Acute Postoperative Pain Management in the Older Patient

Thor Hallingbye; Jacob Martin; Christopher Viscomi

Aging Health. 2011;7(6):813-828.

Pharmacokinetics & Pharmacodynamics: Application to Drug Dosing in the Older Adult

With age, the pharmacokinetics and pharmacodynamics of drugs change. Pharmacokinetics, in simplistic terms, is what the body does to a drug. Absorption, distribution, metabolism and elimination fall into the realm of pharmacokinetics. Hepatic metabolism of drugs relies on two important steps, Phase I and Phase II metabolism. The oxidation, reduction and hydrolysis reactions of Phase I metabolic capability probably decrease with age, but this may or may not be clinically significant.^[41] The Phase II reactions of conjugation through methylation, sulfation, acetylation or glucuronidation are likely unaltered as we age.^[41] Pharmacodynamics is defined as the effect of a drug on a person. Pharmacodynamics is usually related to specific drug receptors, which can change in function and density with age.^[7]

Older adults have a wide range of renal and hepatic function. Decreased hepatic blood flow and mass can lead to reduced metabolism and prolonged elimination especially for drugs with blood flow-limited metabolism, such as morphine. Although the liver experiences a progressive decline in mass, to a large extent it maintains its metabolic capability through its CYP450 system. The consequence of renal impairment on the pharmacokinetics of analgesic drugs typically outweighs the potential impact of reduced hepatic function.^[42] For example, renal insufficiency can play a significant role in the reduced clearance and accumulation of both drugs and drug metabolites. Morphine and its metabolites (morphine-6-glucuronide and morphine-3-glucuronide) and meperidine and its metabolite (normeperidine) are probably the most clinically relevant.^[43]

Older persons have a highly variable number of comorbidities, and therefore, a potentially higher number of medication interactions to consider. The volume of distribution, defined as the theoretical volume into which a drug distributes to produce a certain plasma concentration, may change depending on various factors, such as renal and hepatic function as well as total body water and fat content. These factors make it difficult to generalize the effect a drug will have on an older individual. Table 3 summarizes pharmacokinetic differences between older and younger persons.^[7]

Older adults display pharmacodynamic changes, particularly in the central nervous and cardiac systems. The sedating effects of benzodiazepines can be increased by up to 50% despite the pharmacokinetics being similar between the young and old.^[44] Balance disturbances are quite common after benzodiazepine administration and may be related to an exaggeration of baseline differences between young and older persons. Increased sensitivity to opioids appears to be the result of both pharmacokinetic and pharmacodynamic changes.^[45] Older persons likely express a lower density of µ-opioid receptors making them more vulnerable to the effects of opioids.^[38,43,44] Older patients appear to be more sensitive to the anticholinergic side effects of tricyclic antidepressants and display greater potential for increases in electrocardiogram QT-interval prolongation.^[41]

Because of the wide variation of physiological parameters present between older individuals, the adage 'start low and go slow' should be remembered when initiating drug therapy in the older patient.^[42]

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Next Section

Abstract and Introduction
Challenges of Assessing Pain in the Older Patient
Pain Experience in the Older Adult
Physiologic Changes of Aging
Pharmacokinetics & Pharmacodynamics: Application to Drug Dosing in the Older Adult
Analgesic Drug Classes
Case Presentations
Conclusion
Future Perspective
References
Sidebar

Table 1. Pain assessment tools.
Tool	Description	Discussion
Visual Analogue Scale	A vertical or horizontal 100-mm line anchored by verbal descriptors such as 'no pain' and 'worst pain possible'. Patients make a mark on the line that represents their pain intensity	Requires abstract thought Difficult to use in cognitively or visually impaired May be less valid in older adults
Numerical Rating Scale	Available in a variety of scale ranges and anchors, such as 0–10, with 0 being 'no pain' and 10 being 'worst pain possible'	Requires abstract thought Valid in cognitively impaired Commonly recommended scale for pain assessment in older adults
Verbal Descriptor Scale	Available in a variety of scale types (e.g., pain thermometer, present pain intensity index and graphic rating scale)	Limited amount of choices Requires some command of language Highly preferred by older adults Low failure rate in cognitively impaired
Faces Pain Scale	Consists of seven faces ranging from neutral face (no pain) to grimacing face (worst pain possible)	Requires abstract thought Difficult to use in cognitively impaired May be less preferred by older adults
Behavioral Pain Scale	Observational assessment tool for nonverbal patients compiled by nurse or physician	Generally takes longer to complete Requires knowledge of how scale is used Better results if observer is very familiar with patient

Table 2. Physiologic changes in the older adult.
System	Older vs younger	Importance
Nervous system	Higher prevalence of cognitive impairment Decreased ability to assess pain if demented/delirious Decreases in neurotransmitters and receptors Decreased pain-transmitting nerve fiber function (Aδ and C)	May be worsened by pain medications Use behavioral scale to assess pain level Decrease in autonomic responsiveness (uncompensated hypotension following spinal or epidural anesthesia) Decreased capacity or speed of pain processing Increased pain threshold to short duration pain stimuli
Cardiovascular system	Decreased cardiac output by 1% per year after 30 years of age High frequency of cardiovascular disease	Higher peak arterial concentrations after intravenous dose of medication Severe consequence of untreated hypotension following spinal or epidural anesthesia
Pulmonary system	Decreased sensitivity to hypoxia/hypercarbia Increased incidence of sleep apnea	Postoperative treatment with oxygen Slow titration of opioids Longer interval between doses
Hepatic system	Decreased metabolism of drugs	Decrease dose, increase interval between doses
Renal system	Decreased GFR	Adjust medication dose according to GFR Cautious use of medications with renal toxicity risk (NSAIDs)

Table 3. Pharmacokinetic changes in older adults.
System	Older vs younger	Importance
*Drug absorption and bioavailability*
Gastric pH	5–10% of older patients have decreased gastric acid secretion Widespread PPI and H2 blocker therapy	Drugs requiring acidic environment are poorly absorbed (i.e., ketoconazole and/or iron salts)
Gastrointestinal motility	Delayed gastric emptying, peristalsis and colonic transit	Delay in time to achieve drug plasma levels Risk of constipation
Intestinal permeability	Probably no change in passive permeability
Gastrointestinal blood flow	Probably diminished flow	Limits absorption of highly permeable drugs
Gut wall drug metabolism	Probably diminished	May lead to higher bioavailability (i.e., morphine)
*Volume of distribution*
Serum protein binding of drugs	10% decrease in albumin concentration Increase in α-1-acid glycoprotein	Higher unbound fraction of some drugs (i.e., fentanyl, propofol, midazolam and/or naproxen) Decreased unbound fraction of some drugs (i.e., lidocaine)
Body fat	Increased 20–40%	Higher volume of distribution for lipophilic drugs (i.e., fentanyl and diazepam)
Body water	Decreased 10–15%	Lower volume of distribution for hydrophilic drugs (i.e., morphine)
*Hepatic metabolism*
Hepatic blood flow	Decreased up to 40%	May affect drugs with flow-limited metabolism (i.e., morphine)
Hepatic mass	Decreased up to 40%	May affect drugs with flow-limited metabolism
Phase I metabolism	Potential decrease in some CYP450 enzymes	May affect drugs with capacity-limited metabolism (i.e., theophylline)
Phase II metabolism	No reduction in hydrolysis, reduction or conjugation	Unaffected
*Renal clearance*
Glomerular filtration rate	Reduction by approximately 1 ml/min/year after middle age Wildly variable depending on comorbidities	May require large reductions in dose of renally excreted drugs with narrow therapeutic index and drugs with active metabolites
Renal mass	Decreased up to 25%

Box 1. Opioid dosing in the opioid-tolerant surgical patient.
Step 1: obtain accurate history of opioid consumption Step 2: convert outpatient oral opioids to equivalent dose of parenteral opioids Step 3: multiply the Step 2 dose by 200–400% to predict daily parenteral opioid needs immediately after surgery Step 4: if an intravenous patient-controlled analgesia device will be used, divide Step 3 calculation by 24 to determine hourly maximum dose of opioid to be delivered by patient-controlled analgesia pump

Sidebar

Executive Summary

Background

Acute and chronic pain are increasingly prevalent in the aging population of the USA. Treatment of pain is complicated by medical comorbidities and the risk of postoperative delirium and cognitive decline.

Challenges of assessing pain in the older patient

Numerous pain assessment scales have been validated in the older population. In cognitively intact older adults, self-report scales are very reliable. In cognitively impaired older adults, behavioral scales are more valid.

Pain experience in the older adult

Sex and age-related differences in pain experience probably exist, but the clinical significance is unclear. Misconceptions about pain experience expose older adults to the risk of undertreatment.

Physiological changes of aging

Aging produces physiological changes within the body. There is a higher prevalence of cognitive impairment, cardiac dysfunction and hepatic and renal impairment in the older population.

Pharmacokinetics & pharmacodynamics: application to drug dosing in the older adult

There are wide variations in pharmacokinetic and pharmacodynamic changes apparent between older individuals. Increased body fat composition leads to higher volume of distribution for fat-soluble drugs and lower volume of distribution for water-soluble drugs.
Decreased hepatic and renal function is probable, with the effect of renal impairment being more important on drug metabolism and elimination. Pharmacodynamic changes are prevalent in the central nervous and cardiac systems.

Analgesic drug classes

Opioids are the prototypical pain medication. They can be safely used in older adults, but there are risks, including side effects, tolerance and opioid-induced hyperalgesia.
Acetaminophen has significant opioid-sparing ability, is well tolerated and can be administered by multiple routes.
NSAIDs have significant opioid-sparing ability. Nonselective COX inhibitors have side effects that the clinician must be aware of. COX-2 inhibitors may decrease the risk of gastrointestinal side effects.
Gabapentinoids have been shown to decrease perioperative pain and risk for development of chronic incisional pain.
N-methyl-D-aspartate receptor antagonists have significant opioid-sparing ability, but their use can be limited by side effects.

Case presentations

Cases presented to illustrate evidence-based decision-making regarding perioperative analgesia.

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