Icu pharmacology Sean Forsythe M. D

ICU Pharmacology

• Sean Forsythe M.D.

• Assistant Professor of Medicine

ICU Pharmacology

• Sedatives

• Analgesics

• Paralytics

• Pressors

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.

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

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

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.

Benzodiazepines

Propofol

• 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

• 1% solution of 10% intralipids
• Daily tubing changes, dedicated port

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

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

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.

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.

Opiodes

• Adverse effects

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

Non-opiodes

• Ketamine

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

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

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.

Use of Paralytics

• Intubation

• Facilitation of mechanical ventilation

• Preventing increases in ICP

• Decreasing metabolic demands (shivering)

• Decreasing lactic acidosis in tetanus, NMS.

Paralytics

• Depolarizing agents

• Succinylcholine

• Non-depolarizing agents

• Pancuronium
• Vecuronium
• Atracurium

Paralytics

Paralytics

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.

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.

Shock

• Rapidity of diagnosis is key.

• The types:

• Hypovolemic/ hemorrhagic
• Cardiogenic
• High output

• Fluid bolus is almost always the correct initial therapy.

Pressors

• 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

Dopamine

• “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.

Dobutamine

• 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.

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.

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.

Ephedrine

• Releases tissue stores of epinephrine.

• Longer lasting, less potent than epi.

• Used mostly by anesthesiologists.

• 5-25 mg IVP.

Vasopressin

• Vasoconstrictor that may be useful in septic shock.

• Use evolving to parallel hormone replacement therapy.

• 0.4 units/min

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.

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).

Nitroprusside

• 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.