Analgesic prescribing for patients with kidney disease must consider that: (1) some analgesic medications, so called nephrotoxic drugs, can cause kidney injury or worsen kidney function; (2) kidney dysfunction may impair drug elimination, causing or augmenting adverse effects. 

Because many of the same considerations apply to patients with acute kidney injury and chronic kidney disease, including those on dialysis, we refer to these entities broadly as “kidney dysfunction” throughout the module. In this this module, our objectives are to:

• Identify analgesics that require special consideration in people with kidney dysfunction, either due to nephrotoxicity or impaired elimination
• Identify alternative analgesics that are safer to use in kidney dysfunction
• Provide recommendations on safer prescribing practices for patients with kidney dysfunction

The first step to kidney-safe prescribing is evaluating a patient’s current and baseline kidney function. Kidney function is usually assessed using serum creatinine, which can be used along with a patient’s age and sex to estimate the kidney’s filtration ability through the estimated Glomerular Filtration Rate (eGFR; in mL/min/1.72m^2).

The most recent guidelines for kidney function estimation recommend the use of the race-free 2021 CKD-EPI estimating equations (Delgado C et al, Journal of the American Society of Nephrology, 2021). In Apex, “eGFRcr”  was implemented March 30, 2022 and refers to the race-free estimating equation. Older estimates available in Apex use the CKD-EPI 2012 equation; the “eGFR high estimate” generally applies to younger and/or more muscular patients, “eGFR low estimate” applies to older patients and those with lower muscle mass. Importantly, eGFR equations assume that creatinine is at steady state--this is not the case during acute kidney injury (AKI) when creatinine rises and falls. In addition, clinicians must interpret any given creatinine value in the context of that patient’s baseline, as severe AKI can occur with values in the laboratory reference range. Measurement of cystatin C to guide eGFR estimation should be considered in older patients and those with lower muscle mass as well. Chronic kidney disease (CKD) is most commonly defined by eGFR < 90 and/or persistent proteinuria/albuminuria. Patients with end-stage renal disease (ESRD) generally require RRT and may be treated with either hemodialysis or peritoneal dialysis. Nephrology and/or pharmacy consultation is recommended to guide drug dosing in the following circumstances: at extremes of muscle mass where eGFR estimates may not be accurate; during AKI when creatinine is rapidly changing; with advanced CKD or ESRD. Drug dose adjustment recommendations (LexiComp) are usually based on creatinine clearance (CrCl), which approximates the eGFR reported in Epic.

Pain is common in patients with cirrhosis and other types of liver disease, but is often difficult to manage given concerns about impaired hepatic metabolism, hepatotoxicity and increased risk of adverse events. Cirrhosis patients suffer from musculoskeletal pain at rates that are similar to or higher than the general population, and may also have liver disease-specific causes of pain, including muscle cramps or abdominal pain secondary to ascites. Management of patients with chronic liver disease and pain is particularly challenging in inpatients who may have acute pain or acute-on-chronic pain due to their acute medical illness, and may also have acute hepatic decompensation resulting in increased impairment in hepatic metabolism, further limiting analgesic options. As a result, patients with liver disease are at high risk for undertreatment of their pain across clinical settings.

Challenges 

Managing pain in patients with liver disease is particularly challenging for several reasons:

1. There are potential harms associated with many of the common classes of analgesics (e.g. acetaminophen, NSAIDs, opioids) in this population as many of these agents are largely metabolized by the liver.

2. Liver disease is not a single disease entity, but rather ranges from acute liver injury, to chronic liver disease (e.g. nonalcoholic fatty liver disease, chronic hepatitis B) without significant fibrosis, to cirrhosis. Among patients with cirrhosis, there are different degrees of hepatic dysfunction, and there are no endogenous markers for hepatic clearance (unlike renal clearance) that can be used to guide drug dosing. Additionally, patients with cirrhosis may have particular complications (e.g. hepatic encephalopathy, volume overload), which may predispose them to different types of analgesic risk.

3. There is minimal real-world data on risks and harms of analgesics in this population

Pain is not a normal part of aging.  The underlying causes and treatment strategies are similar, though in older adults pain it is often unrecognized and undertreated. Providing adequate pain control can minimize the potentially serious negative physical, psychological, and social consequences associated with pain.

Pain Management in the pregnant patient is unique as every therapeutic intervention effects two patients at the same time. The goal of avoiding side effects, especially for the developing fetus, makes the goal of satisfactory pain control more complex to achieve.

However, trauma during pregnancy, the need for non-elective surgery, or preexisting chronic pain conditions routinely result in the need to manage pain in pregnant patients.

Furthermore, the physiological changes seen in pregnancy can per se cause pain that in most cases disappears post partum. Increased weight and the hormonal changes associated with pregnancy can put considerable stress on the musculoskeletal system resulting in

• Low Back Pain (impacts approximately half of pregnancies)
• Pelvic Girdle Pain
• Abdominal and Chest Wall Pain
• Hip Pain
• Arthritis

Background: Pregnant individuals on chronic opioids fall into 3 distinct groups. 

1. Those with chronic pain syndromes on opioids. 
2. Those with opioid use disorder on medications (MOUD). 
3. Those with an untreated opioid use disorder.

All 3 groups have unique pain control needs and often suffer from undertreated pain.

• Delirium is a neuropsychiatric syndrome characterized by acute changes in cognition, attentional deficits and altered arousal with a fluctuating course. It affects 11–42% of older people in medical inpatient settings
  • This acute brain dysfunction is associated with an increased risk of death and hospital readmissions within 12-months
• In contrast, dementia is a chronic neurodegenerative syndrome with multiple causes, typically characterized by progressive cognitive changes including memory and executive deficits, and functional decline
  • Approximately 40% of hospitalized adults have dementia or other cognitive impairment (Feast et al., 2018)
  • People with dementia are six times more likely to be admitted to hospital with a delirium
  • Dementia is a significant risk factor for hospital-acquired (incidence) delirium