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864 > Acute Care II > Flashcards

Acute Care II Flashcards

1
Q

Sedative Drugs used in ICU

Properties of the ideal sedative agent:

  • ___ onset and offset
  • minimal ___ depression
  • lack of ___ effects
  • inactive or absent metabolites
  • no drug interactions
  • consistent PK
  • no tolerance or withdrawal
  • ___ sparing
  • inexpensive
  • does not contribute to ___ or long term impairments in cognition
A
  • rapid
  • respiratory
  • CV
  • analgesic
  • delirium
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2
Q

Sedative Drugs used in ICU

  • BZDs: ___ , ___ , ( ___ )
  • propofol
  • dexmedetomidine
A
  • lorazepam, midazolam, diazepam
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3
Q

Benzodiazepines

bind and activate a specific site on the ___ receptor
- facilitate ___ action on neuronal impulse transmission
- ___ cells, more resistant to excitation

A
  • GABA
  • inhibitory
  • hyperpolarizes
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4
Q

Benzodiazepines

  • anxiolysis
  • hypnosis
  • amnesia -> antegrade amnestic effects
  • anticonvulsant and muscle relaxant effects
  • ___ are more sensitive
  • ___ may be seen with chronic administration
  • drugs primarily used in ICU: ___ , ___
A
  • elderly
  • tolerance
  • lorazepam, midazolam
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5
Q

Benzodiazepines

adverse effects:
- ___ depression (dose dependent)
- cardiovascular effects (usually minimal, may include ___ ,
___ )
- ___ possible, especially following large doses, prolonged duration, and ___ d/c
* may be severe, risk of ___
- gradual ___ of doses is required

A
  • respiratory
  • hypotension, tachycardia
  • withdrawal, abrupt
  • seizures
  • tapering
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6
Q

Benzodiazepines

adverse effects:
- ___ emergence from sedation
* prolonged infusion -> __ of peripheral tissues
* advanced ___
* hepatic/renal insufficiency ( ___ )

  • may be associated with longer duration of mechanical ventilation compared
    to ___ or ___
  • potential association with ___
A
  • delayed
  • saturation
  • age
  • midazolam
  • propofol, dexmedetomidine
  • delirium
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7
Q

Lorazepam (Ativan)

IV, PO, IM ( ___ preferred for acute/severe agitation)
- ___ - ___mg/kg q 2-6h
- ___ - ___ mg/kg/h
- ___ lipid soluble of the 2 commonly used BZD’s
- traverses blood brain barrier more ___
- ___ onset, __ duration of effect

A
  • IV
  • 0.02-0.06
  • 0.01-0.1
  • least
  • slowly
  • delayed, prolonged
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8
Q

Lorazepam (Ativan®)

Intermediate t1/2 (10-20 h)
* metabolized into ___ metabolite by glucuronidation (not expected
to ___ in elderly)
* t1/2 may be prolonged by __ disease and end-stage ___ failure
* ___ prone to drug interactions
* long t1/2 makes infusions less ___
* potential association with development of ___

A
  • inactive, accumulate
  • liver, renal
  • least
  • titratable
  • delirium
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9
Q

Lorazepam (Ativan®)

IV formulation contains ___ (PG) solvent
* 2 and 4 mg/ml formulations -> 830 mg/ml PG
* 2 mg/h infusion x 24 h -> >10x WHO max daily intake
* potential ___ acidosis, ___ after high doses or prolonged infusions (e.g., > ___mg/day or __ mg/kg/day )
* serum PG concentrations not widely available
* monitor osmol gap qd or qod if high doses ( > 10 may indicate potential toxicity)

A
  • propylene glycol
  • lactic, nephrotoxicity, 50, 1
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10
Q

Historically had been the workhorse BDZ in many settings
- may use either ___ administration or ___ infusion for sedation of acutely ill patients
* Declining use due to potential association with ___ and trend
to ___ sedation goals
* not the best choice if ___ awakening is required, due to intermediate t1/2

A
  • intermittent, continuous
  • delirium, lighter
  • rapid
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11
Q

Midazolam (Versed)

___ only
* ___ - ___ mg/kg q 0.5-2h
* ___ - ___ mg/kg/h
* At physiologic pH: ___ lipid solubility and ___ onset

A
  • 0.02-0.08
  • 0.04-0.2
  • increased, rapid
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12
Q

Midazolam (Versed)

hepatically metabolized by CYP450 3A
- t1/2 increased in ___ , ___ and ___disease, numerous ___ interactions
- ___ t1/2 (~2 h)
- with ___ use effects of midazolam may be prolonged /
unpredictable
* possibly due to metabolite ___

A
  • elderly, hepatic, renal, drug
  • short
  • prolonged
  • accumulation
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13
Q

Midazolam (Versed)

  • Option for ___ sedation of acutely agitated patients ( ___ onset)
  • Recommended for ___ - term use only (short t1/2 allows rapid titration, potentially shorter awakening times)
  • May use for ___ sedation
  • Not recommended for ___ term sedation (>48-72 h) because may be associated with unpredictable awakening time
  • Declining use due to potential association with ___ and trend to ___ sedation goals
A
  • rapid, fast
  • short
  • procedural
  • long
  • delirium, lighter
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14
Q

Propofol (Diprivan)

alkylphenol ___ and __ agent
- binds sites on ___ receptors (GABA, glycine, nicotinic, M1 muscarinic)
- interrupts neural transmission, facilitates global CNS depression
- ___ onset (easily penetrates ___ )
- rapid ___ (rapidly redistributes to tissues, and high hepatic clearance)
- can be used as general anesthetic at higher doses
- growing popularity for ___ sedation
- no ___ properties
- provides some antegrade amnesia

A
  • sedative, hypnotic
  • multiple
  • rapid, BBB
  • offset
  • procedural
  • analgesic
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15
Q

Propofol (Diprivan)

pharmacokinetics
- t1/2 ___ (~1-7 h in controls), however longer in ICU patients after prolonged infusions (? up to 26-32 h)
- possibly due to tissue saturation
- hepatically metabolized (oxidation), no active metabolites
- highly ___ bound, large Vd (~60 L)
- no PK changes reported with renal or hepatic dysfunction

A
  • variable
  • protein
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16
Q

Propofol (Diprivan)

  • ___ onset (1-2 min) and ___ duration once discontinued
  • continuous IV infusion, dose ___ - ___ μg/kg/min

frequently used in ___ patients:
- may reduce elevated ___
- rapid resolution of ___ effects following discontinuation of infusion

A
  • rapid, short
  • 5-90
  • neurosurgical
  • ICP
  • sedative
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17
Q

Propofol (Diprivan)

emulsion in a phospholipid vehicle
- ___ kcal/ml: need to account for in nutritional assessments
- long term infusions may result in hyper ___ - check ___ following 48 h treatment, periodically thereafter
- requires dedicated IV catheter
- emulsion contains ___ lecithin and ___ oil
- may still be used in patients with egg/soy allergies
- ? risk of infection: do not hang >__ h

A
  • 1.1
  • hypertriglyceridemia, TG’s
  • egg, soybean
  • 12
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18
Q

Propofol (Diprivan)

adverse effects:
* apnea
* ___ tension, ___ cardia
* ___ upon infusion (30-90% of patients)
* hyper ___ (3-10% of patients)
* elevation of ___ enzymes (? causal relationship)
* seizures/neuroexcitory syndrome (controversial)

A
  • hypotension, bradycardia
  • pain
  • hypertriglyceridemia
  • pancreatic
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19
Q

Propofol (Diprivanadverse effects )

Propofol Infusion Syndrome
- ___ , ___ cardia, ___
- rare complication (approx. 1% incidence)
- up to 33% mortality
- common features include sustained treatment (> __ h), high doses (>__ μg/kg/min), metabolic acidosis, rhabdomyolysis, hypotension, arrhythmias (tachycardia or bradycardia) leading to asystole and death

A
  • acidosis, bradycardia, lipidemia
  • 48, 75
20
Q

Propofol Infusion Syndrome
- first described in pediatric patients ( ___ doses and not ___ sedation in pediatric patients)
- extreme caution and close monitoring when administering doses >__ - __ μg/kg/m
- monitor for components of syndrome, including TG’s, CK, LFT’s, metabolic acidosis, bradycardia, hypotension

A
  • high, prolonged
  • 75-80
21
Q

Propofol (Diprivan)

Adverse effects:

preservative:
* Diprivan product -> ___ : manufacturer recommends drug holiday after > __ days treatment in order to avoid electrolyte abnormalities (esp Zn)

generics
* sodium ___ : possible ___ reactions (more frequent in
asthmatics)
* benzyl alcohol and benzyl alcohol/sodium benzoate: ADRs unknown

preservative free formulation: Lusedra® (fospropofol disodium):
WITHDRAWN FROM MARKET
* water soluble prodrug
* pruritis (16%-28%), parasthesias (52%-85%) and hypertension (5%)

A
  • EDTA, 7
  • metabisulfate, allergic
22
Q

Propofol (Diprivan)

Adverse effects:
- ___ possible, especially following large doses, prolonged duration, and abrupt discontinuation
* not well described, may be severe
* gradual ___ of dose is required, especially if > 7 days therapy

A
  • withdrawal
  • tapering
23
Q

Propofol (Diprivan)

May be preferred sedative when ___ awakening is important and in
___ ( may lower ___)
- __ should be monitored after > 48 h and at regular intervals thereafter
* account for total ___ intake
* Propofol Infusion Syndrome
* Has assumed a more prominent role in ICU sedation
* Recommended over ___ for critically ill mechanically ventilated
adults
* Widely used in ___ sedation

A
  • rapid, neurotrauma, ICP
  • TGs
  • caloric
  • benzodiazepines
  • procedural
24
Q

Dexmedetomidine (Precedex )

selective ___ agonist
- within CNS, activation of presynaptic α-2 receptors inhibits ____ release (sedative/hypnotic effects primarily mediated by
actions at locus ceruleus)
- medullary dorsal motor nucleus of vagus has high density of α-2 receptors and may elicit ___ cardic and ___ effects

A
  • a2
  • noradrenalin
  • bradycardic, hypotensive
25
Q

Dexmedetomidine (Precedex)

sedation qualitatively different from that seen with other agents:
- sedation in undisturbed patients
- patients readily ___ with gentle stimulation
- ___ similar to BZD’s
- ___ -sparing effects
- no respiratory depression (can continue post- ___)
- no ___ activity
- should not be used when ___ sedation is required
- may be associated with less ___ than BZD’s
- possibly associated with a lower incidence of ___ than propofol
(controversial)

A
  • arousable
  • anxiolysis
  • analgesic
  • extubation
  • anti-convulsant
  • deep
  • delirium
  • delirium
26
Q

Dexmedetomidine (Precedex)

PK
- ___ distributes, highly ___ bound, Vd~ 100 L
- ___ t1/2 (~2-2.5 h in controls)
- hepatically metabolized and eliminated in urine as a glucuronide
- some impairment of elimination in ____ dysfunction (reduce dose 40-70%)
- no PK changes in renal dysfunction, however may see prolonged duration of effec

A
  • rapidly, protein
  • short
  • hepatic
27
Q

Dexmedetomidine (Precedex)

dose
maintenance infusion: ___ - ___ μg/kg/h
- 10-20% require supplementation with additional ___ agents
- doses >0.7 μg/kg/h (as high as to 1.5 μg/kg/h) seem to overcome need for supplementation
- per PI: loading infusion: 1 μg/kg over 10-20 min -> increased ___ effects
- should avoid ___
- alt: administer over ___ time (> 30 min) or with lower loading dose
(e.g., 0.4 μg/kg)
- only approved for ___ term (< 24 h) however experience with up to 28 days

A
  • 0.2-0.7
  • sedative
  • cardiovascular
  • load
  • longer
  • short
28
Q

Dexmedetomidine (Precedex)

Adverse effects:

CV effects:
- transient ___ BP with rapid administration
- ___ cardia , ___ tension:
* most common with ___ dose
* more likely in volume depleted patients or patients with sympathetic tone

may limit utility of dexmedetomidine in some ICU populations
- ___ instability/high sympathetic tone

A
  • increased
  • bradycardia, hypotension
  • loading
  • hemodynamic
29
Q

Dexmedetomidine (Precedex)

dex (up to 1.4 μg/kg/h) vs. propofol and midazolam in mech. vent patients
on light-mod. sedation for >24h:
- no ___ between D vs. M and D vs. P in time at target sedation
* increased ___ in D (20.6%) vs M (11.6%) (p=0.007)
* increased ___ in D (14.2%) vs M (5.6%) (p=0.007)
* no ___ in hypotension/bradycardia for D vs P
* D pts. were arousable, cooperative, and able to communicate pain than M and P pts.

A
  • difference
  • hypotension
  • bradycardia
  • difference
30
Q

Dexmedetomidine (Precedex)

Expanding role in ICU sedation
* novel sedative effects and beneficial ___ sparing effects
* potentially lower incidence of ___ than other sedatives (especially benzodiazepines)
* recommended over ___ for critically ill mechanically
ventilated adults
* may be limited by adverse ___ effects

A
  • analgesic
  • delirium
  • BZDs
  • CV
31
Q

Assessment of Delirium

___ : high sensitivity, moderate specificity
- 8 item assessment, score 0-8, >4 is considered delirium
- first item assesses level of consciousness

___ : high sensitivity and specificity for delirium and high inter-rater
reliability
- two-step approach (level of sedation is first assessed, then delirium is assessed, delirium is diagnosed when at least 3 of 4 diagnostic criteria are present)

assessment may be limited by level of ___

A
  • ICDSC
  • CAM-ICU
  • arousal
32
Q

Prevention and Treatment of Delirium

Nonpharmacologic
- iatrogenic/environmental causes
- early ___
- optimization of sleep
- optimization of hearing and vision
- improving cognition (reorientation, cognitive stimulation, use of music, use of clocks

A

mobilization

33
Q

Prevention and Treatment of Delirium

Pharmacologic
- NOT recommended for prevention
- not recommended for routine treatment

antipsychotics may be used short term for treatment of delirium associated with significant stress (anxiety, fearfulness, hallucinations,
agitation)
- ___
- ___ antipsychotics (risperidone, olanzapine, quetiapine aripiprazole, ziprasidone)

A
  • haloperidol
  • atypical
34
Q

Prevention and Treatment of Delirium

Pharmacologic
* ___
* recommended for delirium where agitation is precluding weaning of
vent/ ___

A
  • dexmedetomidine
  • extubation
35
Q

Haloperidol (Haldol)

butyrophenone antipsychotic/neuroleptic agent, antagonizes ___
mediated neurotransmission
* mild ___ without analgesia or amnesia
* minimal changes in heart rate, blood pressure, ventilation
* ___ t1/2 (18-54 h)
* parenteral and PO

intermittent dosing
* 1-5 mg IV q 1 h prn
* once stabilized, administer regularly scheduled doses (q 4-6 h) (IV or PO)

no published evidence that haloperidol reduces ___ of delirium

A
  • dopamine
  • sedation
  • long
  • duration
36
Q

Haloperidol (Haldol)

prolongation of ___ interval on ECG
- potential ____ __ ___
* avoid in patients at high risk, patients on other offending drugs
* discontinue if QTc exceeds 450 msec, or increases >25% from baseline

A
  • QT
  • torsades de points
37
Q

Haloperidol (Haldol)

Adverse effects
* __ seizure threshold
* possible ___
* ___ ->symptom-complex probably caused by dysautotonia related to
dopamine antagonism (altered consciousness, anxiety, tachycardia, tachypnea, diaphoresis, hyperthermia, muscle rigidity, increased CPK, granulocytosis, hyperglycemia)

A
  • decreased
  • EPS
  • NMS
38
Q

Atypical Antipsychotics

risperidone (Risperdal® ), olanzapine (Zyprexa® ), quetiapine (Seroquel® ),
aripiprazole (Abilify® ), ziprasidone (Geodon® )
* interest because of potential safety advantages over ___
* similar MOA to haloperidol (affect a variety of other neurotransmitters)
* ___ , ___ , and ___ appear to have efficacy similar to haloperidol

A
  • haloperidol
  • risperidone, olanzapine, quetiapine
39
Q

Atypical Antipsychotics

Adverse effects
* generally better tolerated than haloperidol
* fewer EPS
* of the atypical antipsychotics, ___ causes the highest rate of
prolongation of QT interval
* all atypicals contraindicated (relative) in patients at risk for Torsades de Pointes
* ___ has been associated with NMS in non-ICU patients
* high olanzapine doses may cause ___

A
  • ziprasidone
  • olanzapine
  • hypotension
40
Q

PAD Guidelines

provide adequate ___ 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
* validated sedation assessment scale
* ___ or ___

A
  • analgesia
  • RASS, SAS
41
Q

PAD Guidelines

less is more
* ___ sedation preferred vs. __ 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 ___ patient, able to purposefully follow simple commands
* close titration

A
  • light, deep
  • arousable
42
Q

PAD Guidelines

Sedation Algorithm
protocol based “ ___-first sedation”
recommended
* ___ is often primary source of agitation
* may be associated with more vent-free days, shorter ICU LOS
* must balance with potential adverse effects of opioids
* many patients will require supplementation with traditional ___
* not a universal recommendation

A
  • analgesia
  • pain
  • opioids
43
Q

PAD Guidelines

Sedation Algorithm
* ___ preferred vs. BZDs
* ___ preferred vs. BZDs

benzodiazepines may be associated with adverse clinical outcomes
* prolonged dependence on MV
* increased ICU LOS
* delirium

A
  • dexmedetodime
  • propofol
44
Q

PAD Guidelines

Sedation Algorithm
benzodiazepines still may play role
* treating anxiety
* seizures
* withdrawal

___ may be used for very rapid sedation, procedural sedation

___ has traditionally been used for prolonged sedation of many
patients
* IV -> PG solvent
* ___ is recommended for short-term use only (48-72 h)

A
  • midazolam
  • lorazepam
  • midazolam
45
Q

PAD Guidelines

Sedation Algorithm

___ may be preferred sedative when rapid awakening is desired, in
neurotrauma
- preferred over benzodiazepines in cardiac surgery

dexmedetomidine
- may be associated with less ___ and decreased duration of
mechanical ___
- drug of choice (especially vs. benzodiazepines) in a patient with ___ and ___

A
  • propofol
  • delirium, ventilation
  • delirium, agitation
46
Q

PAD Guidelines

Sedation Algorithm
* prolonged and/or high dose BZD or propofol therapy (>5-7 days)
- risk for ___ : doses should be ___ gradually

A
  • withdrawal
  • tapered

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