Background:  Parenteral opioids are the standard of care for managing moderate-severe pain or dyspnea when the oral/rectal route is unavailable and/or frequent dose adjustments are needed. However, as death nears, the burden of maintaining intravenous (IV) access, especially in the home setting, can be enormous. Intramuscular (IM) administration of opioids is generally not recommended due to patient discomfort and variable absorption. An alternative opioid delivery route that is supported by major pain societies such as European Association of Palliative Care is the subcutaneous (SQ) route for continuous infusions, Patient Controlled Analgesia (PCA), or intermittent bolus injections.

Drugs: Morphine, hydromorphone (Dilaudid), fentanyl, and sufentanil can all be safely administered as SQ bolus doses or continuous SQ infusion. Methadone SQ infusions have been associated with more frequent local skin irritation; case series report successful use of SQ methadone with frequent site rotation. Some authors recommend the addition of hyaluronidase and dilution of 16 mL of 0.9% saline to reduce the risk of skin irritation from SQ methadone.

Dosing equivalents: Dose conversion ratios between the IV and SQ route for all the above listed opioids are not well established.  Many equianalgesic tables suggest a 1:1 conversion between IV to SQ (e.g., 1 mg IV morphine = 1 mg SQ morphine). 

Pharmacokinetics: SQ infusions can produce the same blood levels as chronic IV infusions.  Bolus injections seem to be rapidly absorbed when given SQ with an onset of action around 5 minutes (faster for fentanyl).  Since they bypass first pass metabolism, their bioavailability is high (78-100%) which is why many experts use 1:1 dosing with IV opioids. There is no data to suggest that cachectic, febrile, or hypotensive patients have problems with drug absorption.

Volume and opioid selection:  The limiting feature of a SQ infusion is the infusion rate; in general, SQ tissue can absorb up to 3 ml/hr.  At low opioid requirements morphine is generally the drug of choice based on availability and cost; a switch to hydromorphone is indicated for a high opioid requirement due its higher intrinsic potency (approximately 4-6 times as potent as morphine), thus the need for a smaller infusion volume. 

Administration: Use a 25- or 27-gauge butterfly needle—place on the upper arm, shoulder, abdomen, or thigh.  Avoid the chest wall to prevent iatrogenic pneumothorax during needle insertion.  The needle can be left indefinitely without site change unless a local reaction develops—typically, patients can keep the same needle in place for up to one week at a time.SQ infusions are typically given via SQ infusion devices which are available in most hospitals or small battery-powered syringe drivers.

Toxicity:  Local skin irritation, itching, site bleeding or infection can occur.  Of these, skin irritation is the most common, managed by a needle site change.

Patient acceptance: Patients readily appreciate the ease of SQ administration as an alternative to IV or IM access.

References

1. Caraceni A, Hanks G, et al.  Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.  The Lancet Oncology 2012; 13: e58-e68.
2. Bruera E, Brenneis C, Michaud M, et al. Use of the subcutaneous route for the administration of narcotics in patients with cancer pain.  Cancer. 1988; 62:407-411.
3. Storey P.  Subcutaneous infusion for control of cancer symptoms. J Pain Symptom Manage. 1990; 5:33-41.
4. Waldman CS, Eason JR, Rambohul E, et al.  Serum morphine levels—a comparison between continuous SQ and IV infusion in post-operative analgesia.  Anaesthesia. 1984; 39:768-771.
5. Mathew P, Storey P. Subcutaneous methadone in terminally ill patients: manageable local toxicity. J Pain Symptom Manage. 1999; 18:49-52.
6. Furst P, Lundstrom S, Klepstad P, Strang P.  Continuous subcutaneous infusion for pain control in dying patients: experiences from a tertiary palliative care center.  BMC Palliative Care 2020; 19:172. https://doi.org/10.1186/s12904-020-00681-3
7. Moulin DE, Kreeft JH, Murray-Parsons N, Bouquillon AI. Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain. Lancet. 1991; 337: 465-468

Version History:  This Fast Fact was originally edited by David E Weissman MD.  2^nd Edition published July 2005; 3^rd Edition May 2015; 4^th edition December 2023.
Conflicts of Interest:  None to report.