Use of accelerated postoperative rehabilitation or enhanced recovery after surgery (ERAS) protocols, which are multimodal, multidisciplinary perioperative care pathways designed to achieve rapid recovery after surgery, have increased in recent years.1 There is a significant body of evidence suggesting that implementation of the ERAS protocols can improve perioperative outcomes and reduce healthcare costs. In addition to utilizing surgical techniques such as minimally invasive surgery, which reduce tissue handling and trauma and thus reduce surgical stress response, provision of dynamic pain relief is a prerequisite to improving surgical outcome. Optimal postoperative pain management is aimed to facilitate ambulation and rehabilitation therapy. This article discusses the current evidence that should allow improved postoperative pain control with emphasis on the use of procedure-specific pain management.
PROCEDURE-SPECIFIC PAIN MANAGEMENT
The ERAS protocols, and thus the associated pain management protocols, are procedure specific. However, currently available evidence-based guidelines provide broad recommendations that may not always apply to specific surgical procedures.2,3 Several published systematic reviews and meta-analyses of randomized controlled trials assessing efficacy and adverse effects of analgesic approaches could help guide postoperative pain therapy.4 However, there is a significant heterogeneity in these meta-analyses because they include different surgical procedures rather than being procedure specific.4 Such heterogeneity preclude clinical application of these meta-analyses for specific surgical procedures. Similarly, the clinical use of the number needed to treat (number of patients required to treat to achieve at least 50% pain relief in 1 patient) concept that compares analgesic approaches is also limited due to the lack of procedure specificity.5
An appropriate procedure-specific strategy for optimal postoperative pain management should take into account the variability between surgical procedures with respect to pain characteristics (eg, type: somatic versus visceral, location, intensity, and consequences of pain).6,7 Therefore, the risk to benefit relationship of analgesic techniques would vary based on the surgical procedure. For example, pain after intra-abdominal procedures has a strong visceral component, which is not well controlled by opioids. Use of opioids in an attempt to manage visceral pain may result in high rates of adverse effects, such as nausea, vomiting, ileus, and respiratory depression.6,7 Similarly, adverse effects of certain analgesics may prevent their use after selective surgical procedures. For example, nonselective or traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are considered inappropriate for tonsillectomy due to concerns of increased perioperative bleeding.6,7 Also, because the intensity of pain is directly related to the extent of the surgical trauma, the combinations of analgesics and route of drug administration (eg, oral versus parenteral administration) may vary between surgical procedures.6–8 For example, the combination of acetaminophen and NSAIDs may provide adequate pain relief after minimally invasive surgical procedures that result in mild-to-moderate degree of pain but may not be adequate after extensive surgical procedures. Furthermore, some procedures may have a higher propensity of persistent postoperative pain (eg, mastectomy, thoracotomy, and hernia repair), which is generally neuropathic in origin, suggesting that use of gabapentinoids (eg, gabapentin and pregabalin) may be beneficial.9 Overall, analgesic approaches cannot be generalized and have to be procedure specific.
The concept of procedure-specific pain management was introduced by the PROcedure-SPEcific Postoperative Pain ManagemenT (PROSPECT) Working Group, which is an international panel of anesthesiologists and surgeons (http://www.postoppain.org).6,7 The PROSPECT initiative provides evidence-based recommendations for specific procedures. A rigorous approach is used to develop these guidelines that are further supplemented with evidence from surgical procedures with similar origin of pain. Importantly, the recommendations take into consideration the benefits and risks of an analgesic technique. For example, a systematic review of pain management approaches in patients undergoing laparoscopic colonic surgery found that an optimal multimodal analgesia technique provided acceptable pain relief and similar outcome (eg, time to oral intake, bowel movement, and hospital stay) as epidural analgesia.10 Therefore, epidural analgesia is not recommended for laparoscopic surgery due to its higher risk to benefit ratio. A recent study reported that implementation of PROSPECT recommended procedure-specific multimodal analgesic protocols improve the quality of postoperative pain and reduce opioid requirements.11
PROCEDURE-SPECIFIC MULTIMODAL APPROACH FOR RAPID RECOVERY
The primary goal of an optimal pain management technique is to provide “dynamic” pain relief that would allow early ambulation while reducing opioid consumption. This involves using combinations of nonopioids with opioids reserved as rescue analgesics.12 Unfortunately, opioids still remain the mainstay in managing postsurgical pain, although it is clear that opioid-related adverse effects increased perioperative morbidity and mortality.12–15 Therefore, a recent sentinel event alert from the Joint Commission has emphasized the limitations of opioids and recommended a goal-related approach to pain management where the goal does not have to be to achieve a certain pain score.16
Although multimodal analgesia techniques have assumed increasing importance in the management of perioperative pain, it is commonly misunderstood. Inappropriate analgesic combinations are used, which may not necessarily improve pain control. Also, several analgesic combinations are administered with no regard to the type of surgical procedure, for example, administering all patients acetaminophen, NSAID or cyclooxygenase (COX)-2-specific inhibitor, dexamethasone, ketamine, clonidine, gabapentin, and opioids. Such a “shot gun” approach is not necessary and can be detrimental.
An ideal multimodal analgesic technique would include local/regional analgesic techniques (ie, wound infiltration, peripheral nerve blocks, and neuraxial blocks) as the principle component because they provide excellent dynamic pain relief (ie, pain relief during movement).12 Neuraxial analgesia includes epidural analgesia, paravertebral block, and intrathecal (or spinal) opioid analgesia. Epidural analgesia has been shown to provide excellent dynamic pain relief with improved perioperative outcome compared with systemic analgesia.17 These benefits are generally appreciated when epidural analgesia is used intraoperatively, as well as continued for 48 hours postoperatively. However, there are concerns of potential adverse effects (eg, minor complications such as hypotension and urinary retention and major complications such as epidural hematoma and abscess) and technical failures that may alter the associated risk-benefit ratio.18,19 In addition, the use of minimally invasive surgical approach and increased emphasis on early ambulation and shorter hospital stays may further limit the benefits of epidural analgesia.10 Recent studies suggest that the outcome measures (eg, hospital stay) after minimally invasive surgery are similar after epidural analgesia and appropriately administered multimodal analgesic techniques.10 Therefore, the role of epidural analgesia is being redefined. It seems that epidural analgesia might be considered in high-risk surgical patients (eg, those with significant pulmonary disease) undergoing thoracic and major open abdominal surgery.12,20
Thoracic paravertebral block is an alternative to epidural analgesia for patients undergoing unilateral surgical procedures (eg, thoracotomy). It provides similar analgesic efficacy but has favorable adverse effect profile, as it does not significantly block the sympathetic system.21,22 In addition to thoracic surgery, paravertebral blocks are also being used for breast surgery.23 The success rate of paravertebral blocks can be improved when they are placed under ultrasound guidance.
Peripheral nerve blocks (single injection or continuous perineural local anesthetic infusion) provide excellent dynamic pain relief for extremity surgery.24–26 However, one of the limitations of peripheral nerve blocks is that the associated motor blockade may lead to injury. This is particularly of concern for lower limb nerve blocks, as they may result in delayed ambulation and increase the potential of falls.27 The optimal concentration and volume of the local anesthetic that would provide adequate pain relief without motor blockade remains controversial. Therefore, for lower limb surgery, distal nerve blocks are preferred as they provide site-specific analgesia with minimal motor blockade. For example, in patients undergoing foot and ankle surgery, distal nerve blocks (ie, popliteal sciatic) provide similar pain relief as peripheral nerve blocks at the hip (ie, sciatic nerve block at the gluteus and femoral nerve block) without the concerns of delayed ambulation and risk of falls.
Intravenous (IV) lidocaine infusion during and after surgery has been shown to reduce postoperative pain and opioid requirements, as well as reduce the length of hospital stay.28,29 Pain relief achieved with lidocaine infusion seems to be comparable with that of epidural analgesia. No significant local anesthetic toxicity has been reported in the published systematic reviews. However, the optimal dose and duration of lidocaine infusion remain controversial. Nevertheless, IV lidocaine infusion could be recommended in patients where other analgesic therapies are not adequate or appropriate.
In recent years, numerous studies have reported analgesic efficacy of the transversus abdominis plane (TAP) block in patients undergoing abdominal surgical procedures.30,31 The TAP block is essentially a field block in which the local anesthetic solution is placed under ultrasound guidance between the transversus abdominis and the internal oblique muscles. Interestingly, a recent study comparing the analgesic efficacy of TAP block with surgical wound infiltration in patients undergoing inguinal hernia repair reported similar pain relief and reduction in opioid requirements.32
Infiltration with local anesthetic of the surgical incision, as a component of multimodal analgesia, has been shown to improve pain relief and reduce opioid requirements.33,34 Therefore, it is recommended that in absence of neuraxial blocks or peripheral nerve blocks, wound infiltration should be performed whenever possible. When performing wound infiltration, it is necessary to ensure that all layers of the incision are infiltrated in a controlled and meticulous manner. Of note, local anesthetic toxicity and wound infection and healing are not major concerns with wound infiltration. Although long-acting local anesthetics (ie, bupivacaine or ropivacaine) are generally advocated, there is lack of evidence regarding their optimal concentration. Recently, it has been suggested that the best approach for wound infiltration is to use low concentration and high volume of local anesthetics, similar to tumescent analgesia, as this will allow more extensive wound infiltration. One of the limitations of currently available local anesthetic is that the duration of analgesia is short, usually 12–16 hours, which results in abrupt experience of pain. Therefore, several studies have infused local anesthetics via a catheter that is place in the surgical wound.35 Local anesthetic solutions are sometimes combined with additives, such as clonidine, fentanyl, and ketorolac presumably, to improve efficacy and prolong the duration of analgesia. However, the evidence for benefits of these additives is lacking. The introduction of a liposomal formulation of bupivacaine (Exparel) that allows delivery of bupivacaine for 96 hours with a single local administration has been shown to provide excellent dynamic pain relief for up to 72 hours.36–38 The evidence of prolonged analgesia after wound infiltration with liposomal bupivacaine is accumulating rapidly. Several studies have reported significant pain relief with the combinations of wound infiltration with liposomal bupivacaine, acetaminophen, and NSAID or COX-2 as multimodal analgesic regimens.
Acetaminophen is a widely used over-the-counter analgesic and antipyretic drug; however, it is underutilized in the perioperative period. The IV formulation of acetaminophen has a predictable onset and duration of analgesia, because it avoids the delays in absorption after oral administration due to delayed gastric emptying which is common in the perioperative period.39,40 Because of the differences in mechanisms of action and reports of improved analgesic efficacy, combination of acetaminophen and nonselective NSAIDs or COX-2 selective inhibitors should be used whenever possible.41,42 The analgesic efficacy of equipotent doses of NSAID and COX-2 selective inhibitors is comparable. However, there is a potential risk of increased surgical bleeding with conventional NSAIDs.43 In contrast, the COX-2-specific inhibitors have no effects on platelet function and do not influence surgical bleeding, and thus, they may be administered preoperatively. Overall, the incidences of other adverse effects of NSAIDs (eg, cardiovascular, gastrointestinal, and renal) are similar to that of COX-2-specific inhibitors. A recent meta-analysis of 280 trials of NSAIDs including COX-2-specific inhibitors versus placebo found that the vascular risks of diclofenac (150 mg/d) and ibuprofen (2400 mg/d) were comparable to the cyclooxygenase inhibitors.44 Interestingly, naproxen (1000 mg/d) was associated with less vascular risk than other NSAIDs. The authors concluded that NSAIDs increase vascular and gastroenterology risks to a varying extent, but the size of these risks can be predicted, which can help guide clinical decision making.
The administration of a single dose of dexamethasone 4–8 mg IV in the intraoperative period provides excellent pain relief and reduces postoperative nausea and vomiting.45,46 Therefore, if there are no contraindications, dexamethasone should be considered an integral component of multimodal analgesia regimen. Although there is a concern for increased gastrointestinal side effects, increased wound infection, and delayed wound healing, single dose of dexamethasone has shown to be safe.
The other analgesic adjuncts that have received significant attention include ketamine and gabapentinoids (ie, gabapentin and pregabalin). Several meta-analyses have reported reduced pain scores and/or opioid consumption with the use of these analgesic adjuncts. Overall, these drugs seem to play a significant role in improving pain control in selective patient population and surgical procedures. It is generally accepted that the gabapentinoids may be beneficial in patients and surgical procedures that are at a high risk of persistent postoperative pain (eg, mastectomy).47 Although the duration of administration of gabapentinoids remains controversial, these drugs are best started before surgery and administered for at least to 7–10 days postoperatively. Also, the dose of gabapentin and pregabalin remains controversial. The commonly used dose for gabapentin is 600–800 mg orally 2–3 hours before surgery and 300 mg every 8 hours postoperatively, whereas the dose for pregabalin is 70–150 mg orally before surgery followed by 50–75 mg every 12 hours postoperatively. The doses of these drugs need to be adjusted for renal function (eg, creatinine clearance). With respect to ketamine, it seems to be beneficial in opioid-tolerant patients and major surgical procedures that are generally associated with significant postoperative pain.48 Unfortunately, the dose and duration of ketamine administration remains controversial. Most studies have used a bolus dose of 0.2–0.5 mg/kg followed by an infusion of 0.1–0.2 mg/kg/h. Although rare, one of the major concerns with ketamine is the occurrence of hallucinations, nightmares, and cognitive dysfunction.
With acceptance of preventive analgesia, it is clear that analgesics should be administered at the appropriate time (preoperative or intraoperative) to provide sufficient analgesia in the early recovery period, as well as continued in the postoperative period until the surgical inflammation is resolved.49–51 The above-mentioned nonopioid analgesic combinations should provide adequate pain relief for most surgical procedures that induce mild-to-moderate pain. Weak opioids (eg, tramadol) may be used to supplement the nonopioid analgesics if the pain intensity remains to be moderate, whereas strong opioids (eg, hydrocodone and oxycodone) may be used for moderate-to-high intensity postoperative pain.
There are several patient-related factors that can influence the intensity of postoperative pain.52–56 Preoperative pain intensity is a risk factor for development of severe acute postoperative pain and long-term postsurgical pain.54 Therefore, preoperative analgesic should not be discontinued. If it is necessary to discontinue an analgesic (eg, an NSAID), it should be replaced with another equivalent analgesic. Patients with preoperative anxiety have greater postoperative pain intensity.52 Also, patients with chronic pain conditions such as fibromyalgia have a higher incidence of pain in the postoperative period.54–56 Given the prominent role of emotional and psychosocial factors in the experience of preoperative, postoperative, and chronic persistent postoperative pain, these variables should be routinely assessed preoperatively and postoperatively.
Another factor that has been shown to influence pain management includes the perceptions of healthcare professional. A recent study reported that several “minor” surgical procedures, such as laparoscopic cholecystectomy, tonsillectomy, and hemorrhoidectomy, were associated with higher postoperative pain scores as compared with some major surgical procedures.57 The most likely reason for the paradoxical observations of this study is that patients undergoing less extensive surgical procedures are considered having less pain and therefore received inadequate pain management.
There are several areas where evidence is insufficient or conflicting. Many studies have insufficient design due to use of inappropriate analgesic combinations and/or inadequate duration of analgesia. Most studies evaluating analgesic techniques have evaluated single modality analgesic therapies (ie, 1 drug or technique versus placebo or another drug or technique). There is a need to identify optimal analgesic combinations and optimal route of analgesic administration that would allow improved pain relief while avoiding adverse side effects. Also, it is necessary to follow patients for a prolonged period at least 3–6 months to determine the role of multimodal analgesic techniques in influencing persistent postoperative pain.
The benefits of optimal pain management are well recognized. Nevertheless, treatment of postoperative pain continues to be a major challenge, and inadequate postoperative pain relief remains disturbingly high. One of the reasons for suboptimal pain management may be related to inadequate or improper application of available analgesic therapies. Use of patient-specific and procedure-specific pain management strategies should improve pain control and consequently improve perioperative outcome, including early ambulation, ability to perform rehabilitation activities, and return to activities of daily living.
An optimal multimodal pain therapy would be initiated in the preoperative period with identification of patients at risk of greater pain intensity. Patient counseling and expectation management should improve pain relief and patient satisfaction. Local/regional analgesia techniques should be used as the first-line analgesic therapy, which should be combined with acetaminophen and an NSAID or COX-2 inhibitor if there are no contraindications. In addition, a single dose of dexamethasone would provide additional analgesic efficacy. Analgesic adjuncts such as ketamine and gabapentinoids are generally reserved for select patient population and/or surgical procedures.
Due to the review nature of this article, permission from institutional review board was not considered necessary.
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