Today’s pearl: SEDATION DRIPS

Titrating the sedation regimen on the sickest of patients can be one of the most challenging parts of the MICU. Anecdotally, many COVID+ vented patients in particular need at least 2, sometimes 3 different meds running at high doses to keep them comfortable, a phenomenon that also seems to have been noted in the literature.

Trying to prevent a patient from pulling out their ET tube while also maintaining their already tenuous hemodynamics is a tough balance to achieve for any ED/crit care provider, an obscure question mired with nuance and case-by-case considerations. For this pearl, we will go over the basics of the major players: mechanisms of action, dosing, advantages vs pitfalls, and general effect on hemodynamics.

RASS (Richmond Agitation & Sedation Scale): a common tool to quantitatively describe the level of sedation.

Main Agents:

Mechanism of Actionµ-opioid receptor agonistGABA-mediated Cl channel hyperpolarization of nervesGABA agonistCentral alpha-2 agonist, increases GABA activity by inhibiting noradrenergic neurons in the brain stem
Infusion Dosing0.7-10 mcg/kg/hr
*Usually titrated in 25mcg/hr increments with a max of ~150-200
5-100 mcg/kg/min
*Usually titrated in 5mcg increments with a max of ~50-100
0.02-0.2 mg/kg/hr
*Usually titrated in 2mg/hr increments with a max of ~20
0.2-1.5 mcg/kg/hr
*Usually titrated in 0.1mcg/kg/hr increments with max of ~1-1.4
Time to Onset (mins)<1 to 2<1 to 22 to 5~15
BenefitsFast on, fast off.
Sedative-analgesic but usually used in conjunction with another agent.
Hemodynamically stable.
Fast on, fast off.
Usually our go-to, along with some fentanyl.
Neuroprotective: reduces cerebral blood flow + metabolism, reducing ICP, also an antiepileptic.
Consider when concern for status epilepticus or delirium tremens.
Hemodynamically stable.
No respiratory depression.
Thought to decrease the incidence of ICU delirium and potentially mechanical ventilation time.
Cons/Main Side EffectsConstipation, nausea, respiratory depression.See hemodynamics.
Hypertriglyceridemia. Also rarely, pancreatitis.
Even more rarely, propofol infusion syndrome.
Probably the worst side effect profile of the 4, use as last resort in hypotensive pts.
Respiratory depression.
Higher risk of delirium (avoid in elderly if you can help it) and tolerance, lipophilic which can lead to extended prolonged effects and vent times, memory deficits, withdrawal syndrome.
Paradoxical excitement reactions with long term use.
Midazolam infusion syndrome.
See hemodynamics.
Slowest onset.
Officially only recommended for a maximum of 24hrs, after which FDA warns of risk of tachyphylaxis, tolerance, and other complications like ARDS, resp failure, and agitation.
Effect on HemodynamicsRelatively hemodynamically stable, as it does not induce histamine release like other opioids (i.e. morphine) that results in hypotension.Can cause profound hypotension, bradycardia, respiratory depression, decreased cardiac contractility.Relatively hemodynamically stable, but can induce hypotension 2/2 vasodilation with compensatory tachycardia usually when bolused.Often referred to as relatively hemodynamically stable but known to have biphasic dose-dependent BP effects.
Brady cardia and hypotension at lower doses (and commonly with bolus doses), some studies showing similar incidence rates to propofol if not more.
Hypertension at high doses.

Other Options:

  • Ketamine: NMDA receptor antagonist, onset <1min, dosed at 0.3-10mcg/kg/hr (titrate by 0.1), bronchodilatory effects make it attractive for status asthmaticus, more commonly used for pain management in ICU rather than sedation, intact respiratory drive, favorable hemodynamic profile, risk of tachycardia, hypertension, tachyarrythmias, hypersalivation; can order but unfortunately, and correct me if I’m wrong, but I still don’t think you’re allowed to transport pts on it (i.e. to the ICU) and you will get a lot of nursing pushback.
  • Phenobarbital: GABA agonist, onset <5mins, dosing dependent on use, long half-life (5 days!), can be given as an infusion OR IVP 2-3x per day for basal sedation on top of drips, anti-epileptic (can be used in status epilepticus) and useful in pt with known active alcoholism to prevent withdrawal syndromes, levels can be measured to titrate effect, but long duration of action makes it less desirable if looking to shorten vent times, can cause hypotension and bradycardia, respiratory depression, tissue necrosis if extravasated, and be careful in pts with advanced cirrhosis as it is hepatically metabolized

All that being said, though, don’t forget that you can always start peripheral pressors to offset the hemodynamic effects of your sedation if you absolutely need it. And when you’re up in MICU or CCU on that overnight call, always remember you can always call down to the cardiac room attending/resident for help if you’re feeling overwhelmed or want to run something by someone!

You got this.

May 2022