Post-Intubation Sedation

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

The immediate post intubation period in the ED is a critical time for continued patient stabilization.

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

Administering analgesia and sedation is key to preventing patient awareness during paralysis and preventing PTSD

Author, year | Design/ sample size | Intervention & Comparison | Outcome

Groetzinger, 2018 | Retrospective review/ n=91 | Ketamine 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, 2018 | Prospective Cohort/ n=703 | Light 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, 2013 | Meta-Analysis/ n= 1,235 patients | Benzodiazepines Vs Non-benzodiazepines | Non-benzodiazepine sedatives associated with ↓ ICU LOS and ↓ Ventilator days

Amini, 2013 | retrospective cohort study/ n=100 | rocuronium-assisted RSI) + PharmD vs rocuronium-assisted RSI) – PharmD | PharmD associated with time to sedation 9 min vs 28 min PharmD associated with time to analgesia 21 min vs 44 min PharmD associated with sedation within 5 min 33% vs 11%

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 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), 2012 | Prospective Cohort/ n=251 | Light 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, 2012 | RCT/ N=498 | Dexmedetomidine 0.2-1.4 mcg/kg/hr Vs Midazolam 0.03-0.2 mg/kg/hr | Lighter sedation, fewer ventilation days

Strom, 2010 | RCT/ n=140 | No sedation ( PRN morphine) vs Propofol or midazolam infusion + (PRN morphine) | No sedation group had ↓ ventilator free days,↓ ICU and↓ hospital LOS

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 (GAWAS) 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 | Overview of Evidence | Overview of Evidence | Overview of Evidence

Author, year | Design/ sample size | Intervention & Comparison | Outcome

Groetzinger, 2018 | Retrospective review/ n=91 | Ketamine 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, 2018 | Prospective Cohort/ n=703 | Light 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, 2013 | Meta-Analysis/ n= 1,235 patients | Benzodiazepines Vs Non-benzodiazepines | Non-benzodiazepine sedatives associated with ↓ ICU LOS and ↓ Ventilator days

Amini, 2013 | retrospective cohort study/ n=100 | rocuronium-assisted RSI) + PharmD vs rocuronium-assisted RSI) – PharmD | PharmD associated with time to sedation 9 min vs 28 min PharmD associated with time to analgesia 21 min vs 44 min PharmD associated with sedation within 5 min 33% vs 11%

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 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), 2012 | Prospective Cohort/ n=251 | Light 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, 2012 | RCT/ N=498 | Dexmedetomidine 0.2-1.4 mcg/kg/hr Vs Midazolam 0.03-0.2 mg/kg/hr | Lighter sedation, fewer ventilation days

Strom, 2010 | RCT/ n=140 | No sedation ( PRN morphine) vs Propofol or midazolam infusion + (PRN morphine) | No sedation group had ↓ ventilator free days,↓ ICU and↓ hospital LOS

Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 6, 2018, from http://www.micromedexsolutions.com/

Groetzinger LM. Pharmacotherapy. 2018 Feb;38(2):181-188

Jakob SM. JAMA. 2012 Mar 21;307(11):1151-60.

Shehabi Y. (SPICE Investigators). Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31

Watt JM. Emerg Med J. 2013 Nov;30(11):893-5.

Amini A. Am J Health Syst Pharm. 2013 Sep 1;70(17):1513-7.

Fraser GL. Crit Care Med. 2013 Sep;41(9 Suppl 1):S30-8.

Shehabi Y. Crit Care Med. 2018 Jun;46(6):850-859.

Fentanyl (Sublimaze) | Propofol (Diprivan) | Midazolam (Versed) | Dexmedetomidine (Precedex)

Dose | Bolus: 0.35 to 1.5 mcg/kg IV every 0.5 to 1 hour Infusion: 25-300 mcg/hr | Bolus: Infusion: Titrate in 5-50 mcg/kg/min | Bolus: 0.5 to 4 mg Infusion: 1-10 mg/hr | Bolus: Not recommended Infusion: 0.1-1.4 mcg/kg/hr

Administration | IV Bolus + Infusion | IV Bolus + Infusion | IV Bolus + Infusion | IV Infusion

PK/PD | Onset: IV almost immediate Duration: 30- 60 min Metabolism: CYP3A4 Excretion: > 90% inactive metabolite renally eliminated | Onset: 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 Effects | Chest wall rigidity CNS depression | Hypotension, bradycardia, hypertriglyceridemia | Hypotension, respiratory depression | Hypotension, bradycardia

Drug Interactions | CYP 3A4 inhibitors, serotonergic agents | Bupivacaine, St. John’s Wort | CYP 3A4 inhibitors, CNS depressants | CNS depressants and antihypertensive

Compatibility | Protonix | Calcium chloride. Nimbex, Cipro, gentamicin, phenytoin | Fosphenytoin, sodium bicarbonate, Zosyn, hydrocortisone | Protonix, phenytoin,

Comments per 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 (GAWAS) 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 | Overview of Evidence | Overview of Evidence | Overview of Evidence

Author, year | Design/ sample size | Intervention & Comparison | Outcome

Groetzinger, 2018 | Retrospective review/ n=91 | Ketamine 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, 2018 | Prospective Cohort/ n=703 | Light 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, 2013 | Meta-Analysis/ n= 1,235 patients | Benzodiazepines Vs Non-benzodiazepines | Non-benzodiazepine sedatives associated with ↓ ICU LOS and ↓ Ventilator days

Amini, 2013 | retrospective cohort study/ n=100 | rocuronium-assisted RSI) + PharmD vs rocuronium-assisted RSI) – PharmD | PharmD associated with time to sedation 9 min vs 28 min PharmD associated with time to analgesia 21 min vs 44 min PharmD associated with sedation within 5 min 33% vs 11%

Watt, 2012 | retrospective cohort study/ n=200 | Succinylcholine 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), 2012 | Prospective Cohort/ n=251 | Light 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, 2012 | RCT/ N=498 | Dexmedetomidine 0.2-1.4 mcg/kg/hr Vs Midazolam 0.03-0.2 mg/kg/hr | Lighter sedation, fewer ventilation days

Strom, 2010 | RCT/ n=140 | No sedation ( PRN morphine) vs Propofol or midazolam infusion + (PRN morphine) | No sedation group had ↓ ventilator free days,↓ ICU and↓ hospital LOS