Pain, Agitation/Sedation, Delirium, Immobility, Sleep

Question 1

Pain

Answer 1

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

Question 1

Agitation

Answer 1

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

Question 2

Delirium

Answer 2

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

Question 3

Delirium cardinal features

Answer 3

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)

Question 4

Pain and analgesia

Answer 4

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

Question 5

Pain related stress response

Answer 5

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

Question 6

Pain assessment

Answer 6

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

Question 7

If unable to self report pain assessment

Answer 7

behavioral pain scale
critical care pain observation tool
proxy report

Question 8

Behavioral pain scale (BPS)

Answer 8

facial expression, upper limb movements, compliance with mechanical ventilation

Question 9

Critical care pain observation tool (CPOT)

Answer 9

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

Question 10

Analgesia

Answer 10

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

Question 11

Non-opoiod analgesics may be used to

Answer 11

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)

Question 12

Opioid pharmacology

Answer 12

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

Question 13

Agitation/sedation

Answer 13

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

Question 14

Agitation/sedation may lead to

Answer 14

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

Question 15

Agitation/sedation underlying causes

Answer 15

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

Question 16

Treatment of agitation

Answer 16

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

Question 17

Sedation

Answer 17

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

Question 18

Hypnosis

Answer 18

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

Question 19

Anxiolysis

Answer 19

reduction of emotional and physical responses to real/perceived danger

Question 20

Indications for sedatives poorly defined

Answer 20

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

Question 21

Sedatives may reduce

Answer 21

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

Question 22

Over sedation is problematic

Answer 22

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

Question 23

Goal of treating agitation-sedation

Answer 23

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

Question 24

Assessment of sedation - subjective

Answer 24

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

Question 25

Assessment of sedation - objective

Answer 25

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

Question 26

Bisprectral index (BIS)

Answer 26

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

Question 27

Properties of the ideal sedative agent

Answer 27

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

Question 28

Sedative drugs used in the ICU

Answer 28

benzodiazepines: lorazepam, midazolam, diazepam propofol dexmedetomidine

Question 29

Benzodiazepines MOA

Answer 29

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

Question 30

Benzodiazepines have ideal properties

Answer 30

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

Question 31

Benzodiazepine AEs

Answer 31

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

Question 32

Benzodiazepines dosing

Answer 32

can be used as continuous or bolus dosing

Question 33

Lorazepam

Answer 33

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)

Question 34

Lorazepam

Answer 34

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

Question 35

Lorazepam IV formulation

Answer 35

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

Question 36

Midazolam

Answer 36

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

Question 37

Midazolam hepatically metabolized by

Answer 37

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

Question 38

Midazolam is an option for

Answer 38

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

Question 39

Propofol MOA

Answer 39

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

Question 40

Propofol

Answer 40

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

Question 41

Propofol pharmacokinetics

Answer 41

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

Question 42

Propofol frequently used in

Answer 42

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

Question 43

Propofol is an

Answer 43

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

Question 44

Propofol AEs

Answer 44

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

Question 45

Propofol infusion syndrome

Answer 45

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

Question 46

Propofol AEs - preservatives

Answer 46

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)

Question 47

Propofol may be preferred sedative when

Answer 47

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

Question 48

Dexmedetomidine MOA

Answer 48

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

Question 49

Demedetomidine sedation is qualitatively different from that seen with other agents

Answer 49

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

Question 50

Dexmedetomidine pharmacokinetics

Answer 50

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

Question 51

Dexmedetomidine dosing

Answer 51

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

Question 52

Dexmedetomidine AEs

Answer 52

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

Question 53

Dexmedetomidine has an expanding role in ICU sedation

Answer 53

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

Question 54

Delirium is a syndrome characterized by

Answer 54

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

Question 55

Delirium cardinal features

Answer 55

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

Question 56

2 subtypes of delirium

Answer 56

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

Question 57

Delirium may be associated with

Answer 57

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

Question 58

Delirium risks - modifiable

Answer 58

BZDs blood transfusions

Question 59

Delirium risks - nonmodifiable

Answer 59

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

Question 60

Other potential risks/triggers for delirium

Answer 60

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

Question 61

Assessment of delirium

Answer 61

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

Question 62

Nonpharmacologic treatment for delirium

Answer 62

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

Question 63

Pharmacologic treatment of delirium

Answer 63

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

Question 64

Haloperidol

Answer 64

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

Question 65

Haloperidol AEs

Answer 65

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

Question 66

Neuroleptic malignant syndrome

Answer 66

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

Question 67

Atypical antipsychotics

Answer 67

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

Question 68

Atypical antipsychotics AEs

Answer 68

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

Question 69

Atypical antipsychotics and delirium

Answer 69

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

Question 70

Dexmedetomidine recommended for delirium where

Answer 70

agitation is precluding weaning of vent/extubation

Question 71

PAD guidelines

Answer 71

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

Question 72

PAD guidelines - general

Answer 72

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

Question 73

PAD guidelines - less is more

Answer 73

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

Question 74

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

Answer 74

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

Question 75

Sedation algorithm

Answer 75

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

Question 76

Sedation algorithm - preference of meds

Answer 76

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

Question 77

Sedation algorithm - benzodiazepines

Answer 77

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

Question 78

Sedation algorithm - propofol

Answer 78

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

Question 79

Sedation algorithm - dexmedetomidine

Answer 79

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

Question 80

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

Answer 80

risk of withdrawal --> doses should be tapered gradually

Question 81

PAD guidelines - delirium

Answer 81

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

Question 82

PAD guidelines - delirium and pharmacologic measures

Answer 82

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

Question 83

PAD guidelines - supportive care

Answer 83

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