Sufentanil Sublingual Tablet System Holds Promise as Alternative to I.V. PCA

ASA Monitor 09 2017, Vol.81, 22-24.

The following article was developed by ASA to introduce the ASA Monitor readership to the latest technology and advancements in the specialty. It should not be construed as an endorsement by ASA of any specific product or service.

Despite continued improvements in pain treatment, moderate to severe postoperative pain remains the focus of ongoing research in medicine. A retrospective study in 2003 by Apfelbaum et al. indicated that 35 percent of patients experienced severe postoperative pain at discharge and 22 percent reported severe pain two weeks post-discharge.¹  A 2015 study by Buvanendran et al. found that 12 percent of surgical patients reported severe pain at discharge, with 13 percent reporting severe pain after two weeks.² Although these numbers point to an encouraging improve-ment, the incidence of postsurgical pain remains unacceptably high. Postsurgical pain leads to overall decreased patient satisfaction, decreased mobility, increased costs of care, development of chronic pain and a host of other complications.

As evidenced by the attention and resources given to the current opioid abuse crisis, pain overall has perhaps never been given such intense consideration by all strata of stakeholders, from the medical community to the lay press. Inadequate pain control is no longer considered acceptable in our society.³  And patient satisfaction ratings in regard to pain care are becoming increasingly important for meeting or surpassing quality benchmarks generated by CMS.

Improvements in postsurgical pain strategies will be eagerly embraced by clinicians and patients alike. Alternatives to I.V. patient-controlled analgesia (PCA) may be of particularly high interest considering the well-documented potential for errors and side effects associated with I.V. PCA.⁴ 

The sufentanil sublingual tablet system (SSTS) is a promising noninvasive drug delivery system undergoing a phase 3 clinical trial for approval by the FDA. The device is currently approved in Europe for managing moderate to severe postoperative pain in adults. A manufacturer-funded study in 2015 looked at the efficacy and safety of the SSTS after total hip or knee arthroscopy, indicating that this portable and easy-to-use device could become an effective tool for managing moderate to severe pain after surgery and, if approved in the U.S., a possible alternative to I.V. PCA.⁵ 

SSTS is a PCA system that dispenses 15-ug sublingual tablets of sufentanil on-demand with 20-minute lock-out intervals. The drug can only be dispensed by the patient, who activates a radio-frequency identification thumb tag. The prospective, multicenter, double-blinded, randomized controlled trial followed 315 patients treated with SSTS and 104 who were given placebo with the same device. Study participants were ASA Physical Status 1-3 patients undergoing primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia without intrathecal opioids.

Patients who indicated a pain intensity score of 5 or higher on an 11-point rating scale (0-10) were allowed to self-administer a first dose after discharge from the PACU. Patient pain scores were recorded up to 72 hours after surgery. The primary endpoint of the study was the time-weighted summed pain intensity difference (SPID) to baseline after 48 hours (SPID48), which was derived from patients’ pain intensity scores immediately before dosing and a five-point score demonstrating pain relief, from 0 (no relief) to 4 (complete relief).

Notable study findings include:

• ■ SSTS provided superior pain control in the first 48 hours after the initial dose – SPID48 scores were significantly higher in the SSTS group compared to placebo.
• ■ SPID and total pain relief scores were higher at all time points from two to 72 hours.
• ■ More patients in the placebo group (48 percent) compared to the SSTS group (14 percent) discontinued the study because of inadequate pain control.
• ■ In the placebo group, 73 percent of patients required rescue I.V. morphine compared to 51 percent in the SSTS group.
• ■ Overall patient satisfaction scores were significantly higher in the SSTS group.
• ■ The percentage of patients and nurses who rated pain treatment in the SSTS group as “Good” or “Excellent” was higher than in the placebo group.

Safety findings included a higher incidence of nausea (34.9 percent vs. 22.1 percent) and pruritis (4.8 percent vs. 0 percent) in the SSTS group compared to the placebo group.

Limitations of the study included the fact that the majority of participants were Caucasian women, so applicability of the results to other demographics is not known. And since the comparison group was placebo, the study did not provide information concerning the effectiveness and safety of the SSTS compared to I.V. PCA or other forms of postsurgical pain treatment. Also, the 14 percent rate of withdrawal from the study seen in the SSTS group was high. One reason might have been that since patients were unaware of their group assignment, they might have mistakenly reported inadequate pain relief as a reflection of their belonging to the placebo group. The fact that other modes of pain relief, other than rescue analgesia of no more than morphine 2 mg every hour, were not allowed could have contributed to study with-drawal as well. However, since the use of multimodal strategies after major orthopedic surgery has become standard at many institutions, utilization of other strategies alongside SSTS would likely improve pain control.⁶ 

In conclusion, the SSTS is a preprogrammed and non-invasive investigational system that has been shown to effectively manage moderate to severe pain in the hospital. As it allows patient control over dosing, it could help to improve patient satisfaction over nurse-administered analgesia. If approved in the U.S., it could become an effective addition to analgesic therapies for moderate to severe postoperative pain.

A review of research on the SSTS can also be found in Volume 33A of ASA’s SEE program.

References:

Apfelbaum JL, Chen C, Mehta SS, Gan TJ . Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003; 97(2):534–540.

Buvanendran A, Fiala J, Patel KA, Golden AD, Moric M, Kroin JS . The incidence and severity of postoperative pain following inpatient surgery. Pain Med. 2015;16(12):2277–2283.

Parvizi J . Pain management following total joint arthroplasty: making strides. J Bone Joint Surg Am. 2012;94(16):1441.

Hicks RW, Sikirica V, Nelson W, Schein JR, Cousins DD . Medication errors involving patient-controlled analgesia. Am J Health Syst Pharm.2008;65(5):429–440.

Jove M, Griffin DW, Minkowitz HS, Ben-David B, Evashenk MA, Palmer PP . Sufentanil sublingual tablet system for the management of postoperative pain after knee or hip arthroplasty: a randomized, placebo-controlled study. Anesthesiology. 2015;123(2):434–443.

American Society of Anesthesiologists. SEE 2017, Volume 33A, Item 39:108–110.