Ketamine: A two-pronged approach to sepsis management

EMS providers who can look beyond ketamine’s perception as a street or veterinary drug will find it is uniquely positioned to treat sepsis

By Joseph Tadlock, EMS1 Contributor

Ketamine hydrochloride is a relatively new medication in the arsenal of EMS services across the country. Once used almost exclusively in veterinary practices, it gained popularity in the military due to its wide therapeutic index. As an anesthetic and anxiolytic, it’s only natural that it has an increased presence in ambulances.

Ketamine doesn’t require constant refrigeration, which makes it convenient for services that don’t have refrigerators in their rigs. Overdoses are rare and administering anything over the indicated dose only leads to longer periods of dissociation. These properties make it an excellent choice for treating patients who might need intubation.

Ketamine doesn’t require constant refrigeration, which makes it convenient for services that don’t have refrigerators in their rigs.
Ketamine doesn’t require constant refrigeration, which makes it convenient for services that don’t have refrigerators in their rigs. (Courtesy photo)

Ketamine’s signal blocking side effects

NMDA receptors in the brain are responsible for the transmission of information from neuron to neuron. The NMDA is an ionotropic glutamate receptor and ketamine hydrochloride, much like methadone, is an NMDA antagonist which blocks signal transmission and creates a dissociative state. This affects cognitive abilities, causing dissociation, as well impacting the limbic system, causing retrograde and anterograde amnesia. Its safe efficacy is well documented and hepatotoxicity is non-existent in short-term use, however, long-term recreational abuse can result in biliary and liver complications.

Use of ketamine may result in vivid hallucinations and thereby agitation in patients. Reassuring the patient of his or her safety during its administration can help ease any fears a patient may have resulting from the dissociative state.

Exploring new EMS treatment models for sepsis

Sepsis is a broad term for systemic inflammation that can range from an elevated temperature and infection, to hypotension, to multiple organ dysfunction. Sepsis treatments have improved since The Society of Critical Care Medicine and the American College of Chest Physicians first defined sepsis in 1991.

In spite of the advances in treatment options, the mortality rate is still very high, particularly in those with several comorbidities, such as advanced age or several diagnoses of pneumonia over a short period of time. The best treatment for sepsis by far is early recognition and aggressive treatment, although new approaches are being developed and researched.

Ketamine offers cytokinine release and bacteria growth supression

Cytokine release during an illness is a key factor in a typical patient’s recovery. These cytokines; interleukin 1, interleukin 10, and tumor necrosis factors, are needed to fight infection in the body. While cytokines are necessary for the body’s natural healing process, the over production and release of cytokines can lead to organ and tissue damage.

Sepsis treatment tactics have historically included copious IV fluids, antibiotics and occasionally, corticosteroids. According to research by Kawasaki et al, ketamine suppresses cytokine release, however, the exact mechanism for this suppression isn’t fully understood.[1] Some studies also implicate ketamine in the reduction of bacteria growth due to post-transcription error bacteria suffers following exposure to ketamine. Therefore, ketamine may be a two-pronged attack when used in septic patients: cytokine release suppression and bactericidal effects.

A 2011 study was performed with patient test groups intubated with differing methods. One group was intubated with a sufentanil-propofol/midazolam induction method and the other with ketamine-propofol/midazolam.[2] Both groups underwent similar CABG surgeries and were of approximate age.

Of the two groups, serum levels of leukocytes and other inflammatory cytokines were significantly lower in the ketamine trial. This makes ketamine an appealing option when it comes to rapid sequence intubation of septic patients. Reducing cytokine release improves hemodynamic stability, making it an excellent choice for patients who are hypotensive due to systemic infection.

Ketamine’s wide therapeutic index

Ketamine’s popularity isn’t just limited to the ED and EMS. Researchers are investigating ketamine’s potential in treating depression and other psychiatric disorders, such as PTSD. These studies have shown some promising results with patients. More doctors are prescribing ketamine off label as an adjunct to refractory, suicidal depression and the initial results appear promising with patients reporting relief after just hours after taking the medication and lasting up to four to seven days.

In EMS, we’re typically acutely concerned with the short-term treatments of patients, which makes it easy to lose sight of what happens after we’ve handed patient care off to the ED staff. Eventually, an intubated patient will have to be extubated. Here, ketamine again shines above the others. As the patient’s respiratory drive is seldom removed while using ketamine, the recovery time from invasive respiratory treatment is shorter and patients don’t typically require weaning from a ventilator.

While it’s still new to EMS, ketamine’s role outside the hospital has great potential. Ketamine still carries with it the old image from some practitioners as a veterinary drug or a street drug. Education and research about ketamine’s wide therapeutic index and its potential in treating septic patients is recent and still ongoing.

New information is being uncovered in ketamine’s role in physical and mental health care. Its novelty in EMS hinders its widespread acceptance and some medical directors may lack familiarity with it in the context of prehospital treatments. The good news is that the tide seems to be changing as more EMS services and medical directors are realizing its potential and benefits.

1. Kawasaki T, Ogata M, Kawasaki C, et al. (1999). Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro. Anesthesia and Analgesia, 89(3);665-669.

2. Welters ID, Feurer MK, Preiss V, et al. Continuous S-(+)-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass. Br J Anaesth 2011; 106(2);172-179. doi: 10.1093/bja/aeq341

About the author
Joseph Tadlock is a paramedic located in Texas. He is finishing his bachelor's degree in biology with a minor in education. He enjoys kayaking, bicycling and spending the little spare time he has with his girlfriend and their two dogs. He may be reached at

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