Joe Kras, MD
Hospice and palliative care (HPC) clinicians use medications in an off-label manner, including anesthetic agents. Three such sedatives and adjuvant analgesics will be presented since they are increasingly being considered by clinicians.
Propofol, a sedative hypnotic, only has bioavailability when given intravenously. Three potential uses are painful dressing changes, intractable nausea and vomiting, and palliative sedation. Nonetheless, common side effects include hypotension and apnea. Dosing of propofol for dressing changes may consist of boluses of 10 to 30 mg every 2 to 5 minutes until an appropriate level of sedation is obtained. As propofol has no activity at opioid receptors, it serves a beneficial role, in conjunction with an opioid, for painful procedures. Infusions for either nausea and vomiting or palliative sedation may be initiated at rates of 0.5 to 1.0 mg/kg/hr and increased by the same amount every 5 minutes until sedation starts to occur or symptoms subside. Smaller incremental adjustments may then be used to fine-tune dosing. It can be infused for several days if necessary. If desired, propofol can offer the advantage of predictably causing unconsciousness that other sedatives (such as benzodiazepines and opioids) cannot. The narrow difference between a dose resulting in sedation vs respiratory depression includes factors such as frailty, low body fat, and decreased plasma proteins and requires caution and careful titration. The cost of propofol is approximately $71/400 mg. Although not a federally controlled substance, propofol has been diverted and abused, and thus care must be taken in storage and dispensing it.
Ketamine produces surgical anesthesia while preserving respiratory drive and reflexes without lowering blood pressure like most anesthetics do, due to its prevention of reuptake of endogenous catecholamines. It is approved for intravenous (IV), intramuscular, and intranasal use but is used subcutaneously, by rectum, and by mouth in HPC. The indications for use in HPC include sedation for painful dressing changes, acute and chronic pain analgesia (especially neurogenic or neuropathic pain), opioid-induced hyperalgesia, and depression or anxiety. Side effects occur with moderate to high doses, including hallucinations, paranoia, nystagmus, and excessive salivation. If being used as a continuous infusion, one must remember to decrease the dose after about 1 hour, as its metabolite, norketamine, can accumulate and increase unwanted psychomimetic effects. Daily rotation of subcutaneous (SC) injection sites is usually required secondary to otherwise painful induration. Infusion doses for severe pain range from 0.1 to 0.3 mg/kg/hr typically, but higher doses have been used. When initiating and titrating ketamine, the clinician should consider the following: 1) the patient may experience an elevated blood pressure and should be monitored; 2) doses exceeding 0.3 mg/kg/hr have been used, and side effects such as bronchospasm and secretion production could happen; and 3) the patient may experience disassociation, requiring treatment with lorazepam. Doses by mouth may start at 10 to 25 mg three times a day and may range as high as 100 mg twice a day or higher. Ketamine costs approximately $250/500 mg. It has high abuse potential (street names Special K, Vitamin K, ket, etc).
Dexmedetomidine (an alpha-2 agonist) is a sedative that may produce brief hypertension followed by hypotension, bradycardia, nausea and dry mouth. Dexmedetomidine has been shown to decrease delirium, augment opioid analgesia, and provide adequate sedation for both short procedures and long periods of time. One property of dexmedetomidine that is potentially very advantageous is that it appears to restore a person’s normal sleep pattern while allowing the patient to be awakened.
Dexmedetomidine is used intravenously but also intramuscularly, subcutaneously, intranasally, and buccally, making it advantageous in HPC applications. Nasal bioavailability is approximately 40% to 50% of IV and levels take about 45 minutes to peak, such that nasal dosing for procedural sedation should start in the range of 1 to 2 mcg/kg. Doses used intravenously and subcutaneously in HPC are usually in the 0.2 to 1.0 mcg/kg/hr range, though some higher doses are reported. Although often administered via a loading dose followed by a continuous infusion, caution is advised to decrease or eliminate the loading dose in the frail or when other sedative agents are being coadministered. Dexmedetomidine is also supplied in a sublingual (SL) film in 120 and 180 mcg doses. The films may be cut in half. Initial SL or buccal film dosing for agitation is 120 to 180 mcg, with subsequent doses being half that much spaced 2 hours apart. In all routes of administration, dosing should be reduced in the face of decreased liver function. Dexmedetomidine costs approximately $230/400 mcg. It has low abuse potential.
Anesthetic agents can be prohibitively expensive or require hurdles for HPC providers. There are advantages, and they may help patients with refractory symptoms.
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Joe Kras has been a practicing anesthesiologist for 29 years and is also board-certified in hospice and palliative care.