Developments in combined analgesic regimens for improved safety in postoperative pain management

ABSTRACT

Introduction: Fixed-dose combination analgesic regimens may be similarly effective to opioid monotherapy but with potentially less risk. A number of individualized combination regimens can be created, including nonopioid agents such as acetaminophen and nonsteroidal anti-inflammatory drugs, opioids, and adjunctive agents such as gabapentin, pregabalin, and muscle relaxants.

Areas covered: When such combinations have a synergistic effect, analgesic benefits may be enhanced. Many combination analgesic regimens are opioid sparing, which sometimes but not always results in reduced opioid-associated side effects. Safety concerns for all analgesics must be considered but postoperative analgesia is typically administered for a brief period (days), reducing risks that may occur with prolonged exposure.

Expert opinion: Judiciously considered combination analgesic regimens can be effective postoperative analgesics that reduce opioid consumption without compromising pain control, which are important factors for patient recovery and satisfaction. The specific combinations used must be based on the patient, the type and duration of the surgical procedure, and complementary mechanisms of action of the agents used. In opioid-sparing combination analgesic regimens, the short-term use of small doses of opioids in this setting may be helpful for appropriate patients.

KEYWORDS:

• Acetaminophen
• analgesia
• combination analgesia
• fixed-dose combination analgesics
• nsaids
• opioid-sparing effects
• opioids
• postoperative pain
• postsurgical pain

Article highlights

• Inadequate analgesia in the postoperative period is associated with increased morbidity, mortality, delayed recovery, extended length of stay, delayed ambulation, patient distress, patient dissatisfaction, and may be a gateway to chronic pain syndromes.

• Multimodal analgesic regimens combine analgesic agents with different mechanisms of action to better relieve pain and spare the use of opioids. Multimodal agents include: acetaminophen (paracetamol), nonsteroidal anti-inflammatory drugs, opioids, gabapentinoids, ketamine, lidocaine, and adjuvants such as muscle relaxers.

• Multimodal analgesic combinations may be two nonopioid agents, an opioid plus a nonopioid, and opioid plus opioid regimens. Some are available as a fixed-dose combination products.

• Novel products such as fixed-dose combinations of muscle relaxant plus aspirin plus caffeine are being developed as well as biphasic opioid products that combine NSAID with both immediate-release with extended-release opioids.

• Postoperative pediatric patients are a special population that historically had been administered codeine or tramadol, both of which are no longer recommended by the Food and Drug Administration or the European Medicines Agency due to the risk of serious even potentially life-threatening adverse events.

Declaration of interest

JV Pergolizzi is a principal at Neumentum, Enalare, and NEMA Research, Inc., and has received honoraria from various pharmaceutical companies involved in analgesic research and other areas. RB Raffa is a previous employee of Johnson & Johnson and has re (1986 – 1996) prior to a teaching career in academia and has received research support or honoraria from pharmaceutical companies involved in analgesics research and related areas (e.g., recently BDSI, CerSci, Grünenthal, Insys, NEMA, Salix, and US WorldMeds, etc.) – but he receives no remuneration based on sales of any product. He is a cofounder of CaRafe Drug Innovation and Enalare, and is the consultant CSO of Neumentum, companies involved in drug discovery and development. He declares that he has no financial interest or conflict of interest in the subject matter of this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.