Saturday, December 16, 2023

Ketamine in War, including use in TBI patients

Fast-acting, easy to deliver, and respiratory-drive-sparing, ketamine is becoming an increasingly popular solution for pain control and/or sedation in emergency and combat medicine.

Traditional anesthetic and analgesic medications pose several challenges during wartime conditions. Opiates and benzodiazepines come with side effects, such as hypotension and respiratory depression, which can increase patient-management workload.

In 1958, the search for a safer anesthesia agent yielded PCP. However, severe psychological recovery effects quickly ruled out high-dose PCP as an anesthetic (non-schizophrenic patients tended to experience 1-2 days of artificially-induced withdrawal psychosis, while in schizophrenics existing symptoms were profoundly exacerbated).

200 derivatives of PCP underwent further testing. One of these, ketamine, was found to have a short duration of action and produce less stimulant effects than PCP. Ketamine could be delivered by multiple routes (IV, IM, IN) and spared patients' breathing and airway protection reflexes. Ketamine was first synthesized in 1962, and after testing on animals and volunteer prisoners, was approved for use in humans in 1970.

For many decades, concerns over misuse and hallucinogenic side effects discouraged use of ketamine in mainstream medical practice. However, the drug was used with some success in a number of conflicts during the 70's and 80's. Ketamine's first wartime use was by a composite team of UK, French, and US doctors during the 1970 Jordan-PLO civil war. This team used ketamine to sedate children during treatment of burns. IM administration simplified delivery, and having a sedation option with minimal airway impact freed up caregivers in a resource-poor setting. 

Another early use of ketamine was during the Falklands conflict. Fifty burn patients were given ketamine during wound treatment on the Hospital ship Uganda. The patients came in in a wave of 150 casualties, after the bombing of two landing ships.

By the late 90's and early 2000's, research had disproved many misconceptions surrounding ketamine.
Emerging as one of the safest and most versatile battlefield medicines, the drug saw renewed interest from the
US military and from EMS systems. Various US special operations teams added ketamine to their
protocols during the Afghanistan and Iraq wars. In 2012, the US Defense Health Board added ketamine
to TCCC protocols as a primary pain control option (50mg IN or IM, of a 20mg slow IV/IO push).
Various military studies from this period suggest that ketamine administration had either a neutral or
protective action against development of PTSD in injured soldiers.


Use of ketamine for pain control is an off-label use; however it seems to be a highly effective alternative

to opiates. Ketamine antagonizes NMDA receptors. It interferes with the brain's chemical ability to

receive incoming pain stimuli, and at the same time reduces the emotional reaction to pain. Pain control

is achieved at a fraction of an anesthesia dose.


Several other factors make ketamine an ideal pain control+ sedation option in EMS, wilderness medicine,

and combat situations. Rather than dropping respiratory drive and blood pressure, like opiates and

benzodiapines ketamine produces hyper-adrenergic effects. It stimulates the release of dopamine,

norepinephrine, and serotonin, and blocks re-uptake of catecholamines. This leads to a slight increase in blood pressure and

heartrate. Additional benefits include a long shelf life, a wide storage temperature tolerance, low cost,

good safety profile, ability to administer via IN, IM, IV or IO route, fast action onset, and a variety of

dose-dependent effects. Recent studies have dismissed concerns about use of ketamine in TBI patients,

showing that the drug does not have a negative impact on cranial perfusion pressure. Ketamine is

recommended by the Wilderness Medical Society for use in remote environments, and is on the WHO

essential medications list. In resource-poor countries, ketamine is sometimes used as a sole anesthesia

agent during surgeries.


Ketamine is general very safe, but some considerations must be taken for patient safety. Emergence

reactions are not uncommon and may include hallucinations, disorientation, nausea, and anxiety. Keeping the

patient in a quiet room with low lighting can help avoid emergence reactions. Use with caution in

combination with other drugs, including sedative agents, or in patients who have taken street drugs.

Ketamine may worsen schizophrenia symptoms, and may cause hypotension in severely

catecholamine-depleted patients. Although a major benefit of ketamine is its tendency to leave patient

respiratory and airway protective drives intact, patient level of consciousness and breathing should be

carefully monitored, especially with higher doses. This has recently been demonstrated in the news

stories about the death of actor Matthew Perry, and the manslaughter trial of two Aurora, CO paramedics,

whose patient died after being given ketamine.



2018 JEMS: Should Ketamine Be Contraindicated for Patients with Traumatic Brain Injury?

"The_Drug_of_War"--a_historical_review_of_the_use_of_Ketamine_in_military_conflicts 

2014 US military Study: "The intraoperative administration of ketamine to burned U.S. service members does not increase the incidence of post-traumatic stress disorder"  larger retrospective data analysis of ketamine use and PTSD development in 298 burn patients serving in the US military. This study did not find that ketamine offered PTSD-protective effects seen in previous smaller studies, but ketamine also did not worsen likelihood of PTSD development. 
2021 US military study: Ketamine Use in Operation Enduring Freedom - shows increasing usage of ketamine within the US military during the Afghanistan/Iraq campaigns.
2015 Emergency Physicians Monthly article: Battle Tested: Ketamine Proves its Worth on the Front Line

2014 study: The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review
A review of available literature found that ketamine did not produce significant changes in
cerebral perfusion pressures, neurologic outcomes, length of ICU stay, or mortality.


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