Introduction. Leressè Pillay 1,2 Timothy Hardcastle

Transcription

1 DOI /s 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 Pillay 1,2 Timothy Hardcastle 3,4 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. 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 & Leressè Pillay leresse@gmail.com Department of Anaesthetics, Inkosi Albert Luthuli Central Hospital, Mayville, Durban, KwaZulu-Natal, South Africa Division of Anaesthesiology and Critical Care, University of KwaZulu-Natal, Durban, South Africa Trauma Unit, Inkosi Albert Luthuli Central Hospital, 800 Vusi Mzimela Rd, Mayville, Durban 4058, KwaZulu-Natal, South Africa Trauma Training Unit, Department of Surgical Sciences, University of KwaZulu-Natal, Durban, South Africa Rapid sequence intubation (RSI) is an intubating technique 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].

2 Whatever technique is used, the important principles include: (1) pre-oxygenation, (2) administration of sufficient, 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 lowerand 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 A literature search was conducted via MEDLINE, Google Scholar, ScienceDirect, BioMed Central, Directory of Open Access Journals, African Journals Online Africa Sanguine, and for relevant articles. Keywords included: rapid sequence intubation, 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 previously 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 retrospective and 3 were systematic reviews. The aim of this review is to critically evaluate the evidence 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. Fig. 1 Flow diagram representing studies that were included/excluded 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 relationship and short duration of action. It should produce good intubating conditions without compromising the stability of already vulnerable organ systems (i.e., cardiovascular, respiratory and central nervous systems), as is often found in the case of polytrauma patients. Unfortunately, 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-hypnotic with a rapid onset of action. The duration of anesthesia 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 significant 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

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

4 Table 1 continued References Setting Number of patients Primary finding Smith et al. [25] Patanwala et al. [29] Pouraghei et al. [32] Levitt et al. [33] Prehospital: prospective double-blinded study received vecuronium 44 received Academic ED: retrospective cohort study received succinylcholine 84 received Imam Reza Research and Training Hospital: randomized double-blinded study County teaching ED: prospective randomized double-blind study 90 patients 30 received alfentanil 30 received fentanyl 30 received sufentanil patients received esmolol 14 patients received lidocaine Tracheal intubating conditions were better with Succinylcholine was associated with increased mortality in the severely head-injured patient as compared with No significant difference among groups with respect to hemodynamic parameters Esmolol and lidocaine have similar efficacies to attenuate moderate hemodynamic response to intubation with the use of etomidate along with its ability to decrease cerebral blood flow and intracranial pressure while maintaining 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 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 suppression (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 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 emergency RSI of shocked trauma patients. Hardcastle [12] indicated that while there is clear evidence of the occurrence 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 primarily via antagonism of the N-methyl-D-aspartate receptor. 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 pressure 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

5 ketamine as an induction agent, however, was the reported increase in ICP and cerebral metabolic oxygen consumption (CMRO 2 ), as well as impaired cerebral perfusion in patients with traumatic brain injury. The evidence to support 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 to a second group receiving etomidate and suxamethonium. The first drug combination was found to produce superior laryngoscopic views and fewer hypertensive responses to laryngoscopy. 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 outcomes [15]. In a multicenter randomized controlled trial that included 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 CMRO 2. Contrary 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 isolation 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 standard 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 positivepressure 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 provide 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: hyperkalemia, 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 nondepolarizing 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 (0.6 mg/kg) versus succinylcholine (1 mg/kg), revealed no significant difference in the incidence of oxygen desaturation (decrease in oxygen saturation [5 %) between patients intubated with and those intubated with succinylcholine. Analysis of secondary outcomes revealed that although succinylcholine allowed for quicker intubation (succinylcholine group 81 ± 38 s, group 95 ± 48 s), ease of intubation did not differ with respect to ease of laryngoscopy and the condition of the vocal cords. The study also revealed no difference 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 (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

6 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 intubating conditions than but no statistical difference 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 for producing both excellent and clinically acceptable intubating 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 and succinylcholine groups. The dosage of is a possible contributing factor responsible for the difference in intubating conditions, 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-analysis could not conclusively exclude the possibility that higher doses of could improve intubating conditions. While analysis of a subgroup using at a dose of mg/kg favored succinylcholine for producing better intubating conditions, there were no statistical differences between succinylcholine and the subgroup of patients that received mg/kg of. The review called for further studies to be performed [23]. Even when compared to vecuronium, in the prehospital setting, 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 sustained paralysis post-intubation. However, with the appropriate single bolus dose of mg/kg, return of spontaneous respiratory efforts occurs within approximately 15 min (as opposed to the oft-quoted 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-cyclodextrin, into clinical practice is a major development in the management of neuromuscular blockade with. 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 situations [26, 27]. 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 available, 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, compared to those intubated with succinylcholine. 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 succinylcholine in patients with high-severity TBI was associated with increased mortality [29]. Adjuncts Laryngoscopy and tracheal intubation causes potent sympathetic and parasympathetic nervous system stimulation [30] which produces variable and sometimes unpredictable adverse effects. Trauma patients undergoing emergency intubation 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-oxygenation and nasal-cannula peri-intubation use), smooth laryngoscopy (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), fentanyl (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 statistically significant difference among the three groups with

7 respect to hemodynamic parameters (heart rate, systolic and diastolic blood pressure), concluding that alfentanil, sufentanil 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 (group 2), Lyon et al. [15] demonstrated that a hypertensive response to laryngoscopy and tracheal intubation 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 mentioned. Morphine, a potent and cost-effective opiate analgesic, 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 coupled with regulatory and legal restrictions imposed on distribution, 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 countries 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 ($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]. Additional 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 ventilation 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 intubation, should be used to provide muscle relaxation, especially in patients who may be susceptible to

8 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, produces intubating conditions comparable 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 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 attempting intubation: Appropriate doses of induction agent and neuromuscular blocking agent should be administered 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). 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