Introduction
Patients with advanced dementia commonly exhibit dangerous response agitation. The management of dementia-related agitation requires correction of underlying factors that may be triggering the agitation. Pain is a common factor that increases the risk of dementia-related agitation. In a recent study of patients with advanced dementia it was found that 95% of patients were in pain (Sampson et al., Reference Sampson2011). Mobility is frequently impaired in advanced dementia, and immobility often leads to painful conditions such as contractures, constipation and skin breakdown. Assertive nursing care is vital to help manage these conditions. A recent study of factors predicting the development of aggression in patients with dementia found that the most significant risk factors included pain, depression, baseline caregiver burden, and a decline in the quality of the patient-caregiver relationship (Kunik et al., Reference Kunik2010). Patients with advanced dementia often have a high level of baseline caregiver burden. In these patients, pain-related agitation and resistive behavior further corrupt patient-caregiver relationships, and the risk for aggression worsens in turn. A downward spiral thus ensues and patients often end up in a “catch-22” situation whereby pain causes agitation and resistive behavior which then obstructs assertive nursing care/management of the underlying painful condition(s).
Medications commonly used to manage dementia-related response agitation confer specific risks. Antipsychotic use in patients with dementia has been associated with an increased risk of serious adverse effects including stroke and death (US Food and Drug Administration, 2005). While evidence exists to support the short-term use of antipsychotic medication for the management of dangerous dementia-related agitation (Passmore et al., Reference Passmore, Gardner, Polak and Rabheru2008), treatment guidelines emphasize the importance of employing non-pharmacologic management strategies and correcting factors such as pain that may be underlying dementia-related agitation (Herrmann and Gauthier, Reference Herrmann and Gauthier2008). Benzodiazepine use often leads to side-effects including over-sedation and ataxia. Commonly prescribed opioid analgesic medications have side-effects including delirium and constipation. The use of antipsychotics, benzodiazepines and/or commonly prescribed opioids is therefore often unsafe and/or poorly tolerated. This report details the case of a patient suffering from advanced dementia and pain with response agitation that remitted with the use of sublingual sufentanil given prior to personal care. The patient's next of kin provided written informed consent for publication of this case report.
Case report
A 104-year-old female with a history of dementia of the Alzheimer-type in the severe stage presented with extended care needs after a fall resulting in a hip fracture with subsequent hip replacement surgery. She was unable to walk or transfer independently, requiring total assistance for personal care measures. The patient routinely directed aggression towards nursing staff during toileting, bathing and transfers. Nursing staff noted that the patient seemed to be wincing and guarding against movement of her legs during care. She was usually calm when unattended during the remainder of the day and she slept well most nights.
Investigation of leg pain yielded the hip replacement hardware and degenerative large joint changes attributable to osteoarthritis but no acute or reversible underlying pathology otherwise. Management of pain, including regular dosing of acetaminophen, was ineffective in reducing response agitation during care. The patient had a disappointing response to pharmacotherapy specifically targeting response agitation. This included lorazepam 0.25 mg prior to care (over-sedating), loxapine 2.5 mg prior to care (over-sedating), and quetiapine 12.5 mg prior to care (ineffective).
The palliative care service at the patient's residential care facility occasionally uses sublingual sufentanil for the management of incident pain during procedures such as wound dressing changes. Nursing staff were thus familiar with this novel approach to the treatment of incident pain. A trial of sublingual sufentanil was therefore felt to be a reasonable option for the management of this patient's incident pain and substitute consent was obtained from the patient's next of kin. From an ethical perspective, this was accepted as adequate support for the application of a novel treatment in a patient with dementia, herself incapable of providing informed consent.
Sufentanil citrate injectable solution was given sublingually using a concentration of 50 micrograms/mL. The dosage was started at 5 micrograms (0.1 mL) and given sublingually via syringe 5 minutes prior to personal care or transfers. The patient's response agitation promptly resolved with no consequent over-sedation or other side-effects. Observational data supporting the effectiveness of sublingual sufentanil included reports from nursing staff and care aides. The consensus from nursing staff was that the sublingual sufentanil trial correlated with prompt and enduring resolution of the patient's agitation and resistive behavior during nursing care, with no consequent over-sedation or other apparent side-effect.
Sufentanil is a rapid-onset (3–5 minutes), ultra-brief acting (10–25 minutes) opioid analgesic (Scholz et al., Reference Scholz, Steinfath and Schulz1996). It is available as an injectable solution that is commonly used intravenously during procedural anesthesia. The lipophilic nature of the injectable solution allows for transmucosal absorption during sublingual administration. Sublingual sufentanil use has previously been reported as helpful for management of episodic cancer pain with doses ranging from 2.5 to 75 micrograms (Reisfield and Wilson, Reference Reisfield and Wilson2007). Bioavailability after sublingual administration in healthy adults ranges between 78% and 88% (Palmer et al., Reference Palmer, Hamel and Skowronski2009). Sufentanil undergoes hepatic metabolism via cytochrome p450 3A4 with no active metabolites. It appears to be safe for use in patients with hepatic and renal dysfunction (Reisfield and Wilson, Reference Reisfield and Wilson2007).
In this patient, the use of low-dose sublingual sufentanil prior to personal care was immediately associated with resolution of dementia-related response agitation due to incident pain. Based on this case study, it is recommended that, for patients with incident pain and dementia-related response agitation, consideration be given to a trial of sublingual sufentanil for comfort and to facilitate the provision of nursing care. The suggested starting dose is 5 micrograms (0.1 mL of 50 micrograms/mL injectable solution) given sublingually via eyedropper or syringe 5–10 minutes prior to personal care or transfers, titrating in increments of 5 micrograms as tolerated to induce the required level of analgesia/sedation. In order to reduce the risk of respiratory depression, avoid repeated or incremental dosing more often than every 2 hours, especially during the initial dosage titration when individual opioid sensitivity/tolerability may be uncertain. The usual effective dose is expected to be in the range of 5 to 25 micrograms. To encourage transmucosal absorption, advise the patient to refrain from swallowing for 1–2 minutes after sublingual sufentanil administration. In the case reported above, the patient was not capable of understanding the instruction to refrain from swallowing for 1–2 minutes following sublingual sufentanil administration. Nonetheless, the patient's pain-related agitation remitted and adequate transmucosal absorption of sufentanil was thus presumed based on the patient's prompt and enduring response. Variability in compliance with instructions to refrain from swallowing for 1–2 minutes may confer variability in transmucosal absorption and in serum levels. This underscores the need for caution during the initial dose-titration and for ongoing assessment of tolerability (sedation/respiratory depression) during sublingual sufentanil use in this setting. Careful monitoring for respiratory depression is recommended with a precaution to avoid administration of sufentanil to patients with pre-existing respiratory compromise, decreased baseline respiratory rate or concurrent use of other opioid-based medications or medications known to inhibit cytochrome p450 3A4. Sufentanil-related over-sedation or respiratory depression can be reversed with the opioid inverse-agonist naloxone.
Conflict of interest
None.
