Is the Use of Hypertonic Saline Effective in Reducing Intracranial Pressure After Traumatic Brain Injury in Dogs ? A Knowledge Summary

Clinical bottom line: Hypertonic saline appears to be effective in reducing intracranial pressure after traumatic brain injury in dogs in experimental studies.


The Evidence
Nearly all available evidence for this PICO question comes from experimental studies.How much experimental and clinical traumatic brain injury differ is unclear.Intervention details: After 30 minutes of experimentally induced haemorrhagic shock (MAP <50mmHg) dogs were resuscitated with hypertonic saline solution or LRS.

Clinical bottom line
Hypertonic saline appears to be effective in reducing intracranial pressure after traumatic brain injury in dogs in experimental studies.
Study design: Experimental controlled study.
Outcome studied: Continuous ICP monitoring, blood brain barrier function assessed by degree of Evans Blue staining and cerebral oedema formation assessed by wet brain weights.

Main findings: (relevant to PICO question):
3% hypertonic saline caused lower intracranial pressure and less cerebral oedema than either 0.9% saline or dextran-40, but blood brain barrier integrity is not restored.

Limitations:
 experimental study  no survivors to assess clinical outcome  short term study of only 3h duration  small number of cases

Sample size: 18
Intervention details: Hypovolaemic shock and closed head injury were simulated via bleeding of 40% of blood volume and epidurally inflated balloon.This was maintained for 1h, after that resuscitation with the shed blood and either 3% hypertonic saline, 0.9% saline or dextran-40 Study design: Experimental uncontrolled study.
Outcome studied: Cerebral blood flow and ICP were measured at baseline, at the end of the shock period, during resuscitation and after resuscitation.

Main findings: (relevant to PICO question):
Though the intracranial pressure was lower in the hypertonic saline group, cerebral blood flow did not vary.

Limitations:
 experimental study  no assessment of clinical outcome  short term study of only 3h duration  small number of cases

Sample size: 15
Intervention details: 20 minutes after experimentally induced haemorrhagic shock via bleeding to MAP of 40mmHg and simulated traumatic brain injury via fluid percussion and epidural balloon, volume was replaced with 3% hypertonic saline (8ml/kg over 10 min) or LRS (16ml/kg over 10 ml) in five dogs each.20 minutes later shed blood and more of the previous fluids were given to a haematocrit of 30% and a MAP of >70mm Hg.A control group of five received no fluids at either point.After 60 minutes the epidural balloon was deflated in the treatment groups.
Outcome studied: MAP, cardiac index, ICP, CPP, biochemistry and blood gases.

Main findings: (relevant to PICO question):
3% hypertonic saline results in lower ICP than LRS even though CPP remains similar.Hypertonic saline also causes higher serum sodium concentration and osmolarity than LRS.

Limitations:
 experimental study  no clinical outcome described  small number of cases

Sharma (2015)
Population: Client-owned dogs with head trauma <5 days before hospital admission.Outcome studied: The prognostic value of clinical and laboratory variables, scoring systems and treatments (such as hypertonic saline) in dogs with head trauma was calculated.

Main findings: (relevant to PICO question):
Hypertonic saline administration was associated with lower likelihood of survival to discharge (8 survivors, 4 nonsurvivors).

Limitations:
 retrospective case study  no control group  multiple parameters observed, prognostic value of individual variables on their own hard to quantify  small number of cases

Sample size: 15
Intervention details: 20 minutes after experimentally induced haemorrhagic shock via bleeding to MAP of 40mmHg and simulated traumatic brain injury via fluid percussion and epidural balloon, volume was replaced with 3% hypertonic saline (8ml/kg over 10 min) or LRS (16ml/kg over 10 min) in 5 dogs each.20 minutes later shed blood and more of the previous fluids were given to a haematocrit of 30% and a MAP of >70mm Hg.A control group of five dogs received no fluids at either point.After 1h the epidural balloon was deflated in the treatment groups.All dogs were euthanised after 3h and the brains removed, visually assessed and further analysed after tissue fixation.

Study design: Experimental controlled study.
Outcome studied: MAP and ICP were measured, changes in pupil state were assessed every 10 minutes, macroscopic and microscopic brain pathology and prostaglandoid production were assessed.

Main findings: (relevant to PICO question):
ICP was the lowest in the hypertonic saline cases during the initial 60 minutes.In brains that had received hypertonic saline, no cerebral oedema was identified macroscopically and ischaemic lesions were less evident.In cases with pupil changes, the pupils reversed to normal sooner in the hypertonic saline group.

Limitations:
 experimental study  no survivors to assess clinical outcome  short term study of only 3h duration  macroscopic assessment for cerebral oedema only  small number of cases

Appraisal, application and reflection
The purpose of this Knowledge Summary was to look at the evidence for the use of hypertonic saline in reducing intracranial pressure in head trauma patients.
The experimental studies available in dogs seem to indicate that hypertonic saline might have a good effect on increased intracranial pressure after traumatic brain injury while achieving desirable haemodynamic parameters.
There are no controlled clinical studies that evaluate the use of hypertonic saline as an independent variable.
In the descriptive study from Sharma & Holowaychuck (2015) the decision to use hypertonic saline was the clinician's, and sometimes made after other treatment options had been unsuccessful.The choice to use hypertonic saline appears mostly to have been made in very severe cases, which may explain the negative predictive value of hypertonic saline use on survival until discharge.
In conclusion, hypertonic saline appears to be effective in reducing intracranial pressure after traumatic brain injury in experimental studies.How effective its use might be in clinical settings cannot be answered.Authors of Knowledge Summaries submitted to RCVS Knowledge for publication will retain copyright in their work, but will be required to grant to RCVS Knowledge an exclusive license of the rights of copyright in the materials including but not limited to the right to publish, republish, transmit, sell, distribute and otherwise use the materials in all languages and all media throughout the world, and to license or permit others to do so.

Methodology Section
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