Hypodermoclysis is a relatively simple method of fluid and drug administration that involves infusing a liquid into the SC tissue for distribution throughout the body. It is often a preferred method in the palliative-care setting where obtaining IV access may be very difficult; when patients are no longer able to take anything by mouth; or when a rectal dosage form is not available or is considered culturally unacceptable.

However, information on this route of administration (ROA) is unavailable for most medications. Among the drugs for which this ROA has been utilized include morphine, haloperidol, furosemide, and hydromorphone. Data are lacking on the SC administration of acetaminophen, a medication that is widely used among older adults and those in palliative care.

Researchers conducted an experimental study to assess the efficacy and safety of an acetaminophen SC infusion in the treatment of pain and fever and to characterize the pharmacologic profile (i.e., time course of effects) of this ROA in geriatric and palliative-care patients. Patients were enrolled in the study if they experienced pain or fever that required the administration of acetaminophen in the absence of an IV line.

The primary endpoint of this trial was a mean change in body temperature at 60 minutes, with a mean change of fewer than 0.5 degrees Celsius considered ineffective and a pain score with a minimally clinically important difference of 2 on a numerical evaluation pain scale from 0 to 10. In patients who were noncommunicative, the Algoplus Pain Scale was utilized and the effectiveness was defined as a decrease in score from >2/5 to <2/5. The occurrence of adverse drug events was also assessed. Changes in pain scores and body temperature at 30 minutes and 180 minutes postintervention were secondary outcomes.

To avoid confounding, a specific SC route was established solely for the administration of the acetaminophen; all other medications were administered via an alternative site. The SC route was installed at least 6 hours prior to the first dose of acetaminophen. One gram (1 gram/100 mL) of acetaminophen was infused SC at a dose of 5 mL/minute for 20 minutes. A limit of three doses per day or 21 doses per week was established; following the 21st dose the patient was discontinued from the study.

Thirty-one patients were included in the clinical trial, with a total of 120 doses of SC acetaminophen administered. The mean decrease in pain based on the numerical evaluation pain scale was 5.35 points, and the average temperature decrease was 0.79 degrees Celsius at 60 minutes. At 180 minutes, pain decreased by 6.23 points and temperature by 1.35 degrees Celsius.

Assessing pain using the Algoplus scale, SC acetaminophen was 2.86% effective at 30 minutes in reducing pain scores to less than 2/5, but this increased to 80% at 60 minutes and 88% at 180 minutes. Overall, 75% of patients experiencing pain, and 67% of those who had a fever demonstrated clinically significant improvement at 60 minutes (95% CI were 47.62-92.73 and 38.38-88.17, respectively).

While the analgesic effects may have been somewhat delayed, with only 20% experiencing significant relief at 30 minutes, the effect when it occurred results in analgesia at 180 minutes in 87.5% of the study population. A similar pattern was seen for fever relief, with only 27% experiencing a clinically significant reduction in their temperature after 30 minutes, but this increased to 87% at 3 hours (95% CI, 7.79-55.6 and 59.54-98.63, respectively). Acetaminophen was not effective in one patient with paraneoplastic fever.

Adverse effects were minor, with local edema occurring in 51.6%, but this decreased to only 6.5% at 3 hours.

This study, although preliminary, offers insight into the SC administration of acetaminophen in a setting where administration options are limited. An advantage of this ROA is that it avoids the gastrointestinal-slowing effects of concomitant medications such as opioids and anticholinergics. It also offers alternative access for patients who do not have an IV line in place and for whom rectal administration is culturally inacceptable or who have anorectal disease. Pharmacists should be familiar with this ROA and can assist in identifying medications and patients for whom this would be most appropriate.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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