Ketamine is available throughout the world as an anesthetic. (See Chapter 16, Anesthesia: Ketamine, Ether, and Halothane, for a discussion of its use as an anesthetic.) Its availability combined with its effectiveness as an analgesic makes it an excellent choice for treating severe pain. Ketamine provides good analgesia when administered intramuscularly (IM), intravenously (IV), and in much lower doses, via the oral, intranasal, transdermal, rectal, and subcutaneous routes. It has proven effective for refractory neuropathic pain, such as postherpetic neuralgia, postamputation pain, spinal ischemia, brachial plexopathy, and HIV and cancer neuropathies. It is also effective in nociceptive pain, including myofascial and ischemic pain.8–11
Subanesthetic concentrations of ketamine also provide effective analgesia for short painful procedures, such as burn-dressing changes, radiotherapeutic procedures, bone marrow aspiration, and minor orthopedic procedures.12
Note that ketamine analgesia (1 mg/kg IV) has a pressor effect in circulatory shock and is the analgesic of choice for trauma patients in shock, especially if it is being used within 6 to 12 hours after injury. More care is needed if the patient is farther out from the injury, when it may cause hypotension. In patients with eye injuries, it may cause increased intraocular pressure at low doses.13
Oral and Parenteral Administration
Oral ketamine in a dose of 0.5 mg/kg has an analgesic effect at about 30 minutes post-ingestion. Dilute the parenteral preparation in orange juice or cola to make it more palatable.11
Subcutaneous ketamine can be used to control both acute and chronic pain. Ketamine 0.1 mg/kg subcutaneously controls acute trauma pain better than IV morphine. In addition, it produces less drowsiness, causes no nausea or vomiting, and requires no breakthrough medications.14 In cancer patients with intractable pain, give an initial subcutaneous injection of 10 mg ketamine followed by a continuous subcutaneous infusion of 10 mg/hr. An additional 2.5 mg/day can be added, up to a rate of 15 mg/hr. Most patients obtain pain relief; the side effects are site inflammation, salivation, and insomnia. Over 5 to 7 months, some patients develop a tolerance to ketamine's analgesic effect.10
Ketamine is frequently given IV or IM at a dose of 0.5 mg/kg, which produces rapid and profound analgesia.15 Follow this with 0.25 mg/kg (250 micrograms/kg [mcg/kg]) doses, as necessary.12
In Combination with Other Medications
Ketamine reduces the amount of morphine needed to treat acute severe pain in trauma patients.16 It is safe to use with morphine: Administration of 0.25 mg/kg IV ketamine lessens the pain of patients whose pain is poorly controlled with IV morphine. In addition, their nausea and vomiting is reduced.15,16
When given as 0.4 mg/kg IM (with 0.05 mg/kg midazolam), ketamine provides long-term analgesia in about one-third of patients with constant neuropathic trigeminal pain who have not responded to other modalities.17
Postoperative patients may also benefit from low-dose ketamine's analgesic effects.18,19 Ketamine is especially useful in patients who have a tolerance to opiates.20 While both IV infusions and oral ketamine have been effective, patients appear to experience fewer side effects with oral ketamine.21
For adult patients in severe pain, give a loading dose of 0.5 to 1 mg/kg IM ketamine. Follow this with an infusion of 60 to 180 mcg/kg/hr (4 to 12 mg/hr for a 70-kg adult). A practical regimen is to add 50 mg of ketamine to a 500-mL bag of normal saline or dextrose (0.1 mg/mL of ketamine) and run this at 40 to 120 mL/hr (i.e., over 4 to 12 hours for a 70-kg adult). This regimen is safe, since even the total volume will not deeply anesthetize the patient.21
Local Anesthetics and Blocks
While local anesthetics are frequently used for surgery, they are often neglected for use either postoperatively or in other situations needing analgesia. When an appropriate anatomical region is involved and the clinician has the skills, consider giving local or regional anesthetics, especially blocks with the long-acting anesthetics. Some useful blocks are described in Chapter 14, Anesthesia—Local and Regional and Chapter 23, Dental: Diagnosis, Equipment, Blocks, and Treatment. While these might not result in perfect analgesia, they usually lessen the pain enough for other analgesics to be effective.
Neuropathic pain is much more common that clinicians recognize. It stems from damage to or dysfunction of the peripheral or central nervous system (CNS) and results in pain far greater than that which would be expected from the injury. It is usually characterized by dysesthesias (burning pain, often with a "stabbing" component) and, sometimes, a deep ache. There may also be hyperesthesia (increased sensitivity to sensory stimuli), hyperalgesia (abnormally increased sensitivity to pain), allodynia (pain due to a benign stimulus), and hyperpathia (a particularly unpleasant, exaggerated pain response). Symptoms typically persist after resolution of the primary cause due to CNS remodeling. Although neuropathic pain may respond to opioids, the most effective treatment is often to give antidepressants, ketamine, anticonvulsants, baclofen, and topical medications.
Tricyclic antidepressants have been shown to be effective in most types of neuropathic pain and will often be available and inexpensive. Their analgesic effect may begin immediately (unlike their delayed action when used for depression). This group of medications includes amitriptyline, imipramine, desipramine, and nortriptyline. Their use is contraindicated in patients with liver, renal, or cardiac disease or those with orthostatic hypotension. To reduce side effects, start amitriptyline at 25 to 50 mg hs (before bed) and increase it, as necessary, to 100 mg hs after a week. As with other analgesics, these medications are not effective for all patients. For every two patients treated, only one may get >50% pain relief. Other effective agents that may not be available, and that are more expensive, include antiepileptics (e.g., gabapentin at 300 mg twice a day [bid] to a maximum of 1200 mg tid).22,23
Ketamine successfully treats chronic pain states, such as complex regional pain syndromes,24 phantom-limb pain,25 and central and peripheral neuropathic pain.26 Use 50 mg po (by mouth) in adults 3 times a day (tid). Increase this to 100 mg tid, as needed. Problems with hallucinations and excessive salivation are rare. Gradually decrease the dose after about 3 weeks of good pain relief to see if it is still needed. It can be reinstituted, if necessary.21
Hypnosis provides significant pain relief for most patients, sometimes even better relief than from traditional medications. This relief is different from the relief obtained from acupuncture and that from placebos. Hypnosis offers a moderate to large analgesic effect for many types of pain.27,28 See "Hypnosis" in Chapter 14, Anesthesia—Local and Regional, for instructions on doing clinical hypnosis.
When drug supplies are extremely limited, some drugs may be available from unusual local sources. Whenever medications are obtained from nontraditional sources, extreme care should be taken, since identifying the real drug, dose, and purity may be in doubt. Additional information about using street drugs can be found in Chapter 12, Medications/Pharmacy/Envenomnations.
Methadone is both a prescription medication and a drug used and sold by opiate addicts. When purchased in tablet form, it can usually be identified as coming from a legitimate pharmaceutical company. Methadone has the same actions as morphine and meperidine. Its unique quality is that it is well absorbed orally. It has a prolonged duration of action, making it more suitable for use in chronic rather than acute pain, although it has been used successfully for acute pain. Orally, the dose ranges from 2.5 to 25 mg given every 6 to 12 hours. The parenteral formulation can be administered IM at from 7.5 to 10 mg every 4 to 6 hours.2