By Annette M. Boyle
LOS ANGELES — For 40 years, ketamine remained on the fringes of battlefield medicine. Now, the DoD has embraced ketamine both on the field and in the hospital.
First used in Vietnam as an anesthetic, the versatile drug was officially added as an analgesic to the Tactical Combat Casualty Care Guidelines (TCCC) in 2014, but it had been used by medics in some groups for a few years.
The 4th Infantry Division distributed ketamine nasal sprays to combat medics in Afghanistan, with very positive results. Medics used ketamine to treat 35 wounded servicemembers.
“In every single instance that we’ve used it, it’s been effective,” Army Capt. Seth Mayer, 4th Infantry Division pharmacist, said in a news release on the initiative.
The intranasal spray quickly delivers pain relief superior to morphine, dilaudid or fentanyl, according to Mayer.
The Army Rangers experienced similar success with ketamine from 2009 to 2014, according to a case series published in the Journal of Special Operations Medicine. The 75th Ranger Regiment authorized ketamine for tourniquet pain, amputations, long-bone fractures and refractory pain. Eight of nine patients initially rated their pain as a 9/10, with the other indicating an 8/10. Following treatment, seven reported no pain, and two indicated a pain level of 4.1
“Though ketamine has a storied history in the operating and emergency rooms of the battlefield environment, its use at the point of injury and in the back of a medevac helicopter is entirely new,” Lt. Col. Chris Jarvis explained at a 4th Infantry Division surgeon at an International Security Assistance Force Joint Command conference.
The drug’s use may expand further, based on recent research. Currently, the TCCC recommends use of ketamine to treat a casualty in or at significant risk of hemorrhagic shock or respiratory distress and in moderate to severe pain. For casualties who are still able to fight, the TCCC recommends a combination of acetaminophen and meloxicam.
In hostile conditions, however, wounded warriors with moderate to severe pain may need to continue to perform critical tasks. When acetaminophen and meloxicam are not enough, ketamine may give sufficient relief without overly impairing function, according to research recently published in the Journal of Emergency Medicine.2
Researchers compared the performance of 48 healthy volunteers in a double-blind, placebo-controlled study comparing 10 mg intramuscular morphine to 25 mg intramuscular ketamine. While study participants experienced more dizziness, lack of concentration and feelings of happiness with ketamine than with morphine or placebo, the side effects did not significantly diminish performance on trained task skills. Participants did perform somewhat more slowly, perhaps recognizing some impairment and “trading speed for preservation of task accuracy,” noted the authors.
Expanding Clinical Use
Just as ketamine has found new applications in theater, it has seen significant expansion of its clinical use. Initially used as an anesthetic for surgery in rugged situations with limited ability to monitor patients or provide oxygen, ketamine now is used in the most sophisticated hospitals for some of the most vexing conditions facing wounded warriors — complex regional pain syndrome (CPRS), phantom limb pain and other pain of neuropathic origin.
To see how ketamine worked on patients undergoing limb revision and dealing with unrelenting pain from limb trauma, researchers at what is now the Walter Reed National Military Medical Center in Bethesda, MD, conducted a retrospective review of the outcomes of low-dose intravenous ketamine infusions in conjunction with individualized multimodal analgesia regimens in 19 patients.3
Patients in the study received a three-day adjunctive IV infusion of low-dose ketamine after conventional therapy with opioids, non-opioids, other analgesics and regional anesthesia techniques failed to provide sufficient relief.
All had sustained major limb trauma in Iraq or Afghanistan and had pain of at least 4 on a 10 point scale with 10 being “pain as bad as you can imagine.” Patients were closely monitored during the initial four hours of therapy, then transferred to general wards for the remainder of their three days of infusions.
All patients reported an improvement in daily pain scores with the ketamine infusions, even as their opioid requirements declined. Patients who had baseline pain scores above 7 and did not have phantom-limb pain experienced the most significant drop in worst pain intensity. All patients reported an improvement in global-pain relief when ketamine was added to already aggressive pain regimens.
The results offer hope to those who have suffered major trauma and continue to experience debilitating pain. “We’ve seen a massive number of patients who have survived terrible injuries and repeated surgeries and develop CRPS,” said Rollin “Mac” Gallagher, MD, MPH, deputy national director for Pain Management at the VA.
Stimulation of N-methyl-D-Aspartate (NMDA) receptors appears to be key to the cascade of neurological processes that lead to CRPS and other types of neuropathic pain. Ketamine acts primarily as an NMDA antagonist, allowing it to stop the “wind up” or propagation of nerve pain that makes this pain so challenging to treat.
“While we mostly use it for CRPS, we have also used ketamine for pain associated with diseases as varied as multiple sclerosis and cancer,” said Sanjog Pangarkar, MD, director of the pain service at the West Los Angeles VA Medical Center. “We have also started using it in the intensive care unit setting for post-operative pain recently, which has been successful thus far.”
Pangarkar told U.S. Medicine that he hopes other providers keep ketamine in mind as another resource for pain control.
Both patients with chronic pain and the providers who treat them can take some comfort in knowing that “a team of providers that is educated regarding this medication can provide an adjunctive treatment to help those with recalcitrant pain conditions,” he added.
- Fisher AD, Rippee B, Shehan H, Conklin C, Mabry RL. Prehospital analgesia with ketamine for combat wounds: a case series. J Spec Oper Med. 2014 Winter;14(4):11-7. PubMed PMID: 25399363.
- Gaydos SJ, Kelley AM, Grandizio CM, Athy JR, Walters PL. Comparison of the effects of ketamine and morphine on performance of representative military tasks. J Emerg Med. 2015 Mar;48(3):313-24. doi:10.1016/j.jemermed.2014.06.047. Epub 2014 Sep 27. PubMed PMID: 25271185.
- Polomano RC, Buckenmaier CC 3rd, Kwon KH, Hanlon AL, Rupprecht C, Goldberg C, Gallagher RM. Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat. Pain Med. 2013 Jul;14(7):1088-100. doi: 10.1111/pme.12094. Epub 2013 Apr 16. PubMed PMID: 23590428.