a b s t r a c t

Objective: There are limited data regarding appropriateness of sedative and paralytic dosing of obese patients un- dergoing Rapid Sequence Intubation in the emergency department. The goal of this study was to compare rates of appropriate succinylcholine and Etomidate doses in obese and nonobese patients.

Methods: Retrospective review using a database of endotracheally intubated patients using RSI in an urban, ter- tiary care academic emergency department, from November 2009 to June 2011. Dosing for succinylcholine and etomidate was calculated as milligrams per kilogram of total body weight (TBW) for each patient, defining ap- propriate dosing as succinylcholine 1-1.5 mg/kg TBW and etomidate 0.2-0.4 mg/kg TBW. Logistic regression anal- ysis was used to estimate the association between appropriate dosing and World Health Organization body mass index classification.

Results: A total of 440 patients were included in the study, 311 (70.7%) classified as nonobese and 129 (29.3%) as obese. two hundred thirty-three (56%) received an inappropriate succinylcholine dose and 107 (24%) received an inappropriate etomidate dose. Obese patients were more likely to be underdosed with succinylcholine (odds ratio [OR], 63.7; 95% confidence interval [CI], 17.8-228.1) and etomidate (OR, 178.3; 95% CI, 37.6-844.7). Nonobese patients were more likely to be overdosed with succinylcholine (OR, 62.5; 95% CI, 17.9-250) and etomidate (OR, 166.7; 95% CI, 37.0-1000).

Conclusion: Obese patients were more likely to be underdosed during RSI compared with nonobese patients, whereas nonobese patients were more likely to be overdosed with RSI medications. Most obese and nonobese patients were inappropriately dosed with RSI medications, suggesting that physicians are not dosing these med- ications based on weight.

(C) 2016

Introduction

The prevalence of obesity and obesity-related comorbidities in the United States has risen dramatically in last 20 years, impacting health

? The data were presented at the Society for Academic Emergency Medicine Annual Meeting on May 13, 2016, in new Orleans, LA.

?? This work was supported by a Graduate Medical Education Grant from MedStar

Washington Hospital Center for statistical analysis.

? In accordance with ICJME guidelines, the authors report no conflicts of interest.

?? RB, MA, and MG conceived the study, designed the trial, and provided data monitoring

and oversight. DT, CS, and MD led data extraction and managed the data. CS obtained research funding, provided statistical advice, and drafted the manuscript. ET analyzed the data. MG, RB, MA, and JV performed substantial revisions. All authors subsequently contributed substantially to its revision. RB takes responsibility for the manuscript as a whole.

care in all clinical arenas including the emergency department (ED) [1-3]. Despite the high prevalence of obesity, there is a relative paucity of data guiding medication dosing in obese patients compared with their lean counterparts [4]. In addition, medication product labels gen- erally offer inadequate guidance on dosing of medications in the ex- tremes of weight, as clinical trials are primarily performed in healthy individuals [5]. As a result, the care of this population is not standard- ized and may potentially be suboptimal; however, it is unclear to what extent this deviation from standardized dosing impacts patient outcomes [6].

There are limited data regarding the appropriateness of sedative and paralytic dosing in obese patients undergoing rapid sequence intuba- tion (RSI) in the ED [7]. Dosing medications based on total body weight (TBW) may lead to overdose in obese patients, whereas dosing based on ideal body weight may lead to underdosing of medications. Improper dosing of medications for RSI has the potential to lead to prolonged

http://dx.doi.org/10.1016/j.ajem.2016.09.056

0735-6757/(C) 2016

2424 R. Bhat et al. / American Journal of Emergency Medicine 34 (2016) 2423-2425

Table 1

Distribution of patients in each BMI category by medication and dosage

Medication		Underweight	Normal	Overweight	Class I obesity	Class II obesity	Class III obesity
Etomidate	Appropriate	12/28 (43%)	103/141 (73%)	119/138 (86%)	56/62 (90%)	23/34 (68%)	16/33 (48%)
	Underdose	0/28 (0%)	1/141 (1%)	3/138 (2%)	4/62 (7%)	10/34 (29%)	17/33 (52%)
	Overdose	16/28 (57%)	37/141 (26%)	16/138 (12%)	2/62 (3%)	1/34 (3%)	0/33 (0%)
Succinylcholine	Appropriate	2/28 (7%)	37/139 (27%)	74/132 (56%)	38/56 (68%)	18/32 (56%)	14/29 (48%)
	Underdose	0/28 (0%)	1/139 (b1%)	2/132 (2%)	2/56 (3.5%)	8/32 (25%)	14/29 (48%)
	Overdose	26/28 (93%)	101/139 (73%)	56/132 (42%)	16/56 (28.5%)	6/32 (19%)	1/29 (4%)

paralysis or suboptimal intubating conditions, which can be particularly detrimental given the challenges associated with airway management in this patient population. Particular concerns during airway manage- ment in obese patients include more difficult mask ventilation and more rapid desaturation during apnea [8,9]. Studies have attempted to predict changes in pharmacokinetics and drug disposition in obese pa- tients, and there are some general dosing guidelines for RSI medications in this population [4,10]. At the same time, there is a paucity of con- trolled data and it is unclear to what extent emergency physicians fol- low these dosing recommendations.

There are limited data examining obesity as a risk factor for inappro- priate dosing of patients receiving RSI medications, but existing data suggest that obese patients are more often inappropriately dosed than their nonobese counterparts [6,7]. Our primary objective was to com- pare the rates of inappropriate RSI medication dosing in obese and nonobese patients in the ED.

Materials and methods

An existing database of adults who underwent RSI in an urban, ter- tiary care, academic ED, from November 2009 to June 2011 was queried. The data were retrospectively obtained through medical record review by trained research assistants blinded to the study hypothesis. Data points were collected for each patient, including patient height and weight as well as the type and dose of RSI medications. This study was approved by our institutional review board.

The study population included all ED patients with a current proce- dural terminology code for endotracheal intubation, which was then confirmed by medical record review. Patients were defined as having received RSI if they were given both a sedative and a paralytic agent be- fore endotracheal intubation. Patients who had incomplete data, were intubated in the field, or did not receive medications for intubation were excluded from the study. Any discrepancies that were found in the written record were examined by 2 or more investigators who adju- dicated the categorization of dosing through medical record review. Each patient’s body mass index (BMI) was categorized based on the World Health Organization (WHO) classification (WHO Global Data- base on BMI http://apps.who.int/bmi/index.jsp?introPage=intro_3. html accessed May 18, 2016).

The literature was reviewed for the determination of an evidence- based definition for appropriate RSI dosing for this study by 2 of the study authors, one a clinical pharmacologist and pediatric anesthesiolo- gist and the other an emergency physician, PharmD, and clinical phar- macologist. Based on currently available data [10], we defined appropriate dosing as succinylcholine 1-1.5 mg/kg TBW and etomidate 0.2-0.4 mg/kg TBW. Because most patients intubated in our study pop- ulation received these 2 medications, only those who received etomidate and/or succinylcholine were included for statistical analysis. Patients who received doses outside the defined appropriate ranges were then further categorized as an overdose or an underdose.

Statistical analysis

Logistic regression was used to estimate the relationship between appropriate dosing and WHO BMI category. An odds ratio (OR) was cal- culated to determine the likelihood of underdosing or overdosing obese patients (BMI >=30 kg/m²) compared with nonobese patients (BMI b30 kg/m²) for etomidate alone, succinylcholine alone, and etomidate and succinylcholine together. Predetermined subgroup analyses were also performed for each class of obesity.

Results

A total of 519 patients were included in the initial data set; 47 did not receive any medications for intubation and 32 had incomplete docu- mentation, leaving 440 patients in our study. Among these patients, 311 (70.7%) were classified as nonobese and 129 (29.3%) as obese. Table 1 lists the distribution of the individual BMI categories. A total of 233 (56%) patients received an inappropriate succinylcholine dose and 107 (24%) patients received an inappropriate etomidate dose. Figs. 1 and 2 illustrate the doses of etomidate and succinylcholine by BMI clas- sification with appropriate dose for each medication shaded in gray.

Obese patients were more likely to be underdosed with succinylcho- line (OR, 63.7; 95% confidence interval [CI], 17.8-228.1) and etomidate (OR, 178.3; 95% CI, 37.6-844.7). Nonobese patients were more likely to be overdosed with succinylcholine (OR, 62.5; 95% CI, 17.9-250) and etomidate (OR, 166.7; 95% CI, 37.0-1000).

Fig. 1. Scatter plot of dosing of etomidate in mg/kg (y axis) by BMI (x axis) with appropriate dosing shaded in gray.

R. Bhat et al. / American Journal of Emergency Medicine 34 (2016) 2423-2425 2425

Fig. 2. Scatter plot of dosing of succinylcholine in mg/kg (y axis) by BMI (x axis) with appropriate dosing shaded in gray.

In a post hoc analysis of patients receiving etomidate, we found that 58.6% of patients received 20 mg etomidate, 29.5% of patients received 30 mg etomidate, and 11.8% of patients received another dose. For those paralyzed by succinylcholine, 40.8% received 100 mg, 38.3% re- ceived 120 mg, and 20.9% received another dose.

Discussion

Our single-center study demonstrates that obesity is a significant risk factor for underdosing RSI medications, whereas nonobesity is a risk factor for overdosing of these medications. Two possible explana- tions are that physicians do not routinely dose RSI medications based on weight or that weight is not readily available when performing emergent airway management in the ED. Prior studies suggest that phy- sicians use standard doses for these medications in all patients rather than adjusting them to the specific patient’s weight [7]. This finding was supported by our study, with most patients receiving 1 of 2 doses of both etomidate and succinylcholine. Although there is a paucity of lit- erature regarding appropriate medication dosing in obese patients, our study results are comparable to other studies. Burke et al [6] found that overweight/obese children were more likely to receive doses of com- mon anesthetic medications outside the recommended doses compared with normal-weight patients during noncardiac surgeries.

The optimization of medication dosing during RSI is essential; how- ever, estimations of patient weight and dose calculations can be difficult when intubating in the ED [11,12]. Underdosing RSI medications can re- sult in less than optimal intubating conditions. Poor sedation or paraly- sis can lead to patient discomfort and airway complications with vocal cord or pharyngeal injury as well as increased risk of aspiration [13]. Our study also found an increased risk of overdose of RSI medications in patients who were normal weight or underweight; however, the clin- ical implications of this finding are unclear.

Emergency physicians strive to dose RSI medications appropriately to ensure optimal intubating conditions and prevent adverse drug events. Because there are no concrete dosing guidelines in obese pa- tients, clinicians may rely upon past experience, use best practice judg- ment, or use a fixed dose for all patients regardless of weight. There are several potential interventions that may promote safer use of RSI med- ications in this Vulnerable patient population. Educational modules could be developed and used to educate physicians about appropriate dosing of these medications. In addition, documentation of measured or reported weight should occur as part of the triage process when pos- sible. In the few EDs where pharmacists are readily available, the phar- macist could be delegated the task of calculating RSI doses to allow physicians to focus on preparing for intubation. Another possible solu- tion could be placement of dosing charts for RSI and other code

medications in all code carts or making them a part of an RSI checklist. Similarly, RSI packs can be premade and bundled based on weight ranges so no calculation is needed at the time of intubation.

Limitations

Our study was limited in that this was a single-center retrospective study. In addition, we did not specifically evaluate the rate of complica- tions related to intubation based on underdosing or overdosing, rather, relied on expert opinion to define appropriate dosing. We did not eval- uate other RSI medications that may be used in the ED, such as propofol, ketamine, or rocuronium due to small sample size.

Conclusion

In summary, obese patients undergoing RSI in the ED were more likely to be underdosed with both etomidate and succinylcholine, whereas normal-weight or underweight patients were more likely to be overdosed with these medications. Further study is needed to determine if appropri- ateness of dosing translates to clinically significant outcomes.

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