Multimodal analgesia for perioperative pain

The current armamentarium of analgesic drugs and techniques for the management of postoperative pain continues to grow at a rapid rate. However, the effective treatment of acute postsurgical pain still poses unique challenges for practitioners.(1)

An increasing number of ever more complex operations are being performed on an outpatient basis, in which the use of conventional opioid-based intravenous (IV) patient- controlled analgesia (PCA) and central neuroaxial (spinal and epidural) analgesia are not practical techniques for pain management.

This expanding patient population requires a perioperative analgesic regimen that is highly effective, has minimal side effects, is intrinsically safe and can be easily managed away from the hospital or surgical centre.(2)

The adequacy of postoperative pain control is one of the most important factors in determining when a patient can be safely discharged from a surgical facility. It also has a major influence on the patient’s ability to resume their normal activities of daily living.(3)

Perioperative analgesia has traditionally been provided by opioid analgesics. However, extensive use of opioids is associated with a variety of perioperative complications (e.g. ventilatory depression, drowsiness and sedation, postoperative nausea and vomiting (PONV), pruritus, urinary retention and ileus, constipation), which can contribute to a delayed hospital discharge.(4)

In addition, intraoperative use of large bolus doses or continuous infusions of potent opioid analgesics may actually increase postoperative pain as a result of their rapid elimination and/or the development of acute tolerance.(5)

Use of partial opioid agonists (e.g. tramadol) are also associated with increased side effects (e.g. nausea, vomiting or ileus) and patient dissatisfaction compared with both opioid(6) and nonopioid(7) analgesics. Therefore, anaesthesiologists and surgeons are increasingly turning to nonopioid analgesic techniques as adjuvants for managing pain during the perioperative period.

Local anaesthetic techniques

The routine use of peripheral nerve blocks and wound infiltration with long-acting local anaesthetics as an adjuvant to local, regional and general anaesthetic techniques can improve postoperative pain management after a wide variety of surgical procedures.(4)

When administered before the start of surgery, these simple techniques can also decrease the anaesthetic and analgesic requirements during the operation, as well as reduce the need for opioid- containing analgesics in the postoperative period.

More effective pain relief in the early postoperative period as a result of the residual sensory block produced by local anaesthetics facilitates the recovery process by enabling earlier ambulation and discharge home (i.e. “fast-track” recovery).(8,9)

In addition, use of local anaesthetic-based techniques for preventing pain can decrease the incidence of PONV because of their opioid-sparing effects. However, as reported by Moiniche et al,(10) these techniques are most effective for superficial procedures, and the duration of analgesia is only six to eight hours.

Although local anaesthetic supplementation clearly decreases the severity of incisional pain in the early postoperative period, many patients still experience significant pain when the local anaesthetic effect wears off. Therefore, continuous and/or intermittent perfusion of the surgical wound (or peripheral nerve) with local anaesthetic solutions has been “reintroduced” as a way of extending local anaesthetic-induced incisional pain relief into the postoperative period.

In a recent study by White et al,(11) infusion of 0.5% bupivacaine (4ml/h) at the median sternotomy site reduced postoperative pain and the opioid analgesic requirement after cardiac surgery. As a result of the opioid-sparing effect, these patients more rapidly recovered bowel and bladder function. Similarly, wound instillation with 0.2% ropivacaine (5ml/h) was effective in improving pain control after spine fusion surgery.(12)

These continuous local anaesthetic infusion techniques can be modified to allow for patient-controlled local anaesthetic administration after surgery.(13)

Although improved pain control can be achieved after orthopaedic procedures by continuously infusing local anaesthetic solutions,(14,15) the availability of longer-acting local anaesthetic suspensions and “delayed-release” formulations containing liposomes or polymer microspheres may minimise the need for continuous infusion catheter delivery systems in the future.

Nonsteroidal anti-inflammatory drugs

Early reports suggested that parenteral nonsteroidal anti-inflammatory drugs (NSAIDs) possessed analgesic properties comparable to those of opioid analgesics,(16) but without opioid-related side effects.(17) Compared with the partial opioid agonist tramadol, diclofenac produced better postoperative pain relief with less side effects after cardiac surgery.(7) When administered as an adjuvant during outpatient anaesthesia, ketorolac was associated with improved postoperative analgesia and patient comfort compared with the potent opioid analgesic fentanyl.

In an effort to minimise the potential for operative site bleeding complications, as well as gastrointestinal damage, associated with classic nonselective NSAIDs such as ketorolac and diclofenac, the more highly selective cyclooxygenase (cox)-2 inhibitors are increasingly being utilised as nonopioid adjuvants for minimising pain during the perioperative period.

The early clinical studies in surgical patients evaluated the use of celecoxib, rofecoxib and valdecoxib for preventative analgesia when administered for oral premedication.(18) Although this topic has already been extensively reviewed in the literature,(19,20) additional comparative clinical studies are clearly needed to define the advantages of cox-2 inhibitors over existing nonselective NSAIDs in the perioperative period.

Ketamine and N-methyl-d-asparate antagonists

Ketamine is a unique IV anaesthetic with analgesic-like properties that has been used for both induction and maintenance of anaesthesia, as well as an analgesic adjuvant during local anaesthesia.(21) A single bolus dose of ketamine (0.1–0.15mg/kg IV) during surgery has been reported to produce significant opioid-sparing effects after painful orthopaedic and intra-abdominal procedures, without increasing the incidence of side effects.(22) Ketamine (0.1mg/kg intramuscular) reduced swallowing-evoked pain after tonsillectomy procedures in children receiving a multimodal analgesic regimen.(23)

Dextromethorphan, another N-methyl-D-asparate (NMDA) receptor antagonist that is known to inhibit windup and NMDA-mediated nociceptive responses in dorsal horn neurons, has been alleged to enhance opioid, local anaesthetic and NSAID-induced analgesia. Premedication with dextromethorphan (150mg per oral) reduced the PCA morphine requirement in the early postoperative period after abdominal hysterectomy procedures.(24)

alpha(2)-adrenergic agonists

The alpha(2)-adrenergic agonists clonidine and dexmedetomidine produce significant anaesthetic and analgesic-sparing effects.(25–28) For example, oral–transdermal clonidine administered perioperatively was found to produce a 50% decrease in the PCA morphine requirement after radical prostatectomy surgery.(25) Clonidine has also been found to improve and prolong central neuroaxis analgesia,(26) peripheral nerve blocks(27) and intra-articular analgesia(28) when administered as part of multimodal analgesic regimens.

Miscellaneous nonopioid compounds

A diverse array of nonopioid pharmacological compounds used during the perioperative period have been alleged to possess analgesic-like properties (e.g. adenosine, droperidol,(29) magnesium and neostigmine). Gabapentin, an anticonvulsant that has proven useful in the treatment of chronic neuropathic pain, may also be a useful adjuvant in the management of acute postoperative pain.(30)

Conclusion

Opioid analgesics will continue to play an important role in the management of moderate-to-severe pain after surgical procedures. However, the adjunctive use of nonopioid analgesics will likely assume a greater role as minimally invasive (“keyhole”) surgery continues to expand in the future.(2,4) In addition to the local anaesthetics, NSAIDs, cox-2 inhibitors, acetaminophen, ketamine, dextromethorphan, alpha(2)-agonists, gabapentin, magnesium and neostigmine may all prove to be useful adjuncts in the management of postoperative pain.(31)

Adjunctive use of droperidol(29) and glucocorticoid steroids(32) also appear to provide beneficial effects in the postoperative period. Use of analgesic drug combinations with differing mechanisms of action as part of a multimodal regimen will provide additive (or even synergistic) effects with respect to improving pain control, reducing the need for opioid analgesics and facilitating the recovery process.(33)

Safer, simpler and less costly analgesic drug delivery systems are needed to provide cost-effective pain relief in the postdischarge period as more “major” surgery is performed on an ambulatory (or short-stay) basis in the future.

Authors

Paul F White PhD MD FANZCA
Professor and Holder of the Margaret Milam McDermott Distinguished Chair
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
E:[email protected]

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