World J Surg

DOI 10.1007/s00268-016-3712-x

SURGICAL SYMPOSIUM CONTRIBUTION

Collective Review of the Status of Rapid Sequence Intubation

Drugs of Choice in Trauma in Low- and Middle-Income Settings
(Prehospital, Emergency Department and Operating Room
Setting)
Leressè Pillay1,2 • Timothy Hardcastle3,4

Ó Société Internationale de Chirurgie 2016

Abstract
Introduction Establishing a definitive airway in order to ensure adequate ventilation and oxygenation is an important
aspect of resuscitation of the polytrauma patient .
Aim To review the relevant literature that compares the different drugs used for rapid sequence intubation (RSI) of
trauma patients, specifically reviewing: premedication, induction agents and neuromuscular blocking agents across
the prehospital, emergency department and operating room setting, and to present the best practices based on the
reviewed evidence.
Method A literature review of rapid sequence intubation in the trauma population was carried out, specifically
comparison of the drugs used (induction agent, neuromuscular blocking drugs and adjuncts).
Discussion Studies involving the comparison of drugs used in RSI in, specifically, the trauma patient are sparse. The
majority of studies have compared induction agents, etomidate, ketamine and propofol, as well as the neuromuscular
blocking agents, succinylcholine and rocuronium.
Conclusion There currently exists great variation in the practice of RSI; however, in trauma the RSI armamentarium
is limited to agents that maintain hemodynamic stability, provide adequate intubating conditions in the shortest time
period and do not have detrimental effects on cerebral perfusion pressure. Further, multicenter randomized controlled
studies to confirm the benefits of the currently used agents in trauma are required.

Introduction

Rapid sequence intubation (RSI) is an intubating technique

& Leressè Pillay
leresse@gmail.com
1
Department of Anaesthetics, Inkosi Albert Luthuli Central
Hospital, Mayville, Durban, KwaZulu-Natal, South Africa
2
Division of Anaesthesiology and Critical Care, University of
KwaZulu-Natal, Durban, South Africa
3
Trauma Unit, Inkosi Albert Luthuli Central Hospital, 800
Vusi Mzimela Rd, Mayville, Durban 4058, KwaZulu-Natal,
South Africa
4
Trauma Training Unit, Department of Surgical Sciences,
University of KwaZulu-Natal, Durban, South Africa
aimed at minimizing the risk of aspiration and is employed
in the emergency management of trauma patients. Rapid
establishment of a definitive airway to provide adequate
oxygenation and ventilation in the severely injured trauma
patient has been shown to favorably alter outcomes [1],
whereas there is a demonstrable association between
delayed intubation and increase mortality [2]. The main
aim of this technique is to minimize the duration between
the loss of patients’ airway reflexes and tracheal intubation.
Over the years, the practice of RSI has evolved, with a
resultant wide variation, among clinical practitioners, in
how it is performed and what drugs are utilized [3].

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 World J Surg

Whatever technique is used, the important principles

include: (1) pre-oxygenation, (2) administration of suffi-
cient, predetermined doses of intravenous induction agent
and neuromuscular blocking agent, (3) rapid intubation and
confirmation of placement [4].
Trauma patients, as well as being at risk for aspiration,
may also have factors such as hypotension, hypoxemia,
distortion of airway anatomy and cervical spine injuries
which further complicate airway management. In lower-
and middle-income countries (LMICs) settings, a further
challenge faced is a delay in transporting these patients to a
specialized trauma unit or hospital. This has led to more
RSI being performed by paramedics and emergency
department doctors. Concerns regarding patient safety and
the potential for the occurrence of adverse events highlight
the need for clear and definitive guidelines or institutional
protocols, in order to facilitate training of individuals
performing RSI and improvement of quality of care [5].

Methods Fig. 1 Flow diagram representing studies that were included/ex-

A literature search was conducted via MEDLINE, Google
Scholar, ScienceDirect, BioMed Central, Directory of
Open Access Journals, African Journals Online—Africa
Sanguine, www.opengrey.eu and www.greylit.org for rel-
evant articles. Keywords included: rapid sequence intuba-
tion, trauma, lower- and middle-income countries,
prehospital, emergency department and operating room.
Articles were excluded if they presented information about
RSI in predominantly non-trauma patients, elective surgery
or mainly pediatric patients. Only relevant articles from the
last 15 years have been included. References from review
articles were also examined to identify articles missed. In
addition, textbooks in Anesthesiology were also reviewed.
A total of 45 articles were identified. Thirty articles were
excluded based on the inclusion/exclusion criteria previ-
ously mentioned. Fifteen articles were finally identified as
eligible for use in this systematic review as shown in
Fig. 1. Of the 15 articles, 9 were prospective, 3 were ret-
rospective and 3 were systematic reviews.
The aim of this review is to critically evaluate the evi-
dence that compares the various drugs used in trauma
patients undergoing RSI in the prehospital, emergency
department (ED) and intensive care unit (ICU) and provide
a guideline to assist in selection of the most appropriate
drug(s) to use in RSI.
Results
Table 1 provides an overview of the evidence examined
and a brief summary of the results of each study.
cluded based on the search criteria
Discussion
Induction agent
An ideal induction agent should be easy to administer, have
a rapid onset of action, predictable dose–response rela-
tionship and short duration of action. It should produce
good intubating conditions without compromising the sta-
bility of already vulnerable organ systems (i.e., cardio-
vascular, respiratory and central nervous systems), as is
often found in the case of polytrauma patients. Unfortu-
nately, no such agent exists. Commonly used induction
agents for RSI include: etomidate, ketamine, propofol,
midazolam and barbiturates (thiopentone).
Etomidate, an imidazole derivative, is a sedative-hyp-
notic with a rapid onset of action. The duration of anes-
thesia after a single induction dose (0.3 mg/kg) is linearly
related to the dose. In a prospective observational study
performed by Peter J Zed and colleagues, etomidate was
found to provide appropriate intubating conditions in a
heterogenous group of patients, the majority of which were
trauma patients (192/522, 36.8 %) [6]. Unlike midazolam
which, even at a low dose, was shown to result in signifi-
cant hypotension [7], the minimal effect of etomidate on
cardiovascular function makes it a favorable drug to use in
trauma patients. Zed et al. [6] also demonstrated that
favorable hemodynamic stability was present following
administration of the drug even in patients with a low pre-
RSI blood pressure. The hemodynamic stability [7] found

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Table 1 Studies examining induction agents, neuromuscular blocking agents and adjuncts in RSI
References Setting Number of patients Primary finding

Zed et al. Department of emergency medicine (tertiary 491 receiving Hemodynamic stability and appropriate intubating
[6] referral center): prospective observational etomidate for conditions in a patients undergoing RSI in the ED
study RSI
Deitch Aeromedical ambulance units in San Diego 33 patients Improvement in mean SBP and low incidence of
et al. [7] county received hypotension
Prospective observational study etomidate for
RSI
Choi et al. Emergency department in an Urban district 160 Midazolam, even at low doses, is more likely than
[8] hospital: prospective observational study 77 received etomidate to cause hypotension
midazolam
83 received
etomidate
Baird et al. Urban emergency department: retrospective 525 Induction drug was not related to outcome. Risk of
[9] case series 184 received developing hypotension and requiring vasopressors at
etomidate induction was greatest with propofol
306 received
thiopental
35 received
propofol
Bahn et al. Community regional medical center, level I 1325 No significant difference in mortality, mean ICU days or
[11] trauma center: retrospective chart review 443: liberal mean hospital LOS. Hypotension more common in
etomidate use limited etomidate group
882: limited
etomidate use
Hardcastle Systematic review 38 papers, Etomidate should be avoided in RSI in septic patients. Use
[12] editorial, letters with caution in trauma patient and supplement with
to the editor steroids in the event of vasopressor-resistant shock. No
clear relationship between AI and increased mortality
Sehdev Systematic review 66 articles Ketamine is a suitable agent for induction of anesthesia in
et al. the acute management of head-injured patients
[14]
Jabre et al. Emergency departments and ICU in France: 469 Intubation conditions did not differ between the 2 groups,
[16] prospective randomized controlled single- 234 received percentage of AI patients greater in etomidate group
blind study etomidate
235 received
ketamine
Zeiler et al. Systematic review 7 articles Ketamine does not increase ICP in severe TBI patients that
[17] 4 prospective are sedated and ventilated and may lower ICP in
randomized trials selected cases
2 prospective
single arm trials
1 prospective case
control study
Marsch Tertiary care center (ICU): prospective 401 Incidence and severity of oxygen desaturations, quality of
et al. randomized controlled single-blind trial 200 received intubation conditions and incidence of failed intubations
[21] succinylcholine did not differ between the 2 groups
201 received
rocuronium
Sluga et al. Rural level III center: prospective randomized 180 Excellent intubating conditions greater in succinylcholine
[22] trial 90 received group, no difference in number of failed first intubation
rocuronium attempt or poor intubation condition numbers, between
the groups
90 received
succinylcholine

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Table 1 continued
References Setting
Smith et al. Prehospital: prospective double-blinded study
[25]
Patanwala Academic ED: retrospective cohort study
et al.
[29]
Pouraghei Imam Reza Research and Training Hospital:
et al. randomized double-blinded study
[32]
Levitt et al. County teaching ED: prospective randomized
[33] double-blind study
with the use of etomidate along with its ability to decrease
cerebral blood flow and intracranial pressure while main-
taining cerebral perfusion pressure, makes it a favorable
drug in RSI performed in patients with traumatic brain
injury when compared to propofol or midazolam.
Propofol, an alkylphenol, is a rapid acting induction
agent (time to peak effect of 90–100 s). Recovery from
induction with propofol is also rapid; however, induction
with propofol causes a decrease in arterial blood pressure
independent of cardiovascular disease [3, 9], as well as a
decrease in cerebral blood flow, intracranial pressure and
cerebral perfusion pressure which is undesired in trauma
patients, specifically those with traumatic brain injuries
[10].
A concern about etomidate is the reversible inhibition of
11-beta-hydroxylase and thus a reversible adrenal sup-
pression (AI). The importance of this adverse effect in
trauma patients and whether it results in poorer outcomes
have not been well studied, but current literature does not
support the contention of a higher mortality related thereto.
No difference was found in a study comparing mortality,
hypotension and ICU and hospital length of stay between
two groups of patients—one receiving liberal etomidate
use (259/440, 58.9 %) and one receiving limited etomidate
use (205/882, 23.2 %). A reduction in the use of etomidate
in the ‘‘limited group,’’ however, was associated with an
increase in hypotension [11]. A review by Hardcastle
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Number of patients Primary finding
100 Tracheal intubating conditions were better with
56 received rocuronium
vecuronium
44 received
rocuronium
233 Succinylcholine was associated with increased mortality in
149 received the severely head-injured patient as compared with
succinylcholine rocuronium
84 received
rocuronium
90 patients No significant difference among groups with respect to
30 received hemodynamic parameters
alfentanil
30 received
fentanyl
30 received
sufentanil
30 Esmolol and lidocaine have similar efficacies to attenuate
16 patients moderate hemodynamic response to intubation
received esmolol
14 patients
received
lidocaine
sought to assess the evidence regarding whether or not the
disadvantage of absolute or relative adrenal insufficiency
outweighs the advantages of using etomidate in the emer-
gency RSI of shocked trauma patients. Hardcastle [12]
indicated that while there is clear evidence of the occur-
rence of reversible adrenal insufficiency in patients
receiving etomidate, it has not been established that this
adrenal insufficiency translates to an increase in mortality
in the trauma population. The benefit of cardiovascular
stability and maintenance of cerebral perfusion pressure
outweigh the risk of adrenal insufficiency, and there is
insufficient evidence to suggest avoiding etomidate as an
induction agent in the trauma setting.
Ketamine is a phencyclidine derivative that produces a
dissociative state of hypnosis and analgesia. It acts pri-
marily via antagonism of the N-methyl-D-aspartate recep-
tor. The unique cardiovascular stimulating effects of
ketamine (increase in blood pressure, heart rate and cardiac
output by central stimulation of the sympathetic nervous
system) make it a very attractive drug for use in the trauma
setting. It is also a drug that is widely available in LMICs
and is cost-effective. Losvik et al. [13] demonstrated that in
the low-resource trauma setting, ketamine used as an
analgesic agent was associated with improved blood pres-
sure for patients with severe injuries. This finding may be
indirectly relevant to the question of ketamine’s suitability
as an induction agent in trauma. The concern about using
World J Surg
ketamine as an induction agent, however, was the reported
increase in ICP and cerebral metabolic oxygen consump-
tion (CMRO2), as well as impaired cerebral perfusion in
patients with traumatic brain injury. The evidence to sup-
port the avoidance of ketamine in the head-injured patient
was found to be lacking by Sehdev et al. [14] in their
review which found that this recommendation was based
on a small number of studies which did not look at patients
receiving ketamine for emergency management of head
trauma but rather patients with non-traumatic intracranial
lesions as well as CSF outflow obstruction.
A small comparative cohort study of major trauma
patients undergoing RSI compared a group of patients
receiving fentanyl, ketamine and rocuronium to a second
group receiving etomidate and suxamethonium. The first
drug combination was found to produce superior laryngo-
scopic views and fewer hypertensive responses to laryn-
goscopy. Hypotension was uncommon in both groups, and
despite an admittedly small sample size, ketamine did not
appear to have any adverse outcomes on head-injury out-
comes [15].
In a multicenter randomized controlled trial that inclu-
ded 469 patients (22 % trauma patients) that required
emergency intubation, the 28-day morbidity after a single
dose of etomidate was compared to that of ketamine. While
the percentage of adrenal insufficiency was significantly
higher in the etomidate group, mortality between the 2
groups did not differ significantly. Importantly, the
demonstration of AI in 56/116 of the ketamine group tested
reiterates the fact that the development of AI in critical
illness is multifactorial. The results of this study show,
however, that ketamine is a safe alternative to etomidate
[16].
Ketamine when given as boluses or as an infusion to
sedated and ventilated patients with severe TBI has not
been shown to cause an increase in ICP or CMRO2. Con-
trary to previous belief, ketamine boluses in such patients
caused a dramatic decrease in ICP [17]. Although these
findings were limited to a small number of studies and to
patients with severe TBI that are already ventilated and
sedated, it could be postulated that ketamine used in iso-
lation in carbon dioxide-controlled ventilated patients may
be well tolerated without deleterious affects on ICP and
CPP, or worsening neurologic outcomes [18, 19]. Further
studies are required to confirm this. Ketamine is gaining
increasing acceptance as a safe drug to use in patients with
head injury, in common with etomidate, ketamine has
beneficial effects on the cardiovascular system, and it is
considered a favorable drug to use in trauma patient RSI.
Equally important as the choice of anesthetic agent is
the dose of anesthetic agent used. Administration of stan-
dard doses of an induction agent in a hypovolemic trauma
patient may precipitate profound hypotension and cardiac
arrest secondary to induction-associated sympatholysis and
is exacerbated by raised intrathoracic pressure and resultant
decreased venous return following initiation of positive-
pressure ventilation. Clinical discretion is thus important in
determining the appropriate dose of induction agent to be
used according to the hemodynamic status of the patient
and may even necessitate omitting the induction agent in
patients with life-threatening hypovolemia [20].
Neuromuscular blocking agents
Ideally, in order to provide safe and effective RSI, the
neuromuscular blocking agent (NMBA) used should pro-
vide the best intubating conditions (muscle relaxation) in
the shortest period of time (rapid onset of action), a rapid
recovery and minimal hemodynamic effects.
The rapid onset of action and ultra-short duration of
succinylcholine (a depolarizing muscle relaxant) made it
the traditional drug of choice. However, succinylcholine is
not without its adverse effects, which include: hyper-
kalemia, myalgia, sinus bradycardia, increased intraocular
pressure and transient increase in ICP. Although some of
these side effects may be acceptable, a safer alternative
would be welcomed. Additionally, production shortages in
LMICs have limited access to this agent recently.
Rocuronium, a non-depolarizing muscle relaxant, with
its more rapid onset of action compared to the other non-
depolarizing agents, is a widely accepted alternative to
succinylcholine.
A prospective randomized controlled single-blind trial
conducted by Marsch et al. with the aim of comparing the
incidence of hypoxemia following emergent RSI with
rocuronium (0.6 mg/kg) versus succinylcholine (1 mg/kg),
revealed no significant difference in the incidence of oxy-
gen desaturation (decrease in oxygen saturation [5 %)
between patients intubated with rocuronium and those
intubated with succinylcholine. Analysis of secondary
outcomes revealed that although succinylcholine allowed
for quicker intubation (succinylcholine group 81 ± 38 s,
rocuronium group 95 ± 48 s), ease of intubation did not
differ with respect to ease of laryngoscopy and the condi-
tion of the vocal cords. The study also revealed no dif-
ference in the incidence of failed intubation attempts
between the two groups [21].
Sluga et al. concluded that succinylcholine (1.0 mg/kg)
allows for more rapid endotracheal intubation (confirmed
by Marsch et al.) and creates superior intubating conditions
compared to rocuronium (0.6 mg/kg), in a prospective
randomized trial which took place in a rural, level III
center. Interestingly however, the difference between
scores for intubation conditions resulted almost exclusively
from a difference in a sub-score rating the response to
intubation (limb movement and coughing). There was no
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difference in the sub-scores for laryngoscopy and condition
of vocal cords. Based on the scoring system used in this
study, succinylcholine produced more ‘‘excellent’’ intu-
bating conditions than rocuronium but no statistical dif-
ference was demonstrated in ‘‘clinically acceptable’’/
‘‘good’’ and ‘‘poor’’ intubating conditions and number of
failed first intubation attempts between the two drugs [22].
A recent Cochrane review [23] of 39 randomized control
trials (RCTs), the majority (35/39) of which were in the
elective setting and included the study by Sluga et al.,
favored succinylcholine as being superior to rocuronium
for producing both excellent and clinically acceptable in-
tubating conditions. The review also included a subgroup
analysis of RCTs for patients undergoing emergent RSI (4/
39), which showed no significant difference in clinically
acceptable intubating conditions. In addition, there were no
significant differences in the number of failed intubations
in the rocuronium and succinylcholine groups.
The dosage of rocuronium is a possible contributing
factor responsible for the difference in intubating condi-
tions, as earlier studies have suggested that higher doses of
1.0 mg/kg produce intubating conditions similar to that of
succinylcholine 1.0 mg/kg [24]. The Cochrane meta-anal-
ysis could not conclusively exclude the possibility that
higher doses of rocuronium could improve intubating
conditions. While analysis of a subgroup using rocuronium
at a dose of 0.6–0.7 mg/kg favored succinylcholine for
producing better intubating conditions, there were no sta-
tistical differences between succinylcholine and the sub-
group of patients that received 0.9–1–2 mg/kg of
rocuronium. The review called for further studies to be
performed [23].
Even when compared to vecuronium, in the prehospital
setting, rocuronium was shown to produce better intubating
conditions, in a prospective blinded study of 100 adult
patients (71 % trauma related injuries) [25]. Rocuronium,
however, has a long duration of action resulting in sus-
tained paralysis post-intubation. However, with the
appropriate single bolus dose of 0.6–1.0 mg/kg, return of
spontaneous respiratory efforts occurs within approxi-
mately 15 min (as opposed to the oft-quoted 30–45 min).
In addition, most RSI patients will be ventilated in the
immediate post-intubation phase, so this is not a justified
concern, unless one is unable to intubate or ventilate.
The introduction of sugammadex, a modified c-cy-
clodextrin, into clinical practice is a major development in
the management of neuromuscular blockade with rocuro-
nium. Used in doses of 2–16 mg/kg, it has been shown to
reverse superficial and deep neuromuscular blockade in
2–3 min. This rapid reversal of profound neuromuscular
blockade with sugammadex has led to the suggestion that it
may be beneficial in ‘‘can’t intubate, can’t ventilate’’ sit-
uations [26, 27].
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World J Surg
However, reversal of neuromuscular blockade in an
unstable trauma patient is seldom an option as the initial
pathology necessitating emergency airway control will still
be present. In addition, sugammadex is not widely avail-
able, especially in LMICs, due to the cost of the drug.
Death due to traumatic brain injury (TBI) is significantly
higher in lower- and middle-income countries [28].
Patanwala et al. looked at the difference in mortality
between patients with TBI who were intubated with
rocuronium, compared to those intubated with succinyl-
choline. After adjusting for confounders, their retrospective
cohort study of 233 patients showed no association
between succinylcholine and increase mortality in patients
with low-severity TBI (based on Abbreviated Injury
Severity Score and GCS). However, the use of succinyl-
choline in patients with high-severity TBI was associated
with increased mortality [29].
Adjuncts
Laryngoscopy and tracheal intubation causes potent sympa-
thetic and parasympathetic nervous system stimulation [30]
which produces variable and sometimes unpredictable ad-
verse effects. Trauma patients undergoing emergency intu-
bation are particularly vulnerable as hemodynamic changes
and increases in ICP can adversely affect outcomes, especially
in the traumatic brain injury population [31].
Attempts should therefore be made to attenuate the
pressor response of intubation. Aside from appropriate
depth of anesthesia prior to intubation (with pre-oxygena-
tion and nasal-cannula peri-intubation use), smooth laryn-
goscopy (aided by removal of the anterior portion of the
spinal collar if present) and avoiding multiple intubation
attempts (e.g., with routine use of a bougie and bimanual
laryngeal manipulation), various pharmacological agents
have been used to in an attempt to diminish this intubation
response. Recent evidence evaluating these drugs in the
trauma population is sparse. Some attention has been given
to synthetic opioids, short-acting beta-adrenergic receptor
blockers and the local anesthetic lidocaine.
In a randomized double-blinded study conducted on 90
patients requiring intubation following trauma, Pouraghaei
et al. compared the effects of alfentanil (20 mcg/kg), fen-
tanyl (2 mcg/kg) and sufentanil (5 mcg/kg) on variation of
hemodynamic parameters during intubation. Patients were
premedicated with lidocaine 1.5 mg/kg, followed by the
randomly selected opioid. Patients were then induced with
etomidate, while succinylcholine was administered for
muscle relaxation. Intubation of the trachea was performed
1 min following administration of succinylcholine. Time to
peak effect of the administered agent was therefore not taken
into account. The authors found that there was no statisti-
cally significant difference among the three groups with
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respect to hemodynamic parameters (heart rate, systolic and
diastolic blood pressure), concluding that alfentanil, sufen-
tanil and fentanyl can be used safely as premedication drugs
for trauma patients requiring intubation [32].
In a comparative cohort study comparing patients
undergoing RSI with etomidate and suxamethonium (group
1) versus patients receiving fentanyl, ketamine and
rocuronium (group 2), Lyon et al. [15] demonstrated that a
hypertensive response to laryngoscopy and tracheal intu-
bation was uncommon in the second group while
hypotension was uncommon in both groups.
The effects of esmolol and lidocaine on attenuating the
hemodynamic effects of laryngoscopy and intubation have
been studied only in the setting of intubation in elective
surgery and not in the trauma population. A small
prospective double-blind randomized study of 30 patients
comparing the efficacy of esmolol versus lidocaine in
attenuating the hemodynamic response to intubation found
that esmolol and lidocaine had similar efficacies to attenuate
moderate hemodynamic changes. However, owing to the
small sample size, further research involving a larger sample
population is necessary to determine whether one agent is
superior to the other or whether a combination of both
agents would better attenuate the pressor response [33].
The paucity of resources in LMICs may, however,
preclude the availability of the analgesic adjuncts men-
tioned. Morphine, a potent and cost-effective opiate anal-
gesic, could be used where there are no other options
available. Morphine has been used for many decades to
provide analgesia to trauma patients, especially on the
battlefield. To the best of our knowledge, however, there
are no studies that have examined the use to morphine as an
adjunct in RSI. Trauma patients given either morphine,
fentanyl, ketamine or no medication for analgesia in the
prehospital setting had no difference in vital signs on
arrival to hospital [34]. The theoretical disadvantages of
morphine are the dose-related relative hypotension and
respiratory depression, which are largely not present in
injured patients in pain. In the intubated trauma patient
who may require ventilation for a prolonged duration, the
respiratory depression may not be a concern; however, the
hypotension may pose more of a problem (although this
appears to be more problematic in patients on combined
morphine/midazolam sedation). Further studies need to be
conducted to determine whether morphine is of benefit as
an adjunct to RSI and what doses would be safe to use.
Cost and availability
The costs associated with delivering an anesthetic for RSI
are difficult to measure. They include the direct costs of the
drugs themselves as well as the indirect cost encountered as
a result of adverse effects, prolonged in-hospital stay and
poor outcomes.
There are great cost and availability disparities between
developed and developing countries. Limited resources cou-
pled with regulatory and legal restrictions imposed on distri-
bution, storage and sale of drugs are some of the impediments
to the availability of drugs in LMICs. In the case of opioids, the
Word Health Organization estimates that developing coun-
tries account for only 6 % of the global consumption, despite
having 80 % of the world’s population [35].
The International Drug Price Indicator Guide provides
information on wholesale prices of some of the mentioned
drugs, in the international market, for a limited number of
government agencies at national level. The median prices
of propofol, ketamine and etomidate are $0.07, $0.17 and
$0.37/ml, respectively. There is a marginal difference in
the median price of rocuronium ($0.66/ml) when compared
to succinylcholine ($0.45/ml). The price of fentanyl and
morphine is $0.21 and $0.31/ml, respectively [36]. Addi-
tional research is required to determine the price and
availability of drugs in rural and remote areas.
Conclusion
Timely, safe and effective airway management in the
trauma patient is imperative and forms the cornerstone of
resuscitation of such patients, in combination with venti-
lation support and bleeding control. Delays in securing a
definitive airway, repeated or prolonged periods of
hypoxemia and hemodynamic compromise, as well as
changes in cerebral perfusion pressure can lead to
increased morbidity and mortality. The burden of trauma
and injury continues to increase in low- and middle-income
countries, and where guidelines are available, adherence to
these guidelines can positively affect outcomes.
There is a dearth of literature guiding the use of specific
drugs in the trauma setting and specifically trauma in LMICs.
More research must be performed in order to definitively
delineate the appropriate and best drugs to be used in RSI in
trauma. The evidence reviewed, however, does provide
some guidance. Etomidate and ketamine appear to be
favorable induction agents. Where there is the possibility of
septic shock (which is not common in the acutely presenting
trauma patient), etomidate should be used with caution,
bearing in mind that patients may require low-dose steroids if
they develop vasopressor-dependent shock.
It appears that succinylcholine is the NMBA of choice in
the elective setting; however, there are fewer studies to
confirm this in the trauma setting.
In the absence of the suspicion of a potential difficult intu-
bation, rocuronium should be used to provide muscle relax-
ation, especially in patients who may be susceptible to
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hyperkalemia (as in the case of crush injuries, major burns,
renal failure, etc.) and severe traumatic brain injury. At a dose of
1 mg/kg, rocuronium produces intubating conditions compa-
rable to suxamethonium, as well as a similar onset of action.
However, using higher doses may result in a longer duration of
action, which is countered by providing end-tidal carbon
dioxide-controlled ventilation until the drug has reversed.
Attempts may be made to attenuate the pressor response
to intubation; however, the literature is not clear on this
aspect. Further research is required to determine the best
pharmacological agent to achieve this in trauma RSI.
LMICs face the added challenge of cost constraints and
limited availability of these essential drugs. Additional
research is, once again, required in order to guide future
interventions directed at barriers to access of these drugs.
Suggestions for the selection of drugs for RSI in the
trauma patient in LMIC:
1. Induction agent:
etomidate 0–0.3 mg/kg or ketamine 1–2 mg/kg.
The dose of induction agent administered should be
guided by clinical discretion and decreased or omitted
in patients in hemorrhagic shock.
Other agents (i.e., propofol/thiopentone/midazolam)
may result in decrease in blood pressure in already
hemodynamically compromised patients.
2. Neuromuscular blocking agent:
Rocuronium 1.0 mg/kg.
Succinylcholine should be avoided in patients at risk of
succinyl-induced hyperkalemia and severe TBI but
may be considered in patients with suspected difficult
laryngoscopy and intubation.
3. Adjuncts:
Ensure adequate depth of anesthesia prior to attempt-
ing intubation: Appropriate doses of induction agent
and neuromuscular blocking agent should be admin-
istered and intubation should be attempted at the
expected onset time of the drugs administered.
Avoid multiple attempts at intubation.
Opioids: fentanyl (2 mcg/kg), sufentanil (0.2 mcg/kg)
or alfentanil (20 mcg/kg).
If these agents are not available, consider morphine
(0.1 mg/kg), bearing in mind that it should be admin-
istered at least 10–15 min (time to peak effect) prior to
intubation and should be used with caution in patients
who are hypotensive prior to intubation.
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