Therapeutics Exam 3 (Acute/Critical Care) Flashcards
How is oral absorption altered in critical illness?
Impaired/Unpredictable
-Alterations in gastric emptying and motility (this is caused by high dose opioids)
-Absorption may decrease, we would not expect increases
How is distribution altered in critical illness?
These patients have a higher fluid/hydration status
-hydrophilic drugs have a higher volume of distribution
*consider with aminoglycosides
Decreased albumin levels lead to decreased protein binding of many drugs
Increased acute phase proteins (a1-acid glycoprotein) leads to increased protein binding of drugs that bind a1-acid glycoprotein
How do we detect changes in renal function?
CrCl
-but is challenging because you may not see changes in serum creatinine immediately when renal dysfunction occurs
More immediate way is to determine using urine output
What is sepsis?
Life threatening organ dysfunction that is caused by a dysregulated/exaggerated immune response to that infection
What is the treatment for sepsis?
Antimicrobial therapy (broad spectrum IV antibiotics) and source control of the infection
What is septic shock?
Sepsis associated with cardiovascular collapse/hypotension
*decreased vascular tone is what leads to hypotension
How do we treat septic shock?
Fluids* (crystalloids and colloids)
*note that this is not enough to cure the shock
Vasopressors (increase vascular tone and cardiac output)
What is the target Mean Arterial Pressure (MAP) when using vasopressors?
> or = 65 mmHg
What is the preferred vasopressor to use?
Norepinephrine
Which inotrope (not vasopressor) can be added on to a vasopressor if a patient has mixed shock syndrome with declining cardiac output?
Dobutamine -used to increase cardiac output
What medication may be used as an add-on to vasopressors to provide extra benefit?
Vasopressin
If a patient with septic shock is not responding to vasopressors + add-ons (refractory), what medication can be added?
Corticosteroids (IV hydrocortisone)
What is Acute Respiratory Distress Syndrome (ARDS)?
Life threatening respiratory failure characterized by acute, diffuse inflammatory lung injury
**Often requires mechanical ventilation with sedation
**Potentially need a neuromuscular blockade
What are the elements included in General Supportive Care?
FAST HUGS BID
F: Feeding, Fluids
*A: Analgesia
*S: Sedation
*T: Thromboprophylaxis
H: HOB elevation
*U: Ulcer (stress ulcer) prophylaxis
*G: Glycemic control
*S: Spontaneous Awakening Trial,
B: Bowel regimen
I: Indwelling catheters
*D: Delirium assessment
What is the preferred agent to use in the ICU for thromboprophylaxis?
Low molecular weight heparin (LMWH)
*preferred over unfractionated heparin (UFH)
*use mechanical prophylaxis in patients with contraindications to pharmacological prophylaxis
What is the dosing of UFH thromboprophylaxis?
5000 units Subq q8h or q12h
What is the dosing of Enoxaparin thromboprophylaxis?
30 mg Subq q 12h or 40 mg Subq q24h
CrCl< 30: 30mg subq q24h
Which thromboprophylaxis drug must be renally adjusted?
Enoxaparin (for CrCl <30)
What do we monitor when using thromboprophylaxis?
S/S of bleeding
Complete Metabolic Panel (CPC)
What are the risk factors for getting stress ulcers?
-Shock, coagulopathy, chronic liver disease
-Mechanical ventilation/respiratory failure
-Neurotrauma, burn injury, life support
-Drugs: antiplatelets, anticoagulants, NSAIDs
What drugs should be used for stress ulcer prophylaxis?
Histamine-2 Receptor Antagonists (H2RAs)
Proton Pump Inhibitors (PPIs)
*many people choose PPI’s but no evidence exists to suggest one is better
What are the H2RAs used for stress ulcer prophylaxis?
Famotidine
Ranitidine
*enteral or parenteral
What are the PPIs used for stress ulcer prophylaxis?
Omeprazole
Lansoprazole
Pantoprazole
Esomeprazole
Rabeprazole
PPIs may increase the risk for which disease states?
Clostridium difficile colitis
Nosocomial pneumonia
Stress ulcer prophylaxis is warranted in critically ill patients such as?
Mechanical ventilation
Coagulopathy
Chronic liver disease
Shock
Others
What is the target blood glucose for ICU patients?
144-180 mg/dl
At what BG level do we initiate insulin for ICU patients?
> 180 mg/dl
What is the purpose of a spontaneous awakening trial/ spontaneous breathing trial?
Helps to prevent oversedation
Promotes weaning from mechanical ventilation
When neuromuscular blockers are not present, how does neuromuscular signaling typically occur?
Synaptic vesicles release acetylcholine
Acetylcholine binds receptors on muscle cell, causes depolarization and ultimately muscle contraction
What are the 2 types of neuromuscular blockers?
Depolarizing
Nondepolarizing
What drug is the only depolarizing neuromuscular blocker available?
Succinylcholine
How does succinylcholine work?
Physically resembles acetylcholine
-Binds and activates Ach receptors on the muscle
-Causes sustained depolarization which ultimately leads to a loss of muscle contraction
*Note that this drug may initially cause muscle contraction
*Rapid onset (1 min) and short duration (3-5 mins)
What do we use succinylcholine for?
Rapid sequence intubation (RSI)
**this is its only use, not used for sustained neuromuscular blockade
What are the side effects of succinylcholine?
Apnea (*need to be ready to intubate)
Muscle fasciculations (muscle ache, may last days)
Hyperkalemia
When is succinylcholine contraindicated?
Major burns
Crush injury
Upper motor neuron disease
***risk of life-threatening hyperkalemia
How do nondepolarizing neuromuscular blockers work?
Competitively block the action of acetylcholine (block receptors)
***Do not activate receptors
-this means there are no initial muscle
contractions
What are the 2 classes of nondepolarizing neuromuscular blockers?
Aminosteroidal
Benzylisoquinolinium
What are the aminosteroidal neuromuscular blockers?
Pancuronium
Vecuronium
Rocuronium
What are the benzylisoquinolinium neuromuscular blockers?
Atracurium
Cisatracurium
True or False: Neuromuscular blockers are required in all mechanically ventilated patients
FALSE
-only those with Acute Lung Injury or Acute Respiratory Distress Syndrome (ARDS)
What are the side effects associated with non-depolarizing NMBs?
Paralysis of muscles/apnea
Inadequate pain care and sedation
***note that these drugs DO NOT provide analgesia, sedative, or anxiolytic effects (patients still feel pain but cannot communicate)
-patients must be optimized on sedatives+analgesia before administration
Prolonged paralysis/Muscle weakness
What drugs interact with non-polarizing NMBs?
Corticosteroids
-potentially cause long-term muscle weakness
What is the toxicity endpoint for neuromuscular blockers?
Peripheral nerve stimulation
-Stimulate the nerve 4 times and record the number of muscle twitches
When assessing peripheral nerve stimulation with neuromuscular blockers, what do the different amounts of twitches recorded mean?
4/4: <75% suppression (no saturation)
3/4: 75% suppression
2/4: 80% suppression
1/4: 90% suppression
0/4: 100% suppression (complete saturation)
How many peripheral nerve twitches do we normally hope to see when dosing neuromuscular blockers?
Adjust dose to 1-2 twitches
**avoid 0 twitches
What are the 2 scales used for pain assessment?
Behavioral Pain Scale (BPS)
Critical Care Pain Observation Tool (CPOT)
In critically ill patients, what is the preferred analgesia used for non-neuropathic pain?
IV opioids
*note that these also have sedative effects
What is the role of non-opioid analgesics in critically ill patients?
May be used to decrease opioid requirements
What are the most commonly used opioids and how do we dose these?
Fentanyl
Morphine
Burn patients: Methadone (due to long-term needs)
*these can be administered as continuous infusions and bolus doses
What is the first thing we try when trying to treat agitation?
Nonpharmacologic efforts
-Maintain patient comfort
-Provide adequate analgesia
-Frequent reorientation
-Optimize environment to maintain normal sleep
Note that MANY (not most) patients needing mechanical ventilation will require pharmacological sedation
What are the indications for sedatives?
*Poorly defined
-Adjunct for anxiety and agitation
-Reduce anxiety
-Many patients needing mechanical ventilation (reduce stress)
-Prevent agitation-related harm
Sedation should not be used for what?
Restraint
Coercion
Discipline
Convenience
Retaliation
The degree of sedation in a patient is dependent on what?
Need/ability to protect their airway
Why is over-sedation problematic?
-Increases time on mechanical ventilation
-Increases ICU and hospital length of stay
-Obscures neurological function testing
What are the goals of sedation treatment?
-Adequate but not over sedation
-Less is best
-Obtain a calm, arousable patient able to follow simple commands
What 2 scales are used to assess agitation in patients and consequently to titrate their sedation?
Richmond-Agitation-Sedation Scale (RASS)
Sedation-Agitation Scale (SAS)
What objective assessment can be used to assess sedation?
Bispectral Index (BIS)
When would we use the Bispectral Index (BIS) to assess patient sedation?
When using the other measures are not feasible in a patient (deep sedation, neuromuscular blockade)
True or False: BIS monitoring is recommended in all sedated ICU patients
FALSE
What are the sedative drugs used in the ICU?
Benzodiazepines (lorazepam, midazolam)
Propofol
Dexmedetomidine
What is the moa of benzodiazepines?
Bind + activate the GABA receptor
Inhibit GABA action on neuronal impulse transmission (this hyperpolarizes the cell and makes them more resistant to excitation)
What are the adverse effects of benzodiazepines (lorazepam + midazolam)?
-Respiratory depression
-CV effects (hypotension, tachycardia)
-Withdrawal
risk of seizures
doses need to be tapered off
-Delayed emergence from sedation
*especially with midazolam in hepatic/renal
insufficient patients
-Longer duration of mechanical ventilation
-Delirium**
What is the reason why benzodiazepines are not used as commonly anymore?
They cause delirium!
How do we dose benzodiazepines?
Continuous or bolus doses
What are some points specific to lorazepam?
-Less lipid soluble than midazolam
-Crosses BBB slowly
-Has a delayed onset with prolonged duration of effect
(less titratable)
How is lorazepam metabolized and what effect can this have?
Metabolized to inactive form by glucuronidation
*It is not expected to accumulate in the elderly
*Half-life may be prolonged in liver disease and end-stage renal disease
***What does lorazepam contain that is important to remember?
IV form contains propylene glycol solvent (PG)
*this is a common ingredient in antifreeze
*with high doses, patients could get toxic amounts of this
-there is no easy way to get serum concentrations of thus
Need to calculate an osmol gap qd or qod to detect toxicity
An osmol gap of what may indicate potential propylene glycol toxicity?
> 10
When is lorazepam not a good option?
If rapid awakening is required
What is the onset of midazolam?
Rapid onset
*Has increased lipid solubility at physiological pH
How is midazolam metabolized and what effect can this have?
Hepatically metabolized by CYP450 3A
-Half-life increased in the elderly and hepatic disease
-Numerous drug interactions
What is an important thing to remember about midazolam’s half-life?
It is short, but not reliably short
-Prolonged use makes the half-life more unpredictable
When could we consider using midazolam?
-Rapid sedation of acutely agitated patients
-Short-term use only (<48-72 h)
-Rapid titration needed
-Procedural sedation
What is the maximum amount of time midazolam can be used for?
48-72 hours
What are some benefits to using propofol for sedation?
Rapid onset (1-2min) and Rapid offset
(highly titratable)
No changes reported with renal or hepatic dysfunction
What are some side effects of propofol?
Some antegrade amnesia
CNS depression!
Withdrawal (titrate off)
“Propofol Infusion Syndrome” -acidosis, bradycardia, lipidemia
-leads to asystole and death
-33% mortality
What is the drug of choice for sedation of neurosurgical patients and why?
Propofol
-may reduce elevated intracranial pressure (ICP)
-rapid resolution of sedative effects when stopped
What does propofol contain that is important to remember?
Phospholipid vehicle (contains fat)
1.1 kcal/mL
(need to account for in nutritional assessment)
What labs do we need to check when propofol is administered?
Triglycerides (after 48h)
*because propofol may cause hypertriglyceridemia
What side effects are associated with Propofol Infusion Syndrome?
acidosis
bradycardia
lipidemia
What preservatives are present in propofol and how do these affect how we give the drug?
EDTA: give patient a drug holiday after 7 days of treatment to avoid electrolyte abnormalities
Sodium metabisulfate: Allergic reactions (especially asthmatics)
Benzyl alcohol: unknown ADR
When is propofol preferred?
-Rapid awakening wanted
-Neurotrauma
Recommended over benzodiazepines
What kind of drug is Dexmed?
Selective a-2 agonist
-activation of these receptors in the CNS inhibits noradrenalin release
What are the side effects of Dexmed?
Bradycardia and Hypotension (from agonism of a-2 receptors in the vagus nerve)
**Do not use in patients with low BP or who are on BP meds
How does sedation from dexmed vary from the other agents?
-Patients are readily arousable with gentle stimulation
-Analgesic-sparing effects
-Anxiolytics (similar to BZDs)
*No respiratory depression (can continue post-extubation)
-No anticonvulsant activity
What is the half-life of dexmed?
Short
How is dexmed metabolized?
Hepatically metabolized
-eliminated in urine as glucuronide
-some impaired metabolism in hepatic dysfunction
What quirk should you be aware of with dexmed dosing?
The maintenance infusion dose is 0.2-0.7 BUT higher doses are often used
-Drug was originally designed to be given as a loading dose followed by maintenance
-*LOADING DOSE SHOULD BE AVOIDED because of cardiovascular effects
-Alternative: administer over longer time or with lower loading dose
How long can dexmed be used?
Only approved for <24h
*Experience with longer durations but just remember to use this drug short-term
Which sedation meds should we use first and second line?
First Line:
-Propofol
-Dexmed (limited by duration and CV effects)
Second Line:
-Benzodiazepines (lorazepam + midazolam)
What are the 2 subtypes of delirium?
Hyperactive (agitated)
–associated with hallucinations/delusions
Hypoactive (calm/lethargic)
–associated with confusion/sedation
What are the modifiable risks for delirium?
Benzodiazepines
Blood transfusions
What 2 assessment tools do we use for delirium?
ICDSC
(score >4 is delirium)
CAM-ICU
(2-step approach: first assess level of sedation and then delirium. When at least 3-4 diagnostic criteria are present delirium is diagnosed)
How do we prevent/treat delirium?
Non-pharm:
-Assess intrinsic/environmental causes
***Early mobilization of patient (PT/OT)
-Optimize sleep
-Optimize vision and hearing
-Improve cognition (reorientation, cognitive stimulation, music, clocks)
Pham:
not recommended for prevention
not recommended for routine treatment
-Antipsychotics can be used short-term for delirium associated with stress
-Dexmed (used when agitation is precluding weaning of vent/extubation)
What are our 2 choices when patients require antipsychotics for delirium relating to significant stress?
Haloperidol
Atypical Antipsychotics (risperidone, olanzapine, quetiapine)
What medication would we administer for delirium when agitation is precluding weaning of vent/extubation?
Dexmedetomidine
What are some important points about haloperidol?
-Mild sedation but no analgesia or amnesia
-Long half-life
-Parenteral and PO
-Intermittent dosing (used for acute aggression with delirium so it is dosed aggressively)
**Not shown to reduce delirium duration
What are the side effects of haloperidol?
QT interval prolongation -> *Torsades de points
*note that haloperidol has never been approved as an IV drug so the parenteral dose being used is not approved
Decreased seizure threshold
EPS (involuntary dyskinetic movements) *Contraindicated in parkinson’s disease
What are the side effects of atypical antipsychotics? (risperidone, olanzapine, quetiapine)
-Generally better tolerated than haloperidol
-Fewer EPS
-Still associated with prolonged Qt interval and torsades de points
In what case is propofol preferred over dexmed?
Cardiac surgery
