Abstract
The interplay of pain, anxiety, and delirium makes the achievement of patient comfort in the critically ill challenging. Assessment of pain, anxiety, and delirium is hence central to the management of patient care in the critically ill. Such an assessment will help direct therapy appropriately and provide a more patient-centered treatment based on the underlying pathology. Importantly, the underlying pathophysiology in critically ill patients may limit therapeutic options for pain, anxiety, and delirium necessitating careful selection of treatment options.
Keywords
analgesia, critically ill, delirium, hypnosis, neuromuscular blocking agents, sedation scales
Management of pain, agitation, and delirium is vital in the critical care setting. Within the intensive care unit (ICU), the concepts of analgesia, hypnosis, and cognition are inexorably intertwined. Adequate treatment of pain and anxiety has been shown to decrease the stress response and psychological illness, improving outcomes in critical care patients. Importantly, critically ill patients are at great risk of developing delirium, negatively affecting the trajectory of care. Critically ill patients experience both pain and anxiety from a multitude of factors. Along with obvious etiologies of pain such as preexisting diseases and trauma, patients in critical care settings often experience pain from prolonged immobility, routine nursing care (airway suctioning, dressing changes, and patient mobility), monitoring and therapeutic devices (catheters, drains, and endotracheal tubes), and air hunger. Understandably, critical care patients also experience a significant degree of anxiety. Anxiety may stem from pain, being in an unfamiliar environment, and lack of control or even a fear of impending death. Significant anxiety may lead to agitation and eventually delirium, complicating diagnosis and interfering with treatment, leading to increased morbidity and mortality. Certainly, anxiolysis is difficult to achieve in a patient experiencing significant pain or delirium. Furthermore, many of the medications used to treat pain have hypnotic effects. Thus it is easy to understand how the concepts of hypnosis and analgesia have become interdependent goals of critical care therapy. Complicating matters is the possibility of delirium altering the ability to assess and attain these goals. However, the close relationship between these distinct goals should not confuse the clinician as to the specific aim of each therapeutic agent. By understanding the tools for appropriate patient assessment and management, one can better choose the appropriate pharmaceutical agents for analgesia, hypnosis, and delirium management, providing an integrated, patient-centered therapeutic regimen to the critically ill.
Assessment
Analgesia
Analgesia assessment tools are difficult to implement in the critical care setting. An ideal assessment tool should provide simple, reliable data that guide therapy in a critical care setting. The most reliable and valid indicator of pain is a patient’s self-report. Unidirectional tools such as the numeric rating scale and visual analog scale rely on a patient’s perception of their pain ( Fig. 40.1 ). The numeric rating scale requires patients to rate their pain from 0 to 10, with 0 representing no pain and 10 representing the worst pain possible. The visual analog scale consists of a 10-cm horizontal line with descriptive phrases at either end, from no pain to worst pain ever. Variations of the visual analog scale include simplistic facial images rather than descriptive phrases. Despite the simplicity and reliability of these unidirectional pain assessment tools, they often are not useful in the critical care setting, because patients may be unable to communicate. Behavioral-physiologic scales use pain-related behaviors such as posturing and facial expressions, along with physiologic indicators such as heart rate, blood pressure, and respiratory rate to assess pain intensity in patients who are unable to participate in unidirectional pain assessment scales. However, physiologic markers are not specific for pain and may be misinterpreted in a critical care setting. The Behavioral Pain Scale (BPS; Fig. 40.2 ) and the Critical-Care Pain Observation Tool (CPOT) are the most reliable in critically ill patients who are unable to self-report their pain. The BPS allows for pain assessment in mechanically ventilated patients by assigning a score of 1–4 for three different behaviors. The CPOT allows for evaluation of both intubated and extubated patients by scoring four different behaviors on a scale of 0–2. Both these tools allow for standardized assessment of pain based on patient behaviors. Anxiety and delirium often cloud the behavioral-physiological pain picture, resulting in overestimation of a patient’s pain. Although both unidirectional and behavioral scales provide reliable assessment in a majority of patients, pain assessment in patients requiring critical care therapy remains challenging to assess.
Hypnosis
Titrating therapy to sedation levels allows for better outcomes as sole assessment of pain is complicated in critically ill patients. Both oversedation and undersedation can result in clinically significant adverse events. Undersedation may result in ventilator dyssynchrony, increased oxygen requirements, self-removal of devices, and possibly posttraumatic stress disorder from a stay in the critical care unit. Alternatively, oversedation may result in prolonged tracheal intubation and mechanical ventilation, increasing the chance of pneumonia and respiratory deconditioning. To this end, several sedation monitoring scales ( Table 40.1 ) have been developed to aid in appropriate monitoring and titration of sedation levels. With sedation assessment scales, sedation levels can be maintained by different care providers, and therapeutic agents may be titrated to achieve desired levels of sedation. The Richmond Agitation Sedation Scale (RASS) and Riker Sedation-Agitation Scale (SAS) are the most valid and reliable sedation assessment tools. The RASS is a user-friendly and therefore commonly used sedation scale, with scores ranging from +4 (a violent dangerous patient) to −5 (an unarousable patient). A sedation score of 0 is most often therapeutically targeted, as it correlates with an alert and calm patient. The Ramsay Sedation Scale is the most simplistic and allows for a numeric score from 1 to 6, based on responsiveness of the patient. However, it is more subjective and lacks clear descriptors between different levels. The SAS scores a patient’s level of sedation from 1 to 7 and is especially adapted to warn the clinician of extremes of sedation and agitation, which is not provided by the simplistic Ramsay Sedation Scale. The Motor Activity Assessment Scale has been derived from SAS and categorizes a patient’s sedation level based on behavioral response to stimulation. Other complex sedation scoring systems have also been constructed, but it is most important to become familiar with one system and standardize its use in an ICU. Scoring should be consistent and reliable by different care providers to ensure patients are not oversedated or undersedated. Once sedation goals are met for a particular patient, they should be regularly reevaluated to ensure therapy is being properly guided. Importantly, requirements for sedation are dynamic, generally declining as illness improves, and thus must be reassessed frequently.
| (a) Richmond Agitation Sedation Scale | ||
|---|---|---|
| Score | Term | Description |
| +4 | Combative | Overtly combative or violent; immediate danger to staff |
| +3 | Very agitated | Pulls on tubes or has aggressive behavior toward staff |
| +2 | Agitated | Frequent nonpurposeful movement or ventilator dyssynchrony |
| +1 | Restless | Anxious but movements not aggressive or vigorous |
| 0 | Alert and calm | |
| −1 | Drowsy | Not fully alert but sustained (>10 seconds) awakening |
| −2 | Light sedation | Briefly (<10 seconds) awakens with eye contact |
| −3 | Moderate sedation | Any movement (but no eye contact) to voice |
| −4 | Deep sedation | No response to voice, but any movement to physical stimulation |
| −5 | Unarousable | No response to voice or physical stimulation |
| (b) Ramsay Sedation Scale | ||
|---|---|---|
| Score | Arousal | Description |
| 1 | Awake | Patient anxious, agitated, or restless |
| 2 | Awake | Cooperative, orientated, and tranquil |
| 3 | Asleep | Patient responds to commands only |
| 4 | Asleep | Brisk response to loud auditory stimulus or glabellar tap |
| 5 | Asleep | Sluggish response to loud auditory stimulus or glabellar tap |
| 6 | Asleep | No response to loud auditory stimulus or glabellar tap |
| (c) Riker Sedation Agitation Scale | ||
|---|---|---|
| Score | Term | Description |
| 7 | Dangerous agitation | Pulling at catheters, climbing out of bed, striking staff, thrashing |
| 6 | Very agitated | Does not calm despite verbal reminders; requires restraints |
| 5 | Agitated | Anxious, attempting to sit, calms down with verbal instruction |
| 4 | Calm and cooperative | Calm, awakens easily, follows commands |
| 3 | Sedated | Difficult to arouse, awakens to verbal stimuli but drifts off again |
| 2 | Very sedated | Arouses to physical stimuli but does not follow commands |
| 1 | Unarousable | Minimal or no response to noxious stimuli |
| (d) Motor Activity Assessment Scale | ||
|---|---|---|
| Score | Term | Description |
| 6 | Dangerously agitated | Patient is pulling tubes, striking staff |
| 5 | Agitated | Spontaneously moving and not following commands |
| 4 | Restless and cooperative | Follows but spontaneous uncomfortable activity |
| 3 | Calm and cooperative | Spontaneous movement and patient with calm activity |
| 2 | Response to name/touch | Opens eyes, turns head, moves limb with name or touch |
| 1 | Response to noxious stimuli | Moves in response to noxious stimuli |
| 0 | Unresponsive | Does not move with noxious stimuli |
Few objective measures are available to assess sedation. Vital signs such as heart rate, blood pressure, and respiratory rate are not specific or sensitive to sedation in the critically ill. Heart rate variability and lower esophageal sphincter tone are beginning to be used to objectively measure sedation. The bispectral index (BIS) aims to provide an objective measure of a patient’s sedation by assigning a numerical value to a patient’s electroencephalogram activity. The BIS has been shown to correlate with hypnotic drug effect in healthy elective surgery patients, but the BIS has not been as useful in the critical care setting. BIS scores may vary between individuals with the same subjective level of sedation, resulting in marked variability. Furthermore, the BIS may not correlate with sedation in patients with muscle activity or impairments of the brain. However, there may be a role for the BIS in patients receiving neuromuscular blocking agents (NMBAs), as other assessment tools for hypnosis are useless. Currently, subjective scoring of sedation is the standard for assessing sedation in the critical care setting, until more reliable objective tools are available.
Delirium
Patients requiring intensive care therapy often become delirious, complicating the assessment of pain and anxiety. Delirium is often confused with dementia. Dementia is a progressive disease with a decline in memory and cognitive skills and rarely presents acutely. Conversely, delirium is an acute reversible change in mental status. It is characterized by fluctuating levels of arousal associated with sleep–wake cycle disruption brought on by the reversal of day–night cycles and is associated with worse outcomes and increased long-term mortality. Patients suffering from delirium can be hypoactive, hyperactive, or even have mixed levels of activity. Hyperactive delirium is easily recognized, as patients are agitated and combative interfering with therapeutic measures; however, hypoactive delirium, which is characterized by calm appearance, decreased mobility, and inattention, is actually associated with a worse prognosis. Ideally, delirium should be assessed using the DSM-IV criteria by a psychiatric expert. The DSM-IV assessment, however, is involved and often impossible in an acutely ill patient. The Confusion Assessment Method for the ICU (CAM-ICU; Fig. 40.3 ) and the Intensive Care Delirium Screening Checklist (ICDSC; Fig. 40.4 ) rapidly and accurately assesses delirium in critically ill patients. The CAM-ICU assessment is a flow-diagram assessment, while the ICDSC is a scoring assessment in determining the presence of delirium. In a critically ill patient with an acute change or fluctuating mental status, the CAM-ICU aims to evaluate inattention, altered level of consciousness, and disorganized thinking. In order to be diagnosed with delirium, a patient must not be heavily sedated and demonstrate inattention, along with either altered level of consciousness or disorganized thinking. The ICDSC, on the other hand, does not evaluate disorganized thinking but incorporates alterations in sleep-wake cycle, orientation, psychomotor function, appropriateness, and delusions. The development of delirium assessment has improved the ability to provide appropriate therapy, and more importantly enlightened caregivers, on the occurrence of this complicated disease.
Therapeutic Agents
Patient comfort in the critical care setting is obtained with the use of both hypnotic and analgesic agents. Focusing first on providing analgesia and then on hypnosis may provide more effective sedation. The lack of appropriate analgesia may lead to hyperesthesia and paradoxical agitation in the face of disinhibition from sedative drug administration. Once adequate analgesia has been established, the remainder of the sedation regimen should be targeted at maintaining patient comfort, behavioral control, and an appropriate degree of amnesia with hypnotic agents. The value of a standardized approach to sedation with treatment using analgesic and sedation agents has been demonstrated to reduce oxygen consumption and autonomic hyperactivity, and improve outcomes. Ideally, therapeutic agents should possess a rapid onset and offset of action, with easy titration to therapeutic goals without the development of consequential side effects.
Analgesia
Appropriate attention to analgesia is an important step in all sedation protocols, because most critically ill patients experience some degree of pain. Critical care staff should aim to minimize the production of pain by minimizing irritating stimulation, such as endotracheal tube traction on the carina and prolonged immobility. Despite aims to minimize pain production, supplemental analgesic therapy is often necessary for adequate pain control. Both opioid and nonopioid pharmacologic agents should be used to help control pain. With proper treatment of pain, better outcomes with quicker and more positive return to health can be expected.
Nonopioids
Acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) are recommended first-line therapy for the treatment of pain. Despite this recommendation, their use in the ICU is a frequently forgotten adjunct to pain control. NSAIDs nonselectively inhibit cyclooxygenase, blocking the production of inflammatory mediators. Ketorolac, an NSAID, has been shown to have an efficacy comparable to moderate doses of commonly used opioids at doses of 30 mg intravenously (IV) every 6 hours. However, clinical concerns of renal insufficiency and bleeding from platelet dysfunction and gastrointestinal tract mucosa limit the use of NSAIDs in the ICU. Renal insufficiency results from the decreased of production of prostacyclins that increase renal blood flow. Normally, inhibition of prostacyclin production does not result in a decrease in renal function; however, in patients with hypoperfusion, hypovolemia, or baseline renal impairment, or in older age, ketorolac may increase the incidence of NSAID-induced renal injury. Additionally, use of ketorolac for greater than 5 days has been associated with an increased risk of renal dysfunction and both gastrointestinal and operative site bleeding. Acetaminophen is commonly used to treat mild to moderate pain, and as an antipyretic. The addition of acetaminophen, at doses of 1 g every 6 hours, to opioid therapy has been shown to produce greater pain relief than opioids alone. With the availability of intravenous acetaminophen, use of this medication has shown benefits in conjunction with opioids immediately postoperatively. Care should be taken to ensure that toxic doses of acetaminophen are avoided, given that oral pain medications are routinely given as a combination of opioid and acetaminophen. Particularly, patients with liver dysfunction or a history of alcohol abuse are at risk for hepatoxicity from acetaminophen.
Patients suffering from neuropathic pain may prove difficult to manage with opioid medication alone. Enterally administered gabapentin and carbamazepine are often helpful in the treatment of neuropathic pain. Gabapentin can be administered in doses of 100–1200 mg 3 times a day with precautions in patients with renal dysfunction as the drug is excreted unchanged. Carbamazepine is dependent upon hepatic metabolism, and dosing starts at 50 mg twice a day uptitrated to a maximum of 1200 mg per day. Although opioids remain the mainstay of analgesic therapy in the ICU, nonopioids should be considered as possible supplemental agents.
Analgesic Agents: Opioids
A careful understanding of the properties of individual opioids ( Table 40.2 ) is essential to the appropriate use of these agents in the ICU. Intravenous opioids are first-line agents for the treatment of nonneuropathic pain in the critically ill, with all being equally effective when titrated to patient needs. Lipid solubility, protein binding, and metabolism account for the pharmacokinetic differences between these agents. Opioids produce analgesia, mainly by stimulating μ, δ, and κ-receptors located both centrally and peripherally; however, interaction with other opioid receptors may lead to adverse effects. Unwanted effects of opioids include nausea, constipation, urinary retention, pruritus, and excessive sedation with possible respiratory depression. Severe constipation leading to ileus has been treated with some success using intravenous and parenteral opioid antagonists. Respiratory depression occurs because the ventilatory response to hypercapnia is decreased, while the response to hypoxia is obliterated. These respiratory depressive qualities, however, are often helpful in treating ventilator-patient dyssynchrony. Hypotension is occasionally seen in hypovolemic patients, as a decrease in sympathetic tone occurs after treatment of pain with opioid administration. The full opioid agonists, hydromorphone and fentanyl, are the most frequently used analgesics in critically ill patients. Opioids combined with hypnotic agents result in a synergistic effect that may permit dose reduction, thereby reducing the occurrence of undesirable side effects of both opioids and hypnotics.
