Acute Care II Flashcards
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
- rapid
- respiratory
- CV
- analgesic
- delirium
Sedative Drugs used in ICU
- BZDs: ___ , ___ , ( ___ )
- propofol
- dexmedetomidine
- lorazepam, midazolam, diazepam
Benzodiazepines
bind and activate a specific site on the ___ receptor
- facilitate ___ action on neuronal impulse transmission
- ___ cells, more resistant to excitation
- GABA
- inhibitory
- hyperpolarizes
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: ___ , ___
- elderly
- tolerance
- lorazepam, midazolam
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
- respiratory
- hypotension, tachycardia
- withdrawal, abrupt
- seizures
- tapering
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 ___
- delayed
- saturation
- age
- midazolam
- propofol, dexmedetomidine
- delirium
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
- IV
- 0.02-0.06
- 0.01-0.1
- least
- slowly
- delayed, prolonged
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 ___
- inactive, accumulate
- liver, renal
- least
- titratable
- delirium
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)
- propylene glycol
- lactic, nephrotoxicity, 50, 1
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
- intermittent, continuous
- delirium, lighter
- rapid
Midazolam (Versed)
___ only
* ___ - ___ mg/kg q 0.5-2h
* ___ - ___ mg/kg/h
* At physiologic pH: ___ lipid solubility and ___ onset
- 0.02-0.08
- 0.04-0.2
- increased, rapid
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 ___
- elderly, hepatic, renal, drug
- short
- prolonged
- accumulation
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
- rapid, fast
- short
- procedural
- long
- delirium, lighter
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
- sedative, hypnotic
- multiple
- rapid, BBB
- offset
- procedural
- analgesic
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
- variable
- protein
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
- rapid, short
- 5-90
- neurosurgical
- ICP
- sedative
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
- 1.1
- hypertriglyceridemia, TG’s
- egg, soybean
- 12
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)
- hypotension, bradycardia
- pain
- hypertriglyceridemia
- pancreatic
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
- acidosis, bradycardia, lipidemia
- 48, 75
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
- high, prolonged
- 75-80
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%)
- EDTA, 7
- metabisulfate, allergic
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
- withdrawal
- tapering
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
- rapid, neurotrauma, ICP
- TGs
- caloric
- benzodiazepines
- procedural
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
- a2
- noradrenalin
- bradycardic, hypotensive
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)
- arousable
- anxiolysis
- analgesic
- extubation
- anti-convulsant
- deep
- delirium
- delirium
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
- rapidly, protein
- short
- hepatic
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
- 0.2-0.7
- sedative
- cardiovascular
- load
- longer
- short
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
- increased
- bradycardia, hypotension
- loading
- hemodynamic
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.
- difference
- hypotension
- bradycardia
- difference
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
- analgesic
- delirium
- BZDs
- CV
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 ___
- ICDSC
- CAM-ICU
- arousal
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
mobilization
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)
- haloperidol
- atypical
Prevention and Treatment of Delirium
Pharmacologic
* ___
* recommended for delirium where agitation is precluding weaning of
vent/ ___
- dexmedetomidine
- extubation
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
- dopamine
- sedation
- long
- duration
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
- QT
- torsades de points
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)
- decreased
- EPS
- NMS
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
- haloperidol
- risperidone, olanzapine, quetiapine
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 ___
- ziprasidone
- olanzapine
- hypotension
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 ___
- analgesia
- RASS, SAS
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
- light, deep
- arousable
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
- analgesia
- pain
- opioids
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
- dexmedetodime
- propofol
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)
- midazolam
- lorazepam
- midazolam
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 ___
- propofol
- delirium, ventilation
- delirium, agitation
PAD Guidelines
Sedation Algorithm
* prolonged and/or high dose BZD or propofol therapy (>5-7 days)
- risk for ___ : doses should be ___ gradually
- withdrawal
- tapered
