Hospital Medicine

Pain management

Inpatient Pain Management

I. Problem/Condition.

Pain is highly prevalent in the hospital. Studies suggest that as high as 40-50% of inpatients experience pain of at least moderate severity, and under-assessment and under-treatment are common. Unrelieved pain has a significant impact on patient satisfaction, functional recovery, psychosocial wellbeing, length of stay, as well as readmission.

International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience most often associated with actual or potential tissue damage, or described in terms of such damage. Pain is a warning sign and a protective mechanism. It is not just the unpleasant sensation, not just the perception of the sensation, but also the emotional reaction to or experience of the perceived sensation. Pain is therefore always subjective from the patient's perspective and a multi-dimensional experience. The concept of total pain pioneered by Cicely Saunders states that there are four domains of pain experience, physical, emotional, psychosocial, and spiritual, and they interact with each other and modulate each other's effect. In addition, cultural and social contexts influence the expression of and tolerance of pain.

The neurologic basis of pain involves activation of peripheral and central pain pathways in normal as well as pathologic processes. Pain is a dynamic, bidirectional process that may involve neuroplastic changes that modulate pain sensations, which may explain the pain sensitivity shift in a chronic pain state. Many known pharmacologic and non-pharmacologic treatment modalities target distinct steps and pathways in pain transmission.

Acute pain is usually associated with tissue injury and has a temporal relationship to its onset and disappearance. It is commonly associated with objective physical signs of increased autonomic nervous activity such as tachycardia, elevated blood pressure, diaphoresis, or anxiety. Left untreated, acute pain may lead to the development of chronic pain, which could last for months to years and lead to neuroplastic changes in the nervous conduction system. Moreover, chronic pain is often associated with signs and symptoms of depression and anxiety.

The importance of appropriate pain assessment and management has gained national spot light. It is termed the fifth vital sign by JAHCO and both ACGME and RRC mandate its presence in graduate medical education. It has been incorporated into the HCAHPS patient satisfaction score for hospitals and it is a core competency of hospital medicine.

While pain management is recognized as a high priority for hospitalized patients, there is mounting evidence that the increasing use of opiates chronically has led to significant abuse and overdose leading to nearly 16,500 deaths per year. In March of 2016, the CDC published a guideline to review the indications and evidence for initiating analgesics for pain. While it is critical to address and manage a patient’s pain, practitioners must use caution and assess the risk factors and comorbidities of the patients that are being initiated on a specific regimen, and make comprehensive follow-up plans to avoid leading to adverse events.

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

Pain is a subjective experience that could be physical, emotional, psychosocial, and spiritual in origin. Several primary psychiatric disorders such as anxiety or depression can manifest as pain.

B. Describe a diagnostic approach/method to the patient with this problem.

The initial diagnostic approach should focus on assessment. It should include the location, intensity, frequency, duration, timing, and quality of the pain, as well as previous pain management strategies and their effectiveness, psychological evaluation, and substance abuse history. It should also include an assessment of the impact of the pain on patient’s function, since an intervention that does not increase function should not be continued. The initial assessment should be followed by physical examination and appropriate diagnostic workup to try to determine the cause of the pain. Patient should also be reassessed at regular intervals and with changes in clinical condition to monitor the effect of treatment.

A numeric rating scale, 0-10, is most commonly used in the hospital. However, it does require some abstract thinking. In some patients, it may be easier to administer a picture based pain intensity assessment scale such as the Wong-Baker Faces Pain Scale. Even patients with moderate cognitive impairment, i.e., MMSE 12-23, can still reliably report pain. For patients with severe dementia or non-verbal patients, several behavior pain assessment tools exist. Non-verbal pain indicators include facial expression (grimacing), vocalization (calling out, crying, moaning, groaning), body movement (guarding), and changes in interpersonal interactions, mental status, and usual activities as judged by their caregivers.

1. Historical information important in the diagnosis of this problem.

Deep somatic pain is typically localized and described as aching, stabbing, throbbing, or squeezing. Superficial somatic pain is usually sharper and may have a burning or pricking sensation. Bone pain intensifies on movement and is often tender to palpation.

Visceral pain is usually not well-localized because viscera do not contain many nociceptors. Visceral pain is often described as spastic, cramping, gnawing, squeezing, or pressure. It may change with eating and/or bowel movements.

Pain descriptors associated with neuropathic pain include burning, shooting, tingling, stabbing, scalding, and painful numbness. Aberrant sensations may follow the distribution of a sensory nerve and may also present with tactile allodynia (pain from light touch or mild pressure) or hyperalgesia (increased response to a noxious stimulus).

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Detailed musculoskeletal and neurological examinations are essential, in particular for the joint and neuropathic pain.

3. Laboratory, radiographic, and other tests may or may not be useful in diagnosing the cause of pain.

While imaging may show clinical evidence of a mass or lesion causing symptoms, pain is widely understood as subjective and not always easy to assess, as each patient will experience it differently.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

See B1.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.


III. Management of Pain

A. Management of Clinical Problem Pain Management.

General principles of acute pain treatment utilize a multidisciplinary approach combining pharmacologic and non-pharmacologic modalities with the goal of allowing maximal functional status for the patient, as well as anticipation and management of treatment side effects. The gate theory of pain perception states that pain is an interaction between excitatory and inhibitory neurological pathways which integrate information from nociceptive, inflammatory, neuropathic, and emotional components. Successful treatment strategies thus require coordination of efforts directed at different components.

There are growing interests among patients and providers in using complementary, non-pharmacologic therapies for acute pain. For example, immobilization with bracing and bed rest is common in orthopedic populations, along with heat pack, cold pack, or massage. Other modalities include cognitive behavioral therapy and graded exercise for patients with fibromyalgia. Non-pharmacologic treatment of acute lower back pain appears to be best studied. Only heat wrap application shows moderate efficacy and appears superior to NSAIDs and acetaminophen. Physical therapy has marginal, if any, benefits.

The main stay of treatment for acute pain is pharmacotherapy. However, its effectiveness is greatly enhanced by patient education and multimodality interventions, such as physical therapy (PT), psychosocial support, and complementary and alternative treatments. The key to successful pain management is frequent assessment and targeted treatment according to the type of pain.

The World Health Organization (WHO) Analgesic Ladder was developed in 1986 and has been widely used as a tool to address the management of cancer and non-cancer pain. In step 1, WHO recommends the use of non-opioid analgesics, with and without adjuvants for the treatment of mild pain. In step 2, WHO recommends adding weaker opioids, with or without adjuvants, for moderate pain. In step 3, stronger opioids were added to the above drugs for severe pain. Commonly used adjuvants include topicals (lidocaine patch, capsaicin), acetaminophen, NSAIDs, steroids, PT, heat/cold pack, massage, transcutaneous electrical nerve stimulation (TENS) etc.

Neuropathic pain is surprisingly common in the hospital setting. Its prevalence is grossly underestimated and undertreated, or mistreated with opiates. Guidelines suggest first line treatments for neuropathic pain include anticonvulsants, antidepressants, and topicals.

General principles of opioid use

Opioids are classified as full morphine-like agonists, partial agonists, or mixed agonist-antagonists, depending on the specific receptors to which they bind and their activity at these receptors. While morphine is the most commonly used opioid, there is wide inter-individual variability in response to both the analgesic and adverse effects of opioids. Currently there is little evidence to suggest that one opioid is superior over another in terms of clinical analgesia and/or side effect profile.

The routes of administration are PO, PR, IV, SQ, transdermal, or intra-spinal. IM is discouraged, due to variable bioavailability and SQ is as effective as IV.

Short-acting opioids are generally recommended when opioid therapy is being initiated for the first time or when the pain intensity is highly variable. For acute pain, the CDC recommends a short course of 3-7 days with a plan for close outpatient follow-up. In certain instances, once stable, patients may be switched to a controlled-release or slow-release formulation. Individual patient needs should be considered in planning as those with high-risk comorbidities and those with a history of substance abuse or psychiatric illness may have increased rates of complications.

The initial opioid dose finding for acute pain is largely patient driven, as determined by the balance of analgesia with side effects. The minimal starting dose is based on patient age and body weight, usually ranging from 0.05-0.1 mg/kg for IV morphine, or from 0.0075-0.015 mg/kg for hydromorphone (lower limits usually apply to elderly patients). If no adequate pain relief is achieved within 15-30 minutes, a second or third dose can be given, and the effective analgesic dose will be the total doses.

The severity of the pain and the opioid formulation chosen determines the rate of titration. The dose of immediate-release formulation can be adjusted instantly, while long acting opioids can be adjusted daily or every 2- 3 days (Fentanyl or methadone). For mild to moderate pain, a dose increase of 25-50% is desired, while for severe and uncontrolled pain, a dose increase of 50-100% is desired.

Opioid switching is a technique used to overcome inadequate pain control and dose-limiting toxic side effects, since there is a wide inter-individual variability in response. The current guideline recommends using equi-analgesic tables and reducing the total dose by 25-50% due to incomplete cross-tolerance.

Most patients with constant pain require fixed-schedule dosing, along with as-needed rescue dosing for breakthrough pain, typically calculated at 10-20% of the total fixed dose.

Patient controlled analgesia (PCA) refers to the method where the patient self-administers analgesics, most commonly opioids, to control his or her own pain. The primary advantage is patient convenience and rapid calculation of daily analgesia requirement. Use of PCA consists of demand dose, dosing interval (6-12 minutes), and/or rate for continuous infusion.

The key to safe use of PCA is close monitoring with ready availability of naloxone. Every institution should set up its own monitoring parameters. The first 24 hours after surgery represent a high-risk period for a respiratory event, and sedation is highest. Thus post-op PCA use needs to be monitored closely. Continuous infusion should be used with caution in patients with sleep apnea and those who are morbidly obese.

Common medications used in the treatment of acute pain

Acetaminophen is an effective analgesic without anti-inflammatory properties. It is taken at 325-650 mg every 4-6 hours and the maximum daily dose is 4 grams, for mild to moderate pain of various etiologies. It has significant opioid sparing and synergistic effects. The effect lasts 4-6 hours and the major side effect is hepatotoxicity, particularly in elderly patients with concomitant liver disease. A recently approved IV formulation may be appropriate for certain patients who are unable to take oral medication.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications effective for mild to moderate pain through its inhibition of prostagladin production, mediators of pain. They are also used as adjuvant analgesics with opioids, given their significant opioid sparing effect, which in turn reduces opioid side effects. NSAIDs have analgesic ceiling effects without ceilings in side effects, meaning that increasing the dose will not increase efficacy. Major side effects are renal, GI (in particular elderly and steroids users), renal toxicity in high doses, MI and stroke risks, as well as hematologic effects (platelet inhibition and bleeding risk).

Corticosteroids are commonly used adjuvant therapy for bone, visceral, and neuropathic pain. Its mechanism of action is related to reduction of inflammation, edema, and local mechanical effects of tumor growth. Corticosteroids may reduce symptoms and improve neurological recovery in malignant bowel obstruction, malignant spinal cord compression, or certain types of neuropathic pain.

Lidoderm patch is a targeted peripheral analgesic approved for the treatment of neuropathic pain, in particular post herpetic neuralgia. Pharmacokinetics studies show that 12-24-hour dosing of lidoderm patch has minimal systemic absorption, toxicity, or drug-drug interactions. The most common side effect is mild local skin reaction.

Tricyclic antidepressants are classes of drugs commonly used for depression and neuropathic pain. Within the class, Amitriptyline is metabolized to the active compound nortriptyline, while Imipramine is metabolized to desipramine. As a result, both nortriptyline and desipramine have less side effects and higher potency. Their major advantages are low cost, once a day dosing, and anti-depressant effect, although they are equally analgesic in non-depressed patients. The major side effects are orthostatic hypotension, cardiac arrhythmias, and anticholinergic effects.

Anticonvulsants are classes of drug including carbamazepine, gabapentin, and pregabalin, most commonly used for neuropathic pain. Carbamazepine is particularly effective in trigeminal neuralgia. Gabapentin and pregabalin are medications that bind to calcium channels and modify neurotransmitter release. Gabapentin has complicated, non-linear pharmacokinetics and needs to be administered three times a day and titrated to a narrow therapeutic window. In contrast, pregabalin is more straightforward, and it is only administered twice a day. They are both excreted from kidney and require dose reduction in renal failure, although they have very few drug interactions. Major side effects for this class of drugs are sedation, dizziness, ataxia, and peripheral edema.

Tramadol can be considered an atypical analgesic that has a dual action. It is a weak mu opioid agonist that also inhibits the reuptake of norepinephrine and serotonin. Tramadol has one tenth of potency of oral morphine, equal to that of codeine. Because of its serotonin and norepinephrine reuptake inhibition, tramadol has a unique place in managing neuropathic pain. Tramadol is metabolized by the liver and eliminated by the kidney, and its half-life is 5-6 hours. Common side effects of tramadol are drowsiness, constipation, dizziness, nausea, and orthostatic hypotension.

Codeine is a weak analgesic (1/12 of morphine) and antitussive. It is commonly given together with acetaminophen as a combination pill (300 mg acetaminophen/30 mg codeine or 300 mg acetaminophen/60 mg codeine.) Its mechanism of action is hepatic conversion to morphine, and its onset of action is 0.5-1 hour for PO, peak effect 1-1.5 hour for PO and 0.5-1 hour for IM/SQ. Not recommended to use in hepatic failure, renal failure, and nursing mothers. Use for mild to moderate pain, lower dose (10-20 mg) as antitussive (non-productive cough), but dextromethorphan is better because it has equivalent antitussive activity but has much lower toxicity in accidental overdose.

Oxycodone is a strong opioid (1.5-2 times of Morphine). It is commonly given alone or together with acetaminophen every 4-6 hours. It also has a long acting form that can be given every 8-12 hours. The long acting form should not be crushed. Its mechanism of action is hepatic conversion to oxymorphone, noroxycodone, and noroxycodol (weak and inactive metabolites). Onset of action for PO is 10-15 minutes with peak effect 0.5-1 hour. Duration of action is 3-6 hours and <12 hours for long acting form. Not recommended to use in renal failure and nursing mothers. Used in moderate to severe pain, often it’s the surgical and postoperative analgesics of choice at doses over 5 mg, with or without acetaminophen.

Hydromorphone is a strong opioid analgesic - 4 times that of PO morphine. Dose forms are PO, IV, SQ, rectal, or spinal. Preferred methods of administration are PO, IV, or SQ. There is no long acting form. Its mechanism of action is 62% bioavailability in the parental drug form, and hepatic conversion to inactive metabolites. For immediate release form, its onset of action is 15-30 minutes for PO, and 5-10 minutes for IV/IM/SQ. Peak effect is 1 hour for PO and 15-30 minutes for IM/SQ/ IV. Dose may need to be reduced in patients with hepatic failure and renal failure. PO and SQ/IV conversion factor is 5:1.

Morphine Sulfate is the standard opioid analgesic. Dose forms are PO, IV, SQ, rectal, or spinal. Preferred methods of administration are PO, IV, or SQ. Its mechanism of action is hepatic conversion to active morphine-6-glucoronide. For immediate release form, its onset of action is 0.5 hour for PO, and 5-10 minutes for IV/IM/SQ. Peak effect is 1 hour for PO and 15-30 minutes for SQ/IV. Not recommended in hepatic failure, renal failure, and nursing mothers. PO and SQ/IV conversion factor is 3:1.

Fentanyl: Transdermal fentanyl patch is used to provide analgesia lasting up to 72 hours, although in some individuals, it only lasts 48 hours. Dose forms are IV, transmucosal, and transdermal. Onset of action is almost immediate for IV and transmucosal, and 16-24 hours for transdermal patch. Absorption from the fentanyl patch is increased during fever and decreased in cachetic patients. Its mechanism of action is hepatic conversion to inactive metabolites and excreted in the urine. For transdermal patch, its half-life is 17 hours, 80-85% protein bound, lipophilic. May need dose adjustment in hepatic failure, renal failure, and nursing mothers. Oral transmucosal fentanyl citrate tabs can be used for the relief of cancer breakthrough pain, given its lipophilic property and rapid onset of action.

Methadone is a synthetic opioid agonist with oral bioavailability of 80%. It has no known active metabolites, prolonged duration of analgesia resulting in longer administration intervals, and lower cost. Dose forms are IV and PO. Onset of action is 10-20 minutes for IV and 0.5-1 hour for PO, and peak effect is 1-2 hours for IV, and 3-5 days for continuously PO dosing with expected analgesia lasting 48 hours. Many drugs can change its metabolism. For example, rifampin can speed metabolism enough to cause severe withdrawal reaction. Its mechanism of action is hepatic conversion to inactive metabolites and excreted in the urine.

Half-life is extremely long, can last 72 hours. May need dose adjustment in renal failure, and avoid in severe hepatic failure. Usual dose for acute severe pain is 2.5-10 mg every 8-12 hours and titrated up to suitable PO dose (PO: IV=2:1), divided to 2-3 doses/day for maintenance. The adjustment of PO dose should be done every 3-5 days.

Because of its NMDA receptor antagonist function, methadone has been used in the treatment of neuropathic pain. The conversion of other opioids to methadone is highly variable, and several methods and conversion tables have been developed. Prolongation of QTc resulting in arrhythmias is a real concern, in particular when other conditions predisposing to QTc prolongation exist. Therefore, screening EKG before and during the methadone treatment has been recommended.

For the use of any of the short- or long-acting opiates, screening of appropriate patients is critical to ensure avoidance of adverse events. High-risk patients that may have negative outcomes related to opiate analgesics include those patients who have obesity and obesity hypoventilation syndrome or obstructive sleep apnea, postoperative patients who are recovering from sedating anesthesia that may compound depressed respiratory drive, or patients with poor baseline respiratory or cardiac function such as COPD or advanced CHF.

Additionally, the initiation of opiates on any given individual should only be done after initiating an Opioid Risk Tool such as that of the National Institute on Drug Abuse which elicits a personal or family history of alcohol, illicit, or prescription drug abuse or addiction within the family, or previously by the patient, as well as a history of mental illness that may predispose patients and create a higher likelihood of abuse potential. In those patients, it is advised to exhaust other modalities or ensure adequate short-term follow-up with appropriate outpatient providers.

Regional/spinal/epidural analgesia are interventional techniques commonly used in the operative setting. They involve the introduction of local anaesthetics and/or opiates into the distribution of certain spinal as well as peripheral nerves preoperatively. Regional techniques can block or reduce pain anywhere from several hours to several days, depending on the technique that is used. Pre-emptive pain management may reduce subsequent pain in the days to weeks following surgery. Greater pain control has the potential to allow for earlier hospital discharge and may improve the patient's ability to tolerate physical therapy. Peripheral nerve block has also been successfully used in trauma related somatic pain such as hip fracture, as well as in combination of somatic and neuropathic pain associated with pancreatic cancer by celiac block.

Patient controlled analgesia (PCA) refers to the method where the patient self-administers analgesics, most commonly opioids, to control his or her own pain. The primary advantage is patient convenience and rapid calculation of daily analgesia requirement. Use of PCA consists of demand dose, dosing interval (6-12 minutes), and/or rate for continuous infusion. The key to safe use of PCA is close monitoring with ready availability of naloxone. Every institution should set up its own monitoring parameters. The first 24 hours after surgery represent a high-risk period for a respiratory event, and sedation is highest. Thus post-op PCA use needs to be monitored closely. Continuous (basal rate) infusion should be used rarely, due to concerns for oversedation in patients with sleep apnea and those who are morbidly obese.

Common inpatient pain syndromes

Sickle cell disease pain crisis: Both acute and chronic components - acute pain related to vascular occlusion and chronic pain related to ulcerations, bone, and joint pain. Most sickle cell disease patients manage pain at home without physician contact. Prevention of pain includes avoidance of risk factors such as dehydration, infections, hypothermia, hypoxia, acidosis, and altitude. Hydroxyurea consistently lowers HgbS concentration and raises HgF concentration. It reduces mortality and morbidity associated with pain crisis.

Based on experience, expert opinion, and very limited evidence, guidelines recommend scheduled parenteral morphine as the drug of choice for sickle cell disease vascular occlusive crisis. Fentanyl, methadone, and hydromorphone are sometimes used in patients with stable pain. There is reasonable evidence that PCA should be the first line treatment modality for sickle cell disease acute vaso-occlusive crisis as it reduces overall analgesic requirement as well as duration of hospitalization.

Neuropathic pain results from damage to or dysfunction of a nerve, in contrast to activation of nociceptors in somatic and visceral pain. Neuropathic pain is common in patients with DM, shingles, herniated disk, multiple sclerosis, and AIDS. It is also commonly seen after surgery, radiation, or chemotherapy. Neuropathic pain may be resistant to standard opioid therapies or other nociceptive pain treatment strategies. Anticonvulsants and tricyclic antidepressants are mainstays of therapy. Complaints of continuous burning may respond best to antidepressants, whereas lancinating complaints may respond best to anticonvulsants.

A recent review of published guidelines suggested first line therapy for neuropathic pain includes TCAs, dual serotonin and norepinephrine inhibitors, gabapentin, pregabalin, and topical lidocaine, all of which are based on strong evidence from RCTs. Opioids and tramadol are second line therapy, and topical capsiacin, certain antidepressants and anticonvulsants, mexiletine, and NMDA receptor antagonists are third line therapies. Chemotherapy induced peripheral neuropathy is unique in that it poorly responds to antidepressants and anticonvulsants. NSAID drugs are the first line therapy, followed by opioids. In HIV neuropathy, antidepressants were shown to be ineffective, while gabapentin was shown to be modestly effective. Peripheral nerve stimulation may be particularly useful in post-trauma and post-surgical neuropathy, occipital neuralgia, complex regional pain syndrome, and migraines and daily headaches.

Acute abdominal pain can be somatic or visceral. Early IV opioid analgesic treatment may result in altered physical examination findings, but does not affect management decision or result in delay of surgery. Therefore, IV Morphine is now the drug of choice for treating patients with undifferentiated acute abdominal pain. NSAIDs have no role in treating acute abdominal pain except for acute renal colic, where they are as efficacious as, or slightly better than, opioids. Therefore, NSAIDs such as IV Ketorolac is the treatment of choice.

Acute postoperative pain is best managed through a multimodal and preemptive analgesic approach. Preemptive analgesia may include NSAIDs and Gabapentin. Predictors of postoperative pain and analgesic consumption include preoperative pain, anxiety, age, and type of surgery in a recent high quality systemic review. For patients with prolonged surgery or with extensive incisions, or who are on chronic opioids, neuraxial analgesia provided by spinal or epidural anesthesia with either morphine or fentanyl is recommended to decrease postoperative analgesic requirement. PCA is the preferred mode of post-operative pain control. Ketamine is a NMDA receptor antagonist with significant opioid sparing effect. It is particularly useful in patients who are on chronic opioids or methadone.

Acute cancer pain: New onset pain or worsening of pre-existing, well-controlled pain may signal the progression of underlying disease. Cancer pain can be somatic, visceral, or neuropathic. Several cancer-specific, systemically developed and validated pain classification schemes exist. Some of which offer prognostic information and/or predict opioid usage. Opioids, along with co-analgesics such as NSAIDs, Tylenol, antidepressants, and anticonvulsants, are the backbone of managing cancer pain. For malignant bony pain, consider NSAIDs, corticosteroids, bisphosphonates, hormonal/chemotherapy, systemically administered radioisotopes, and XRT. For cancer pain associated with nerve compression, consider corticosteroids and/or XRT.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.

Opioid side effects, which are rare, differ from true allergy, which is related to histamine release and symptoms of hives, rashes, itching, and other severe symptoms. Nausea and vomiting is a common side effect, and it usually goes away in the first week and responds to typical anti-emetics. CNS side effects of opioids include sedation, delirium, hallucinations, and hyperalgesia. Treatment includes tapering of opioids, identifying and treating other contributing factors, and judicious use of anti-psychotics.

Patients receiving long-term opioid therapy usually develop tolerance to respiratory suppression side effects. When indicated for reversal, small doses of naloxone are usually sufficient. Constipation is a common GI side effect that never goes away. The cornerstone of treatment is effective prophylaxis and initiation with regular laxative treatment. There is evidence that transdermal fentanyl may have less constipating effects than other opioids. Methylnaltrexone, an opioid antagonist with restricted ability to cross blood brain barrier, is efficacious in treating severe opioid induced constipation.

Opioid tolerance is the need to increase the amount of a drug to achieve the same effect. It usually develops within days of starting an opioid, similar to side effects such as nausea, respiratory suppression, and sedation. The analgesic tolerance develops in the first 2 weeks, and does not recur after that. Patients who require higher doses of analgesia after 2 weeks should be evaluated for other causes of increased pain, such as progression of cancer. Physical dependence is common in patients taking opioids. The manifestations of withdrawal symptoms are anxiety, irritability, tachycardia, abdominal pain, nausea, and vomiting. The drug half-life dictates the time course of the symptoms. It can happen after just a few weeks of opioid use.

Opioid addiction is an abnormal behavioral condition that may include compulsive use, impaired control over drug use, continued use despite harm, and craving. They commonly include illicit drug users. Pseudo-addiction is a term used to describe patient behavior when their pain is under-treated. It usually goes away when the patient is adequately treated.

Management in patients with comorbidities

Different opioids are metabolized differently in liver and kidney. Therefore, cautions should be made when using opioids in patients with hepatic and/or renal failure. Table I summarizes their use.

Table I.

Use of opioids in patients with comorbidities
Renal Failure Dialysis Liver Disease
Morphine Do not use Do not useNot dialyzed Caution, reduce dose/frequency
Oxycodone Caution, reduce dose/frequency Caution, reduce dose/frequency Caution, reduce dose/frequency
Hydromorphone Preferred PreferredNot dialyzed Caution, reduce dose/frequency
Fentanyl Preferred PreferredNot dialyzed Preferred
Codiene Do not use Do not use Do not use
Methadone Preferred PreferredNot dialyzed Preferred

In the aging medical inpatients, physicians should pay attention to the traditional geriatric principle of medication management, which means starting low and titrate slowly. It is reasonable to start opioids at 50-75% of dose normally given. It is imperative that the pain and pain medications, in particularly opioids, are monitored carefully in the elderly. In additional, non-pharmacologic treatments of pain, such as rehabilitation and PT, should be emphasized to prevent functional decline in the hospital.

The use of opioids in patients with history of addictions is challenging, and it requires collaborations between the patients and providers. Management of acute pain in patients with substance abuse problems should focus on prevention of withdrawal, effective analgesia, and symptomatic management of affective disorders and behavior problems. Establishing a behavioral contract may be necessary and it is important that the physician and staff take a non-judgmental approach. Many guidelines suggest history of addiction to opioids or alcohol is a relative contraindication for prescribing chronic opioids for non-malignant pain. There is little evidence that chronic opiate use in non-cancer, non-palliative pain is beneficial for long-term use. However, there is significant mounting evidence on the harms of chronic opiate use that practitioners should take significant precautions to avoid. Providers should use prescription monitoring programs and evaluate the risks and benefits of the various modalities at hand.

IV. What's the evidence?

Dowell, D, Haegerich, TM, Chou, R.. "CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016". JAMA.

"Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council". J Pain. vol. 17. 2016 Feb. pp. 131-57.

"Research Gaps in Practice Guidelines for Acute Postoperative Pain Management in Adults: Findings From a Review of the Evidence for an American Pain Society Clinical Practice Guideline". J Pain. vol. 17. 2016 Feb. pp. 158-66.

"The Opioid Risk Assessment Tool".

Meldrum, ML.. "A capsule history of pain management". JAMA.. vol. 290. 2003. pp. 2470-5.

"Pain: Current understanding of assessment, management, and treatments". 2009.

Helfand, M, Freeman, M.. Assessment and management of acute pain in adult medical inpatients: a systemic review. VA Health Services Research and Development Service. 2008.

Relieving pain in America: a blueprint for transforming prevention, care, education, and research. IOM. 2011.

Wu, CL, Raja, SN.. "Treatment of acute postoperative pain". Lancet. vol. 377. 2011. pp. 2215-25.

Turk, DJ, Wilson, HD, Cahana, A.. "Treatment of chronic non-cancer pain". Lancet. vol. 377. 2011. pp. 2226-35.

Portenoy, R.. "Treatment of cancer pain". Lancet. vol. 377. 2011. pp. 2236-47.

"Pain Management CME series from the American Medical Association".

(This 2013 update to the popular CME series addresses biology, pathophysiology, and evidence based pain management for practicing physicians. Good coverage of substance abuse and opioid misuse.)

Blondell, RD, Azadfard, M, Wisniewski, AM.. "Pharmacologic therapy for acute pain". Am Fam Physician.. vol. 87. 2013. pp. 766-772.

(Good basic review on common pain medications, especially the table summary.)

Viscusi, ER, Pappagallo, M.. "A review of opioids for in-house pain management". Hosp Practice.. vol. 40. 2012. pp. 149-159.

(Advanced review of opioids from anesthesiologists’ point of view and most relevant to acute postoperative pain. Has great coverage of opioid tolerance and substance abuse issue, as well as in-depth discussion of PCA use.)

Fishman, SM, Young, HM, Arwood, EL. "Core competencies for pain management: results of an interprofessional consensus summit". Pain Med.. vol. 14. 2013. pp. 971-981.

(Interprofessional, consensus-derived competencies in multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. A set of core values and guiding principles are discussed.)
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