Shiraz E-Med J. 2020 September; 21(9):e96024.
Published online 2020 September 6.
doi: 10.5812/semj.96024.
Systematic Review
Midazolam, Etomidate, Propofol, Fentanyl, Ketamine, and
Propofol/Ketamine for Procedural Sedation and Analgesia Among
Adults in the Emergency Departments: A Systematic Review
Maryam Massaeli
1
, Soheil Nasouhi
1
, Afshin Motallebzadeh
2
and Masoud Shahabian
1, *
1
Department of Emergency Medicine, AJA University of Medical Sciences, Tehran, Iran
2
Department of Cardiac Surgery, Razavi Hospital, Mashhad, Iran
*
Corresponding author: Resident, Department of Emergency Medicine, AJA University of Medical Sciences, Tehran, Iran. Email: elmpajooh.ac.ir@gmail.com
Received 2019 July 10; Revised 2020 February 24; Accepted 2020 February 28.
Abstract
The current systematic review aimed at investigating different medications commonly used for procedural sedation and analgesia
(PSA) in emergency departments (EDs) for adults. The articles related to the subject of interest were searched in five electronic
databases, including Google Scholar, PubMed, Medline, Web of Science, Scopus, and Embase, up to 2019. The blinded, randomized,
controlled, clinical trials comparing common PSA medications, including midazolam, etomidate, propofol, fentanyl, ketamine, and
ketofol, among the adults undergoing PSA in EDs were included in the study. The search process resulted in the inclusion of 35
papers in the study. The main information, including clinical features, sedation duration, recovery time, and incidence of adverse
events, was extracted from the selected studies. Based on the reviewed studies, various combinations of medications are used for
PSA depending on the hospital protocols and policies; however, there is still controversy over the best choice. As the results of the
retrieved articles indicated, propofol is the most common medication used for PSA in EDs due to the shorter time of induction, rapid
recovery of consciousness, and fewer side effects. Etomidate and ketamine were also identified as other common sedatives applied
for PSA.
Keywords: Procedural Sedation, Emergency Department, Midazolam, Etomidate, Propofol, Ketofol
1. Context
Procedural sedation and analgesia (PSA) is commonly
used in emergency departments (EDs) to facilitate the im-
plementation of potentially painful procedures (1). Pa-
tients undergoing painful procedures need moderate or
deep procedural sedation to achieve appropriate thera-
peutic outcomes; accordingly, the provision of all levels of
sedation in ED is necessary (2). The PSA can be induced by a
wide range of medications, such as midazolam, etomidate,
propofol, fentanyl, ketamine, and propofol/ketamine-i e,
ketofol. Some short-acting sedative agents, such as propo-
fol (3), etomidate, (4), and ketamine, are extensively ap-
plied for PSA in EDs (3). These agents allow patients to
maintain their airway reflexes and respond to verbal stim-
uli. In this regard, the use of short-acting sedative agents
that provide adequate sedation with minimum adverse ef-
fects is optimal (5).
Propofol is a non-opioid, non-barbiturate, sedative-
hypnotic agent that has a rapid onset of action and short
recovery time (6). The onset time of propofol action is ap-
proximately 45 seconds, and its redistribution time from
the blood to the fat and muscles ranges 3 - 5 minutes (5, 7, 8).
Ketamine is an analgesic and sedative agent with amnestic
properties, derived from phencyclidine. This agent facili-
tates the preservation of the muscle tone and protection of
the airway reflexes and spontaneous respiration (9). More-
over, ketamine is effective in preventing injection pain
(10, 11) and improving hemodynamic depression caused by
propofol (12). The possible side effects of ketamine include
emergence phenomena, postoperative dysphoria, vomit-
ing, or laryngospasm (13-15). However, the combined use of
ketamine and propofol can decrease the dose-dependent
side effects of these agents (15). Ketofol is commonly used
in the bolus form in EDs, operating rooms, and ambulatory
settings (15-17).
Etomidate is another ultrashort-acting sedative agent
with an action onset of approximately one minute and
an action duration of 5 - 15 minutes. This sedative has
the least hemodynamic effect in comparison with other
PSA agents (5). The main problems of this agent include
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