icu pharmacology sean forsythe m.d. assistant professor of medicine
TRANSCRIPT
![Page 1: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/1.jpg)
ICU Pharmacology
Sean Forsythe M.D.
Assistant Professor of Medicine
![Page 2: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/2.jpg)
ICU Pharmacology
Sedatives
Analgesics
Paralytics
Pressors
![Page 3: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/3.jpg)
Sedation
Relieve pain, decrease anxiety and agitation, provide amnesia, reduce patient-ventilator dysynchrony, decrease respiratory muscle oxygen consumption, facilitate nursing care.
May prolong mechanical ventilation and increase costs.
![Page 4: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/4.jpg)
Goals of Sedation
Old- Obtundation
New- Sleepy but arousable patient
Almost always a combination of anxiolytics and analgesics.
![Page 5: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/5.jpg)
What is Agitation?
Pain
Anxiety
Delirium
Fear
Sleep deprivation
Patient-ventilator interactions
Encephalopathy
Withdrawal
Depression
ICU psychosis
![Page 6: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/6.jpg)
Benzodiazepines
Act as sedative, hypnotic, amnestic, anticonvulsant, anxiolytic.No analgesia.Develop tolerance.Synergistic effect with opiates.Lipid soluble, metabolized in the liver, excreted in the urine.Interact with erythro, propranolol, theo
![Page 7: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/7.jpg)
Benzodiazepines
Diazepam (Valium) Repeated dosing leads to accumulation Difficult to use in continuous infusion
Lorazepam (Ativan) Slowest onset, longest acting Metabolism not affected by liver disease
Midazolam (Versed) Fast onset, short duration Accumulates when given in infusion >48 hours.
![Page 8: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/8.jpg)
Benzodiazepines
Onset Peak Equianalgesic doseDiazepam (valium) 1-3 min 3-4 min 2-5 mgLorazepam (ativan) 5-15 min 15-20 min 1-2 mgMidazolam (versed) 1-3 min 5-30 min 1-5 mg
![Page 9: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/9.jpg)
Propofol
Sedative, anesthetic, amnestic, anticonvulsantRespiratory and CV depressionHighly lipid solubleRapid onset, short duration Onset <1 min, peak 2 min, duration 4-8 min
Clearance not changed in liver or kidney disease.
![Page 10: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/10.jpg)
Propofol- Side effects
Unpredictable respiratory depression Use only in mechanically ventilated
patients
Hypotension First described in post-op cardiac patients
Increased triglycerides 1% solution of 10% intralipids Daily tubing changes, dedicated port
![Page 11: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/11.jpg)
Butyrophenones
Haldol Anti-psychotic tranquilizer Slow onset (20 min) Not approved for IV use, but is probably
safe No respiratory depression or hypotension. Useful in agitated, delirious, psychotic
patients Side effects- QT prolongation, NMS, EPS
![Page 12: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/12.jpg)
Sedation studies
Propofol vs. midazolam Similar times to sedation, faster wake-up time with
propofol AJRCCM, 15:1012, 1996.
Nursing implemented sedation protocol duration of mech vent, ICU stay, trach rate Crit
Care Med 27:2609, 1999.
Daily interruption of sedation duration of mech vent, ICU LOS, hosp LOS
NEJM 342:1471, 2000.
![Page 13: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/13.jpg)
Monitoring Sedation
Many scoring systems, none are validated.Ramsey 1: Anxious, agitated, restless 2: Cooperative, oriented, tranquil 3: Responds to commands 4: Asleep, brisk response to loud sounds 5: Asleep, slow response to loud sounds 6: No response
![Page 14: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/14.jpg)
Pain in the ICU
Pain leads to a stress response which causes: Catabolism Ileus ADH release Immune dysregulation Hypercoaguable state
– Increased myocardial workload
– Ischemia
![Page 15: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/15.jpg)
Pain in the ICU
What causes pain in the ICU? Lines Tubes Underlying illness Interventions Everything else
![Page 16: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/16.jpg)
Analgesics
Relieve Pain
Opioides
Non-opiodes
Can be given PRN or continuous infusion PRN avoids over sedation, but also has
peaks and valleys and is more labor intensive.
![Page 17: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/17.jpg)
Opiodes
Metabolized by the liver, excreted in the urine. Morphine- Potential for histamine release
and hypotension. Fentanyl- Lipid soluble, 100X potency of
MSO4, more rapid onset, no histamine release, expensive.
Demerol- Not a good analgesic, potential for abuse, hallucinations, metabolites build up and can lead to seizures.
![Page 18: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/18.jpg)
Opiodes
Adverse effects Respiratory depression Hypotension (sympatholysis, histamine
release) Decreased GI motility (peripheral effect) Pruritis
![Page 19: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/19.jpg)
Non-opiodes
Ketamine Analog of phencyclidine, sedative and
anesthetic, dissociative anesthesia. Hypertension, hypertonicity, hallucinations,
nightmares. Potent bronchodilator
![Page 20: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/20.jpg)
Non-opiodes
Ketorolac NSAID Limited efficacy (post-op ortho) Synergistic with opiodes No respiratory depression Increased side effects in the critically ill Renal failure, thrombocytopenia, gastritis
![Page 21: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/21.jpg)
Paralytics
Paralyze skeletal muscle at the neuromuscular junction.
They do not provide any analgesia or sedation.
Prevent examination of the CNS
Increase risks of DVT, pressure ulcers, nerve compression syndromes.
![Page 22: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/22.jpg)
Use of Paralytics
Intubation
Facilitation of mechanical ventilation
Preventing increases in ICP
Decreasing metabolic demands (shivering)
Decreasing lactic acidosis in tetanus, NMS.
![Page 23: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/23.jpg)
Paralytics
Depolarizing agents Succinylcholine
Non-depolarizing agents Pancuronium Vecuronium Atracurium
![Page 24: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/24.jpg)
Paralytics
Adjust for Adjust for Drug Onset Duration Route of elimination renal liverSuccinylcholine 1-1.5 min 5-10 min acetylcholinesterase No YesPancuronium 1.5-2 min 60 min 85% kidney Yes YesVecuronium 1.5 min 30 min biliary, liver, kidney No YesAtracurium 2 min 30 min Plasma (Hoffman) No NoRocuronium 1 min 30-60 min Hepatic No YesTubocurare 6 min 80 min 90% kidney Yes Yes
![Page 25: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/25.jpg)
Paralytics
Drug Advantages Side effectsSuccinylcholine rapid onset, short acting K, ICP, IOPPancuronium Inexpensive, long acting tachycardiaVecuronium Less CV effects bradycardiaAtracurium Hoffman elim rash, histamine releaseRocuronium No hemodynamic effects expensive
![Page 26: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/26.jpg)
Complications of Paralysis
Persistent neuromuscular blockade Drug accumulation in critically ill patients Renal failure and >48 hr infusions raise risk
In patients given neuromuscular blockers for >24 hours, there is a 5-10% incidence of prolonged muscle weakness (post-paralytic syndrome).
![Page 27: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/27.jpg)
Post-paralytic syndrome
Acute myopathy that persists after NMB is gone
Flaccid paralysis, decreased DTRs, normal sensation, increased CPKs.
May happen with any of the paralytics
Combining NMB with high dose steroids may raise the risk.
![Page 28: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/28.jpg)
Monitoring Paralysis
Observe for movement
Twitch monitoring, train of four, peripheral nerve stimulation.
![Page 29: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/29.jpg)
Shock
Hypoperfusion of multiple organ systems.
May present as tachycardia, tachypnea, altered mental status, decreased urine output, lactic acidosis.
Not all hypotension is shock and not all shock has hypotension.
![Page 30: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/30.jpg)
Shock
Rapidity of diagnosis is key.
The types: Hypovolemic/ hemorrhagic Cardiogenic High output
Fluid bolus is almost always the correct initial therapy.
![Page 31: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/31.jpg)
Pressors
1 myocardium- contractility
2 arterioles- vasodilation
1 SA node- chronotropy
2 lungs- bronchodilation
peripheral- vasoconstriction
![Page 32: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/32.jpg)
PressorsAlpha
PeripheralBeta 1
CardiacBeta 2
Peripheral
Norepinephrine ++++ ++++ 0
Epinephrine ++++ ++++ ++
Dopamine ++++ ++++ ++
Isoproterenol 0 ++++ ++++
Dobutamine +/0 ++++ +
Methoxamine ++++ 0 0
NEJM, 300:18, 1979.
![Page 33: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/33.jpg)
Dopamine (Intropin)
Renal (2-4 mcg/kg/min)- increase in mesenteric blood flow
(5-10 mcg/kg/min)- modest positive ionotrope
(10-20 mcg/kg/min) vasoconstriction
![Page 34: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/34.jpg)
Dopamine
“Renal dose” dopamine probably only transiently increases u/o without changing clearance.
There are better and agents.
Adverse effects- tachyarrhythmias .
![Page 35: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/35.jpg)
Dobutamine (Dobutrex)
Primarily 1, mild 2.Dose dependent increase in stroke volume, accompanied by decreased filling pressures.SVR may decrease, baroreceptor mediated in response to SV.BP may or may not change, depending on disease state.
![Page 36: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/36.jpg)
![Page 37: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/37.jpg)
Dobutamine
Useful in right and left heart failure.
May be useful in septic shock.
Dose- 5-15 mcg/kg/min.
Adverse effects- tachyarrhythmias.
![Page 38: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/38.jpg)
Isoproteronol (Isuprel)
Mainly a positive chronotrope.
Increases heart rate and myocardial oxygen consumption.
May worse ischemia.
![Page 39: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/39.jpg)
PDE Inhibitors
Amrinone, Milrinone
Positive ionotrope and vasodilator.
Little effect on heart rate.
Uses- CHF
AE- arrhythmogenic, thrombocytopenia
Milrinone dosing- 50mcg/kg bolus, 0.375-0.5 mcg/kg/min infusion.
![Page 40: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/40.jpg)
Epinephrine
at very low doses, at higher doses.Very potent agent.Some effects on metabolic rate, inflammation.Useful in anaphylaxis.AE- Arrhythmogenic, coronary ischemia, renal vasoconstriction, metabolic rate.
![Page 41: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/41.jpg)
Norepinephrine (Levophed)
Potent agent, some Vasoconstriction (that tends to spare the brain and heart).
Good agent to SVR in high output shock.
Dose 1-12 mcg/min
Can cause reflex bradycardia (vagal).
![Page 42: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/42.jpg)
Phenylephrine (Neosynephrine)
Strong, pure agent.
Vasoconstriction with minimal in heart rate or contractility.
Does not spare the heart or brain.
BP at the expense of perfusion.
![Page 43: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/43.jpg)
Ephedrine
Releases tissue stores of epinephrine.
Longer lasting, less potent than epi.
Used mostly by anesthesiologists.
5-25 mg IVP.
![Page 44: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/44.jpg)
Vasopressin
Vasoconstrictor that may be useful in septic shock.
Use evolving to parallel hormone replacement therapy.
0.4 units/min
![Page 45: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/45.jpg)
Nitroglycerine
Venodilator at low doses (<40mcg/min)
Arteriolar dilation at high doses (>200 mcg/min).
Rapid onset, short duration, tolerance.
AE- inhibits platelet aggregation, ICP, headache.
![Page 46: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/46.jpg)
Nitroprusside (Nipride)
Balanced vasodilatorRapid onset, short elimination timeUseful in hypertensive emergency, severe CHF, aortic dissectionAccumulates in renal and liver dysfunction.Toxicity= CN poisoning (decreased CO, lactic acidosis, seizures).
![Page 47: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/47.jpg)
Nitroprusside
Dosing- 0.2- 10 mcg/kg/min
Other AE- ICP
![Page 48: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/48.jpg)
Labetolol (Normodyne)
1 and non-selective blocker.
Dose related decrease in SVR and BP without tachycardia.
Does not ICP
Useful in the treatment of hypertensive emergencies, aortic dissection.
Bolus= 20mg, infusion= 2mg/min.
![Page 49: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/49.jpg)
Types of Shock
HypovolemicCardiogenicHigh output
![Page 50: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/50.jpg)
Hypovolemic Shock
Cold and clammy, thready pulse, clear lungs.GI bleeds, trauma, dehydration.Treatment-Volume, volume, volume
![Page 51: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/51.jpg)
Cardiogenic Shock
Cold and clammy, thready pulse, crackles, S3.Left heart failure, right heart failure, valvular disease.Treatment- preload reduction(diuretics), afterload reduction (ACE-I), increase contractility (PDE inhibitor, dobutamine)
![Page 52: ICU Pharmacology Sean Forsythe M.D. Assistant Professor of Medicine](https://reader036.vdocument.in/reader036/viewer/2022081511/56649c805503460f94936abf/html5/thumbnails/52.jpg)
High Output Shock
Warm and well perused, bounding pulsesSepsis, sepsis, sepsis, and then other thingsTreatment- Volume first, then norepi +/- dobutamine.