Stony Brook Medicine
SEDATION AND ANALGESIA
OBJECTIVES
1. To understand the reasons and choices of analgesics and sedatives
2. To become familiar with opioids, benzodiazepines, and other therapies
CAVEAT: THIS SYLLABUS DOES NOT DEAL WITH PROCEDURAL SEDATION
PATIENT ASSESSMENT
-- must decide whether the patient is in pain vs having anxiety vs needs sedation
-- if anxiety or the patient is not alert but awake, is the patient or healthcare staff in danger
-- what are the patient’s signs and symptoms? What is the frequency of agitation?
-- In SBUH, we use the SBS Evaluation Tool
DEFINITIONS
1. Sedation – state of calm or drowsiness
2. Anxiolytic – drug that eases anxiety
3. Amnestic – drug that induces memory loss
4. Hypnotic – drug that induces sleep
DRUGS (information provided here is not all-inclusive – see Lexicomp for more)
OPIOIDS
-- Uses
-- Treat pain; alter perception and response to pain
-- Act as sedatives
-- Mechanism of Action
--Act on opiate receptors (m, d, etc) and interfere with neurotransmitter release
-- Metabolized by liver and excreted in kidney; in patients with renal failure or in newborns, smaller doses may be needed
-- Adverse effects:
-- CV: hypotension, brady or tachycardia
-- Resp: decr RR, size of breath, response to CO2; rigid chest
-- Other: constipation, urinary retention, pruritis, etc
-- Dependence: can occur after ~ 1 week; more common if continuous infusion
-- Continuous vs. Bolus Dosing
-- Bolus dosing of sedatives and analgesics has been shown to be more effective than continuous infusions in getting people off of mechanical ventilation and out of the ICU
-- If, however, the pain is predictably severe and constant, use of a continuous infusion should be considered
-- Patients should be given prn analgesics intermittently prior to painful interventions (i.e. suctioning)
-- Morphine
-- Dose: 0.1 – 0.2 mg/kg/dose q1 – 4 hrs; can be less in neonates
-- Usual max dose ~ 10 – 15 mg; truly max dose is “enough”
-- Onset: 5 – 15 min; Duration: 2 - 3 hrs
-- PCA: 0.01-0.02 mg/kg/hr + intermittent 0.02-0.03 mg/kg q 6 min
-- Fentanyl
-- Dose: 1-5 mcg/kg/dose; if continuous, 1-3mcg/kg/hr
-- Onset: 3-5 min; Duration: 30-60 min
-- Associated with rigid chest
BENZODIAZEPINES
Uses
-- sedation
-- anxiolysis
-- provide amnesia
-- hypnotic
Mechanism of Action and Pharmacokinetics
-- facilitate GABA inhibitory effect on neuronal transmission
-- most are metabolized by the cyt P-450 system in liver; Ativan is metabolized by glucuronyl transferase, which is preserved in liver disease and, so, may be used judiciously in liver dysfunction
-- versed has no active metabolites so it is used in drips
-- renally cleared but renal dysfx usually doesn’t alter clearance
Midazolam (Versed)
-- Dose: 0.1 mg/kg/dose (or per hr); usual adult doses ~ 4-6 mg
-- Onset: 3-5 min; Duration: 2 hr
Lorazepam (Ativan)
-- Dose: 0.1 mg/kg/dose; adult doses ~4-6 mg but can be more
-- Onset: 15 min: Duration: up to 8 hrs
-- Cannot be used in a drip because its preservative contains ethylene glycol
ADJUNCTIVE THERAPIES
Barbiturates
-- Sedatives and hypnotics
-- Also produce physical dependence
-- Work at the GABA receptor but in a different way from the benzodiazepines
Pentobarbital
Dose: 2-4 mg/kg
Onset: 5 min; Duration: 8 hrs
Thiopental
Dose: 4-6 mg/kg
Onset: 30-60 sec: Duration: 10 min
Chloral Hydrate
-- Sedative and hypnotic
-- Dose: 25-100 mg/kg po or pr
-- Onset: 30-60 min; Duration: 6 hrs
Haloperidol (Haldol)
-- Antipsychotic; causes sedation
-- Side effects: extrapyramidal symptoms; decreases the seizure threshold, neuroleptic malignant syndrome, etc.
-- Safety has not been established in kids < 3 years of age
-- Doses: 1-3 mg/dose (IV, IM,or PO); can be more in adults
Dexmedetomidine (Precedex)
-- Sedative, analgesic, hypnotic, and anxiolytic
-- Acts by stimulating α2 receptors in brain, like clonidine
-- DOES NOT SUPPRESS THE RESPIRATORY DRIVE
-- Side effects: can cause bradycardia, hypotension, and sleep- associated seizures, rebound hypertension/tachycardia
-- Doses: Loading dose = 0.5 – 1 microgram/kg
Maintenance = 0.2 – 0.7 micrograms/kg/hour
Propofol (Diprivan)
-- Inductive anesthetic, sedative, hypnotic: not analgesic
-- Unclear mechanism of action
-- Short onset and short half-life
-- MAJOR SIDE EFFECTS: respiratory and cardiovascular depression significant
-- Older preparations were formulated in egg whites so presence of egg or soy allergies MUST be ascertained
-- Prolonged sedation in children is contraindicated as it can cause a metabolic syndrome characterized by rhabdomyolysis, arrhythmia, and death
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