Sufentanil Sublingual Tablet (Dsuvia)

Number: 0944

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References


Policy

Aetna considers sufentanil sublingual tablet (Dsuvia) as not medically necessary for the treatment of acute pain severe enough to require an opioid analgesic because the safety for this indication has not been established.

Aetna considers sufentanil sublingual tablet (Dsuvia) experimental and investigational for all other indications because the safety and effectiveness have not been established in the peer-reviewed published medical literature.

Dosage and Administration

Note: Aetna considers Dsuvia as not medically necessary. The dosing recommendations are for informational purposes.

The recommended dosage of Dsuvia (sufentanil) is 30 mcg sublingually, administered by a healthcare provider in a certified medically supervised healthcare setting.  Dsuvia is available in a disposable, single-dose applicator (SDA), as needed with a minimum of 1 hour between doses, not to exceed 12 tablets in 24 hours, with maximum cummulative daily dose of 360 mcg or 12 tablets (12 tablets x 30 mcg/dose).

It is recommended that individuals not eat or drink and minimize talking for 10 minutes after receiving the tablet.

Source: AcelRx Pharmaceuticals, Inc., 2021


Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :

HCPCS codes not covered for indications listed in the CPB:

Sufentanil (Dsuvia) - no specific code :

ICD-10 codes not covered for indications listed in the CPB (not all inclusive):

G89.11 - G89.18 Acute pain

Background

U.S. Food and Drug Administration (FDA)-Approved Indications

  • Dsuvia contains sufentanil, an opioid agonist, and is indicated for use in adults in a certified medically supervised healthcare setting, such as hospitals, surgical centers, and emergency departments, for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

    Limitations of Use:

    • Not for home use or for use in children. Discontinue treatment with Dsuvia before patients leave the certified medically supervised healthcare setting.
    • Not for use for more than 72 hours.
    • Only to be administered by a healthcare provider.
    • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Dsuvia for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:

      • Have not been tolerated, or are not expected to be tolerated,
      • Have not provided adequate analgesia, or are not expected to provide adequate analgesia.

Sublingual sufentanil is available as Dsuvia (AcelRx Pharmaceuticals, Inc) in the United States. Sufentanil is a Schedule II controlled synthetic opioid analgesic that has been marketed for intravenous (IV) and epidural anesthesia and analgesia. The principle therapeutic action of sufentanil is analgesia and sedation, thought to be mediated through opioid-specific receptors throughout the central nervous system (CNS). Like all full opioid agonists, there is no ceiling effect to analgesia.

Sufentanil is 5 to 10 times more potent than its analogue, fentanyl, and 1000 times more potent than morphine (Brooks, 2018). In efforts to offer acute pain management for persons unable to take anything by mouth and have difficulty achieving IV access, sufentanil sublingual tablet was developed. This includes potential uses on the battlefield. For this reason, the Department of Defense (DoD) worked in collaboration with AcelRX Pharmaceuticals on the development of sublingual sufentanil. This opioid formulation was a priority medical product for the Pentagon because it fills an unmet medical need in treating the nation’s soldiers on the battlefield (FDA, 2018). The sufentanil pharmacokinetic profile when delivered sublingually avoids the high peak plasma levels and short duration of action observed with IV administration (AcelRx, 2018a). The high lipophilicity of sufentanil allows it to be administered subligually and achieve a rapid onset of analgesic effect (NICE, 2016).

The National Institute for Health and Care Excellence (NICE) has not published guidance on managing acute post‑operative pain.  Sufentanil was not considered appropriate for a NICE technology appraisal and is not currently planned into any other work program (NICE, 2016).

The NICE website includes an evidence summary which reviewed two placebo-controlled, phase III, randomized clinical trials (RCT) on the safety and efficacy of sufentanil and management of post-operative pain (Jove et al, 2015 following knee or hip arthroplasty, and Ringold et al, 2015 following open abdominal surgery) and 1 randomized phase III study with an active control (IV morphine patient-controlled analgesia [PCA], Melson et al, 2014).  The Jove et al 2015 and Ringold et al 2015 studies found that sufentanil was statistically significantly better at reducing pain intensity over 48 hours following elective major surgery compared with placebo.  Treatment differences for pain intensity scores at 48 hours were 87.6 (p < 0.001) following knee and hip replacement (Jove et al, 2015) and 50.0 (p = 0.001) after open abdominal surgery (Ringold et al, 2015).  However, these outcomes were difficult to interpret and the clinical importance of these findings was unclear.  These 2 RCT showed that participant withdrawals due to inadequate analgesia were statistically significantly less frequent in the sufentanil group compared with placebo (14.3 % compared with 48.1 % of people following hip or knee replacement, p < 0.001 and 17.4 % compared with 31.6 % after open abdominal surgery, p = 0.035, for sufentanil and placebo, respectively).  The studies only included people in relative good health who underwent elective major open abdominal and hip and knee replacement, limiting generalizability to other populations or types of surgery.  People on chronic opioid therapy were excluded from both RCTs (NICE, 2016).

Melson et al (2014) is a randomized, open-label, Phase III, non-inferiority trial that compared sufentanil with IV morphine PCA, for the management of acute post‑operative pain. The treatment difference for the proportion of participants reporting successful pain control achieved the pre‑defined criteria for non‑inferiority of the sufentanil sublingual tablet system compared with morphine at 48 hours (p<0.001, the primary outcome). Sufentanil was also found to be statistically significantly superior to morphine for pain control at 48 hours (p=0.007). Healthcare professionals also reported statistically significantly more successful pain control with sufentanil compared with morphine (p≤0.012 at all time‑points). However, the clinical importance of the difference between the 2 treatments for the primary endpoint was difficult to interpret. The European public assessment report (EPAR) noted that the strength of the endpoint is uncertain because of the subjective nature of the patient assessment, the open‑label setting and limitations around the non‑inferiority design. For secondary endpoints, there was no statistically significant difference between sufentanil and morphine for pain intensity (p=0.569) or pain relief (p=0.055) over 48 hours. Participant withdrawals due to inadequate analgesia were less frequent in the sufentanil group compared with the morphine group (no analysis reported). The investigators reported that, although participants in the sufentanil group used more supplemental morphine than those in the IV morphine PCA group (p<0.001) the difference of 1.6 mg over 48 hours was not clinically meaningful. People on chronic opioid therapy were also excluded from this RCT (NICE, 2016).

“The EPAR reports that, because the primary endpoint was difficult to interpret, the [Committee for Medicinal Products for Human Use] CHMP requested further responder analyses to be performed to determine the clinical relevance of the achieved effect in pain reduction with sufentanil sublingual tablet system from the results of the 3 studies. These post‑hoc analyses for Ringold et al. 2015 and Jove et al. 2015 showed that a clinically important 50% pain reduction was achieved in 37% and 31% of sufentanil participants in these trials compared with 17.5% and 9.6% of placebo participants. The responder analysis for Melson et al. 2014, comparing sufentanil and morphine, determined there was a similar clinically important pain reduction in both treatment groups (30% and 32% of participants, respectively). The CHMP concluded that the 3 phase III studies provide sufficient evidence of the efficacy of sufentanil sublingual tablets in acute post‑operative pain” (NICE, 2016).

On November 2, 2018, AcelRx Pharmaceuticals, Inc., announced the U.S. Food and Drug Administration (FDA) approval of Dsuvia, a single-strength solid dosage form of sufentanil administered sublingually via a single-dose applicator, for the management of acute pain in adults that is severe enough to require an opioid analgesic in a certified medically supervised healthcare setting, such as hospitals, surgical centers, and emergency departments.

Because of the potential for life-threatening respiratory depression due to accidental exposure, Dsuvia (sufentanil) is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) program and is only to be administered by a healthcare professional in a certified medically supervised setting. In addition, Dsuvia must be discontinued prior to the patient leaving the certified medically supervised setting. As with all opioid usage, individuals require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use (FDA, 2018).

The most commonly reported adverse reactions (2 % or greater) were nausea, headache, vomiting, dizziness and hypotension.

Contraindications include significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or suspected gastrointestinal obstruction, including paralytic ileus, and known hypersensitivity to sufentanil or components of Dsuvia (AcelRx, 2018b).

Warnings and precautions include life-threatening respiratory depression in those with chronic pulmonary disease or in elderly, cachectic, or debilitated persons; serotonin syndrome; adrenal insufficiency; severe hypotension; risks of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness (AcelRx, 2018b).

Specialists consulted during the development of the evidence summary noted on the NICE website advised that anyone having major surgery sufficient to need strong opioid analgesia will probably have an IV infusion in situ. In addition, the recommendation for the patient not to eat or drink and to minimize talking for 10 minutes post‑sufentanil dose may be inconvenient, particularly after the first 24 hours post‑surgery. Furthermore, the marketing authorization for sufentanil sublingual tablet system is limited to the management of post‑operative pain for up to 72 hours; therefore, analgesia may potentially have to be altered in patients who need treatment for longer than this (NICE, 2016).

In July 2018, the European Medicines Agency approved sufentanil under the brand name Dzuveo. According to the FDA, Dzuveo and Dsuvia entail a feature that allows the drug to be delivered in a stable form, making it a viable option suited for certain special circumstances where patients may not be able to swallow oral medication, and where access to IV pain relief is not possible, such as soldiers on the battlefield. For that reason, the Department of Defense collaborated with the sponsor on the development of this non-invasive opioid analgesic option that could provide rapid pain relief for soldiers (FDA, 2018).

FDA approval of Dsuvia was based on results from one phase-3, prospective, randomized, double-blind, placebo-controlled trial (SAP301, NCT 02356588) evaluating the efficacy and safety of sufentanil subligual 30 mcg tablet (SST) for the management of pain after ambulatory abdominal surgery.

Minkowitz and colleagues (2017) state that SST has shown to be an effective opioid analgesic in postoperative pain management following abdominal surgery. A total of 161 patients (age 18 to 69 years) scheduled to undergo abdominoplasty, open tension-free inguinal hernioplasty, or laparoscopic abdominal surgery under general or spinal anesthesia that did not include intrathecal opioids during the operation, were randomized to SST (n=107) or placebo (n=54). Patients were dosed with SST 30 mcg or placebo as needed with a minimum of 60 minutes between doses. The primary endpoint was the time-weighted summed pain intensity difference to baseline (SPID) over 12 hours. Secondary endpoints included SPID over 24 and 48 hours, total pain relief, and patient and healthcare professional (HCP) global assessments. Pain scores were recorded for up to 48 hours. SPID 12 was higher (greater pain intensity reduction from baseline) in the SST group compared with placebo (p < 0.001). In the SST group, a greater proportion of patients and HCPs responded "good" or "excellent" on the global assessments compared with placebo (p < 0.001 for both). Approximately 22% of patients in the Dsuvia group and 65% of patients in the placebo group took rescue medication (morphine sulfate 1 mg IV) within the first 12 hours of the treatment phase. There was a numerically, but not statistically, higher incidence of nausea and headache in the SST group. The investigators found that Dsuvia (sufentanil) sublingual tablet demonstrated a statistically greater summed pain intensity difference from baseline over the first 12 hours of the study compared to placebo. In addition, the pain intensity difference from baseline was superior to that of the placebo group within 15 minutes and median meaningful pain relief occurred following a single dose. Thus, they concluded that not only was SST an effective opioid analgesic postoperatively, but SST was also well tolerated with mild-to-moderate side effects, similar to those found in placebo-treated patients.

The study had several limitations that required careful interpretation of results. The study was meant to reflect the typical surgical population; however, patient enrollment was not limited by age and the elderly were under-represented (1.2 percent of patients were older than 65 years). The primary endpoint included a 12-hour evaluation period, as ambulatory care surgery typically results in same-day discharge; thus, this study cannot fully interpret the longer term effects of SST in this population. Nonetheless, the majority of patients were followed for 24 hours. In addition, the sample size was limited, which may also affect the generalizability of the results.  Futhermore, all patients, including those in the SST group, were permitted to receive IV opioids in the operating room as well as IV morphine for rescue analgesia. However, according to Mindowitz and colleagues, SST demonstrated superior pain relief compared with placebo despite this potential confound (Minkowitz et al, 2017). 

Scardino and co-workers (2018) noted that currently many total knee arthroplasty (TKA) protocols rely on multi-modal analgesic protocols with PCA systems that administer opioids through a patient controlled IV infusion pump, in addition to concomitant peripheral nerve blocks (PNBs) and local anesthetics.  Although effective, PCA IV opioids do not provide optimal results with fast track rehabilitation protocols.  In a retrospective, pilot study, these researchers compared the novel sublingual sufentanil PCA system (SSTS) to their standard of care foreseeing continuous femoral nerve block (cFNB) within a multi-modal analgesic in a TKA fast-track protocol.  The study evaluated 95 patients on SSTS (SSTS group) and 87 on cFNB (cFNB/control group) and collected data on numeric rating scores (NRS) for pain from day 1 to 3 after surgery (T1, T2, T3), both at rest (NRS) and during movement (mNRS), patient's ability to walk, need for supplementary analgesia (rescue dose), occurrence of adverse effects, length of hospital stay (LOS), and usability rating for SSTS by both patients and hospital staff.  NRS at rest was lower in the cFNB than in the SSTS group for all 3 days after surgery, whereas mNRS scores were lower in the SSTS group at all time-points measured.  Adverse effects were significantly fewer among patients of the SSTS group (6 % patients) than those of the cFNB (74 % patients) (p <  0.001).  Rescue doses were needed by 5 % of SSTS patients versus 60 % of cFNB.  The fewer adverse events (AEs) and lower pain scores for the SSTS group were associated to a notably better ability to ambulate, with all patients (100 %) of the SSTS group being able to stand and walk for 10 m from T1 on; patients in the cFNB group showed a slower recovery with only 40 % being able to stand and walk on T1, 70 % on T2 and 85 % on T3.  All patients of the SSTS group had a LOS of 4 days (day of surgery plus 3 after) as foreseen by the fast track protocol, in comparison only 36 % of cFNB.  Lastly, patient and nursing staff judged SSTS easy to use.  The authors concluded that their experience suggested that SSTS was a valuable strategy for routine post-operative analgesia following TKA in the context of a multi-modal analgesic approach within the fast-track setting.  Moreover, these researchers stated that these results must be considered as evidence of real-life clinical practice, and could not have the strength of a RCT.  They stated that future targeted randomized studies could further evaluate SSTS by addressing parameters such as “minimally important difference” and “threshold of improvement”, as suggested recently by several working groups on patient reported outcomes on pain.

Hutchins et al (2018) conducted a multicenter, open-label, single-arm study to evaluate sufentanil sublingual tablet 30 mcg (SST 30 mcg) for postoperative pain in an older patient population with comorbidities. Patients with a postoperative pain intensity score greater than or equal to 4 on an 11-point numeric rating scale (NRS) were allowed to enter the study and receive SST 30 mcg as requested for pain (minimum 60-minute redosing interval) over the 12-hour study period. Efficacy was assessed by patient reports of pain intensity on the NRS and a five-point pain relief scale. Safety was monitored throughout the study; plasma sufentanil concentrations were also measured. The primary efficacy endpoint was the time-weighted summed pain intensity difference (SPID) to baseline over 12 hours (SPID12). Of the 140 patients enrolled, 69% were American Society of Anesthesiologists Physical Class II or III, 44% had a body mass index (BMI) ≥30 mg/kg2, and 29% had hepatic and/or renal impairment. Average age was 54.7 years (SD = 9.9 years), and average baseline pain intensity was 6.2 (SD = 1.9). The most common surgeries were abdominal (59%) and orthopedic (20%). The mean SPID12 was 36.0 (standard error of the mean = 2.2); mean scores were similar, regardless of age, sex, race, and BMI. From baseline, mean pain intensity decreased significantly starting 30 minutes postdose, and mean pain relief increased significantly starting 15 minutes postdose, remaining relatively stable through 12 hours (P < 0.001 at each time point). Four (3%) patients discontinued due to inadequate analgesia, and 45 (32%) patients had one or more adverse events that were considered possibly or probably related to the study drug. Mean plasma sufentanil concentrations were generally similar regardless of age, sex, BMI, or organ impairment status. The authors concluded that SST 30 mcg was effective and well tolerated for the management of moderate-to-severe acute postoperative pain.

Leykin and co-workers (2019) stated that gynecological procedures are among the most frequent surgical interventions, and effective post-operative analgesia is associated with improved patient comfort.  Despite the efficacy of neuraxial analgesia, limitations and potential complications have led investigators to seek new strategies for pain relief.  A novel, pre-programmed, non-invasive, hand-held system (SSTS) is approved for use in PCA; however, it has never been used in gynecological procedures.  In a retrospective, observational, case-series study, these researchers examined SSTS for post-operative analgesia.  Data from 42 consecutive patients undergoing open gynecological surgery with Pfannenstiel incision were retrieved from medical charts in 2 Italian hospitals.  The mean age was 49 ± 11 years, and mean body mass index (BMI) was 24.4 ± 4.6 kg/m2.  These investigators reported effective relief on both static and dynamic pain all along the peri-operative period, with good effect on patient's rehabilitation.  Post-operative nausea and vomiting was the most common adverse effect, but the incidence was strongly decreased with medical prophylaxis; SSTS was easy to prepare, use and manage by both patients and care providers.  The authors concluded that SSTS may be an interesting option for post-operative analgesia in gynecologic procedures.  The efficacy in the management of dynamic pain is an interesting outcome that needs to be compared with the other standards of pain management, such as neuraxial techniques.  These researchers stated that rigorous studies are needed to give conclusive evidence, but this was the first report, to the authors’ knowledge, of SSTS use in open gynecologic procedures.  They stated that these preliminary experience encouraged the routine application of SSTS in gynecologic surgery and would help designing future RCTs on the topic.

Noel et al (2020) compared sufentanil sublingual tablet system (SSTS) with oral oxycodone for management of postoperative pain after total knee arthroplasty (TKA) within an enhanced recovery after surgery (ERAS) protocol. The authors conducted a pragmatic, parallel, open label, randomized controlled, trial enrolled 72 adult patients scheduled for TKA under spinal anesthesia following ERAS pathway. In addition to multimodal analgesia, patients received SSTS 15 mcg (SSTS group) or oral oxycodone extended release 10 mg twice daily and oral oxycodone immediate-release 5 mg up to four times daily on demand (Oxy group) to control pain during 48 h postoperatively. The primary endpoint was pain measured using a numeric rating scale at 24 h postoperatively. Time to first mobilization, side effects and patient satisfaction were also recorded. Median pain score at 24 h at rest was 3 for Oxy group vs 2 for SSTS group (p = 0.272) whereas median pain score on movement was 4 vs 3 respectively (p = 0.059). No difference in time to first mobilization was found between the two groups. The method of pain control was judged good/excellent for 83.9% of patients in the SSTS group compared with 52.9% in the Oxy group (p = 0.007). The incidence of nausea was 33% in SSTS group and 9% in Oxy group (p = 0.181). The authors concluded that in complement to ERAS multimodal analgesia, sublingual sufentanil 15 mcg tablet system did not show clinically significant pain improvement compared to oral oxycodone after total knee arthroplasty.

Scardino et al (2020) conducted a prospective observational study to evaluate the efficacy, safety and usability of SSTS for post-surgical analgesia in the real-life setting. Two-hundred-ninety-eight subjects who were undergoing a surgical intervention with a necessity for postoperative analgesia in a hospital setting, were analyzed for SSTS efficacy and safety. The primary end point (success of treatment according to Patient Global Assessment of the Method of Pain Control [PGA] on the second postoperative day) was achieved in 89.8% (p≤0.001 from a presumed value of 60%). During the first 24 hours, pain was below the baseline score (1.2±1.4 after four hours and 1.8±1.6 after 20 hours). The mean impairment in quality of sleep was 1.7±1.7 on postoperative day 1. The overall nurse ease of care (EOC) and nurses' satisfaction questionnaire score was 4.6±0.6, and 4.1±0.9, respectively. The overall patient EOC score was 4.3±0.5; 93.5% patients were extremely satisfied/satisfied with pain control and 93.2% were extremely satisfied/satisfied with the way of the administration. The authors concluded that under a real-life clinical practice setting, SSTS provides effective pain management and is easy to use for patients and nurses.

Leiman et al (2021) state that global assessments and treatment-related adverse events (AEs) were analyzed from patients treated with sufentanil sublingual tablets (SST) 30 mcg for moderate-to-severe acute pain following surgery (abdominal, orthopedic, or other) or in the emergency department (ED). A total of 283 patients were included in the HPGA/PGA analyses. Overall, SST 30 mcg was highly rated by both healthcare professionals and patients across the demographic subgroups. A total of 323 patients were included in the safety evaluation. The majority of patients did not experience any SST-related AEs; however, those that did experienced common opioid-related side effects such as nausea, headache, dizziness, and vomiting. No patients experienced unexpected AEs or required the use of naloxone. The potential limitations of this analysis include the relatively smaller percentage of elderly patients and the fact that opioid-tolerant patients were not enrolled in any of these studies. These data highlight the efficacy and safety of SST in non-opioid tolerant patients, but additional evaluation of real-world data may be warranted in opioid-tolerant patients, as well as in larger numbers of elderly patients. Another limitation associated with the interpretation of these data is based on the fact that these scores were obtained in a controlled clinical trial environment. Because healthcare provider communication with patients is commonly associated with increased patient satisfaction scores, simply being in these clinical trials could have resulted in slightly higher patient global assessments. However, in general, the healthcare professional global assessments were largely consistent with the patient global assessments, suggesting minimal bias in patients treated with SST 30 mcg. Future study should focus on global satisfaction scores after treatment with SST 30 mcg in real-world scenarios.

Zalviso

Zalviso is a drug / device combination product designed to deliver 15 mcg sufentanil via a novel hand-held, pre-programmed, patient-controlled analgesia system. Zalviso is approved in the European Union, it remains an investigational product in the United States (AcelRx, 2022).

Turi and colleagues (2019) stated that the SSTS is a new, pre-programmed, non-invasive, hand-held system for PCA that may allow a faster post-operative recovery compared with standard PCA.  To the authors’ knowledge, SSTS has never been examined in patients undergoing major surgery within an Enhanced Recovery After Surgery (ERAS) protocol.  This observational, retrospective analysis included consecutive patients who underwent elective major abdominal and gynecological surgery.  All patients received the SSTS device once they were fully awake and had a good control of pain at the end of the surgery.  These researchers analyzed changes in pain intensity according to the NRS throughout the treatment as well as its duration, the number of administrations, and possible related AEs.  Patients were also interviewed to assess their quality of sleep and overall satisfaction with the SSTS device.  The study included 308 patients.  Compared to the first SSTS administration, pain intensity decreased from a median NRS of 6 to 0 at day 3, for an overall reduction of 79 %.  Results were already statistically significant at post-operative day 1 (p < 0.01).  Adverse reactions were observed in 62 patients, with nausea being the most frequent (12 %), and in 93 % of patients SSTS was discontinued because it was considered no longer necessary.  Patient satisfaction was high, with 89 % of them judging the device as "easy" or "very easy" to use.  The authors concluded that although the retrospective and observational nature of the study as well as the absence of a comparative group limited the strength of evidence, these findings showed that SSTS was a safe and effective tool for the management of post-operative pain following major abdominal and gynecological surgery within an ERAS protocol.  Moreover, a small proportion of missing data was not available for the final evaluation.  These researchers stated that further large RCTs are needed to confirm these positive preliminary results and to examine the involvement of different healthcare providers in the management of SSTS therapy.

Fabio and associates (2019) noted that SSTS (Zalviso) is a sublingual system for PCA.  These researchers presented a prospective observational study on the use of SSTS for the management of post-operative pain after thoracic surgery.  They examined the efficacy of Zalviso in reducing pain scores and increasing respiratory ability during post-operative period.  A total of 40 patients who underwent video assisted thoracoscopy were included in the study.  All the enrolled patients signed the informed consent were educated to the use of the device.  Pain NRS were recorded at awakening from anesthesia (T0) and during the next hours, both at rest and with cough.  These investigators evaluated the time to obtain a mean NRS value of less than or equal to 3 and difference in pain scores between first and subsequent measurements as the primary outcomes.  The ability to use incentive spirometer and eventual drug adverse effect were evaluated as secondary outcomes.  All patients in recovery room experienced moderate-to-severe pain.  Pain score at rest and coughing decreased to a mean NRS value of less than or equal to 3 (mild pain) respectively after 2 and 6 hours and the pain score difference continued to increase significantly after repeated measurements; 67.5 % of patients resumed the original spirometric ability in pod 1; 9.5 % in pod 2; 12 % in pod 3.  Only 3 patients out of 40 (7.5 %) experienced nausea; 1 patient (2.5 %) had a vomiting episode.  The authors concluded that the findings of this study showed SSTS as an effective option for post-operative pain management in thoracic surgery, improving pain scores and respiratory ability.  Moreover, these researchers stated that this study lacked a control group; and they assumed pain relief and the increase in spirometry performance as the proof of efficacy for SSTS -- this represented a limitation.  They noted that their data were derived from a small sample (n = 40) analysis; RCTs are needed to confirm these findings.

Van Tittelboom et al (2021) conducted an open-label, prospective, randomized control trial to assess the effectiveness and side effects of a patient-controlled sublingual sufentanil tablet system for postoperative analgesia after cardiac surgery and to compare it to a nurse-controlled continuous morphine infusion. The study included a total of 483 cardiac surgery patients of whom 64 patients completed the study. No statistically significant differences were found for baseline characteristics between both groups. All mean numeric rating scale (NRS) pain scores from after extubation until intensive care unit discharge were less than or equal to 3 in both groups. The cumulative mean NRS pain score from 24 hours after extubation (primary outcome) (t = hours after extubation) was significantly different in favor of the morphine group: (t = 0-24) (0.8 [0.7] v 1.3 [0.8]; p = 0.006). Later cumulative mean pain scores were also in favor of the morphine group: (t = 24-48) (0.2 [0.3] v 0.6 [0.5]; p = 0.001) and (t = 48-63) (0.0 [0.0] v 0.1 [0.2]; p = 0.013). The cumulative opioid dose (in milligrams intravenous morphine equivalents) was significantly higher in the morphine group compared with the sublingual sufentanil group (241.94 [218.73] v 39.84 [21.96]; p = 0.0001). No differences were found for the incidences of postoperative nausea and vomiting, sedation, hypoventilation, bradycardia, or hypotension between both groups (secondary outcomes). The authors concluded that despite resulting in statistically significantly higher pain scores, a patient-controlled sublingual sufentanil tablet system offers adequate analgesia after cardiac surgery and reduces opioid consumption when compared with continuous morphine infusion. The authors point out limitations of the study showed postoperative analgesia in the continuous morphine pump (CMP) group was nurse-driven and not patient-controlled. It was the purpose not to alter the present analgesia protocol. A second limitation comprised the high number of excluded patients (greater than 83%) due to the strictness of the exclusion criteria and the high number of patients who declined to participate (n = 93). The exclusion criteria for this feasibility study were stringent to ensure that a homogeneous study population was obtained and confounding was minimized. Because of the high number of excluded patients and the fact that the majority of the included patients (greater than 79%) were men, the results of the present study may not apply to the general cardiac surgery population. Furthermore, this study was not double-blinded. Finally, patient satisfaction and mobility were not included in the authors’ outcome scores. Further research is needed for the evaluation of cost-effectiveness, the difference in length of ICU stay, and patient and staff satisfaction of the use of STSS after cardiac surgery.

Lomangino et al (2022) conducted a single-center randomized prospective study to evaluate sublingual sufentanil in pain management after pulmonary resection. The study explored the use of sublingual sufentanil cartridges (Zalviso) as a noninvasive alternative to postoperative analgesia. Patients who underwent major thoracoscopic lung resection surgery were randomly allocated to receive either intravenous pain management, or patient-controlled analgesia by the Zalviso system. Pain assessment scores were collected for a 72-hour time window, and requests for additional medication due to insufficient pain control were recorded. Of the 80 patients enlisted, 40 were assigned to the Zalviso group and 40 to the control group. The groups were not statistically different from each other. The difference in the mean pain scores reported was statistically significant in the first 24 hours in favor of the Zalviso group (p = .046), and the need for additional pain medication was significantly higher in the control group (p = .004). The authors concluded that patient-controlled analgesia using sublingual sufentanil cartridges can provide effective pain relief for patients undergoing video-assisted thoracic surgery and can reduce the need for additional medication, offering a noninvasive alternative to traditional intravenous therapy.


References

The above policy is based on the following references:

  1. AcelRx Pharmaceuticals, Inc. AcelRx announces FDA approval of Dsuvia. News Release. Redwood City, CA: AcelRx; November 2, 2018a.
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  4. AcelRx Pharmaceuticals, Inc. Zalviso US [website]. Redwood City, CA: AcelRx; 2022. Available at: https://www.acelrx.com/products/zalviso-us. Accessed June 15, 2022.
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