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A Fixed-Dose Ketamine Protocol for Adolescent Sedations in a Pediatric Emergency Department
A Fixed-Dose Ketamine Protocol for Adolescent Sedations in a Pediatric Emergency Department Megan H. Street, MD1, and James M. Gerard, MD2 Objectives To assess provider and patient satisfaction with a fixed-dose ketamine protocol for procedural sedation of adolescent subjects. We further compared data for normal weight (body mass index [BMI] #25 kg/m2) vs overweight/obese subjects (BMI >25 kg/m2). Study design Prospective, observational cohort study of adolescent patients undergoing procedural sedation in a pediatric emergency department. Adequate sedation was defined as a Ramsay Sedation Score (RSS) $5. Subjects received an initial 50 mg intravenous ketamine dose followed by 25 mg intravenous doses to maintain an RSS $5. The sedating physician, procedural physician, and sedating nurse independently rated the sedations on a 100 mm visual analog scale (0 = “very unsatisfied”, 100 = “very satisfied”). Subjects and their guardians were contacted 12-24 hours postsedation. Results Forty-three subjects (26 normal weight, 17 overweight/obese), aged 12-17 years, were enrolled in the study. An RSS $5 was observed in 35 (81.4%) of the subjects following the initial 50 mg ketamine dose and in the remaining 8 subjects following the first additional 25 mg dose. The median combined provider satisfaction score for the sedations was 92.7 (IQR 83.7-95.0) and was similar for the normal weight and overweight/obese groups (93.1 [IQR 84.6-95.9] vs 89.7 [IQR 83.7-93.5], respectively, P = .27). Subjects and guardians in both groups reported high rates of satisfaction. Conclusion The fixed-dose ketamine protocol resulted in an adequate level of sedation and high provider/patient satisfaction for the majority of patients regardless of weight or BMI status. (J Pediatr 2014;-:---). See editorial, p
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he dissociative agent ketamine is one of the most commonly used agents to facilitate painful emergency department (ED) procedures in children.1-3 The safety and efficacy of ketamine as a procedural sedative have been well described in the pediatric2,3 and, to a lesser extent, adult literature.4-8 In 2 large meta-analyses of 8282 pediatric ketamine sedations, Green et al identified a number of risk factors that predict ketamine-associated adverse events that include the adolescent age group.2,3 The authors found a higher incidence of airway and respiratory adverse events in patients aged $13 years (OR 2.72, 95% CI 1.97-3.75)2 and a peak age of 12 years for ketamine-associated emesis (17%).3 Despite the considerable literature on ketamine, there remains some degree of uncertainty regarding optimal ketamine dosing for adolescent patients, particularly those who are overweight or obese. Previous authors have concluded that, based on its pharmacokinetics, ketamine should be dosed based on ideal body weight.7,9-11 As with most pediatric medications, however, current references including a published clinical practice guideline suggest milligram-per-kilogram doses based on total body weight and do not address the issue of adjusting ketamine doses for those who are overweight or obese.1,12-16 In addition, standard references and guidelines do not state a maximum ketamine dose or a cutoff weight or age to begin using a fixed, “adult” ketamine dose. Given that adolescent patients are at an increased risk of adverse events, the underlying reason for which remains unknown, studies specifically designed to assess ketamine dosing in this age group appear to be warranted. The present study was designed to collect data on ketamine dosing in adolescent patients. We evaluated the dose of ketamine required to achieve an adequate level of sedation in this age group of patients. In addition, we assessed provider and patient satisfaction with a fixed-dose ketamine protocol. We further compared this data between normal weight and overweight/obese subjects. We hypothesized that the fixed-dose regimen would result in an adequate level of sedation and high provider/patient satisfaction for the majority From the Department of Pediatric Emergency Medicine, of subjects regardless of weight or body mass index (BMI). 1
University of Texas Southwestern School of Medicine and Children’s Medical Center of Dallas, Dallas, TX; and 2 Department of Pediatrics, Saint Louis University School of Medicine and SSM Cardinal Glennon Children’s Medical Center, St. Louis, MO The authors declare no conflicts of interest.
ASA BMI ED IV RSS
American Society of Anesthesiologists Body mass index Emergency department Intravenous Ramsay Sedation Score
Portions of this study were presented as an abstract at the Pediatric Academic Societies’ meeting, Washington, DC, May 7, 2013. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.03.021
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Methods This prospective, observational cohort study was approved by the Institutional Review Board at the Saint Louis University Health Sciences Center. Written informed consent was obtained from the parents or guardians of the subjects. Written assent was obtained from the subjects themselves. Between July 9, 2012, and March 9, 2013, ED patients aged 12-18 years with a weight $35 kg who required procedural sedation and met American Society of Anesthesiologists (ASA) class I or II criteria17 were invited to participate in the study. ASA classification of potential subjects was determined by an attending emergency pediatrician or fellow based on standard definitions,17 which are displayed on our electronic medical record system presedation evaluation forms. Exclusion criteria were craniofacial, airway, and cardiorespiratory abnormalities (other than asthma), history of sedation-related adverse events, pregnancy, subjects requiring oral procedures, and subjects with a history of central nervous system masses, hydrocephalus, globe trauma, or schizophrenia. All sedations and recoveries were performed in accordance with our institutional sedation and analgesia protocol and occurred in an ED treatment room fully equipped for monitoring and resuscitation. Patients received narcotics for treatment of pain, as needed, before sedation. Per study protocol, on arrival to our ED, patients did not receive benzodiazepines or antiemetics before sedation. For subjects who were transferred to our ED from another facility, the referring facilities’ medical records were reviewed and administered medications were recorded. Before sedation, subjects were placed on 2 L oxygen via nasal cannula. Before and throughout sedation, standard cardiopulmonary functions, oxygen saturations, electrocardiography, and end-tidal carbon dioxide levels were continuously monitored. A sedating physician, sedating nurse, and procedural physician were present during each sedation and observed the subjects directly throughout the sedation and procedure periods. Typically, parents remained in the room until adequate sedation was achieved but were not present during the procedure. Fourteen attending emergency pediatricians or fellows, familiar with the study protocol, served as the sedating physician. Twenty-eight registered nurses served as the sedating nurse. Nineteen physicians served as the procedural physician, the majority of who (68.4%) were orthopedic surgery residents. Before the start of the study, on 2 separate occasions, the investigators met as a group with the sedating physicians and reviewed the study protocol, the Ramsay Sedation Scale, and assessment instruments including adverse event definitions. Also before the start of the study, on 3 separate occasions, the principal investigator met as a group with ED nursing staff to discuss the data collection instruments. The sedating physician explained the data collection instruments to the procedural physician before each sedation. For the purpose of this study, we defined an adequate level of sedation as a Ramsay Sedation Score (RSS) $5 (sluggish or 2
Vol. -, No. no response to a light glabellar tap or loud auditory stimulus).18 We chose to use the RSS as we believed it would provide sedating physicians with a more objective end point than that of dissociation. The authors further believe that an RSS $5 would equate to the dissociated state. Sedating physicians were instructed not to allow the procedure to begin until an RSS $5 was achieved. Per study protocol, patients received an initial 50-mg intravenous (IV) ketamine dose administered over 30-60 seconds. The RSS was applied throughout the procedure and used to assess depth of sedation. Repeat ketamine doses of 25 mg IV were given as needed to achieve and maintain an RSS $5 before and throughout the procedure. The main outcome measure was provider satisfaction with the sedation. On completion of the procedure, the sedating physician, sedating nurse, and procedural physician independently rated their satisfaction with the sedation on a 100-mm visual analog scale with 2 anchor points (0 = “very unsatisfied”, 100 = “very satisfied”). This scale was modified from a Likert scale reported by Godambe et al.19 Before patient discharge, sedating physicians completed a standardized form to report any sedation-related adverse events and necessary interventions. Adverse events were defined on this form as apnea (a minimum 20-second cessation of breathing), oxygen desaturation (pulse oximetry #90% at any point in time with no minimum time requirement), airway obstruction (stridor that resolved with airway maneuvers), laryngospasm (stridor or other evidence of airway obstruction with associated desaturation not relieved with airway maneuvers), nausea, vomiting, and recovery agitation (severe agitation or crying, hallucinations, nightmares). At 12-24 hours after the sedation, subjects and their guardians were contacted to identify any postsedation adverse events and to assess their overall satisfaction with the sedation. Before discharge, subjects and guardians were given a handout that detailed the questions that would be asked at the time of follow-up. Postsedation adverse events included prolonged sleep (excessively sleepy or hard to arouse), agitation (severe and unpleasant state of arousal), restlessness (difficulty getting comfortable or being settled), recall of sedation (remembering any pain or unpleasant thoughts), motor imbalance (difficulty with balance or coordination), vomiting, and the need for any sedation-related medical followup. After discharge, study investigators reviewed the subjects’ electronic medical records to collect data regarding the number and time of administered medications, total dosages of medications administered, and time to discharge following sedation. Weights and heights were measured on all of the subjects at the time of presentation. The BMI for each subject was calculated based on the formula: BMI = weight (kg)/[height (m)]2. Subjects were categorized as either normal weight (BMI #25) or overweight/obese (BMI >25). In addition to calculating ketamine dose per kg for actual weight, for overweight/obese subjects, we calculated the dose of ketamine received based on their ideal body weight for age and sex using a BMI of 25. Street and Gerard
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Statistical Analyses Based on data by Godambe et al,19 we calculated that with 17 subjects in each group, we could detect a 5% difference in satisfaction scores with a power of 80% at the .05 significance level. Categorical variables were analyzed by c2 or Fisher exact test where indicated. These data are presented as counts with corresponding percentages. Normally distributed continuous variables were analyzed by using Student t-tests. These data are presented as means with SDs. Provider satisfaction scores and ketamine dosages were non-normally distributed and were therefore analyzed by using MannWhitney U tests. These data are presented as medians with IQRs. In addition to assessing satisfaction scores for each individual provider group, we calculated a mean provider satisfaction score (combined score), which was the mean of the scores given by the 3 providers for each sedation. An intraclass correlation coefficient was calculated to assess agreement between the sedation raters. A 2-sided P value of <.05 was considered statistically significant. Analyses were performed using SPSS version 17.0 (SPSS Inc, Chicago, Illinois).
Results A total of 46 subjects were approached to enter the study; the parents of 2 subjects declined to participate. One subject was enrolled but later removed from the study due to a protocol violation. Thus, 43 subjects were included in the analyses. Characteristics for the entire cohort were as follows: mean age 13.9 1.5 years (range 12-17 years), mean weight 68.8 23.3 kg (range 40.8-146.7 kg), and mean BMI 24.4 5.9 (range 15.6-45.3). An RSS $5 was observed in 35 (81.4%) of the subjects following the initial 50-mg IV ketamine dose. An RSS $5 was observed in the remaining 8 subjects following the first additional 25-mg dose. The median dose of ketamine required to achieve an RSS $5 was 50.0 mg (IQR 50.050.0). The median dose of ketamine per kg to achieve an RSS $5 was 0.79 mg/kg (IQR 0.64-1.10). The median total dose of ketamine administered to subjects was 100.0 mg (IQR 75.0-100.0). The median total ketamine dose per kg was 1.25 mg/kg (IQR 1.06-1.88). The mean sedation time was 27.4 11.2 minutes (range 8-56 minutes). All of the procedures were successfully completed. The mean time to discharge following sedation was 116.9 35.6 minutes (range 41-184 minutes). Median provider satisfaction scores for the entire cohort were as follows: sedating physician, 92.0 (IQR 84.0-97.0); procedural physician, 92.0 (IQR 86.0-96.0); sedating nurse, 93.0 (IQR 85.0-95.0); and combined score, 92.7 (IQR 83.795.0). The intraclass correlation coefficient for agreement among raters was 0.84, suggesting excellent agreement per the classification scheme of Landis and Koch.20 Of the 43 subjects, 9 (20.9%) had a BMI of 25-30 and 8 (18.6%) had a BMI >30. These 17 (39.5%) subjects were therefore classified as overweight/obese. Table I shows the characteristics of subjects for the normal weight and overweight/obese groups. In addition to having a higher
Table I. Subject characteristics
Age, y, mean SD Sex, male, n (%) Race, n (%) White Black Other Weight, kg, mean SD Height, m, mean SD BMI, mean SD PMHx,* n (%) Asthma ADHD ASA class,† n (%) 1 2 Medications before arrival, n (%) Narcotic Benzodiazepine Antiemetic Morphine administered in ED, n (%) Dose, mg, mean SD Procedure, n (%) Fracture reduction Abscess drainage Chest tube placement
Normal weight (n = 26)
Overweight/ obese (n = 17)
P value
13.6 1.6 21 (80.8)
14.3 1.3 14 (82.4)
.13 .61
18 (69.2) 8 (30.8) 0 (0.0) 56.1 9.1 1.65 0.09 20.6 2.3
8 (47.1) 7 (41.2) 2 (11.8) 88.2 20.1 1.70 0.09 30.2 4.9
<.001 .06 <.001
3 (11.5) 3 (11.5)
6 (35.3) 2 (11.8)
.12 .98
24 (92.3) 2 (7.7)
11 (64.7) 6 (35.3)
.04
10 (38.5) 2 (7.7) 4 (15.4) 15 (57.7)
6 (35.3) 0 (0.0) 2 (11.8) 10 (58.8)
.83 .51 .74 .94
3.82 2.05
4.10 1.20
.71
22 (84.6) 2 (7.7) 2 (7.7)
15 (88.2) 2 (11.8) 0 (0.0)
.47
.12
ADHD, attention-deficit/hyperactivity disorder; PMHx, past medical history. *No subjects with history of obstructive sleep apnea, gastroesophageal reflux disease, or autism. †ASA criteria.
mean weight and BMI, a higher percentage of the overweight/obese subjects were ASA class II compared with the normal weight group (35.3 % vs 7.7%, respectively, P = .04). All of the overweight/obese patients appeared to have been assigned an ASA II classification based on a coexisting history of asthma. The groups were similar with respect to the other characteristics. Table II shows the sedation data for the 2 groups of subjects. An RSS $5 was found in a similar percentage of subjects in each group following the initial 50 mg IV ketamine dose (76.9% normal weight vs 88.2% overweight/obese, P = .45). Subjects in the overweight/obese group received a median total dose of 100.0 mg of ketamine vs 75.0 mg in the normal weight group (P = .18). Based on total body weight, subjects in the overweight/obese group received less ketamine per kg than those in the normal weight group (1.16 mg/kg [IQR 0.82-1.30] vs 1.31 mg/kg [IQR 1.16-1.95], respectively, P = .01). When calculated based on ideal body weight, subjects in each group received a similar total dose of ketamine (overweight/obese 1.35 mg/kg [IQR 1.02-1.64] vs normal weight 1.31 mg/kg [IQR 1.16-1.95], P = .67). One subject (2.3%) developed partial airway obstruction and desaturation relieved with airway positioning. Eight subjects (18.6%) developed nausea during recovery. Six subjects (14.0%) vomited during recovery. One subject (2.3%) developed recovery agitation requiring midazolam. There were no differences between the groups with respect to sedation-related adverse events. Time to discharge
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Table II. Sedation data RSS $5 achieved with initial 50 mg IV ketamine dose, n (%) Total ketamine doses, median (IQR) Total ketamine administered, mg, median (IQR) Total ketamine administered based on actual weight, mg/kg, median (IQR) Total ketamine administered based on ideal weight, mg/kg, median (IQR) Sedation time, min, mean SD Time to discharge, min, mean SD Sedation-related adverse events, n (%)* Airway obstruction/desaturation Nausea Vomiting Recovery agitation
Normal weight (n = 26)
Overweight/obese (n = 17)
P value
20 (76.9) 2.0 (2.0-3.3) 75.0 (75.0-106.3) 1.31 (1.16-1.95) 1.31 (1.16-1.95) 27.2 10.5 126.0 37.6
15 (88.2) 3.0 (2.0-3.5) 100.0 (75.0-112.5) 1.16 (0.82-1.30) 1.35 (1.02-1.64) 27.8 12.5 102.9 27.9
.45 .18 .18 .01 .67 .86 .04
1 (3.8) 7 (26.9) 5 (19.2) 0 (0.0)
0 (0.0) 1 (5.9) 1 (5.9) 1 (5.9)
1.00 .12 .38 .40
*No cases of apnea or laryngospasm were reported.
following sedation was shorter for subjects in the overweight/obese group than for those in the normal weight group (102.9 27.9 minutes vs 126.0 37.7 minutes, respectively, P = .04; Table II). Table III shows the provider satisfaction scores for the 2 groups of subjects. No differences were seen for any of the provider groups with respect to their satisfaction with the sedations. The median combined satisfaction score for the overweight/obese group was 89.7 (IQR 83.7-93.5) vs 93.1 (IQR 84.6-95.9) for the normal weight group (P = .27). Table IV shows the 12- to 24-hour postsedation follow-up data. There were no differences between the groups with respect to postsedation adverse events or satisfaction with the ketamine sedation. Only 1 subject reported any recall of the sedation. Forty-one (95.3%) of the guardians/subjects indicated they were satisfied or very satisfied with the sedation and that they would want ketamine if needed for sedation in the future.
Discussion Despite considerable literature on ketamine, there remains some degree of uncertainty regarding its optimal dosing in adolescent patients, and clinical practice guidelines are unable to sufficiently address ketamine dosing in this group of patients. To reliably achieve dissociation, references typically recommend an initial dose of 1.0-2.0 mg/kg IV for pediatric patients and 1.0 mg/kg IV for adult patients. However, these references do not provide a weight or age at which to begin using the 1.0 mg/kg adult dose. In addition, maximum doses are not provided for either pediatric Table III. Provider sedation satisfaction scores*
Sedating physician Procedural physician Sedating nurse Combined score
Normal weight (n = 26)
Overweight/obese (n = 17)
P value
92.5 (86.8-97.0) 93.5 (85.5-96.3) 93.8 (82.5-95.3) 93.1 (84.6-95.9)
92.0 (76.5-96.5) 90.0 (85.5-94.0) 90.0 (84.5-94.5) 89.7 (83.7-93.5)
.67 .21 .56 .27
Data presented as median (IQR). *Satisfaction measured on a 100 mm visual analog scale (0 = “very unsatisfied,” 100 = “very satisfied”).
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or adult patients. Furthermore, current recommendations are based on total body weight and do not address the issue of adjusting ketamine doses for those who are overweight or obese.1,12-16 To address this issue, we conducted the present study to collect data regarding the dose of ketamine required to achieve a satisfactory sedation in adolescentaged patients. We further sought to determine if ketamine requirements differed in adolescent patients who were overweight or obese. We found that an adequate level of sedation was achieved in the majority of patients (81.4%) with 50 mg of ketamine and that none of the patients required >75 mg to reach an RSS $5. Based on total body weight, an adequate level of sedation was achieved in these subjects with a median dose of 0.79 mg/kg (IQR 0.64-1.10), a dose lower than the range of initial doses typically recommended for pediatric patients. Based on this finding, it would seem reasonable to stop using pediatric doses and begin administering fixed doses of ketamine to patients of adolescent age. Furthermore, based on our data, we conclude that an IV ketamine dose of 75 mg should achieve an adequate initial level of sedation in the majority of patients in this age group. There would appear to be no benefit in administering initial ketamine doses in excess of 75 mg. Our protocol appeared to perform well in achieving satisfactory sedations with a median combined provider satisfaction score of 92.7 (IQR 83.7-95.0) and only 4 combined scores (9.3%) at <70 mm. On follow-up, only 1 of the patients had any recall of the sedation. Due to differences in study design and assessment/reporting methods, it is difficult to exactly compare our efficacy results with those in other studies that administered ketamine on a mg/kg basis. The provider satisfaction scores found in our study appear to be slightly lower than those reported by Godambe et al, who evaluated a younger group of patients (mean age 9.3 3.9 years) who received 1-2 mg/kg ketamine in addition to midazolam.19 On the other hand, our provider satisfaction scores appear to be higher than those reported by Sener et al, who evaluated adult patients who received 1.5 mg/kg ketamine with or without midazolam.8 None of the patients in our study received >150 mg as a total dose of ketamine. This is consistent with data for adult Street and Gerard
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Table IV. Follow-up data Follow-up question Prolonged sleep Agitation Restlessness Recall of sedation Satisfied/very satisfied with sedation Would want ketamine for future sedations
Normal weight (n = 26)
Overweight/obese (n = 17)
P value
1 (3.8) 2 (7.7) 0 (0.0) 1 (3.8) 25 (96.2)
1 (5.9) 1 (5.9) 1 (5.9) 0 (0.0) 17 (100.0)
.76 .82 .21 1.00 .26
26 (100.0)
16 (94.1)
.21
No cases of vomiting, motor imbalance, or sedation-related medical follow-up were reported. Data presented as n (%).
patients weighing 50-141 kg, in whom adequate sedation was achieved in 91 (98.9%) of 92 patients with total ketamine doses that did not exceed 1.0 mg/kg.6 The pediatric literature is silent with respect to ketamine dosing in obese patients. We found no difference in satisfaction with sedation for those who were overweight or obese vs those who were normal weight when administered ketamine per our fixed-dose protocol. We found that overweight and obese patients received less ketamine per kg based on their total body weight; mg/kg doses that were similar to those for normal weight patients were calculated based on ideal body weight. This finding suggests that a fixed-dose protocol could be used to adequately sedate adolescent patients regardless of weight or BMI. In the present study, the incidence of adverse events was consistent with previous reports.2,3 We found no differences between the normal weight and overweight/obese groups for any of the adverse events. The authors note, however, that our study was not powered to detect differences for these variables. In part, due to concerns over the reliability of collecting accurate data, we did not evaluate recovery time from sedation. When compared with normal weight subjects, however, we did find that the time to discharge following sedation was shorter for the overweight/obese patients. The potential impact on reducing sedation-related adverse events in the adolescent population if a fixeddosed ketamine protocol were broadly implemented is unknown. In the past, ketamine doses significantly higher than those currently recommended were used without an apparent increased incidence of adverse events.2,21 However, given that studies have not included data on the obesity status of subjects, it is unknown if dosing ketamine based on actual body weight as opposed to ideal body weight is a contributing factor in sedation-related adverse events. For example, in the meta-analysis by Green et al, when the authors compared adolescent patients who developed adverse airway or respiratory events with those who did not, they found that both groups received similar initial (median 1.0 mg/kg [IQR 1.0-1.5] vs 1.0 mg/kg [IQR 1.0-1.6], respectively) and total doses of ketamine (median 1.2 mg/kg [IQR 1.0-1.9] vs 1.3 mg/kg [IQR 1.0-2.0], respectively).2 One could question if these adverse events occurred more
frequently in obese patients. Although they would have received a similar mg/kg dose based on actual body weight, obese patients may have received excessively high ketamine doses relative to their ideal body weight. Given the absence of data on the obesity status of subjects enrolled in ketamine studies, this remains a speculative question. Among those who are obese, if dosing ketamine based on actual body weight is a contributing factor to adverse events, a clinical benefit might exist for using a fixed-dose protocol that would provide ketamine doses closer to those for ideal body weight for these patients. The present study has several important limitations. The main outcome measure that we used to assess sedation quality was the level of providers’ satisfaction with the sedation. The authors believe that providers would consider adequate depth of sedation and analgesia as the main determinants when responding to this question. Given this limited assessment method, however, there is the potential concern that some raters may have reported a high satisfaction score simply because they were able to complete the procedure regardless of the true quality of the sedation. More objective assessment tools, such as the Observational Scale of Behavioral Distress–Revised,22 have been used in other studies to assess sedation quality19,23,24 and should be used in future studies to validate our findings. Given our small sample size, we are unable to assess how the fixed-dose protocol performed with respect to sedation-related adverse events, an important outcome measure when evaluating sedation quality. In addition, the sedation raters in our study were not blinded to the study protocol. As such, there is the potential for scoring bias. The authors believe that the potential for this bias was mitigated by having a large number of raters, who were not investigators in the study, score the sedations. Although the sedating physicians were knowledgeable to the purpose of the study, the sedating nurses and procedural physicians generally had little or no knowledge of the purpose of the study or the specific hypotheses being tested. Furthermore, it is reassuring that raters showed excellent agreement in rating their satisfaction with the sedations, which included several sedations that were uniformly given poor ratings. Finally, it is important to note that although parents remained in the room for the initial sedation, they were not typically present in the room during the actual procedure. Parents had some information on which to base their satisfaction (initial level of sedation, postsedation recall, and postsedation adverse events), but most did not have knowledge of their child’s physical appearance during the pain-provoking portions of the sedations. This approach significantly limits our ability to draw definitive conclusions regarding parental satisfaction with the fixed-dose ketamine protocol. Our results suggest that a fixed-dose ketamine protocol can be used to effectively sedate adolescent patients, regardless of weight or BMI. This approach minimizes the potential for administering excessively large ketamine doses to this higher-risk group of patients. Further studies are needed to
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replicate our findings and to assess the impact of this approach on reducing ketamine-associated adverse events. n Submitted for publication Oct 28, 2013; last revision received Feb 20, 2014; accepted Mar 12, 2014.
References 1. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med 2011;57:449-61. 2. Green SM, Roback MG, Krauss B, Brown L, McGlone RG, Agrawal D, et al. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med 2009;54: 158-68. 3. Green SM, Roback MG, Krauss B, Brown L, McGlone RG, Agrawal D, et al. Predictors of emesis and recovery agitation with emergency department ketamine sedation: an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med 2009;54:171-80. 4. Chudnofsky CR, Weber JE, Stoyanoff PJ, Colone PD, Wilkerson MD, Hallinen DL, et al. A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. Acad Emerg Med 2000;7:228-35. 5. Vardy JM, Dignon N, Mukherjee N, Sami DM, Balachandran G, Taylor S. Audit of the safety and effectiveness of ketamine for procedural sedation in the emergency department. Emerg Med J 2008;25:579-82. 6. Newton A, Fitton L. Intravenous ketamine for adult procedural sedation in the emergency department: a prospective cohort study. Emerg Med J 2008;25:498-501. 7. Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med 2008;26:985-1028. 8. Sener S, Eken C, Schultz CH, Serinken M, Ozsarac M. Ketamine with and without midazolam for emergency department sedation in adults: a randomized controlled trial. Ann Emerg Med 2011;57:109-14. 9. Wulfsohn NL. Ketamine dosage for induction based on lean body mass. Anesth Analg 1972;51:299-305.
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Vol. -, No. 10. Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage: implications for drug therapy. Clin Pharmacokinet 1994;26:292-307. 11. Brunette DD. Resuscitation of the morbidly obese patient. Am J Emerg Med 2004;22:40-7. 12. Manzi SF. Sedation and analgesia. In: Fleisher GR, Ludwig S, eds. Textbook of pediatric emergency medicine. 6th ed. Philadelphia, PA: Lippincott; 2010. 13. Truven Health Analytics. 2013. Micromedex (Version 2.0). Available from: http://www.micromedexsolutions.com/micromedex2/librarian. 14. Athenahealth, Inc. 2013. Epocrates Essentials for Apple iOS (Version 13.9.1) [Mobile application software]. Available from: http://www. epocrates.com/mobile/iphone/essentials. 15. PDR Network, LLC. 2013. PDR.net [Internet]. Available from: http:// www.pdr.net. 16. Baxter AL. In: Strange GR, Ahrens WR, Schafermeyer RW, Wiebe R, eds. Pediatric emergency medicine. 3rd ed. New York, NY: McGraw-Hill; 2009. 17. Dripps RD, Lamont A, Eckenhoff JE. The role of anesthesia in surgical mortality. JAMA 1961;178:261-6. 18. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxolone-alphadalone. Br Med J 1974;2:656-9. 19. Godambe SA, Elliot V, Matheny D, Pershad J. Comparison of propofol/ fentanyl versus ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department. Pediatrics 2003;112: 116-23. 20. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159-74. 21. Green SM, Johnson NE. Ketamine sedation for pediatric procedures: part 2, review and implications. Ann Emerg Med 1990;19:1033-46. 22. Elliot CH, Jay SM, Woody P. An observational scale for measuring children’s distress during medical procedures. J Pediatr Psychol 1987;12: 543-51. 23. Lee-Jayaram JJ, Green A, Siembieda J, Gracely EJ, Mull CC, Quintana E, et al. Ketamine/midazolam versus etomidate/fentanyl: procedural sedation for pediatric orthopedic reductions. Pediatr Emerg Care 2010;26: 408-12. 24. Kennedy RM, Porter FL, Miller JP, Jaffe DM. Comparison of fentanyl/ midazolam with ketamine/midazolam for pediatric orthopedic emergencies. Pediatrics 1998;102:956-63.
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he dissociative agent ketamine is one of the most commonly used agents to facilitate painful emergency department (ED) procedures in children.1-3 The safety and efficacy of ketamine as a procedural sedative have been well described in the pediatric2,3 and, to a lesser extent, adult literature.4-8 In 2 large meta-analyses of 8282 pediatric ketamine sedations, Green et al identified a number of risk factors that predict ketamine-associated adverse events that include the adolescent age group.2,3 The authors found a higher incidence of airway and respiratory adverse events in patients aged $13 years (OR 2.72, 95% CI 1.97-3.75)2 and a peak age of 12 years for ketamine-associated emesis (17%).3 Despite the considerable literature on ketamine, there remains some degree of uncertainty regarding optimal ketamine dosing for adolescent patients, particularly those who are overweight or obese. Previous authors have concluded that, based on its pharmacokinetics, ketamine should be dosed based on ideal body weight.7,9-11 As with most pediatric medications, however, current references including a published clinical practice guideline suggest milligram-per-kilogram doses based on total body weight and do not address the issue of adjusting ketamine doses for those who are overweight or obese.1,12-16 In addition, standard references and guidelines do not state a maximum ketamine dose or a cutoff weight or age to begin using a fixed, “adult” ketamine dose. Given that adolescent patients are at an increased risk of adverse events, the underlying reason for which remains unknown, studies specifically designed to assess ketamine dosing in this age group appear to be warranted. The present study was designed to collect data on ketamine dosing in adolescent patients. We evaluated the dose of ketamine required to achieve an adequate level of sedation in this age group of patients. In addition, we assessed provider and patient satisfaction with a fixed-dose ketamine protocol. We further compared this data between normal weight and overweight/obese subjects. We hypothesized that the fixed-dose regimen would result in an adequate level of sedation and high provider/patient satisfaction for the majority From the Department of Pediatric Emergency Medicine, of subjects regardless of weight or body mass index (BMI). 1
University of Texas Southwestern School of Medicine and Children’s Medical Center of Dallas, Dallas, TX; and 2 Department of Pediatrics, Saint Louis University School of Medicine and SSM Cardinal Glennon Children’s Medical Center, St. Louis, MO The authors declare no conflicts of interest.
ASA BMI ED IV RSS
American Society of Anesthesiologists Body mass index Emergency department Intravenous Ramsay Sedation Score
Portions of this study were presented as an abstract at the Pediatric Academic Societies’ meeting, Washington, DC, May 7, 2013. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.03.021
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Methods This prospective, observational cohort study was approved by the Institutional Review Board at the Saint Louis University Health Sciences Center. Written informed consent was obtained from the parents or guardians of the subjects. Written assent was obtained from the subjects themselves. Between July 9, 2012, and March 9, 2013, ED patients aged 12-18 years with a weight $35 kg who required procedural sedation and met American Society of Anesthesiologists (ASA) class I or II criteria17 were invited to participate in the study. ASA classification of potential subjects was determined by an attending emergency pediatrician or fellow based on standard definitions,17 which are displayed on our electronic medical record system presedation evaluation forms. Exclusion criteria were craniofacial, airway, and cardiorespiratory abnormalities (other than asthma), history of sedation-related adverse events, pregnancy, subjects requiring oral procedures, and subjects with a history of central nervous system masses, hydrocephalus, globe trauma, or schizophrenia. All sedations and recoveries were performed in accordance with our institutional sedation and analgesia protocol and occurred in an ED treatment room fully equipped for monitoring and resuscitation. Patients received narcotics for treatment of pain, as needed, before sedation. Per study protocol, on arrival to our ED, patients did not receive benzodiazepines or antiemetics before sedation. For subjects who were transferred to our ED from another facility, the referring facilities’ medical records were reviewed and administered medications were recorded. Before sedation, subjects were placed on 2 L oxygen via nasal cannula. Before and throughout sedation, standard cardiopulmonary functions, oxygen saturations, electrocardiography, and end-tidal carbon dioxide levels were continuously monitored. A sedating physician, sedating nurse, and procedural physician were present during each sedation and observed the subjects directly throughout the sedation and procedure periods. Typically, parents remained in the room until adequate sedation was achieved but were not present during the procedure. Fourteen attending emergency pediatricians or fellows, familiar with the study protocol, served as the sedating physician. Twenty-eight registered nurses served as the sedating nurse. Nineteen physicians served as the procedural physician, the majority of who (68.4%) were orthopedic surgery residents. Before the start of the study, on 2 separate occasions, the investigators met as a group with the sedating physicians and reviewed the study protocol, the Ramsay Sedation Scale, and assessment instruments including adverse event definitions. Also before the start of the study, on 3 separate occasions, the principal investigator met as a group with ED nursing staff to discuss the data collection instruments. The sedating physician explained the data collection instruments to the procedural physician before each sedation. For the purpose of this study, we defined an adequate level of sedation as a Ramsay Sedation Score (RSS) $5 (sluggish or 2
Vol. -, No. no response to a light glabellar tap or loud auditory stimulus).18 We chose to use the RSS as we believed it would provide sedating physicians with a more objective end point than that of dissociation. The authors further believe that an RSS $5 would equate to the dissociated state. Sedating physicians were instructed not to allow the procedure to begin until an RSS $5 was achieved. Per study protocol, patients received an initial 50-mg intravenous (IV) ketamine dose administered over 30-60 seconds. The RSS was applied throughout the procedure and used to assess depth of sedation. Repeat ketamine doses of 25 mg IV were given as needed to achieve and maintain an RSS $5 before and throughout the procedure. The main outcome measure was provider satisfaction with the sedation. On completion of the procedure, the sedating physician, sedating nurse, and procedural physician independently rated their satisfaction with the sedation on a 100-mm visual analog scale with 2 anchor points (0 = “very unsatisfied”, 100 = “very satisfied”). This scale was modified from a Likert scale reported by Godambe et al.19 Before patient discharge, sedating physicians completed a standardized form to report any sedation-related adverse events and necessary interventions. Adverse events were defined on this form as apnea (a minimum 20-second cessation of breathing), oxygen desaturation (pulse oximetry #90% at any point in time with no minimum time requirement), airway obstruction (stridor that resolved with airway maneuvers), laryngospasm (stridor or other evidence of airway obstruction with associated desaturation not relieved with airway maneuvers), nausea, vomiting, and recovery agitation (severe agitation or crying, hallucinations, nightmares). At 12-24 hours after the sedation, subjects and their guardians were contacted to identify any postsedation adverse events and to assess their overall satisfaction with the sedation. Before discharge, subjects and guardians were given a handout that detailed the questions that would be asked at the time of follow-up. Postsedation adverse events included prolonged sleep (excessively sleepy or hard to arouse), agitation (severe and unpleasant state of arousal), restlessness (difficulty getting comfortable or being settled), recall of sedation (remembering any pain or unpleasant thoughts), motor imbalance (difficulty with balance or coordination), vomiting, and the need for any sedation-related medical followup. After discharge, study investigators reviewed the subjects’ electronic medical records to collect data regarding the number and time of administered medications, total dosages of medications administered, and time to discharge following sedation. Weights and heights were measured on all of the subjects at the time of presentation. The BMI for each subject was calculated based on the formula: BMI = weight (kg)/[height (m)]2. Subjects were categorized as either normal weight (BMI #25) or overweight/obese (BMI >25). In addition to calculating ketamine dose per kg for actual weight, for overweight/obese subjects, we calculated the dose of ketamine received based on their ideal body weight for age and sex using a BMI of 25. Street and Gerard
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Statistical Analyses Based on data by Godambe et al,19 we calculated that with 17 subjects in each group, we could detect a 5% difference in satisfaction scores with a power of 80% at the .05 significance level. Categorical variables were analyzed by c2 or Fisher exact test where indicated. These data are presented as counts with corresponding percentages. Normally distributed continuous variables were analyzed by using Student t-tests. These data are presented as means with SDs. Provider satisfaction scores and ketamine dosages were non-normally distributed and were therefore analyzed by using MannWhitney U tests. These data are presented as medians with IQRs. In addition to assessing satisfaction scores for each individual provider group, we calculated a mean provider satisfaction score (combined score), which was the mean of the scores given by the 3 providers for each sedation. An intraclass correlation coefficient was calculated to assess agreement between the sedation raters. A 2-sided P value of <.05 was considered statistically significant. Analyses were performed using SPSS version 17.0 (SPSS Inc, Chicago, Illinois).
Results A total of 46 subjects were approached to enter the study; the parents of 2 subjects declined to participate. One subject was enrolled but later removed from the study due to a protocol violation. Thus, 43 subjects were included in the analyses. Characteristics for the entire cohort were as follows: mean age 13.9 1.5 years (range 12-17 years), mean weight 68.8 23.3 kg (range 40.8-146.7 kg), and mean BMI 24.4 5.9 (range 15.6-45.3). An RSS $5 was observed in 35 (81.4%) of the subjects following the initial 50-mg IV ketamine dose. An RSS $5 was observed in the remaining 8 subjects following the first additional 25-mg dose. The median dose of ketamine required to achieve an RSS $5 was 50.0 mg (IQR 50.050.0). The median dose of ketamine per kg to achieve an RSS $5 was 0.79 mg/kg (IQR 0.64-1.10). The median total dose of ketamine administered to subjects was 100.0 mg (IQR 75.0-100.0). The median total ketamine dose per kg was 1.25 mg/kg (IQR 1.06-1.88). The mean sedation time was 27.4 11.2 minutes (range 8-56 minutes). All of the procedures were successfully completed. The mean time to discharge following sedation was 116.9 35.6 minutes (range 41-184 minutes). Median provider satisfaction scores for the entire cohort were as follows: sedating physician, 92.0 (IQR 84.0-97.0); procedural physician, 92.0 (IQR 86.0-96.0); sedating nurse, 93.0 (IQR 85.0-95.0); and combined score, 92.7 (IQR 83.795.0). The intraclass correlation coefficient for agreement among raters was 0.84, suggesting excellent agreement per the classification scheme of Landis and Koch.20 Of the 43 subjects, 9 (20.9%) had a BMI of 25-30 and 8 (18.6%) had a BMI >30. These 17 (39.5%) subjects were therefore classified as overweight/obese. Table I shows the characteristics of subjects for the normal weight and overweight/obese groups. In addition to having a higher
Table I. Subject characteristics
Age, y, mean SD Sex, male, n (%) Race, n (%) White Black Other Weight, kg, mean SD Height, m, mean SD BMI, mean SD PMHx,* n (%) Asthma ADHD ASA class,† n (%) 1 2 Medications before arrival, n (%) Narcotic Benzodiazepine Antiemetic Morphine administered in ED, n (%) Dose, mg, mean SD Procedure, n (%) Fracture reduction Abscess drainage Chest tube placement
Normal weight (n = 26)
Overweight/ obese (n = 17)
P value
13.6 1.6 21 (80.8)
14.3 1.3 14 (82.4)
.13 .61
18 (69.2) 8 (30.8) 0 (0.0) 56.1 9.1 1.65 0.09 20.6 2.3
8 (47.1) 7 (41.2) 2 (11.8) 88.2 20.1 1.70 0.09 30.2 4.9
<.001 .06 <.001
3 (11.5) 3 (11.5)
6 (35.3) 2 (11.8)
.12 .98
24 (92.3) 2 (7.7)
11 (64.7) 6 (35.3)
.04
10 (38.5) 2 (7.7) 4 (15.4) 15 (57.7)
6 (35.3) 0 (0.0) 2 (11.8) 10 (58.8)
.83 .51 .74 .94
3.82 2.05
4.10 1.20
.71
22 (84.6) 2 (7.7) 2 (7.7)
15 (88.2) 2 (11.8) 0 (0.0)
.47
.12
ADHD, attention-deficit/hyperactivity disorder; PMHx, past medical history. *No subjects with history of obstructive sleep apnea, gastroesophageal reflux disease, or autism. †ASA criteria.
mean weight and BMI, a higher percentage of the overweight/obese subjects were ASA class II compared with the normal weight group (35.3 % vs 7.7%, respectively, P = .04). All of the overweight/obese patients appeared to have been assigned an ASA II classification based on a coexisting history of asthma. The groups were similar with respect to the other characteristics. Table II shows the sedation data for the 2 groups of subjects. An RSS $5 was found in a similar percentage of subjects in each group following the initial 50 mg IV ketamine dose (76.9% normal weight vs 88.2% overweight/obese, P = .45). Subjects in the overweight/obese group received a median total dose of 100.0 mg of ketamine vs 75.0 mg in the normal weight group (P = .18). Based on total body weight, subjects in the overweight/obese group received less ketamine per kg than those in the normal weight group (1.16 mg/kg [IQR 0.82-1.30] vs 1.31 mg/kg [IQR 1.16-1.95], respectively, P = .01). When calculated based on ideal body weight, subjects in each group received a similar total dose of ketamine (overweight/obese 1.35 mg/kg [IQR 1.02-1.64] vs normal weight 1.31 mg/kg [IQR 1.16-1.95], P = .67). One subject (2.3%) developed partial airway obstruction and desaturation relieved with airway positioning. Eight subjects (18.6%) developed nausea during recovery. Six subjects (14.0%) vomited during recovery. One subject (2.3%) developed recovery agitation requiring midazolam. There were no differences between the groups with respect to sedation-related adverse events. Time to discharge
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Table II. Sedation data RSS $5 achieved with initial 50 mg IV ketamine dose, n (%) Total ketamine doses, median (IQR) Total ketamine administered, mg, median (IQR) Total ketamine administered based on actual weight, mg/kg, median (IQR) Total ketamine administered based on ideal weight, mg/kg, median (IQR) Sedation time, min, mean SD Time to discharge, min, mean SD Sedation-related adverse events, n (%)* Airway obstruction/desaturation Nausea Vomiting Recovery agitation
Normal weight (n = 26)
Overweight/obese (n = 17)
P value
20 (76.9) 2.0 (2.0-3.3) 75.0 (75.0-106.3) 1.31 (1.16-1.95) 1.31 (1.16-1.95) 27.2 10.5 126.0 37.6
15 (88.2) 3.0 (2.0-3.5) 100.0 (75.0-112.5) 1.16 (0.82-1.30) 1.35 (1.02-1.64) 27.8 12.5 102.9 27.9
.45 .18 .18 .01 .67 .86 .04
1 (3.8) 7 (26.9) 5 (19.2) 0 (0.0)
0 (0.0) 1 (5.9) 1 (5.9) 1 (5.9)
1.00 .12 .38 .40
*No cases of apnea or laryngospasm were reported.
following sedation was shorter for subjects in the overweight/obese group than for those in the normal weight group (102.9 27.9 minutes vs 126.0 37.7 minutes, respectively, P = .04; Table II). Table III shows the provider satisfaction scores for the 2 groups of subjects. No differences were seen for any of the provider groups with respect to their satisfaction with the sedations. The median combined satisfaction score for the overweight/obese group was 89.7 (IQR 83.7-93.5) vs 93.1 (IQR 84.6-95.9) for the normal weight group (P = .27). Table IV shows the 12- to 24-hour postsedation follow-up data. There were no differences between the groups with respect to postsedation adverse events or satisfaction with the ketamine sedation. Only 1 subject reported any recall of the sedation. Forty-one (95.3%) of the guardians/subjects indicated they were satisfied or very satisfied with the sedation and that they would want ketamine if needed for sedation in the future.
Discussion Despite considerable literature on ketamine, there remains some degree of uncertainty regarding its optimal dosing in adolescent patients, and clinical practice guidelines are unable to sufficiently address ketamine dosing in this group of patients. To reliably achieve dissociation, references typically recommend an initial dose of 1.0-2.0 mg/kg IV for pediatric patients and 1.0 mg/kg IV for adult patients. However, these references do not provide a weight or age at which to begin using the 1.0 mg/kg adult dose. In addition, maximum doses are not provided for either pediatric Table III. Provider sedation satisfaction scores*
Sedating physician Procedural physician Sedating nurse Combined score
Normal weight (n = 26)
Overweight/obese (n = 17)
P value
92.5 (86.8-97.0) 93.5 (85.5-96.3) 93.8 (82.5-95.3) 93.1 (84.6-95.9)
92.0 (76.5-96.5) 90.0 (85.5-94.0) 90.0 (84.5-94.5) 89.7 (83.7-93.5)
.67 .21 .56 .27
Data presented as median (IQR). *Satisfaction measured on a 100 mm visual analog scale (0 = “very unsatisfied,” 100 = “very satisfied”).
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or adult patients. Furthermore, current recommendations are based on total body weight and do not address the issue of adjusting ketamine doses for those who are overweight or obese.1,12-16 To address this issue, we conducted the present study to collect data regarding the dose of ketamine required to achieve a satisfactory sedation in adolescentaged patients. We further sought to determine if ketamine requirements differed in adolescent patients who were overweight or obese. We found that an adequate level of sedation was achieved in the majority of patients (81.4%) with 50 mg of ketamine and that none of the patients required >75 mg to reach an RSS $5. Based on total body weight, an adequate level of sedation was achieved in these subjects with a median dose of 0.79 mg/kg (IQR 0.64-1.10), a dose lower than the range of initial doses typically recommended for pediatric patients. Based on this finding, it would seem reasonable to stop using pediatric doses and begin administering fixed doses of ketamine to patients of adolescent age. Furthermore, based on our data, we conclude that an IV ketamine dose of 75 mg should achieve an adequate initial level of sedation in the majority of patients in this age group. There would appear to be no benefit in administering initial ketamine doses in excess of 75 mg. Our protocol appeared to perform well in achieving satisfactory sedations with a median combined provider satisfaction score of 92.7 (IQR 83.7-95.0) and only 4 combined scores (9.3%) at <70 mm. On follow-up, only 1 of the patients had any recall of the sedation. Due to differences in study design and assessment/reporting methods, it is difficult to exactly compare our efficacy results with those in other studies that administered ketamine on a mg/kg basis. The provider satisfaction scores found in our study appear to be slightly lower than those reported by Godambe et al, who evaluated a younger group of patients (mean age 9.3 3.9 years) who received 1-2 mg/kg ketamine in addition to midazolam.19 On the other hand, our provider satisfaction scores appear to be higher than those reported by Sener et al, who evaluated adult patients who received 1.5 mg/kg ketamine with or without midazolam.8 None of the patients in our study received >150 mg as a total dose of ketamine. This is consistent with data for adult Street and Gerard
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Table IV. Follow-up data Follow-up question Prolonged sleep Agitation Restlessness Recall of sedation Satisfied/very satisfied with sedation Would want ketamine for future sedations
Normal weight (n = 26)
Overweight/obese (n = 17)
P value
1 (3.8) 2 (7.7) 0 (0.0) 1 (3.8) 25 (96.2)
1 (5.9) 1 (5.9) 1 (5.9) 0 (0.0) 17 (100.0)
.76 .82 .21 1.00 .26
26 (100.0)
16 (94.1)
.21
No cases of vomiting, motor imbalance, or sedation-related medical follow-up were reported. Data presented as n (%).
patients weighing 50-141 kg, in whom adequate sedation was achieved in 91 (98.9%) of 92 patients with total ketamine doses that did not exceed 1.0 mg/kg.6 The pediatric literature is silent with respect to ketamine dosing in obese patients. We found no difference in satisfaction with sedation for those who were overweight or obese vs those who were normal weight when administered ketamine per our fixed-dose protocol. We found that overweight and obese patients received less ketamine per kg based on their total body weight; mg/kg doses that were similar to those for normal weight patients were calculated based on ideal body weight. This finding suggests that a fixed-dose protocol could be used to adequately sedate adolescent patients regardless of weight or BMI. In the present study, the incidence of adverse events was consistent with previous reports.2,3 We found no differences between the normal weight and overweight/obese groups for any of the adverse events. The authors note, however, that our study was not powered to detect differences for these variables. In part, due to concerns over the reliability of collecting accurate data, we did not evaluate recovery time from sedation. When compared with normal weight subjects, however, we did find that the time to discharge following sedation was shorter for the overweight/obese patients. The potential impact on reducing sedation-related adverse events in the adolescent population if a fixeddosed ketamine protocol were broadly implemented is unknown. In the past, ketamine doses significantly higher than those currently recommended were used without an apparent increased incidence of adverse events.2,21 However, given that studies have not included data on the obesity status of subjects, it is unknown if dosing ketamine based on actual body weight as opposed to ideal body weight is a contributing factor in sedation-related adverse events. For example, in the meta-analysis by Green et al, when the authors compared adolescent patients who developed adverse airway or respiratory events with those who did not, they found that both groups received similar initial (median 1.0 mg/kg [IQR 1.0-1.5] vs 1.0 mg/kg [IQR 1.0-1.6], respectively) and total doses of ketamine (median 1.2 mg/kg [IQR 1.0-1.9] vs 1.3 mg/kg [IQR 1.0-2.0], respectively).2 One could question if these adverse events occurred more
frequently in obese patients. Although they would have received a similar mg/kg dose based on actual body weight, obese patients may have received excessively high ketamine doses relative to their ideal body weight. Given the absence of data on the obesity status of subjects enrolled in ketamine studies, this remains a speculative question. Among those who are obese, if dosing ketamine based on actual body weight is a contributing factor to adverse events, a clinical benefit might exist for using a fixed-dose protocol that would provide ketamine doses closer to those for ideal body weight for these patients. The present study has several important limitations. The main outcome measure that we used to assess sedation quality was the level of providers’ satisfaction with the sedation. The authors believe that providers would consider adequate depth of sedation and analgesia as the main determinants when responding to this question. Given this limited assessment method, however, there is the potential concern that some raters may have reported a high satisfaction score simply because they were able to complete the procedure regardless of the true quality of the sedation. More objective assessment tools, such as the Observational Scale of Behavioral Distress–Revised,22 have been used in other studies to assess sedation quality19,23,24 and should be used in future studies to validate our findings. Given our small sample size, we are unable to assess how the fixed-dose protocol performed with respect to sedation-related adverse events, an important outcome measure when evaluating sedation quality. In addition, the sedation raters in our study were not blinded to the study protocol. As such, there is the potential for scoring bias. The authors believe that the potential for this bias was mitigated by having a large number of raters, who were not investigators in the study, score the sedations. Although the sedating physicians were knowledgeable to the purpose of the study, the sedating nurses and procedural physicians generally had little or no knowledge of the purpose of the study or the specific hypotheses being tested. Furthermore, it is reassuring that raters showed excellent agreement in rating their satisfaction with the sedations, which included several sedations that were uniformly given poor ratings. Finally, it is important to note that although parents remained in the room for the initial sedation, they were not typically present in the room during the actual procedure. Parents had some information on which to base their satisfaction (initial level of sedation, postsedation recall, and postsedation adverse events), but most did not have knowledge of their child’s physical appearance during the pain-provoking portions of the sedations. This approach significantly limits our ability to draw definitive conclusions regarding parental satisfaction with the fixed-dose ketamine protocol. Our results suggest that a fixed-dose ketamine protocol can be used to effectively sedate adolescent patients, regardless of weight or BMI. This approach minimizes the potential for administering excessively large ketamine doses to this higher-risk group of patients. Further studies are needed to
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replicate our findings and to assess the impact of this approach on reducing ketamine-associated adverse events. n Submitted for publication Oct 28, 2013; last revision received Feb 20, 2014; accepted Mar 12, 2014.
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Vol. -, No. 10. Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage: implications for drug therapy. Clin Pharmacokinet 1994;26:292-307. 11. Brunette DD. Resuscitation of the morbidly obese patient. Am J Emerg Med 2004;22:40-7. 12. Manzi SF. Sedation and analgesia. In: Fleisher GR, Ludwig S, eds. Textbook of pediatric emergency medicine. 6th ed. Philadelphia, PA: Lippincott; 2010. 13. Truven Health Analytics. 2013. Micromedex (Version 2.0). Available from: http://www.micromedexsolutions.com/micromedex2/librarian. 14. Athenahealth, Inc. 2013. Epocrates Essentials for Apple iOS (Version 13.9.1) [Mobile application software]. Available from: http://www. epocrates.com/mobile/iphone/essentials. 15. PDR Network, LLC. 2013. PDR.net [Internet]. Available from: http:// www.pdr.net. 16. Baxter AL. In: Strange GR, Ahrens WR, Schafermeyer RW, Wiebe R, eds. Pediatric emergency medicine. 3rd ed. New York, NY: McGraw-Hill; 2009. 17. Dripps RD, Lamont A, Eckenhoff JE. The role of anesthesia in surgical mortality. JAMA 1961;178:261-6. 18. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxolone-alphadalone. Br Med J 1974;2:656-9. 19. Godambe SA, Elliot V, Matheny D, Pershad J. Comparison of propofol/ fentanyl versus ketamine/midazolam for brief orthopedic procedural sedation in a pediatric emergency department. Pediatrics 2003;112: 116-23. 20. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159-74. 21. Green SM, Johnson NE. Ketamine sedation for pediatric procedures: part 2, review and implications. Ann Emerg Med 1990;19:1033-46. 22. Elliot CH, Jay SM, Woody P. An observational scale for measuring children’s distress during medical procedures. J Pediatr Psychol 1987;12: 543-51. 23. Lee-Jayaram JJ, Green A, Siembieda J, Gracely EJ, Mull CC, Quintana E, et al. Ketamine/midazolam versus etomidate/fentanyl: procedural sedation for pediatric orthopedic reductions. Pediatr Emerg Care 2010;26: 408-12. 24. Kennedy RM, Porter FL, Miller JP, Jaffe DM. Comparison of fentanyl/ midazolam with ketamine/midazolam for pediatric orthopedic emergencies. Pediatrics 1998;102:956-63.
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