Pain, Agitation/Sedation, Delirium, Immobility, Sleep Flashcards by Alexa Carnahan

Pain

unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

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Agitation

condition characterized by apprehension, increased motor activity, and autonomic arousal; may also be manifested by fearful withdrawal
agitation - state of anxiety accompanied by motor restlessness

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Delirium

syndrome characterized by acute cerebral dysfunction with a change or fluctuation in baseline mental status, inattention, and either disorganized thinking or altered level of consciousness

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Delirium cardinal features

disturbed level of consciousness (decreased clarity of awareness of environment) with a reduced ability to focus, sustain, or shift attention
either a change in cognition (memory/disorientation/language) or development of a perceptual disturbance (hallucinations/delusions)

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Pain and analgesia

pain is poorly treated in hospitalized pts
most (>/=50%) ICU pts experience pain: report as a significant source of stress, many unable to self report pain, may be procedural (intubation, surgery, changing wounds) and at rest
associated with physiologic + psychological consequences: agitation, chronic pain (potentially debilitating), health-related QOL

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Pain related stress response

increases sympathetic nervous system activation, raises catcholamine levels
vasoconstriction, impaired tissue perfusion
catabolism/hypermetabolism
impaired wound healing/increased wound infection
immunosuppression
can alter breathing patterns and mechanics, can contribute to hypermetabolic response to trauma

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Pain assessment

needs to be routinely monitored in ICU (not all pts will be able to speak/assess pain)
gold standard - avoid stigma

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If unable to self report pain assessment

behavioral pain scale
critical care pain observation tool
proxy report

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Behavioral pain scale (BPS)

facial expression, upper limb movements, compliance with mechanical ventilation

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Critical care pain observation tool (CPOT)

facial expression, body movements, muscle tension, compliance with mechanical ventilation OR vocalization

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Analgesia

preemptive analgesia should generally be used in advance of painful procedures
in general, IV opioids preferred for non-neuropathic pain in critically ill pts: all available IV opioids are equally effective when titrated to similar endpoints; opioids may have sedative effects

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Non-opoiod analgesics may be used to

decrease opioid requirements (multi-modal approach)
acetaminophen, neuropathic pain meds (gabapentin, pregabalin, carbamazepine), potentially NSAIDs (routine use not recommended, may be used for procedural analgesia, drawback is bleeding risk), ketamine (post surgery)

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Opioid pharmacology

fentanyl and morphine are most common
also have hydromorphone, methadone, and remifentanil
respiratory depression is dependent factor on how aggressive tx is
can administer as bolus dosing or continuous infusion

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Agitation/sedation

agitation = state of anxiety accompanied by motor restlessness
frequent in critically ill pts, associated with adverse clinical outcomes: ventilatory dysynchrony, inappropriate verbal behavior, physical aggression, increased motor activity, increases in oxygen consumption, inadvertent removal of devices and indwelling lines and catheters

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Agitation/sedation may lead to

harm of pts and/orcaregivers
up to 70% of ICU pts, 40% may exhibit severe or dangerous agitation

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Agitation/sedation underlying causes

pain (one of the big causes), mechanical ventilation, delirium, hypoxia, hypotension, withdrawal (ETOH, drugs)

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Treatment of agitation

nonpharmacologic efforts: maintenance of pt comfort, provision of adequate analgesia, frequent reorientation, optimization of environment to maintain normal sleep pattern (to decrease other consequences), many pts requiring mechanical ventilation will require some pharmacological sedation
pharmacologic treatment to supplement our non-pharmacologic efforts

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Sedation

act of calming, especially by the administration of a sedative drug; mainstain for treatment of agitation/anxiety in ICU

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Hypnosis

state of minimal motor activity that is physically similar to sleep; state of altered consciousness, artifically induced

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Anxiolysis

reduction of emotional and physical responses to real/perceived danger

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Indications for sedatives poorly defined

adjuncts for anxiety and agitation
nonpharmacologic efforts to reduce anxiety may be supplemented with sedatives
many pts requiring mechanical ventilation will require some pharmacological sedation

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Sedatives may reduce

the stress of mechanical ventilation, relieve anxiety, and prevent agitation-related harm
pharmacologic sedation should be started after providing adequate analgesia and treating reversible physiological causes
should NOT be used as a method of restraint, coercion, discipline, convenience, or retaliation

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Over sedation is problematic

leads to increase time on mechanical ventilation, increase ICU and hospital length of stay, obscure neurological function testing, and neurotrauma/neurologic disorders

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Goal of treating agitation-sedation

adequate sedation, but not over sedatino
LESS is BEST –> light sedation
calm arousable pt, able to purposefully follow simple commands; potential benefits: decrease duration of mechanical ventilation, decrease ICU length of stay, possible decrease in mortality
efforts to achieve light sedation should be employed - daily sedation interruption (spontaneous awakening trial), nursing-protocolized targeted sedation

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Assessment of sedation - subjective

assessment facilitates titration of sedatives to pre-determined endpoints
subjective assessment is difficult in pts with altered level of mentation or inability to outwardly express anxiety; scales used - richmond-agitation-sedation scale (RASS) and sedation-agitation scale (SAS); both used to assess agitation and titrate the sedation

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Assessment of sedation - objective

objective assessment: tools/algorithms using quantifiable parameters; ex. bispectral index, autidory evoked potentials

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Bisprectral index (BIS)

EEG assessment
digital scale from 100 (completely awake) to 0 (isoelectric EEG)
guidelines suggest using in pts in whom other measures are not feasible (ex. deep sedation, neuromuscular blockade)
do NOT recommend BIS monitoring in all sedation ICU pts
recommend EEG monitoring for non-convulsive seizure activity in ICU pts with known/suspected seizures or to titrate meds to achieve burst suppression

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Properties of the ideal sedative agent

rapid onset and offset; minimal respiratory depression; lack of cardiovascular effects; inactive or absent metabolites; no drug interactions; consistent PK; no tolerance or withdrawal; analgesic sparing; inexpensive; does not contribute to delirium or long term impairments in cognition

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Sedative drugs used in the ICU

benzodiazepines: lorazepam, midazolam, diazepam
propofol
dexmedetomidine

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Benzodiazepines MOA

bind and activate a specific site on GABA receptor –> facilitate inhibitory action of GABA on neuronal impulse transmission –> hyperpolarizes cells, more resistant to excitation

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Benzodiazepines have ideal properties

anxiolysis; hypnosis; amnesia –> antegrade amnestic effects; anticonvulsant and muscle relaxant effects; elderly more sensitive; tolerance may be seen with chronic administration; drugs primarily used in ICU: lorazepam, midazolam

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Benzodiazepine AEs

respiratory depression (dose dependent; @ high doses)
cardiovascular effects (usually minimal, may include hypotension, tachycardia)
withdrawal possible, esp following large doses, prolonged duration, and abrupt discontinuation: may be severe, risk of seizures (more careful with underlying seizure disorder), gradual tapering of doses is required
delayed emergence from sedation: prolonged infusion –> saturation of peripheral tissues, advanced age, hepatic/renal insufficiency (midazolam)
may be associated with longer duration of mechanical ventilation compared to propofol or dexmedetomidine
potential association with delirium

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Benzodiazepines dosing

can be used as continuous or bolus dosing

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Lorazepam

IV, PO, IM (IV preferred for acute/severe agitation
least lipid soluble of the 2 commonly used BZDs - traverses blood brain barrier more slowly, delayed onset, prolonged duration of effect (less titratable)

Lorazepam

intermediate half-life (longer than midazolam and propofol): metabolized into inactive metabolite by glucuronidation –> no expected to accumulate in elderly; half-life may be prolonged by liver disease and end-stage renal failure; least prone to drug interactions; long half-life makes infusions less titratable
potential association with development of delirium

Lorazepam IV formulation

IV formulation contains propylene glycol (PG) solvent (in antifreeze) - potential lactic acidosis, nephrotoxicity after high doses or prolonged infusions; serum PG concentrations not widely available, monitor osmol gap qd or qod if high doses (used to detect potential PG toxicity)
osmol gap > 10 may indicated potential toxicity

Midazolam

IV only
much faster onset than lorazepam
at physiologic pH –> increase lipid solubility –> rapid onset

Midazolam hepatically metabolized by

CYP450 3A: half-life increased in elderly, hepatic disease, numerous drug interactions (due to a decrease in elimination)
short half-life otherwise: with prolonged use effects of midazolam may be prolonged/unpredictable; possibly due to metabolite accumulation; effect may be prolonged in renal disease due to metabolite accumulation

Midazolam is an option for

rapid sedation of acutley agitated pts (fast onset)
recommended for short-term used only (short half-life allows rapid titration, potentially shorter awakening times); not recommended for long term sedation because may be associated with unpredictable awakening time
may use for procedural sedation

Propofol MOA

alkylphenol sedative and hypnotic agent: binds sites on multiple receptors (GABA, glycine, nicotinic, M1 muscarinic) and interrupts neural transmission, facilitates global CNS depression

Propofol

rapid onset (easily penetrates BBB)
rapid offset (rapidly redistributes to tissues, and high hepatic clearance, highly titratable)
can be used as general anesthetic at higher doses, growing popularity for procedural sedation
no analgesic properties, provides some antegrade amnesia

Propofol pharmacokinetics

half-life is variable, possibly due to tissue saturation
hepatically metabolized (oxidation), no active metabolites
highly protein bound, large Vd
no PK changes reported with renal/hepatic dysfunction

Propofol frequently used in

neurosurgical pts (sedative of choice) - may reduced elevated intracranial pressure, rapid resolution of sedative effects following discontinuation of infusion

Propofol is an

emulsion in a phospholipid vehicle: need to account for its 1.1 kcal/mL in nutritional assessments
long term infusions may result in hypertriglyceridemia (check TGs following 48 h treatment)
requires dedicated IV catheter (incompatible with essentially everything)
emulsion contains egg lecithin and soybean oil (may still be used in pts with egg/soy allergies)
risk of infection –> do not hang >12h

Propofol AEs

apnea, hypotension, bradycardia, pain upon infusion, hypertriglyceridemia, elevation of pancreatic enzymes, seizures/neuroexcitory syndrome
withdrawal possible especially following large doses, prolonged duration, and abrupt discontinuation (gradual tapering of dose is required

Propofol infusion syndrome

acidosis, bradycardia, lipidemia
rare complication
common features include sustained treatment (>48h), high doses (>75 ug/kg/min), metabolic acidosis, rhabdomyolysis, hypotension, arrhythmias (tachycardia or bradycardia) leading to asystole and death
monitor for components of syndrome, including TGs, CK, LFTs, metabolic acidosis, bradycardia, hypotension

Propofol AEs - preservatives

preservative: diprivan product –> EDTA (chelating agent): manufacturer recommends drug holiday after >7 dyas treatment in order to avoid electrolyte abnormalities (esp Zn)
generics: sodium metabisulfate, benzyl alcohol and benzyl alocohol/sodium benzoate
preservation free: lusedra (fospropofol disodium), water soluble prodrug (NO longed USED)

Propofol may be preferred sedative when

rapid awakening is important and in neurotrauma (may aid in ICP managemnent)
TGs should be monitored after ?48h and at regular intervals therafter; account for total caloric intake from propofol; propofol infusion syndrome
recommended over BZDs for critically ill mechanically ventilated adults
widely used in procedural sedation

Dexmedetomidine MOA

selective alpha-2 agonist
within CNS, activation of presynaptic alpha-2 receptors inhibits noradrenaline release (sedative/hypnotic effects primarily mediated by action at locus ceruleus)
medullary dorsal motor nucleus of vagus has high density of alpha-2 receptors and may elicit bradycardic and hypotensive effects

Demedetomidine sedation is qualitatively different from that seen with other agents

sedation in undisturbed patients; patients readily arousable with gentle stimulation; anxiolysis similar to BZDs; analgesic-sparing effects; NO respiratory depression (can continue post-extubation); no anticonvulsant activity
should not be used when deep sedation is required
may be associated with less delirium than BZDs - possibly associated with lower incidence of delirium than propofol

Dexmedetomidine pharmacokinetics

rapidly distributes, highly protein bound
short half life
hepatically metabolized and eliminated in urine as glucuronide
some impairment of elimination in hepatic dysfunction
no PK changes in renal dysfunction, however may see prolonged duration of effect

Dexmedetomidine dosing

doses >0.7 seem to overcome need for supplementation
loading dose –> increases cardiovascular effects (hypotension)- should AVOID loading dose; instead administer over longer time or with lower loading dose
only approved for short term, however experience with up to 28 days

Dexmedetomidine AEs

CV effects: transient increase BP with rapid administration; bradycardia, hypotension most problematic - most common with loading dose, more likely in volume depleted pts or pts with increased sympathetic tone, may limit utility of dexmedetomidine in some ICU populations - hemodynamic instability/high sympathetic tone

Dexmedetomidine has an expanding role in ICU sedation

novel sedative effects and beneficial analgesic sparing effects
potentially lower incidence of delirium than other sedatives
recommended over BZDs for critically ill mechanically ventilated adults
may be limited by adverse CV effects

Delirium is a syndrome characterized by

acute onset of cerebral dysfunction with a change or fluctuation in baseline mental status, inattention, and either disorganized thinking or altered level of consciousness

Delirium cardinal features

disturbed level of consciousness: decreased clarity of awareness of environment with a reduced ability to focus, sustain, or shift attention AND either a change in cognition (memory/disorientation/language) or development of a perpetual disturbance (hallucinations/delusions)
other sx: sleep disturbances, abnormal psychomotor activity, emotional disturbances

2 subtypes of delirium

hyperactive (agitated) –> more often associated with hallucinations/delusions
hypoactive (calm/lethargic) –> more often associated with confusion/sedation
can see pts go between the 2

Delirium may be associated with

long term cognitive impairment; longer duration of delirium potentially associated with greater chance for prolonged and irreversible impairment
commonly observed in critically ill pts, substantial health problem
associated with length of ICU stay, overall length of stay, and potentially mortality

Delirium risks - modifiable

BZDs
blood transfusions

Delirium risks - nonmodifiable

older age, preexisting dementia, prior coma, pre-ICU emergency surgery or trauma, high severity of illness at admission

Other potential risks/triggers for delirium

history of hypertension, use of psychoactive drugs, environmental (prolonged physical restraint, immobility), sepsis, hypoglycemia, hyponatremia, other endocrine disorders, metastatic diseases of the brain, head injury, CNS infections

Assessment of delirium

regular assessment recommended:
ICDSC - high sensitivity, moderate specificity
CAM-ICU - high sensitivity and specificity for delirium and high inter-rater reliability

Nonpharmacologic treatment for delirium

multicomponent strategy recommended: iatrogenic/environmental causes; early mobilization - possible to decrease delirium, depth of sedation, ICU length of stay, hospital LOS, days on vent; optimization of sleep; optimization of hearing and vision; improving cognition

Pharmacologic treatment of delirium

NOT recommended for prevention; NOT recommended for routine treatment: in available RCTs, not associated with shorter duration of delirium, shorter duration of MV, shorter ICU LOS, or reduced mortality
antipsychotics may be used short term for treatment of delirium associated with significant stress (anxiety, fearfulness, hallucinations, agitation) - haloperidol, atypical antipsychotics (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone); dexmedetomidine - recommended for delirium where agitation is precluding weaning of vent/extubation

Haloperidol

butyrophenone antipsychotic/neuroleptic agent, antagonizes dopamine mediated neurotransmission
mild sedation w/o analgesia/amnesia
minimal changes in HR, BP, ventilation; long half-life
parenteral and PO
intermittent dosing if pt acutely agitated, once stabilized, administer regular doses; no evidence haloperidole reduces duration of delirium

Haloperidol AEs

prolongation of QT interval on ECG –> potential torsades de points!
d/c is QTc exceeds 450 msec or increases >25% from baseline
decreases seizure threshold
possible EPS (involuntary dyskinetic movements; contraindicated in parkinson’s disease)
neuroleptic malignant syndrom

Neuroleptic malignant syndrome

symptom-complex probably caused by dysautotonia related to dopamine antagonism
altered consciousness, tachycardia, diaphoresis, muscle rigidity, granulocytosis, anxiety, tachypnea, hyperthermia, increased CPK, hyperglycemia

Atypical antipsychotics

risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone
interest b/c of potential safety advantages over haloperidol (decreased risk of torsades)
similar MOA to haloperidol
risperidone, olanzapine, quetiapine appear to have efficacy similar to haloperidol

Atypical antipsychotics AEs

generally better tolerated than haloperidol
fewer EPS
ziprasidone causes highest rate of prolongation of QT interval! - all atypicals contraindicated in pts at risk for torsades de pointes
olanzapine associated with NMS in non-ICU pts; high olanzapine doses may cause hypotension

Atypical antipsychotics and delirium

not used for prevention of delirium in critically ill pts
not routinely used for tx of delirium in critically ill pts
may be used short term for tx of delirium associated with significant stress
concern: prolongation of QT interval/TDP - dose dependent, increased likely with IV haloperidol, monitor QTc

Dexmedetomidine recommended for delirium where

agitation is precluding weaning of vent/extubation

PAD guidelines

protocols = good: facilitate implementation of EBM/best practices, improve outcomes, guide for QI
should include guidelines for assessment AND treatment of PAD: best way to avoid over sedation
protocols frequently underutilized, improperly utilized

PAD guidelines - general

provide adequate analgesia and treat reversible physiological causes: active and preemptive analgesia, sleep promotion, mobility
sedation goal or endpoint should be established and regularly redefined
regular assessment and response to therapy should be systematically documented: validation sedation assessment scale - RASS and SAS

PAD guidelines - less is more

light sedation preferred vs. deep sedation
sedation only if required
sedation strategies that encourage deep sedation may lead to worse outcomes: increased mortality, prolongs mechanical ventilation, ICU LOS, long term neuropsychological dysfunction
goal: calm arousable pt, able to purposefully follow simple commands, close titration

Measures that encourage light sedation, patient assessment, and clost titration of sedation may be beneficial

daily interruption of sedative infusions with retitration: decrease duration of MV and LOICUS, may not be feasible in all pts, may be combined with vent weaning protocol
nursing protocolized targeted sedation

Sedation algorithm

protocol bases “analgesia-first sedation” recommended: pain is often primary source of agitation (treat pain, can prevent agitation); may be associated with more vent-free days, shorter ICU LOS; must balance with potential AEs of opioids; many pts will require supplementation with traditional sedatives; not a universal recommendation

Sedation algorithm - preference of meds

dexmedotodime preferred vs BZDs
propofol preferred vs BZDs
sedative choice is pt specific, should be driven by - indications/sedation goals, drug pharmacology, overall costs
BZDs may be associated with adverse clinical outcomes: prolonged dependence on MV, increased ICU LOS, and delirium

Sedation algorithm - benzodiazepines

BZDs still may play role in - treating anxiety, seizures, and withdrawal
midazolam may be used for very rapid sedation, procedural sedation
lorazepam has traditionally been used for prolonged sedation of many pts (has gradual onset): IV –> PG solvent, monitor osmol gap
midazolam is recommended for short term use only

Sedation algorithm - propofol

may be preferred sedative when rapid awakening is desired, in neurotrauma (preferred over dexmed b/c of hemodynamic effects)
preferred over BZDs in cardiac surgery

Sedation algorithm - dexmedetomidine

may be associated with less delirium and decreased duration of mechanical ventilation
drug of choice in pt with delirium and agitation

Prolonged and/or high dose BZD or propofol therapy (>5-7 days)

risk of withdrawal –> doses should be tapered gradually

PAD guidelines - delirium

regularly assess pts
nonpharmacologic measures
pharmacologic measures should NOT be used for prevention

PAD guidelines - delirium and pharmacologic measures

pharmacologic measures should NOT be routinely used for treatment
antipsychotics may be used SHORT term for treatment of delirium associated with signigicant stress (anxiety, fearfulness, hallucinations, agitation) - haloperidol, atypical antipsychotics (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone)
dexmedetomidine recommended for delirium where agitation is precluding weaning of vent/extubation

PAD guidelines - supportive care

nonpharmacologic measures to decrease agitation, improve pt comfort
prevention of sedation related complications

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Pain, Agitation/Sedation, Delirium, Immobility, Sleep Flashcards

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