Introduction
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.
Key Points
- The immediate post-intubation period in the ED is a critical time for continued patient stabilization.
- Do not let an ongoing paralytic mask the need for sedation — a still patient may still be in pain or distress.
- An analgesia-first (analgosedation) approach can be built from common agents reviewed here.
- The cited evidence favors lighter over deeper sedation and non-benzodiazepine strategies.
Clinical Detail
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. The agents below summarize dosing, pharmacokinetics, and safety considerations for common post-intubation analgesia and sedation options.
| Parameter | 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 | CYP3A4 inhibitors, serotonergic agents | Bupivacaine, St. John’s Wort | CYP3A4 inhibitors, CNS depressants | CNS depressants and antihypertensive |
| Compatibility | Protonix | Calcium chloride, Nimbex, Cipro, gentamicin, phenytoin | Fosphenytoin, sodium bicarbonate, Zosyn, hydrocortisone | Protonix, phenytoin |
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 discontinued 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 days, ↓ ICU LOS, and ↓ hospital LOS |
Conclusions
- The immediate post-intubation period is a critical time for continued stabilization, and providing analgesia and sedation is key to preventing patient awareness during paralysis and preventing PTSD.
- Do not let an ongoing paralytic mask the need for sedation: a still patient may appear to tolerate the ventilator while remaining aware, so analgesia and sedation should not be withheld simply because the paralytic is still working.
- An analgesia-first (analgosedation) approach can be built from common agents reviewed here, fentanyl, propofol, midazolam, and dexmedetomidine, selected by their dosing, pharmacokinetics, adverse effects, and compatibility.
- The cited evidence favors lighter over deeper sedation and non-benzodiazepine strategies, and pharmacist involvement at the bedside was associated with faster time to post-intubation sedation and analgesia.
References
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.
Source Artifact
No pain to keep em sane. Post-Intubation Sedation in RSI Pharmacy Friday 08_6_2022.docx (local DOCX source artifact; public source link pending)No pain to keep em sane. Post-Intubation Sedation in RSI Pharmacy Friday 08_6_2022.pdf
A short weekly clinical Pearl for acute care pharmacists.
Get the Friday Pearl email
Get a short weekly clinical Pearl for acute care pharmacists. No spam.
Free forever. Unsubscribe anytime. No spam.