Analgesia & Sedation

Analgesia & Sedation in critical care

Overview

Some critically ill patients receive inadequate analgesia

Reason: to avoid side effects of opiate:

	respiratory depression
	hypotension, especially in hypovolemia
	gastric retention and ileus

Despite these concerns, adequate analgesia remains a primary goal in the care of the critically ill.

Morphine Sulfate

	Most frequently used intravenous analgesic agent
	Advantages: low cost, potent, effective and euphoric effect.
	Half-life of 1.5 to 2 hrs after IV.
	In ICU patient, distribution volume and protein binding may be abnormal, may have exaggerated or diminished response.
	May induce histamine release, causing hypotension.

	Loading dose of 0.05 mg/kg over 5 to 15 mins. Most adults require 4 to 6 mg/hr.
	With bolus therapy, need redosing every 1 to 2 hrs.

Fentanyl (Sublimaze®)

A synthetic opiate with greater potency and more lipophilic than morphine, faster onset of action.

The preferred Analgesic Agent when

	Hemodynamically unstable
	Symptoms of Histamine Release With Morphine, or Morphine Allergy

	Does not cause histamine release, which may explain the reduced frequency of hypotension.
	Short half-life of 30 to 60 mins from rapid redistribution.
	Prolonged administration leads to accumulation in peripheral compartments, results in a progressive increase in half-life to 9 to 16 hrs.
	Little euphoric effect, no active metabolites, and does not crossreact in patients with morphine allergy.
	Most patients need a loading doses of 1 to 2 µg/kg, then 1 to 2 µg/kg/hr by continuous intravenous infusion.

Hydro-morphone (Dilaudid)

	An acceptable alternative to Morphine
	A semisynthetic morphine derivative
	More potent analgesic/sedative properties than morphine. Less euphoria.
	Dose: initiate at 0.5 mg and titrated by 0.5 mg increments, most patients requiring 1 to 2 mg every 1 to 2 hrs.

Not recommended for routine use in ICU

Meperidine (Demerol)

Active metabolite, normeperidine, may accumulate and produce central nervous system excitation.

Opiate agonist -antagonists (nalbuphine, butorphanol)

May reverse other opiate agents.

NSAID

	No analgesic advantage over opiates
	Potential risks of gastrointestinal bleeding, platelet inhibition, renal insufficiency in critical patients.

SEDATIVES in critical care

Midazolam (Versed)

	Short-term ( <24 Hrs ) treatment of anxiety in the ICU.
	Short-acting, water-soluble benzodiazepine that becomes a lipophilic compound in the blood.
	Rapid onset of sedation: about 2 mins
	Effect is similar to diazepam, except for its brief duration of clinical effect due to rapid redistribution.
	Long-term administration results in a prolongation of the clinical effects of the drug.
	Loading doses 0.03 mg/kg, maintenance dose 3 mg/kg/hr.

Propofol (Diprivan)

	Has sedative, hypnotic, anxiolytic, and anterograde amnestic properties at subanesthetic dosages.
	Onset of action after single subanesthetic IV dose: 1 to 2 mins, effect is brief 10 to 15 mins.
	By continuous infusion only when used for sedation. Long-term infusions result in accumulation within lipid stores, resulting in a prolonged half-life of up to 300 to 700 mins.
	Subtherapeutic plasma concentrations are maintained after discontinuation of the drug by rapid clearance.
	Initial infusion rate 0.5 mg/kg/hr and titrated rapidly upward in increments of 0.5 mg/kg every 5 to 10 mins, according to clinical response. Typical maintenance dose 0.5 to 3.0 mg/kg/hr.
	Propofol should be administered via a central vein.

Lorazepam (Ativan)

	Preferred Agent for the Prolonged Treatment of Anxiety in ICU.
	An intermediate-acting benzodiazepine that is less lipophilic than diazepam, which decreases its potential for peripheral accumulation.
	Compared with midazolam, lorazepam is longer acting, causes less hypotension, causes an equally effective anterograde amnesia, is lower in cost, and with prolonged administration produces more rapid awakening.
	Most conveniently administered by intermittent intravenous bolus injection, but continuous intravenous infusion is an equally acceptable method of administration. The usual starting dosage is 0.044 mg/kg every 2 to 4 hrs as needed, requirement is highly variable.
	Has a slightly delayed onset of action, a single dose of midazolam or diazepam may be utilized to initiate sedative therapy when rapid sedation is required.

Haloperidol (Haldol)

	Preferred Agent for the Treatment of Delirium in ICU
	Delirium is frequent in the ICU and is often incorrectly termed "ICU psychosis."
	Opiates or benzodiazepines as initial therapy for delirium may cause a paradoxical worsening of symptoms because of the alteration in sensory perception.
	Not approved by the FDA for IV use, but has been reported to be safe and effective.
	Clinical effects observed 30 to 60 mins after IV, effect may last 4 to 8 hrs.
	May cause QT prolongation on the electrocardiogram and should be used with caution in conjunction with other drugs that may prolong the QT interval.
	Uual starting dosage is 2 to 10 mg intravenously and the dosage is repeated every 2 to 4 hrs.
	Further reading on Delirium and Haldol

Thiopental (Pentothal)
Pentobarbital (Nembutal)

	Used in ICU primarily to control intracranial pressure or as anticonvulsants.
	Using subanesthetic doses, are effective sedative agents but lack amnestic and analgesic properties.
	Produce myocardial depression and vasodilation that may result in tachycardia and hypotension.

Diazepam (Valium)

Not recommended for routine IV use in the ICU

Reasons:

	Pain and thrombophlebitis are common
	Dilution is required for continuous infusion, requiring large volumes of fluid.

Further reading

	Shapiro BA et al. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: An executive summary. Critical Care Medicine. Vol 23. No 9. Sept 1995.
	Commonly used critical care medications