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Charleston, SC

jimmy@pharmacyfridaypeals.com

Airway Series: Post-Intubation Sedation

Introduction

  1. Rapid sequence intubation (RSI) is a process whereby an induction agent and a neuromuscular blocking agent are given in rapid succession to facilitate endotracheal intubation 
  2. The immediate post intubation period in the ED is a critical time for continued patient stabilization. 
  3. While physical adjuncts like securing the tube, in line suctioning, and elevating the head of the bed are part of general post intubation management, post intubation analgesia and sedation is a key component to remember.
  4. Depending on the paralytic used, clinicians can be eased into the assumption that the patient is tolerating the ventilator and not in need of sedation or analgesia
  5. Administering analgesia and sedation is key to preventing patient awareness during paralysis and preventing PTSD
 Fentanyl  (Sublimaze)Propofol (Diprivan)Midazolam (Versed)Dexmedetomidine (Precedex)
DoseBolus: 0.35 to 1.5 mcg/kg IV every 0.5 to 1 hour   Infusion:  25-300 mcg/hrBolus: 25-50 mg    Infusion: Titrate in 5-50 mcg/kg/minBolus: 0.5 to 4 mg    Infusion: 1-10 mg/hrBolus: Not recommended   Infusion: 0.1-1.4 mcg/kg/hr
AdministrationIV Bolus + InfusionIV Bolus + Infusion IV Bolus + InfusionIV Infusion
PK/PDOnset: IV almost immediate   Duration: 30- 60 min   Metabolism: CYP3A4     Excretion: > 90% inactive metabolite renally eliminatedOnset: 10-40 sec   Duration- 3-10 min   Metabolism: Hepatic Phase II    Excretion:  Urine (~88% metabolites)Onset:  3-5 min   Duration: 30-80 min   Metabolism: CYP3A4 (active metabolites)   Excretion: 45% to 57% Renally eliminated (metabolites)Onset: 15-30 min Duration: 4 hours   Metabolism: Hepatic Phase II+ CYP2A6   Excretion:
Adverse EffectsChest wall rigidity CNS depressionHypotension, bradycardia, hypertriglyceridemia   Hypotension, respiratory depressionHypotension, bradycardia  
Drug Interactions CYP 3A4 inhibitors, serotonergic agentsBupivacaine, St. John’s WortCYP 3A4 inhibitors, CNS depressants CNS depressants and antihypertensive
CompatibilityProtonixCalcium chloride. Nimbex, Cipro, gentamicin, phenytoinFosphenytoin, sodium bicarbonate, Zosyn, hydrocortisone Protonix, phenytoin,

 Comments by  EM Physicians
Fentanyl“I love fentanyl. short acting, quick action, has least hemodynamic effect of IV narcotics”
Propofol“I’m a big propofol fan. It has reliable sedation, quick onset. The hypotension is not ideal but these are sick patients anyway so I’m ok with starting pressors or more fluid if they can tolerate it to keep up with adequate propofol dosing.”
Dexmedetomidine““I’m also a Precedex fan!  It has same quick on, quick off. Bradycardia I’ve seen has been related to infusion rate, but we used to use it primarily as part of CIWA protocol where I worked and it saved us many an intubation.”
Midazolam“Versed has an onset slower than I would like, especially if we have to bolus from the pump for acute agitation on the vent. Sometimes sedation is prolonged. In my practice it has less reliable in dose effects than propofol. I’ve seen people chew through a lot of versed without adequate sedation, but all of the side effects. I tend not to use it.”


Overview of Evidence
Author, year Design/ sample sizeIntervention & ComparisonOutcome
Groetzinger, 2018Retrospective review/ n=91Ketamine infusion 0.125 to 1.2 mg/kg/hr 63% of patients  discontinue other sedatives or analgesic within 24 hours of initiating ketamine   ↑ in the number of sedation scores at goal   ↓ in agitation, defined as SAS >4, after the initiation of ketamine
Shehabi, 2018Prospective  Cohort/ n=703Light Sedation vs  Deep Sedation (using sedation intensity score)Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation
Fraser, 2013Meta- Analysis/ n= 1,235 patientsBenzodiazepines  Vs Non-benzodiazepinesNon-benzodiazepine sedatives associated with ↓ ICU LOS and ↓ Ventilator days
Watt, 2012retrospective cohort study/ n=200Succinylcholine  1.7 ± 0.7 mg/kg     vs Rocuronium 1.3 ± 0.4 mg/kg After intubation, 77.5% (n=155) of patients were initiated on a sedative infusion of propofol (n=148) or midazolam (n=7).   Mean time to post intubation sedation was significantly greater with rocuronium compared to succinylcholine  (27 min vs 15)
Shehabi (SPICE), 2012Prospective  Cohort/ n=251Light Sedation  vs  Deep Sedation  4 hours after starting mechanical ventilation 76% of patients were deeply sedated RASS, -3 to -5   Early deep sedation was a significant independent predictor of death and time to extubation.
Jakob, 2012RCT/ N=498Dexmedetomidine 0.2-1.4 mcg/kg/hr Vs Midazolam 0.03-0.2 mg/kg/hrLighter sedation, fewer ventilation days
Strom, 2010RCT/ n=140No sedation ( PRN morphine) vs Propofol  or midazolam infusion + (PRN morphine)  No sedation group had ↓ ventilator free days,↓ ICU and↓  hospital LOS 

References

  1. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/
  2. Groetzinger LM. Pharmacotherapy. 2018 Feb;38(2):181-188 3.       Jakob SM. JAMA. 2012 Mar 21;307(11):1151-60.
  3. Shehabi Y. (SPICE Investigators). Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31
  4. Watt JM. Emerg Med J. 2013 Nov;30(11):893-5.
  5. Amini A. Am J Health Syst Pharm. 2013 Sep 1;70(17):1513-7.
  6. Fraser GL. Crit Care Med. 2013 Sep;41(9 Suppl 1):S30-8.
  7. Shehabi Y. Crit Care Med. 2018 Jun;46(6):850-859.

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