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Rapid Sequence Intubation in Traumatic
Nicholas Kramer , David Lebowitz , Michael Walsh , Latha Ganti
1. Emergency Medicine, University of Central Florida 2. University of Central Florida College of Medicine
3. Pharmacy, University of Central Florida 4. Clinical Sciences, University of Central Florida
Corresponding author: Nicholas Kramer, firstname.lastname@example.org
Disclosures can be found in Additional Information at the end of the article
Deciding on proper medication administration for the traumatic brain injury (TBI) patient
undergoing intubation can be daunting and confusing. Pretreatment with lidocaine and/or
vecuronium is no longer recommended; however, high-dose fentanyl can be utilized to help
blunt the sympathetic stimulation of intubation. Induction with etomidate is recommended;
however, ketamine can be considered in the proper patient population, such as those with
hypotension. Paralysis can be performed with either succinylcholine or rocuronium, with the
caveat that rocuronium can lead to delays in proper neurological examinations due to
prolonged paralysis. Recommendations for post-intubation continuous sedation medications
include a combination propofol and fentanyl in the normotensive/hypertensive patient
population. A combination midazolam and fentanyl or ketamine alone can be considered in the
Categories: Anesthesiology, Emergency Medicine
Keywords: rapid sequence intubation, traumatic brain injury (tbi), intubation, ketamine, emergency
medicine, rocuronium, succinylcholine, pretreatment, induction agents, intracranial pressure
Introduction And Background
Rapid sequence intubation (RSI) in the patient with traumatic brain injury (TBI) is a changing
area of research. Airway control is essential for patients with TBI, as hypoxemia and
hypercarbia lead to significant morbidity and mortality. However, we must take into
consideration the fact that RSI also has the potential to worsen brain injury. The simple but
essential act of laryngoscopy and placing of the endotracheal (ET) tube may stimulate the dense
sympathetic and parasympathetic network traversing the pharynx and trachea. In addition to
risks posed directly by the gag and cough reflex, sympathetic stimulation can cause an
increased heart rate (HR), increased blood pressure (BP), and increased intracerebral pressure
(ICP), while parasympathetic stimulation may trigger bronchospasm. It has been shown that
the act of laryngoscopy alone increases systolic blood pressure (SBP) by a mean of 20 mmHg [1-
2]. The effect on ICP has not been studied directly, but endotracheal suctioning has been shown
to increase ICP by a minimum of 5 mmHg [3-4]. The increase in ICP from the sympathetic surge
can cause an increase in cerebral blood volume, cerebral edema, and development of worsening
hemorrhage or hematoma [5-6]. In addition, we must balance this against the risk of
hypotension, as this can also increase both mortality and brain injury. Sedation carries many of
the same concerns in addition to the needs to minimize anxiety, prevent agitation, allow
manipulation of mechanical ventilation, and facilitate neurological assessments . In this
article, the authors explore the latest adult literature and summarize the data regarding agents
for pretreatment, induction, paralysis, and sedation with the goal of preventing secondary
1 2 3 4
Open Access Review
Article DOI: 10.7759/cureus.2530
How to cite this article
Kramer N, Lebowitz D, Walsh M, et al. (April 25, 2018) Rapid Sequence Intubation in Traumatic Brain-
injured Adults. Cureus 10(4): e2530. DOI 10.7759/cureus.2530
Lidocaine has historically been used as a pretreatment in TBI as it was believed to lessen the
sympathetic stimulation associated with RSI. However, evidence has been mixed. Two small
studies have shown that lidocaine minimized an increase in ICP during neurosurgical
procedures  or ET suctioning , while three studies showed no benefit during RSI [10-11] or
ET suctioning . Due to a lack of evidence in blunting ICP, weighed with the risk of potential
side effects including hypotension , experts now recommend against using lidocaine for
pretreatment in RSI for TBI [6, 14].
Defasciculating Dose of a Non-Depolarizing Agent
Pretreating with a low dose of a non-depolarizing agent, such as vecuronium, theoretically may
blunt the rise in ICP due to muscle fasciculations when succinylcholine is used for RSI. There is
strong evidence that succinylcholine increases ICP in patients undergoing neurosurgery for
brain tumors (Marsh ML et al.: Succinylcholine-intracranial pressure effects in neurosurgical
patients (Abstract). Anesth Analg 1980; 59: 550-1) and that a defasciculating dose of a non-
depolarizing agent reduced increases in these select patients [15-16]. However, there are
multiple small studies that suggest that succinylcholine does not increase ICP in head-injured
patients and no studies that demonstrate that a non-depolarizing agent would affect ICP in
these patients . The current recommendation is against the use of a defasciculating dose of
a non-depolarizing agent in TBI patients undergoing RSI with succinylcholine .
Several studies demonstrate that fentanyl attenuates rises in BP and HR in RSI [18-20]. By
decreasing the cardiovascular response of sympathetic stimulation, fentanyl is thought to blunt
increases in ICP related to laryngotracheal stimulation in RSI. One study by Kim et
al. compared remifentanil versus lidocaine for attenuating the hemodynamic response during
RSI. It found that lidocaine (at 1.5 mg/kg) had no effect, whereas remifentanil (at 1 mcg/kg) did
blunt the hemodynamic response associated with RSI . Fentanyl (at 2-3 mcg/kg) is currently
recommended for neuroprotection in patients with increased ICP .
Etomidate is well liked in the RSI world due to its mild hemodynamic profile [22-26]. This is
particularly true during RSI in TBI, as a drop in mean arterial pressure (MAP) will cause a
decrease in the cerebral perfusion pressure (CPP). In addition, etomidate has been shown to
decrease cerebral blood flow and cerebral metabolic demand, all while preserving CPP . One
downside to this drug is that it has no analgesic properties; thus, neuroexcitation can be a
concern if not properly mitigated .
Like etomidate, ketamine is exceptionally hemodynamically stable [28-29] but has the added
benefit of possessing analgesic properties. Despite this, ketamine has been generally
contraindicated for use in patients with TBI due to concerns of sympathetic stimulation,
2018 Kramer et al. Cureus 10(4): e2530. DOI 10.7759/cureus.2530 2 of 10
leading to an increase in the ICP. A study by Filanovsky et al. in 2010 examined the origins of
this practice and determined that many of the studies that concluded that ketamine increased
ICP were from the 1970s and were of questionable quality . Additionally, ketamine may, in
fact, be neuroprotective due to an increase in MAP and CPP [30-31], without increasing cerebral
oxygen consumption or reducing regional glucose metabolism [32-33]. In a 2016 retrospective
study of 968 adult trauma patients who underwent RSI with using either etomidate or ketamine,
the authors found no difference in mortality or other patient-centered outcomes between the
two induction agents . In the 2011 Update from American College of Emergency Physicians
(ACEP) Clinical Practice Guidelines for Ketamine Sedation, head trauma is no longer a relative
contraindication, though ketamine remains relatively contraindicated for patients with central
nervous system masses, abnormalities, or hydrocephalus . Ketamine may best be suited for
use in TBI patients with normal to low BP due to its potential for increasing the MAP and CPP
Succinylcholine is a depolarizing neuromuscular blocking agent with rapid onset and offset
properties. The rapid offset is beneficial as it allows for early neurological examinations.
Concerns have been raised over the theory that muscle fasciculations could lead to increased
ICP in these delicate patients; however, a 2001 study summarized the available literature on
this subject and, though limited, concluded that the evidence does not support the hypothesis
that succinylcholine causes an increase in ICP for head-injured patients .
Strong opinions exist when comparing succinylcholine to rocuronium. While a large systematic
review demonstrated superior intubating conditions when using succinylcholine , it is likely
the agents are nearly identical in clinical practice . In 2015, the Cochrane database
investigators updated a previous review of RSI medications to include 11 additional studies to
the previous 37 randomized controlled trials (RCT) and controlled clinical trials analyzed in
2008 . Overall, the reviewers found succinylcholine was superior to rocuronium at achieving
both acceptable intubating conditions and excellent intubating conditions when
succinylcholine was dosed at least 1 mg/kg and rocuronium was dosed at least 0.6 mg/kg for
RSI. However, further analysis revealed no statistical difference in intubation conditions when
succinylcholine was compared to rocuronium dosed at 1.2 mg/kg.
While the majority of studies comparing succinylcholine to rocuronium have evaluated their
effect on intubation conditions for RSI, intubation conditions may not necessarily translate into
success of intubation or the number of intubation attempts required. In 2011, a retrospective
study of all RSIs performed using succinylcholine or rocuronium was collected from a tertiary
care emergency department over 15 months . Of the total 327 RSIs performed, the rate of
first attempt intubation success was similar between the succinylcholine and rocuronium
groups (72.6% vs. 72.9%, p = 0.95). While the results of this study found the two paralytic agents
to be equivalent with regard to first attempt intubation, the median dose of rocuronium used
was 1.19 mg/kg (interquartile range (IQR) = 1 - 1.45 mg/ kg). The authors of the study concluded
that higher doses of rocuronium may be necessary to achieve the equivalent effects of
succinylcholine. A 2016 retrospective cohort study of 233 TBI patients requiring intubation in
the emergency department was performed to help fill an important gap in the literature on the
preferred paralytic for RSI in patients with TBI . Patients either received succinylcholine or
rocuronium to facilitate RSI. The two patient groups were similar and shared the same mortality
rate of 23%. For patients with a low head Abbreviated Injury Scale (AIS) severity (AIS 0 to 3),
there was no difference in mortality between the two groups. However, for patients with a high
2018 Kramer et al. Cureus 10(4): e2530. DOI 10.7759/cureus.2530 3 of 10
head AIS score (4 to 6), succinylcholine was associated with increased mortality compared with
rocuronium (44% vs 23%, odds ratio (OR) 4.10, 95% confidence interval (CI) 1.18 - 14.12; p =
0.026). This was the first comparative study between succinylcholine and rocuronium to
evaluate their effects on mortality in TBI patients. While succinylcholine use for RSI in patients
with severe TBI was associated with increased mortality, it may not be possible to discriminate
which patients are likely to benefit from avoiding succinylcholine at the time of presentation.
Prospective clinical trials would help confirm these findings.
Due to its long duration of action, sustained paralysis with rocuronium can prevent repeat
neurologic assessments. Patients receiving rocuronium have also been shown to receive less
sedation and analgesia in the immediate post-intubation phase because the induced paralysis
may make it appear as if they are calm and sedated . A recent study published in 2015 found
the average time to sedation in patients who received rocuronium for RSI was 55 minutes .
Considering the elimination half-life of etomidate, ketamine, and propofol are all less than 15
minutes, this reveals an alarmingly high incidence of patients paralyzed after RSI but without
sedation. Additionally, care needs to be taken if opioids are used as remifentanil may delay the
onset of paralysis by 30 - 45 seconds . Currently, there is not enough data to recommend
rocuronium over succinylcholine for RSI in TBI.
Propofol is advantageous over other medications in this category in that it as a rapid onset of
action and short duration of action. This allows the effects to be rapidly eliminated from the
patient, allowing for neurological examination, and then quickly titrated back to full effect. Care
must be taken when selecting propofol in the hypotensive patient as it may lower the patient’s
MAP, decreasing the body’s ability to maintain cerebral blood flow. Propofol’s cerebrovascular
effects result in a reduction of episodes of intracranial hypertension (in the continuously
monitored patient), and while there is some evidence that this agent may have neuroprotective
effects in cases of mild TBI, this result has not been demonstrated in moderate to severe cases
[41-42]. Finally, it must be noted that propofol has no analgesic effect, necessitating the use of
additional medications for pain and comfort.
Midazolam boasts a relatively neutral hemodynamic profile, though some have raised concerns
regarding its potential to lower systemic BP and thus, CPP . Midazolam has a relatively fast
onset and offset of action initially (half-life one hour), though tissue accumulation over time
may result in delayed awakening. This effect may be the reason that midazolam has been
associated with prolonged coma, increased ventilator days, and more ICU days when compared
to propofol . Midazolam’s additional benefits to the patient include its anxiolytic and
anticonvulsant properties . In a comparison study by Sandiumenge et al. , no significant
difference was noted between midazolam and propofol in regard to a decrease in ICP and both
agents demonstrated similar CPP. Analogous to propofol, midazolam also lacks analgesic
properties and thus, is often paired with an opioid (such as fentanyl).
Fentanyl is a commonly utilized medication for analgesia after intubation, though it lacks
appropriate sedation properties. As discussed above, attenuating pain may benefit the patient
by minimizing the sympathetic response of elevated MAP and HR. While the hemodynamic
properties of fentanyl are thought to be relatively neutral compared to other opioids, multiple
2018 Kramer et al. Cureus 10(4): e2530. DOI 10.7759/cureus.2530 4 of 10
studies have shown that bolus doses produce clinically significant increases in ICP, while
decreasing MAP and CCP [45-46]. Thus, care must be taken to utilize the minimal appropriate
dose for these patients. Fentanyl has a short duration of action, when given intravenously (IV),
with the analgesic effect lasting approximately 30 - 60 minutes. Remifentanil is an ultra-short-
acting opioid with analgesic effects lasting five to 10 minutes, which may allow for earlier neuro
checks than fentanyl .
As discussed above, ketamine has historically been avoided in TBI patients due to the concern
over raising the ICP. This dogma has been shown to be based on little, poorly conducted
research from the 1970s. More recent studies have countered this data and shown that
ketamine may have beneficial properties when utilized in the appropriate patient population
[30-33, 48]. In a small study of eight TBI patients under propofol sedation, the addition of
ketamine had no effect on HR, MAP, or CPP, while demonstrating the beneficial effect of
lowering ICP . Additionally, ketamine has the unique property of simultaneous sedation
and analgesia, which may minimize the need for additional medications. Ketamine has a
relatively long half-life at 2.5 hours, which limits the ability for neurological checks. As
discussed in the Induction section, ketamine may best be utilized in TBI patients with normal
to low BP as it may increase the patient’s MAP and CPP .
RSI in the TBI patient is complex. The coordinated stages of pretreatment, induction, paralysis,
sedation, and analgesia each present their own benefits and pitfalls. Much of this information
is based on theoretical risks and benefits, as large randomized case-control studies looking at
specific questions of interest with patient-centered outcomes are scarce, inadequate, or non-
existent at this time.
The fundamental aim of our recommendations is to limit secondary brain injury due to RSI as
measured by neurologic outcomes and mortality. When these indicators are not available, we
focus on the effects on MAP, ICP, and CPP to the best of our current knowledge. A protocol for
RSI in the TBI patient can be broken down into two arms: the hypotensive patients and the
normotensive/hypertensive patients. We believe that the medication choices in these two
groups should differ significantly as the cerebrovascular effects are diverse.
The authors recommend no pretreatment medications in the hypotensive group. In the
normotensive/hypertensive population, fentanyl IV bolus (2-3 mcg/kg) 3 minutes prior to
induction is recommended. Fentanyl has been shown to blunt the sympathetic response of
elevated MAP and HR during RSI. While fentanyl is relatively hemodynamically neutral, it does
have the potential to decrease MAP and CCP when given at bolus doses [45-46]. This is why we
recommend it as pretreatment only in the patients where hypotension is not a significant
concern. Lidocaine and low-dose non-depolarizing agents are not recommended by current
guidelines as the most recent evidence does not support their use.
For induction, the authors recommend ketamine in the hypotensive group and etomidate in the
normotensive/hypertensive group. The previously held beliefs that ketamine was
contraindicated in RSI have been successfully dispelled, and the most recent evidence suggests
that it can be neuroprotective without increasing cerebral oxygen consumption or reducing
2018 Kramer et al. Cureus 10(4): e2530. DOI 10.7759/cureus.2530 5 of 10
regional glucose metabolism [30-31]. Ketamine may have sympathetic stimulation properties
which lead to an increase in MAP and CPP; thus, the authors only recommend it in the
For the normotensive/hypertensive group, we believe the best induction medication is
etomidate. Etomidate’s mild hemodynamic profile, along with evidence that it may decrease
cerebral blood flow and cerebral metabolic demand while preserving CPP , makes it a strong
candidate for this patient population.
The authors recommend succinylcholine as the paralytic agent of choice for both categories in
our RSI protocol. Concerns regarding fasciculations and increased ICP with succinylcholine use
have not been shown to be valid in the literature . Succinylcholine’s rapid offset is
exceptionally beneficial as it permits early neurological examinations. Rocuronium is gaining
some traction for RSI in the TBI patient; however, with its prolonged duration of paralysis and
limited data supporting its use over succinylcholine, we cannot yet recommend its use, except
when succinylcholine is contraindicated.
A systematic review from 2011 of many of the commonly used agents for sedation in TBI,
including propofol, ketamine, etomidate, and agents from the opioid, benzodiazepine, α-2
agonist, and antipsychotic drug classes, concluded that no drug was superior in terms of
neurological outcomes or mortality in the general traumatic brain injured patient .
Regardless, we believe that certain populations may benefit from one medication over another,
though more research is certainly required.
In the hypotensive patient, we suggest a combination of midazolam and fentanyl, as this
pairing has limited hemodynamic effects while simultaneously owning relatively short half-
lives. Ketamine may be considered for this population as well, as its sympathetic effects may
slightly elevate the MAP. However, ketamine has a relatively long duration of action which will
limit neurological checks.
For the normotensive/hypertensive patient, our protocol calls for propofol and fentanyl.
Propofol has the potential to lower the MAP further than other agents in this class, which may
be beneficial in the hypertensive patient. Additionally, propofol may have neuroprotective
effects in cases of mild TBI . Fentanyl is added for comfort and may further benefit the
hypertensive patient by blunting the sympathetic response to pain. Remifentanil may be
substituted for fentanyl as the two medications have similar hemodynamic effects, with
remifentanil allowing for a much more rapid offset of action for neurological checks.
Our recommendations, based on the above evidence, are summarized in Figure 1.
2018 Kramer et al. Cureus 10(4): e2530. DOI 10.7759/cureus.2530 6 of 10
FIGURE 1: Summary Recommendations
Medication administration for RSI in the patient with TBI is controversial and still not
definitive. Patients with TBI are very sensitive to changes in hemodynamics; hence, adverse
events can occur with improper medication administration. Further research and randomized
control trials are needed to make formal recommendations.
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors
declare the following: Payment/services info: All authors have declared that no financial
support was received from any organization for the submitted work. Financial relationships:
All authors have declared that they have no financial relationships at present or within the
previous three years with any organizations that might have an interest in the submitted work.
Other relationships: All authors have declared that there are no other relationships or
activities that could appear to have influenced the submitted work.
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