Sublingual, transdermal and intravenous patient-controlled analgesia for acute post-operative pain: systematic literature review and mixed treatment comparison.
OBJECTIVE
To conduct a systematic literature review (SLR) and quantitative analysis to assess the comparative efficacy and safety of the sufentanil sublingual tablet system (SSTS) against other available patient controlled analgesia (PCA) options for post-operative analgesia.


METHODS
An SLR was conducted for studies published between 2004 and 2016. Due to study heterogeneity, subgroup analyses were conducted controlling for differences in imputation methods for missing values, baseline pain severity, and type of surgery. Where sufficient data was available, a mixed treatment comparison (MTC) was performed.


RESULTS
The MTC and subgroup analyses used 13 studies. In direct meta-analysis, there was a statistically significant difference in favor of SSTS compared with intravenous (IV) PCA (morphine) at 24 hours for the patient global assessment (PGA) scores of "good" or "excellent". For the Pain Intensity Score, there were numerical but not statistically significant differences in favor of the SSTS versus IV PCA (morphine) and the patient controlled transdermal system (PCTS) (fentanyl) in the MTC at 6 hours (standardized mean difference -0.27 [credible interval -2.78, 2.09] and -0.36 [-3.89, 3.03], respectively). The onset of pain relief was earlier with the SSTS versus IV PCA (morphine) as shown by the Pain Intensity Difference. Likewise, the onset was earlier compared with PCTS (fentanyl) where data was available. There was a significant difference in favor of SSTS compared with IV PCA (morphine) and with PCTS (fentanyl) for any adverse event, and numerical improvements for withdrawals due to adverse events.


CONCLUSIONS
This meta-analysis shows that SSTS is an option for non-invasive management of moderate-to-severe post-operative pain which can be more effective, faster in onset and better tolerated than IV PCA (morphine) and PCTS (fentanyl).
a Grünenthal GmbH , Aachen , Germany.
Pablo
P
Katz
b Parexel International , Chandigarh , UT , India.
Shweta
S
Takyar
c AcelRx Pharmaceuticals , Redwood City , CA , USA.
Pamela
P
Palmer
a Grünenthal GmbH , Aachen , Germany.
Hiltrud
H
Liedgens
D059787:Acute Pain / Q000188:drug therapy; D000279:Administration, Cutaneous; D000286:Administration, Sublingual; D016058:Analgesia, Patient-Controlled / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D005283:Fentanyl / Q000008:administration & dosage; D006801:Humans; D009020:Morphine / Q000008:administration & dosage; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D017409:Sufentanil / Q000008:administration & dosage*; D013607:Tablets / Q000627:therapeutic use; D057968:Transdermal Patch
D000701:Analgesics, Opioid; D013607:Tablets; D009020:Morphine; D017409:Sufentanil; D005283:Fentanyl
Administration; analgesia; analgesics; cutaneous; meta-analysis; opioid; pain; patient-controlled; post-operative; sufentanil; systematic literature review