Osmotherapy
Polytrauma
A B S T R A C T
Traumatic brain injuries (TBI) are common in dogs and cats that have sustained head trauma from a variety of 
causes. In moderate to severe TBI, damage from both the primary and secondary injuries can be life-threatening. 
TBI management may be further complicated by concurrent injuries in polytrauma patients. Thorough initial and 
serial examinations are key in detecting neurologic changes quickly and guiding treatment. Intensive treatments 
such as nursing care, fluid therapy, hyperosmolar agents, analgesia, sedation, anticonvulsants, oxygen supple-
mentation, surgery, and rehabilitation may be employed in TBI management. Prognostication resources for an 
individual patient are limited and a perceived poor prognosis may worsen clinical outcomes. In this paper, we 
review the pathophysiology of TBI, identification, injury stratification and prognosis of patients with TBI as well 
as propose treatment and monitoring recommendations for companion animals based on severity of TBI.
Introduction
Traumatic brain injury (TBI) patients can require intensive man-
agement and be complex to care for, particularly following polytrauma. 
Mechanisms of TBI in veterinary patients are most often blunt trauma, 
such as being hit by a car, but can involve penetrating injuries, pre-
dominantly related to canine bite wounds.1 In a 2009 study of 235 dogs 
suffering severe blunt trauma, 91.1 % of the cases were the result of 
vehicular trauma and 72.3 % of the patients were polytrauma victims. 
Twenty five percent of all dogs had a clinical diagnosis of head trauma.2
In military working dogs, head injury was the second leading cause of 
death on the battlefield after hemorrhage, accounting for 21 % of 
traumatic deaths.3 The purpose of this review is to discuss the patho-
physiology of TBI, identification and injury stratification, current 
treatment and monitoring recommendations, and prognosis of patients 
with TBI.
Pathophysiology humans and animals
TBI is “an alteration in brain function, or other evidence of brain 
pathology, caused by an external force”.4 These injuries can be divided 
into two stages, primary injury and secondary injury. Primary injury 
occurs at the time of injury and results in physical disruption of intra-
cranial structures.5 Primary injuries are classified as mild, moderate, 
and severe and may be due to penetrating or blunt mechanisms. The 
least severe, mild TBI, may sometimes be interchangeably termed 
concussion. A mild injury may result in brief loss of consciousness but is 
not associated with the development of histopathologic lesions.6 Mod-
erate and severe brain injuries may result in extended periods of un-
consciousness, contusions, and hemorrhage. A hemorrhage-producing 
injury results in physical disruption of the brain parenchyma and can 
lead to severe neurologic dysfunction.5,7 The brain may also be affected 
by other lesions of the skull and intracranial region including cerebral 
edema and skull fractures. Intracranial hemorrhage can occur with 
variable degrees of severity. In a study of cats and dogs that experienced 
a severe TBI, 96 % were found to have intracranial hemorrhage on 
Abbreviations: TBI, traumatic brain injury; ICH, intracranial hypertension; CPP, cerebral perfusion pressure; MAP, mean arterial pressure; ICP, intracranial 
pressure; EDH, epidural hematoma; EVD, external ventricular drain; SIH, stress-induced hyperglycemia.
* Corresponding authors at: School of Veterinary Medicine, Texas A&M University, College Station, TX 77843.
E-mail address: wartm@tamu.edu (M. Wart). 
Contents lists available at ScienceDirect
Topics in Companion Animal Medicine
journal homepage: www.elsevier.com/locate/tcam
https://doi.org/10.1016/j.tcam.2024.100927
Topics in Companion An Med 63 (2024) 100927 
Available online 25 October 2024 
1938-9736/© 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. 
mailto:wartm@tamu.edu
www.sciencedirect.com/science/journal/19389736
https://www.elsevier.com/locate/tcam
https://doi.org/10.1016/j.tcam.2024.100927
https://doi.org/10.1016/j.tcam.2024.100927
http://crossmark.crossref.org/dialog/?doi=10.1016/j.tcam.2024.100927&domain=pdf
imaging.8
Secondary injury occurs in the minutes to days following primary 
injury. It is the result of numerous systemic processes that ultimately 
increase excitatory neurotransmitter activity and promote reactive ox-
ygen species and proinflammatory cytokine production.9 The forces of 
the primary injury disrupt axons, leading to swelling and initiating 
impact depolarization, characterized by sodium entering and potassium 
leaving the cells (Fig. 1).10 The release of large quantities of excitatory 
neurotransmitters results in an energy imbalance as metabolic activity 
increases and ATP levels decrease.11 Without sufficient ATP, sodium, 
potassium, and calcium can move freely in and out of the cells.9,10
Depolarized cells cause additional excitatory neurotransmitter release, 
which can then act to further increase intracellular calcium levels. High 
intracellular calcium causes severe intracellular damage by activating 
proteases, lipases, and endonucleases, often resulting in neuronal 
death.5,9 The brain enters a glycolytic metabolic state which increases 
accumulation of lactic acid as the blood-brain barrier breaks down and 
further cell death occurs. By four to six hours post-injury, local inflam-
matory responses lead to additional release of neurotransmitters that 
cause widespread cellular injury.10
Secondary injury is also influenced by increased release of inflam-
matory mediators as well as changes in cell membrane permeability. 
Blood vessel damage, reactive oxygen species, and nitric oxide produc-
tion can exacerbate secondary injury leading to decreased cerebral 
blood flow and hypoxia. It is important to remember, particularly in 
cases of polytrauma-associated TBI, that other systemic derangements 
can worsen secondary brain injury by decreasing cerebral perfusion and 
promoting neuronal cell death. These derangements may include sys-
temic inflammation, ischemia, hypoxia, electrolyte or acid-base distur-
bances, increases in intracranial pressure, blood brain barrier 
compromise, cerebral edema, and infection.5,7,12,13
Both primary and secondary injury changes can alter intracranial 
pressure. As described by the Monro-Kellie doctrine, the skull is a rigid 
compartment and contains three components (brain parenchyma, arte-
rial and venous blood, and cerebrospinal fluid) which can shift to 
maintain equilibrium.14–16 Increases in intracranial pressure result if a 
change to any of these components overwhelms the other components’ 
ability to compensate. This creates a state of intracranial hypertension 
(ICH). In TBI, potential causes of ICH include cerebral edema and 
intracranial hemorrhage. ICH can reduce cerebral perfusion pressure, 
leading to ischemia, furthering secondary injury.17 Cerebral perfusion 
pressure, or CPP, is a reflection of cerebral blood flow and is equal to 
mean systemic arterial blood pressure (MAP) minus intracranial pres-
sure (ICP). Normal ICP in adult humans is 7-15 mmHg with a CPP > 50 
mmHg.18 In a normal adult dog, ICP ranges between 3.4 and 11 mmHg 
with a CPP of 71 mmHg. The regulatory mechanisms of the brain can 
maintain adequate perfusion with MAPs in the range of 50 – 150 
mmHg.19,20http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0031
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0031
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0032
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0032
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0032
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0032
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0033
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0033
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0033
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0034
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0034
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0034
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0035
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0035
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0035
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0036
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0036
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0036
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0037
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0037
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0039
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0039
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0039
https://www.liebertpub.com/doi/10.1089/neu.2023.0051
https://www.liebertpub.com/doi/10.1089/neu.2023.0051
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0041
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0041
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0041
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0042
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0042
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0042
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0042
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0043
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0043
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0043
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0043
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0043
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0044
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0044
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0044
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0044
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0045
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0045
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0045
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0045
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0046
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0046
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0046
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0047
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0047
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0047
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0048
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0048
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0048
http://www.ncbi.nlm.nih.gov/books/NBK558915/
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0050
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0050
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0050
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0051
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0051
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0051
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0052
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0052
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0053
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0053
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0053
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0053
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0054
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0054
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0055
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0055
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0055
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0056
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0056
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0056
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0057
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0057
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0057
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0058
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0058
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0058
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0059
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0059
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0059
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0059
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0060
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0060
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0061
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0061
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0061
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0062
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0062
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0062
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0062
63. Roquilly A, Moyer JD, Huet O, Lasocki S, Cohen B, Dahyot-Fizelier C, et al. Effect 
of continuous infusion of hypertonic saline vs standard care on 6-month 
neurological outcomes in patients with traumatic brain injury. JAMA. 2021;325 
(20):1–11.
64. Madieh J, Hasan B, Khamayseh I, Hrizat A, Salah T, Nayfeh T, et al. The safety of 
intravenous peripheral administration of 3% hypertonic saline: A systematic 
review and meta-analysis. Am J Med Sci. 2023;366(2):135–142.
65. Alenazi AO, Alhalimi ZM, Almatar MH, Alhajji TA. Safety of peripheral 
administration of 3% hypertonic saline in critically Ill patients: a literature review. 
Crit Care Nurse. 2021;41(1):25–30.
66. Robba C, Poole D, McNett M, Asehnoune K, Bösel J, Bruder N, et al. Mechanical 
ventilation in patients with acute brain injury: recommendations of the European 
Society of Intensive Care Medicine consensus. Intensive Care Med. 2020;46(12): 
2397–2410.
67. Wiener J, McIntyre A, Janzen S, Mirkowski M, MacKenzie HM, Teasell R. Opioids 
and cerebral physiology in the acute management of traumatic brain injury: a 
systematic review. Brain Inj. 2019;33(5):559–566.
68. Zeiler FA, Teitelbaum J, West M, Gillman LM. The Ketamine Effect on ICP in 
Traumatic Brain Injury. Neurocrit Care. 2014;21(1):163–173.
69. Bhaire VS, Panda N, Luthra A, Chauhan R, Rajappa D, Bhagat H. Effect of 
combination of ketamine and propofol (Ketofol) on cerebral oxygenation in 
neurosurgical patients: a randomized double-blinded controlled trial. Anesth Essays 
Res. 2019;13(4):643–648.
70. Choo YH, Seo Y, Oh HJ. Deep Sedation in Traumatic Brain Injury Patients. Korean J 
Neurotrauma. 2023;19(2):185.
71. Hemphill S, McMenamin L, Bellamy MC, Hopkins PM. Propofol infusion syndrome: 
a structured literature review and analysis of published case reports. Br J Anaesth. 
2019;122(4):448–459.
72. Karakaya D, Cakir-Aktas C, Uzun S, Soylemezoglu F, Mut M. Tailored therapeutic 
doses of dexmedetomidine in evolving neuroinflammation after traumatic brain 
injury. Neurocrit Care. 2022;36(3):802–814.
73. Xu J, Xiao Q. Assessment of the effects of dexmedetomidine on outcomes of 
traumatic brain injury using propensity score analysis. BMC Anesthesiol. 2022;22: 
280.
74. Vrettou CS, Mentzelopoulos SD. Second- and third-tier therapies for severe 
traumatic brain injury. J Clin Med. 2022;11(16):4790.
75. Trieu C, Rajagopalan S, Kofke WA, Cruz Navarro J. Overview of hypothermia, its 
role in neuroprotection, and the application of prophylactic hypothermiain 
traumatic brain injury. Anesth Analg. 2023;137(5):953.
76. Hayes GM. Severe seizures associated with traumatic brain injury managed by 
controlled hypothermia, pharmacologic coma, and mechanical ventilation in a 
dog. J Vet Emerg Crit Care. 2009;19(6):629–634.
77. Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, Farrell B. Final results 
of MRC CRASH, a randomised placebo-controlled trial of intravenous 
corticosteroid in adults with head injury—outcomes at 6 months. The Lancet. 2005; 
365(9475):1957–1959.
78. DiFazio J, Fletcher DJ. Updates in the management of the small animal patient 
with neurologic trauma. Vet Clin North Am Small Anim Pract. 2013;43(4):915–940.
79. Huo X, Xu X, Li M, Xiao L, Wang Y, Li W, et al. Effectiveness of antiseizure 
medications therapy in preventing seizures in brain injury patients: A network 
meta-analysis. Front Pharmacol [Internet]; 2022 [cited 2023 Nov 2];13. Available 
from https://www.frontiersin.org/articles/10.3389/fphar.2022.1001363.
80. Kirmani BF, Robinson DM, Fonkem E, Graf K, Huang JH. Role of Anticonvulsants 
in the Management of Posttraumatic Epilepsy. Front Neurol [Internet]; 2016 [cited 
2023 Nov 2];7. Available from http://journal.frontiersin.org/Article/10.33 
89/fneur.2016.00032/abstract.
81. Grohmann KS, Schmidt MJ, Moritz A, Kramer M. Prevalence of seizures in cats 
after head trauma. J Am Vet Med Assoc. 2012;241(11):1467–1470.
82. Friedenberg SG, Butler AL, Wei L, Moore SA, Cooper ES. Seizures following head 
trauma in dogs: 259 cases (1999–2009). J Am Vet Med Assoc. 2012;241(11): 
1479–1483.
83. Steinmetz S, Tipold A, Löscher W. Epilepsy after head injury in dogs: a natural 
model of posttraumatic epilepsy. Epilepsia. 2013;54(4):580–588.
84. Hunter J, Palmer JF. Lectures on the Principles of Surgery. Philadelphia: Haswell, 
Barrington, and Haswell; 1839:400.
85. Fong R, Konakondla S, Schirmer CM, Lacroix M. Surgical interventions for severe 
traumatic brain injury. J Emerg Crit Care Med. 2017;1(10):28.
86. Kolias AG, Adams H, Timofeev IS, Corteen EA, Hossain I, Czosnyka M, et al. 
Evaluation of outcomes among patients with traumatic intracranial hypertension 
treated with decompressive craniectomy vs standard medical care at 24 months: a 
secondary analysis of the RESCUEicp randomized clinical trial. JAMA Neurol. 
2022;79(7):664–671.
87. Cooper DJ, Rosenfeld JV, Murray L, Arabi YM, Davies AR, D’Urso P, et al. 
Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011; 
364(16):1493–1502.
88. Morton BA, Selmic LE, Vitale S, Packer R, Santistevan L, Boudrieau B, et al. 
Indications, complications, and mortality rate following craniotomy or 
craniectomy in dogs and cats: 165 cases (1995–2016). J Am Vet Med Assoc. 2022; 
260(9):1048–1056.
89. Hodgson N, Walters A, Lawson C, Hague D, Joslyn S, McMichael M. Acute surgical 
intervention for a depressed skull fracture causing a laceration to the brain 
parenchyma from a bite wound in a dog. Can Vet J. 2018;59(1):31–35.
90. Bilderback AL, Faissler D. Surgical management of a canine intracranial abscess 
due to a bite wound. J Vet Emerg Crit Care. 2009;19(5):507–512.
91. Shi J, Dong B, Mao Y, Guan W, Cao J, Zhu R, et al. Review: Traumatic brain injury 
and hyperglycemia, a potentially modifiable risk factor. Oncotarget. 2016;7(43): 
71052–71061.
92. Syring RS, Otto CM, Drobatz KJ. Hyperglycemia in dogs and cats with head 
trauma: 122 cases (1997–1999). J Am Vet Med Assoc. 2001;218(7):1124–1129.
93. Yuan T, He H, Liu Y, Wang J, Kang X, Fu G, et al. Association between blood 
glucose levels and Glasgow Outcome Score in patients with traumatic brain injury: 
secondary analysis of a randomized trial. Trials. 2022;23(1):38.
94. Kurtz P, Rocha EEM. Nutrition therapy, glucose control, and brain metabolism in 
traumatic brain injury: a multimodal monitoring approach. Front Neurosci. 2020; 
14:190.
95. Acosta-Escribano J, Fernández-Vivas M, Grau Carmona T, Caturla-Such J, Garcia- 
Martinez M, Menendez-Mainer A, et al. Gastric versus transpyloric feeding in 
severe traumatic brain injury: a prospective, randomized trial. Intensive Care Med. 
2010;36(9):1532–1539.
96. Mathis S, Lamy M, Ciron J, Iljicsov A, Arjmand R, Agius P, et al. Paroxysmal 
sneezing at the onset of syncopes and transient ischemic attack revealing a 
papillary cardiac fibroelastoma. Case Rep Neurol Med. 2014;2014(1), 734849.
97. Syncope: Classification and risk stratification - ClinicalKey [Internet]. [cited 2024 
Sep 19]. Available from: https://www.clinicalkey.com/#!/content/playContent/1 
-s2.0-S0914508713003924?scrollTo=%23hl0000343.
98. Altmayer T, O’Dell MW, Jones M, Martin V, Hawkins HH. Cisapride as a treatment 
for gastroparesis in traumatic brain injury. Arch Phys Med Rehabil. 1996;77(10): 
1093–1094.
99. Chen YH, Huang EYK, Kuo TT, Miller J, Chiang YH, Hoffer BJ. Impact of traumatic 
brain injury on dopaminergic transmission. Cell Transplant. 2017;26(7): 
1156–1168.
100. Nursal TZ, Erdogan B, Noyan T, Cekinmez M, Atalay B, Bilgin N. The effect of 
metoclopramide on gastric emptying in traumatic brain injury. J Clin Neurosci. 
2007;14(4):344–348.
101. Makkar JK, Gauli B, Jain K, Jain D, Batra YK. Comparison of erythromycin versus 
metoclopramide for gastric feeding intolerance in patients with traumatic brain 
injury: A randomized double-blind study. Saudi J Anaesth. 2016;10(3):308–313.
102. Hoffberg JE, Koenigshof A. Evaluation of the safety of early compared to late 
enteral nutrition in canine septic peritonitis. J Am Anim Hosp Assoc. 2017;53(2): 
90–95.
103. Liu DT, Brown DC, Silverstein DC. Early nutritional support is associated with 
decreased length of hospitalization in dogs with septic peritonitis: A retrospective 
study of 45 cases (2000–2009). J Vet Emerg Crit Care. 2012;22(4):453–459.
104. Liu X, Zhang G, Wei P, Zhong L, Chen Y, Zhang J, et al. Three-dimensional-printed 
collagen/chitosan/secretome derived from HUCMSCs scaffolds for efficient neural 
network reconstruction in canines with traumatic brain injury. 9. Regen Biomater; 
2022:rbac043.
105. Stevens AR, Soon WC, Chowdhury YA, Toman E, Yim S, Veenith T, et al. External 
Lumbar drainage for refractory intracranial hypertension in traumatic brain injury: 
a systematic review. Cureus. 14(10):e30033.
106. Shakkour Z, Habashy KJ, Berro M, Takkoush S, Abdelhady S, Koleilat N, et al. Drug 
repurposing in neurological disorders: implications for neurotherapy in traumatic 
brain injury. The Neuroscientist. 2021;27(6):620–649.
107. Ma J, Huang S, Qin S, You C, Zeng Y. Progesterone for acute traumatic brain injury. 
Cochrane Database Syst Rev. 2016;2016(12), CD008409.
108. Sorjonen D, Thomas W, Myers L, Cox N. Radical cerebral cortical resection in dogs. 
Prog Vet Neurol. 1991;2:225–236.
109. Chai O, Peery D, Bdolah-Abram T, Moscovich E, Kelmer E, Klainbart S, et al. 
Computed tomographic findings in dogs with head trauma and development of a 
novel prognostic computed tomography–based scoring system. Am J Vet Res. 2017; 
78(9):1085–1090.
110. Beltran E, Platt SR, McConnell JF, Dennis R, Keys DA, De Risio L. Prognostic value 
of early magnetic resonance imaging in dogs after traumatic brain injury: 50 cases. 
J Vet Intern Med. 2014;28(4):1256–1262.
111. Oberholzer M, Müri RM. Neurorehabilitation of Traumatic Brain Injury (TBI): a 
clinical review. Med Sci. 2019;7(3):47.
112. Shaw L, Yoquelet R, Bowditch J, Buckley C, Murakami M, Thomovsky S. The use of 
physical rehabilitation to improve outcome following traumatic brain injury in 
dog- a case report. J Am Holist Vet Med Assoc. 2023;72:26–35.
M. Wart et al. Topics in Companion Animal Medicine 63 (2024) 100927 
10 
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0063
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0063http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0063
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0063
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0064
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0064
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0064
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0065
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0065
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0065
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0066
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0066
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0066
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0066
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0067
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0067
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0067
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0068
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0068
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0069
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0069
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0069
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0069
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0070
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0070
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0071
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0071
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0071
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0072
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0072
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0072
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0073
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0073
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0073
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0074
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0074
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0075
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0075
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0075
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0076
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0076
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0076
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0077
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0077
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0077
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0077
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0078
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0078
https://www.frontiersin.org/articles/10.3389/fphar.2022.1001363
http://journal.frontiersin.org/Article/10.3389/fneur.2016.00032/abstract
http://journal.frontiersin.org/Article/10.3389/fneur.2016.00032/abstract
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0081
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0081
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0082
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0082
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0082
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0083
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0083
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0084
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0084
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0085
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0085
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0086
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0086
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0086
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0086
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0086
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0087
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0087
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0087
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0088
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0088
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0088
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0088
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0089
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0089
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0089
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0090
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0090
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0091
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0091
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0091
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0092
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0092
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0093
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0093
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0093
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0094
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0094
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0094
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0095
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0095
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0095
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0095
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0096
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0096
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0096
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0914508713003924?scrollTo=%23hl0000343
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0914508713003924?scrollTo=%23hl0000343
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0098
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0098
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0098
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0099
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0099
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0099
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0100
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0100
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0100
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0101
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0101
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0101
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0102
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0102
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0102
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0103
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0103
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0103
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0104
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0104
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0104
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0104
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0106
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0106
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0106
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0107
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0107
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0108
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0108
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0109
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0109
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0109
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0109
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0110
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0110
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0110
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0111
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0111http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0112
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0112
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0112
	Traumatic brain injury in companion animals: Pathophysiology and treatment
	Introduction
	Pathophysiology humans and animals
	Assessment and injury stratification
	Imaging assessment
	Brain Injury Guidelines
	Monitoring
	Intracranial pressure monitoring
	Brain tissue oxygenation monitoring
	Treatment considerations in humans and animals
	Fluid therapy
	Hyperosmolar fluids
	Oxygen and ventilation
	Analgesics and sedation
	Hypothermia
	Steroids
	Anticonvulsant therapy
	Surgery
	Glycemic control and nutrition
	Novel therapies
	Prognosis
	Rehabilitation
	Conclusion
	DoD disclaimer
	CRediT authorship contribution statement
	Declaration of competing interest
	Acknowledgements
	ReferencesThe severe inflammation of TBI results in failure of cerebral 
pressure regulation, which causes systemic blood pressure to become a 
primary determinant of cerebral perfusion pressure.19
In the event of ICH, a Cushing reflex may be clinically observed. This 
is characterized as a widened pulse pressure – more commonly refer-
enced as systemic hypertension, bradycardia, and irregular respiration. 
The systolic blood pressure is raised via the sympathetic nervous system 
response to high ICP and its resulting reduced cerebral perfusion pres-
sure.21 Initially, patients are tachycardic but will become bradycardic 
while the widened pulse pressure persists. Periodic apnea may be seen. 
Findings consistent with a Cushing reflex are concerning for brainstem 
compression and potential herniation.21 In a study of dogs, an admission 
systolic blood pressure > 140mmHg and a heart ratethe optic nerve sheath diameter via transocular ultrasound and esti-
mation of ICP via transcranial doppler. Pilot studies estimating ICP 
based on MRI and CT imaging have also shown potential, but do not 
have established reliable criteria.37 A measured optic nerve diameter of 
>0.6cm on non-contrast CT is sensitive but not specific to ICH.40
Similar monitoring systems have been studied in dogs, although EVD 
are not commonly used due to multiple difficulties with placement, 
including variation in relevant landmarks (such as ventricles), and dif-
ficulty maintaining the scale at the level of the head. ICP transducers 
that did not require a fluid pressure scale showed potential as accurate 
gauges of ICP in cats and dogs, but again are not favored because of 
complexities of placement and system fragility (Fig. 2).20 More recently, 
a miniature intracranial strain-gauge pressure-sensing device that sits 
outside the brain parenchyma in the subdural space has been tested in 
dogs. This option was found to have relatively easier placement than 
other methods and provided ICP readings, although the accuracy of 
subdural vs intraparenchymal lesions is not well described. Unfortu-
nately, these ICP readings continue to vary with head positioning similar 
to intraparenchymal devices.20 Indirect ICP assessments may provide a 
more accessible option for ICP monitoring in veterinary patients. In 
dogs, transocular ultrasound for estimation of optic nerve sheath 
diameter has been found to be reliably measurable. However, it is not 
yet a validated method of assessing intracranial hypertension in dogs.41
Brain tissue oxygenation monitoring
Measuring brain tissue oxygen (PbtO2) is an active area of research 
in human medicine, but it is not currently a standard monitoring 
recommendation for severe TBI. Severe TBI can result in cerebral hyp-
oxia which can contribute to worsening secondary injuries. PbtO2 
measurements may help to more specifically guide therapy because 
vascular and microvascular damage from TBI may impair the normal 
correlation between ICP and PbtO2.42 The Boost-II, human multi-center 
clinical trial assessed the management of severe TBI by measuring ICP 
alone vs ICP and PbtO2 and found the addition of PbtO2 monitoring to 
be safe and feasible with those patients experiencing decreased periods 
of brain tissue hypoxia.43 It may also be used in combination with 
intracranial pressure monitoring and be of particular use for ICH when 
rescue therapies such as hyperventilation are being considered.18,42
At the time of writing measuring PbtO2 for TBI has not been reported 
in dogs or cats.
Treatment considerations in humans and animals
Management algorithms have been proposed for human patients 
with ICP monitoring alone and those with ICP and brain hypoxia 
monitoring. The algorithms were developed by the Seattle International 
Severe Traumatic Brain Injury Consensus Conference (SIBICC) to pro-
vide a tiered approach to ICP management in severe TBI, where riskier 
treatments are reserved for patients with more refractory ICP. The rec-
ommendations are based on a consensus, not a proven standard of care 
or ideal choice for every patient/situation.44 Below is a proposed 
adaptation of the SIBICC recommendations for application to small an-
imal veterinary care.
Initial treatment should focus on triage of vital systems and patient 
stabilization basics including airway, breathing, and circulation. Vet-
erinary patients may have sustained unknown trauma necessitating 
screening for additional traumatic injuries, such as screening thoracic 
and abdominal radiographs. Alternatively, if a head CT is being already 
performed or considered due to clinical concerns for additional pa-
thology, thoracic and/or abdominal CT could be added.
Proposed TBI management (Table 1) in small animal veterinary pa-
tients is adapted from SIBICC and BIG/mBIG recommendations. Patients 
should be grouped by their most severe criteria: e.g. MGCS of 13 with a 
displaced skull fracture is Group 3.
Basic TBI Care – Adaptation of SIBICC Tier Zero Severe TBI 
Management.44,45
M. Wart et al. Topics in Companion Animal Medicine 63 (2024) 100927 
3 
• Fluid resuscitation as appropriate to achieve systolic pressure 
≥100mmHg
• Serial evaluation of neurological status and pupillary reactivity
• Elevate the head 15-30 degrees on a gradual slope without kinking of 
the jugular vein 
○ This positioning increases venous drainage and cerebral perfusion 
while decreasing ICP.20
• Analgesia to manage signs of pain 
○ Consider continuous rate infusion of full mu opioids (fentanyl, 
methadone)
• Sedation to prevent agitation and associated elevation in ICP
• Temperature management to prevent fever; treat temperatures >
103.5◦F
• Avoid hyponatremia
• Maintain SpO2 ≥ 94 %
Reassessment is crucial for guiding therapy choices, particularly in 
the event there is a sudden change in patient status. Repeat CT could be 
considered to detect a surgical lesion. Thorough evaluation should 
consider changes in extracranial causes of ICH and additional specialist 
consultation.44
Fluid therapy
Appropriate fluid resuscitation should be performed as indicated to 
correct hypovolemia, and maintain adequate blood pressure and 
appropriate cerebral perfusion pressure. Laboratory studies suggest that 
gradual resuscitation may be associated with less cerebral tissue 
swelling than bolus infusions.47 However, hypotensive resuscitation 
strategies are considered contraindicated in humans and a study of 
people with severe TBI found that a single incidence of hypotension 
resulted in a 150 % increase in mortality.48 Hypotensive resuscitation 
strategies involve purposefully allowing a patient’s blood pressure to 
remain lower than normally accepted in hemodynamically unstable 
patients with the goal of permitting vasoconstriction and reducing 
negative effects of resuscitation efforts.49 This is different than 
low-volume resuscitation strategies that employ more targeted fluid 
therapy options to reduce the total volume of fluid administered while 
achieving adequate blood pressures and hemodynamic stability. 
Low-volume resuscitation has not been evaluated for TBI patients spe-
cifically, but has been shown to have potential benefits compared to 
traditional fluid therapy in hemorrhagic shock patients.50
Regarding fluid choice, laboratory studies on animals and human 
clinical trials do not reveal an obvious fluid type choice.19 There is some 
support for usage of 0.9 % NaCl in patients with normal electrolytes due 
to its low volume of free water and potential for having less impact on 
worsening cerebral edema compared to large volumes of isotonic crys-
talloids.51 However, other studies report patients receiving 0.9 % NaCl 
required larger fluid volumes to achieve adequate MAP. Plasma trans-
fusion has also shown potential in human TBI patients, but again, cur-
rent studies provide conflicting results. Nitric oxide, ROS scavengers, 
and the role of lactate are being studied as potential future adjuncts to 
fluid resuscitation with the goal of decreasing fluid volume requirements 
to achieve similar MAPs.52–54 Current recommendations for fluid ther-
apy in cases of human TBI give an endpoint goal of maintaining systolic 
blood pressure ≥100 mmHg.38 The Brain Trauma Foundation guidelines 
for humans do not make a recommendation on fluid type.19
While multiple species, including dogs and cats, have been used as 
models for resuscitation in laboratory settings, clinical trials evaluating 
veterinary TBI patients and resuscitation fluid types have not been well 
evaluated. The same endpoint goal of a systolic blood pressure ≥ 100 
mmHg is also used in veterinary medicine reviews.5 Current fluid 
therapy recommendationsare to correct systemic hypotension with the 
clinician’s fluid therapy of choice.19
If fluid therapy is insufficient to maintain MAPs, vasopressors may be 
indicated. The ideal vasopressor use strategy is unknown and there are 
not recommendations for a specific vasopressor in human medicine. A 
retrospective study in humans with severe TBI found phenylephrine was 
the most commonly single agent vasopressor followed by norepineph-
rine with a potential increased risk of in-hospital mortality identified 
with norepinephrine.55 There are not TBI specific studies for vasopressor 
therapy in dogs and cats.
Hyperosmolar fluids
Hyperosmolar agents, most often hypertonic saline or mannitol, are 
commonly used to improve MAP and reduce interstitial edema 
contributing to ICH. Comparison studies in human medicine suggest that 
hypertonic saline may be more effective in decreasing intracranial 
pressure.56,57 Hypertonic saline also has the added benefit of providing 
support for hypovolemic patients that mannitol does not. However, 
benefits of using hypertonic saline over mannitol are not demonstrated 
Fig. 2. Intraoperative placement of an intracranial pressure monitor in a cat. The pressure-measuring probe is inserted through a small diameter burr hole in the skull 
following a small incision in the dura mater. (Courtesy of Dr. Daisuke Ito, Nihon University, Japan).
M. Wart et al. Topics in Companion Animal Medicine 63 (2024) 100927 
4 
with regards to survival or neurologic deficits. Therefore, the Brain 
Trauma Foundation (BTF) guidelines do not give a recommendation of 
one over the other.38,58 Furosemide to reduce cerebral edema is also not 
recommended by the BTF.38 The decision between hyperosmolar agents 
is often based on additional patient criteria including hydration status 
and pre-existing hypernatremia.59,60
Prolonged usage of hyperosmolar fluids can result in resistance or 
compensation by the brain through the formation of idiogenic osmoles. 
Sudden discontinuation of the hyperosmolar agent leads to an osmotic 
gradient that pulls water into the brain, instead of out, and can ulti-
mately result in worsened or rebound ICH and cerebral edema. Simi-
larly, intracranial hemorrhage or other disruptions of the blood brain 
barrier also allow the administered osmotically active molecules to 
accumulate within the cranium and pull water in with them. This can 
cause similar complications regarding ICH and cerebral edema.61 As a 
result, there are competing TBI management strategies in human med-
icine such as “The Lund Concept” which discourages usage of hyper-
osmolar agents while the SIBICC algorithm incorporates them.44,61
Choice between mannitol and hypertonic saline in veterinary med-
icine is also uncertain. A pilot study in two cats and a dog found that 
when using a single dose both mannitol and 3 % hypertonic saline were 
effective in reducing intracranial pressure and increasing cerebral 
perfusion pressure, but the effects of mannitol were shorter lived and a 
rebound increase in intracranial pressure may have occurred after the 
initial positive effects.59
Hyperosmolar fluids are most often given as boluses rather than 
continuous infusions. In a review of human studies, continuous hyper-
osmolar therapy infusions to treat ICH were found to be safe and asso-
ciated with improved survival at 90 days.62 However, continuous 
infusion of 20 % hypertonic saline for human patients with moderate to 
severe TBI did not result in improved neurologic outcomes vs treatment 
with the standard of care at 6 months post-injury.63 Administration of 3 
% hypertonic saline via a peripheral catheter has been found to be safe 
with a low risk of complications in people with an increasing risk at 
higher infusion rates and for longer durations (≥ 6 h).64,65 Due to the 
lack of clear benefit and the risks of prolonged infusion, continuous rate 
infusion is not currently a generalized recommendation for severe TBI in 
human guidelines. There is not currently information regarding 
continuous hyperosmolar agent infusions to dogs or cats with TBI.
Oxygen and ventilation
Supplemental oxygen is indicated for initial treatment of all patients 
suffering from head injuries. The goal of oxygen supplementation is to 
maintain normoxemia because hypoxemia and hyperoxia can worsen 
clinical outcomes.48,66 Abnormal CO2 levels can also worsen secondary 
injury. Hypercapnia causes cerebral vasodilation thereby increasing 
intracranial blood volume, causing increased intracranial pressure. 
However, hypocapnia is also problematic in that it causes cerebral 
vasoconstriction that can cause cerebral ischemia.37 In severe TBI, 
SIBICC guidelines recommend maintaining PaCO2 at the low end of 
normal (35-38mmHg).45 It should be noted, that human medicine rec-
ommendations consider short-term hyperventilation as a rescue therapy 
for suspected brain herniation, but not for long-term maintenance.45,66
Recommendations for hyperventilation for refractory ICH aim for a 
PaCO2 of 30-32mmHg when brain tissue oxygenation monitors are in 
place. In the event of suspected herniation and initiation of rescue 
therapy, the lower limit of 30mmHg does not apply.44,45
Veterinary medicine recommendations in prior reviews have been 
based on human guidelines due to the lack of veterinary studies and 
suggest CO2 should be maintained at the low end of the normal range 
(venous CO2 40-45mmHg, arterial 35-40mmHg).7 Oxygen should be 
given in a way that achieves desired patient oxygenation parameters and 
minimizes patient stress including anxiety, sneezing, and coughing to 
avoid increasing ICP. Additional sedation may be needed to properly 
administer oxygen. Options for administration include oxygen kennels, 
oxygen hoods, or nasal cannulas. Nasal cannulas may provide a higher, 
more consistent, flow rate but could result in patient stress or nasal 
irritation. An oxygen hood or kennel may cause less nasal irritation than 
nasal cannulas, but impairs full access to the patient. More advanced 
Table 1 
Proposed TBI management guidelines adapted from SIBICC guidelines.
ABRIdGe Group 
(Animal Brain 
Injury Groups)
Diagnostics Treatment Comments
ABRIdGe 1 – Mild 
TBI 
Criteria: 
MGCS 13-15 
No history of 
anticoagulant/ 
antiplatelet 
therapy
Complete 
blood count 
Chemistry 
panel
Observation for 6-12 h 
Q2h neurological 
assessment
Escalate group 
number if there is 
evidence of 
decline 
Criteria for 
discharge: MGCS 
≥ 15
ABRIdGe 2 – 
Moderate TBI 
Criteria: 
MGCS 9-12 
No history of 
anticoagulant/ 
antiplatelet 
therapy 
Nondisplaced 
skull fracture
All from 
Group 1 
Head CT*
Admission to hospital 
for minimum 24-48 h 
Treatments of Group 1 
Hypertonic saline 3-7.5 
% by intermittent 
bolus; 1 - 5 ml/kg 
based on concentration 
used IV q6h as needed 
Mannitol by 
intermittent bolus, 
pending the patient is 
adequately hydrated; 
0.5-1g/kg IV q6h as 
needed 
Consider placement of 
central line**
Escalate group 
number if there is 
evidence of 
decline 
Criteria for 
discharge: MGCS 
≥ 15
ABRIdGe 3 – 
Severe TBI 
Criteria: 
MGCS ≤8 
Current 
anticoagulant/ 
antiplatelet 
therapy 
Displaced skull 
fracture 
Evidence of EDH
All from 
Groups 1 
and 2
Admission to ICU 
Treatments of Groups 1 
and 2 
Anti-seizure 
medications for 1 week 
(in the absence of an 
indication to continue) 
(bolus midazolam 0.2- 
0.5 mg/kg IV/IM/IN or 
diazepam 0.5-1 mg/kg 
IV/IN/PR for dogs; 
midazolam 0.2-0.5 
mg/kg IV/IM/IN for 
cats; levetiracetam 20- 
30mg/kg IV/PO q8h) 
Consider 
dexmedetomidine 
(0.5-1mcg/kg IV bolus 
vs 0.5-2mcg/kg/hr IV 
CRI) for additional 
sedation 
Consider placement of 
a feeding tube, to the 
level of the stomach or 
beyond with 
concurrent 
administration of a 
prokinetic (cisaprideor 
erythromycin) vs 
central parenteral 
nutrition 
Consider mechanical 
ventilation to maintain 
PaCO2 of 35-38mmHg 
Consider arterial line 
blood pressure 
monitoring
In the event of 
decline: 
Repeat CT 
Consider 
craniectomy for 
addressing a new/ 
developing 
hematoma or 
depressed skull 
fragment 
Consider mild 
hypothermia (33- 
35◦C) 
Consider 
additional pain 
management with 
ketamine 0.5-2 
mg/kg/hr IV CRI; 
consider up to 
5mg/kg/hr IV CRI 
for sedation 
Consider 
additional 
sedation with 
barbiturates, 
mechanical 
ventilation may be 
required
* Recommendations based on the size of hemorrhage evaluated on CT to guide 
grouping criteria may be difficult with the highly variable veterinary patient 
size.
** Jugular vein central line placement does not significantly alter ICP in 
neurocritically ill humans.46
M. Wart et al. Topics in Companion Animal Medicine 63 (2024) 100927 
5 
interventions like high flow nasal oxygen or mechanical ventilation may 
be indicated based on the patient’s response to traditional oxygen 
therapy.
Analgesics and sedation
Analgesic management is essential in any trauma patient because 
pain and agitation can increase ICP. It is important to consider the po-
tential effects of a chosen analgesic on the cardiovascular and respira-
tory systems that could worsen secondary injuries. Analgesics may also 
cause sedation and impair accurate mentation assessment. Management 
options for human TBI patients often start with full mu opioids because 
they are effective analgesics and reversible. Continuous infusion of 
fentanyl or morphine allows for close titration and is preferred over 
bolus administration. Opioids can result in respiratory depression and 
hypotension which may negatively impact patients with ICH.67 Keta-
mine may have neuroprotective properties while being relatively car-
diovascular and respiratory-sparing with less blood pressure reduction 
and therefore less potential adverse effects on cerebral perfusion pres-
sure. Previously, ketamine was not recommended due to concerns for 
increasing ICP but more recent literature does not support this 
concern.68 Ketamine can result in increased cerebral oxygen consump-
tion, an effect which may be reduced by pairing with propofol.69 Pro-
pofol is often used for initial sedation and contributes to reducing ICP 
through reductions in cerebral blood flow and MAP.70 Propofol provides 
no analgesic properties and can be associated with hypotension. Pro-
longed usage or high doses can result in propofol infusion syndrome and 
increased morbidity.71
Alpha-2 agonist use, particularly dexmedetomidine, has been a 
recent area of research focus in human medicine. While there is concern 
for potential adverse cardiovascular and perfusion effects, such as hy-
potension and bradycardia, there is also evidence of dexmedetomidine 
infusion being associated with improved survival in human TBI patients 
and reduced neuroinflammation in mouse models.72,73 Total intrave-
nous anesthesia is recommended in patients with increased ICP because 
inhalants can further increase ICP. High-dose barbiturates may be 
considered in cases of refractory intracranial hypertension in humans.38
Barbiturates carry risks of hypotension and myocardial depression in 
addition to obscuring repeated neurologic examinations. Barbiturates 
can also accumulate in the body with extended use and their long 
half-life can result in prolonged sedation even after discontinuation.74
Hypothermia
Hypothermia has been studied for its potential neuroprotective ef-
fects in reducing inflammation and metabolic demands of the brain after 
TBI. Hypothermic states are known to reduce brain energy re-
quirements, thereby allowing the brain to tolerate hypoxia for longer 
periods of time. It may also have benefits in reducing early inflamma-
tion. Risks of inducing hypothermia include coagulopathies, reduced 
healing, electrolyte abnormalities, cardiac arrhythmias, infection, as 
well as worsening ICP elevations due to physiologic stress (hyperten-
sion, catecholamine release) if the patient is inadequately sedated.75
Induction of hypothermia may also potentially result in rebound hy-
perthermia upon rewarming the patient, which carries its own detri-
mental effects. Additional risks of rewarming include vasodilation, 
which may increase ICP and edema and cause abnormal vascular 
permeability. The ideal rate for rewarming has not been established.75
Due to lack of high-quality evidence, hypothermia is currently only 
recommended in human medicine as a last resort option for manage-
ment of intracranial hypertension. The goal of therapy is to maintain a 
core body temperature of 32-34◦C.75 Prophylactic hypothermia is not 
currently recommended for human patients with severe TBI injury.38
Hypothermia in canine patients with TBI is not well studied with a 
single case report available.76 Resources to properly induce and main-
tain hypothermia and facilitate controlled rewarming may be a current 
limiting factor for usage in veterinary medicine.
Steroids
Treatment of TBI with systemic corticosteroids is contraindicated in 
people. The ground-breaking CRASH study in human medicine reported 
worse mortality at both 2 weeks and 6 months after injury when corti-
costeroids at a dose of 2g of methylprednisolone sodium succinate (to 
approximate 30 mg/kg) were administered followed by a continuous 
infusion at 0.4g/hr (to approximate 5.88mg/kg/day) for 48 h.77 There 
are not equivalent studies in dogs and cats looking at steroid usage for 
TBI. However, based on evidence in human literature, steroids should 
likely not be routinely used for the acute treatment of TBI in companion 
animals.
Anticonvulsant therapy
The development of seizure activity has been documented in both 
humans and animals following TBI. Seizures can worsen the risk of 
secondary brain injury by increasing intracranial pressure, increasing 
metabolic demand, and furthering the release of excitatory neuro-
transmitters.78 Seizure activity is classified as immediate (within 24 h), 
early (within 7 days), or late (greater than 7 days). In humans, the 
incidence of developing epilepsy correlates with severity of the injury 
sustained: mild – 2 %, moderate 4 %, and severe – 15 %.79
The benefit of prophylactic anticonvulsant therapy is not well 
defined. In humans, anticonvulsants are recommended for the first seven 
days after injury to reduce early post-traumatic seizure activity, but they 
have not been shown to reduce the risk of developing late or recurrent 
seizures.80 However, anticonvulsant therapy’s effectiveness in reducing 
early post-traumatic epilepsy is debated.79 Phenytoin was the treatment 
of choice, although levetiracetam is often preferred now for its reduced 
adverse effects compared to phenytoin.80
Studies in cats show 0-5.6 % prevalence of seizures after TBI without 
a detected relationship between severity of injury and the occurrence of 
seizures.81 In a study of dogs, ~7 % of patients with head trauma went 
on to develop epilepsy within the following year and this risk increased 
with the severity of TBI.82,83 This same study found that ~15 % of dogs 
with skull fractures went on to develop seizures.83 A 2019 survey found 
that boarded veterinary specialists were split on usage of anticonvulsant 
therapy in TBI cases demonstrating the lack of clarity on the benefits of 
prophylactic therapy.60 In dogs, phenytoin is not a viable option because 
of its rapid metabolism. Specific recommendations regarding prophy-
lactic anticonvulsants in general as well as recommendations for indi-
vidual anticonvulsants are not well documented in veterinary medicine.
Surgery
Surgery to address TBI has been long documented in human his-
tory.84 Human surgicaloptions include a craniotomy to open the skull, 
evacuate a mass lesion (e.g. hematoma), and close it in the same pro-
cedure or a craniectomy where a flap of skull is removed and can be 
replaced in the future once swelling has resolved (Fig. 3A).10 Indications 
for surgical intervention in human TBI include open depressed skull 
fractures impacting the underlying structures, epidural or subdural he-
matomas of sufficient volume (>20-30 cm) or impact on neurologic 
function (GCSdrainage has been investigated for refractory 
intracranial hypertension in human TBI. This strategy allows for CSF 
diversion in patients with small lateral ventricles that may not allow for 
EVD insertion. Preliminary results indicate successful reduction of ICP 
but further research is needed to determine safety and efficacy; 
including the risk of cerebral herniation.105
There have been multiple studies on repurposing existing pharma-
ceuticals for TBI management in humans. Proposed therapeutics that 
show promise include edaravone (a free radical scavenger), glyburide (a 
type-2 diabetes mellitus medication that triggers insulin release and may 
contribute to improved blood brain barrier integrity and reduction of 
cerebral edema), and ceftriaxone (a third-generation cephalosporin 
which may contribute to reduced astrogliosis). These effects have been 
explored in preclinical models but are not yet widely evaluated in 
clinical trials.106 Progesterone has also been evaluated in human TBI for 
its neuroprotective properties of reducing inflammation and cerebral 
edema but results do not provide consistent evidence of a clinical benefit 
and one study reported increased phlebitis when progesterone was given 
intravenously.106,107
Prognosis
Limited criteria for predicting prognosis of an individual patient are 
available. When faced with a poor prognosis, the families of both human 
and veterinary patients may elect to pursue comfort care. Long-term 
studies and non-survival outcomes are difficult to assess in veterinary 
patients because of the option of humane euthanasia. Dogs that sus-
tained blunt trauma and had a clinical diagnosis of head trauma expe-
rienced a decreased survival rate (45/206 survivors vs 14/29 non- 
survivors) than those without evidence of head trauma,2 although this 
outcome is likely to have been affected by the prognostic predictions 
made by the attending clinician. Dogs and cats have a notable ability to 
recover even after significant loss of cerebral parenchyma.108
Studies have demonstrated that lower MGCS scores are strong pre-
dictors of non-survival in canine TBI patients.27,28 MGCS was found to 
predict a survival rate of 50 % in the first 48 h for patients with a score of 
less than 8.27 The ATT score has been validated in dogs and was found to 
have good prognostic utility when looking specifically at dogs with head 
trauma. An ATT score of 9 was associated with a 50 % probability of 
survival.28 However, scoring systems like MGCS and ATT are not 
designed to indicate survival and make prognostic predictions of an 
individual patient and when used by attending clinicians for this pur-
pose may lead to a circular argument resulting in high rates of 
euthanasia.28
A higher mortality rate has been identified in dogs with new onset 
seizure activity within the first week following a TBI with 14 % of dogs 
exhibiting early seizures within the first 24 h after injury.83
Multiple classification systems have been developed to help predict 
prognosis from CT in human medicine; unfortunately, these systems do 
not directly translate to canine patients.33 However, the Koret-CT 
scoring (KCTS) system was developed in 2017 for dogs and acts as a 
7-element prognostic scale. Patients acquire points for any of the 
following CT abnormalities: hemorrhage, midline shift or lateral 
ventricle asymmetry, cranial vault fracture, any depressed fractures, and 
any infratentorial lesions.109 Increasing KCTS have a significant nega-
tive association with short- and long-term survival. KCTS of ≤3 points is 
associated with a survival with an 85 % sensitivity and 100 % 
specificity.33
In canine TBI patient, early CT analysis based on a Modified 
Advanced Imaging System, which grades the location and extent of le-
sions on a scale of I to VI, in addition to the presence and degree of 
midline shift, evidence of herniation, and presence and location of skull 
fractures, has been studied for potential prognostic indicators. However, 
results did not reveal any early CT imaging features as prognostically 
significant regarding survival to discharge.1 A similar study, looking at 
early MRI evaluation of canine TBI found a significant negative associ-
ation between the severity of MRI lesions and prognosis.110
Rehabilitation
Rehabilitation is considered essential in humans recovering from 
TBI. Rehabilitation after severe TBI has been associated with faster 
functional recovery in people. Very early rehabilitation has also been 
associated with an improvement in favorable outcomes compared to 
delayed rehabilitation. TBI-specific rehabilitation programs are tailored 
to the needs and goals of the affected individual.111 A case report in 
veterinary medicine is available describing physical rehabilitation in a 
dog following severe TBI. A variety of methods including passive range 
of motion, massage, assisted standing exercises, and aqua therapy were 
employed.112 Further research is needed to elucidate the potential of 
rehabilitation in veterinary TBIs.
Conclusion
There are numerous areas for further research and improvement of 
information available regarding recommendations for treatment of TBI 
in veterinary patients. Similarly, there exists very limited prognostica-
tion guidelines for individual patients and current studies may be 
heavily influenced by a perceived poor prognosis. The proposed severity 
classification and management recommendations may serve as a refer-
ence to assist TBI management.
No financial support was provided for the preparation of this 
manuscript.
DoD disclaimer
The views expressed in this manuscript are those of the authors and 
do not reflect the official policy or position of the U.S. Army Medical 
Department, the Department of the Army, DoD, or the U.S. Government.
CRediT authorship contribution statement
Molly Wart: Writing – original draft. Thomas H. Edwards: Writing 
– review & editing, Supervision. Julie A. Rizzo: Writing – review & 
editing. Geoffrey W. Peitz: Writing – review & editing. Armi Pigott: 
Writing – review & editing. Jonathan M. Levine: Writing – review & 
editing. Nicholas D. Jeffery: Writing – review & editing.
Declaration of competing interest
The authors declare that they have no known competing financial 
interests or personal relationships that could have appeared to influence 
the work reported in this paper.
Acknowledgements
The authors are thankful to Dr. Daisuke Ito, of Nihon University, for 
the use of his images.
References
1. Wyatt S, Llabres-Diaz F, Beltran E. Early CT in dogs following traumatic brain 
injury has limited value in predicting short-term prognosis. Vet Radiol Ultrasound. 
2020;62(2):181–189.
2. Simpson SA, Syring R, Otto CM. Severe blunt trauma in dogs: 235 cases 
(1997–2003). J Vet Emerg Crit Care. 2009;19(6):588–602.
3. Storer AP, Edwards TH, Rutter CR, Young G, Mullaney SB. Causes or mortality in 
military working dogs from traumatic injuries. In: Veterinary Trauma and Critical 
Care Conference. 2024.
4. Menon DK, Schwab K, Wright DW, Maas AI. Position statement: definition of 
traumatic brain injury. Arch Phys Med Rehabil. 2010;91(11):1637–1640.
M. Wart et al. Topics in Companion Animal Medicine 63 (2024) 100927 
8 
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0001
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0001
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0001
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0002
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0002
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0003
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0003
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0003
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0004
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref00045. Kuo KW, Bacek LM, Trauma Taylor ARHead. Vet Clin North Am Small Anim Pract. 
2018;48(1):111–128.
6. Silverberg ND, Iverson GL, Cogan A, Dams-O-Connor K, Delmonico R, Graf MJP, 
et al. The american congress of rehabilitation medicine diagnostic criteria for mild 
traumatic brain injury. Arch Phys Med Rehabil. 2023;104(8):1343–1355.
7. Syring R, Fletcher DJ. Traumatic Brain Injury. Small Animal Critical Care Medicine. 
2023:751–755.
8. Dewey CW, Downs MO, Aron DN, Mahaffey EA. Acute traumatic intracranial 
haemorrhage in dogs and cats. Vet Comp Orthop Traumatol. 1993;06(3):153–159.
9. Sande A, West C. Traumatic brain injury: a review of pathophysiology and 
management. J Vet Emerg Crit Care. 2010;20(2):177–190.
10. Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic Brain Injury. Med Clin North 
Am. 2020;104(2):213–238.
11. Bullock R, Zauner A, Woodward JJ, Myseros J, Choi SC, Ward JD, et al. Factors 
affecting excitatory amino acid release following severe human head injury. 
J Neurosurg. 1998;89(4):507–518.
12. Marmarou A, Fatouros PP, Barzó P, Portella G, Yoshihara M, Tsuji O, et al. 
Contribution of edema and cerebral blood volume to traumatic brain swelling in 
head-injured patients. J Neurosurg. 2000;93(2):183–193.
13. Stein NR, McArthur DL, Etchepare M, Vespa PM. Early cerebral metabolic crisis 
after TBI influences outcome despite adequate hemodynamic resuscitation. 
Neurocrit Care. 2012;17(1):49–57.
14. Monro A. Observations on the structure and functions of the nervous system, 
illustrated with tables. Lond Med J. 1783;4(2):113–135.
15. Kellie G. An account of the appearances observed in the dissection of two of three 
individuals presumed to have perished in the storm of the 3d, and whose bodies 
were discovered in the vicinity of leith on the morning of the 4th, november 1821; 
with some reflections on the pathology of the brain. Trans Medico-Chir Soc Edinb. 
1824;1:84–122.
16. Lecture Cushing H. 1: The Third Circulation and Its Channels. Sudies in intracranial 
physiology & surgery: the third circulation, the hypophysis, the gliomas. 3rd ed. London: 
Oxford University Press; 1926:1–51.
17. Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. 
Neurology. 2001;56(12):1746–1748.
18. Tasneem N, Samaniego EA, Pieper C, Leira EC, Adams HP, Hasan D, et al. Brain 
multimodality monitoring: a new tool in neurocritical care of comatose patients. 
Crit Care Res Pract. 2017;2017, 6097265.
19. Pigott A, Rudloff E. Traumatic brain injury—A review of intravenous fluid therapy. 
Front Vet Sci. 2021;8, 643800.
20. Sturges BK, Dickinson PJ, Tripp LD, Udaltsova I, LeCouteur RA. Intracranial 
pressure monitoring in normal dogs using subdural and intraparenchymal 
miniature strain-gauge transducers. J Vet Intern Med. 2019;33(2):708–716.
21. Dinallo S, Waseem M. Cushing Reflex. StatPearls [Internet]. Treasure Island (FL): 
StatPearls Publishing; 2024 [cited 2024 Jan 30]. Available from http://www.ncbi. 
nlm.nih.gov/books/NBK549801/.
22. Her J, Yanke AB, Gerken K, Yoon J, Peters AA, Hofmeister E, et al. Retrospective 
evaluation of the relationship between admission variables and brain herniation in 
dogs (2010–2019): 54 cases. J Vet Emerg Crit Care. 2022;32(1):50–57.
23. Her J, Merbl Y, Gerken K, Kim M, Hofmeister E, Bacek LM, et al. Relationship 
between admission vitals and brain herniation in 32 cats: a retrospective study. 
J Feline Med Surg. 2022;24(8):770–778.
24. Munakomi S, M Das J. Brain Herniation. StatPearls [Internet]. Treasure Island (FL): 
StatPearls Publishing; 2024 [cited 2024 Apr 16]. Available from http://www.ncbi. 
nlm.nih.gov/books/NBK542246/.
25. Agrawal N, Iyer SS, Patil V, Kulkarni S, Shah JN, Jedge P. Comparison of admission 
GCS score to admission GCS-P and FOUR scores for prediction of outcomes among 
patients with traumatic brain injury in the intensive care unit in India. Acute Crit 
Care. 2023;38(2):226–233.
26. Wijdicks EFM, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. 
Validation of a new coma scale: The FOUR score. Ann Neurol. 2005;58(4):585–593.
27. Platt SR, Radaelli ST, McDonnell JJ. The prognostic value of the modified glasgow 
coma scale in head trauma in dogs. J Vet Intern Med. 2001;15(6):581–584.
28. Sharma D, Holowaychuk MK. Retrospective evaluation of prognostic indicators in 
dogs with head trauma: 72 cases (January–March 2011). J Vet Emerg Crit Care. 
2015;25(5):631–639.
29. Rockar RA, Drobatz KS, Shofer FS. Development of a scoring system for the 
veterinary trauma patient. J Vet Emerg Crit Care. 1994;4(2):77–83.
30. Currie S, Saleem N, Straiton JA, Macmullen-Price J, Warren DJ, Craven IJ. Imaging 
assessment of traumatic brain injury. Postgrad Med J. 2016;92(1083):41–50.
31. Vali Y, Gielen I, Soroori S, Ludewig E. The diagnostic value of intravenous contrast 
computed tomography in addition to plain computed tomography in dogs with 
head trauma. BMC Vet Res. 2021;17(1):46.
32. Sepuya RG, Dozeman ET, Prittie JE, Fischetti AJ, Weltman JG. Comparing 
diagnostic findings and cost of whole body computed tomography to traditional 
diagnostic imaging in polytrauma patients. J Vet Emerg Crit Care. 2022;32(3): 
334–340.
33. Rapoport K, Mateo I, Peery D, Mazaki-Tovi M, Klainbart S, Kelmer E, et al. The 
prognostic value of the Koret CT score in dogs following traumatic brain injury. Vet 
J. 2020;266, 105563.
34. Joseph B, Friese RS, Sadoun M, Aziz H, Kulvatunyou N, Pandit V, et al. The BIG 
(brain injury guidelines) project: defining the management of traumatic brain 
injury by acute care surgeons. J Trauma Acute Care Surg. 2014;76(4):965–969.
35. Khan AD, Elseth AJ, Brosius JA, Moskowitz E, Liebscher SC, Anstadt MJ, et al. 
Multicenter assessment of the Brain Injury Guidelines and a proposal of guideline 
modifications. Trauma Surg Acute Care Open. 2020;5(1), e000483.
36. Chesnut RM, Temkin N, Carney N, Dikmen S, Rondina C, Videtta W, et al. A trial of 
intracranial-pressure monitoring in traumatic brain injury. N Engl J Med. 2012;367 
(26):2471–2481.
37. Harary M, Dolmans RGF, Gormley WB. Intracranial pressure monitoring—Review 
and avenues for development. Sensors. 2018;18(2):465.
38. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GWJ, Bell MJ, et al. 
Guidelines for the management of severe traumatic brain injury. 2016.
39. Liu X, Zimmerman L, Ho N, Vespa P, Liao X, Hu X. Evaluation of a new catheter for 
simultaneous intracranial pressure monitoring and cerebral spinal fluid drainage: a 
pilot study. Neurocrit Care. 2019;30(3):617–625.
40. Kahan J, Ong H, Elnaas H, Ch’ang JH, Murthy SB, Merkler AE, et al. Optic nerve 
diameter on non-contrast computed tomography and intracranial hypertension in 
patients with acute brain injury: a validation study. J Neurotrauma [Internet]; 2023 
[cited 2024 Jan 31]; Available from https://www.liebertpub.com/doi/10.10 
89/neu.2023.0051.
41. Smith JJ, Fletcher DJ, Cooley SD, Thompson MS. Transpalpebral ultrasonographic 
measurement of the optic nerve sheath diameter in healthy dogs. J Vet Emerg Crit 
Care. 2018;28(1):31–38.
42. Hoffman H, Abi-Aad K, Bunch KM, Beutler T, Otite FO, Chin LS. Outcomes 
associated with brain tissue oxygen monitoring in patients with severe traumatic 
brain injury undergoing intracranial pressure monitoring. J Neurosurg. 2021;135 
(6):1799–1806.
43. Bernard F, Barsan W, Diaz-Arrastia R, Merck LH, Yeatts S, Shutter LA. Brain 
Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, 
randomised, blinded-endpoint, comparative effectiveness study of brain tissue 
oxygen and intracranial pressure monitoring versus intracranial pressure alone. 
BMJ Open. 2022;12(3), e060188.
44. Chesnut R, Aguilera S, Buki A, Bulger E, Citerio G, Cooper DJ, et al. A management 
algorithm for adult patients with both brain oxygen and intracranial pressure 
monitoring: the Seattle International Severe Traumatic Brain Injury Consensus 
Conference (SIBICC). Intensive Care Med. 2020;46(5):919–929.
45. Hawryluk GWJ, Aguilera S, Buki A, BulgerE, Citerio G, Cooper DJ, et al. 
A management algorithm for patients with intracranial pressure monitoring: the 
Seattle International Severe Traumatic Brain Injury Consensus Conference 
(SIBICC). Intensive Care Med. 2019;45(12):1783–1794.
46. Akbik F, Shi Y, Press D, Foster N, Williams M, Andea S, et al. 836: Intracranial 
pressure is not altered by jugular vein central line placement. Crit Care Med. 2023; 
51(1):409.
47. Sillesen M, Jin G, Johansson PI, Alam HB. Resuscitation speed affects brain injury 
in a large animal model of traumatic brain injury and shock. Scand J Trauma Resusc 
Emerg Med. 2014;22(1):46.
48. Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, et al. 
The role of secondary brain injury in determining outcome from severe head 
injury. J Trauma. 1993;34(2):216–222.
49. Das JM, Anosike K, Waseem M. Permissive Hypotension. StatPearls [Internet]. 
Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Sep 19]. Available 
from http://www.ncbi.nlm.nih.gov/books/NBK558915/.
50. Zhao G, Wu W, ming Feng Q, Sun J. Evaluation of the clinical effect of small- 
volume resuscitation on uncontrolled hemorrhagic shock in emergency. Ther Clin 
Risk Manag. 2017;13:387–392.
51. Shapira Y, Artru AA, Qassam N, Navot N, Vald U. Brain edema and neurologic 
status with rapid infusion of 0.9% saline or 5% dextrose after head trauma. 
J Neurosurg Anesthesiol. 1995;7(1):17.
52. Ichai C, Orban JC, Fontaine E. Sodium lactate for fluid resuscitation: the preferred 
solution for the coming decades? Crit Care. 2014;18(4):163.
53. Shellington DK, Du L, Wu X, Exo J, Vagni V, Ma L, et al. Polynitroxylated pegylated 
hemoglobin: a novel neuroprotective hemoglobin for acute volume-limited fluid 
resuscitation after combined traumatic brain injury and hemorrhagic hypotension 
in mice. Crit Care Med. 2011;39(3):494–505.
54. Wyss MT, Jolivet R, Buck A, Magistretti PJ, Weber B. In vivo evidence for lactate as 
a neuronal energy source. J Neurosci. 2011;31(20):7477–7485.
55. Toro C, Ohnuma T, Komisarow J, Vavilala MS, Laskowitz DT, James ML, et al. 
Early vasopressor utilization strategies and outcomes in critically ill patients with 
severe traumatic brain injury. Anesth Analg. 2022;135(6):1245.
56. Kamel H, Navi BB, Nakagawa K, Hemphill JC, Ko NU. Hypertonic saline versus 
mannitol for the treatment of elevated intracranial pressure: a meta-analysis of 
randomized clinical trials. Crit Care Med. 2011;39(3):554–559.
57. Patil H, Gupta R. A comparative study of bolus dose of hypertonic saline, mannitol, 
and mannitol plus glycerol combination in patients with severe traumatic brain 
injury. World Neurosurg. 2019;125:e221–e228.
58. Shi J, Tan L, Ye J, Hu L. Hypertonic saline and mannitol in patients with traumatic 
brain injury: a systematic and meta-analysis. Medicine (Baltimore). 2020;99(35): 
e21655.
59. Ballocco I, Evangelisti MA, Deiana R, Cubeddu F, Pinna Parpaglia ML, Serra G, 
et al. A pilot study evaluating the effect of mannitol and hypertonic saline solution 
in the treatment of increased intracranial pressure in 2 cats and 1 dog naturally 
affected by traumatic brain injury. J Vet Emerg Crit Care. 2019;29(5):578–584.
60. Evans EK, Fernandez AL. Current trends in the management of canine traumatic 
brain injury: an Internet-based survey. Can Vet J. 2019;60(1):73–79.
61. Boone MD, Oren-Grinberg A, Robinson TM, Chen CC, Kasper EM. Mannitol or 
hypertonic saline in the setting of traumatic brain injury: what have we learned? 
Surg Neurol Int. 2015;6:177.
62. Asehnoune K, Lasocki S, Seguin P, Geeraerts T, Perrigault PF, Dahyot-Fizelier C, 
et al. Association between continuous hyperosmolar therapy and survival in 
patients with traumatic brain injury – a multicentre prospective cohort study and 
systematic review. Crit Care. 2017;21:328.
M. Wart et al. Topics in Companion Animal Medicine 63 (2024) 100927 
9 
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0005
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0005
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0006
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0006
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0006
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0007
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0007
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0008
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0008
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0009
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0009
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0010
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0010
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0011
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0011
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0011
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0012
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0012
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0012
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0013
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0013
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0013
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0014
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0014
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0015
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0015
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0015
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0015
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0015
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0016
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0016
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0016
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0017
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0017
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0018
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0018
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0018
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0019
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0019
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0020
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0020
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0020
http://www.ncbi.nlm.nih.gov/books/NBK549801/
http://www.ncbi.nlm.nih.gov/books/NBK549801/
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0022
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0022
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0022
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0023
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0023
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0023
http://www.ncbi.nlm.nih.gov/books/NBK542246/
http://www.ncbi.nlm.nih.gov/books/NBK542246/
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0025
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0025
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0025
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0025
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0026
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0026
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0027
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0027
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0028
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0028
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0028
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0029
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0029
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0030
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0030
http://refhub.elsevier.com/S1938-9736(24)00082-5/sbref0031