Analgesia, Sedation, and Neuromuscular Blockade

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5 Analgesia, Sedation, and Neuromuscular Blockade

Pearls

Analgesia entails assessment and treatment of pain; sedation entails assessment and treatment of agitation; neuromuscular blockade entails pharmacologic inhibition of voluntary muscle movement.

Analgesia often improves agitation, but does not necessarily provide sedation; sedation often improves pain, but does not necessarily provide analgesia; neuromuscular blockade provides neither analgesia nor sedation, and should never be induced without first ensuring adequate levels of both analgesia and sedation.

Most critically ill children experience some degree of pain and agitation: optimal nursing care of critically ill children asks how best to provide appropriate analgesia and sedation, not whether analgesia or sedation should be provided.

Pain and agitation are usually dynamic processes. Nurses should perform appropriate assessments to monitor pain, agitation, and effectiveness of interventions; reassess patients regularly using consistent tools and modify interventions as needed.

Change in pharmacologic analgesia and sedation to different agents, or to different routes of administration, requires equipotent conversion to ensure ongoing efficacy and to prevent inadequate or excessive dosing.

All opioid analgesics and many systemic sedatives can induce physiologic tolerance, and should be weaned gradually after prolonged administration to prevent withdrawal. Appropriate use of these agents does not cause addiction, and they should not be avoided because of such concern.

Introduction

Pain and agitation are common in critically ill patients. As our understanding of these processes in critically ill children has evolved, we now recognize the vital importance of appropriate analgesia and sedation in such patients.48 In 1986, the World Health Organization first published its Analgesic Ladder for the management of cancer pain (Fig. 5-1). This paradigm and others like it are now widely accepted as guidelines for analgesia and sedation in all patients. Despite such advances, considerable progress remains to be made. Caregiver education should enhance awareness of the crucial need for appropriate analgesia and sedation in critically ill children. Practice patterns must continue to change to include appropriate analgesia and sedation as essential components of pediatric critical care. Ongoing research must continue to explore the nature of these complex processes and their optimal management.

In the past, many caregivers mistakenly assumed the immature pediatric nervous system rendered children incapable of experiencing pain or agitation, or caregivers mistakenly believed that children could not safely tolerate analgesics or sedatives. Particularly in pediatric patients, caregivers often interpreted lack of request for analgesia or sedation as indicating lack of pain or agitation, so pediatric patients often received inadequate analgesia. We now know that children of all ages can feel pain and experience pain without expressing the need for analgesia and they can safely receive a wide variety of analgesic interventions. We also know that agitation is common in pediatric patients, and children often receive inadequate sedation.

Assessment of pain and agitation is especially challenging when patients are unable to articulate their experiences and feelings, and analgesia and sedation may be particularly inadequate in these patients. Critically ill children are at risk for significant pain and agitation, and pediatric critical care providers must be vigilant in providing appropriate analgesia and sedation.

Appropriate analgesia and sedation have been shown to attenuate the stress response associated with critical illness, hastening recovery while lessening incidence and severity of complications. Nurses should assess each patient individually, and interventions including pharmacologic agents should be tailored to the patient and the setting. Nurses should regularly assess patient status, including response to interventions, and modify interventions as appropriate.

All pharmacologic agents used to provide analgesia, sedation, and neuromuscular blockade have potential side effects and complications, particularly a risk of respiratory depression and cardiovascular compromise. Risk may be higher in pediatric patients, especially when they are developmentally immature or medically fragile.54 Ongoing patient monitoring is essential.

Anatomy, physiology, and embryology of pain

Pain is a complex phenomenon, representing the interaction of many anatomic pathways, physiologic processes, and psychosocial factors. Pain has thus proven remarkably difficult to define, particularly in children. A widely accepted definition of pain is that suggested by the International Association for the Study of Pain: an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. This definition underscores the degree to which pain is a highly personal and subjective experience.

Clinical care of patients in pain is complicated by lack of objective indicators: no vital sign, radiologic study, or laboratory value can reliably quantify or even indicate pain. Except perhaps in the setting of malingering or drug-seeking, rare in pediatric practice, the best clinical approach is usually to accept the patient’s description or indication of pain as truthful and accurate, and to provide analgesia as appropriate.

Nociception

Nociception is the normal process through which pain is experienced (Fig. 5-2). Nerve pathways underlying pain sensation in humans are fully developed at term (see Anatomy, Physiology and Embryology of Pain in the Chapter 5 Supplement on the Evolve Website). Most pain in critically ill children is nociceptive in nature and tends to respond to conventional antinociceptive analgesics.

Nociception appears to involve four steps: transduction, transmission, perception, and modulation. Transduction refers to the initiation of pain sensation through activation of sensory nerve endings, or nociceptors. Stimulation above the nociceptor activation threshold causes depolarization of the nerve cell membrane, with subsequent propagation of a nerve impulse, or action potential, along the sensory nerve fiber. Nerve cell depolarization, propagation of the action potential, and subsequent repolarization all result from transmembrane flow of ions through channels in the nerve cell membrane.

Transmission refers to the propagation of a nerve impulse, or action potential, along sensory nerve fibers of the peripheral nervous system to the dorsal horn of the spinal cord, and from there to other locations in the central nervous system. Peripheral transmission relies primarily on two types of sensory nerve fibers, A-delta (δ) and c-fibers. A-delta fibers are larger, high-threshold, myelinated fast fibers that transmit fairly localized, acute, sharp pain. The c-fibers are smaller generalized-stimulus unmyelinated slow fibers that transmit less well-localized dull or aching pain. The c-fibers can remain stimulated, even after cessation of painful stimuli, and can play an important role in chronic pain.

Nociceptive sensory nerve fibers terminate in the dorsal horn of the spinal cord, where they synapse with dorsal horn nerve cells. The pain impulse is then carried toward the brain primarily via the spinothalamic tracts. These tracts receive input from sensory nerve fibers in laminae of the dorsal horn of the spinal cord, cross to contralateral spinal cord laminae, and ascend to the thalamus and other higher centers. Further transmission then occurs from the thalamus to the cerebral cortex with extensive cross-connections throughout the central nervous system.

Perception refers to the complex and poorly understood process by which pain becomes a conscious experience. Perception includes the physical sensation of noxious stimuli and the entire conscious experience of such stimuli with attendant emotional and behavioral components.22 Perception is a unique process in each patient and is affected by age, developmental maturity, and underlying medical condition. Perception is also a highly dynamic process, varying among patients and in the same patient at different times.

Modulation refers to modification of pain by other nervous system input. Modulation can ameliorate or exacerbate pain and may explain some of the tremendous variability in subjective pain experience, especially in children. Modulation is a highly complex process and can take place at any point in transduction, transmission, and perception. A particularly important modulatory pathway is the descending pain system, with nerve axons projecting from the brainstem and other supraspinal centers to various laminae of the spinal cord. These descending fibers inhibit transmission of painful sensory stimuli, enhancing analgesia. Anxiety can also modulate pain, causing increased sensitivity to pain and resultant pain-related disability, particularly in chronic pain.40

Hypersensitization and Preemptive Analgesia

Acute pain warns of actual or potential tissue injury. Persistent or severe pain, however, can contribute to adverse processes. Inadequately treated surgical pain may impair breathing and compromise pulmonary toilet, promoting inadequate ventilation, atelectasis, and pneumonia. Pain also induces a neuroendocrine stress response, increasing sympathetic activity and releasing stress hormones and inflammatory mediators. The resultant hypermetabolic, catabolic state may be complicated by impaired immune function that can increase morbidity and mortality.

Tissue injury and inflammation potentiate nociceptor activity, leading to hypersensitivity to painful stimuli. Dorsal horn neurons respond to sustained afferent stimulation with neurophysiologic and morphologic changes consistent with increased excitability. Hypersensitization can alter normal sensory perception, accentuate pain caused by stimuli, and even produce pain in response to normally innocuous stimuli, suggesting that hypersensitization at the cellular level correlates with clinical hypersensitivity to pain.

Administration of preemptive analgesia before tissue injury can inhibit nociception, blunting neuroendocrine stress response and preventing development of peripheral and central hypersensitization. General anesthesia alone is not sufficient for such purposes; nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and a variety of regional anesthetic techniques have been used with variable results. Although animal models suggest that preemptive analgesia decreases overall pain severity and duration, clinical human studies have yielded conflicting and frequently negative results, particularly in children. As a result, preemptive analgesia as a strategy for blunting hypersensitization and reducing pain remains a subject of ongoing investigation. Timing of analgesia appears less important than its administration.

Classification of Pain

Pain is often classified temporally as acute or chronic, anatomically as somatic or visceral, and pathophysiologically as nociceptive or neuropathic (Table 5-1). Such classifications are not mutually exclusive; clinical presentations may suggest considerable overlap, and clear distinctions are not always possible.

Table 5-1 Classifications of Pain

Temporal Classification*
Acute Pain Chronic Pain
Expected duration, often hours to days Prolonged duration, often weeks to months
Somatic or visceral Somatic or visceral
More commonly nociceptive Nociceptive or neuropathic
Anatomic Classification
Somatic Pain Visceral Pain
Originates in somatic innervation of periphery Originates in autonomic innervation of viscera
Acute or chronic Acute or chronic
Nociceptive or neuropathic Nociceptive or neuropathic
Pathophysiologic Classification
Nociceptive Pain Neuropathic Pain
Result of normal nervous system function Associated with nervous system dysfunction
Acute or chronic More commonly chronic
Somatic or visceral More commonly somatic
Typically responds to conventional analgesics Responds poorly to conventional analgesics

* Classifications are not mutually exclusive: clinical presentations frequently suggest considerable overlap, and clear distinctions are not always possible.

Neuropathic Pain

Neuropathic pain is thought to arise from nervous system dysfunction, although underlying pathophysiologic mechanisms are incompletely understood. Hypersensitivity of sensory nerve fibers causing repetitive depolarization has been proposed, as has wind-up hyperexcitability of dorsal horn neurons secondary to prolonged noxious stimuli. Subjective reporting of neuropathic pain is frequently disproportionate to observed physical findings and to objective assessment of patient comfort. Neuropathic pain can be described as a more intermittent shock-like, shooting, radiating, or stabbing pain, or a more constant burning, prickling, tingling, or aching pain. These descriptors often overlap.

Neuropathic pain often responds poorly to conventional antinociceptive analgesics, but may respond favorably to other medications, particularly some anticonvulsants and some antidepressants. Aggressive physical rehabilitation services and ongoing mental healthcare are often helpful, particularly for chronic neuropathic pain.

Phantom or deafferentation pain is a variant of neuropathic pain associated with central nervous system dysfunction following disruption of peripheral sensory input. Phantom pain can occur long after denervation of affected areas and may persist chronically or even permanently. Phantom pain may be seen following traumatic or surgical amputation and has even been described after dental extraction.46 The pathophysiology of phantom pain is complex and incompletely understood.

Complex regional pain syndrome (CRPS) is a variant of neuropathic pain associated with autonomic dysfunction. Signs can include changes in skin color or appearance, alterations in hair distribution or texture, and eventually musculocutaneous atrophy. CRPS pain may be associated with prior nerve injury (CRPS type 2, formerly referred to as causalgia) or may be idiopathic (CRPS type 1, formerly referred to as reflex sympathetic dystrophy). The pathophysiology of CRPS is complex and poorly understood, and a significant psychosocial component is often present.

Patient assessment

Recognition and treatment of pain and agitation can be particularly challenging in the absence of reliable objective quantitative assessments on which to base clinical decisions. Patient descriptions can guide analgesic and sedative interventions. However, even verbal children may find it difficult to express this information, particularly in the setting of critical illness. Children may be nonverbal or otherwise incommunicative secondary to age, developmental immaturity, medical illness, surgical procedures, or interventions such as intubation. Caregivers must recognize patient behaviors or behavioral patterns that provide clues to the presence, location, severity, and even cause of pain and agitation, and must monitor changes to guide therapy. No single objective assessment strategy will be sufficient or appropriate for every patient in every setting.31

Pain, particularly when acute, may produce evidence of increased sympathetic tone, the so-called fight-or-flight response. This response includes pupil dilation, tachycardia, hypertension, alteration in respiratory pattern, hyperglycemia, and change in emotional state. These indicators, however, are not sensitive in discriminating pain from other sources of distress, and do not reliably quantify or even indicate pain. Limited evidence supports the use of vital signs as indicators of pain, but only in the context of acute onset or acute increase in pain. Significant pain may be present without physiologic evidence of distress.

A common cause of inadequate analgesia and sedation is failure of the caregiver to accept and act on the patient report of pain and agitation. Although the patient report must always be taken in context, it is the most reliable assessment of patient experience and should be considered the standard for patient assessment. Caregivers must respect any patient report of pain and agitation, performing timely assessment and providing appropriate treatment.

In the absence of a patient report, caregivers must perform regular and appropriate objective assessments. Caregiver reliance on subjective impression, gut feeling, or personal belief introduces significant potential for variation and bias among caregivers, often leading to inconsistent or inadequate analgesia and sedation.

Patient or family fears and beliefs can hinder adequate analgesia and sedation. Patients or families may not wish to bother busy nursing staff. Children may deny distress, fearing painful injections or unpalatable oral preparations. Patients or families may hope to facilitate early discharge by minimizing reports of pain or agitation, or by limiting requests for analgesia and sedation. Distress may be regarded as a sign of weakness or failure. Fear of side effects, in particular addiction, leads many patients and families to avoid even appropriate analgesia and sedation. Nurses should address these concerns directly and provide education as necessary.

Caregiver fears and beliefs may also hinder adequate analgesia and sedation. Caregivers may fear providing unnecessary analgesia or sedation, particularly controlled substances. They may misinterpret regulations and legal requirements associated with these medications, or may fear promoting patient addiction. In terminal or palliative care settings, caregivers may fear hastening or even causing death. These issues must be addressed within the healthcare team (see Chapter 3).

Nurses should seek accurate and thorough information from the patient, family, and other caregivers to clarify onset, nature, severity, and time course of pain and agitation, as well as response to interventions. This history is particularly important when patients receive significant pharmacologic analgesia or sedation that can produce tolerance. What has helped? What has been ineffective or made things worse? Do interventions provide complete or only partial relief? How long does relief persist? Incomplete relief can suggest a need for additional interventions or increased medication dose, whereas complete but transient relief may suggest a need for more frequent or longer-acting interventions. The psychosocial component of pain and agitation can be significant, and nurses should assess available social and emotional support systems.

Regulatory guidelines and legal mandates require that patient care regimens be reviewed and reconciled at admission, at transfer of location or level of care, and at discharge. This helps ensure accuracy and efficacy of interventions, and it is particularly important when critically ill children transition to care settings where previous interventions may be unavailable. Continuation of medications at equipotent doses without inadvertent omission or unnecessary addition helps maintain analgesia and sedation while minimizing the risk of inadequate or excessive dosing.

Pediatric Pain Behavior

Patient behaviors or behavioral patterns can provide powerful clues to the presence, location, severity, and even cause of pain and agitation. Changes in patient behaviors or behavioral patterns may help guide analgesic and sedative interventions. Pain and agitation can be difficult to recognize even in healthy children who are young or developmentally immature; recognition in critically ill children may be complicated by the child’s illness or interventions.

Agitation itself can indicate pain. Children in pain are often restless and cannot be easily distracted. They may cry or fuss, have a short attention span, or fail to respond to previously effective interventions. Facial expression can indicate pain; infants in particular may fail to make or hold eye contact. Children often hold or guard painful body parts rigidly. Pain can produce sleep disturbance, anxiety, nausea, anorexia, and lethargy. Pain—particularly when chronic—may precipitate profound changes in affect and emotional state. Formal psychiatric diagnoses such as anxiety disorder, acute or posttraumatic stress disorder, and major depression are frequently associated with chronic pain. Critical illness itself can produce many of these same behaviors.

Pediatric pain behaviors may be affected by psychosocial stressors and other factors, varying considerably among children or in the same child over time. Children in pain may be frightened or may exhibit developmental regression. Some children may seek attention through dramatic or disruptive behavior; others may be conditioned by gender or parental admonishment to be stoic. Children may fear upsetting or disappointing family and caregivers by admitting distress, or may feel they are being punished. Parents and other caregivers can be valuable interpreters of pediatric behavior.

Sedation or sleep can be mistaken for comfort. Patients of all ages may sleep despite severe pain, particularly if the pain is chronic. Pain itself can induce a state of decreased interaction that inaccurately suggests adequate analgesia. Critical illness and its treatment often exact a tremendous physiologic and emotional toll on patients. The resultant fatigue can produce decreased responsiveness to stimuli including pain. The nurse must consider overall patient status, combining data from assessment tools and other behavioral evaluation as appropriate.

Assessment Tools

Assessment tools typically are scales that can help to quantify pain and agitation in many clinical settings. However, the numeric scores generated must not be taken in isolation; they represent one component of comprehensive patient evaluation, just as vital signs represent one component of physical assessment. Any score must be considered in overall clinical context.

Assessment tools generally rely on subjective patient report, or on objective caregiver evaluation of patients who are unable to provide subjective report. Many assessment tools of both types have been developed for and validated in children. Scores generated using one tool will not necessarily correlate directly with those obtained using another. Caregivers should select an assessment tool appropriate for the patient and use it consistently over time.

Subjective Patient Report

Assessment tools relying on a subjective patient report ask the patient to indicate status on a continuum. Pain scales commonly range from 0 (no pain) to 10 (maximum possible pain); sedation scales vary more widely. Verbal children who are able to count may simply be asked to indicate their pain score on a 0-10 scale. Interactive but nonverbal children, or children unable to count, may be asked to indicate their pain score on a continuum scale using colors, pictures of children, or drawings of faces that represent degrees of distress. Three such pain assessment tools commonly used in pediatric practice are the Oucher! (see Evolve Fig. 5-1 in the Chapter 5 Supplement on the Evolve Website), the McGrath Faces Pain Scale, and the Hicks Faces Pain Scale-Revised (Fig. 5-3). See Patient Assessment in the Chapter 5 Supplement on the Evolve Website.

Tools are also available to help children quantify their pain experience through activities such as counting poker chips (the Hester Poker Chip Scale) or coloring an outline drawing of a child (the Eland Color Tool). Use of such activity tools requires patient interaction and caregiver time that may be impractical in the critical care setting.

Management Planning

With appropriate intervention, most critically ill children should experience little pain and minimal distress. Following comprehensive patient assessment, an appropriate management plan is developed to address patient pain and agitation.48 The goals of any management plan should be to maximize analgesia and sedation, minimize side effects and complications, and if possible aid in diagnosis and treatment of underlying critical illness. Ideally, all caregivers should be involved in development of this plan and should be aware of planned interventions. During and after interventions, caregivers must perform regular and periodic patient reassessment to evaluate patient response and guide further interventions. Management must be individualized for each patient, combining nonpharmacologic and pharmacologic interventions as appropriate.

Nonpharmacologic interventions

Nonpharmacologic interventions are important adjuncts in pediatric analgesia and sedation. Because pain and agitation include significant cognitive and affective components, the child often responds to cognitive interventions that invoke the child’s imagination, suggestibility, and sense of play. Behavioral interventions help the child focus on relaxation and deep breathing rather than on the pain or painful stimulus. Biophysical modalities may affect nociceptive transmission and have a significant psychological component. Noninvasive and generally inexpensive, nonpharmacologic interventions can provide patients and families a sense of personal involvement in their care.

Family involvement in nonpharmacologic interventions often increases their effectiveness. Although the child may appear more distressed when family members are present, this may indicate that the child is more willing to express pain, fear and agitation in their presence. Children should receive positive reinforcement for engagement in nonpharmacologic interventions, but should never be punished or ridiculed for being frightened or uncooperative. Child Life specialists and other trained professionals, if available, provide valuable support.

Analgesia and sedation are generally optimized when appropriate treatment modalities are combined. For mild to moderate pain and agitation, nonpharmacologic interventions alone may suffice. For moderate to severe pain, nonpharmacologic interventions should complement, but not necessarily replace, pharmacologic therapy. Comprehensive care of critically ill children uses suitable nonpharmacologic techniques in combination with appropriate medications to optimize analgesia and sedation, minimize side effects, and facilitate recovery.

Cognitive and Behavioral Modalities

Cognitive and behavioral modalities are likely to enhance analgesia and sedation by influencing perception and modulation of pain at the supraspinal level. They also address cognitive and affective causes of anxiety. Cognitive modalities include distraction, relaxation and guided imagery, music therapy and hypnosis. Behavioral modalities include deep breathing and relaxation techniques. Cognitive and behavioral interventions are used most successfully in combination with other nonpharmacologic techniques and in conjunction with appropriate medications.

Music Therapy

Music therapy can provide both distraction and relaxation in children. It has been used effectively in the operating room, postanesthesia care unit, neonatal critical care unit,4,32 and oncology ward. Music choice should be based on patient age, culture, and preference, guided as necessary by parents, other family members, and friends. Listening to music through headphones offers the added benefit of masking chaotic auditory stimuli.

Biophysical Modalities

Biophysical modalities are thought to affect nociceptive transmission at or below the level of the spinal cord, although precise mechanisms of action are incompletely understood. These modalities may also have a significant psychological component. Many modalities may be more effective when combined. Use of biophysical modalities is limited by time and logistical constraints, and some require specific training or equipment.

Systemic analgesics

Numerous systemic analgesics are available for use in children (Table 5-3). Systemic analgesics can have a wide range of physiologic effects, particularly in critically ill children. Knowledge of the agents being administered is essential for optimal efficacy and patient safety. Nurses must be aware of expected clinical effect, usual time of onset, likely duration, and potential side effects of each agent administered. Medications ordered on an as-needed basis are effective only when given appropriately with ongoing and recurring patient assessment. Frequent requirement for a drug ordered only on an as needed basis should prompt consideration of scheduled administration and additional interventions. Intramuscular injection is painful and absorption variable; it should be avoided except perhaps in the setting of difficult intravenous access. Although many systemic analgesics can produce sedation, they should not be used primarily for this purpose.

Table 5-3 Systemic Analgesics

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Drug Dose Comments
Acetaminophen
Acetaminophen and NSAIDs are generally synergistic and may be given together without need to alternate or stagger doses.
Acetaminophen Load: 20 mg/kg PO (maximum 1000 mg), then Good antipyretic; hepatic toxicity with overdose
Main: 15 mg/kg PO (maximum 1000 mg) q4-6 h Loading dose especially useful for procedural or perioperative analgesia
Load: 40 mg/kg PR (maximum 1300 mg), then FDA now advises maximum single adult dose of 650 mg for over-the-counter use
Main: 20 mg/kg PR (maximum 1300 mg) q4-6 h
Maximum 4 g/24 h PO/PR
Nonsteroidal Antiinflammatory Drugs (NSAIDs)
Acetaminophen and NSAIDs are generally synergistic, and may be given together without the need to alternate or stagger doses.
Choline magnesium trisalicylate 10 mg/kg PO/PR (maximum 1500 mg) q6-8 h Only NSAID without platelet dysfunction