Written by: Brian Lin, MD

Edited by: Anand Swaminathan, MD

Posted: August 3, 2016

Updated by: Victor Lei, MD

Edited by: Gregg Chesney, MD

 

Background: The immediate post intubation period in the ED is a critical time for continued patient stabilization. While physical adjuncts like securing the tube, in line suctioning, and head positioning are part of general post intubation management, a better understanding of analgesics and sedatives have offered newer approaches and improved outcomes down the line during the patient’s hospital stay. The reality of ever increasing ED volumes and longer boarding times to the ICU makes it imperative for emergency physicians to learn how to manage these critical patients.

Early Interventions in the ED Can Have an Effect: 

  • The SPICE trial was a multi-center cohort study examining the hospital courses of 251 mechanically ventilated patients. Assessments of the administration of sedative agents, ventilation time and sedation depth via RASS were made. Outcomes measured included delirium and hospital plus 180 day mortality. The authors found that deep early sedation within the first four hours was an independent predictor for delayed extubation and increased mortality. (Shehabi 2012)
  • The multi-center cohort ED-SED study examined 324 mechanically ventilated patients. It was found that patients exposed to deep sedation in the ED had an independent higher incidence of continued deep sedation on ICU day one (Fuller, 2019).

Analgesia: 

Rapid Sequence Intubation (RSI) provides paralysis and amnesia to the patient during the process of endotracheal intubation however analgesia is typically not administered peri-intubation. Immediately following intubation, it is important to address analgesia as part of the post-intubation management.

  • Endotracheal tubes are painful
    • A study measuring hemodynamic and respiratory variables during endotracheal suctioning showed a significant increase in RASS scores, systolic, and diastolic blood pressure in mechanically ventilated patients in patients receiving sedation only when compared to patients also receiving analgesia (Jeitziner 2012)
  • Not all mechanically ventilated patients require sedatives.
    • A randomized controlled trial of 140 patients compared a protocol of analgesia alone (Morphine IV bolus) versus sedation + analgesia (Propofol/Midazolam IV infusion + Morphine IV bolus). Patients in the analgesia only group had statistically significantly more days without mechanical ventilation and on average shorter ICU length of stays. (Strom 2010)
    • Non-opiate adjuncts such as acetaminophen, intravenous lidocaine, ketamine infusion, and neuropathic medications may all improve pain relief and decrease opiate requirements and should be considered in addition to opiates for appropriate patients.
Analgesic Onset Elimination Half Life IV Infusion Rates Side Effects and Other Information
Fentanyl 1 – 2 min 2 – 4 hr 0.7 – 10 μg/kg/hr Rapid onset. Lipophilic with adipose deposition, withdrawal symptoms after prolonged infusion
Hydromorphone 5 – 15 min 2 – 3 hr 0.5 – 3 mg/hr No active metabolites however parent drug can accumulate in renal failure
Morphine 5 – 10 min 3 – 4 hr 2 – 30 mg/hr Active metabolites can accumulate in renal failure
Remifentanil 1 – 3 min 3 – 10 min Loading dose: 1.5 μg/kg IV
Maintenance dose: 0.5 – 15 μg/kg/hr		 Rapid onset. Short acting. Not affected by hepatic or renal failure. Associated with development of hyperalgesia
Ketamine*

(subdissociative pain dose is lower than infusion dose used for sedation)

 30-40 sec 2 – 3 hr Loading dose 0.1 – 0.5 mg/kg IV followed by 0.05 – 0.4 mg/kg/hr Attenuates the development of acute tolerance to opioids. Can cause hallucinations and other psychological disturbances.

Adapted from Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Critical Care Medicine 2018

Sedation: 

After absence of pain is ensured, pharmacologic sedation may be indicated to help relieve discomfort, improve synchrony with mechanical ventilation and decrease oxygen requirements and overall work of breathing. (Patel 2012)

  • Peri and Immediate Post Intubation Sedation
    • When using a long-acting paralytic (rocuronium and vecuronium), it is essential to provide a sedative and amnestic through the duration of the paralysis.
  • Assessing the Sedated Patient
    • Goal in the emergency department should be to titrate to light sedation as objectively measured by a validated scale like the Richmond Agitation-Sedation Scale (RASS)
    • Patients in the immediate post-intubation period may require escalating doses to control initial agitation and assist in ventilator tolerance and synchrony and may require deeper levels of sedation initially

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Richmond Agitation Sedation Scale (RASS) – resus.com.au

  • Light Sedation vs Deep Sedation
    • Various studies have shown detrimental effects of prolonged deep sedation including longer mechanical ventilation times, 6 month mortality and increased incidence of delirium (Shehabi 2013).
    • Depth of sedation should be regularly assessed in the emergency department
    • When clinically appropriate, sedation should be titrated to achieve light sedation (RASS 0 to -2) as early as possible in the emergency department

Pharmacology of Sedative Medications

Agent Onset Elimination Half Life  Loading Dose (IV)  Usual Maintenance Dose (IV)  Side Effects and Other Information
Midazolam 2 – 5 min 3 – 11 hr 0.01 mg – 0.05 mg/kg over several minutes 0.02 – 0.1 mg/kg/hr Respiratory depression, hypotension
Lorazepam 15 – 20 min 8 – 15 hr 0.02 – 0.04 mg/kg 0.01 – 0.1 mg/kg/hr Respiratory depression, hypotension; nephrotoxicity, propylene glycol toxicity
Diazepam 2 – 5 min 20 – 120 hr 5-10 mg 0.03 – 0.1 mg/kg Respiratory depression, hypotension, phlebitis
Propofol 1 – 2 min Short term ~ 3- 12 hr
Long term ~ 50 + 18.6 hr		 5 μg/kg/min over 5 min 5 – 50 μg/kg/min Pain on injection, hypotension, respiratory depression, hypertriglyceridemia, pancreatitis, propofol related infusion syndrome
Dexmedetomidine 5 – 10 min 1.8 – 3.1 hr No bolus 0.2 – 0.7 (up to 1.5) μg/kg/hr Bradycardia hypotension, loss of airway reflexes
Ketamine 1 – 2 min ~80 mins 0.5 – 1 mg/kg 0.5 – 4 mg/kg/hr Hypertension, hypersalivation, agitation, emergence reactions, transient respiratory depression

Adapted from Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Critical Care Medicine 2013

  • Nonbenzodiazepines vs benzodiazepines for sedation
    • SCCM PADIS guidelines recommended a preference for infusions of nonbenzodiazepine sedatives (propofol, dexmedetomidine) over benzodiazepine infusions (midazolam or lorazepam) as some trials have demonstrated that benzodiazepines may be associated with longer mechanical ventilation, longer time to light sedation, and higher rates of delirium.
    • With studies suggesting that early onset analgosedation affects downstream ICU outcomes, we suggest that this concept should also be applied in the ED.
    • Benzodiazepines may still be considered in the appropriate patient such as resistant alcohol withdrawal or refractory seizures.
  • Propofol vs dexmedetomidine
    • Propofol is a highly lipophilic GABA-agonist that rapidly crosses the blood brain barrier to provide sedation.
    • Dexmedetomidine is a centrally acting α-2 agonist sedative that provides light sedation without respiratory depression.
    • Two recent high profile RCTs comparing propofol to dexmedetomidine demonstrated no difference in outcomes between the two medications.
    • The SPICE III trial was multicenter RCT of nearly 4000 patients comparing dexmedetomidine as the primary sole sedation agent versus usual care (propofol or midazolam or both) and demonstrated no difference in 90-day (primary outcome) or 180-day mortality. 74% of patients in the dexmedetomidine arm required additional sedation (with propofol or midazolam or both) because sedation goals were not met with dexmedetomidine alone and dexmedetomidine was associated with high rates of bradycardia and hypotension (Shehabi 2019).
    • The MENDS2 trial was a multicenter double blind RCT with 422 patients comparing sedation with dexmedetomidine versus propofol for mechanically ventilated patients with sepsis and demonstrated no differences in any outcomes such as number of days alive without delirium or coma, ventilator-free days, and death at 90 days, with no difference in safety outcomes. Patients in this trial were on relatively low doses of both dexmedetomidine and propofol and higher doses of fentanyl which may limit the ability to adequately compare the two agents well (Hughes 2021).
    • Given the lack of outcome difference, the longer time to onset of peak effect, frequently inadequate level of sedation, and the risk of hypotension and bradycardia, propofol may be a more practical choice of sedative in the emergency department when clinically appropriate.
  • Ketamine 
    • NDMA antagonist that provides analgesia as well as dissociative sedation, tends to afford hemodynamic stability
    • May be used as a primary or adjunctive sedation agent for continuous infusion
    • Well demonstrated to be safe and effective in retrospective studies but a lack of prospective RCTs evaluating its use
    • When used as an adjunctive sedative has been shown in a multicenter retrospective review, when used as an adjunct, patients receiving ketamine achieved pain and sedation goals more often and had decreased requirements for opiates and for other sedative medications (Groth 2022).

Take Home Points

  1. Employ an analgesic-first approach to post intubation pharmacologic management to ensure that pain is adequately addressed.
  2. Once pain is addressed, additional sedation may be needed. If sedation is needed, after initial sedation goals are met (e.g. ventilator synchrony), sedation dosing should be titrated early to target light sedation (RASS 0 to -2) and degree of sedation should be routinely assessed.
  3. When using a long-acting paralytic for induction for intubation, ensure sedation and amnesia for the duration of paralysis.
  4. We recommend considering fentanyl plus propofol or dexmedetomidine as the routine first options for the choice of analgosedation agents in the emergency department. Propofol may often be preferable in the emergency department due to its rapid onset, ease of titration, and reliable capacity for sedation.

Read More

emDocs: Post-intubation analgesia/sedation regimens in ED: Pearls & Pitfalls

PulmCrit: Internet Book of Critical Care: Sedation

References

Barr J, Gilles L, Puntillo K, et al: Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Critical Care Medicine 2013; 41: 263-295 PMID: 23269131

Jeitziner MM, Schwendimann R, Hamers JP, et al: Assessment of pain in sedated and mechanically ventilated patients: An observational study. Acta Anaesthesiol Scand 2012; 56: 645-654 PMID: 22404146

Patel S, Kress J: Sedation and Analgesia in the Mechanically Ventilated Patient: Am J Respir Crit Care Med 2012; 185: 486-497 PMID: 22016443

Shehabi Y, Bellomo R, Reade M, et al: Early Intensive Care Sedation Predicts Long-Term Mortality in Ventilated Critically Ill Patients. Am J Respir Crit Care Med 2012; 186: 724-731 PMID: 22859526

Shehabi Y, Chan L, Kadiman S, et al: Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators: Sedation depth and long-term mortality in mechanically ventilated critically ill adults: A prospective longitudinal multicenter cohort study. Intensive Care Med 2013; 39: 910-918 PMID: 23344834

Strom T, Martinussen T, Toft P: A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomized trial. The Lancet 2010; 375: 475-480 PMID: 20116842

Fuller BM, Roberts BW, Mohr NM, et al: The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients. Crit Care Med. 2019 Nov;47(11):1539-1548. PMID: 31393323; PMCID: PMC7323907.

Shehabi Y, Howe BD, Bellomo R, Arabi YM, et al: Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. PMID: 31112380.

Hughes CG, Mailloux PT, Devlin JW, et al: Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021 Apr 15;384(15):1424-1436. PMID: 33528922.

Groth CM, Droege CA, Connor KA, et al: Multicenter Retrospective Review of Ketamine Use in the ICU. Crit Care Explor. 2022 Feb 10;4(2):e0633. PMID: 35187497