Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways

  • Mingjuan Tan
  • Lawrence Siu-Chun Law
  • Tong Joo GanEmail author
Review Article/Brief Review



The optimal management of postoperative pain using multimodal analgesia is a key component of Enhanced Recovery After Surgery (ERAS). Pain has adverse clinical implications on postoperative recovery, including prolonging the time to recovery milestones and length of hospital stay. Moreover, the ubiquity of opioids in postoperative analgesic regimens results in adverse effects, such as sedation, postoperative nausea and vomiting, urinary retention, ileus, and respiratory depression, which can delay discharge. Thus, multimodal analgesia, i.e., the use of more than one analgesic modality to achieve effective pain control while reducing opioid-related side effects, has become the cornerstone of enhanced recovery. The purpose of this review is to address the analgesic techniques used as part of multimodal analgesic regimens to optimize postoperative pain control and to summarize the evidence for their use in reducing opioid requirements and side effects.

Principal findings

There is a wide variety of analgesic techniques available for multimodal postoperative analgesia. These modalities are divided into pharmacological and non-pharmacological techniques. Systemic pharmacological modalities involve opioids and non-opioids such as acetaminophen, non-steroidal anti-inflammatory drugs, N-methyl-D-aspartate receptor antagonists, anticonvulsants (e.g., gamma-aminobutyric acid analogues), beta-blockers, alpha-2 agonists, transient receptor potential vanilloid receptor agonists (capsaicin), and glucocorticoids. Other pharmacological modalities include central neuraxial techniques, surgical-site infiltration, and regional anesthesia. Evidence supports the use of these pharmacological techniques as part of multimodal analgesia, but each has its own advantages and specific safety profile, which highlights the importance of selecting the appropriate analgesics for each patient. Adjunctive non-pharmacological techniques include acupuncture, music therapy, transcutaneous electrical nerve stimulation, and hypnosis. There is mixed evidence regarding such techniques, although a lack of harm is associated with their use.


There are continuing advancements in multimodal analgesic techniques; however, postoperative pain in general continues to be undermanaged. Furthermore, a continuing challenge in multimodal pain research related to ERAS is the difficulty in carrying out randomized trials to determine the relative importance of any one component, including analgesia.


Bupivacaine Dexmedetomidine Enhance Recovery After Surgery Levobupivacaine Music Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Optimiser le contrôle de la douleur pour faciliter la Récupération rapide après la chirurgie



La gestion optimale de la douleur postopératoire à l’aide d’une analgésie multimodale est un élément essentiel de la Récupération rapide après la chirurgie (RRAC). La douleur a des implications cliniques préjudiciables sur la récupération postopératoire, notamment l’allongement du délai des étapes de récupération des éléments de référence et de la durée de séjour à l’hôpital. De plus, l’omniprésence des opioïdes dans les schémas thérapeutiques d’analgésie postopératoire a pour conséquence des effets secondaires, tels que la sédation, les nausées et vomissements postopératoires, la rétention urinaire, l’iléus et la dépression respiratoire qui peuvent retarder le congé. Ainsi, l’analgésie multimodale, c’est-à-dire l’utilisation de plus d’une modalité analgésique pour obtenir un contrôle de la douleur tout en réduisant les effets secondaires liés aux opioïdes, est devenue la pierre angulaire de la récupération rapide. L’objet de cette synthèse est de revoir les techniques analgésiques utilisées dans le cadre des schémas thérapeutiques d’analgésie multimodale pour optimiser le contrôle de la douleur postopératoire et résumer les données probantes concernant leurs effets sur la réduction du besoin en opioïdes et des effets secondaires.

Constatations principales

Différentes techniques analgésiques peuvent être utilisées pour l’analgésie multimodale postopératoire. Ces modalités sont divisées en techniques pharmacologiques et non pharmacologiques. Les modalités pharmacologiques systémiques font appel aux opioïdes et aux non-opioïdes, tels que l’acétaminophène, les anti-inflammatoires non stéroïdiens, les antagonistes du récepteur du N-méthyl-D-aspartate, des anticonvulsants (par exemple, les analogues de l’acide gamma-aminobutyrique), les bêta-bloqueurs, les agonistes alpha-2, les agonistes du récepteur vanilloïde à potentiel de récepteur transitoire (capsaïcine) et les glucocorticoïdes. Les autres modalités de traitements pharmacologiques incluent les techniques neuraxiales centrales, l’infiltration du site chirurgical et l’anesthésie régionale. Des données probantes soutiennent l’utilisation de ces techniques pharmacologiques dans le cadre de l’analgésie multimodale, mais chacune a ses propres avantages et son propre profil d’innocuité, ce qui souligne l’importance de la sélection des analgésiques appropriés pour chaque patient. Les techniques non pharmacologiques d’appoint incluent l’acuponcture, la musicothérapie, la stimulation nerveuse électrique transcutanée et l’hypnose. La force des données probantes concernant ces techniques est mitigée, bien que leur utilisation soit associée à une absence d’effet néfaste..


Les progrès des techniques d’analgésie multimodales sont en constante évolution. Toutefois, d’une manière générale, la douleur postopératoire continue à être insuffisamment traitée. En outre, la difficulté à mener des essais randomisés pour déterminer l’importance relative de l’un des composants, y compris de l’analgésie, reste un défi constant de la recherche sur le contrôle multimodal de la douleur dans le cadre des programmes de RRAC.


In recent years, there has been an increasing emphasis on ambulatory and short-stay surgeries, with almost a threefold increase in visits to ambulatory surgery centres in the United States from 1996-2006, nearing 14.9 million. Nevertheless, the rate of visits to hospital-based surgery centres has remained largely unchanged during the same period.1 Pain control modalities have been studied in more invasive operations, such as major abdominal surgery, where Enhanced Recovery After Surgery (ERAS) programs have addressed the key factors that delay postoperative recovery and prolong hospital stay. These include parenteral opioid analgesia, the need to maintain intravenous fluids due to gut dysfunction, and bed rest secondary to lack of mobility.2 The knowledge acquired from studying these pain control modalities has facilitated improvements in pain control to accelerate recovery and discharge in the short-stay and ambulatory population.

Enhanced recovery pathways vary amongst institutions but include key elements such as hemodynamic optimization, early oral intake with prokinetic agents, early ambulation, and standardized multimodal pain control regimens.3 While some maintain that there is the need for more research on the efficacy of ERAS protocols,4 thus far, evidence has shown that such protocols significantly reduce postoperative hospital stay without increasing morbidity and mortality. This results in a decrease in hospital costs and an increase in patient satisfaction.3,5,6

A key component of enhanced recovery is optimal management of acute postsurgical pain, particularly given its adverse clinical implications on patient recovery. Firstly, pain itself prolongs time to recovery milestones and delays discharge after surgery.7 Recovery milestones, including functional parameters such as mobilization from bed and ambulation, both with and without a walking frame, are particularly pertinent in orthopedic and spine surgeries as inadequate pain management impedes postoperative rehabilitation and achievement of such milestones.8 Secondly, opioids are the mainstay of most postoperative analgesic regimens. While they are effective even for severe pain, their use prolongs hospital length of stay (LOS) due to dose-related side effects such as respiratory depression, sedation, postoperative nausea and vomiting (PONV), urinary retention, and ileus.9 Indeed, analgesic-related side effects are a concern for patients to the extent that some patients would choose less effective analgesia as a trade-off for fewer side effects.10 Moreover, patients with documented opioid-related adverse events were found to incur higher adjusted mean costs ($22,077 USD vs $17,370 USD; P < 0.0001), longer mean LOS (7.6 vs 4.2 days; P < 0.0001) and increased readmission rates (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 to 1.09).11 Lastly, opioids may not be particularly effective in controlling postoperative pain as they provide an initial analgesic effect but subsequently cause rapid development of tolerance and a reduction in pain threshold (i.e., opioid-induced hyperalgesia).12,13

Given the importance of effective analgesia and the significance of opioid-related side effects, multimodal postoperative analgesia has become a key element of ERAS pathways. Multimodal analgesia is defined as the use of more than one modality of pain control to achieve effective analgesia while reducing opioid-related side effects.14 This may involve systemic administration of different analgesics with separate mechanisms of action or concurrent application of regional and systemic analgesia (e.g., paravertebral block with non-opioid analgesia). The goals of multimodal analgesia are to reduce postoperative pain, minimize opioid-related adverse effects, and ultimately, to accelerate postsurgical recovery and decrease LOS.

There are many exciting developments in the management of acute postoperative pain regarding both routine clinical practice and the use of more novel techniques. Despite increased awareness and clinical advancements, however, there has been limited improvement in control of post-surgical pain.15 A recent study found that more than 80% of patients still experience pain after surgery, and 75% of those have moderate to extreme pain in the immediate postoperative period. It is therefore hardly surprising that post-surgical pain is the patient’s greatest concern before surgery.15 Hence, there is paramount importance in harnessing multimodal techniques to achieve effective analgesia. With an emphasis on multimodal analgesia, this review covers techniques to optimize pain management and thus facilitate enhanced post-surgical recovery. Current evidence regarding various multimodal analgesic regimens is also reviewed, including their impact on reducing opioid requirements and their adverse effects. The papers selected for this review present clinically relevant evidence pertinent to the ever evolving field of multimodal analgesia.


Multimodal analgesia modalities are subdivided into pharmacological (central neuraxial, regional, local, and systemic analgesia) and non-pharmacological techniques, and their recent advances are discussed below. The Table 1 summarizes the evidence from key reviews and meta-analyses on analgesic techniques in various common surgeries.
Table 1

Evidence-based ERAS regimens incorporating multimodal analgesia

Surgery type

Preoperative Analgesia

Intraoperative Analgesia

Postoperative Analgesia


Open or laparoscopic colorectal surgery

(Miller et al. 2014)117


- Thoracic epidurals rarely performed due to enoxaparin thromboprophylaxis


- Not standardized; intravenous opioids often administered


- Not standardized

ERAS Benefits

- Significantly less total postoperative morphine equivalents (mg) required [median (range) 29.8 (10-85) mg vs 120 (69-267) mg]

- Significantly lower average (SD) pain scores throughout days 0 to 5 [3.3 (1.9) vs 4.9 (2.1)]

- Significantly shorter median hospital LOS (5 vs 7 days)

ERAS Disadvantages

- None


- Thoracic epidurals placed at the T8-T10 level in preoperative holding area, together with small doses of midazolam and fentanyl to facilitate epidural insertion and maintain patient comfort

(Thromboprophylaxis with subcutaneous heparin 5,000 IU after epidural placement and before incision)


- Single epidural bolus of hydromorphone at induction (0.4-0.8 mg based on body weight), followed by bupivacaine infusion (2.5 mg·mL−1 at 3-6 mL·hr−1)

- No intraoperative intravenous opioids given after induction unless approved by attending anesthesiologist


- Epidural local anesthetic/opioid infusion (0.125% bupivacaine and hydromorphone 10 µg·mL−1) for up to 72 hr.

- Adjunctive analgesia with acetaminophen and NSAIDs whenever possible

- Transition to oral opioids after removal of epidural catheter

Spine surgery

(Requiring elective posterior instrumented fusion on > 3 levels for non-malignant and non-infectious conditions)

(Mathiesen et al. 2013)118


- Not standardized; typically opioids


- Remifentanil and propofol

At anesthesiologist’s discretion:

- Fentanyl and morphine

- Epidural

- PONV prophylaxis


- Not standardized

- Acetaminophen 1 g po × 4

- If epidural placed, infusion given for up to 72 hr or PCA morphine for 48 hr if no epidural

ERAS Benefits

- Significantly less opioid consumption (oral morphine equivalent) on POD 1 [median (range) 110 (55-180) mg vs 15 (0-120) mg] and on POD 2 [100 (40-149) mg vs 30 (0-120) mg], but not on POD 3-6

- Pain scores not analyzed

- Significantly earlier mobilization from bed (median [IQR] of 1 [1-1] day vs 1 [1-2.5] days) and ambulation, both with and without a walking frame (2 [1-2.5] days vs 3 [1-5] days and 5 [3-7] days vs 7 [5-9.3] days, respectively)

- Lower nausea, sedation and dizziness scores on POD 1-6

- Significantly shorter LOS in the PACU [median (range) 270 (173-353) min vs 345 (240-480) min], but no difference in hospital LOS

- No postoperative infections in either group

ERAS Disadvantages

- None


- Acetaminophen 2 g po (sustained release)

- Celecoxib 400 mg po

- Gabapentin 900 mg po


- Remifentanil and propofol

- Morphine iv 0.3 mg·kg−1 at 45 min before end of surgery

- S-ketamine 0.5 mg·kg−1 iv + 0.3 mg·kg−1·hr1 until 45 min before end of surgery

- Epidural catheter placed at middle tip of surgical field, boluses of bupivacaine 0.5 mg·mL−1 10 mL

- If epidural not possible, subfascial local infiltration (40 mL of bupivacaine 2.5 mg·mL−1)

- PONV prophylaxis with dexamethasone iv 24 mg


- Acetaminophen 1 g × 4 po

- Ibuprofen 400 mg × 4 po until discharge

- Gabapentin 400 + 1,000 mg po for 5 days

- Epidural bupivacaine 2.5 mg·mL−1 with 50 μg·mL−1 of morphine 5-8 mL·hr−1 for 96 hr

- If no epidural, PCA morphine (bolus 2 mg, lockout 15 min for 48 hr) background infusion 1 mg·hr−1 during first 24 hr

- Sustained-release oral morphine 20 mg × 2 after end of epidural or PCA

- Opioid at anesthesiologist’s discretion

Primary hip and knee arthroplasty

(Khan et al. 2014)119


- Not standardized


- General anesthesia, spinal or epidural per anesthesiologist and patient preference


- Patient-controlled intravenous analgesia

ERAS Benefits

- Pain and opioid consumption not analyzed

- Significantly shorter median hospital LOS (3 vs 6 days)

- Significantly lower return-to-theatre rates (40/3,000 vs 60/1,000)

- Significantly lower 30-day MI rates (12/3,000 vs 26/1,000) and death rates (5/3,000 vs 16/1,000)

- No difference in 30-day complication rates (stroke, GI bleed, pneumonia, DVT and PE)

- No difference in readmission rates

ERAS Disadvantages

- None


- Premedication with Gabapentin 300 mg po on night before surgery


- Low-dose spinal anesthesia without intrathecal opioids with Propofol ± Ketamine, and Paracetamol 1 g iv ± Parecoxib 40 mg iv; administered with sedation or light general anesthesia

- Local anesthetic via intraoperative infiltration and postoperative infusion of 0.125% levobupivacaine 80 mL in a wide and layered field, including joint capsule, muscle, fat, and skin

- Routine PONV prophylaxis with dexamethasone initially, but later discontinued due to immunosuppression concerns


- Epidural infusion via catheter placed intraoperatively; a single levobupivacaine bolus 20 mL after skin closure, and 3 postoperative boluses at 6, 14, and 24 hr (20 mL for THA, 40 mL for TKA)

- Gabapentin (300 mg twice daily for 5 days) and Oxycontin (5-20 mg twice daily for 2 days) followed by Tramadol (50-100 mg every 4-6 hr)

Gynecologic surgery (Complex cytoreductive, staging and pelvic organ prolapse surgeries)

(Kalogera et al. 2014)120


- Not standardized


- Local wound infiltration generally not used

- Triple antiemetics and prokinetics generally not used


- Opioid PCA

ERAS Benefits

- Significantly decreased PCA opioid use in cytoreductive group (98.7% vs 33.3%) and decreased postoperative opioid use (80% decrease in the first 48 hr) with no change in pain scores

- Significantly shorter hospital LOS for all surgery types (4-day reduction)

- Significantly faster return of bowel function for complex cytoreductive [median (range) 3 (2-3) days vs 4 (3-5) days] and staging surgeries [2 (1-3) days vs 2 (2-3) days]

- Significantly faster return to general diet for all surgery types (1-5 days median difference)

- No difference in rate of severity of 30-day complications (ileus, bowel perforation, anastomotic leak, abscess) or mortality

- No difference in 30-day readmission rates or stay

- Insignificant 30-day cost savings of > $7,600 USD per patient (18.8% reduction)

ERAS Disadvantages

- None


- Celecoxib 400 mg po once

- Acetaminophen 1,000 mg po once

- Gabapentin 600 mg po once


- Intravenous opioids at discretion of anesthesiologist supplemented with ketamine, ketorolac, or both

- Local anesthetic infiltration of bupivacaine at incision site after closure

- PONV prophylaxis with single dexamethasone bolus 4 mg iv plus droperidol 0.625 mg iv (± 30 min before incision); and single bolus of granisetron 0.1 mg iv (± 30 min before incision closure)


- Goal: no intravenous PCA

- Oxycodone 5-10 mg po q4 h prn pain > 3 or greater than patient stated comfort goal (5 mg for pain rated 4-6 or 10 mg for pain rated 7-10); for patients who received intrathecal analgesia, start 24 hr after intrathecal dose

- Acetaminophen 1 g po q6-12 h

- Ketorolac 15 mg iv q6 h for 4 doses, then ibuprofen 800 mg po q6 h. For NSAID-intolerant patients, tramadol 100 mg po q6-12 hr starting on POD 1

- For breakthrough pain (pain more than 7 > 1 hr after receiving oxycodone), hydromorphone 0.4 mg iv once if patient did not receive intrathecal medications; may repeat once after 20 min if first dose ineffective

- Hydromorphone PCA started only if continued pain despite 2 doses of intravenous hydromorphone

ERAS = Enhanced Recovery After Surgery; LOS = length of stay; NSAIDs = non-steroidal anti-inflammatory drugs; po = oral; PONV = postoperative nausea and vomiting; PCA = patient-controlled analgesia; POD = postoperative day; IQR = interquartile range; PACU = postanesthesia care unit; MI = myocardial infarction; THA = total hip arthroplasty; TKA = total knee arthroplasty; GI = gastrointestinal; DVT = deep vein thrombosis; PE = pulmonary embolism

Central neuraxial, regional, and local analgesia

Central neuraxial techniques (epidural and spinal analgesia)

Epidural analgesia as part of ERAS protocols accelerates return of bowel function and reduces pain, although there is inconclusive evidence that it reduces LOS.16,17 A multimodal epidural infusion comprising drugs with different pharmacological pathways is more effective than a single-agent infusion. The combination of local anesthetics and adjuvants provides both intraoperative and postoperative analgesia after a wide range of surgeries (e.g., thoracic, abdominal, lower limb).18 Epidural adjuvants, such as clonidine (0.08-0.12 µg·kg1·hr−1) added to a continuous epidural infusion of 0.08% ropivacaine (0.16 mg·kg−1·hr−1), reduce the required dose of anesthetic and enhance analgesia.19 A local anesthetic-opioid combination is also effective. For example, a double-blind randomized comparison of three solutions administered by continuous epidural infusion (15 mL·hr−1) for postoperative analgesia (0.125% bupivacaine in 0.9% saline, diamorphine in 0.9% saline [0.5 mg in 15 mL], ordiamorphine mixed with 0.125% bupivacaine) was shown to be superior to each modality alone, yielding better pain relief with fewer adverse effects following major gynecological surgery.20 In addition to their analgesic effects, central neuraxial techniques reduce the surgical stress response and cardiac, pulmonary, thromboembolic, and renal complications.21 A systematic review and meta-analysis showed that epidural analgesia significantly decreases risk of mortality (3.1% vs 4.9%; OR 0.6; 95% CI 0.4 to 0.9) as well as the risk of cardiac arrhythmias (atrial fibrillation and supraventricular tachycardia), deep vein thrombosis, respiratory complications (respiratory depression, atelectasis, and pneumonia), and gastrointestinal complications (ileus, PONV).22

Spinal analgesia is another central neuraxial block technique that can facilitate faster postoperative recovery with careful choice and dosing of drugs. Spinal anesthetic techniques, which use a multimodal “minidose” of lidocaine (10-30 mg), bupivacaine (3.5-7 mg), or ropivacaine (5-10 mg) with a potent opioid (e.g., fentanyl 10-25 μg), results in quicker recovery of sensory and motor function and lowers the risk of hypotension compared with conventional spinal techniques.23 The “minidose” spinal technique has been shown to facilitate faster recovery than general anesthesia for short-duration outpatient laparoscopy.24 Nevertheless, clinicians must be cognizant of the potential side effects of intrathecal opioids, such as PONV, which may delay discharge. This highlights the importance of tailoring analgesic regimens to patient type. For example, elderly patients are more susceptible to the adverse effects of spinal analgesia and require lower doses, as their reduced volume of nerve myelination and cerebrospinal fluid (CSF) results in greater diffusion of local anesthetics and wider extension of nerve block.25

Despite the advantages of central neuraxial techniques, there are potential adverse effects, including technical block failures (6.1% of patients in a recent meta-analysis on epidural blocks),22 inadvertent motor blockade, postdural puncture headache, and infection. Moreover, such blocks are resource-intensive due to the need for ongoing monitoring. Epidural blocks may lead to a significant increase in the risk of arterial hypotension, pruritus, urinary retention, and motor blockade22; hence, administration by experienced clinicians and individual risk-benefit analyses are paramount. Surgery type is one such consideration, as neuraxial analgesia may be more suitable for open rather than laparoscopic surgeries. A systematic review and meta-analysis found epidural analgesia to be effective for both open and laparoscopic surgeries22; however, another systematic review argued that the risk-benefit ratio for laparoscopic surgeries may not favour the use of neuraxial techniques.26 The latter review found that, while the non-epidural group had higher pain scores, the level of pain was nevertheless acceptable (i.e., < 4/10) and thus did not warrant the use of epidural analgesia.

Surgical site infiltration

The incorporation of local anesthetics as part of multimodal analgesia decreases opioid requirements and side effects when used at several surgical sites (e.g., bupivacaine 50-100 mg or lidocaine 400 mg for intraperitoneal block after laparoscopic abdominal surgeries, including fundoplication, appendectomy, hernia repair, and cholecystectomy).27 Nevertheless, there is lack of evidence for effective analgesia with infiltration at laparoscopic port sites. This may be due to inadequate doses of local anesthetics and the short duration of local anesthetics in some studies.28 Intra-articular analgesic infiltration reduces pain and opioid consumption after orthopedic procedures such as arthroscopic surgery and total knee replacement, although the evidence is less clear for its effects on time to discharge readiness and LOS.29,30 A review found that a multimodal infusion comprising high-dose ropivacaine (150-400 mg) with adrenaline (0.1-0.5 mg) and ketorolac (typically 30 mg) is most effective for analgesia.30 Continuous and patient-controlled intra-articular infusions after surgery should not be used, as prolonged exposure to analgesics may trigger chondrolysis, a rare condition of the shoulder which involves rapid dissolution of articular cartilage, eventually causing osteoarthritis and long-term disability.31 All 23 cases in a case series featuring patients with chondrolysis following shoulder arthroscopy were administered an intra-articular injection of 0.25% bupivacaine ≥ 20 mL with epinephrine, and 17/23 patients had used a high-volume intra-articular infusion pump for 48 hr postoperatively.32 More research is needed on the doses of local anesthetic that will safely manage pain without causing chondrolysis as well as on whether chondrolysis can occur in other joints, e.g., the knee.

Consideration must be given to the risks resulting from local anesthetics, including cardiac effects (e.g. bradycardia, hypotension) and effects on the central nervous system (e.g., blurred vision, seizures, and hypoventilation). These risks can be minimized by aspirating before administration to avoid intravascular injection, administering test doses, and adhering to the safe dose range for each drug. Allergic reactions are rare but include skin rash, nausea and vomiting, loss of consciousness, fever, and hypotension.

Regional techniques

Regional techniques, such as transversus abdominis plane (TAP) block and paravertebral block (PVB), are increasingly incorporated into multimodal analgesic regimens, with good evidence for their efficacy in ERAS protocols. Addition of the bilateral TAP block to an established enhanced recovery pathway using general anesthesia was found to decrease postoperative opioid requirements and LOS after laparoscopic colorectal surgery.33 A TAP block decreases postoperative opioid use and PONV after abdominal surgery and possibly reduces acute postoperative pain compared with placebo.34 Some studies have compared the efficacy of TAP block with neuraxial techniques. One study found that, after laparoscopic colorectal surgery, a four-quadrant TAP block with continuous infusion via bilateral posterior TAP catheters (0.365% levobupivacaine 2.5 mg·kg−1 preoperatively; 0.25% levobupivacaine for 48 hr postoperatively) results in pain control and postoperative tramadol consumption equivalent to a postoperative epidural infusion (0.25% bupivacaine 20 mL preoperatively; 0.125% bupivacaine 8-12 mL·hr−1, and fentanyl 2 μg·mL−1 postoperatively).35 In contrast, a systematic review and meta-analysis on Cesarean delivery found that TAP block alone was less effective than intrathecal morphine in managing pain at 24 hr (mean difference [MD] 0.98; 95% CI 0.06 to 1.91) and resulted in greater 24-hr morphine consumption (MD 8.42 mg; 95% CI 1.74 to 15.10), while the former was associated with an increased incidence of side effects such as sedation and PONV.36 There are generally few risks associated with TAP block, including intraperitoneal injection of local anesthetic (< 2%) as well as a few case reports of transient femoral nerve palsy and bowel hematoma. TAP block also carries a slight risk of damage to visceral structures such as the liver (one reported case with a blindly administered block), which is minimized with ultrasound guidance.37

As for PVB, a large retrospective analysis of patients undergoing thoracotomy for lung resection found that, when added to a morphine patient-controlled analgesia (PCA)-based regimen, a continuous PVB catheter (with an initial infusion of 0.25% bupivacaine or levobupivacaine 0.1 mL·kg−1·hr−1 and titrated down with adequate analgesia) was at least as effective as a thoracic epidural catheter (TEA) (with an initial infusion of 0.1% bupivacaine or levobupivacaine 0.1 mL·kg−1·hr−1 and titrated to adequate analgesia, combined with fentanyl 5 μg·mL−1) in reducing postoperative complications. Moreover, PVB use is associated with a shorter LOS, thus supporting its utility in fast-track thoracic surgery, for which TEA is typically considered the optimal technique for post-thoracotomy pain.38 Evidence also points to PVB as a good analgesic choice in outpatient surgeries such as inguinal herniorrhaphy. Compared with fast-track general anesthesia, PVB provides a speedier recovery, longer-lasting analgesia, shorter stays in the postanesthesia care unit (PACU), and earlier time to home readiness.39 Nevertheless, PVB is associated with an overall complication rate of 2.6-5%, including block failure (6.8-10%), hypotension (4.6%), vascular puncture (3.8%), pleural puncture (1.1%), and pneumothorax (0.5%).40 As PVB cannulae are small, pneumothorax may not always follow even if pleural puncture occurs, and a related pneumothorax is usually small and can be managed conservatively.

Systemic analgesia


Opioids are the mainstay of postoperative analgesia for many surgeries. While they are effective for moderate to severe pain, their usage is limited by dose-related adverse effects, including PONV, urinary retention, ileus, pruritus, and most dangerously, respiratory depression.28 These side effects have led to an increasing emphasis on multimodal analgesic regimens that reduce opioid demand, with opioids used as rescue analgesics when non-opioid medications are inadequate for pain control.

Acetaminophen (paracetamol)

Acetaminophen is an effective analgesic for mild to moderate pain. When used as an opioid adjunct, oral or rectal acetaminophen reduces pain intensity41 and opioid consumption by up to 30%,42 although several systematic reviews and meta-analyses have shown no concurrent reduction in opioid-related side effects.43 The use of oral over rectal acetaminophen is preferred, as the absorption of rectal acetaminophen is erratic and may therefore result in variable analgesic efficacy. There is increasing usage of intravenous acetaminophen, which has more favourable pharmacokinetics (earlier plasma and CSF peaks) than oral and rectal formulations,44 but is more costly than the latter two. Studies are currently lacking that directly compare oral with intravenous acetaminophen, but thus far, studies of intravenous acetaminophen have been encouraging. Intravenous acetaminophen also reduces opioid consumption by up to 30%, although this is not associated with a reduction in opioid-induced adverse events.45 A recent meta-analysis found that prophylactic intravenous acetaminophen (typically a 1 g dose) as part of a multimodal analgesic regimen reduces nausea if administered before surgery or PACU arrival, but not if given after the onset of pain.46 Interestingly, the reduction in nausea (compared with placebo) was associated with less pain, but not with a reduction in postoperative opioids.

Adding to the value of acetaminophen in multimodal analgesia is its apparent synergistic effect with non-steroidal anti-inflammatory drugs (NSAIDs).47 The efficacy of an acetaminophen-NSAID combination also applies in multimodal analgesic regimens that do not utilize opioids. For instance, the combination of single-dose acetaminophen (0.5-1 g) and ibuprofen (200-400 mg) after dental surgery provides better acute postoperative analgesia than either drug alone, with reduced analgesic needs and reduced risk of adverse events.48

Acetaminophen has a very favourable safety profile and is much safer than other drugs such as NSAIDs. Adverse effects are rare and include nausea and vomiting (< 1% individuals) and skin irritation (e.g., urticaria, erythema, dermatitis) (< 0.1%), with more serious adverse effects being much rarer (e.g., thrombocytopenia, leucocytosis, agranulocytosis, and liver enlargement) (< 0.01%).49

Lidocaine infusion

A meta-analysis of randomized controlled trials found that an intravenous lidocaine infusion reduces acute postoperative pain (6 hr postoperatively) at rest (weighted mean difference [WMD] −8.70; 95% CI −16.19 to −1.21), with cough (WMD −11.19; 95% CI −17.73 to −4.65), and with movement (WMD −9.56; 95% CI −17.31 to −1.80).50 Intravenous lidocaine infusion also reduced postoperative opioid (morphine) consumption (WMD −8.44 mg; 95% CI −11.32 to −5.56) as well as opioid-related side effects. These included time to first flatus (WMD −7.62 hr; 95% CI −10.78 to −4.45), time to first bowel movement (WMD −10.71 hr; 95% CI −16.14 to −5.28), PONV (relative risk [RR] 0.71; 95% CI 0.57 to 0.90), and LOS (WMD −0.17 days; 95% CI −0.41 to 0.07). The greatest benefit occurred with abdominal surgery. Although the same meta-analysis found that only 12 of 29 eligible studies screened for adverse events, incidences of cardiac and neurologic adverse events were comparable between control and treatment groups in these studies.

Non-steroidal anti-inflammatory drugs and COX-2 inhibitors

Non-steroidal anti-inflammatory drugs (including cyclooxygenase-2 [COX-2] inhibitors) reduce opioid consumption and opioid-related side effects when used in multimodal regimens.51 Nevertheless, their use is not without risk. One case-control study found that ketorolac in particular was associated with a significant increase in anastomotic leaks (OR 2.09; P = 0.021), while the use of any NSAID was associated with a non-significant increase in anastomotic leaks (OR 1.81; P = 0.06).52 Moreover, evidence from animal models shows that NSAIDs (particularly selective COX-2 inhibitors) may impair bone healing and even cause bone resorption, although data from human studies remain equivocal, with some studies even purportedly showing decreased bone resorption rates with NSAID use.53 In light of these findings, NSAIDs should be used judiciously in patients at increased risk for anastomotic leak (e.g., patients with stapled anastomoses).54 In most patients, however, NSAIDs are recommended as part of the multimodal analgesic regimen.

Cyclooxygenase-2 inhibitors do not have the adverse effects associated with conventional non-selective NSAIDs, which cause COX-1 inhibition and a corresponding increased risk for surgical-related bleeding, gastrointestinal ulceration, and renal dysfunction.43 Cyclooxygenase-2 inhibitors have been shown to reduce opioid requirements in surgeries such as laparoscopic cholecystectomy55 and knee replacement surgery,56 with fewer opioid-related symptoms and quicker functional recovery. Nevertheless, safety concerns about the prothrombotic cardiovascular side effects of COX-2 inhibitors57 have led to some products being discontinued, e.g., rofecoxib and valdecoxib.

N-methyl-D-aspartate (NMDA) receptor antagonists

Ketamine is an NMDA receptor antagonist that reduces postoperative opioid requirements. An opioid-free epidural regimen of ketamine and bupivacaine was found to be superior to a bupivacaine-fentanyl combination in fast-track colonic resection, with shorter PACU stays, shorter LOS, and fewer opioid-related side effects.58 Ketamine may be especially useful as part of a multimodal analgesic regimen in postsurgical patients with high opioid requirements or opioid-refractory pain. As NMDA receptors are involved in the development of pathological pain states, such as hyperalgesia, ketamine has also been shown to decrease chronic postsurgical pain and opioid consumption after total hip arthroplasty (ketamine 0.5 mg·kg−1 iv before incision and a 24-hr infusion of 2 µg·kg−1·min−1)59 and even in opioid-dependent patients undergoing lumbar spine surgery.59,60 Importantly, the specific use of ketamine for patients with chronic pain, whether perioperatively or otherwise, is currently off-label and not well-studied. Ketamine is U.S. Food and Drug Administration (FDA) approved as a supplement for low-potency agents (e.g., nitrous oxide) as well as for diagnostic and surgical procedures that do not require skeletal muscle relaxation for induction of anesthesia before the administration of other general anesthetic agents.

Other NMDA receptor antagonists include dextromethorphan, memantine, and magnesium sulfate. In a review of these three agents, 67% of the included studies on dextromethorphan (0.5-1 mg·kg−1) and 58% of the studies on ketamine (0.15-1.0 mg·kg−1) showed reduced postoperative pain and/or opioid consumption, whereas none of the studies on magnesium showed any effect.61 Memantine (20-30 mg·day−1) is better tolerated, more potent, and more slowly eliminated than ketamine (half-lives: 60-80 hr vs 2.5 hr, respectively).62 Memantine reduces chronic postoperative pain and may have potential as an opioid adjunct for acute postoperative analgesia.62 Lastly, magnesium (50 mg·kg−1 preoperatively and 8 mg·kg−1·hr−1 intraoperatively) also appears to act via NMDA receptor antagonism and inhibition of calcium influx. Some studies have found that it reduces postoperative opioid requirements,63 although a meta-analysis showed no evidence for its efficacy in decreasing postoperative opioid demand and pain.61 N-methyl-D-aspartate receptor antagonists have potentially unpredictable and unpleasant adverse effects, such as psychosis, but low doses (e.g., < 1 mg·kg−1 epidural or intravenous ketamine) have been found to aid pain management without these adverse effects.58 In summary, low-dose ketamine and dextromethorphan should be considered for usage in multimodal regimens, including patients with opioid-refractory pain, opioid dependence or tolerance, and those who do not have risk factors for psychosis (e.g., psychiatric disorders such as schizophrenia).

Anticonvulsants (gamma-aminobutyric acid (GABA) analogues)

Gabapentin and pregabalin are GABA analogues that reduce postoperative opioid requirements and lessen both acute and chronic postoperative pain when used in multimodal analgesia for a wide range of surgeries (e.g., gynecological, abdominal, orthopedic, and dental surgeries).64,65 Despite their GABA-like structure, their mechanism of action involves binding to α2-d subunits of voltage-dependent presynaptic calcium channels, thus reducing excitatory neurotransmitter release and subsequent postsynaptic calcium influx.28 Gabapentin decreases opioid requirements and lessens both acute and chronic postoperative pain. Evidence supports oral gabapentin 600-1,200 mg doses up to one hour preoperatively for varicocele, otolaryngological, and laparoscopic sterilization surgeries.66, 67, 68 As for timing of preoperative dose, both pre- and post-incision oral gabapentin were equivalent in reducing PCA morphine and postoperative pain after lumbar laminectomy. The 900 and 1,200-mg doses were equally effective and more efficacious than placebo and a 600-mg dose.64 One three-armed study compared prophylactic gabapentin (oral gabapentin 1,200 mg preoperatively with a saline bolus and an intraoperative infusion) and ketamine (oral placebo capsules preoperatively, ketamine bolus 0.3 mg·kg−1 iv before incision, and intraoperative ketamine infusion 0.05 mg·kg−1·hr−1 until end of surgery) with a control group (oral placebo capsules with a saline bolus and infusion).69 Both preoperative gabapentin and ketamine reduced postoperative pain and PCA morphine consumption (42% and 35%, respectively) after hysterectomy, while only gabapentin reduced chronic incisional and related pain at one, three, and six months.

Pregabalin has better bioavailability and reaches therapeutic levels more quickly than gabapentin. A meta-analysis confirmed that both preoperative and postoperative pregabalin reduce postoperative narcotic requirements and reduce PONV, albeit with no reduction in postoperative pain.65 The studies analyzed used varied doses of oral pregabalin. Doses < 300 mg (typically 75 or 150 mg) reduced cumulative opioid consumption by 8.8 mg (WMD), with a reduction of 13.4 mg (WMD) for doses of 300-600 mg.65 The disadvantages of GABA analogues are their adverse effects, including sedation, visual disturbances, dizziness, and headache.65 More research is needed on the optimal dose of GABA analogues that produces minimal adverse effects while reducing pain as part of multimodal analgesia.


A small but growing body of evidence shows that beta-blockers, such as esmolol, reduce both intraoperative and postoperative opioid requirements due to their anti-nociceptive effects.70 Beta-blockers have the additional advantage of blunting cardiovascular responses to surgical stimuli and reducing postoperative adverse cardiac events. Furthermore, perioperative esmolol has been proposed as an alternative to remifentanil for maintaining stable intraoperative hemodynamics.71 An intraoperative continuous esmolol infusion (5-15 µg·kg−1·min−1 with no supplemental intraoperative opioids) in place of intraoperative opioids (continuous remifentanil infusion 0.1-0.5 µg·kg−1·min−1) has been used successfully in ambulatory laparoscopic cholecystectomy, resulting in reduced PONV, decreased postoperative pain, and shorter LOS than when supplemental intraoperative fentanyl was used.72

Alpha2 agonists

Clonidine and dexmedetomidine have received increasing interest as adjunct analgesics, given that the basic mechanism behind analgesia is thought to be stimulation of central and peripheral α2 receptors. A systematic review and meta-analysis confirmed that systemic α2 agonists (clonidine or dexmedetomidine) decrease postoperative opioid consumption, pain intensity, and opioid-related side effects (i.e., nausea) when added to an opioid-based regimen.73 There is much variability in administration route (intravenous, oral, transdermal, and other routes) and time of administration (before, during, or after surgery), and more research is needed to ascertain the optimal route and dose timing. Clonidine is also a useful addition to multimodal regional anesthetic infusions. A small randomized controlled trial on patients undergoing elective colorectal surgery found that the addition of epidural clonidine (150 µg in 9 mL of normal saline 30 min before surgery and 1.5 µg·mL−1 postoperatively) to patient-controlled epidural analgesia with morphine (0.1 mg·mL−1) and 0.2% ropivacaine (100 mL) reduces time to first flatus, albeit without any difference in LOS.74 The addition of dexmedetomidine to intravenous regional anesthetic solutions prolongs analgesia and motor blockade.75 Additionally, an intravenous dexmedetomidine infusion (0.2-0.8 µg·kg−1·hr−1) before wound closure was shown to decrease PACU opioid requirements, PACU stay, and PONV after laparoscopic bariatric surgery.76

Capsaicin (transient receptor potential vanilloid receptor 1(TRPV1) agonist)

Capsaicin is a non-narcotic agent with agonist activity at peripheral TRPV1 receptors. It selectively stimulates unmyelinated C-fibre afferent neurons, causing the continued release and subsequent depletion of substance P, which ultimately decreases C-fibre activation.77 Its advantages are its long analgesic duration and lack of effect on motor and autonomic functions. Thus, it has potential value in facilitating earlier rehabilitation and functional recovery after painful surgeries (e.g., orthopedic procedures). Following total knee arthroplasty, directly instilling capsaicin 15 mg prior to wound closure can decrease postoperative pain, opioid requirements, and side effects (e.g., pruritus) as well as improve functional recovery.78 The caveat is that capsaicin must be administered before the end of anesthesia as it causes an acute burning sensation immediately after application.


Glucocorticoids reduce postoperative pain as well as decrease opioid requirements and side effects such as PONV.79 They exert their analgesic effect via several mechanisms; they have anti-nociceptive effects at the spinal level, prevent the production of cytokines involved in inflammatory pain, and inhibit the production of inflammatory prostaglandins and leukotrienes by preventing arachidonic acid production.28 A major consideration is their potential adverse effects in postoperative patients, as glucocorticoids administered in high doses (e.g., dexamethasone 1 mg·kg−1) and for long periods (> 21 days) increase the risk of infection and impair wound healing.80 Some studies have shown that a single prophylactic dose of dexamethasone can cause mild hyperglycemia for 24 hr postoperatively, although one randomized controlled trial found this was associated with a lower risk of some postoperative complications such as pneumonia and catheter-related infection.81 Furthermore, a recent randomized controlled trial has refuted the claim that a single low dose of dexamethasone (up to 8 mg at induction of anesthesia) raises blood glucose concentrations for 24 hr after administration, as blood glucose levels did not differ from those observed after saline administration.82 The exact dose of glucocorticoids at which potential harm outweighs benefit is unknown. Nevertheless, current literature supports a single prophylactic dose of dexamethasone 4 mg at induction for PONV prophylaxis, with 8 mg providing additional opioid-sparing effects and quicker recovery without an increase in postoperative complications such as infection, wound separation, and dehiscence.83, 84, 85

Non-pharmacological techniques

Non-pharmacological analgesia, when used as an adjunct to pharmacological methods of postoperative pain management, can reduce total analgesic requirements and corresponding side effects.


Several studies have shown reduced opioid consumption and side effects (e.g., PONV, urinary retention) when acupuncture is used as part of multimodal postoperative analgesia,86 although clinical opinion on its efficacy remains divided.87 Considerable clinical heterogeneity remains between studies; for instance, some studies use penetrating needles as the sham intervention, which has been proposed to have a physiological effect. The mechanisms of action of acupuncture remain unclear, but hypotheses include the “gate control theory” and endogenous opioid release. A randomized sham-controlled trial found that electroacupuncture, a variant of acupuncture involving the addition of electric current, resulted in reduced postoperative analgesic requirements at 45 min and lower cortisol levels when added to a multimodal regimen (tramadol and ketamine) for radical prostatectomy.88

Music therapy

Music therapy may have a short-term effect on lessening pain and anxiety by decreasing perception of pain through mechanisms such as attention shift or cognitive coping.28 Compared with noise-cancelling headphones alone, music with noise-cancelling headphones was associated with less increase in pain scores from baseline in patients undergoing transrectal prostate biopsy.89 Post-biopsy diastolic blood pressure remained stable in the music group but increased in the control and headphones groups, suggesting reduced physiological response to anxiety and pain in the former. Music therapy may also reduce opioid consumption.90 More research is needed on the optimal type and duration of music therapy.

Transcutaneous electrical nerve stimulation (TENS)

Current evidence is limited, but some studies suggest a positive effect of TENS in reducing acute postoperative pain.91, 92, 93 Given its safety profile, TENS can be considered as an adjunct in patients who do not respond to conventional analgesic techniques or who experience severe side effects.


Hypnosis can be used as an adjunct technique to reduce pain by altering a patient’s perception of pain, although not all patients may respond similarly.28 A randomized controlled trial on breast cancer surgery patients found hypnosis reduced propofol and lidocaine use compared with attention control. It also reduced pain, nausea, fatigue, discomfort, and emotional upset at discharge.94 Evidence also suggests that hypnosis can decrease pain after pediatric and adolescent surgeries and certain procedures (e.g., bone marrow aspiration), and it is at least as effective as distraction as an adjunct strategy for pain reduction.95

Future directions

Local infiltration of long-acting local anesthetics

Long-acting local anesthetics include liposomal bupivacaine, a recently FDA-approved formulation of bupivacaine for single-dose local infiltration at the surgical site. This formulation aims to sustain safe therapeutic levels of bupivacaine for up to 72 hr after administration, allowing prolonged analgesia and thus early hospital discharge. Compared with conventional bupivacaine HCl, liposomal bupivacaine reduces post-surgical pain and decreases opioid consumption and opioid-related adverse events after surgeries such as hemorrhoidectomy.96 A combined analysis of results from six Phase IV prospective single-centre sequential cohort studies found that a multimodal regimen incorporating local infiltration of liposomal bupivacaine (266 mg administered intraoperatively) reduced postoperative opioid requirements, LOS, and opioid-related adverse events after laparoscopic colectomy when compared with opioid PCA (morphine or hydromorphone).97 Specifically, one of the included studies found that intraoperative liposomal bupivacaine 266 mg used in a fast-track protocol for ileostomy reversal significantly reduced mean (SD) total postoperative opioid consumption [38 (46) mg vs 68 (47) mg] and resulted in a nonsignificant but clinically meaningful reduction in LOS (0.8 days, 21% reduction) and total hospitalization costs ($6,611 USD vs $6,790 USD).98 Future research will confirm the extent of its safety and efficacy relative to plain bupivacaine as well as evaluate its use via routes other than local infiltration (e.g., intrathecal, epidural, and perineural).99

SABER®-Bupivacaine is another extended-release formulation currently awaiting FDA approval. It comprises bupivacaine 12% in a resorbable semi-viscous matrix of sucrose acetate isobutyrate (SAIB) and provides local analgesia for up to 72 hr. In a multicentre randomized controlled trial on open inguinal hernia repair, a 5 mL dose of SABER-Bupivacaine locally administered at the surgical site significantly reduced acute postoperative pain compared with placebo and reduced supplemental opioid consumption by 26% (although this was not significant).100

Lidocaine patch

The lidocaine patch is usually administered as a 10 × 14 cm transdermal patch with lidocaine 700 mg (5% on an aqueous base).101 As with systemic local anesthetics, transdermal lidocaine reduces pain sensation by blocking the sodium channels of nociceptors. The lidocaine 5% patch has been used for many different chronic pain conditions102, 103, 104, 105 and some acute pain conditions, such as traumatic rib fractures.106 Evidence for the lidocaine 5% patch for acute postoperative pain is limited.107, 108, 109, 110 A meta-analysis of lidocaine patch shows that lidocaine patches may not be an effective adjunct for acute and postoperative pain management.111 No significant difference of postoperative pain intensity, opioid consumption and length of hospital stay was found between the lidocaine group and the placebo group. The suggested reason is that the concentration of lidocaine within the wound may be insufficient because of diffusion barriers (skin), location of the patches (around but not on the wound) and minimal systematic absorption (unlike fentanyl patch).111

Novel opioids and opioid delivery techniques


Tapentadol is a recently FDA-approved central-acting analgesic with a dual synergistic mode of action on μ opioid receptors and norepinephrine reuptake inhibition. Tapentadol achieves equipotent analgesia to strong opioids (e.g., oxycodone) while conferring the advantages of decreased PONV, fewer gastrointestinal disturbances, and lower potential for abuse.112 It has the potential to decrease LOS and hospital costs while providing effective acute postoperative analgesia.

Transdermal iontophoretic delivery of fentanyl

Patient-controlled transdermal fentanyl utilizes needleless iontophoresis technology, allowing patients to self-administer pre-programmed doses of fentanyl, much like conventional PCA. Iontophoresis makes use of an electric current to drive ionized drug molecules across the skin and into the systemic circulation. This differs from the traditional fentanyl patch, which simply involves a slow extended-release fentanyl formulation that cannot be controlled by the patient. Apart from greater ease of administration and patient comfort, a recent review showed fewer opioid-related adverse events and pain control comparable with intravenous opioids.113 Future implications for research include its efficacy and optimal dose in different patient populations (e.g., by age, body weight, and surgery type) as well as the duration and severity of reactions at the application site.114

Sublingual sufentanil microtablet

Sufentanil has a relatively large therapeutic index, and evidence suggests that it results in less respiratory depression than other opioids, although its rapid tissue redistribution following intravenous administration has precluded its frequent use in PCA regimens. Sublingual sufentanil, which is currently awaiting FDA approval, can provide a prolonged duration of action (80-90 min plasma half-time compared with 15 min for intravenous administration) while harnessing its advantages over other opioids.115 Two Phase II studies on knee replacement surgery and abdominal surgery showed that 15-µg sublingual sufentanil microtablets reduce postoperative pain compared with placebo and result in fewer opioid-related adverse events.115 In one study, a handheld PCA device with a 20-min lockout period was used to dispense sublingual sufentanil microtablets, providing a novel method of noninvasive postoperative PCA.116

Multimodal regimens in ERAS

The Table 1 outlines several key papers on evidence-based ERAS regimens by surgery type. Such regimens utilize a comprehensive perioperative care pathway, with multimodal analgesia as a key component to improve recovery. One such ERAS protocol for colorectal surgery has been implemented at a major U.S. teaching hospital since 2010.117 The multimodal pain management regimen involves thoracic epidural catheters at T8-T12, with 0.25% bupivacaine (3-6 mL·hr−1) continuously infused intraoperatively and opioids prohibited unless approved by attending anesthesiologists. Postoperatively, the epidural catheter is used for PCA (0.125% bupivacaine /hydromorphone 10 µg·mL−1; infusion 4-6 mL, bolus 2 mL/30 min). Where possible, regular adjunctive analgesia (intravenous acetaminophen and NSAIDs) is used, and oral opioids are administered after the removal of the epidural catheters. Compared with non-ERAS patients, whose analgesic regimens were based on provider preferences and rarely involved epidurals, a retrospective analysis showed that the ERAS patients had significantly reduced LOS, average pain scores, opioid consumption, urinary tract infection, and readmission rates.

Similar results are seen with other ERAS regimens, with some studies (e.g., for spinal surgery)118 showing decreased opioid consumption and side effects (i.e., PONV) along with improved recovery parameters, such as shorter time to mobilization and ambulation. Some other studies even indicate that ERAS is associated with better outcomes with lower 30-day myocardial infarction and death rates.119

In general, it appears that incorporating multimodal analgesia into ERAS regimens provides better pain control with more favourable side-effect profiles and faster postoperative recovery and may be associated with improved outcomes.


There have been many advances in optimizing management of postoperative analgesia to facilitate enhanced recovery, with multimodal analgesia regimens now the standard practice in ERAS protocols. Despite the clinically observable benefits of these protocols, some challenges in pain research remain within the context of ERAS. By design, ERAS protocols comprise many elements, and these many factors make it difficult to carry out randomized trials controlling for each specific modifiable intervention. Hence, it is difficult to determine the relative importance of individual aspects of the multimodal drugs and elements of ERAS.

Another continuing challenge is that, despite the continuously expanding array of multimodal analgesic methods, data indicate that postoperative pain in general continues to be undermanaged.15 Given the importance of effective analgesia in patient recovery, the significance of poor pain management is obvious. Moreover, in addition to the consequences of pain in the immediate postoperative period, acute pain may trigger long-term neuronal changes that result in the development of chronic pain.28 As such, healthcare providers must be vigilant about using the tools at hand to individualize multimodal regimens to patient and surgery type and thus best manage acute postoperative pain.

Key points

  • Enhanced recovery pathways facilitate evidence-based comprehensive perioperative care, including postoperative pain management, with the aim of accelerating recovery and discharge after surgery.

  • The use of more than one analgesic modality (i.e., multimodal analgesia) to achieve effective pain control while minimizing the side effects of opioids that delay discharge has become the standard of care in ERAS protocols.

  • Systemic pharmacological analgesic modalities include opioids, acetaminophen, NSAIDs, intravenous lidocaine infusions, NMDA receptor antagonists, anticonvulsants (e.g., GABA analogues), beta-blockers, a2 agonists, TRPV1 agonists (capsaicin), and glucocorticoids. Other regional/local pharmacological techniques include central neuraxial techniques, surgical site infiltration, and regional anesthesia.

  • Non-pharmacological techniques are low-risk potentially valuable additions to pharmacological modalities and include acupuncture, music therapy, TENS, and hypnosis.

  • Future directions in postoperative analgesia for enhanced recovery include long-acting local anesthetics as well as opioid rescue using novel patient-controlled delivery techniques such as iontophoretic transdermal delivery of fentanyl and transmucosal sufentanil microtablets.

  • A key challenge in multimodal ERAS-related pain research is the difficulty in carrying out randomized trials to determine the relative importance of any one component, including analgesia. Furthermore, despite the ever expanding availability of multimodal analgesic methods, postoperative pain in general continues to be undermanaged.


Conflicts of interest

None declared.

Author Disclosures

M. Tan and L.S.C. Law have no disclosures to report. T.J. Gan has grant support and honoraria from Baxter, Cubist Pharmaceuticals Inc., DURECT corporation, Fresenius Medical Care AG & co. KGaA, Mallinckrodt Pharmaceuticals, and Pacira Pharmaceuticals Inc.


  1. 1.
    Cullen KA, Hall MJ, Golosinskiy A. Ambulatory Surgery in the United States, 2006. National Health Statistics Reports; Number 11. National Center for Health Statistics 2009.Google Scholar
  2. 2.
    Gustafsson UO, Scott MJ, Schwenk W, et al. Guidelines for perioperative care in elective colonic surgery: enhanced recovery after surgery (ERAS((R))) Society recommendations. World J Surg 2013; 37: 259-84.PubMedGoogle Scholar
  3. 3.
    Khoo CK, Vickery CJ, Forsyth N, Vinall NS, Eyre-Brook IA. A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer. Ann Surg 2007; 245: 867-72.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Spanjersberg WR, Reurings J, Keus F, van Laarhoven CJ. Fast track surgery versus conventional recovery strategies for colorectal surgery. Cochrane Database Syst Rev 2011; 2: CD007635.PubMedGoogle Scholar
  5. 5.
    Muller S, Zalunardo MP, Hubner M, Clavien PA, Demartines N. Zurich Fast Track Study Group. A fast-track program reduces complications and length of hospital stay after open colonic surgery. Gastroenterology 2009; 136: 842-7.PubMedGoogle Scholar
  6. 6.
    Serclova Z, Dytrych P, Marvan J, et al. Fast-track in open intestinal surgery: prospective randomized study (Clinical Trials Gov Identifier no. NCT00123456). Clin Nutr 2009; 28: 618-24.PubMedGoogle Scholar
  7. 7.
    American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2012; 116: 248-73.Google Scholar
  8. 8.
    Horlocker TT, Kopp SL, Pagnano MW, Hebl JR. Analgesia for total hip and knee arthroplasty: a multimodal pathway featuring peripheral nerve block. J Am Acad Orthop Surg 2006; 14: 126-35.PubMedGoogle Scholar
  9. 9.
    Oderda GM, Evans RS, Lloyd J, et al. Cost of opioid-related adverse drug events in surgical patients. J Pain Symptom Manage 2003; 25: 276-83.PubMedGoogle Scholar
  10. 10.
    Gan TJ, Lubarsky DA, Flood EM, et al. Patient preferences for acute pain treatment. Br J Anaesth 2004; 92: 681-8.PubMedGoogle Scholar
  11. 11.
    Oderda GM, Gan TJ, Johnson BH, Robinson SB. Effect of opioid-related adverse events on outcomes in selected surgical patients. J Pain Palliat Care Pharmacother 2013; 27: 62-70.PubMedGoogle Scholar
  12. 12.
    Parker RK, Holtmann B, White PF. Patient-controlled analgesia. Does a concurrent opioid infusion improve pain management after surgery? JAMA 1991; 266: 1947-52.PubMedGoogle Scholar
  13. 13.
    Koppert W, Schmelz M. The impact of opioid-induced hyperalgesia for postoperative pain. Best Pract Res Clin Anaesthesiol 2007; 21: 65-83.PubMedGoogle Scholar
  14. 14.
    Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg 1993; 77: 1048-56.PubMedGoogle Scholar
  15. 15.
    Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin 2014; 30: 149-60.PubMedGoogle Scholar
  16. 16.
    Khan SA, Khokhar HA, Nasr AR, Carton E, El-Masry S. Effect of epidural analgesia on bowel function in laparoscopic colorectal surgery: a systematic review and meta-analysis. Surg Endosc 2013; 27: 2581-91.PubMedGoogle Scholar
  17. 17.
    Gendall KA, Kennedy RR, Watson AJ, Frizelle FA. The effect of epidural analgesia on postoperative outcome after colorectal surgery. Colorectal Dis 2007; 9: 584-98; discussion 598-600.Google Scholar
  18. 18.
    Jorgensen H, Wetterslev J, Moiniche S, Dahl JB. Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database Syst Rev 2000; 4: CD001893.PubMedGoogle Scholar
  19. 19.
    De Negri P, Ivani G, Visconti C, De Vivo P, Lonnqvist PA. The dose-response relationship for clonidine added to a postoperative continuous epidural infusion of ropivacaine in children. Anesth Analg 2001; 93: 71-6.PubMedGoogle Scholar
  20. 20.
    Lee A, Simpson D, Whitfield A, Scott DB. Postoperative analgesia by continuous extradural infusion of bupivacaine and diamorphine. Br J Anaesth 1988; 60: 845-50.PubMedGoogle Scholar
  21. 21.
    Rodgers A, Walker N, Schug S, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ 2000; 321: 1493.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Popping DM, Elia N, Van Aken HK, et al. Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials. Ann Surg 2014; 259: 1056-67.PubMedGoogle Scholar
  23. 23.
    Vaghadia H, McLeod DH, Mitchell GW, Merrick PM, Chilvers CR. Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration outpatient laparoscopy. I. A randomized comparison with conventional dose hyperbaric lidocaine. Anesth Analg 1997; 84: 59-64.PubMedGoogle Scholar
  24. 24.
    Lennox PH, Vaghadia H, Henderson C, Martin L, Mitchell GW. Small-dose selective spinal anesthesia for short-duration outpatient laparoscopy: recovery characteristics compared with desflurane anesthesia. Anesth Analg 2002; 94: 346-50.PubMedGoogle Scholar
  25. 25.
    Bettelli G. Anaesthesia for the elderly outpatient: preoperative assessment and evaluation, anaesthetic technique and postoperative pain management. Curr Opin Anaesthesiol 2010; 23: 726-31.PubMedGoogle Scholar
  26. 26.
    Joshi GP, Bonnet F, Kehlet H. PROSPECT collaboration. Evidence-based postoperative pain management after laparoscopic colorectal surgery. Colorectal Dis 2013; 15: 146-55.PubMedGoogle Scholar
  27. 27.
    Moiniche S, Jorgensen H, Wetterslev J, Dahl JB. Local anesthetic infiltration for postoperative pain relief after laparoscopy: a qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block. Anesth Analg 2000; 90: 899-912.PubMedGoogle Scholar
  28. 28.
    Pyati S, Gan TJ. Perioperative pain management. CNS Drugs 2007; 21: 185-211.PubMedGoogle Scholar
  29. 29.
    Moiniche S, Mikkelsen S, Wetterslev J, Dahl JB. A systematic review of intra-articular local anesthesia for postoperative pain relief after arthroscopic knee surgery. Reg Anesth Pain Med 1999; 24: 430-7.PubMedGoogle Scholar
  30. 30.
    Gibbs DM, Green TP, Esler CN. The local infiltration of analgesia following total knee replacement: a review of current literature. J Bone Joint Surg Br 2012; 94: 1154-9.PubMedGoogle Scholar
  31. 31.
    Young A, Buvanendran A. Multimodal systemic and intra-articular analgesics. Int Anesthesiol Clin 2011; 49: 117-33.PubMedGoogle Scholar
  32. 32.
    Bailie DS, Ellenbecker TS. Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg 2009; 18: 742-7.PubMedGoogle Scholar
  33. 33.
    Favuzza J, Delaney CP. Laparoscopic-guided transversus abdominis plane block for colorectal surgery. Dis Colon Rectum 2013; 56: 389-91.PubMedGoogle Scholar
  34. 34.
    Johns N, O’Neill S, Ventham NT, Barron F, Brady RR, Daniel T. Clinical effectiveness of transversus abdominis plane (TAP) block in abdominal surgery: a systematic review and meta-analysis. Colorectal Dis 2012; 14: e635-42.PubMedGoogle Scholar
  35. 35.
    Niraj G, Kelkar A, Hart E, et al. Comparison of analgesic efficacy of four-quadrant transversus abdominis plane (TAP) block and continuous posterior TAP analgesia with epidural analgesia in patients undergoing laparoscopic colorectal surgery: an open-label, randomised, non-inferiority trial. Anaesthesia 2014; 69: 348-55.PubMedGoogle Scholar
  36. 36.
    Mishriky BM, George RB, Habib AS. Transversus abdominis plane block for analgesia after cesarean delivery: a systematic review and meta-analysis. Can J Aneth 2012; 59: 766-78.Google Scholar
  37. 37.
    Jankovic Z, Ahmad N, Ravishankar N, Archer F. Transversus abdominis plane block: how safe is it? Anesth Analg 2008; 107: 1758-9.PubMedGoogle Scholar
  38. 38.
    Elsayed H, McKevith J, McShane J, Scawn N. Thoracic epidural or paravertebral catheter for analgesia after lung resection: is the outcome different? J Cardiothorac Vasc Anesth 2012; 26: 78-82.PubMedGoogle Scholar
  39. 39.
    Akcaboy EY, Akcaboy ZN, Gogus N. Comparison of paravertebral block versus fast-track general anesthesia via laryngeal mask airway in outpatient inguinal herniorrhaphy. J Anesth 2010; 24: 687-93.PubMedGoogle Scholar
  40. 40.
    Tighe SQ, Green MD, Rajadurai N. Paravertebral block. Contin Educ Anaesth Crit Care Pain 2010; 10: 133-7.Google Scholar
  41. 41.
    Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth 2013; 23: 475-95.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Cobby TF, Crighton IM, Kyriakides K, Hobbs GJ. Rectal paracetamol has a significant morphine-sparing effect after hysterectomy. Br J Anaesth 1999; 83: 253-6.PubMedGoogle Scholar
  43. 43.
    Maund E, McDaid C, Rice S, Wright K, Jenkins B, Woolacott N. Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review. Br J Anaesth 2011; 106: 292-7.PubMedGoogle Scholar
  44. 44.
    Singla NK, Parulan C, Samson R, et al. Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen. Pain 2012; 12: 523-32.Google Scholar
  45. 45.
    McNicol ED, Tzortzopoulou A, Cepeda MS, Francia MB, Farhat T, Schumann R. Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: a systematic review and meta-analysis. Br J Anaesth 2011; 106: 764-75.PubMedGoogle Scholar
  46. 46.
    Apfel CC, Turan A, Souza K, Pergolizzi J, Hornuss C. Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and meta-analysis. Pain 2013; 154: 677-89.PubMedGoogle Scholar
  47. 47.
    Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010; 110: 1170-9.PubMedGoogle Scholar
  48. 48.
    Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain. Cochrane Database Syst Rev 2012; 6: CD010210.Google Scholar
  49. 49.
    Zukowski M, Kotfis K. Safety of metamizole and paracetamol for acute pain treatment (Polish). Anestezj Intens Ter 2009; 41: 170-5.Google Scholar
  50. 50.
    Vigneault L, Turgeon AF, Cote D, et al. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anesth 2011; 58: 22-37.PubMedGoogle Scholar
  51. 51.
    Cepeda MS, Carr DB, Miranda N, Diaz A, Silva C, Morales O. Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial. Anesthesiology 2005; 103: 1225-32.PubMedGoogle Scholar
  52. 52.
    Subendran J, Siddiqui N, Victor JC, McLeod RS, Govindarajan A. NSAID use and anastomotic leaks following elective colorectal surgery: a matched case-control study. J Gastrointest Surg 2014; 18: 1391-7.PubMedGoogle Scholar
  53. 53.
    Konstantinidis I, Papageorgiou SN, Kyrgidis A, Tzellos TG, Kouvelas D. Effect of non-steroidal anti-inflammatory drugs on bone turnover: an evidence-based review. Rev Recent Clin Trials 2013; 8: 48-60.PubMedGoogle Scholar
  54. 54.
    Gorissen KJ, Benning D, Berghmans T, et al. Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery. Br J Surg 2012; 99: 721-7.PubMedGoogle Scholar
  55. 55.
    Gan TJ, Joshi GP, Zhao SZ, Hanna DB, Cheung RY, Chen C. Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects. Acta Anaesthesiol Scand 2004; 48: 1194-207.PubMedGoogle Scholar
  56. 56.
    Buvanendran A, Kroin JS, Tuman KJ, et al. Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial. JAMA 2003; 290: 2411-8.PubMedGoogle Scholar
  57. 57.
    Fosbol EL, Folke F, Jacobsen S, et al. Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals. Circ Cardiovasc Qual Outcomes 2010; 3: 395-405.PubMedGoogle Scholar
  58. 58.
    Omar SH, Radwan KG, Youssif MA, et al. A non opioid fast track anesthetic regimen for colonic resection. J Egypt Soc Parasitol 2009; 39: 849-64.PubMedGoogle Scholar
  59. 59.
    Remerand F, Le Tendre C, Baud A, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Anesth Analg 2009; 109: 1963-71.PubMedGoogle Scholar
  60. 60.
    Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology 2010; 113: 639-46.PubMedGoogle Scholar
  61. 61.
    McCartney CJ, Sinha A, Katz J. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesth Analg 2004; 98: 1385-400.PubMedGoogle Scholar
  62. 62.
    Suzuki M. Role of N-methyl-D-aspartate receptor antagonists in postoperative pain management. Curr Opin Anaesthesiol 2009; 22: 618-22.PubMedGoogle Scholar
  63. 63.
    Koinig H, Wallner T, Marhofer P, Andel H, Horauf K, Mayer N. Magnesium sulfate reduces intra- and postoperative analgesic requirements. Anesth Analg 1998; 87: 206-10.PubMedGoogle Scholar
  64. 64.
    Khan ZH, Rahimi M, Makarem J, Khan RH. Optimal dose of pre-incision/post-incision gabapentin for pain relief following lumbar laminectomy: a randomized study. Acta Anaesthesiol Scand 2011; 55: 306-12.PubMedGoogle Scholar
  65. 65.
    Zhang J, Ho KY, Wang Y. Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br J Anaesth 2011; 106: 454-62.PubMedGoogle Scholar
  66. 66.
    Bartholdy J, Hilsted KL, Hjortsoe NC, Engbaek J, Dahl JB. Effect of gabapentin on morphine demand and pain after laparoscopic sterilization using Filshie clips. A double blind randomized clinical trial. BMC Anesthesiol 2006; 6: 12.PubMedCentralPubMedGoogle Scholar
  67. 67.
    Kazak Z, Meltem Mortimer N, Sekerci S. Single dose of preoperative analgesia with gabapentin (600 mg) is safe and effective in monitored anesthesia care for nasal surgery. Eur Arch Otorhinolaryngol 2010; 267: 731-6.PubMedGoogle Scholar
  68. 68.
    Koc S, Memis D, Sut N. The preoperative use of gabapentin, dexamethasone, and their combination in varicocele surgery: a randomized controlled trial. Anesth Analg 2007; 105: 1137-42.PubMedGoogle Scholar
  69. 69.
    Sen H, Sizlan A, Yanarates O, et al. A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy. Anesth Analg 2009; 109: 1645-50.PubMedGoogle Scholar
  70. 70.
    Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth 2004; 93: 799-805.PubMedGoogle Scholar
  71. 71.
    Coloma M, Chiu JW, White PF, Armbruster SC. The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery. Anesth Analg 2001; 92: 352-7.PubMedGoogle Scholar
  72. 72.
    Collard V, Mistraletti G, Taqi A, et al. Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy. Anesth Analg 2007; 105: 1255-62.PubMedGoogle Scholar
  73. 73.
    Blaudszun G, Lysakowski C, Elia N, Tramer MR. Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology 2012; 116: 1312-22.PubMedGoogle Scholar
  74. 74.
    Wu CT, Jao SW, Borel CO, et al. The effect of epidural clonidine on perioperative cytokine response, postoperative pain, and bowel function in patients undergoing colorectal surgery. Anesth Analg 2004; 99: 502-9.PubMedGoogle Scholar
  75. 75.
    Ramadhyani U, Park JL, Carollo DS, Waterman RS, Nossaman BD. Dexmedetomidine: clinical application as an adjunct for intravenous regional anesthesia. Anesthesiol Clin 2010; 28: 709-22.PubMedGoogle Scholar
  76. 76.
    Tufanogullari B, White PF, Peixoto MP, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesth Analg 2008; 106: 1741-8.PubMedGoogle Scholar
  77. 77.
    Young A, Buvanendran A. Recent advances in multimodal analgesia. Anesthesiol Clini 2012; 30: 91-100.Google Scholar
  78. 78.
    Hartrick CT, Pestano C, Carlson N, Hartrick S. Capsaicin instillation for postoperative pain following total knee arthroplasty: a preliminary report of a randomized, double-blind, parallel-group, placebo-controlled, multicentre trial. Clin Drug Investig 2011; 31: 877-82.PubMedGoogle Scholar
  79. 79.
    Henzi I, Sonderegger J, Tramer MR. Efficacy, dose-response, and adverse effects of droperidol for prevention of postoperative nausea and vomiting. Can J Anesth 2000; 47: 537-51.PubMedGoogle Scholar
  80. 80.
    Ali Khan S, McDonagh DL, Gan TJ. Wound complications with dexamethasone for postoperative nausea and vomiting prophylaxis: a moot point? Anesth Analg 2013; 116: 966-8.PubMedGoogle Scholar
  81. 81.
    Dieleman JM, Nierich AP, Rosseel PM, et al. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA 2012; 308: 1761-7.PubMedGoogle Scholar
  82. 82.
    Murphy GS, Szokol JW, Avram MJ, et al. The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients. Anesth Analg 2014; 118: 1204-12.PubMedGoogle Scholar
  83. 83.
    Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS. Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis. Br J Anesth 2013; 110: 191-200.Google Scholar
  84. 84.
    Karanicolas PJ, Smith SE, Kanbur B, Davies E, Guyatt GH. The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis. Ann Surg 2008; 248: 751-62.PubMedGoogle Scholar
  85. 85.
    Colin B, Gan TJ. Cancer recurrence and hyperglycemia with dexamethasone for postoperative nausea and vomiting prophylaxis: more moot points? Anesth Analg 2014; 118: 1154-6.PubMedGoogle Scholar
  86. 86.
    Sun Y, Gan TJ, Dubose JW, Habib AS. Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials. Br J Anaesth 2008; 101: 151-60.PubMedGoogle Scholar
  87. 87.
    Colquhoun D, Novella SP. Acupuncture is theatrical placebo. Anesth Analg 2013; 116: 1360-3.PubMedGoogle Scholar
  88. 88.
    Ntritsou V, Mavrommatis C, Kostoglou C, et al. Effect of perioperative electroacupuncture as an adjunctive therapy on postoperative analgesia with tramadol and ketamine in prostatectomy: a randomised sham-controlled single-blind trial. Acupunct Med 2014; 32: 215-22.PubMedGoogle Scholar
  89. 89.
    Tsivian M, Qi P, Kimura M, et al. The effect of noise-cancelling headphones or music on pain perception and anxiety in men undergoing transrectal prostate biopsy. Urology 2012; 79: 32-6.PubMedGoogle Scholar
  90. 90.
    Cepeda MS, Carr DB, Lau J, Alvarez H. Music for pain relief. Cochrane Database Syst Rev 2006; 2: CD004843.PubMedGoogle Scholar
  91. 91.
    Meissner W. The role of acupuncture and transcutaneous-electrical nerve stimulation for postoperative pain control. Curr Opin Anaesthesiol 2009; 22: 623-6.PubMedGoogle Scholar
  92. 92.
    Sbruzzi G, Silveira SA, Silva DV, Coronel CC, Plentz RD. Transcutaneous electrical nerve stimulation after thoracic surgery: systematic review and meta-analysis of 11 randomized trials (Portuguese). Rev Bras Cir Cardiovasc 2012; 27: 75-87.PubMedGoogle Scholar
  93. 93.
    Chandra A, Banavaliker JN, Das PK, Hasti S. Use of transcutaneous electrical nerve stimulation as an adjunctive to epidural analgesia in the management of acute thoracotomy pain. Indian J Anaesth 2010; 54: 116-20.PubMedCentralPubMedGoogle Scholar
  94. 94.
    Montgomery GH, Bovbjerg DH, Schnur JB, et al. A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. J Natl Cancer Inst 2007; 99: 1304-12.PubMedGoogle Scholar
  95. 95.
    Accardi MC, Milling LS. The effectiveness of hypnosis for reducing procedure-related pain in children and adolescents: a comprehensive methodological review. J Behav Med 2009; 32: 328-39.PubMedGoogle Scholar
  96. 96.
    Haas E, Onel E, Miller H, Ragupathi M, White PF. A double-blind, randomized, active-controlled study for post-hemorrhoidectomy pain management with liposome bupivacaine, a novel local analgesic formulation. Am Surg 2012; 78: 574-81.PubMedGoogle Scholar
  97. 97.
    Candiotti A, Sands LR, Lee E, et al. Liposome bupivacaine for postsurgical analgesia in adult patients undergoing laparoscopic colectomy: results from prospective phase IV sequential cohort studies assessing health economic outcomes. Curr Ther Res Clin Exp 2013; 76: 1-6.PubMedCentralPubMedGoogle Scholar
  98. 98.
    Vogel JD. Liposome bupivacaine (EXPAREL®) for extended pain relief in patients undergoing ileostomy reversal at a single institution with a fast-track discharge protocol: an IMPROVE phase IV health economics trial. J Pain Res 2013; 6: 605-10.PubMedCentralPubMedGoogle Scholar
  99. 99.
    Chahar P, Cummings KC 3rd. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res 2012; 5: 257-64.PubMedCentralPubMedGoogle Scholar
  100. 100.
    Hadj A, Hadj A, Hadj A, et al. Safety and efficacy of extended-release bupivacaine local anaesthetic in open hernia repair: a randomized controlled trial. ANZ J Surg 2012; 82: 251-7.PubMedGoogle Scholar
  101. 101.
    Argoff CE. New analgesics for neuropathic pain: the lidocaine patch. Clin J Pain 2000; 16(2 Suppl): S62-6.PubMedGoogle Scholar
  102. 102.
    Kivitz A, Fairfax M, Sheldon EA, et al. Comparison of the effectiveness and tolerability of lidocaine patch 5% versus celecoxib for osteoarthritis-related knee pain: post hoc analysis of a 12 week, prospective, randomized, active-controlled, open-label, parallel-group trial in adults. Clin Ther 2008; 30: 2366-77.PubMedGoogle Scholar
  103. 103.
    Nalamachu S, Wieman M, Bednarek L, Chitra S. Influence of anatomic location of lidocaine patch 5% on effectiveness and tolerability for postherpetic neuralgia. Patient Prefer Adherence 2013; 7: 551-7.PubMedCentralPubMedGoogle Scholar
  104. 104.
    Kirson NY, Ivanova JI, Birnbaum HG, et al. Descriptive analysis of Medicaid patients with postherpetic neuralgia treated with lidocaine patch 5%. J Med Econ 2010; 13: 472-81.PubMedGoogle Scholar
  105. 105.
    Lin YC, Kuan TS, Hsieh PC, Yen WJ, Chang WC, Chen SM. Therapeutic effects of lidocaine patch on myofascial pain syndrome of the upper trapezius: a randomized, double-blind, placebo-controlled study. Am J Phys Med Rehabil 2012; 91: 871-82.PubMedGoogle Scholar
  106. 106.
    Ingalls NK, Horton ZA, Bettendorf M, Frye I, Rodriguez C. Randomized, double-blind, placebo-controlled trial using lidocaine patch 5% in traumatic rib fractures. J Am Coll Surg 2010; 210: 205-9.PubMedGoogle Scholar
  107. 107.
    Kwon YS, Kim JB, Jung HJ, et al. Treatment for postoperative wound pain in gynecologic laparoscopic surgery: topical lidocaine patches. J Laparoend Adv Surg Tech A 2012; 22: 668-73.Google Scholar
  108. 108.
    Saber AA, Elgamal MH, Rao AJ, Itawi EA, Martinez RL. Early experience with lidocaine patch for postoperative pain control after laparoscopic ventral hernia repair. Int J Surg 2009; 7: 36-8.PubMedGoogle Scholar
  109. 109.
    Habib AS, Polascik TJ, Weizer AZ, et al. Lidocaine patch for postoperative analgesia after radical retropubic prostatectomy. Anesth Analg 2009; 108: 1950-3.PubMedGoogle Scholar
  110. 110.
    Khanna M, Peters C, Singh JR. Treating pain with the lidocaine patch 5% after total knee arthroplasty. PM R 2012; 4: 642-6.PubMedGoogle Scholar
  111. 111.
    Bai Y, Miller T, Tan M, Law LS, Gan TJ. Lidocaine patch for acute pain management: a meta-analysis of prospective controlled trials. Curr Med Res Opin 2014. DOI: 10.1185/03007995.2014.973484.Google Scholar
  112. 112.
    Tzschentke TM, Christoph T, Kogel BY. The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MOR-NRI) concept in analgesia: the case of tapentadol. CNS Drugs 2014; 28: 319-29.PubMedGoogle Scholar
  113. 113.
    Hartrick CT, Bourne MH, Gargiulo K, Damaraju CV, Vallow S, Hewitt DJ. Fentanyl iontophoretic transdermal system for acute-pain management after orthopedic surgery: a comparative study with morphine intravenous patient-controlled analgesia. Reg Anesth Pain Med 2006; 31: 546-54.PubMedGoogle Scholar
  114. 114.
    Power I. Fentanyl HCl iontophoretic transdermal system (ITS): clinical application of iontophoretic technology in the management of acute postoperative pain. Br J Anaesth 2007; 98: 4-11.PubMedGoogle Scholar
  115. 115.
    Minkowitz HS, Singla NK, Evashenk MA, et al. Pharmacokinetics of sublingual sufentanil tablets and efficacy and safety in the management of postoperative pain. Reg Anesth Pain Med 2013; 38: 131-9.PubMedGoogle Scholar
  116. 116.
    Griffin D, Skowronski R, Palmer P. A phase 2 open-label functionality, safety, and efficacy study of the sufentanil nano taba PCA System in patients following elective unilateral knee replacement surgery. Reg Anesth Pain Med 2010; 19 (abstract).Google Scholar
  117. 117.
    Miller TE, Thacker JK, White WD, et al. Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol. Anesth Analg 2014; 118: 1052-61.PubMedGoogle Scholar
  118. 118.
    Mathiesen O, Dahl B, Thomsen BA, et al. A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery. Eur Spine J 2013; 22: 2089-96.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Khan SK, Malviya A, Muller SD, et al. Reduced short-term complications and mortality following enhanced recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthopaed 2014; 85: 26-31.Google Scholar
  120. 120.
    Kalogera E, Bakkum-Gamez JN, Jankowski CJ, et al. Enhanced recovery in gynecologic surgery. Obstet Gynecol 2013; 122(2 Pt 1): 319-28.PubMedCentralPubMedGoogle Scholar

Copyright information

© Canadian Anesthesiologists' Society 2014

Authors and Affiliations

  • Mingjuan Tan
    • 1
  • Lawrence Siu-Chun Law
    • 1
  • Tong Joo Gan
    • 2
    Email author
  1. 1.Duke-NUS Graduate Medical SchoolSingaporeSingapore
  2. 2.Department of AnesthesiologyStony Brook MedicineStony BrookUSA

Personalised recommendations