Exam 3 lecture 6 Flashcards
Monitoring sustained NMB (neuromuscular blockade)? How to avoid giving too much NMB?
it is challenging.
Toxicity endpoint- we want to avoid giving too much neuromuscular blocker. Side effect of giving too much neuromuscular blocker would be prolonged paralysis. Which means patient is on the ventilator longer, which means they cant get out of the ICU which means they are associated with ventilator associated pneumonia.
Peripheral nerve stimulation is how we avoid giving too much NMB (Otherwise known as train-of-four (TOF) assessment).
Define TOF assessment? What is the goal?
It is a series of electrical stimulations administered to patient (4 times) administered at 0.5 second intervals. It is administered on ulnar nerve. When there is no neuromuscular blockade, each time there is a stimulation, we see a twitch. As we increase neuromuscular blockade the number of twitches we see decrease.
3/4 twitches- 75% suppression, 2/4- 80% suppression, 1/4 -90%
Usually adjust dose to 1-2 twitches of train. This is a TOXICITY ENDPOINT
Define PADIS
Pain, agitation/sedation, delirium, immobility, sleep
Define pain and agitation
Pain- unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
Agitation- Condition characterized by apprehension, increased motor activity and autonomic arousal; may also be manifested by fearful withdrawal.
Agitation is a state of anxiety accompanied by motor restlessness
define delirium? What are the cardinal features?
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.
Cardinal feature- disturbed level of consciousness and either a change of cognition or development of perceptual disturbance
What are the physiologic responses seen with pain?
-Increased sympathetic nervous system activation, raises catecholamine levels.
-Vasoconstriction, impaired tissue perfusion
- catabolism/hypermetabolism
-impaired wound healing
-immunosuppression
- can alter breathing patterns and mechanics
Biggest challenge of pain assessment? Gold standard for pain? What if patient is unable to self report?
Gold standard for pain management is whatever the patient says. Pain is usually treated poorly in hospitals.
If unable to self report- BPS (behavioral pain scale), CPOT (critical pain observation tool)
How should analgesia be used in ICU? What drugs to use in ICU for analgesia? What are the non opioid drugs we can use?
If we know a patient is going to undergo a painful procedure we do preemptive analgesia.
IV opioids preferred for non-neuropathic pain in critically ill patients
Non-opioid analgesics may ben used to decrease opioid requirements
-acetaminophen
- for neuropathic pain (Gabapentin, pregabalin)
potentially NSAIDs
Ketamine
What are the two most common analgesic drugs given in ICU? How are they given?
Morphine and fentanyl
Can be given as a bolus dose or a continuous infusion or combination
How frequent is agitation in critically ill patients? What are the adverse clinical outcomes?
Agitation- state of anxiety accompanied by motor restlessness. Frequent in critically ill pts.
Adverse clinical outcomes
- ventilator desynchrony
- inappropriate verbal behavior
- physical aggression
- Increased motor activity
- increases in O2 consumption
- inadvertent removal of devices
Underlying cause of agitation
Pain
mechanical ventilation
Delirium
hypoxia
Hypotension
Withdrawal
Treatment of agitation
non pcol- maintenance of patient comfort
Provide adequate analgesia
Frequent reorintation
Optimization of environment to maintain normal sleep pattern
Pcol- Sedatives may reduce stress of mechanical ventilation, relieve anxiety and prevent agitation related harm
- pcol sedation should be strated after providing adequate analgesia and treating reversible causes
Why is over sedation problematic
- increases time on mechanical ventilation
- increase ICU and hospital length stay
- obscure neurological function testing
What is the goal of treatement of agitation
Adequate sedation, but not oversedation
Less is best–> Light sedation
Daily sedation interruption (spontaneous awakening trial) used
Assessment if sedation>
Assessment is difficult in patients with altered level of mentation or inability to outwardly express anxiety
Most valid and reliable
- richmond-agitation sedation (RASS)
- Sedation- Agitation scale (SAS)
what do we use when we can not use a RASS or a SAS
BIS (Bispectral index)
What are sedative drugs used in the ICU
Benzodiazepines
- lorazepam, midazolam
propofol
Dexmedetomidine
What ideal properties do BZDs have to be ICU sedation agents? Who is more sensitive? What drusg commonly used?
Anxiolytic
Hypnotic/sedative effect
Amnestic effect
Anticonvulsant effect
Elderly are more sensitive.
Tolerance seen with chronic administration.
Drugs primarily used in ICU (lorazepam, midazolam)
adverse effects of BZDs
-Respiratory depression
-CVD effects (hypotension/tachycardia) but usually minimal especially compared to propofol
-Withdrawal possible
- Delayed emergence from sedation
a) occurs if patient is on benzo for a long time
b) Advanced age
C) Hepatic/renal insufficiency
compare BZDs to propofol and dexmedetomidine for duration of mechanical ventilation and association with delirium?
BZDs may be associated with longer duration of mechanical ventilation compared to propofol or dexmedetomidine.
Potential association with delirium!!
How can lorazepam be given? Compare lipid solubility with other BZDs. What effect does this half? Half life?
Lorazepam can be continuous or bolus.
It is the least lipid soluble BZD. So it takes a while to get through BBB. So it has a delayed onset and prolonged duration of effect.
Half life is longer than propofol and midazolam so it is less titratable.
how is lorazepam metabolized? How does this affect its action? How prone are they to drug i/a? How does the longer t 1/2 affect it?
Metabolized by glucuronidation–> not expected to accumulate in elderly
Because of glucuronidation, it tends to be prolonged in liver disease and ESRD
Least prone to drug i/a
long t 1/2 makes infusions less titrateable
potential association with delirium
What is a unique thing about lorazepam (EXAM)
IV formulation contains propylene glycol (PG) solvent
it is very toxic
We can look at osm gap to detect potential PG toxicity on patients with prolonged lorazepam exposure.
How is midazolam given? What is it metabolized by?
How long is t1/2?
When is this t1/2 altered?
continuous or IV
metabolized by CYP3A
T 1/2 is short, but is increased in elderly, hepatic disease, numerous drug interactions.
also prolonged in renal disease due to metabolite accumulation
Summarize midazolam (onset, when is it recomended, when is it not recommended, why does it have declining use in hospitals?
- fast onset
- recommended for short term use only, may be used for procedural sedation
not recommended for long term sedation due to unpredictable awakening time
declining use due to potential association with delirium
propofol MOA? onset/offset? What other uses other than sedative/hypnotic agent? does it have analgesic properties
MOA- causes global CNS depression
Quick onset and offset
Can also be used as general anesthetic
No analgesia
PK of propofol (half life, metabolized by, Vd, PK changes with renal or hepatic failure)
Fast half life
hepatically metabolized
highly protein bound, large Vd
No PK changes reported with renal or hepatic dysfunction
calories from propofol? What type of liquid is it? Long term infusions may result in what?
1.1 kcal/ml
long term infusions may result in hypertriglyceridemia
it is an emulsion in a phospholipid vehicle
adverse effects of propofol
APnea
hypotension, bradycardia
pain upon infusion
hypertrilyceridemia
elevation of pancreatic enzymes
seizures/neurotoxicity
What is the biggest thing we worry about when we give propofol
Propofol infusion syndrome
How common is propofol infusion syndrome? MOrtality rate? Symptoms?
Rare ( 1% incidence)
Mortality rate- 33%
symptoms- acidosis, bradycardia, lipidemia. Hypotension
When and what to monitor for propofol infusion syndrome?
Pedatric patients and high dose propofol need monitoring
monitor- TG, CK, LFTs, metabolic acidosis, bradycardia, hypotension
What is a unique thing about propofol?
Available formulations contain preservatives like diprivan.
Diprivan can have adverse effect’s. Monitor zinc and other electrolytes since diprivan contains EDTA
when is propofol preferred?
may be preferred sedative when rapid awakening is important and in neurotrauma.
What to monitor on propofol
TG should be monitored after >48 hour and at regular intervals thereafter. Account for that 1.1 kcal/ml
monitor for propofol infusion syndromes
Is propofol recommended over BZDs for critically Ill mechanically ventilated adults? Why or why not?
Yes it is recommended over BZDs. Due to lack of delirium.
What type of drug is dexmedetomidine? How does it differ from the other agents? disadvantage of this dexmed?
It is a selective alpha-2 agonist.
Sedation is different from other sedative agents in that dexmed causes sedation that is arousable with gentle stimulation. Disadvantage could be that degree of sedation is much lighter compared to bzd and propofol.
How does dexmeds anxiolysis compared to BZDs what about delirium?? Does it have analgesic sparing effects? What is unique about dexmed?
Anxiolysis similar to BZDs, less delirium than BZDs
Analgesic sparing effect
unique- NO RESPIRATORY DEPRESSION (can continue post extubation)
pharmacokinetics of dexmed (What is it bound to, t 1/2, metabolized by? Eliminated by? HOw does hepatic dysfunction affect it? Renal dysfunction?
Highly protein bound and rapidly distributes. Short T1/2
Hepatically ,etabolized and eliminated in urine as glucuronide
Some impairment of elimination in hepatic dysfunction (decrease dose 40-70%)
-No PK changes in renal dysfunction, however may see prolonged duration of effect
What is something about dosing dexmed that we need to know for exam
Avoid loading dose (even if it does say to give the loading dose on package) due to CV side effects
Administer over longer time
Only approved for short term use (<24 hrs)
We can also give doses higher than what package insert says (above 0.7 ug/kg/h)
adverse effects of dexmed
Cardiovascular effects (bradycardia and hypotension) Especially with loading dose
More likely in volume depleted patients with increased sympathetic tone (patients with hemodynamic instability/high sympathetic tone)
summary of dexmed (What use does it have in ICU? Compare delirium to other sedatives? What are its adverse effects? Do we use tdexmed of BZDs for critically ill mechanically ventilated adults?
Novel sedative effects and beneficial analgesic sparing effects
Potentially lower incidence of delirium than others
May be limited by CV effects
Recommended over BZDs
(less sedation than the otehrs) You can wake patient up
Define delirium? What are its cardinal features?
acute onset of cerebral function with disturbed level of consciousness in addition to disorganized thinking
cardinal feature
- disturbed level of consciousness
- change in cognition (memory/disorientation/language) or development of perpetual disturbances (hallucinations/delusions)
other symptoms of delirium
sleep disturbances
abnormal psychomotor activity
emotional disturbances (fear, anxiety, anger, depression, euphoria)
What are the two subtypes of delirium
Hyperactive (agitated)- more often associated with hallucinations/delusions
Hypoactive (calm/lethargic)- more often associated with confusion/sedation
long term complications of delirium
May be associated with long term cognitive impairment
Longer duration of delirium potentially associated with greater chance for prolonged and irreversible impairement
What are the two types of risks that could cause delirium?
- modifiable
- BZDs
- Blood transfusion - Non- modifiable
- old age
- preexisting dementia
-prior coma
- pre ICU surgery or trauma
What are other potential triggers of delirium
Hx of hypertension
Use of psychoactive durgs
Sepsis
Hypoglycemia
Prolonged physical restraint, immobility
CNS injury, head injury, meningitis
What are the tools to assess Delirium
ICDSC
CAM-ICU
non pharm prevention of delirium
Multicomponent strategy recommended
- early mobilization is important to decrease delirium.
- optimization of sleep
- optimization of hearing and vision
- improving cognition
when is pharmacologic treatment of delirium not recommended
NOT recommended for prevention
not recommended for routine treatment
When do we use pcol tx for delirium? What drugs are used?
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)
When is dexmed used for delirium treatment
Dexmed is used where agitation is precluding weaning of vent/extubation
MOA of haloperidol? Does it cause sedation? Analgesia? Amnesia? CV side effects? t1/2? Parenteral and PO?
butyrophenine antipsychotic/ neuroleptic agent, antagonizes dopamine mediated neurotransmission
mild sedation without sedation analgesia or amnesia
minimal changes in heart rate, BP, ventilation
long t 1/2
parenteral and PO
How is haloperidol dosed?
Intermittent dosing
adverse effects of haloperidol
QT interval prolongation and potential torsades de pointes
lowers seizure threshold
- possible extrapyramidal symptoms (EPS)
- Neuroleptic Malignant syndrome (NMS)
Name the atypical antipsychotics? Safety compared to haloperidol? MOA?
Risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone
Has potential safety advantages over haloperidol
similar MOA to haloperidol
adverse effects of antipsychotics? Which antipsychotic causes most QT prolongation? CI?
-generally better tolerated than haloperidol
-Fewer EPS
- Of the atypical antipsychotics, ziprasidone causes highest rate of prolongation of QT interval
Contraindication- patients at risk for torsades de pointes
Do we use anti psychotics for prophylaxis of delirium? Are they routinely used for tx of delirium in critically ill patients?
Not used for prevention
Not routinely used for treatment of delirium in critiically ill patients
use of antipsychotics in delirium? Concern with use of antipsychotics? What to monitor?
- May be used for short term treatment of delirium associated with significant stress (anxiety, fearfulness, hallucinations, agitation)
COncern- prolongation of QT interval
Monitor- QTc
What is recommended for delirium where agitation is precluding weaning of vent/extubation
Dexmed
Define the sedation algorithim
Protocol is based on analgesia first sedation
- Pain is often primary source of agitation
dexmed is preferred over BZDs
Propofol prefrred over BZDs
BZDs cause delirium
