Chapter 42. Acute Pain Management in Adults

Pain relief in an acute pain situation, besides having a humane value, has an important bearing in the well-being of an individual. Although it may not be possible to achieve total relief in all situations, a serious effort should be made.

Since the discovery of opioid receptors in 1978, efforts have been made to improve the delivery of analgesic drugs in a more effective way. Thanks to these advances in basic science on the clinical front, the last two decades have witnessed major strides in postoperative analgesia with the creation of acute pain services, the increased use of epidural analgesia, and the introduction of the concept of patient-controlled analgesia.

The tissue damage produced by surgery is similar to that of acute injury. It causes local and systemic noxious stimuli that initiate nociceptive impulses, relays, and reflexes throughout the nervous system. In addition to the disturbances associated with the conscious interpretation of theses impulses, there are autonomic effects generated that may disrupt the healing and recovery process. The deleterious physiologic side effects of acute pain are well recognized. In the patient who is breathing spontaneously, muscle splinting (seen in conjunction with discomfort of chest or abdominal origin) may result in decreased vital capacity, decreased functional residual capacity, and ultimately decreased alveolar ventilation. Atelectasis is a frequent postoperative complication. Discomfort experienced during coughing may result in retention of secretions and subsequent pneumonia. The sympathetic response to pain may cause increased cardiovascular demands. This may be apparent clinically by signs of tachycardia, increased peripheral resistance, and hypertension; these signs are associated with increased cardiac work and myocardial oxygen consumption. The potential for myocardial ischemia and infarction is obvious. Muscle spasm produced by segmental and suprasegmental reflex motor activity may perpetuate pain. In the chest wall and abdomen, pain and muscle spasm may compromise respiratory function. The gastrointestinal tract similarly is affected by increased sympathetic activity. Pain increases intestinal secretions and smooth muscle sphincter tone and decreases intestinal motility. By similar mechanisms, pain may produce urinary retention. Acute injury also has an impact on the endocrine system, causing sodium and water retention and hyperglycemia. Immobility from acute postoperative pain may predispose the patient to deep vein thrombosis and pulmonary embolism as a result of venostasis and platelet aggregation. In a complex intertwined relationship, psychological alterations may occur concomitantly with the physiologic ones.1

Numerous guidelines have been published about the management of postoperative pain. First the Agency for Health Care Policy and Research (AHCPR) took the lead in educating caregivers as well as the public. The American Pain Society as well as the American Society of Anesthesia then followed suit, and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has published “Standards for Pain Management in Hospital Settings” that were implemented in 2001.2,3

The guidelines from JCAHO incorporate pain measurements in the bedside chart in addition to tracking the patient’s temperature, blood pressure, heart rate, and respiratory rate, thus making pain rating the fifth vital sign.

However, a simple numerical assessment of pain on the visual analog scale or verbal rating scale does not differentiate between pain at rest and pain with movement or incident pain, which is usually more challenging to manage.

Also, to effectively adjust the analgesic regimen, one needs to track sedation and other possible adverse effects associated with the administration of analgesics such as nausea and vomiting, respiratory depression, and cognitive impairment.

The importance of good postoperative analgesia and its impact on favorable postsurgical outcomes are undeniable. Pain in the postoperative period may contribute to adverse outcomes including thromboembolic and pulmonary complications.

Many factors influence our perception of postoperative pain. Determinants of the intensity, quality, and duration of postoperative pain include:

• The site, nature, and duration of the operation, including the type of incision and the amount of intraoperative trauma
• The physiologic and psychological makeup of the patient
• The preoperative psychological, physical, and pharmacologic preparation of the patient
• The presence of serious related complications
• The anesthetic management
• The quality of postoperative care. Some of the ineffectiveness of current medical analgesic therapy can be attributed to inadequate understanding by nurses of the pharmacology of narcotics.

Inadequate understanding by physicians of the nature of pain also has been demonstrated. A structured interview of 37 medical inpatients showed that 32% had severe distress despite a narcotic analgesic regimen; an additional 41% declared themselves to be in moderate distress. As part of the study, a questionnaire survey of 102 staff physicians showed an underestimation of effective dose ranges, overestimation of the duration of action, and an exaggerated concern with the addictive potential of meperidine in a therapeutic dosing range. It is thought that the development of addiction in patients with no previous addictive history is rare. Children, perhaps the most dependent group in the hospital population, also bear the burden of postoperative suffering. As a reaction to discomfort, many children withdraw and vegetate. This may be misinterpreted as coping with the pain. Many immature patients fear injection, deny pain, and are unable to realize that a short-term discomfort may grant a longer period of analgesia.4,5

In summary, at least three major factors contribute to the inadequacy of traditional analgesic therapy. Foremost is the incomplete comprehension by medical personnel of analgesic pharmacodynamics. This lack of knowledge coupled with overconcern about respiratory depression and addiction liability leads to the administration of inadequate doses. Second, the logistics of administering narcotics often leads to a long lag period between the onset of pain and the administration of pain-relieving drugs. Coupled with the delay in absorption of intramuscularly administered analgesics, this interval may distress the patient greatly. A third barrier to adequate analgesia is a common hospital community attitude that stoicism is a virtue. The suffering patient may sense such an attitude and, rather than attacking this formidable barrier, refrain from requesting appropriate medication.6

A surgical incision cuts through a variety of tissues including nerve endings and activates specific nociceptors (pain receptors) as well as free nerve endings. It is associated with the release of inflammatory mediators such as bradykinin, serotonin, and histamine, which contribute to peripheral sensitization. Clinically, this phenomenon is manifested by hyperalgesia, which is an amplification of noxious pain signals. These painful signals are transmitted to the dorsal horn of the spinal cord in an amplified fashion and are increased in duration.

The nociceptor information is transmitted to the cord via the A-δ (myelinated) fibers and the C (unmyelinated) fibers. When peripheral sensitization occurs, painful information can also be carried by A-α and A-β fibers. This is manifested by allodynia, a pain state where non-noxious stimuli are transformed and expressed as painful. Signals entering the central nervous system from the periphery will be increased in amplitude and duration. This is the phenomenon of “wind up” or central sensitization.7

Analgesic techniques, to be effective, will need to counteract these activations of nociceptors at the periphery as well as centrally, thus the need for a multimodal or “balanced” analgesia to ensure patient comfort, to improve early mobilization, and decrease the consequences of the postsurgical stress.

Traditional methods of intermittent on request, intramuscular, or subcutaneous administrations of opioids have failed to provide satisfactory analgesia. Failure to adequately relieve postoperative pain contributes not only to discomfort, but to postoperative morbidity, poor patient outcome, and prolonged hospital stay.

Endocrine and Metabolic Response

Any injury provokes a neurohumoral response involving the hypothalamic-pituitary-adrenal axis, activation of sympathetic nervous system, and an increase in glucagon secretion.1 Surgery leads to a similar reproducible response, which causes hyperglycemia, increased lipolysis, lipid oxidation, accelerated protein breakdown, and nitrogen loss.2,3

These responses begin during surgery and may be maintained for days, especially after major abdominal or thoracic surgery. The stress response peaks in the postoperative period.4 Clinically, this presents as hypertension, tachycardia, arrhythmias, myocardial ischemia, protein catabolism, immune system suppression, and impaired renal excretory function. Suppression of the stress response is possible, though not completely. The intensity of the stress response depends on the site of surgery (extremities versus thoracic or abdominal), pain control modality, (neuraxial versus systemic), medication used (local anesthetic versus opioid), and initiation and maintenance of treatment (intraoperative versus postoperative). Studies have shown that stress response and morbidity in the first 24 hours is less in patients receiving epidural analgesia with local anesthetics with or without opioids.8,9

Pulmonary Function

Pulmonary dysfunction is commonly seen after thoracic and upper abdominal surgery and is more important than after extremity or laproscopic surgery. This is a major source of morbidity and mortality in the perioperative period. Primary mechanisms are decreased phrenic nerve activity and diaphragmatic dysfunction, reflex increased spinal arc activity causing increased intercostals, and abdominal muscle tone. Clinically, it is manifested as a decrease in functional residual capacity and a decrease in tidal volume. Existing pulmonary disease or respiratory depression due to opioid analgesics may compound these problems.10

Gastrointestinal Motility

A combination of surgery and anesthesia in addition to pain produces a decrease in gastric motility, especially in the colon. The stomach and small intestines recovers within 12 to 24 hours after abdominal surgery, whereas the colon is inhibited for at least 48 to 72 hours. Early enteral feeding is known to decrease the surgical stress response, thus making a difference to the postoperative morbidity.11

Possible mechanisms to explain illeus are sympathetic hyperactivity in response to surgical stress and pain, especially after abdominal surgery, and abdominal pain that activates spinal reflex, which inhibits intestinal motility. Use of opioids for pain control would further promote illeus. Epidural opioids also inhibit gastrointestinal motility, but somewhat less than systemic opioids.12

Cardiovascular

Uncontrolled pain causes increased sympathetic tone and a resetting of baroreceptors that cause an increase in heart rate and blood pressure. The neural outflow also causes redistribution of blood to and within various organs. This predisposes to myocardial ischemia in the presence of coronary artery disease and may induce arrhythmias. Stress per se is also arrhythmogenic in nonischemic myocardium.13

Besides the increase seen in catecholamines and sympathetic neural outflow, there is a reflex decrease in parasympathetic outflow due to pain. This imbalance in the autonomic system alters the baroreceptors settings.14

Immune System

There is a large amount of clinical evidence showing suppression of both humoral and cellular mechanisms of the immune system following trauma and surgery. There is a decrease in responsiveness to antigen and mitogen, delayed hypersensitivity, natural killer cell activity, and antibody response.15 The exact causative mechanism is not known. Increased release of glucocorticoids is seen as one of the reasons, but other stress response hormones may also cause immune modulation.16

Coagulation System

Changes in the coagulation system primarily occur from surgery in the form of activation of the coagulation cascade, increased platelet activity, and decreased fibrinolytic activity leading to increased coagulability. Use of epidural analgesia in the perioperative period has been found to produce less platelet activity and improved fibrinolysis, which may be related to the systemic effects of local anesthetic.17

Cognitive Dysfunction

Postoperatively, 10% to 50% of patients develop transient cognitive impairment, which is worse on the second day, but they usually recover within a week. Elderly patients may take up to 3 months to recover baseline cognitive function. Exact mechanisms are not clear and there is no conclusive data to suggest a particular choice of anesthetic technique. Delirium occurs in about 10% of patients undergoing noncardiac surgery after age 50. Electrolyte abnormality, sleep apnea, history of alcohol abuse, and benzodiazepines and meperidine intake are risk factors for delirium. Studies have found that high levels of postoperative pain can cause delirium and, vice versa, delirium can impair cognition and cause exacerbation of pain.

Options for pain management in the postoperative period include the following:

• 1. Systemic analgesics
• 2. Neuraxial opioids and local anesthetics
• 3. Regional anesthetic techniques
• 4. Adjunct treatments, e.g., transcutaneous electrical nerve stimulation (TENS) unit, heat application, and self-hypnosis.

Opioids

Opioids remain the mainstay of postoperative analgesia and have demonstrated their efficacy in the management of severe pain. The main concerns about the use of opioids remain their side effects: nausea, vomiting, ileus, biliary spasms, respiratory depression, and the potential for abuse, although in the immediate postoperative period this is rarely an issue. Opioids can be administered intramuscularly, subcutaneously, or intravenously.

The administration of opioids by intramuscular injections prescribed on an as-needed basis provide fluctuating opioids levels resulting in sedation and other adverse effects when levels are high and inadequate analgesia when levels are low. A better method of administration of opioids is via a microprocessor-controlled infusion pump or patient-controlled analgesia (PCA).18

A preset dose of opioids is delivered to the patient when activating the demand switch, given that a predetermined time has elapsed since the previous dose; this is the “lockout” time. An upper limit per hour or per 4 hours is predetermined and set in the program as an additional safety device. Numerous studies have demonstrated the safety and opioid-sparing effect of PCA (Table 42-1).

Patients taking opioids preoperatively will show some tolerance intraoperatively and postoperatively. One can safely assume that patients taking two tablets of combination analgesics such as Percocet (5 mg oxycodone/tablet) or Vicodin (5 or 7, 5 mg hydrocodone) four times daily will require 1 mg of morphine per hour postoperatively to replace their regular opioids.

Non-Opioid Analgesics

With opioids alone, intramuscularly or intravenously, the analgesia may be marginal and side effects intolerable (nausea, vomiting, sedation), thus the need for synergy, choosing drug classes that will overlap for analgesia but not for side effects. Drug classes that fit these requirements are as follows: cyclooxygenase inhibitors, alpha2 agonists, nitric oxide synthetase inhibitors, NMDA (N-methyl-D-aspartate) receptor blockers, and local anesthetics when delivered by thoracic epidural catheters. This balanced analgesia or delivery of different classes of analgesics will result in effective pain relief by synergistic or additive effect with reduced incidence of side effects.19

Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their effect by inhibiting the prostaglandin synthesis and releasing at the level of cyclooxygenase. These drugs have proven efficacy as the sole analgesic agent for management of mild to moderate pain in minor surgical procedures.

Ketorolac, the only parenteral NSAID presently available, is a nonspecific inhibitor of both cyclooxygenase isoenzymes (COX-1 and COX-2). The COX-1 isoenzyme is normally found in blood vessels, platelets, the gastrointestinal tract, and the kidney. On the other hand, the COX-2 isoenzyme is induced by inflammation in peripheral tissues. The inhibition of the COX-1 isoenzyme is responsible for the gastric and renal side effects of NSAIDs and for its inhibitory effect on platelet function.20,21

One should be cautious when using NSAIDs in the immediate postoperative period, taking into consideration such risk factors as a history of bleeding peptic ulcers, volume depletion (for NSAID-induced acute renal failure), especially in elderly patients, or when the risk of hemorrhage is considerable and the surgical site involves the airway. The usual dose of ketorolac is 15 mg intravenously every 6 hours for 24 to 48 hours. COX-2 inhibitors appear to be safer but parenteral forms of these molecules are not yet available.

Analgesic Adjuvants

Other classes of drugs may enhance the effects of opioids or may have independent analgesic effects. Most of these drugs are not available in parenteral forms and are usually reserved for patients not responding to more routine therapies. The addition of an alpha2 agonist may be beneficial and opioid sparing. Clonidine, dexmedetomidine, and tizanidine are representative of that class but only clonidine is Federal Drug Administration (FDA) approved and may contribute to hypotension in the perioperative period.

Antihyperalgesic drugs, which block the effect of the transmitter release, include nitric oxide synthetase inhibitors and NMDA receptor blockers. There is no available pure nitric oxide synthetase inhibitor. However, there is some evidence that acetaminophen exerts its action by inhibition of nitric oxide production. For this reason, acetaminophen administered around the clock in the immediate postoperative period may be very useful. Proparecetamol, the precursor of acetaminophen, is being clinically investigated in a parenteral form. Otherwise, acetaminophen is available orally (pill form and elixir) and rectally. The only concern may be that acetaminophen, because of its antipyretic properties, will mask febrile states in the immediate postoperative period.

Dextrometorphan is the most readily available NMDA blocker, although it is often in combination with other drugs such as cough suppressants.22 The clinically useful dose appears to be 30 to 60 mg every 4 to 6 hours. Ketamine in low doses (up to 10 mg per hour intravenously) may also be a useful NMDA blocker for postoperative pain.23

These agents can be provided by the epidural or intrathecal route. Of these, the epidural catheter infusion is the most commonly used method and, recently, a cumulative meta-analysis of various postoperative therapies shows that epidural opioids and epidural local anesthetics with or without opioids decreased the incidence of pulmonary complications as opposed to systemic opioids. Epidural analgesia is also associated with a lower incidence of cardiovascular events and provides a decreased stress response to surgery, earlier ambulation, rapid return of bowel function, shortened hospitalization, reduced costs and, overall, a lower mortality.

Large surveys show that the most effective placement of the epidural catheter for infusion of local anesthetic (bupivacaine or ropivacaine in dilute concentration) with a lipophilic opioid such as fentanyl is the upper thoracic region (T3) for thoracic surgery, the mid-thoracic region (T6) for upper abdominal surgery, and the lower thoracic region (T9) for lower abdominal surgery (Table 42-2).

The amount of opioids needed by the neuraxial route to provide effective analgesia is less than by the systemic route, especially when combined with local anesthetics. This is definitely the case with morphine, and to a lesser degree with fentanyl and hydromorphone, but systemic side effects of opioids may be less frequent.

When using a combination of local anesthetic and opioids, an infusion technique is required. The advantages of the combination are a synergistic effect with lower opioid doses and overall fewer side effects. However, with an infusion technique there is a risk of local anesthetic toxicity, a risk for catheter migration, potential sympathetic block, and orthostatic hypotension (Table 42-3).24–26

A large recent study shows an incidence of respiratory depression of 0.07%, nausea and vomiting 22%, and pruritus 22%. Another equally large study showed an overall rate of complications of 3% associated with the placement of thoracic epidural catheters. The complications included dural perforation (0.7%), unsuccessful catheter placement (1.1%), postoperative radicular type of pain (0.2%), responsive to catheter withdrawal in all cases, and peripheral nerve lesions (0.6%), 0.3% of which were peroneal nerve palsies probably related to surgical positioning and other transient peripheral nerve lesions (0.2%).27

Coagulopathy and systemic infection associated with bacteremia are definite contraindications to neuraxial techniques.

Anticoagulation is a relative contraindication. The American Society of Regional Anesthesia recently published a concern statement on neuraxial anesthesia and anticoagulation.27 For postoperative analgesia, the timing of the epidural catheter removal is important since most case reports of epidural hematomas have been documented on removal of the epidural catheter.

Patients receiving low-dose warfarin therapy during epidural analgesia should have their prothrombin time and internationalized normalized ratio (INR) monitored on a daily basis, and checked before catheter removal, if the initial dose was >36 hours before. Initial studies evaluating the safety of epidural analgesia in association with oral anticoagulation utilizing low-dose warfarin may require more intensive monitoring of the coagulation status.

Neurologic testing of sensory and motor function should be performed routinely on patients on anticoagulation with epidural analgesia and continued for at least 24 hours after.

An INR >3 should prompt the physician to withhold or reduce warfarin dose in patients with indwelling neuraxial catheters.

The use of antiplatelet drugs alone does not create a level of risk that will interfere with the performance of neuraxial blockade. When used in combination with other anticoagulant regimens, there may be an increased chance of hematoma formation.

It is recommended that indwelling catheters be removed prior to initiation of low-molecular-weight heparin thromboprophylaxis. If a continuous technique is selected, the epidural catheter may be left indwelling overnight and removed the following day, with the first dose of low-molecular-weight heparin administered 2 hours after the catheter removal.

For any low-molecular-weight heparin prophylaxis regimen, catheter removal should be delayed for at least 10 to 12 hours after a dose of low-molecular-weight heparin.

A single intrathecal opioid injection can also be used either alone or in combination with epidural infusion and other methods for pain control. However, the pain relief achieved with this method usually is not longer than 12 to 18 hours and the need for monitoring for possible respiratory depression is the same as for epidural opioid administration.28

With the use of neuraxial opioids, it is paramount to adequately educate the nursing and support staff to the monitoring and possible side effects of the techniques. Policies and protocols need to be in place to ensure patient safety, and it has been demonstrated that an organized acute pain service provided superior postoperative analgesia care compared to standard delivery of analgesics.

Interpleural Analgesia

Interpleural analgesia (IPA) has been well studied for its use in providing postoperative analgesia. IPA may also be utilized for analgesia in trauma victims with multiple rib fractures. The major mechanism of action of IPA is thought to be local anesthetic diffusion through the parietal pleura, which yields multiple segmental intercostals nerve blocks. The efficacy of IPA has been variable and factors, which may be partially related to affecting efficacy include: catheter position; presence of blood/clot; infection; scar adhesions fibrosis; presence of thoracostomy drainage tubes; and abnormal distribution of local anesthetic possibly secondary to altered lung mechanics (e.g., postsurgery).

IPA may be administered via:

• 1. Surgical placement of a catheter under direct vision
• 2. Percutaneous insertion of an interpleural catheter
• 3. Injection through a double-lumen chest tube.

If there is no chest tube on continuous suction present, the catheter may be bloused with 0.4 mL/kg of 0.5% bupivacaine with 1: 200,000 epinephrine, followed by a continuous infusion of 0.125 mL/kg/h of 0.25% bupivacaine. If a chest tube on continuous suction is present, the chest tube should be clamped for about 30 minutes following an interpleural bolus (assuming that there is no surgical contraindication for clamping the chest tube for that period of time). Bupivacaine 0.5% with 1:200,000 epinephrine may be bloused interpleurally every 6 hours (or, alternatively, lidocaine or ropivacaine).

There are multiple possible contraindications of interpleural analgesia but the major ones include positive end-expiratory pressure, pleuritis, pleural fibrosis/adhesions, pleural effusion pneumonothorax, bullous emphysema, recent pulmonary infection, local anesthetic allergy, and infection at the insertion site/bleeding diathesis (especially if percutaneous placement is planned). Advantages of IPA include surgical placement under direct vision is less operator-dependent than epidural placement; the catheter can be “transduced” to confirm “interpleural” placement, and it avoids potential epidural hematoma/abcess. Although there are multiple complications of IPA, the major ones include local anesthetic toxicity, pneumothorax, Horner’s syndrome, allergic reaction, shoulder pain, bronchopleural fistula, and intrapulmonary injection.29,30

Femoral Nerve Analgesia

Femoral nerve analgesia (FNA) is a technique that may be utilized as a potentially useful adjunct to opioids and other acute pain analgesic regimens. FNA has been used for analgesia in patients with femoral shaft fracture and various knee surgeries for postoperative analgesia. FNA is generally administered using 0.25% bupivacaine by continuous infusion 7 to 10 mL per hour. Potential advantages of FNA include decreased quadriceps muscle spasm/splinting and diminished opioid usage. A pitfall of the technique is that it is only effective for the anterior aspects of the knee; the sciatic nerve supplies the posterior aspects of the knee joint.

Many other techniques have been utilized for acute pain management, including continuous intercostal nerve block, continuous thoracic paravertebral block, and continuous brachial plexus catheter techniques.29,30 Although some of these techniques can be extremely useful (especially in certain circumstances), most continuous catheter techniques remain underutilized, potentially because of fears of complications, unfamiliarity, time constraints, and possibly reimbursement issues.

For both PCA and epidural analgesia, standard orders for monitoring and for medications such as antiemetics (e.g., droperidol), anti-pruritus agents (e.g., diphenlydromine), as well as orders for small titrations greatly facilitate the delivery of postoperative care (See Appendix A).

Nonpharmacologic methods of pain management and stimulation-induced analgesia can be used in the postoperative period with either acupuncture or TENS. With TENS, a small electrical current presumably stimulates the touch pressure and proprioception fiber (A-β) to release endogenous opiates and closes the “gate” of pain transmission at the spinal level. The TENS technique is considered safe but does not reliably provide analgesia in all cases. It is best used for amputations, back surgery, and postcesarian sections. Sterile electrodes are available to be placed close to surgical sites. TENS is contraindicated for patients with demand pacemakers and may interfere with electrocardiogram monitoring.

Behavioral techniques such as relaxation therapy and hypnosis have also been successfully used in the treatment of postoperative pain, but these techniques require postoperative preparation and motivation on the part of the patient to be effective in the immediate postoperative period.