Pain Control and Sedation

John D. Lang Jr.

Onuma Chaiwat

Trauma is a major cause of morbidity and mortality worldwide. Injuries and complications due to motor vehicle accidents, gunshots, stabbings, and burns are frequently associated with both short- and long-term physical suffering and mental anguish. In 2000, more than 50 million Americans suffered injuries requiring medical treatment, with approximately 150,000 injuries being fatal. This resulted in projected lifetime costs of approximately $406 billion; $80 billion for medical treatment, and $326 billion for lost productivity.¹ In recent years, pain control has been of particular concern because improving pain management has not only shown to improve comfort but has also been demonstrated to reduce morbidity and improve short- and long-term outcomes.²,³,⁴ According to Whipple et al.,⁵ 74% of polytrauma patients in intensive care unit (ICU) rated their pain intensity by a verbal pain intensity scale as either moderate or severe, whereas 95% of house staff and 81% of nurses reported analgesia to be “adequate.” Additionally, Choiniere et al.,⁶ demonstrated that approximately 50% of burn patients studied reported little or no analgesia from the doses of medication administered before and during dressing changes. There are multiple reasons for inadequate pain control in trauma patients including excessive concern about hemodynamic instability, fear of inducing addiction, and respiratory depression. However, the effect of inadequate pain control in trauma patients can result in remarkable physiologic stress responses that may potentiate disability and prolong the healing process. Consequently, it is essential to treat pain aggressively because the ramifications of inadequate pain control are more than psychological. However, most pain research involving trauma patients is based on so called iatrogenic trauma, also referred to as elective surgery. Hence, care must be limited by extrapolating these studies to the nonelective trauma patient.

Apart from pain control, sedation in the critically ill trauma patient also plays a vital role. Administration of sedatives is a common adjunct for the treatment of anxiety, delirium, and agitation in those critically ill patients especially in the ICU. Although the frequency of delirium varies from 15% to 50% among general medical or surgical patients,⁷,⁸,⁹ these statistics did not apply to the critically ill trauma patient and few data exist concerning delirium in patients admitted in ICU.¹⁰,¹¹,¹²,¹³ Most previous studies have been focused on patients with hip fractures, in which the incidence of delirium varied from 4% to 53.3%.¹⁴ Additionally, the causes of anxiety in critically ill trauma patients are multifactorial including an inability to communicate, excessive stimulation, and sleep deprivation. The attempt to reduce the anxiety and delirium including frequent reorientation, maintenance of patient comfort, and optimization of environment may be supplemented with sedatives. To review the necessity and value of pain and sedation control in the trauma patients, the author will discuss the following:

The stress response of critical illness
Physiologic impact of trauma
Evaluation of pain and sedation in critically ill trauma patients
Analgesia and sedation for trauma patients
Pain management in outpatients.

THE STRESS RESPONSE OF CRITICAL ILLNESS

The effect of severe trauma, disease, infection, and surgery can cause remarkable metabolic stress on the human body. The ability of the body to cope with stress is known as physiologic reserve. Critical illness is a state in which this
reserve is inadequate to maintain life, and exogenous organ support is needed. Tissue injuries elicit marked neuroendocrine changes that result in predictable alterations. These neuroendocrine responses to critical illness have been discussed and characterized for decades and are recognized as appropriate mechanisms of adaptation.¹⁵ There is also alteration in the autonomic nervous system, which is accompanied by diffuse changes in endocrine function. In addition to changes in the autonomic nervous system and endocrine function, other alterations occur such as the pattern of protein synthesis within the liver increasing coagulation pathways. Recently, it has been found that traumatic injuries are associated with increased plasma concentrations of select cytokines that may contribute to adverse outcomes.¹⁶,¹⁷

The Neuroendocrine Response to Critical Illness

In acute illness, the mean levels of growth hormone (GH) become elevated. There is an increase in both peak and trough levels; however, the response may be variable.¹⁸,¹⁹,²⁰ The rising levels lead to lipolysis and inhibit lipid uptake. In addition, GH also has direct insulin antagonizing effects. In normal people, the overall hormonal effect of GH is for protein anabolism as opposed to critically ill patients in whom acute protein degradation, liberation of amino acids, glucose, and free fatty acid occur instead of anabolism.

Active thyroid hormones (T3 and T4) are essential for regulation of cardiac, pulmonary, and neurologic function. In acute phase of critical illness, T3 levels decrease as a result of a drop in peripheral conversion of T4 to T3.²¹ This drop in T3 levels tends to persist during critical illness. There are studies that report the magnitude of the decrease in T3 levels correlates well with patient mortality.²²,²³ On the other hand, T4 levels may remain in the normal range although there maybe an early transient rise during the illness. Under normal circumstances, a drop in T3/T4 levels would inhibit the feedback loops that results in an increase in thyroidstimulating hormone (TSH) level. However, TSH tends to remain in a normal or low range during stress.²⁴,²⁵,²⁶ This fact has been attributed to a change in thyroid hormone set point.²⁷ Interestingly, such seriously ill patients generally do not show evidence of thyroid illness. This condition (low T3/T4 and normal TSH level) has been termed sick euthyroid syndrome, low-T3 syndrome, or nonthyroidal illness.

A state of hypercortisolism is generally known to occur during acute critical illness. Cortisol shifts energy production and substrates to vital organs and delays anabolic process.¹⁸,²⁸ This creates the immediate source of energy during the initial phase response (“fight or flight”). At the same time, there is an increase in catecholamine levels. The major functions of epinephrine and norepinephrine are stimulation of heart rate; increased myocardial contractility; and vasoconstriction of gut, skin, and skeletal muscle vascular beds. These actions maintain perfusion to vital organs in the setting of acute critical illness. In addition to an increase in both cortisol and catecolamines, the renin-angiotensin system is stimulated and aldosterone is produced, which results in fluid retention, hypokalemia, sodium retention, and vasoconstriction. With regard to other axes, testosterone levels are acutely reduced during the stress stage state, resulting in a decrease in anabolism.²⁹,³⁰ If the critical illness is protracted, hypogonadism is frequently the result of this hormone change.³¹ Prolactin levels also fluctuate during the acute and critical illness, rising acutely³² followed by demonstrating a blunted pulsatile secretion in the chronic phase. It may play a role in the stimulation of inflammatory cascade.²⁸

Another important physiologic alteration of critical illness involves renal function. There is a significant increase in plasma vasopressin (ADH) concentration especially in patients undergoing surgery³³ and it remains elevated for approximately 7 days postoperatively. The consequence of rising of plasma ADH is retention of free water. Other electrolyte changes include an increase in sodium retention mediated by sympathetic outflow to the kidney.

Regarding the hematologic system, there appears to be a tendency toward hypercoagulability. In surgical patients, plasma fibrinogen concentrations are increased as a result of augmented synthesis of this protein by the liver. There is also an increase in platelet aggregation and a decrease in fibrinolysis. The latter occurs as a result of increased plasma concentration of plasminogen activator inhibitor-1.³⁴ In addition, traumatic injuries also alter the pattern of protein synthesis in the liver. There is an increase in production and release of the so-called acute phase reactants, whereas synthesis of albumin and other hepatic products is decreased. Finally, recent data demonstrated that cytokines can be a component of stress response. In the setting of tissue inflammation, macrophages produce many different cytokines including tumor necrosis factor α (TNF-α), interleukin (IL)-1, IL-6, and IL-8. High circulating levels of IL-1 and TNF-α can induce and stimulate the release of classic stress hormones. They can also contribute to the synthesis of acute phase reactants and lead to the upregulation of nitric oxide synthase that ultimately yields the biomolecule, nitric oxide. However, it has been found that traumatic injury is associated with increased plasma concentration of IL-6. On the contrary, TNF-α rises only slightly and IL-1 concentrations do not appear to alter with isolated trauma.¹⁶,¹⁷

PHYSIOLOGIC IMPACT OF TRAUMA

The stress response after major trauma is much greater than that after elective surgery. If moderate to severe, it may lead to catabolic and thromboembolic stages that are associated with decreased survivability, increased morbidity, and slow recovery of function. Although the
initial process of stress response is neurohormonal, the secondary effects involve multiple organ systems including cardiovascular, pulmonary, gastrointestinal (GI), musculoskeletal, immunologic, renal, and even central nervous system (CNS). A previous study reviewed the components of the stress response and determined that analgesic interventions that do not adversely modify the stress response will have minimal impact on patient outcome.³⁵ Untreated pain can potentiate the adverse effects on normal physiology. For instance, trauma-related pain primarily caused by chest and upper abdomen injuries can lead to impaired pulmonary function from chest splinting and reflex-activated diaphragmatic dysfunction. Functional residual capacity, cough, and vital capacity are all decreased, resulting in serious complications such as atelectasis and ventilator-associated pneumonia. In addition to adverse pulmonary effects, GI tract motility might be adversely affected due to an increase in sympathetic tone from pain, producing an ileus, which impedes early enteral nutritional absorption. Over the last 2 decades, several studies have reported that the persistence of severe and inadequately treated pain can lead to anatomic and physiologic changes in nervous system.³⁶ The phenomenon is described as “neuroplasticity” and defined as the ability of neuronal tissue to change in response to repeated incoming stimuli. This can lead to the development of chronic, disabling neuropathic pain. In addition, neuroma formation, complex regional pain syndromes associated with sympathetic dysfunction, and neuralgia can also occur following traumatic injuries. Nevertheless, there has been an effort to interrupt the stress response by both skilled surgical and anesthetic management such as using high doses of intravenous narcotic technique to blunt the cardiovascular stress response in patients undergoing cardiac surgery or implementing regional anesthetic techniques to attenuate the stress response.

EVALUATION OF PAIN AND SEDATION IN CRITICALLY ILL TRAUMA PATIENTS

Pain Assessment

There are a limited number of studies that address pain assessment in the critically ill patient. Although it has been publicized that methodic documentation and pain evaluation lead to the improvement in the quality of pain management,³⁷ pain control in these patients, especially when they are admitted in ICUs with hemodynamic instability, is not often considered a priority. However, accurate evaluation of pain in the critical care setting is very challenging for a number of reasons. Patients frequently have impaired cognitive function and may be unable to communicate because of having sedation and/or neuromuscular blockage agents on board. It has also been found that a high percentage of health care extenders in this setting are not able to evaluate the pain correctly.

Sources of Pain for Critically III Patients

There are many sources of pain for these patients. The sources can be from either acute or chronic pain conditions or both. Nevertheless, acute pain is more prevalent due to direct traumatic injuries, surgical wounds, and invasive procedures conducted in the acute care setting. In addition, one should keep in mind that immobility can lead to remarkable discomfort or “frozen” joints from prolonged bed rest or extremity stabilizers. Finally, pain originating from occult infections such as sinusitis in nasotracheally intubated patients, otitis media, perianal abscesses, and diabetic ulcers should not be overlooked. With regard to the chronic pain conditions, a careful history of prior pain medication useand dosage before the injury is important. If significant doses of narcotics were used on a chronic basis, one must consider tolerance when administering opioids. In this setting, if the doses of opioids given in the acute setting are inadequate, withdrawal syndromes, which can contribute to agitation and altered mental status, can occur. A similar situation can occur with benzodiazepines, tricyclic antidepressants (TCA), and selective serotonin reuptake inhibitors (SSRI) as well.³⁸,³⁹

Pain Evaluation Methods in the Fully Conscious Patients

“All critically ill patients have the right to adequate analgesia and management of their pain.”⁴⁰ The most reliable and valid indicator of pain is the patient’s selfreport.⁴¹ There are a variety of existing tools to assess pain. It is essential to use those that are brief, simple, reliable, and sensitive in their ability to accurately detect the changes in pain severity, and reflect the effect of analgesic intervention.

Present and Past History

As mentioned in the preceding text, the patient’s report of pain is the ideal way for assessing pain. Moreover, it should include the characteristics of pain such as burning, stabbing, aching and stinging, the frequency and duration, the distribution of the pain, and which factors those make it worse or better. For critically ill adults who are unable to communicate effectively, it would be very useful to receive this information from their relatives. A prior pain history may be helpful in interpreting patient’s reaction to the current pain management being utilized. In addition, a past history of previous hospital or ICU admission, pertinent psychiatry, and alcohol or recreation drug usage are important for health care providers to obtain. Finally, the patient’s ethnic⁴²,⁴³,⁴⁴ and cultural background⁴⁵,⁴⁶ is vitally important in understanding how pain control implementation and assessment are to be interpreted.

Unidirectional Tools

A visual analog scale (VAS) is a reliable and valid tool for many patient populations⁴⁷ and is considered the gold standard for pain assessment. It comprises a 10 cm horizontal line with the one end labeled “no pain” and the other end labeled “severe pain or worst pain ever.” Patients are asked to make marks along the line in the areas that best represent their pain. There are also a vertical VAS or pain thermometer versions that might be easier to understand by younger children. Although there are no specific tests for the ICU, VAS is often used in this setting.⁴⁸,⁴⁹,⁵⁰,⁵¹ VAS performance may suffer when applied to elderly patients because of the impairment of their visual and cognitive function. Moreover, postoperative patients and especially the elderly require sedation and sleep at night, which might be an obstacle to perform VAS.⁴⁸
Numeric rating scale (NRS) is a scale of 11 points ranging from 0 to 10. Patients choose a number that describes the pain in which 0 corresponds to no pain and 10 represents the worst pain. NRS correlates with VAS and can be used with patients of different ages. In addition, patients are able to complete the NRS by either writing or speaking. Consequently, it is the preferred tool of ICU staff.
Verbal descriptor scales (VDS) is a word(s) scale that represents the intensity of patients’ pain from a vertical list of words or from words evenly spaced along a horizontal line.⁵² Although this scale can be used effectively in chronic pain patients, it requires the ability of patients to understand the words. Not surprisingly, it is not frequently used for critically ill patients.
The verbal graphic scale (VGS), originated from the emergency department, was subsequently adapted for the ICU for the continuity of treatment. It consists of a numeric scale from 1 to 10 (0 = no pain; 1 to 3 = mild pain; 2 to 4 = moderate pain; 5 to 7 = severe pain and 8 to 10 = really severe pain).⁵³ Previous studies have demonstrated strong intercorrelation among VGS, VAS, NRS, and VDS.⁵⁴,⁵⁵

Pain Evaluation Methods in Patients Unable to Communicate

The evaluation of the physiologic parameters such as heart rate, blood pressure, and respiration rate may be reproducible;⁵⁶ however, the confounding factors found in critical illness make the use of a single set of these parameters questionable.
Physical examination is as important as the informational history. In addition to the routine examination, emphasis should be placed on the injuries where the pain may have originated. Also, the presence of agitation, lacrimation, papillary dilation, and perspiration may be helpful.
The behavioral-physiologic scale is a tool that assesses pain-related behaviors (movement, facial expression, and posturing) and physiologic indicators (heart rate, blood pressure, and respiration rate). The behavioral-physiologic scales have been compared with an NRS and a moderate-to-strong correlation was found between them.⁵⁷

All in all, it is essential to insert pain among the parameters routinely assessed in critically ill patients and the response to pain treatment should be controlled utilizing appropriate scales for individual patients. In fact, The Joint Commission on Accreditation of Health Care Organizations declared pain level to be the “fifth vital sign.” This has led to increased efforts to reduce patients’ pain scores. The level of pain reported by the patient must be considered the current standard for pain assessment and response to analgesia whenever possible. In ICUs, the NRS is recommended for pain assessment. Finally, patients who are unable to communicate should be assessed through both subjective observation of pain-related behaviors and physiologic indicators.⁴⁰

Sedation Evaluation

Agitation is frequently seen in critically ill patients. According to Fraser et al., it occurred at least once in 71% of patients in a medical-surgical ICU.⁵⁸ Agitation can be caused by many factors, for example, extreme anxiety, delirium, adverse drug effects, and pain.⁵⁸ Nevertheless, when patients develop signs of agitation or anxiety, the first priority is to identify and treat the underlying physiologic abnormality such as hypoxemia, hypercarbia, hypoglycemia, hypotension, and pain. In addition, the patient population that incurs trauma has a high prevalence of drug and alcohol abuse, so withdrawal syndromes particularly from alcohol is high.⁵⁹,⁶⁰,⁶¹ As with pain control, assessment of sedation should be evaluated as part of the comprehensive assessment of the critically ill patient at the time of admission, and should be recorded with particular attention to detail. An ideal scale should provide simple and recordable data and accurately describe the degree of sedation and agitation within well-defined categories. The scales should also be able to guide the titration of therapy, and more importantly should have validity and reliability in critically ill patients. Although many scoring systems are available, a true gold standard has not existed.⁶²,⁶³ The major methodological problems encountered with these scales were that they were, for the most part, studied in patients who had undergone anesthesia and were recovering in the postanesthesia care units, and not among patients admitted to the ICU with injuries resulting from trauma.

The methods to evaluate the depth of sedation and agitation can be divided into two groups:

Subjective Assessment

These methods are on the basis of clinical observation. The data are recorded after the direct observation by the
observers. The Riker Sedation-Agitation Scale (SAS) was the first scale proved to be reliable and valid in critically ill patients.⁶⁴,⁶⁵ There are several items listed describing patient consciousness, agitation, and behavior (see Table 1). The Motor Activity Assessment Scale (MAAS) was adapted from SAS. It comprises seven items to describe patient behavior in response to noxious stimuli (Table 1) MAAS also has demonstrated validity and reliability in critically ill patients.⁶⁶ In addition to SAS and MAAS, the Ramsay scale assesses three levels of awake and asleep states (Table 1).⁶⁷ Although it has been used in many sedation trials and clinical practices, it has been criticized for lack of clear explanations and discrimination between categories (Table 1).⁶⁵,⁶⁸ Another scale, the COMFORT scale, has been widely used in the ICUs but is limited to children.⁶⁹ Although in a systemic review by De Jonghe et al.,⁶³ this group showed high reliability and satisfactory correlation among other scales with the Ramsey scale and the COMFORT scale. Many previous sedation assessment instruments have focused exclusively on the level of consciousness alone or with another dimension such as agitation. Furthermore, in these instruments, the assessment of both consciousness and agitation have been minimized in a single scale containing multiple dimensions resulting in unclearly defined levels of sedation leading to loss of useful clinical information. Recently, De Jonghe et al.⁶² established a new instrument, the Adaptation to the Intensive Care Environment (ATICE), which is highly reproducible for patients in the ICU who are
receiving mechanical ventilation. ATICE consists of five items, awakeness and comprehension combined in a consciousness domain, calmness, ventilator synchrony, and face relaxation combined in a tolerance domain. However this instrument did not include the assessment of delirium, which is the major contributing factor to ICU agitation.

TABLE 1 SCALES USED TO ASSESS SEDATION AND AGITATION

Score	Description		Definition
			*Riker Sedation-Agitation Scale (SAS)*
7	Dangerous agitation		Pulling at endotracheal tube (ETT), trying to remove catheters, climbing over bedrail, striking staff, thrashing side to side
6	Very agitated		Does not calm despite frequent verbal reminding of limits, requires physical restraints, biting ETT
5	Agitated		Anxious or mildly agitated, attempting to sit up, calm down to verbal instructions
4	Calm and cooperative		Calm, awakens easily, follows commands
3	Sedated		Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands
2	Very sedated		Arouse to physical stimuli but does not communicate or follow commands, may move spontaneously
1	Unarousable		Minimal or no response to noxious stimuli, does not communicate or follow commands
			*Motor Activity Assessment Scale (MAAS)*
6	Dangerous agitation		No external stimulus is required to elicit movement and patient is uncooperative pulling at tubes or catheters or thrashing side to side or striking at staff or trying to climb out of bed and does not calm down when sedated
5	Agitated		No external stimuli is required to elicit movement and attemping to sit up or move limbs out of bed and does not consistently follow commands (e.g., will lie down when asked but soon reverts to attempts to sit up or move limbs out of bed)
4	Restless and cooperative		No external stimuli is required to elicit movement and patient is picking at sheets or tubes or uncovering self and follows commands
3	Calm and cooperative		No external stimuli is required to elicit movement and patient is adjusting sheets or clothes purposefully and follows commands
2	Responsive to touch or name		Open eyes or raises eyebrows or turns head toward stimulus or moves limbs when touched or name is loudly spoken
1	Responsive only to noxious stimulus^a		Opens eyes or raises eyebrows or turns head toward stimulus or moves limbs with noxious stimuli
0	Unresponsive		Does not move with noxious stimuli
			*Ramsay Scale*
1	Awake		Patient anxious and agitated or restless or both
2		—	Patient cooperative, oriented, and tranquil
3		—	Patient responds to commands only
4	Asleep		A brisk response to a light glabellar tap or loud auditory stimulus
5		—	A sluggish response to light glabellar tap or loud auditory stimulus
6		—	No response to a light glabellar tap or loud auditory stimulus
^aNoxious stimuli = suctioning or 5 seconds of vigorous orbital, sterna, or nail bed pressure Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med. 1999;27:1325-1329; Devlin JW, Boleski G, Mlynarek M, et al. Motor activity assessment scale: A valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. Crit Care Med. 1999;27:1271-1275; Ramsay MA, Savege TM, Simpson BR, et al. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974;2:656-659.