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Pain Management 

Pain Management
Chapter:
Pain Management
Author(s):

Eelco F. M. Wijdicks

and Sarah L. Clark

DOI:
10.1093/med/9780190684747.003.0004
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date: 19 May 2019

Many central (brain and spinal cord) and peripheral (nerve roots and peripheral nerve) neurologic disorders are demonstrably painful. Pain control is important, and pain has been arguably considered by the Joint Commission a vital sign next to blood pressure, heart rate, temperature, airway and breathing. Adequate pain control has a high priority, but pain control does not manage major other discomforts (4). Moreover, overprescribing with opioids may be common resulting in the American Medical Association to re-emphasize that pain is a symptom and not a vital sign.

The pharmacopeia of pain management in hospital setting is growing and changing, and several trends have been noted. Tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, and antiepileptic drugs found their way in pain treatment.

Grading Pain

Patients in the intensive care unit (ICU) who are communicative can be asked to rate the pain on a visual analog scale of 0 to 10 (0, no pain; 10, excruciating and unbearable pain). The numeric pain-rating scale using faces has been validated (Fig. 4.1) (1,2,3). In less responsive patients, pain is signaled by moaning, grimacing, and extreme restlessness, but these remain very subjective measures and could lead to overtreatment.

Figure 4.1 Numerical Pain Rating Scale

Figure 4.1 Numerical Pain Rating Scale

Tables 4.1 and 4.2 show commonly used nursing scales, and high scores are triggers to give pain medication. The Critical-Care Pain Observation Tool (CPOT) (Table 4.1) and the Behavioral Pain Scale (BPS) (Table 4.2) are validated and useful in most ICU patients, including those with acute brain and spine injury. The critical care pain observation tool identifies several domains: facial expression, movements, muscle tension, and how well the ventilator is tolerated. In non-intubated patients, sounds and moaning are graded. Inadequate pain control leads to disturbed sleep, fighting the ventilator, rapidly escalating anxiety and restlessness but also endocrine changes, delayed gastric emptying (and vomiting), as well as very obvious tachycardia, hypertension, and dyspnea. It is just as important to grade pain at rest or during turning. Wide pupils have been used as indirect markers of pain but are not very useful in neurologic patients.

Table 4.1 Critical-Care Pain Observation Tool (CPOT)

Indicator

Description

Score

Facial expression

No muscular tension observed

Relaxed, neutral

0

Presence of frowning, brow lowering, orbit tightening, and levator contraction

Tense

1

All of the above facial movements plus eyelid tightly closed

Grimacing

2

Body movements

No movement at all (may not mean absence of pain)

Absence of movements

0

Slow, cautious movements, touching or rubbing the pain site, seeking attention through movements

Protection

1

Pulling tube, attempting to sit up, moving limbs/thrashing, not following commands, striking at staff, trying to climb out of bed

Restlessness

2

Muscle tension

No resistance to passive movements

Relaxed

0

Resistance to passive movements

Tense, rigid

1

Strong resistance to passive movements, inability to complete them

Very tense or rigid

2

Ventilator Compliance

Alarms not activated

Tolerating ventilator or movement

0

OR

Alarms stop spontaneously

Coughing but tolerating ventilator

1

Asynchrony: blocking ventilation, alarms frequently activated

Fighting ventilator

2

Vocalization

Normal conversational tone or no sound

0

Sighing, moaning

1

Crying out, sobbing

2

Total, range

0–8

Table 4.2 Behavioral Pain Scale

Categories

0

1 Rare

2 Occasional

3 Frequent

4 Constant

FACE (Expression)

Relaxed, no particular expression or smile

Grimacing, frowning, or wrinkled forehead

Grimacing, tearing, frowning, or wrinkled forehead

ACTIVITY (Movement)

Lying quietly, normal position, no guarding

Uneasiness, splinting areas of the body, tenseness, or slow, cautious movement

Restlessness, excessive movement of arms or legs, withdrawal reflexes, rigidness, or stiffness

VITAL SIGN CHANGE*

0

1

2

Stable or no change in past 4 hours:

Change over past 4 hours greater than:

Change over past 4 hours greater than:

SpO2

Decreased SpO2 5

Decreased SpO2 10

RR

Increased RR 10

Increased RR 20

HR

Increased HR 20

Increased HR 25

SBP

Increased SBP 20

Increased SBP 30

* Vital Sign Change = change in 1 or more vital signs: SpO2 = pulse oximetry, RR = respiratory rate, HR = heart rate, SBP = systolic blood pressure

In 2013 the American College of Critical Care Medicine published a comprehensive update on pain and delirium management (5). Pain is underreported in the ICU and should be treated when indicated. Opioids are considered the main analgesic of choice in critically ill patients with non-neuropathic pain, and non-opioid drugs are recommended to reduce the dose of opioid drugs. Gabapentin or carbamazepine is considered a first-line choice for patients with neuropathic pain. So called “bundle strategies” (comprehensive order sets) are encouraged.

Types of Pain in the Neurosciences ICU

Conditions in the neurosciences ICU associated with headache are hemorrhagic stroke (often with a rapid decline in consciousness), cerebellar infarcts, meningitis, and cerebrospinal fluid hypotension headache (with upright position). Excruciating pain associated with a ruptured cerebral aneurysm has not subsided in patients who have been admitted to the neurosciences ICU, and often there is a severe lingering, holocephalic pain causing nausea and vomiting. Typically we see a curled-up, immobilized patient trying to find any relief.

The headache associated with a ruptured aneurysm starts as a split-second excruciating head pain moving quickly into the neck. A “thunderclap” headache refers to a split-second, extremely intense (“10 out of 10”), totally unexpected headache. The sudden onset can often be recognized by the patient if the examiner demonstrates a handclap or finger snap. The headache with an arteriovenous malformation is much less explosive and may have migrainous characteristics.

Pain is generated from meningeal vessels containing pain-sensing fibers as the result of an inflammatory response and subsequent meningeal irritation. Less severe pain is seen after a craniotomy, but it is still often severe enough to warrant strong analgesics. Because it associated with vomiting, oral medication is not always effective or appropriate. Pain is associated with increased intracranial pressure and often proven with resolution after reduction of pressure (e.g., ventriculostomy). Conversely, low-pressure headache (i.e., spontaneous intracranial hypovolemia syndrome) causes headache in a sitting position. In any event, a worsening headache may signal a new problem (Box 4.1) (6,7).

Another category is patients with an acute spinal cord injury or acute poly-radiculoneuropathy. Pain can be defined as allodynia (pain with a stimulus not usually causing pain) or hyperalgesia (exaggerated pain with a painful stimulus), but also pain can be absent in areas that should be normally painful (analgesia). Pain in acute polyneuropathy may appear in several forms, including hyperalgesia, sciatica, muscle pain and cramps, and joint stiffness. Patients may complain of tingling or burning, prickling, tightness, or shooting (lancinating) pain. Typical is the nocturnal aggravation of pain that keeps patients from rest and sleep. Neuropathic pain may be electric and shock-like (8,9,10,11,12,13). Pain associated with avulsion of nerves can cause excruciating deafferentation pain, and the best-known is avulsion of the brachial plexus, but this usually occurs much later. These types of pain can be continuous, often a burning or throbbing pain (assumed to be due to thalamic neuroplasticity), or shooting paroxysms (assumed to be due to dorsal horn hyperactivity).

Drugs for Pain

Acetaminophen should be the first agent used in pain management. Next are weak narcotic analgesics (e.g., codeine and tramadol), which could have less severe side effects than stronger opioid analgesics. They must be reserved for patients who cannot tolerate acetaminophen or who have mild to moderate pain. They must be used preferentially in patients with acute brain injury in whom sedation is unacceptable. If opioids are the only option, oral codeine is the agent of choice for relief of severe pain in acute central nervous system disorders. Intravenous (IV) medication is generally preferred in the critically ill patient because of varying degrees of gastrointestinal dysfunction in this population. There is evidence of serious underuse of analgesics when neurosciences ICUs are surveyed (14). Suggestions for pain treatment in subarachnoid hemorrhage are shown in Box 4.2, and pain treatment for post-neurosurgical patients is covered in Box 4.3.

Several drug options are available (15,16). First-choice headache drugs are acetaminophen, codeine, tramadol, and, recently, gabapentin (17). Intravenous acetaminophen is expensive but is currently explored as an option in craniotomy to reduce the need for opioids (18). Ketamine is emerging as a possible alternative to opioids in acute pain management (19).

Control of Specific Headaches

Posttraumatic Headache

Valproic Acid

  • 1,000–1,500 mg orally once daily

  • Best avoided in patients with unstable brain contusions

  • Do not use in pregnancy or in patients with liver disease

  • Major side effects include hyperammonemia, hepatitis, pancreatitis and thrombocytopenia

  • Assess baseline liver function test results and pancreatic enzymes if there is a strong suspicion of dysfunction

  • Multiple drug formulations are available; extended-release formulation is marketed for headache prevention

Propranolol

  • Nonselective beta-blocker

  • 80 mg orally daily in divided doses initially; titrate to maximum (tolerated) dose of 240 mg/day in divided doses

  • Major side effects: hypotension, bradycardia

  • Use caution in patients with airway disease due to risk of bronchospasm

  • Do not discontinue use abruptly, but taper off slowly

  • Extensive first-pass liver metabolism, higher drug exposure noted in liver dysfunction

Reversible Cerebral Vasoconstriction Syndrome

Nimodipine

  • Dihydropyridine calcium-channel blocker, with greater central-acting than peripheral-acting effects (on blood pressure)

  • 60 mg orally every 4 hours; reduce dose to 30 mg every 4 hours in patients with cirrhosis

  • Administer on an empty stomach 1 hour before or 2 hours after food

  • Large, solution-filled capsules; patients with dysphagia may have difficulty swallowing. Could puncture capsules and withdraw solution with a needle

  • Major side effect: hypotension

  • Avoid use with strong CYP3A4 inhibitors

Verapamil

  • Non-dihydropyridine calcium-channel blocker. Decreases calcium efflux into smooth muscle and reduces vasodilation and vasoconstriction of blood vessels

  • 360 mg orally daily, in three divided doses

  • Common side effects: constipation, hypotension, bradycardia, peripheral edema

Cerebrospinal Fluid Hypotension Syndrome

Dexamethasone

  • 4 mg orally once daily for 4 days

  • Long-acting corticosteroid with very few mineralocorticoid properties

  • Common side effects: gastrointestinal irritation, hyperglycemia, insomnia

Caffeine

  • Causes cerebral vasoconstriction; stimulates cerebrospinal fluid production by stimulating Na/K ATPase pumps

  • 300 mg orally as needed (every 4 hours)

  • 500 mg IV in 1 L saline infused over 1 hour

  • Major side effects: insomnia, agitation, restlessness

Acetaminophen PO

Pain Management

Pharmacologic Characteristics

  • Analgesic and antipyretic

  • Inhibits prostaglandin synthesis in the central nervous system

  • Effect in <1 hour orally

  • Effect in 5–10 min for IV (peak analgesic effect IV in 1 hour)

  • Effect lasts 4–6 hours (both IV and orally)

  • Half-life may be doubled with severe renal failure (glomerular filtration rate [GFR] <30 ml/min)

Dosing and Administration

  • 1,000 mg orally or enterally (maximal 4000 mg in 24 hours)

  • IV given as infusion over 15 minutes (not “pushed”)

  • IV only if no oral route (IV is no more effective than oral and is more costly)

  • IV use is contraindicated in hepatic disease

Monitoring

  • Pain response

  • Regular liver and kidney function tests

  • Stop use if liver function test results are abnormal

  • Increase administration interval with kidney failure (GFR ≤10–50 ml/min)

Side Effects

  • Hypotension (decrease of >15%) with IV administration

  • Nausea and vomiting with IV infusion

  • Caution with 6GPD deficiency (accumulation of toxic metabolite)

Codeine PO

Pain Management

Pharmacologic Characteristics

  • Mu-receptor agonist

  • Metabolized rapidly by CYP2D6 to morphine. If patient is a poor metabolizer, will not achieve adequate patient response; if patient is an ultra-rapid metabolizer, will potentially “overdose” on analgesia

  • Use with strong CYP2D6 inhibitors may prevent codeine conversion to morphine (decreased analgesia response)

  • Duration: 4–6 hours

  • Onset: 30–60 minutes

Dosing and Administration

  • 30–60 mg orally every 4 hours as needed

  • Maximum 360 mg/24 hours

Monitoring

  • Pain response

  • Degree of sedation

  • Respiratory rate

Side Effects

  • Nausea and vomiting

  • Constipation (i.e., reduced bowel sounds, abdominal distention)

  • Respiratory depression

Morphine IV

Pain Management

Dosing and Administration

  • 2–4 mg IV every 3–4 hours, over slow IV push (4–5 minutes)

  • Continuous infusion: 2–30 mg/hr (0.07–0.5 mg/kg per hour) Peak: 30 minutes for oral, 5–10 minutes for IV

  • Decrease doses in patients with renal dysfunction

  • duration 4 hours

Monitoring

  • Renal function tests

  • Pain control

  • Respiratory rate

  • Heart rate and blood pressure

Side Effects

  • Nausea and vomiting

  • Respiratory depression

  • Hypotension

  • Bronchospasm

  • Bradycardia

  • Constipation, ileus

  • Urinary retention

  • Seizures (rare)

Fentanyl IV

Pain Management

Pharmacologic Characteristics

  • 50–100 times more potent than morphine

  • Synthetic derivative of morphine

  • Short half-life with intermittent doses (2–4 hours)

  • Long half-life with infusion (9–16 hours)

  • Highly lipophilic, fast onset; may accumulate in adipose tissue, causing prolonged sedation when discontinued

Dosing and Administration

  • Slow IV push 25–35 mcg every 30 minutes (0.5 mcg/kg)

  • Continuous infusion: 0.7–10 mcg/kg per hour

  • Patient-controlled analgesia

    • <50 mcg/hr basal rate

    • 10–20 mcg demand dose

Monitoring

  • Respiratory rate

  • Heart rate and blood pressure

  • Pain response

Side Effects

  • Respiratory depression

  • Hypotension

  • Bronchospasm

  • Bradycardia

  • Impaired gastrointestinal motility, constipation, ileus

  • Seizures (rare)

  • Nausea and vomiting

  • Urinary retention

Oxycodone PO

Pain Management

Pharmacologic Characteristics

  • Semisynthetic derivative of morphine

  • Onset: 10–15 minutes

  • Peak effect: 0.5–1 hour

Dosing and Administration

  • Dosing: 5–15 mg orally every 4–6 hours

  • Decrease initial dose by 33–50% in patients with renal dysfunction

Monitoring

  • Pain response

  • Respiratory rate

  • Heart rate and blood pressure

Side Effects

  • Respiratory depression

  • Hypotension

  • Bronchospasm

  • Bradycardia

  • Impaired gastrointestinal motility, constipation, ileus

  • Seizures (rare)

  • Nausea and vomiting

  • Urinary retention

Tramadol PO

Pain Management

Pharmacologic Characteristics

  • Indirect binding of mu-opioid receptors and inhibition of norepinephrine and serotonin reuptake

  • Used as pain management when pain is severe enough to require daily opioids (“opioid-sparing” drug)

  • Effect within 1 hour, peak 2–3 hours

Dosing and Administration

  • 50–100 mg every 4 hours

  • Maximum 400 mg/day with normal renal function

  • Renally cleared, dose reduced in diminished renal function (maximum 200 mg/day when creatinine clearance [CrCl] <30 ml/min), extend interval to every 12 hours

  • Removed by hemodialysis

Monitoring

  • Respiratory rate

  • Liver function tests

  • Renal function tests

Side Effects

  • Potential for seizures

  • Respiratory depression

  • Constipation

  • Bradycardia in high doses

  • Sedation

  • Do not use within 14 days of monoamine oxidase inhibitors

Ketorolac IM

Pain Management

Pharmacologic Characteristics

  • Fast onset of analgesia: 30 minutes for injection (intramuscular [IM] or IV)

  • Less sedation than opioids

  • Nonselective nonsteroidal anti-inflammatory (NSAID; blocks both cyclooxygenase [COX]-1 and COX-2 enzymes), resulting in decreased prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

  • Useful in patients with postoperative pain

  • Half-life is doubled in patients with renal failure

Dosing and Administration

  • Single dose 30 mg IM, slowly and deeply into muscle tissue

  • IV administration over 15 seconds

  • Adjust dose for weight <50 kg and age >65 years (maximum 15 mg per dose, 60 mg/day); there is an increased risk of adverse events in these patients

Monitoring

  • Pain response

  • Laboratory or clinical signs of gastrointestinal bleeding

  • Renal function tests

Side Effects

  • Risk of renal injury; use is contraindicated in patients with advanced renal disease

  • Limited to 5 days of consecutive use due to risk of serious gastrointestinal adverse events (bleeding)

  • Renal dysfunction

Celecoxib PO

Pain Management

Pharmacologic Characteristics

  • Selective inhibitor of COX-2 non-opioid NSAID, resulting in decreased prostaglandin precursors; has analgesic, anti-inflammatory, and antipyretic properties

Dosing and Administration

  • Dose: 100–200 mg orally, twice a day

  • Reduce dose by 50% in patients with hepatic dysfunction

Monitoring

  • Pain response

  • Laboratory or clinical signs of gastrointestinal bleeding

  • Avoid in patients with severe renal disease

  • Avoid in patients with sulfa allergy

Side Effects

  • NSAIDs carry the risk of increased cardiovascular adverse events, including fatal myocardial infarction and stroke

  • Increased risk of gastrointestinal adverse events, including bleeding, ulceration, or perforation

Gabapentin PO

Pain Management

Pharmacologic Characteristics

  • Structurally related to GABA but does not bind to GABA-A or GABA-B receptors. Binds to voltage-gated Ca channels in the central nervous system (alpha-2-delta-1 subunit) to modulate release of excitatory neurotransmitters (effecting pain response).

  • Bioavailability is inversely related to dose administered (i.e., higher absorption with lower doses).

Dosing and Administration

  • Initial dosing: 100 mg three times daily maintenance 300–1,200 mg/day, rapid titration (with normal renal function) (17)

  • Postoperative pain: 300–1,200 mg the night prior to surgery, and 1–2 hours before surgery or immediately following surgery (17)

  • Neuralgic pain (up to 3,600 mg/day, in divided doses [i.e., 1,200 mg three times a day]), with normal renal function (17)

  • Renally cleared; reduce dose in patients with renal dysfunction

Monitoring

  • Space antacids and other cation medications (e.g., calcium, magnesium, iron) at least 2 hours before gabapentin administration

  • Level of alertness

  • Pain response

  • Renal function

Side Effects

  • Dizziness

  • Ataxia

Carbamazepine PO

Pain Management

Pharmacologic Characteristics

  • Anticholinergic, antineuralgic, muscle relaxant, and antidepressant properties

  • Chemically related to tricyclic antidepressants; decreased neural impulse transmission by blocking sodium impulse through membranes

Dosing and Administration

  • Oral: 50–100 mg twice daily

  • Maintenance 100–200 mg every 4–6 hours; maximum 1,200 mg/day (in divided doses)

  • Reduce dose in patients with renal dysfunction; give 75% of normal dose

  • Often combined with IV opioids

Monitoring

  • Complete blood count

  • Renal function tests

  • Liver function tests

  • Serum sodium

  • Dermatologic reactions

Side Effects

  • Dizziness

  • Drowsiness

  • Ataxia

  • Nausea and vomiting

  • Hyponatremia, Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

  • Agranulocytosis (rare) and anemia

  • Hepatotoxicity

  • Hypersensitivity reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrosis)

Ketamine IV

Pain Management

Pharmacologic Characteristics

  • NMDA receptor antagonist, blocks glutamine release by binding to opioid receptors

  • Adjunctive or opioid-sparing agent

  • Used with opioids to help manage tolerance, withdrawal, hyperalgesia, and neuropathic pain

Dosing and Administration

  • Bolus: 0.2–0.5 mg/kg

  • Infusion: 0.05–0.4 mg/kg per hour

Monitoring

  • Pain control

  • Level of sedation

  • Heart rate and blood pressure

Side Effects

  • Hypertension

  • Tachycardia

  • Theoretical increase in intracranial pressure

  • Emergence reactions after discontinuation

Patient-Controlled Analgesia

Commonly used in patients with longstanding, refractory pain, this treatment is a last resort and requires patient cooperation. Mistakes can be made in programming the pump, and oversedation seen at the end of a lockout period can cause respiratory depression. Monitoring of the patient involves specific attention in five areas: (1) at least 4 hours at stable dose, (2) patient’s pain level is rated 4 or less (on a traditional 1-to-10 scale), (3) oxygen saturations are greater than 90%, (4) respirations are more than 10 per minute, and (5) level of sedation is a Richmond Agitation Sedation Scale (RASS) score of 0/1 (Box 4.4).

Key Pointers

  1. 1. Pain has many distinguishing features, and they need to be recognized and treated.

  2. 2. Pain in alert patients may be underrated, and use of nursing pain scales may be helpful.

  3. 3. Acetaminophen and codeine are preferred drugs for mild to moderate pain.

  4. 4. Patient-controlled analgesia can be used in patients with refractory pain but is discouraged in the neurosciences ICU.

  5. 5. Ketamine can be used as an opioid-sparing agent (19).

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