Joshua Long, MD
Christina Shenvi, MD, PhD
Managing acute pain in elderly patients presents a unique challenge, especially in a busy Emergency Department (ED). Altered physiology and pharmacokinetics, as well as polypharmacy, comorbidities, and practitioner experience with older patients all affect the care of this population. According to US Census data from 2012, adults age 65 years and older will total 70 million and make up nearly 20% of the entire US population by 2030, up from 13% of the population in 2010 (US Census Bureau). Older adults are projected to make up 25% of ED patients by the year 2030. Some institutions have developed specialized treatment areas or protocols to address the specific needs of the older population (Wilber 2003). However, all emergency providers should be able to safely and effectively manage pain in older adults.
Older adults are less likely to receive opioid analgesia, either oral or parenteral, both in the ED and on discharge, when compared to their younger counterparts (Shah 2015, Platts-Mills 2012, Terrell 2010). Even with improved pain assessment strategies, only a fraction of patients receive opioid pain medication, and those who do receive treatment are often undertreated (Herr 2009, Terrell 2010). While treating chronic pain with opioid medication has come under recent scrutiny from the Centers for Disease Control (Dowell 2016), and opioid-related deaths are increasing in the general population, there are several appropriate uses for opioids analgesics in elderly patients in the acute setting. In addition, there are concerns in the elderly with some of the alternative medications used for acute pain. However, special caution is needed in older patients because of the risk of introducing a drug-drug or drug-disease interaction or another consequential adverse effect from a pain reliever upon ED discharge (Hastings 2007).
While there are harms associated with the use of pain medications, under-treatment of pain can also be problematic. Untreated, chronic pain can lead to decreased mobility, functional decline, increased dependency on family or care providers, delayed healing, compromised immune response, and has even been shown to increase tumor growth rate and metastasis (Berry 2000, Ferrell 1990, Sasamura 2002). Poorly controlled pain is one of the leading predictors of functional decline in older adults. In addition, older adults with acute pain are more likely to develop chronic pain further complicating their clinical course and emotional health, with greater healthcare costs (Dworkin 1997, Hughes 1997). Acute pain should be aggressively managed with non-opioids and short courses of opioids if needed. Chronic pain should be managed with a multi-modal approach including non-pharmacologic modalities such as physical therapy, and opioids used only after a careful consideration of the likelihood of the patient to benefit and be harmed.
Pharmacology
There are many barriers to appropriate assessment and management of pain in older adults. One area of particular concern is changes in normal physiology as people age and the risk of side effects from medications. Physiologic changes in aging can put older adults at higher risk of side effects from commonly used medications such as NSAIDs and opioids. Drug absorption, distribution, metabolism, and elimination are all different in older adults. Gastric motility, pH, and blood flow change as people age and alter drug absorption profiles. Older people experience a 20-40% increase in body fat and 10-15% decrease in body water changing drug distribution volumes (Crome 2003). Older adults, in general, have lower concentrations of serum albumin, leading to reduced protein binding and increased free (unbound) concentrations of protein-bound drugs in the serum (Grandison 2000).
Drug clearance rates are affected by the reduced ability of the liver and kidney to metabolize and clear medications. Age, blood flow, genetics, lifestyle, and underlying hepatic disease all contribute to decreased hepatic clearance, which may reach 50% of baseline. (Zeeh J 2002). Renal clearance is similarly affected, especially by non opioid pain medications. Non-steroidal anti-inflammatory drugs (NSAIDs) as a class tend to inhibit prostaglandin-mediated renal vasodilation thereby reducing renal blood flow, which is directly linked to renal drug clearance (Swedko PJ 2003).
In addition to these pharmacokinetic changes, older adults are also at much greater risk for experiencing adverse drug events, drug-drug interactions, and drug-disease interactions (Yang 2001). As medication lists grow with age, older patients are at even greater risk of being prescribed a medication that interacts in a dangerous way with an existing medication or disease state. One study looking at older patients treated in a Veterans Administration Emergency Department found that 11.6% of patients were given a “drug to avoid” based on Beers Criteria guidelines. [Hastings 2007] Furthermore, a potential drug-drug interaction was introduced in 12.6% of patients, and 5.7% introduced a potential drug-disease interaction (Hastings 2007). Although introducing new potential interactions is sometimes unavoidable, in other instances, there are potential alternative medications that may be safer. Providers must be aware of this altered pharmacology whenever considering medication administration, dosing, and appropriate monitoring.
Acetaminophen
Acetaminophen is considered first-line therapy in older adults for both acute and chronic pain. It has a better safety profile than other analgesics and is widely available. Cardiovascular, gastrointestinal, and renal side effects are minimal when compared to NSAIDs. Despite the marked hepatotoxicity when taken in excessive doses, there is no evidence that long-term therapeutic acetaminophen use leads to liver damage (Watkins 2006). The total daily dose is 3-4g per day unless the patient has an underlying liver disease or is a heavy user of alcohol. Acetaminophen is available in oral and rectal forms, and an intravenous formulation is available in many hospitals. The provider must use caution and specifically warn patients to avoid excessive doses of acetaminophen, particularly because it is included in many other analgesics and cough/cold formulations. For example, to better calculate the dose of acetaminophen, it is preferable to prescribe acetaminophen and an opioid separately if needed than to prescribe a combination medications such as oxycodone/acetaminophen (Percocet) or hydrocodone/acetaminophen (Vicodin, Norco, Lortab), because patients who take a combination analgesic must increase their acetaminophen intake if an increase in opioid dose is required. Patients on coumadin who are started on regular acetaminophen therapy should have their INR checked 3-5 days later. (Lopes 2011)
NSAIDs
Non-steroidal medications are routinely listed as a medication to avoid by the AGS due to the risk of gastrointestinal bleeding, renal failure, and acute coronary syndrome with chronic use. Special caution should be taken in prolonged use in individuals over the age of 75, those on corticosteroids, anticoagulants, or anti-platelets (American Geriatrics Society 2015). Renal impairment and resulting hyperkalemia may also occur, even with brief courses of treatment. (Platts-Mills 2013, Bowling CB 2012). Indomethacin can cause drowsiness and impaired motor coordination and is specifically cited in the 2015 Beers Criteria update as a drug to avoid. Ketorolac is associated with increased risk of cardiovascular events (Kim 2015). If an NSAID is thought to be indicated in an elderly patient despite these risks, the AGS recommends that a proton pump inhibitor be prescribed concurrently. However, use of PPIs for more than 8 weeks is not recommended because of the increased risk of C. difficile, bone loss, and fractures (Ro Y 2016). As physicians move away from chronic NSAID use for osteoarthritis pain they are increasingly prescribing opioid medications, which have been linked to an increased risk of falls and fractures in elderly adults (Rolita L 2013) as well as constipation, confusion, and depression. As with all analgesics, providing the lowest dose for the shortest duration to achieve adequate pain relief is the overall goal.
Opioids
Opioid analgesics are effective for some elderly patients with acute pain, but are associated with significant morbidity and mortality. The 2016 CDC guideline for prescribing opioids for chronic pain strongly discouraged their routine use. (Dowell 2016)
The 2015 Beers list recommends avoiding ≥ 3 CNS-active drugs (antipsychotics, benzodiazepines, tricyclic antidepressants, selective serotonin reuptake inhibitors, and other opioids) if opioids are to be used, citing an increased fall risk with multiple centrally acting medications. (American Geriatric Society 2015) Treatment with opioids in the monitored ED setting or at home may be appropriate in certain situations and providers should consider the patient’s existing medication list, living situation, baseline mental and ambulation status, and nature of the underlying painful condition prior to prescribing these medications.
An additional concern when prescribing opioids is the resulting constipation, which can lead to significant morbidity in the elderly population. This alone can precipitate delirium, poor feeding, and physician visits. All patients treated with opioids should receive additional medication to stimulate gastrointestinal tract motility in addition to a stool softener. Senna is a common stimulant laxative and can be prescribed in combination with docusate, a stool softener. Prescribing both a stimulant laxative along with a stool softener is recommended for older patients prescribed even a brief course of opioids. (Serrano 2016)
Topical Pain Medications
For patients with musculoskeletal pain, there are several additional options for pain control. Topical NSAIDs, such as diclofenac gel, can be used, specifically to decrease the pain associated with knee osteoarthritis. Back pain or post-herpetic neuralgia can be treated topically with a lidocaine patch. These topical medications can be highly effective, and have fewer side effects than systemically administered medications.
Regional Anesthesia
Another alternative to pain medication while in hospital is nerve or compartment blocks. The femoral nerve block or fascia iliaca block is effective and recommended as routine care following hip and proximal femur fractures (Lees 2014, Mouzopulos 2009, Hogh 2008, Monzon 2007, Morrison 2016). Hematoma blocks may provide effective analgesia, replacing or reducing the need for oral/parental agents, following wrist and ankle fractures. (Ross 2011, Funk 1997)
Procedural Sedation
Older adults are more likely to suffer dangerous complications during procedural sedation; performing PSA in this group is therefore a challenge for even the experienced provider. In this section we will provide a literature-based review of the common procedural sedation drugs as they pertain to the elderly population.
Propofol
Propofol’s rapid onset and brief duration of action make it an attractive procedural sedation agent, although its dosing and safety profile are different in the elderly. One ED study comparing midazolam with propofol for procedural sedation in elderly patients found no significant difference in complication rates between younger age groups and those over age 65. They did find, however, that lower doses were sufficient in the ≥ 65 age group (Weaver 2011). Another ED study found that, on average, patients ≥ 65 years of age required a lower induction dose (0.9 mg/kg) compared to younger adults (1.4 mg/kg). The total dose given was also lower in the older group (1.2 mg/kg compared to 2 mg/kg). (Patanwala 2013)
Respiratory depression and loss of airway reflexes are important dangerous effects of propofol administration. Though one review of multiple RCTs found that propofol administered alone had no statistically significant increase of respiratory depression when compared to other agents combining propofol with opioids led to more hypotension and respiratory adverse events. (Black 2013) Given the lower doses needed for effective sedation in older adults it is prudent to reduce the induction dose and prepare for airway and respiratory support.
Ketamine
Ketamine is a dissociative sedative popular among emergency physicians for procedural sedation, especially in pediatrics. It uniquely provides amnesia, analgesia, and sedation while preserving airway reflexes, increasing blood pressure, and raising heart rate. The standard adult induction dosing is 1-2 mg/kg IV followed by 0.25-0.5 mg/kg as needed for continued sedation.
Literature evaluating the safety and efficacy of ketamine for procedural sedation in the older adult population is sparse. There are several small, older studies in the anesthesiology literature evaluating this issue. One study examined the hemodynamic effects in elderly patients, mean age of 83 years, undergoing procedural sedation in the operating room for reduction of hip fractures. Patients were noted to have elevated blood pressure and cardiac index with no serious adverse events (Stefánsson 1982, Wickström 1982). Additional small studies have found that ketamine increases myocardial oxygen demand, although this was not associated with any hemodynamic instability (Maneglia 1988).
The combination of ketamine and propofol as “ketofol” has been adopted by many providers as an alternative approach to procedural sedation. Some studies suggest that using this combination is safe and that the catecholamine release caused by ketamine may counter the hypotension associated with propofol. Smaller doses of each medication are required to achieve appropriate sedation when using this combination (Andolfatto 2012, Willman 2007). While promising, few older adults were enrolled in these studies making generalization difficult.
Benzodiazepines +/- an Opioid
Benzodiazepines, as a class, are generally regarded as drugs to avoid for outpatient use in the older adult population . However, they are effective and have been used for decades for procedural sedation. Several studies have examined procedural sedation in older adults with either diazepam or midazolam plus fentanyl. One common theme in the literature is that lower doses of drug are necessary in older patients. In one study from the dentistry literature, to achieve the same level of sedation, patients > 80 years old required 0.1 mg/kg of midazolam while those 30-39 years of age required 0.25 mg/kg. Desaturation events, however, we also more common in the older age group although no one required intubation or experienced a serious adverse event as a result (Kitagawa 1992). A similar study evaluated 200 adults ≥ 65 years of age and found no serious complications when using intravenous diazepam or midazolam along with 100 mcg of fentanyl. These patients remained NPO prior to sedation and received an intravenous fluid bolus prior to medication administration (Campbell 1997). Recognizing the need for lower dosing in older adults, Yano et al looked at adults under 60 and those over 60 years old undergoing sedation for colonoscopy. The younger age group received midazolam 0.05 mg/kg while those > 60 years received 0.025 mg/kg. Even with the decreased dosing, more desaturation events occurred in the older patients. (Yano 1998) The provider must recognize the need to use a lower initial dose in older adults, pretreat with intravenous fluids, and anticipate respiratory complications. Midazolam has a shorter duration of action than diazepam and is generally preferred for procedural sedation, as benzodiazepines can have prolonged effects in older adults and can contribute to delirium. Flumazenil is available as a possible benzodiazepine reversal agent but must be used cautiously in patients using benzodiazepines chronically, because flumazenil may precipitate benzodiazepine withdrawal including refractory seizures in this group.
Summary
The management of acute pain and procedural sedation in older adults can be challenging. Several guiding principles can help physicians provide safe, adequate pain control.
In the ED for pain control:
- Be aware of the tendency to under-treat pain in older adults, and the importance of assessing pain in patients who are cognitively intact as well as those with cognitive impairment, in whom you may have to rely on non-verbal clues as to their pain, such as facial expression, vocalizations, posture, and vital signs.
- Start with lower doses of medication but reassess frequently and re-dose as needed in order to provide adequate analgesia with the lowest dose possible.
- Consider using nerve blocks or topical medications when appropriate to reduce the risk of side effects from systemic administration.
- When giving IV opioids, place the patient on a monitor in case of respiratory suppression or hypotension.
In the ED for procedural sedation:
- Most medications are reasonably safe and tolerated well in older adults, though evidence is sparse for ketamine.
- Older adults usually need a lower dose for procedural sedation and medication effect may be longer-acting, so patients should be monitored closely until their mental status returns to baseline.
At discharge:
- When prescribing a medication at discharge, review a patient’s home medications and past medical history to assess for potential drug-drug interactions or complications such as acute renal failure with NSAIDs.
- When prescribing opioids, prescribe scheduled acetaminophen, possibly with a PRN opioid that does not contain acetaminophen, at a low dose. Warn patients about the risk of sedation and falls.
- When prescribing opioids, also prescribe a short course of a stimulant laxative such as Senna and stool softener, such as Colace.
- Try to help ensure early follow up for older adults with their primary care physician both to reassess the condition causing their pain, the adequacy of their pain control, as well as for any side effects from the newly prescribed medications.
The authors report no relevant conflicts of interest.
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