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

 OCT 11TH, 2016  KYLIE BIRNBAUM  CATEGORIES: PRACTICE UPDATES

Authors: Kylie Birnbaum, MD, MA (EM Resident at SUNY Downstate / Kings County Hospital) and James Willis, MD (Associate Residency Director
/ Clinical Assistant Professor at SUNY Downstate / Kings County Hospital) // Edited by: Courtney Cassella, MD (@Corablacas, EM Resident
Physician, Icahn SoM at Mount Sinai) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Intubation is an important intervention in the ED. We see a critical or impending airway problem and we secure the airway with intubation–very
satisfying! Yet our job does not stop there. In addition to maintaining an appropriate ventilation strategy after intubation, it is crucial that we use
appropriate post-intubation sedation and analgesia regimens for the continued care of these critical patients. This post will review sedation and
analgesia regimens for different clinical scenarios after intubation, as well as some common pitfalls that we must be diligent to avoid.

http://www.123rf.com/photo_6276315_secure-
the-airway-with-this-intubation-equipment–
laryngoscope-with-medium-curved-macintosh-
3-blade-.html

Case #1: No analgesia or sedation

It’s a busy weekday shift with many critical patients under your care. You’ve just intubated a 63 year-old man who presented with severe pneumonia
causing hypoxia and altered mental status. His vital signs seem to be improving after intubation when another critical patient comes in. You leave this
newly intubated patient to examine the new patient, only to be called back to the bedside by nursing 15 minutes later. He has become agitated, bucked
the ventilator and self-extubated! You realize then that you forgot to give post-intubation analgesia and sedation.

Mechanical ventilation is painful and stressful, as are the multiple other invasive procedures we tend to do on intubated patients (Foley catheters,
blood draws, CVC insertions, arterial lines, etc.). The psychological stress of these interventions causes anxiety and can lead to PTSD and delirium.
Importantly, psychological stress and pain also have adverse physiologic consequences. Pain and stress increase sympathetic tone, causing a rise in
heart rate, blood pressure, intracranial pressure, and oxygen demands [1,2].

While we may understand why it is important to properly sedate and address pain in ventilated patients, in practice we as EM physicians too often
neglect post-intubation analgesia and sedation. One retrospective study of intubated patients in the ED found that 33% had no anxiolytic, 53% had no
analgesic, and 20% had neither anxiolytic nor analgesic in the peri-intubation period [3]. Another study found that 18% of patients who had received
long-acting neuromuscular blockade in the ED had no concurrent sedation [4]. Providers should be especially diligent in patients receiving a long-
acting paralytic as they are unable to communicate any sort of discomfort. One tip in avoiding these errors is to order the post-intubation
medications while ordering RSI medications. Think about RSI and post-intubation as one event to have everything ordered together, and
communicate this to your nurses.

https://www.hospira.com/en/products_and_services/drugs/FENTANYL_CITRATE

The rst element to address after intubation is the noxious stimuli of mechanical ventilation. Ideally, start with an opioid like fentanyl from the outset
either given with your RSI medications or directly after intubation to control pain early as they wake from the induction. Fentanyl is easy to titrate
with a rapid onset and short duration of action and appropriate for most cases in the ED. Fentanyl works well as an infusion for continuous pain
[ ]
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control, or—if you can be diligent about pain reassessment—you can use fentanyl boluses. [5]

Adequate analgesia alone may be suf cient in certain intubated patients and associated with better outcomes. Research conducted in ICUs
supports the practice of little to no sedation in ventilated patients. Sedation has been associated with increased ICU stays and increased time on
mechanical ventilation [6]. Indeed, while we may not think our sedation choices in the ED will have a prolonged effect, one prospective study has
shown a correlation between the depth of sedation achieved in the ED with prolonged time to extubation and increased mortality [7].

However, little or no sedation is not possible for all patients and may be especially dif cult to avoid within the acute presentation and resuscitation of
these critical patients. ED patients are often undifferentiated and heavier sedation may be necessary while in the ED where diagnostic imaging and
procedures must be performed urgently. So how can we tell who is comfortable and who needs analgesic adjustment or additional sedation? Use an
objective scale, such as the Richmond Agitation Sedation Scale (RASS). Our general goal (depending on clinical situation) is a patient sleeping
comfortably but arousable and opening eyes to verbal command; this correlates to a RASS of -1 to -3 [8, 9].

(http://www.emdocs.net/wp-content/uploads/2016/10/RASS.png)
(From Sessler et al. [9]) In patients with adequate pain control who still seem agitated,

anxious, or ghting the ventilator, add a sedative/anxiolytic. The choice will vary based on the clinical scenario. Guidelines support non-benzodiazepines as the rst choice
for sedation [10]. A meta-analysis of randomized control trials comparing benzodiazepine vs nonbenzodiazepine (propofol and dexmedetomidine) sedation in intubated
ICU patients found the latter associated with reduced ICU length of stay and duration on mechanical ventilation [11]. Benzodiazepines are associated with a higher rate of
delirium and worse outcomes [1].   While propofol and dexmedetomidine have the most research to support this use, ketamine has also shown to be a good non-
benzodiazepine option in appropriate patients [12].

Another pitfall we encounter is polypharmacy—too many drips and medications ordered without enough venous access or nursing support, and
increasing adverse effects with multiple medications. Even in a patient with decent access the multiple infusions and medications ordered may not be
feasible to receive concurrently. Ketamine and dexmedetomidine both have analgesic properties in addition to their sedative properties, making
them an especially good choice for patients who need extra pain control or have limited access.

Let’s review the usual arsenal of sedative medications available in most EDs as a framework for other cases: 

Medication (Initial
Loading Dose)
Properties
Mechanism and HD effects Ideal for
  metabolism

Liver and
Midazolam Benzodiazepine
renal Status
Dose-
metabolism. epilepticus or
dependent
  Pro-GABA Rapid onset, delirium
hypotension
accumulates tremens
with infusion
(0.01-0.05 mg/kg)

Liver Status
Lorazepam Benzodiazepine metabolism. epilepticus or
Propylene Dose- delirium
glycol in dependent tremens with
  Pro-GABA
formulation hypotension decreased
can cause renal
(0.02-0.04 mg/kg) acidosis function

Usually Most
Liver stable; patients with
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Liver stab e; patients with
 
metabolism. hypotension normal liver
Central-acting and function.
Dexmedetomidinealpha-2 agonist bradycardia;
+ analgesia. less often
Increased hypertension Light
  Norepinephrine
interaction, and sedation +
inhibition tachycardia. analgesia,
easier to
(1 mcg/kg) wake decreased
  delirium

Lipophilic,

rapid
  clearance /
arousal,
neuro- Intracranial
Propofol GABA-agonist,
rapid onset protective. Hypotension, pathology,
seizures,
quickly crosses Rarely can decreased
  delirium
blood-brain cause ICP
tremens,
barrier propofol- hypertension
(5mcg/kg/min) related
infusion
syndrome
(PRIS)

  Liver
metabolism.
Sedation +
Ketamine Hypertension
analgesia,
Dissociation
NMDA receptor broncho-
and
  antagonist tachycardia dilation,
analgesia,
refractory
sympathetic hypotension
(0.1-0.5 mg/kg) surge

[1,9,13]

Case #2: Persistent hypotension

77 year-old woman brought in by EMS from a nursing home for lethargy and fever, in severe urosepsis with blood pressure of 78/44, heart rate of 110,
agonal breathing and labs with acute kidney injury. She is intubated in the ED and given aggressive uid resuscitation with minimal improvement in
vital signs, so you prepare for a central line to give her vasopressors. You think that while intubation and CVC insertion may be painful, she can’t afford
to have her pressure drop any more. What are your options for pain control and sedation?

Hypotension shouldn’t prevent you from providing adequate pain control and analgesia. Look for medications with fewer hemodynamic side effects,
but realize you can also start vasopressors. Fentanyl has less hemodynamic instability than other opioids and does not rely on renal clearance,
making it a good analgesic for this situation. Ketamine is also an appropriate choice here for its pro-hemodynamic effects which will not worsen the
hypotension and can actually increase blood pressure [12]. Ketamine has dissociative and analgesic properties allowing extra pain control, plus
amnesia and anxiolysis. Considering how we use it for procedural sedation, this will be a good medication to administer before inserting a central line
and may be suf cient alone for both sedation and analgesia.

https://www.hospira.com/en/products_and_services/drugs/DEXMEDETOMIDINE

Dexmedetomidine, a central alpha-2 agonist and norepinephrine inhibitor, is another possible choice for this patient as it is often hemodynamically
neutral. It can cause hypotension and bradycardia, but these effects are more common when administered as a bolus rather than an infusion [9].
Studies have also shown a biphasic hemodynamic reaction with tachycardia and hypertension observed [13]. The highlight of dexmedetomidine is the
ability to achieve adequate sedation and comfort while maintaining easy arousability and interaction.

Case #3: A very reactive airway

A 21 year-old woman is brought by EMS with a severe asthma attack. She is tachypneic, hypoxic to 85%, speaking in one word sentences, and in
obvious distress. She gets epinephrine, magnesium, steroids, and NIPPV with multiple nebulizer treatments with minimal improvement. You’ve tried
NIPPV but she is not tolerating it. She is tiring out and her oxygen saturation is dropping. You intubate her. What post-intubation meds do you grab
rst?

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http://ketamine.com/ketamine-
overdose/effects-of-a-
ketamine-overdose/

This is a good scenario to reach for ketamine. Ketamine is associated with bronchodilation which will help open reactive airways while providing
sedation and analgesia. It preserves airway re exes which is helpful if you want to try to avoid intubation in the rst place. With intubation however,
higher doses or additional medication is usually needed to allow complete relaxation for ideal ventilator synchrony and for the lower respiratory rate
needed in intubated asthma patients.

Opioids can also be used in this situation for pain, but be aware of the potential side effect of chest wall rigidity. Rigidity is more often described with
high doses of fentanyl and in pediatric patients, but cases have also been reported with standard fentanyl dosing and in adults [14]. It can cause muscle
rigidity affecting the chest wall, which interferes with mechanical ventilation. If you suspect this side effect in concurrence with decreased ventilator
compliance (and lack of another cause like obstruction, tube dislodgement, etc.), stop the opioid and give naloxone. [9,13]

Case #4: Status epilepticus (and/or delirium tremens)

https://www.epilepsysociety.org.uk/news/%20status-
epilepticus-given-new-
de nition-14-01-2016

A 42 year-old man with a history of epilepsy brought in by EMS for generalized tonic clonic seizures. He received midazolam 10mg IM in the eld but
continues seizing now in the ED with EMS stating it has been more than 30 minutes without return to baseline. He does not respond to 2 doses of
lorazepam in the ED. You decide to intubate the patient for refractory status epilepticus. What choices do you have for post-intubation? Note that we
can think of patients with severe alcohol withdrawal and delirium tremens (DTs) in a similar way.

For sedation after seizure intubation there are two good choices: benzodiazepines and propofol. Both medications target excitatory neurons with
GABA-agonist properties, crucial for seizure treatment. Traditionally we reach for benzodiazepines; these are rst line medications to treat both
seizures and DT in addition to being a sedative for the mechanically ventilated patient. Consider starting the patient on a midazolam drip. However, a
patient in refractory status epilepticus or DT that requires intubation will have received very high doses of benzodiazepines so far and receptors may
be saturated without optimal effect. This is especially true for severe DT [5].

An alternative tool is propofol for additional seizure control/continued sedation in refractory status or unstable alcohol withdrawal. Propofol is a
GABA agonist that is lipophilic and quickly crosses the blood-brain barrier, acting within seconds to minutes [9]. It has neuroprotective and anti-
epileptic properties [9,10]. Another bene t is that as quickly as propofol works, it is also rapidly cleared. This makes propofol an excellent sedative
choice in patients that will need neurologic reassessment. Benzodiazepines, on the other hand, accumulate and become long-acting (even “short-
acting” midazolam is only short-acting when given as one bolus—these pharmacokinetics do not hold true for continuous infusions).

Case #5: Intracerebral hemorrhage

Mattiello JA1, Munz

MI i li i l
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1/4/2018 emDOCs.net – Emergency Medicine EducationPost-intubation analgesia/sedation regimens in ED: Pearls & Pitfalls - emDOCs.net - Emergency …
M. Images in clinical
medicine. Four types
of acute post-
traumatic
intracranial
hemorrhage. N Engl J
Med. 2001 Feb
22;344(8):580.

You’ve just intubated a middle aged man with a GCS of 8 found to have a spontaneous intracerebral hemorrhage (ICH) and severe hypertension. You
are arranging transportation to another hospital for de nitive neurosurgical management. What is the best choice of sedative in this case?

First, don’t forget about pain control during mechanical ventilation. For a critically-ill hypertensive patient with ICH, blood pressure control is
important and this must include adequate pain control to prevent increasing sympathetic response and intracranial pressure. Use an opioid like
fentanyl. Second, reach for propofol. We can use the blood pressure lowering effects of propofol to our advantage here, as well as the neuroprotective
effects. This is a patient who would bene t on the deeper end of sedation while waiting for transfer and neurosurgical management, so don’t be afraid
to reach for a heavier sedative like propofol. Additionally, propofol’s rapid clearance to regain consciousness after stopping the infusion will help the
transporting and receiving teams for a quicker neurological assessment. [5, 15]

Conclusion / Take-Home Points

Don’t forget about post-intubation sedation/analgesia. Order these medications with your RSI meds and communicate with your nurses.
Mechanical ventilation hurts and pain control is always primary. Every intubated patient should have adequate analgesia. An objective scale like RASS should be
used to assess additional sedation needs after primary analgesia is started.
Nonbenzodiazepines like ketamine, propofol, and dexmedetomidine are rst-line recommendations for sedation over benzodiazepines and are associated with
better outcomes.
Consider the hemodynamic pro le when choosing medications and don’t neglect analgesia/sedation out of fear for hypotension. Use ketamine for sedation and
analgesia in patients with persistent hypotension. Use propofol for hypertensive patients and primary neurological problems (seizures, delirium tremens,
hemorrhagic stroke, head trauma).

References / Further Reading

[1] Patel SB, Kress JP. Sedation and analgesia in the mechanically ventilated patient. Am J Respir Crit Care Med. 2012;185(5):486-497.

[2] Wood S, Winters ME. Care of the intubated emergency department patient. J Emer Med. 2011; 40(4): 419-427.

[3] Bonomo JB, Butler AS, Lindsell CJ, Venkat A. Inadequate provision of postintubation anxiolysis and analgesia in the ED. Am J Emerg Med.
2008;26:469-472.

[4] Chong ID, Sandefur BJ, Rimmelin DE, et al. Long-acting neuromuscular paralysis without concurrent sedation in emergency care. Am J Emerg Med.
2014; 32:452-456.

[5] Weingart S. EMCrit Podcast #115: A new paradigm for post-intubation pain, agitation and delirium. Jan 13, 2014. http://emcrit.org/podcasts/post-
intubation-sedation-2014/

[6] Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomized trial. Lancet 2010;
75(9713):475-480.

[7] Shehabi Y, Bellomo R, Reade MC, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir
Crit Care Med 2012; 186(8):724-731.

[8] Sessler CN, Gosnell MS, Grap MJ et al. The Richmond agitation-sedation scale: validity and reliability in adult intensive care unit patients. Am J
Resp Crit Care Med. 2002; 186:1338-1344.

[9] Lawner B, Farzad A. Sedation of the mechanically ventilated patient in the Emergency Department. EM Critical Care / EB Medicine. 2014;
(4)2. www.ebmedicine.net

[10] Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive
care unit. Crit Care Med. 2013; 41(1):263-306.

[11] Fraser GL, Devlin JW, Worby CP, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults:
A systematic review and meta-analysis of randomized trials. Crit Care Med. 2013;41(9 Suppl):S30-S38.

[12] Asad EP, Martin JR, Erstad BL. Ketamine for analgosedation in the intensive care unit: a systemic review. J Intensive Care Med. December 2015;
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1/4/2018 emDOCs.net – Emergency Medicine EducationPost-intubation analgesia/sedation regimens in ED: Pearls & Pitfalls - emDOCs.net - Emergency …
epub ahead of print.

[13] Devlin JW, Mallow-Corbett S, Riker R. Adverse drug events associated with the use of analgesics, sedatives, and antipsychotics in the intensive
care unit. Crit Care Med. 2010; 38 (Supplement): S231-S243.

[14] Coruh B, Tonelli MR, Park DR. Fentanyl-induced chest wall rigidity. Chest. 2013; 143(4):1145-1146.

[15] Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H. The experimental and clinical pharmacology of propofol, an anesthetic agent with
neuroprotective properties. CNS Neurosci Ther. 2008; 14(2):95-106.

4 THOUGHTS ON “POST-INTUBATION ANALGESIA/SEDATION REGIMENS IN ED: PEARLS & PITFALLS”

romanov59 (http://gravatar.com/romanov59)
OCTOBER 11, 2016 AT 5:59 PM (HTTP://WWW.EMDOCS.NET/POST-INTUBATION-ANALGESIASEDATION-REGIMENS-ED-PEARLS-PITFALLS/#COMMENT-1592)

Very nice review article. Thanks for the effort

 REPLY (HTTP://WWW.EMDOCS.NET/POST-INTUBATION-ANALGESIASEDATION-REGIMENS-ED-PEARLS-PITFALLS/?REPLYTOCOM=1592#RESPOND)

theresa
OCTOBER 20, 2016 AT 11:29 PM (HTTP://WWW.EMDOCS.NET/POST-INTUBATION-ANALGESIASEDATION-REGIMENS-ED-PEARLS-PITFALLS/#COMMENT-1593)

thanks you.

 REPLY (HTTP://WWW.EMDOCS.NET/POST-INTUBATION-ANALGESIASEDATION-REGIMENS-ED-PEARLS-PITFALLS/?REPLYTOCOM=1593#RESPOND)

Therese Abboud
OCTOBER 22, 2016 AT 9:10 AM (HTTP://WWW.EMDOCS.NET/POST-INTUBATION-ANALGESIASEDATION-REGIMENS-ED-PEARLS-PITFALLS/#COMMENT-1594)

Great article that addresses an mportant topic that is very common nowadays.good job kyle

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Ghazwan
JANUARY 2, 2017 AT 5:30 AM (HTTP://WWW.EMDOCS.NET/POST-INTUBATION-ANALGESIASEDATION-REGIMENS-ED-PEARLS-PITFALLS/#COMMENT-1595)

Amazing topic , I enjoyed the reading

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