Table 3.

The five principles of pain management within the context of advanced CKD

Principle	Description	Specific Considerations in Advanced CKD
“By mouth”	• Oral administration is the safest and therefore usually preferred.	• Patients on HD have easy intravenous access. However, this is to be avoided as the route of administration for analgesics to optimize safety and minimize the risk of abuse and addiction.
	• If ingestion or absorption is uncertain, analgesics need to be given by alternative routes such transdermal, rectal, or subcutaneous.
“By the clock”	• For continuous or predictable pain, analgesics should be given regularly. Additional “breakthrough” or “rescue” medication should be available on an “as needed” basis in addition to the regular dose.	• Some patients with mild-to-moderate pain may achieve adequate pain relief with analgesic dosing post-HD only. An example would be mild-to-moderate neuropathic pain dosed with gabapentin postdialysis.
“By the ladder”	• Pharmacologic management proceeds stepwise from nonopioids to low-dose opioids.	• Careful selection of analgesics with gradual titration is essential (Figure 3).
	• The drug should be used at its full tolerated dose before moving to the next level.	• Sustained-release preparations are generally not recommended, at least until the individual patient’s response to the medication has been observed, due to the narrow therapeutic window in patients with advanced CKD. There is also some evidence for increased mortality with long-acting opioids (34).
“For the individual”	• The “correct” dose for strong opioids is the amount needed to relieve the pain without producing intolerable side effects. Evaluation of benefit and toxicity is essential. • If an individual finds that a particular strong opioid causes unacceptable adverse effects, an alternative must be sought.	• Chronic pain is often experienced in the context of numerous other physical, psychosocial, and spiritual concerns, including end-of-life issues. Close attention to these other issues must not be forgotten if the pain management strategy is to be successful.
“Attention to detail”	• Pain changes over time; therefore, there is the need for ongoing reassessment.	• There are no studies on the long-term use of analgesics in patients with CKD. Careful attention must be paid to efficacy and safety.
	• Side effects of opioids should be explained and managed actively; e.g., constipation and nausea with anticipatory prescribing of a bowel routine (e.g., PEG 3350) and antiemetic (e.g., Zofran 4–8 mg).	• The effect on overall symptom burden, physical function, emotional state, cognition, and QOL should be assessed routinely.

HD, hemodialysis; QOL, quality of life.