Ketamine infusion therapy for acute pain management


As the opioid epidemic continues to devastate the United States, ketamine use has grown as a pain management alternative, yet more than one in three patients may experience side effects such as hallucinations and visual disturbances, suggests new research presented at the ANESTHESIOLOGY 2019 annual meeting.

Ketamine is a powerful anesthetic that is also used to treat acute and chronic pain and depression.

While the drug is known for some side effects that negatively affect mental status, there are many other potential risks.

Recent consensus guidelines from the American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine and American Society of Anesthesiologists (ASA) support ketamine infusion therapy for acute pain management, but the groups note more studies are needed to determine the best approach for using it safely and effectively.

“Despite the U.S. Food and Drug Administration’s approval of ketamine for multiple uses, including general anesthesia and treatment of depression, the effects of using the drug at low doses to treat pain have not been extensively studied,” said Padma Gulur, M.D., lead author, member of ASA’s Committee on Pain Medicine and professor of anesthesiology at Duke University in Durham, North Carolina.

“Our research aimed to determine both short- and long-term side effects of low dose ketamine when used for pain treatment.”

Researchers conducted a review of side effects related to ketamine infusions for pain management.

Reported side effects were categorized into two groups: those directly linked to ketamine (hallucinations, vivid dreams, out-of-body experience and/or unusual thoughts) and those associated with using ketamine in combination with other drugs (sedation, visual disturbances and urinary dysfunction).

Reported side effects were categorized into two groups: those directly linked to ketamine (hallucinations, vivid dreams, out-of-body experience and/or unusual thoughts) and those associated with using ketamine in combination with other drugs (sedation, visual disturbances and urinary dysfunction). The image is in the public domain.

Of 297 Duke University pain patients who received ketamine infusion therapy between January and June 2017, 104 (35%) reported significant side effects.

Twenty percent of these patients suffered side effects directly linked to ketamine, while 15% experienced side effects associated with the use of ketamine in combination with other drugs.

“Although the opioid epidemic has prompted the medical community to thoroughly investigate pain management alternatives, our number one priority is to ensure the safety of patients receiving ketamine,” said Dr. Gulur.

“More than one in three patients reported significant side effects from ketamine infusions that required ongoing monitoring or resulted in discontinuation of therapy. More research on the impact of ketamine use for pain on the population is needed.”

Acute pain often follows trauma or surgery and constitutes a signal to the brain regarding the presence of noxious stimuli or ongoing tissue damage.[3] This pain signal is adaptively useful, providing a warning of danger to the individual.

Thus, acute pain results directly from the outcome of a noxious event and presents as a symptom of underlying tissue damage or disease. Acute injuries, including surgery, typically manifest as nociceptive pain.[4]

Whereas acute pain symptoms dissipate with the removal of the painful stimulus, chronic pain persists beyond the useful period of the pain signal and often continues after the initial tissue damage has resolved.

Chronic pain may not be directly related to the initial tissue injury or disease condition, but instead may result secondarily to changes in the pain detection system, either as neuropathic pain (e.g., post-traumatic neuropathy, CRPS type II) or nocicplastic pain (e.g., CRPS type I).[2][3] 

Therefore, while acute pain and traumatic injury may precede the development of chronic pain, the mechanisms underlying chronic pain may differ from those implicated in acute pain.[3]

Experiencing acute or chronic pains are co-morbidities and complications, respectively, after nerve or tissue injury.

As a result of this and a host of overlapping pain mechanisms at multiple sites (e.g., periphery, spinal cord, brain, descending modulatory systems), the etiology of pain remains complex.

The four most common causes of pain are cancer, osteoarthritis, and rheumatoid arthritis, surgeries and non-iatrogenic trauma, and spinal problems.[4] 

Back pain and arthritis, in particular, are among the most commonly reported causes of chronic pain, accounting for up to one-third of all reported cases.[1][5] These conditions, along with depression, are also among the top three causes of years lost to disability.  Other disease states and conditions also associated with acute and chronic pain are diabetes, heart disease, depression, fibromyalgia, and asthma.

There is significant overlap between chronic pain and depression in terms of co-morbidity and treatment, with many therapies effective for both indications.[6]

Issues of Concern

Pain, in both acute and chronic forms, remains a significant health problem both in the U.S. and worldwide. Aging of the world’s population has led to an increased number of individuals experiencing both acute injuries and chronic disease.[7]

 Although mortality for these conditions has decreased, their non-fatal dimensions and associated psychiatric and other comorbidities have resulted in an increase in years lost to disability.[8]

Among the leading causes of years lost to disability worldwide, four of the top ten low-back pain, neck pain, migraine, musculoskeletal disorders are pain-related.[8] 

Globally, estimates suggest that 20% of adults suffer from chronic pain with another 10% diagnosed each year.[1] Although some estimates suggest that 20 to 25% of the world’s population suffers from acute or chronic pain, others indicate its prevalence may be as high as 45%.[9][10]

 In the U.S., the Institute of Medicine estimates that chronic pain impacts 1 in 3 persons.[8] Among those with chronic pain, 15 to 25% of these patients experience pain of neuropathic etiology.[11] 

Chronic pain has also been observed to have an increased frequency in women and older individuals.[3][12][13] Women present more often with headaches, abdominal pain, and widespread chronic pain. Furthermore, non-Hispanic whites and blacks report the highest rates of chronic back pain, leg, feet, arm, and hand pain, and widespread pain.[14]

Chronic pain is among the most prevalent reasons persons seek medical care, with chronic pain patients utilizing health care services almost five times more frequently than the rest of the population.[15] 

This increased usage is often due to ill-defined conditions, lower priority chronic disease, acute disease, and concomitant psychopathology.[16] Acute pain often presents in the postoperative period, with estimates suggesting that as many as 80% of surgical patients experience significant postsurgical pain.[17]

Media Contacts:
LaSandra Cooper – ASA
Image Source:
The image is in the public domain.

Original Research: The findings will be presented at ANESTHESIOLOGY 2019.


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