Icu pharmacology Sean Forsythe M. D

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ICU Pharmacology

  • Sean Forsythe M.D.

  • Assistant Professor of Medicine

ICU Pharmacology

  • Sedatives

  • Analgesics

  • Paralytics

  • Pressors


  • 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.

Goals of Sedation

  • Old- Obtundation

  • New- Sleepy but arousable patient

  • Almost always a combination of anxiolytics and analgesics.

What is Agitation?

  • Pain

  • Anxiety

  • Delirium

  • Fear

  • Sleep deprivation


  • 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


  • Diazepam (Valium)

  • 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.



  • Sedative, anesthetic, amnestic, anticonvulsant

  • Respiratory and CV depression

  • Highly lipid soluble

  • Rapid onset, short duration

    • Onset <1 min, peak 2 min, duration 4-8 min
  • Clearance not changed in liver or kidney disease.

Propofol- Side effects

  • Unpredictable respiratory depression

    • Use only in mechanically ventilated patients
  • Hypotension

    • First described in post-op cardiac patients
  • Increased triglycerides


  • 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

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.

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

Pain in the ICU

  • Pain leads to a stress response which causes:

    • Catabolism
    • Ileus
    • ADH release
    • Immune dysregulation
    • Hypercoaguable state

Pain in the ICU

  • What causes pain in the ICU?

    • Lines
    • Tubes
    • Underlying illness
    • Interventions
    • Everything else


  • 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.


  • 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.


  • Adverse effects

    • Respiratory depression
    • Hypotension (sympatholysis, histamine release)
    • Decreased GI motility (peripheral effect)
    • Pruritis


  • Ketamine

    • Analog of phencyclidine, sedative and anesthetic, dissociative anesthesia.
    • Hypertension, hypertonicity, hallucinations, nightmares.
    • Potent bronchodilator


  • Ketorolac

    • NSAID
    • Limited efficacy (post-op ortho)
    • Synergistic with opiodes
    • No respiratory depression
    • Increased side effects in the critically ill
    • Renal failure, thrombocytopenia, gastritis


  • 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.

Use of Paralytics

  • Intubation

  • Facilitation of mechanical ventilation

  • Preventing increases in ICP

  • Decreasing metabolic demands (shivering)

  • Decreasing lactic acidosis in tetanus, NMS.


  • Depolarizing agents

    • Succinylcholine
  • Non-depolarizing agents

    • Pancuronium
    • Vecuronium
    • Atracurium



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).

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.

Monitoring Paralysis

  • Observe for movement

  • Twitch monitoring, train of four, peripheral nerve stimulation.


  • 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.


  • Rapidity of diagnosis is key.

  • The types:

    • Hypovolemic/ hemorrhagic
    • Cardiogenic
    • High output
  • Fluid bolus is almost always the correct initial therapy.


  • 1 myocardium-  contractility

  • 2 arterioles- vasodilation

  • 1 SA node-  chronotropy

  • 2 lungs- bronchodilation

  • peripheral- vasoconstriction

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


  • “Renal dose” dopamine probably only transiently increases u/o without changing clearance.

  • There are better  and  agents.

  • Adverse effects- tachyarrhythmias .

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.


  • Useful in right and left heart failure.

  • May be useful in septic shock.

  • Dose- 5-15 mcg/kg/min.

  • Adverse effects- tachyarrhythmias.

Isoproteronol (Isuprel)

  • Mainly a positive chronotrope.

  • Increases heart rate and myocardial oxygen consumption.

  • May worse ischemia.

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.


  •  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.

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).

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.


  • Releases tissue stores of epinephrine.

  • Longer lasting, less potent than epi.

  • Used mostly by anesthesiologists.

  • 5-25 mg IVP.


  • Vasoconstrictor that may be useful in septic shock.

  • Use evolving to parallel hormone replacement therapy.

  • 0.4 units/min


  • 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.

Nitroprusside (Nipride)

  • Balanced vasodilator

  • Rapid onset, short elimination time

  • Useful in hypertensive emergency, severe CHF, aortic dissection

  • Accumulates in renal and liver dysfunction.

  • Toxicity= CN poisoning (decreased CO, lactic acidosis, seizures).


  • Dosing- 0.2- 10 mcg/kg/min

  • Other AE-  ICP

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.

Types of Shock

  • Hypovolemic

  • Cardiogenic

  • High output

Hypovolemic Shock

  • Cold and clammy, thready pulse, clear lungs.

  • GI bleeds, trauma, dehydration.

  • Treatment-Volume, volume, volume

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)

High Output Shock

  • Warm and well perused, bounding pulses

  • Sepsis, sepsis, sepsis, and then other things

  • Treatment- Volume first, then norepi +/- dobutamine.

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