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Summary of Articles

Ketamine for chronic pain: Risks and benefits.

Only 30-40% of patients with neuropathic pain respond to standard treatment with anti-depressants, anti-epileptics and opioids. Ketamine has been successfully used with CRPS, post-herpetic neuralgia and neuropathic pain from peripheral nerve damage. Ketamine has been studied for CRPS, migraine, breakthrough non-cancer pain, central neuropathic pain, chemotherapy induced neuropathy, fibromyalgia, painful limb ischemia, traumatic peripheral nerve injury, phantom limb pain, post herpetic neuralgia, spinal cord injury, temporomandibular joint pain, trigeminal neuropathic pain and whiplash.

Ketamine is an NMDA antagonist. It also influences descending inhibition of pain by activating areas of the brainstem. There is no consensus as to how to deliver IV ketamine. Longer-term infusions seem better. Schwartzman used a 4 hour/10 day infusion in CRPS. Only three randomized controlled studies looked at 4 to 10 day infusions. A meta-analysis showed that the effect lasted at least 4 weeks, after which pain returned Ketamine has been used for depression, starting within one hour. The article discussed ketamine risks in detail, including auditory hallucinations, paranoid idea, anxious feelings and the inability to control thoughts and derealization in time and space, visual hallucinations, increased awareness of sound and color, along with a “drug high” that can be either euphoric or unpleasant. One can also have dizziness, blurred vision, vertigo, nausea/vomiting, dysphasia, nystagmus, nightmares or vivid dreams, impair motor function and memory deficits. These effects decrease quickly after stopping the infusions. Cardiac stimulation can occur along with liver side effects. Ketamine is popular as a recreational drug. Ketamine can provide prolonged pain relief.

Niesters M, Martini C, Dahan A. Ketamine for chronic pain: Risks and benefits. British journal of clinical pharmacology. 2014;77:357-367.

The Use Of Ketamine In Neuropathic Pain.

This review discusses the role of ketamine in treating neuropathic pain. Neuropathic pain is pain associated with disorders of the nervous system. It is different from nociceptive pain, which happens when you are subject to something painful, like someone stepping on your toe, or stepping on a hot coal or a sharp nail. Neuropathic pain is a broad tent, with many different ways of having improper functioning of the nervous system.

The N-methyl-D-aspartate (NMDA) receptor is involved with neuropathic pain. Ketamine helps block the action of the NMDA receptor. This blockage, or antagonism, is the likely way that it stops neuropathic pain. This article provides a very detailed discussion of our current understanding of how ketamine works. They review the literature on ketamine in treating neuropathic pain.

Infusions have ranged from about 15 mg per hour to 350 mg per hour for a 110 pound person. Infusions last from minutes to a month.

Side effects include confusion, delirium, vivid dreams, hallucinations and feelings of detachment from the body. These are treated with midazolam or clonidine, which also have side effects.

Ketamine has been used as a drug of abuse for hits hallucinogenic and euphoric effects. It can have liveide effects and urinary problems such as frequency and urgency. The authors found the best benefit for CPRS and have had limited success with non CRPS pain. They have found improvement in depression, also.

O’Brien SL, Pangarkar S, Prager J. The use of ketamine in neuropathic pain. Current Physical Medicine and Rehabilitation Reports. 2014;2:128-145.

A Systematic Review Of Ketamine For Complex Regional Pain Syndrome.

Ketamine is a dissociative anesthetic, meaning that it produces analgesia without loss of consciousness. NMDA receptors increase pain, windup, by increasing glutamate in acute and chronic pain pathways. Ketamine helps block this process. Ketamine has short-term efficacy in treating phantom limb pain and has antidepressant effects. Some randomized controlled trials suggest ketamine might be useful for complex regional pain syndrome, post herpetic neuralgia, migraine, burns, and fibromyalgia. It works best with neuropathies involving central sensitization. The review summarizes the literature. Side effects are discussed. IV ketamine probably helps, but the evidence is weak. There is no consensus about how to provide ketamine. Topical ketamine might help.

Connolly SB, Prager JP, Harden RN. A systematic review of ketamine for complex regional pain syndrome. Pain Medicine. 2015;16:943-969.

A Review Of The Use Of Ketamine In Pain Management.

Ketamine is useful for both neuropathic pain and depression. It was approved as an anesthetic and is used as a “horse tranquilizer.” It is related to PCP or “Angel Dust.” The review discuss the pharmacological properties of ketamine. Ketamine is the most potent clinically used NMDA antagonist. Ketamine causes anesthesia, analgesia and amnesia. It can cause a cataleptic like state with open eyes and nystagmus. It can cause vivid dreams which can be either pleasant or unpleasant, delirium and hallucinations, which are more common during high dose infusions. Ketamine may have an effect on brain dopamine receptors. Tolerance can occur with chronic use.

Tawfic QA. A review of the use of ketamine in pain management. J Opioid Manag. 2013;9:379-388.

Ketamine: An Update for Its Use in Complex Regional Pain Syndrome and Major Depressive Disorder.

A discussion of the racemic forms and metabolic products of ketamine.

Bentley W, Sabia M, Goldberg M, Wainer I. Ketamine: An update for its use in complex regional pain syndrome and major depressive disorder. Clin Exp Pharmacol. 2015;5:2161-1459.1000169.

Multi-Day Low Dose Ketamine Infusion for The Treatment Of Complex Regional Pain Syndrome.

A study defining the protocol of 40-80 mg/day, 4 hours a day for 10 days for the treatment of CRPS.

Goldberg ME, Domsky R, Scaringe D, Hirsh R, Dotson J, Sharaf I, Torjman MC, and Schwartzman RJ. Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome. Pain Physician. 2005;8:175-179.

Analgesic Effect Of Subanesthetic Intravenous Ketamine In Refractory Neuropathic Pain: A Case Report.

A case report of IV ketamine for the idiopathic polyneuropathy. He was given a 5-day inpatient treatment titrating up from 10 mg/hr to 20 mg/hours. He had excellent relief for up to 10 weeks, when his infusion was repeated. He has been maintained for over three years. They recommend a dose of 0.1 -0.3 mg/kg/hr.

The review has a detailed description of the NMDA receptor. Ketamine’s use in post-operative pain and chronic non-cancer pain is discussed. Ketamine may be useful in CRPS, pain from spinal cord injury, post stroke pain, phantom limb pain, post-herpetic neuralgia and orofacial pain. It has also been used un fibromyalgia and chronic ischemic pain. The literature suggests that multiple day infusions, up to 2 weeks, can improve chronic pain.

Several protocols have been used, but doses between 0.125 and 0.3 mg/kg/hr are most commonly used. Oral ketamine is less effective because of first pass effect, with hepatic metabolism. Ketamine cream may or may not be effective.

Elsewaisy O, Slon B, Monagle J. Analgesic effect of subanesthetic intravenous ketamine in refractory neuropathic pain: A case report. Pain Med. 2010;11:946-950.

Ketamine-A Narrative Review Of Its Uses In Medicine.

This review provides a detailed discussion of ketamine’s pharmacology and mode of action. Its psychiatric uses, including depression and post traumatic stress disorder, are discussed, along with its uses in chronic pain.

Radvansky BM, Puri S, Sifonios AN, Eloy JD, Le V. Ketamine-a narrative review of its uses in medicine. American journal of therapeutics. 2015.

Therapeutic Reviews: Ketamine.

Ketamine has side effects, mainly occurring in the abuse community, including neuropsychiatric, urinary tract and hepatic toxicity. Its use should be restricted to pain specialists. The article provides a detailed discussion of the pharmacology of ketamine.

Quibell R, Fallon M, Mihalyo M, Twycross R, Wilcock A. Therapeutic reviews: Ketamine. Journal of pain and symptom management. 2015;50:268-278.

Pharmacodynamic Profiles Of Ketamine (R)- And (S)- With 5-Day Inpatient Infusion For The Treatment Of Complex Regional Pain Syndrome.

A study showing that patients had significant relief after day 3 of a 5-day infusion of ketamine at 10-40 mg/hr.

Goldberg ME, Torjman MC, Schwartzman RJ, Mager DE, Wainer IW. Pharmacodynamic profiles of ketamine (r)- and (s)- with 5-day inpatient infusion for the treatment of complex regional pain syndrome. Pain Physician. 2010;13:379-387.

Efficacy Of Outpatient Ketamine Infusions In Refractory Chronic Pain Syndromes: A 5-Year Retrospective Analysis.

A study from the University of Chicago looking at over 300 infusions. 37% of patients had CRPS. The largest group of the remaining had headaches or severe back pain. Four patients had fibromyalgia and one had cervical radiculopathy. There was better relief in patients with CRPS, although there was relief from other conditions. Relief lasted up to three weeks.

They gave .5 mg/kg for 30-45 minutes. If this gave relief, the patients had repeat injections. The infusions lasted 60 minutes for CRPS and up to 2 ½ hours for other diagnosis. The dose was about 1 mg/kg. Adverse of any type occurred in 50% of patients, with high blood pressure, sedation and hallucinations occurring in about 10% of patients, confusion occurring in about 6%, and dissociation occurring in only one patients.

Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: A 5-year retrospective analysis. Pain Medicine. 2012;13:263-269.

NMDA Receptor Antagonists For The Treatment Of Neuropathic Pain.

This paper is a review of the literature dealing with NMDA receptor antagonists. IV ketamine was reviewed for complex regional pain syndrome (CRPS) and post amputation (phantom limb) pain. This review found no significant effect on pain reduction could be established for IV ketamine in CRPS or post amputation pain. More studies are needed.

Collins S, Sigtermans MJ, Dahan A, Zuurmond WW, Perez RS. NMDA receptor antagonists for the treatment of neuropathic pain. Pain Med. 2010;11:1726-1742

Effects Of Low-Dose Iv Ketamine On Peripheral And Central Pain From Major Limb Injuries Sustained In Combat.

A study from Walter Reed looking at nineteen servicemen suffering from refractory neuropathic pain after having limb injuries. They were give up to .12 mg/kg/hr for 3 days. They had a significant reduction in their pain.

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;14:1088-1100.

A Preliminary Naturalistic Study Of Low-Dose Ketamine For Depression And Suicide Ideation In The Emergency Department.

This study looks at IV ketamine for MDD, bipolar disorder and suicidal ideation in the ER. They looked at patients with major depressive disorder, as defined by the Mini-International Neuropsychiatric Interview and scoring more than 24 on the Montgomery-Asberg Depression Rating Scale and greater than 2 on the Scale for Suicide Ideation. They were given .2 mg/kg of ketamine (10 mg for a 110 pound person) over a few minutes.

Two of fourteen patients had some psychiatric side effects, unpleasant dissociative symptoms, which resolved in 40 minutes.

The study found that the rapid infusion of ketamine provided improvement in depression in the Emergency Room setting.

IV ketamine has been effective in treating phantom limb pain and ischemic limb pain. Ketamine has also helped in fibromyalgia syndrome. Ketamaine is best studied for complex regional pain syndrome (CRPS).