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9 Articles in Volume 13, Issue #9
Perioperative Pain Plan: Why is it Needed
A Case for Spinal Cord Stimulation Therapy—Don’t Delay
History of Pain: The Nature of Pain
Safe Usage of Analgesics in Patients with Chronic Liver Disease: A Review of the Literature
PROP Versus PROMPT: FDA Speaks
Editor's Memo: Long-Acting Opioids: More Than a Labeling Issue
Use of Long-term Muscle Relaxants
PAINWeek Highlights: Coping Skills, Insomnia, and Opioid Abuse Deterrence
Letters to The Editor

Perioperative Pain Plan: Why is it Needed

Acute postoperative pain can lead to persistent postoperative pain in 10%-50% of patients. Effective pain management before, during, and immediately after surgery can prevent this development.

More than 45 million surgical procedures are performed in the United States each year.1 Despite improved understanding of pain mechanisms, interpretation of pain signals, and development of new analgesic techniques,2 the under-treatment of postoperative pain continues.3 In fact, it has been estimated that acute postoperative pain will develop into persistent postoperative pain in 10% to 50% of individuals after common operations.4 Since chronic pain can be severe in up to 10% of these patients, persistent postoperative pain represents a major clinical problem—affecting at least 450,000 people each year. Today, many hospital systems are graded based on how well they manage postoperative pain. Therefore, effective and timely preemptive pain control not only benefits patients, it can improve hospital ranking and reduce health-care expenditures.5

Defining the Problem

Pain, as defined by the International Association for the Study of Pain (IASP), is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.6 Perioperative pain management refers to actions before, during, and after a surgical procedure that are intended to reduce or eliminate postoperative pain before the patient is discharged after the procedure.2 Preoperative pain management strategies involve many of the same techniques as postoperative pain management, with the one exception being the temporal relationship to the surgical procedure. Intraoperative pain techniques may involve multiple systemic pharmacologic agents and, in some cases, regional pharmacologic therapy (epidural administration and selective peripheral nerve blockade). Chronic postsurgical pain is defined as pain lasting more than 3 to 6 months after surgery. The pain differs in quality and location from pain experienced prior to surgery, and is usually associated with iatrogenic neuropathic pain caused by surgical injury to a major peripheral nerve.3

Scope of Risk: Assessing Pain

Patients at the highest risk for untreated postoperative pain include the elderly and those with lower socioeconomic status. Many of the reasons for this stem from lack of patient understanding regarding acute perioperative pain, lack of appropriate patient education regarding the management of perioperative pain, and inability to afford the treatments for that perioperative pain from pharmacies and other postoperative health care providers. Approximately one-half of older patients who have unmanaged postoperative pain continue to experience that same pain chronically 1 year after discharge.7 Children are also at risk for inadequately managed postoperative pain. Some of the more prominent factors for this include inability to assess pain and concerns regarding addiction.8

Since pain is experienced differently in all patients, it is imperative to use appropriate pain assessment scales along with a focused physical examination for defining and rating pain in patients. Age, cognitive status, language barriers, and cultural background are some of the key considerations. There are many different validated pain-rating scales available to “objectively” quantify a patient’s pain. Table 1 lists some of assessment scales.9-13 Each of these scales, and others not listed, are validated assessments in specific patient populations. For example, a patient with advanced dementia would be most appropriately assessed for pain using the pain assessment in advanced dementia (PainAD) scale rather than a visual analog scale (VAS), as a VAS requires the patient to be able to interact with the assessor and reliably point on the scale to determine how much pain he or she is experiencing. The PainAD scale relies on mostly non-verbal assessments in order to calculate the patient’s pain. It is also important to note that not all scales have the same numerical rating of pain. The VAS rates pain from 0 to 10, while the neonatal infant pain scale (NIPS) rates pain from 0 to 12.

Using the same assessment scale throughout the perioperative period has multiple advantages. The ability to show trends during the preoperative and postoperative period allows the clinician to direct pain therapies based on efficacy as determined by the patient. If multiple assessment scales are used, it can lead to inappropriately high or low scoring of the patient’s pain because many of the validated scales do not use the same metrics to evaluate for pain. Consistencies in pain assessment scoring and following the patient score trends provides invaluable data for the clinician managing perioperative pain.

The Pain Pathway

Multimodality therapy is controversial and has had mixed results in the setting of postoperative pain.2 However, it is important to see how the concept of multimodal therapy is assembled, the different aspects of multimodal therapy, and how they each relate to a different facet of perioperative pain management. Non-pharmacological methods include physical therapy, music or art therapy, biofeedback, and a host of other modalities not covered in this review.

In order to adequately address the different pharmacologic options, it is important to review the pain pathways and how each of the pharmacologic options presented here can affect transduction, transmission, modulation, and perception of pain (Figure 1).14 Transduction involves a noxious stimulus (mechanical and/or thermal in nature) causing activation of A-delta or C fibers in peripheral nerves. These nerve impulses are then transmitted though A-delta, which are larger diameter myelinated nerve fibers, and C fibers, which are smaller-diameter unmyelinated nerve fibers, from the periphery to the dorsal horn within the spinal column where they synapse with the spinal tracts and ascend into the brain.

Modulation occurs within the dorsal horn and within the brain. (Thalamus, somatosensory cortex, and periaqueductal grey matter are noteworthy landmarks within the brain that aid in localization of pain.) Modulation involves the amplification or dampening of pain signals from the periphery within the central nervous system (CNS). This is a prime target for many of the non-pharmacologic and pharmacologic treatments used in management of pain.

Perception of pain takes transduction, transmission, and modulation and combines that with the patient’s previous experiences of pain and emotional or psychological aspects of pain sensation.



Opioids are effective pain management tools that can be used during the preoperative, intraoperative, and postoperative period (Table 2). However, opioid use is also associated with postoperative nausea, vomiting, pruritus, urinary retention, and respiratory depression. For patients who are on chronic opioid therapy prior to surgery, there are certain evidence-based approaches to provide adequate analgesia in the postoperative period.15 These include:

  • Ensuring the patients receive their maintenance dose of opioid prior to surgery
  • Utilizing patient-controlled analgesia (PCA)
  • Considering the amount of maintenance opioid the patient takes preoperatively and adjusting the postoperative doses of opioids accordingly to prevent inadequate pain management due to patient tolerance with “usual or standard” postoperative opioid doses.

One example of the need to adjust opioid dosages is the oncology patient who is currently taking 160 mg of controlled-release oxycodone every 12 hours, in addition to breakthrough doses of oxycodone on a daily basis. In this case standard doses of postoperative opioids may be insufficient to allow the patient to achieve comfort or pain relief. Higher doses of opioids are generally necessary, accounting for the patient’s physical tolerance to opioids.

There are many routes of administration available for opioids in the perioperative arena. Epidural, intrathecal, transmucosal, transdermal, and intravenous are some of the more common routes utilized during the perioperative period. For the purposes of this review, neuraxial will refer to the intrathecal and epidural routes of administration. Using neuraxial administration, small doses of opioid have been shown to be effective in modulation of pain during transmission of pain signals through the spinal cord. These neuraxial routes of administration decrease systemic opioid exposure and, therefore, can decrease systemic side effects and toxicity. Neuraxial blockade poses the risk of respiratory depression and vigilant hourly assessment and monitoring of respiratory rate should be done. In addition, neuraxial administration of opioids also has an increased risk of causing pruritus and urinary retention compared to traditional oral and intravenously-administered opioids.

Another concern for clinicians in the perioperative period is the development of opioid-induced hyper-algesia. This occurs when opioids given to manage pain actually make the pain worse. The current literature is inconclusive with regards to the phenomenon of opioid-induced hyperalgesia, yet it should be part of any differential diagnosis when caring for patients who experience worsening of pain when administered opioids.

Anti-inflammatory Agents

Anti-inflammatory agents are also excellent options for many postoperative patients. Non-steroidal anti-inflammatory agents (NSAID) are known to be opioid-sparing in the postoperative setting.16,17 NSAIDs aid in decreasing inflammation through inhibition of the cyclooxygenase (COX) enzyme system—more specifically, COX-2, which is stimulated by multiple proinflammatory cytokines, including interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor alpha, and lipopolysaccharide. These cytokines induce COX-2 to produce prostaglandin E2, an inflammatory mediator that leads to progression of inflammation and pain. Inhibition of the COX-2 enzyme is how a majority of NSAIDs help to decrease pain.

However, one prominent side effect of NSAIDs—increased risk of bleeding—is a concern for the perioperative patient, especially those undergoing procedures involving solid organs. Risk of bleeding is especially a concern with ketorolac when used for greater than 5 days, in the elderly, and at higher doses.18 There is long-standing controversy regarding the use of NSAIDs in patients undergoing orthopedic procedures (hip and knee arthroplasty, spinal fusions, etc) because of concern that NSAIDs impair bone healing. A recent review of available NSAIDs, including meloxicam, celecoxib (Celebrex), indomethacin, ibuprofen, and aspirin yielded no robust data that these agents are an absolute contraindication in orthopedic procedures.19 The full extent of delayed healing or the time-course of fracture development is not well defined. Other potential risks of NSAIDs include renal toxicity and thromboembolitic complications.

Local Anesthesics

Local anesthetics have a large role in the intraoperative and postoperative pain management environments. Local anesthetics offer the advantage of decreased peripheral sensory input (transduction). The mechanism of action for local anesthetics is by stabilizing nerve membranes and decreasing the rate of depolarization, therefore decreasing transduction. There are data from the orthopedic literature on the use of single peripheral nerve and plexus blocks for hip and knee procedures, which allows for earlier mobilization and decreased opioid consumption postoperatively.20 Peripheral nerve and plexus blocks are carried out using local anesthetics such as ropivacaine or bupivacaine and can be combined with epinephrine. The purpose of the epinephrine is to prevent spreading of the local anesthetic agent away from the targeted nerves. This also allows for prolonged nerve blockade and prevention of side effects, which can be associated with systemic exposure.

Local anesthetics, like opioids, can be administered through multiple routes of administration during the perioperative periods. Thoracic epidurals can assist with patients after a thoracotomy. These epidurals can contain local anesthetics such as bupivacaine or ropivacaine alone or in combination with opioid agonists such as fentanyl. This method of delivery decreases total opioid consumption and decreases systemic effects, while providing patients with the ability to cough and continue with deep breathing, attenuating hypoxemic episodes.21 Respiratory depression is a primary concern when patients are given epidural or intrathecal analgesia and careful monitoring of respiratory function must be done to ensure safe and optimal patient outcomes. Potential side effects from the use of local anesthetics include seizures, cardiovascular compromise including arrhythmias or hypotension in high doses or with non-epidural systemic local anesthetic exposure. The development of paresthesias, while rare in clinical practice, is another possible side effect.

Adjuvant Therapy

The use of gabapentin and pregabalin (Lyrica) in the perioperative period is relatively new compared to the use of opioids and NSAIDs, but could be beneficial in some cases. There is promising data on the use of gabapentin and pregabalin preoperatively to decrease postoperative pain. Gabapentin and pregabalin bind to the alpha2delta calcium channels that are widely distributed in the CNS and peripheral nervous system. By reducing the hyperexcitability of the dorsal root ganglion activated by surgery, gabapentin and pregabalin may prevent the development of chronic postsurgical pain.

The orthopedic22 and obstetric23 surgical populations have data that show that gabapentin, given in the immediate preoperative period, resulted in a significant decrease in opioid consumption, as well as fewer side effects, compared with the use of systemic opioids. The doses of gabapentin administered ranged widely (from 300 mg to 1,200 mg as a single dose prior to the procedure). Therefore the question remains: what is the optimal dose for preemptive pain prevention for orthopedic and obstetric procedures?

In addition, there are promising recent reports regarding the use of pregabalin in the neurosurgical perioperative patient. In a trial of lumbar discectomy patients, pregabalin 150 mg was administered preoperatively. The pregabalin patients had a decreased VAS 4 hours after reversal of anesthesia. However, one week after surgery, there was no difference in VAS between pregabalin treated and placebo groups.24 Common side effects include sedation, visual disturbances, and dizziness. Further research is still needed into the use of these adjuvants.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is also employed during the perioperative period as an adjuvant in pain management. Primarily used during induction or maintenance of anesthesia, ketamine has analgesic and sedative properties and does not cause respiratory suppression to the same degree as other sedative agents like midazolam or propofol. Other applications of ketamine have included the use of subanesthetic dose, continuous infusions as an adjunct to opioids for patients with severe pain not responsive to opioids alone, such as chronic regional pain syndrome. The primary side effects of ketamine include hallucinations, dizziness, euphoria, and tachycardia or hypersalavation secondary to its muscarinic antagonist properties. Hallucinations have limited ketamine’s utility among the general population as a first-line analgesic in adults in the perioperative period.

Other adjuvant medication options such as clonidine and partial agonist opioids (eg, nalbuphine) are also utilized in nerve blockade. Clonidine, through its central alpha2 adrenergic agonist mechanism, has been shown to increase analgesia and allow for lower doses of local anesthetics and opioids to be administered through epidural administration. Side effects include hypotension; and with clonidine, a withdrawal phenomenon comparable to that from withdrawal from opioids.

Preventing Chronic Pain

As noted, a growing concern among pain practitioners is that undertreated postoperative pain will lead to the development of chronic pain. Chronic pain has a significant impact on patient quality of life. In an effort to provide a single repository for perioperative pain management strategies based on surgical procedures, the PROSPECT working group has compiled a range of recommendations from general to orthopedic to obstetric and gynecologic surgical procedures. Their evidence, methods, and recommendations are available online at www.postoppain.org.25

Postoperative patients require the cooperation of the surgeon, anesthesiologist, and the primary care provider in order to minimize postoperative pain. Rehabilitation after any surgical procedure takes time, in some cases significant lengths of time. Follow up of cases with the operative clinician and subsequent adjustments—such as increasing and decreasing postoperative opioids and other modalities to minimize pain—are critical. These efforts should be made concurrently with the primary care clinician, taking note of the patient’s quality of life and which pain management modalities have been tried, and continuing those effective modalities after the procedure. Information sharing between these clinicians provides patients with better understanding of their acute postoperative pain, prevents medical errors due to lack of communication, and strengthens further open lines of communication between all clinicians involved.

For more on preventing acute pain from becoming chronic, read Sean Mackey's article.

Last updated on: November 21, 2013
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