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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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