ischemia

Global brain ischemia

A recent article by Dr. Harper Crawford and colleagues from the UK caught my attention. Global brain ischemia can be seen following minutes of poor blood flow including during cardiopulmonary arrest during general anesthesia, severe bite injuries and strangulation. It has also been associated with the use of mouth gags during dental procedures in cats. (Yikes! You probably knew this, but I was surprised by this!) This article was an enlightening review of global brain ischemia as well as a retrospective look at several cases with a focus on treatment, survival and prognosis. 

What is the consequence of failure?

The authors suggest that cerebral perfusion failure can simply be defined as failing to meet the energy demands of the brain and failure of adequate waste removal products. Simple, yes? Irreversible failure can start within minutes of ischemia through loss of ATP. After ATP is depleted, Na+ and K+ will influx intracellular dragging water with it and the neuron will depolarize. This is the start of cytotoxic edema. From there, a secondary release of excitatory neurotransmitters, particularly glutamate will be released which results in eventual mitochondrial dysfunction, lipid peroxidation and vascular injury. The final nail in the proverbial coffin is rising intracellular Ca++ which triggers cell death. The most sensitive cells are in the cerebral cortex, hippocampus and Purkinje neurons in the cerebellum.

Materials and Methods

Short term outcome was defined as survival (or not) for the first 72 hours. Long-erm was defined as the neurologic examination at the last follow-up examination available for review.
The study utilized an outcome scale as follows:
0: dead or euthanized due to severe neurologic deficits
1: poor recovery with severe persistent neurologic deficits
2: good recovery with mild persistent deficits
3: excellent recovery with normal function.

Results

10 animals were included: 8 dogs and cats with in hospital cardiopulmonary arrest and 2 dogs with out of hospital arrest (1 vehicular trauma, 1 asphyxiation from food). The duration of suspected arrest ranged from 1-5 minutes (median 3 minutes) for animals with in-hospital cardiopulmonary arrest and 10-22 minutes for the 2 animals with out of hospital cardiopulmonary arrest. The neurologic exam for the animals with in hospital cardiopulmonary arrest was reported at a median of 9 hours post insult. Median hospital duration was 7 days. Short term survival occurred in 8/10 cases including 1 case that did not survive to long-term. Seven animals survived to discharge and were re-evaluated at a median of 67 days. Outcome scale results:
Grade 0: 3
Grade 1: 1
Grade 2: 2
Grade 3: 4
The patients with an outcome score of 2 or 3 all showed consistent neurologic improvement in the first 48-72 hours. For the animals that experienced seizures during hospitalization (3), anti-epileptic medication was continued for between 2-8 months after starting. Levetiracetam was used in 1 cat and 1 dog, and phenobarbital was used in 1 dog. No additional seizures were reported in any pet following discharge.
This report demonstrated that although global ischemia can cause severe neurologic deficits, successful long-term outcomes are possible. Furthermore, they noted that an association with duration from onset of cardiopulmonary arrest to spontaneous breathing is a factor in recovery in rodent models and human studies, but this study was too small to draw those conclusions.

References: DOI: 10.1111/jvim.16790 Harper Crawford A, Beltran E, Danciu CG, Yaffy D. Clinical presentation, diagnosis, treatment and outcome in 8 dogs and 2 cats with global hypoxic-ischemic brain injury (2010-2022). JVIM 2023.
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