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10 Articles in Volume 7, Issue #7
Burning Mouth Syndrome
Chronic Pain Program in a Primary Care Setting
Chronic Persistent Pain Can Kill
Education and Exercise Program for Chronic Pain Patients
Managing Pain in Intensive Care Units
Oxycodone to Oxymorphone Metabolism
Patulous Eustachian Tube: Part 1
Rational, Emotive, Ethical Approaches to Bio-psychosocial Pain Care
Smoking and Aberrant Behavior in Chronic Pain Patients
Structuring Opioid Therapy

Managing Pain in Intensive Care Units

Aggressive pain management for the typically very ill and unstable patients in the ICU must be individualized based on the circumstances of each patient's pathology and condition.

Inadequately relieved pain is often described after intensive care unit (ICU) hospitalization. Pulmonary dysfunction, cardiac dysfunction, and difficulty weaning from mechanical ventilation are potential consequences caused by ongoing pain. Managing pain in ICUs may seem daunting due to the patients’ serious and often unstable health status, healthcare providers’ lack of awareness regarding pain’s impact on overall health status, coupled with the physical care demands within the critical care environment. Factors contributing to the overall under-treatment of pain in ICUs include pain assessment challenges for nonverbal patients, staff and family concerns about the consequences of using analgesic medications, and prioritization of complex medical needs. To mitigate these obstacles while providing optimal pain control, proper identification of underlying pain symptoms through the use of behavioral assessment tools and continual monitoring of physiologic markers should occur. Patients and professional caregivers must become more knowledgeable about the necessity of simultaneously managing pain and stabilizing underlying medical conditions. The desired goal for patients receiving care in ICUs should be their medical recovery and transfer out of the ICU and, if this is not possible, relief of their pain and discomfort during the withdrawal of life sustaining treatment or when their death is imminent.


Patients in ICUs vary in their range of pathologies and ages. Patients between the ages 60 to 69 years account for most of ICU admissions.1 Two large cohort studies show that the most common pathologies treated in ICUs are (in descending order): postoperative complications, acute lung disease with and with out multi-organ failure, chronic lung disease, and neurologic disorders. Importantly, five to ten percent of adult ICU patients are chronically and critically ill, as defined by receiving mechanical ventilation for at least 21 days or requiring tracheostomy.2

Depending upon geographic area, patients in ICUs also vary in terms of their ethnicity, culture, level of education, and social background. These factors have relevance when addressing pain. Members of some cultural and ethnic groups may have underlying beliefs and understandings about pain and its treatment. Some groups interpret pain as a part of the healing process and neglect to inform their health care providers about pain’s presence. Others interpret pain reporting as a sign of weakness and so may also neglect to report its occurrence. Some tend to overestimate their pain intensity and significance.3 Because there are so many contributing variables to the experience of an individual’s understanding about pain, it is difficult to make broad, general assumptions based solely upon culture, ethnicity, education, or socio-economic class. It is more important clinically for healthcare providers to be sensitive to, and respectful of, cultural, educational, ethnic and other variations when assessing and treating each patient’s pain.

“Ideally, pain assessments should include location, characteristics, severity, onset, progression, duration, quality, radiation, alleviating and exacerbating factors, and effects of previous therapies.”

Need for Pain Treatment in the ICU Patients in the ICU are often in need of pain medicine for a myriad of reasons, including weaning off ventilatory support, pulmonary dysfunction, and cardiac dysfunction.

Prolonged Mechanical Ventilation. People receiving ICU care should be weaned from mechanical ventilation as soon as possible to prevent complications such as barotrauma, atelectasis, and infection. Mechanical ventilation also indirectly leads to other medical complications such as pressure ulcers, gastric ulcers, muscular weakness, and renal failure. Inappropriately managed pain may inhibit weaning from ventilatory support.4

Pulmonary Dysfunction. This may also result from inadequate pain control in postoperative patients—particularly following upper abdominal and thoracic surgeries—and for those with abdominal pathology such as pancreatitis.2 Sustained abdominal muscle contractions caused by unrelieved pain result in decreased lung volumes, decreased functional residual capacity (FRC), and decreased functional vital capacity (FVC). The cough reflex is compromised with reduced FRC and FVC, leading to retained pulmonary secretions and the potential for pneumonia. Pain may also induce vasoconstriction which, when coupled with venous stasis from immobility, may ultimately lead to thrombus formation and fatal pulmonary embolism.5

Cardiac Dysfunction. Treatment of pain for patients with myocardial infarction (MI) or acute coronary syndrome is critically important. It has been recommended that morphine or other opioid analgesics should be administered for chest pain refractory to nitroglycerin. It is theorized that morphine reduces oxygen consumption by decreasing sympathetic activity and increases blood delivery through its vasodilatory affects.6 In contrast, the administration of NSAIDs counteracts the effects of angiotensin converting enzyme inhibitor (ACEI) and diuretics, thereby increasing the incidence of congestive heart failure (CHF) and MI.7,8 It is necessary to not only treat the underlying cause of chest pain, but to use the proper type of analgesics.

Assessment Of Pain

A thorough pain assessment is essential regardless of the clinical setting. Ideally, pain assessments should include location, characteristics, severity, onset, progression, duration, quality, radiation, alleviating and exacerbating factors, and effects of previous therapies. This information guides clinicians toward the underlying cause for pain, as well as determines which therapeutic interventions will be utilized.

Choosing the Proper Assessment Tool. Assessment of pain severity serves to gauge the effectiveness of therapeutic interventions. Pain severity is determined through assessment tools used by healthcare providers, surrogates, or directly by patients. Patients’ self reports about their pain are considered to be the most accurate.9

Since patients in ICUs are commonly unable to work with typical pain assessment scales requiring them to give a verbal response, the Behavioral Pain Scale (BPS) is considered to be an alternative tool for assessing pain in critically ill, sedated, and mechanically ventilated patients. The BPS assesses pain through evaluation of facial expression, upper limb movements, and compliance with mechanical ventilation.

During a six-month prospective validation study, Aissaoui et al performed 360 observations of 30 patients in ICUs. They measured BPS and two physiologic markers—arterial blood pressure and heart rate—at rest and during two painful procedures, tracheal suctioning and peripheral venous cannulation; at three different times of the day. Significant increases in BPS scores occurred between rest and the two painful procedures. There was an indirect correlation between the degree of sedation and BPS. They showed that the BPS was a valid pain assessment tool for critically ill patients.10

Another behavioral assessment tool, the Critical Care Pain Observation Tool (CPOT), also measures the presence and intensity of pain through changes in facial expression, body movements, muscle tone, and compliance to mechanical ventilation. Initially written in French, a recent study validated an English version of this assessment tool in mechanically ventilated patients, both conscious and unconscious, and looked at the relationships between patients’ self reports of pain, painful and nonpainful procedures, and physiologic changes (heart rate, respiratory rate, mean arterial pressure, and transcutaneous oxygen saturation).11 In conscious patients, increased CPOT scores and increased physiologic changes were found during events identified as painful by patients. This was additionally seen for unconscious patients, although differences were not as marked. Response differences between conscious versus unconscious patients may reflect the level of sedation and/or degree of hemodynamic instability of unconscious patients. Despite differences between conscious and unconscious patients, the CPOT is another valid tool for assessing pain in critically ill patients.11

There has been reluctance to use surrogates (individuals who make medical decisions when patients cannot do so) to report patients’ pain because of their emotional attachment to these patients and their potential for overestimating pain. Analysis of over 2000 SUPPORT study patients, finds that surrogates correctly identify the existence of pain 73% of the time, but estimate its severity with 53% accuracy.12 Although surrogates may be less accurate about estimating pain’s severity, they are able to assist with pain’s assessment when patients cannot give self-reports.

Factors That Influence Pain Response

Many factors alter the response to pain and analgesic interventions. Anxiety, delirium, sleep deprivation, and psychosocial history all make patients more susceptible to pain, even for the smallest stimuli. These factors are interdependent and so it is necessary to address and alleviate each of them. Pain itself may precipitate anxiety and sleeplessness which, in turn, worsens the pain.

Anxiety can also be both a factor for, and a result of pain. Patients who are intubated are particularly prone to anxiety because of their inability to communicate and express their fears. Anxiety makes it difficult for people to be weaned from ventilatory support due to heightened experiences of breathlessness. Uncontrolled anxiety can lead to agitation and is a common finding most commonly associated with uncontrolled pain in the ICU. However, underlying hypotension, hypoxemia, hypercarbia, and medication effects must be ruled out prior to treating anxiety or agitation as consequences of inadequate pain control.13

Delirium ,a common event in the ICU, may be caused by metabolic, intracranial, endocrine, organ failure, medication-related, and respiratory conditions.13 The ICU environment itself can cause delirium due to the “high noon” level of stimulation, continuous sleep deprivation, and ever-changing staff. It can be challenging to appropriately assess and treat pain for patients with delirium. Certain measures that may lessen the incidence of delirium include environmental factors such as having windows, calendars, clocks, and other familiar, personal objects in the ICU. Efforts should be made to provide continuity of care when possible and provide clear explanations of treatments and procedures even when patients are not able to verbally respond.13

Sleep deprivation may increase the experience of pain. In a study of hospitalized adult burn patients, a poor night’s sleep was followed by a significantly more painful day; however, the reverse was not found.14 Sleep deprivation in the ICU can result from psychological states, environmental conditions (eg, bright lighting and noise from ventilators and monitors), and disrupted circadian rhythms.13 Sleep may be improved by reducing exposure to bright light, reducing ambient noise, respecting circadian rhythms, and using sedative-hypnotics if necessary.

Use of Sedation in the ICU

Sedation may be used in conjunction with pain control efforts, but sedation should not replace analgesic methods. The goals of sedation include: reduction of anxiety, enhancement of patients’ cooperation, lessening of voluntary motor activity to allow better control of mechanical ventilation, provision of an amnestic state; and an antitussive effect to improve endotracheal intubation tolerance.13 Target levels vary on an individual basis and with the type of therapeutic intervention. The desired goal is a calm, yet easily arousable patient, with normal sleep-wake cycles. However, some patients may require deeper levels of sedation while on mechanical ventilation.15 Continuous sedation may provide greater comfort for patients, as compared to bolus methods of sedation, but creates the risk of prolonging duration of ventilation and longer periods of intensive care unit hospitalization.13

Analgesic Medications for Pain Treatment in the ICU

Opioids are the principal analgesics used in the ICUs because of potency, concomitant mild sedative and anxiolytic properties, and their ability to be administered by multiple routes. Opioids typically used in ICUs are morphine, fentanyl, and hydromorphone.4 Through binding to opioid receptors, these agents produce analgesia and some sedation. Side effects of opioids can include respiration depression, bradycardia, constipation, nausea, vomiting, urinary retention, and pruritus.4 Amnestic properties are generally lacking and, for many patients, additional sedation is required if amnesia is desired.16 When opioids are used for extended periods of time, there is a risk of opioid withdrawal. One-third of patients in ICUs for longer than 7 days and receiving large doses of opioids experience some degree of withdrawal.17 To avoid opioid withdrawal, it is important that opioids be weaned when they have been administered for more than one week.

“Opioids are the principal analgesics used in the ICUs because of potency, concomitant mild sedative and anxiolytic properties, and their ability to be administered by multiple routes.”

Morphine has been the most widely used medication for cancer pain. It is the standard by which other opioids are compared. Morphine, like other medications directly extracted from opium poppies, stimulates the release of histamine which produces allergic and vasodilation-induced cardiovascular instability.17 Bolus IV morphine may be initiated with a 2 mg dose administered slowly over 4-5 minutes and then may be titrated with 1-2 mg every 10-15 minutes until analgesia is achieved. Continuous IV morphine can be administered with an initial 2-5 mg bolus dose followed by 1 mg/hr. Morphine is primarily metabolized in the liver and its metabolites are renally excreted. It has active metabolites of concern, morphine-3-glucuronide (M-3-G) and morphine-6-gluconoride (M-6-G). Accumulation of M-6-G in those with renal insufficiency can produce opioid toxicity and adverse effects such as nausea, sedation, and respiratory depression.17

Accumulation of M-3-G may lead to myoclonus and seizures.4 Morphine use should be avoided for patients with known renal insufficiency or failure.

Fentanyl is a synthetic opioid that is 100 times more potent than morphine. It is far more lipid soluble than morphine and is easily taken into the CNS, thereby producing analgesia with 1/100th of the morphine dose. Unlike morphine, it does not cause histamine release, which can cause vasodilation and hypotension. Fentanyl is preferred for hemodynamically unstable patients who compromise the vast majority of patients in ICUs. Its IV onset is immediate with a short duration of 30 minutes to one hour, and it is hepatically extracted. For moderate pain intensity, fentanyl is given IV in 25-100 mcg boluses over 1-2 minutes, and then is repeated every 10-15 minutes to achieve its adequate pain control. For moderate-severe pain, a loading dose of 50-200 mcg IV followed by 25-50 mcg/hr is typically administered.17 Administration of fentanyl for more than 5 days causes accumulation in adipose tissue which is mobilized once the drug is stopped, but may cause prolonged sedation. The fentanyl patch can be used for chronic pain relief in stable patients, but not in ICUs or for acute pain relief because of the 12 to 24 hour delay before peak serum levels occur.18

Hydromorphone is a semisynthetic opioid which is 5-6 times more potent parenterally than morphine. For opioid naïve patients with moderate-to-severe pain, hydromorphone may be started at 0.2 - 0.6 mg IV every 1 hour, and may be given continuous IV hydromorphone starting at 0.5-1 mg /hr. Hydromorphone has a longer duration of action than fentanyl. Hydromorphone does not significantly accumulate in patients with renal failure and thus may avoid neuroexcitability and cognitive impairment relative to what is typically seen for those receiving morphine.17

Meperidine use should be avoided in ICUs because it is first metabolized to normeperidine in the liver with a half-life of 15-20 hours, and then is renally excreted. Accumulation of normeperidine, which cannot be reversed with naloxone, has direct neurotoxic effects resulting in seizures, hallucinations, and delirium. As many patients in ICUs are already renally impaired, it is not recommended that meperidine be used in this setting.16,17

Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally not used in ICUs because of their many side effects and mostly oral route of administration. They inhibit vasodilatory prostaglandins which regulate glomerular blood flow, decrease creatinine clearance, and attenuate renin-angiotensin-aldosterone induced hyperkalemia.17 One parenteral NSAID, ketorolac, may be used for pain relief in ICUs for limited periods of time for patients younger than 65 years-old without a history of renal insufficiency or a gastrointestinal bleeding. An initial IV dose of 30 mg may be followed by 30 mg IV every 6 hours for up to 5 days. Use of ketorolac for greater than 5 days leads to greater risk of acute renal failure and gastrointestinal bleeding.17

Adjuvant analgesics are often used for neuropathic pain. Commonly used agents, anti-depressants and anticonvulsants, are generally not available as intravenous preparations and so limits their use in ICUs. However, there should always be a treatment plan for future use of these agents if there is a neuropathic component of pain.

Dosing Strategies

Route of Administration. Intravenous administration is the preferred route of administration. Three methods of IV administration include: bolus dosing for moderate pain, continuous infusion for moderate or severe pain that is poorly controlled with boluses and, for conscious patients, patient-controlled analgesia (PCA).18

Continuous versus PRN analgesia. Patients receiving ventilatory support or at the end of life in ICUs often need around-the-clock analgesia. Intermittent, as needed (PRN), medication administration may lead to inadequate pain control and is not recommended unless pain is only incidental to a certain activity such as repositioning or performing wound care.4 In general, continuous IV infusion is the preferred route of administration to provide consistent analgesia for dying patients. However, interruption of both sedation and analgesia may provide an opportunity for family members to say goodbye to patients.16 Sufficient breakthrough medication (at least 10% of the total daily dose) should be given on a PRN basis, especially during times when patients are stimulated or moved (i.e.; bathing, turning, suctioning).16 Patient Controlled Analgesia (PCA) is optimal when patients are able to participate because it can provide a continuous infusion for those who need continuous opioids and/or can provide controlled bolus doses with short lockout periods for breakthrough or incidental pain. Oral, sublingual, buccal or rectal opioid administration can be used with patients able to tolerate such methods, but generally are not started until patients are leaving ICUs and intravenous access is discontinued.16

“Patients must be evaluated hourly to ensure appropriate response to therapeutic interventions so that health care providers can proactively act to relieve pain.9

Regional Anesthesia

Regional anesthesia has been considered an alternative to systemic administration of analgesic medication to prevent complications associated with opioid use. Challenges for using regional anesthesia in ICUs include: positioning patients during catheter insertion, coagulopathy or use of anticoagulants, sepsis/bacteremia, hemodynamic instability, hypovolemia, and local infection.19 Peripheral nerve blocks in either the upper or lower extremities are another form of regional anesthesia which may be useful for certain surgical and trauma populations.


Patients must be evaluated hourly to ensure appropriate response to therapeutic interventions so that health care providers can proactively act to relieve pain.9 When reassessment reveals inadequate pain control despite initiation of therapeutic interventions, one must consider titration of medications, rotation of medications, or changes in the route of administration. When it is necessary to rotate opioids or use different routes of administration, the sum of opioids given during the previous 24 hour period in units of oral morphine equivalents is calculated. From this calculation, the new agent can be dosed up to 50-80% of the new agent’s equivalent dose and given as continuous or intermittent dosing.16

Managing Side Effects

Side effects to opioids are a common occurrence and should be anticipated and treated. Most of the guidelines for treatment are based on consensus guidelines and expert opinion due to the lack of randomized controlled studies in this area.20

Nausea and vomiting occurs in about 25% of persons on opioid therapy. There are multiple mechanisms including decreased gastrointestinal activity, stimulation of the chemoreceptive trigger zone, and enhanced vestibular sensitivity. Treatment options include the use of prokinetics, antipsychotics, serotonin antagonists, antihistamines, and corticosteroids. Optimally, the choice should depend on the mechanism of action, patient characteristics, risk of adverse effects, and cost.20 Trials of anti-emetics from different classes may be necessary to control nausea. If nausea persists despite the use of anti-emetics of different classes, one should consider opioid rotation.

Constipation is the most common side effect of chronic opoid use and must be controlled prophylactically. This may not be an initial concern for ICU patients who are not taking anything orally. However, once oral intake is initiated, measures such as adequate fluid intake, routine administration of stool softeners, and peristaltic agents should be instituted to prevent opioid-induced constipation.20 As with the treatment of all side effects, rotation of agents may be necessary to minimize this complication.

Pruritis is a side effect—more commonly seen with intraspinal opioids—precipitated by the release of histamine from mast cells or a centrally-mediated process. Antihistamines are often used but evidence from prospective studies is lacking.,20 In some cases of refractory pruritis, the use of low dose parenteral naloxone may be warranted. Consider opioid rotation if pruritis persists.

Sedation and cognitive adverse effects may occur with opioids. Since many patients in the ICU are sedated for ventilatory support, these side effects may be difficult to assess. If the patient begins to take oral medications but sedation or cognitive changes persists, the treatment of sedation may include reduced doses or rotation of opioids, adjuvant therapy, and possibly the use of psychostimulants.

Respiratory depression can occur with opioid use and can be a concern for the patient who is not on ventilatory support. This adverse effect can usually be avoided through careful monitoring and adjustment of opioid medications. If patients are not arousable with respiratory rates of less than 8 breaths per minute, naloxone should be given by diluting 0.4 mg in 10 mL of normal saline and administering it in 1 mL increments over 2 minutes until respiratory rates increase and patients are arousable.21


It is important to manage pain in ICUs but a universal approach for the management of pain during ICU treatment is not possible. There must be individualization of care provided for very ill and typically unstable patients. Provision of analgesia is often compromised by circumstances associated with the underlying pathology. Practitioners must carefully assess and aggressively manage pain, while working to resolve the pathology or provide sensitive end of life care in ICUs. Through appropriate education, health care providers can provide safe and effective pain management in ICU settings.

Last updated on: February 26, 2013
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