Acute care Flashcards
Absorption
Oral:
Impaired and unpredictable in critically ill patients
Alterations in gastric emptying and motility–>opioids, C.diff
Interactions with enteral feeding and tubing–>fluoroquinolines, phenytoin, GI injury/disease
IV: preferred in many of those cases
Distribution
Relates to fluid and hydration status
-Hydrophilic drugs have high Vd in critically ill patients than regular medical floor patients
Alterations in protein binding
-Decreased albumin–>less protein binding of drugs
-Increased acute phase proteins–>more protein binding of drugs
Ex: lidocaine
Metabolism (hepatic)
Enzyme expression and activity may be decreased in critically ill patients
Metabolism (renal)
Renal dysfunction and HD/CRRT is common
Decreased: shock, sepsis, nephrotoxic drugs
Increased: burn, trauma
How to assess?
CrCl–>delayed
Urine output–>immediate
Sepsis
Life threatening dysfunction caused by dysregulated response to infection
-Immune dysregulation
-Coagulation and thrombosis leading to endothelial injury
Occurs in response to any pathogen–>bacterial is most common
Occurs in any site of injection–>lungs, bloodstream, urinary tract
Treatment: early detection and supportive care + broad spectrum IV antibiotics/antifungals and source control
Septic shock
Sepsis associated with cardiovascular collapse and hypotension
-Hypotension caused by decreased vascular tone
Treatment:
Fluids
+
Vasopressors–> increase vascular tone and cardiac output via vasoconstriction
1st line: norepinephrine
others: epinephrine, phenylephrine, dopamine, add- on vasopressin, dobutamine
Target MAP > 65 mmHg
If refractory–>IV hydrocortisone
Respiratory failure
MECHANICAL VENTILATION IS COMMON
Causes: airway compromise, hypoventilation, hypoxic failure, inability to protect airways
Acute Respiratory Distress Syndrome (ARDS)
Characterized by acute, diffuse inflammatory lung injury
1st phase: mucous
2nd phase: fibrotic
Risk for ARDS: pneumonia, sepsis, trauma, aspiration
Treatment: mechanical ventilation + sedation +/- neuromuscular blockade
Corticosteroids may be used
Analgesia treatment
Preemptive analgesia in advance to painful procedures (dressing changes, chest tubes, insertion of lines)
IV opioids: Bolus or continuous infusion or both
SE: sedation, respiratory depression, do not have to worry about respiratory depression if on vent
Non-opioids: Tylenol
NSAIDS–>procedural
Ketamine–>post-surgery
Gabapentin/pregabalin/carbamazepine–>neuropathic
Underlying causes of agitation
Pain
Mechanical ventilation
Hypoxia
Delirium
Hypotension
Withdrawal
Non-pharmacological treatment of agitation
Maintain patient comfort
Provide adequate analgesia
Reorient the patient–> where and why they are in the hospital
Optimize environment for sleep patterns
Pharmacologic treatment of agitation
Sedatives
-Adjunct for anxiety and agitation
-Adjunct to non-pharmacological
-Many mechanical ventilation patients
ANALGESIA-FIRST SEDATION
Goal: Less is best–>light sedation
Desire a calm arousable patient, able to purposefully follow simple commands
Methods: spontaneous awakening trial, nursing-protocolized targeted sedation
Lorazepam MOA
Binds to the allosteric site of GABAa receptor increasing frequency of Cl- channel opening
Inhibits GABA activity on neuron impulses–>hyper-polarizes cells leading to resistance to excitation
IV contains propylene glycol solvent that can cause lactic acidosis and nephrotoxicity after high doses or prolonged infusions–>MONITOR OSMOL GAP
Lorazepam side effects
Respiratory depression
Hypotension, tachycardia
Withdrawal (seizures)–> gradually taper dose
Delayed sedation: prolonged infusion, advanced age, hepatic/renal insufficiency (midazolam)
DELIRIUM
Lorazepam properties
Anxiolysis
Sedation
Amnesia
Anticonvulsant and muscle relaxant
Lorazepam pearls
Tolerance with chronic administration
Metabolized into inactive metabolite via glucuronidation–>less accumulation
Least lipid soluble crossing the BBB more slowly leading to delayed onset and prolonged duration of action (long t1/2 life)–>LESS TITRATABLE
Midazolam
IV only
Hepatically metabolized by CYP3A4–> increased t1/2 in elderly, hepatic disease, drug interactions
At physiological pH, very high lipid solubility leading to rapid onset (short 1/2 life)–> TITRATABLE
After 48 hours, t1/2 becomes prolonged or unpredictable especially in renal disease due to metabolite accumulation
Recommended for short term use only, not for long term sedation because of unpredictable awakening time
Propofol MOA
Binds sites on multiple receptors (GABA, glycine, nicotinic, M1 muscarinic) interrupting neural transmission leading to global CNS depression
IV
Diprivan–>contains EDTA that can cause electrolyte abnormalities, recommended drug holiday after > 7 days treatment
Sodium metabisulfate–>allergic reactions in asthmatics
Propofol Indications
General anesthetic
Procedural sedation
Neurosurgical–>may reduce ICP and rapid offset of sedative effects
Propofol side effects
Hypertriglyceridemia–>check q48 hours
Apnea
Hypotension, bradycardia
Pain with infusion
Withdrawal–> gradual taper if > 7 days of therapy
Propofol Infusion Syndrome–>acidosis, bradycardia, lipidemia
**sustained treatment > 48 hours
**high doses >75-80 ug/kg/min
**metabolic acidosis
**rhabdomyolysis
**hypotension, arrhythmias
**asystole (rare)
Propofol PK
Hepatically metabolized with no active metabolite
No changes in renal or hepatic function
High protein bound
Large Vd
Propofol pearls
Easily penetrates BBB–> rapid onset
Rapidly redistributes tissues and rapid hepatic clearance–>rapid offset
Provides some amnesia
Phospholipid emulsion–>1.1 kcal/mL
DO NOT HANG > 12 hours–>risk of infection
Dexmedetomidine MOA
selective alpha-2-agonist within CNS inhibiting norepinephrine release
Dexmedetomidine ROA
IV
Avoid loading dose
May push doses higher than guidelines due to weak sedation
May use for longer than > 24 hours compared to guidelines
Dexmedetomidine properties
Patients readily arousable with gentle stimulation–>not used for deep sedation
Anxiolysis
Analgesic sparing effects
No respiratory depression
No anticonvulsant
Dexmedetomidine Side effects
Increase in blood pressure with rapid administration
Hypotension, bradycardia
**more common in volume depleted patients with high sympathetic tone–>AVOID IN HEMODYNAMIC UNSTABLE PATIENTS
Dexmedetomidine PK
Highly protein bound
High Vd
Short t1/2
Hepatically metabolized and eliminated in urine as glucuronide
**no changes in renal dysfunction
**decrease dose by 40-70% in hepatic dysfunction
Monitoring–>hourly assessment
Subjective: assessment is difficult due to inability to outward express anxiety
Richmond-agitation-sedation scale (RASS)
Sedation-agitation scale (SAS)
Objective:
Bispectral index (BIS)
-Utilizing EEG to find objective number
-Guidelines suggest using in patients who other measures are not feasible (sedation, NMBA)
NOT RECOMMENDED IN ALL PATIENTS
Thromboprophylaxis
Receive unless sufficiently mobile, low risk of VTE, contraindications
Enoxaparin
DOC
30 mg SQ q12h or 40 mg SQ q24h
monitor s/sx of bleeding, CBC
CrCl < 30 mL/min: 30 mg SQ q24h
Daltaparin
5000 units SQ q24h
monitor s/sx of bleeding, CBC
No renal adjustment
Unfractionated heparin
5000 units SQ q8-12 hours
monitor s/sx of bleeding, CBC
No renal adjustment
Ulcer risk factors
Shock, coagulopathy, chronic liver dx
Neurotrauma, burn injury, extracorporeal life support
Mechanical ventilation
Drugs: antiplatelets, anticoagulants, NSAIDS
Glycemic control
Causes: stress, TPN
Balance risk between hypo/hyperglycemia
BG goal: 144-180 mg/dL
> 180 mg/dL: initiate insulin
Avoid long-acting agents due to long t1/2 life
Two subtypes of delirium
Hyperactive (agitated)–>hallucinations, delusions
Hypoactive (calm, lethargic)–>confusion, sedation
Modifiable risk factors of delirium
Benzodiazepines
Blood transfusions
Non-modifiable risk factors of delirium
Older age
Preexisting dementia
Prior coma
Pre-ICU emergency surgery or trauma
High severity of illness at admission
Other risk factors of delirium
HTN
Psychoactive drugs
Prolonged physical restraint, immobility
Sepsis
Hypoglycemia, hyponatremia
Metastatic disease of the brain, head injury, CNS infections
Assessment of delirium
ICDSC
CAM-ICU
Non-pharm treatment of delirium
Early mobilization
Optimize sleep
Optimize hearing and vision
Improve cognition
Pharmacological treatment of delirium
NOT RECOMMENDED FOR PREVENTION
NOT RECOMMENDED FOR ROUTINE THERAPY
Haloperidol MOA
Short-term treatment
typical antipsychotic–>D2 antagonist
IV, PO
Haloperidol properties
Mild sedation without analgesia
Minimal CV effects
Haloperidol PK
long t1/2 life
Haloperidol SE
QTc prolongation and TdP
-Avoid in high risk patients
-Avoid with other Qtc prolonging agents
-D/C if QTc >450 msec or > 25% increase from baseline
Lower seizure threshold
EPS
Neuroleptic Malignant Syndrome
Atypical antipsychotics
Risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone
MOA: 5HT2A and D2 antagonist
Atypical antipsychotic SE
Lower EPS
QTc prolongation: avoid in high risk patients, avoid with other QTc prolonging agents, D/C if QTc > 450 msec
NMS–>olanzapine most common
Hypotension–>olanzapine most common
Dexmedetomidine for delirium
May be used for delirium-related agitation precluding weaning off vent/extubating
Depolarizing NMBA
initial inactivation of Ach receptors then inhibition
Non-depolarizing NMBA
Competitively block the action of Ach
Amino steroidal
Benzylisoquinolinium
Reversal agents
Pyridostigmine, neostigmine–>Ach inhibitors
Sugammadex: modified A cyclodextrin for reversal of rocuonium/vecuronium
Succinylcholine MOA
physically resembles Ach to bind to Ach and activate receptors–>depolarization of neuromuscular junction–>muscle contraction blocked
Succinylcholine indication
Rapid sequence intubation (RSI)
NOT USED FOR SUSTAINED NEUROMUSCULAR BLOCKAGE
Succinylcholine SE
Initial muscle contractions: may pre-administer with non-depolarizing MNDA agent
APNEA–>MUST BE READY TO INTUBATE IMMEDIATELY
Prolonged apnea–>impaired pseudocholinesterase activity or lower levels
Muscle fasciculations–>deep aching muscle pain lasting for days
Hyperkalemia: contraindicated in major burns, crash injury, and upper motor neuron disease
Succinylcholine PK
onset: 1 minute
Duration: 3-5 minutes
Elimination: rapidly hydrolyzed by pseudocholinesterase
Non-depolarizing agents indications
Immediate/sustained paralysis
Mechanical ventilation
Muscle relaxation operations
RSI if contraindicated to succinylcholine
-Rocuonium if CI to succinylcholine
Increased ICP
Hypothermia
Non-depolarizing NMBA SE
Paralysis of respiratory muscles/apnea
Inadequate pain/sedation: NMDA do not provide analgesic, sedative, or anxiolytic effects, assessment can be hard when they cannot talk, MUST BE OPTIMIZED ON SEDATIVE AND ANALGESIC DRUGS PRIOR
Prolonged paralysis: caused by accumulation of medication and chronic administration
Solution: drug holidays
Drug interactions: corticosteroids
Toxicity endpoint–>peripheral nerve stimulation
Twitch monitoring or train-of-four
4/4–> < 75% suppression
3/4–> 75% suppression
2/4–> 80% suppression
1/4–> 90% suppression
0/4–> 100% suppression
Goal: 1-2 out of 4
