A Randomized, Controlled Trial of IV Versus IM Ketamine for Sedation of Pediatric Patients Receiving Emergency Department Orthopedic Procedures

doi:10.1016/j.annemergmed.2006.06.001

Annals of Emergency Medicine

Volume 48, Issue 5, November 2006, Pages 605-612

Presented at the Pediatric Academic Societies’ meeting, May 2005, Washington, DC.

https://doi.org/10.1016/j.annemergmed.2006.06.001 Get rights and content

Study objective

We compare adverse events, efficacy, and length of sedation of intravenous (IV) versus intramuscular (IM) ketamine procedural sedation and analgesia for orthopedic procedures in the emergency department (ED).

Methods

Pediatric patients receiving ketamine for orthopedic procedures were enrolled in a prospective, randomized, controlled trial in a children’s hospital ED. All patients were initially randomized to receive ketamine either 1 mg/kg IV or 4 mg/kg IM. Demographics, adverse events, sedation efficacy, and length of sedation were recorded.

Results

Two hundred twenty-five patients were randomized (116 IV, 109 IM). Two hundred eight patients, aged 14 months to 15 years, completed the study, 109 IV and 99 IM. Respiratory adverse events were similar between groups (IV 8.3% versus IM 4.0%; odds ratio [OR] 0.47; 95% confidence interval [CI] 0.14 to 1.6). Vomiting in the ED was more common in the IM group (26.3% versus 11.9%; OR 2.60; 95% CI 1.2 to 5.9). Using the Faces Pain Scale, patients in the IM group reported significantly less pain from the procedure. Video observers reported significantly lower distress in the IM group during the painful procedure (Observation Score of Behavioral Distress scores 0.35 IM versus 0.74 IV; mean difference 0.38; 95% CI 0.04 to 0.72). Length of sedation was significantly longer in the IM group (median 129 versus 80 minutes). Satisfaction of sedation was high in parents and physicians, with no difference in reported satisfaction between groups. This study was terminated early because of nursing resistance based on the longer recovery times observed in patients receiving ketamine IM.

Conclusion

In this study of pediatric sedation for orthopedic procedures, we found that ketamine 4 mg/kg IM was more effective than 1 mg/kg IV but demonstrated significantly longer recovery times and more vomiting.

Introduction

Ketamine has been administered extensively through the intravenous (IV)1, 2, 3, 4 and intramuscular (IM)5, 6, 7, 8 routes for pediatric procedural sedation and analgesia in the emergency department (ED) setting. Despite the existence of several studies that support the relative safety of ED pediatric ketamine procedural sedation and analgesia,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 some controversy about its use still exists,15, 16, 17 and the need for IV access during sedation to ensure patient safety and ease of rescue, if needed, continues to be discussed.¹⁸

To our knowledge, no prospective comparisons of IV versus IM ketamine for pediatric procedural sedation and analgesia in the emergency setting have been reported. By performing a prospective, randomized, controlled trial comparing IV to IM ketamine we hope to broaden the available information about the effects of ketamine administered IV and IM, which may help clinicians make decisions about how ketamine may be best used for pediatric procedural sedation and analgesia in their ED setting.

The goal of this study was to compare the incidence of adverse events, efficacy, and length of sedation between ketamine procedural sedation and analgesia administered IV versus IM for pediatric orthopedic reduction in the ED.

Section snippets

Study Design

This is a randomized, controlled trial of ketamine administered IV versus IM for pediatric procedural sedation and analgesia. Written, informed consent was obtained from all patients’ parents or guardians, as well as assent from all patients 7 years of age or older, before enrollment in the study. The study was approved by the Colorado Multiple Institutional Review Board.

Setting

This study was conducted at a university-affiliated, urban children’s hospital, which is a regional pediatric referral center

Results

This study was conducted from July 2000 to October 2004. Patients eligible and enrolled during the study period are shown on the patient flow diagram (Figure 1). Two hundred twenty-five patients were entered onto the randomization table. Demographics of enrolled patients are listed (Table 1). Characteristics of patients who met inclusion criteria during the study period but were not enrolled, who withdrew, or who were excluded (n=915) were compared with those of patients enrolled (Table 2).

Limitations

Essentially no blinding occurred in this study. Subjects were not blinded to route of administration, which may have led to biased reporting of pain. Bedside nurses and videotape observers were also not blinded to route of administration, which could have resulted in biased recording of adverse events and documentation of distress scores. However, through review of the videotapes, adverse events were confirmed for most cases, and interrater agreement of distress scores was high.

Significant

Discussion

To our knowledge, our study represents the first prospective comparison of ketamine administered IV versus IM for pediatric procedural sedation and analgesia in the ED. We found no significant differences in rates of respiratory adverse events between the 2 groups. However, the study is underpowered to definitely comment on differences in respiratory adverse events. Respiratory adverse events reported here were consistent with those reported in previous studies of ketamine procedural sedation

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Cited by (96)

Is ketamine sedation without local anesthesia sufficient for pediatric laceration repair? A double-blind randomized clinical trial
2021, American Journal of Emergency Medicine
The objective of this study was to evaluate whether sedation with ketamine without local anesthesia was sufficient in children undergoing primary repair.
Randomized, double-blind trial conducted between December 2013 and October 2016 in a tertiary care pediatric emergency department in Korea. Children aged 1 to 10 years requiring sedation for primary repair were randomly assigned to receive local lidocaine anesthesia with ketamine sedation or local saline injection with ketamine sedation. Children's Hospital of Eastern Ontario Pain Scale scores was recorded during the procedures. The pain scales were recorded by nurses who were blinded to the study drugs, before ketamine sedation, after sedation, during the first injection of the study drugs for wound repair, during the first stitch, and after the procedure.
Twenty-five were randomized to receive ketamine sedation with local anesthesia and twenty-two to receive ketamine sedation without local anesthesia. There was no significant difference in pain scale before ketamine sedation (difference (mean): −1.11, CI: −2.78-0.55, P value: 0.18), after sedation (difference (mean): −0.60, CI: −2.20-1.01, P = 0.46), during the first injection of the study drugs for wound repair (difference (mean): −0.03, CI: −0.31-0.25, P = 0.84), during the first stitch (difference (mean): −0.15, CI: 6.19–6.79, P = 0.62), during the primary repair (difference (mean): 0.20, CI: −55-0.95, P = 0.59), and after the procedure (difference (mean): 0.17, CI: −0.48-0.82, P = 0.59).
Sedating with ketamine for primary wound repair, there was no difference in pain and sedation scales between the patients treated with or without lidocaine local anesthesia, and local anesthesia was not needed.
Sedation/anxiolysis for pediatric imaging
2021, Pediatric Imaging for the Emergency Provider
Sedation/anxiolysis for imaging is not always indicated. However, the clinician should be familiar with sedation and anxiolysis agents that may be required when clinically indicated. Appropriate preparation includes being familiar with sedation principles and practice, proper use of the various agents used for sedation/anxiolysis (including dosages and routes), and rescue techniques should the level of sedation progress to a deeper state.
Prehospital Use of Ketamine in Mountain Rescue: A Survey of Emergency Physicians of a Single-Center Alpine Helicopter-Based Emergency Service
2020, Wilderness and Environmental Medicine
Although ketamine use in emergency medicine is widespread, studies investigating prehospital use are scarce. Our goal was to assess the self-reported modalities of ketamine use, knowledge of contraindications, and occurrence of adverse events associated with its use by physicians through a prospective online survey.
The survey was administered to physicians working for Air-Glaciers, a Swiss alpine helicopter-based emergency service, and was available between September 24 and November 23, 2018. We enrolled 39 participants (participation rate of 87%) in our study and collected data regarding their characteristics, methods of ketamine use, knowledge of contraindications, and encountered side effects linked to the administration of ketamine. We also included a clinical scenario to investigate an analgesic strategy.
Ketamine was considered safe and judged irreplaceable by most physicians. The main reason for ketamine use was acute analgesia during painful procedures, such as manipulation of femur fractures. The doses of ketamine administered with or without fentanyl ranged from 0.2 to 0.7 mg·kg^-1 intravenously. Most physicians reported using fentanyl and midazolam along with ketamine. The median dose of midazolam was 2 (interquartile range 1–2) mg for a 70-kg adult. Monitoring and oxygen administration were used infrequently. Hallucinations were the most common adverse events. Knowledge of ketamine contraindications was poor.
Ketamine use was reported by mountain rescue physicians to be safe and useful for acute analgesia. Most physicians use fentanyl and midazolam along with ketamine. Adverse neuropsychiatric events were rare. Knowledge regarding contraindications to the administration of ketamine should be improved.
Dexmedetomidine Provides Fewer Respiratory Events Compared With Propofol and Fentanyl During Third Molar Surgery: A Randomized Clinical Trial
2020, Journal of Oral and Maxillofacial Surgery
Propofol and fentanyl can cause airway obstruction and respiratory depression when used together for intravenous sedation. This study investigated whether dexmedetomidine and midazolam would decrease respiratory events requiring intervention during deep sedation compared with propofol, fentanyl, and midazolam.
A prospective, randomized, double-blinded, controlled trial was designed to assess 2 intravenous treatment groups during third molar surgery. Patients were randomized into 2 groups. The control group (group P) received 0.8 μg/kg of fentanyl followed by propofol infusion at 125 μg/kg per minute over a 10-minute period with intraoperative boluses of 0.1 μg/kg. The study group (group D) received dexmedetomidine bolus infusion of 1 μg/kg over a 10-minute period followed by maintenance infusion at 0.5 μg/kg per hour. Both groups were given 0.03 mg/kg of midazolam before infusion. Scorers, masked to group, viewed the procedure remotely and evaluated the primary outcome variable of respiratory events requiring intervention. Secondary outcome variables evaluated by the scorers included the Behavioral Pain Scale for non-intubated patients at initial injection, cooperation score at 5 and 15 minutes, and time to ambulation and discharge. Patient satisfaction and hemodynamic stability were measured. The difference between groups regarding the occurrence of respiratory events was tested using the Fisher exact test, and mixed-effects models were used to compare repeated vital signs.
The sample was composed of 141 patients randomly assigned to either group P (n = 67) or group D (n = 74). No statistically significant differences in the distribution of study variables were found between groups at baseline. A statistically significant difference in respiratory events requiring deliberate intervention existed between group P (25.4%) and group D (2.7%) (P < .0001). No statistically significant difference was found between groups for Behavioral Pain Scale score, cooperation score, time to ambulation or discharge, and patient satisfaction.
Using dexmedetomidine and midazolam for outpatient surgery resulted in fewer respiratory events requiring deliberate intervention compared with propofol, fentanyl, and midazolam. Ambulation and discharge times were not prolonged using dexmedetomidine.
Evidence based guideline on use of ketofol (Ketamine and Propofol admixture) for procedural sedation and analgesia (PSA) in pediatrics surgery: Review article
2020, International Journal of Surgery Open
Procedural sedation and analgesia (PSA) implies the state of drug induced tolerance of uncomfortable or painful diagnostic, interventional medical and surgical procedures. Ketofol (ketamine and Propofol mixture) is a good combination of drugs for PSA in painful procedures in pediatrics resulting in hemodynamic and respiratory safety. A combination of these drugs provides sedation, analgesia, and rapid recovery with hemodynamic stability and minimal respiratory depression. The objective of sedation during such procedures is to reduce the discomfort of the patient and to facilitate the performance of the procedure.
This systematic review was conducted according to the preferred reporting items for systematic review and meta-analysis protocol (PRISMA). Evidences for this guideline development were searched from PubMed, Google Scholar, Google search, and Medline databases with keywords.
During the review of searched literature for the guideline, important concerns discussed were patient selection and assessment (indication for PSA), monitoring of children including depth of sedation, medication administration (a combination of the agents), and criteria for postoperative discharge.
Generally, in the presence of adequate resuscitation equipment and monitoring ketamine and Propofol mixture can be used in the proportion of 1:1, 1:2, 1:3, and 1:4 safely with good respiratory and hemodynamic stability.
Ketamine versus ketamine pluses atropine for pediatric sedation: A meta-analysis
2018, American Journal of Emergency Medicine
The application of atropine for pediatric sedation in the emergency department remains controversial. Our objective was to perform a comprehensive review of the literature and assess the clinical indexes in groups with and without atropine use.
PubMed, EMBASE, and the Cochrane Library were searched for randomized and non-randomized studies that compared ketamine and ketamine plus atropine for pediatric sedation. The risk ratio with 95% confidence interval was calculated using either a fixed- or random-effects model according to the value of I².
One retrospective study and four randomized controlled trials were identified to compare the clinical indexes. For the clinical indexes, the ketamine plus atropine group had better outcomes than the ketamine group in hypersalivation (P < 0.05), but indexes of rash and tachycardia were worse. The two methods of sedation were comparable for nausea, vomiting, desaturation, agitation and laryngospasm (P > 0.05).
Based on the current evidence, the group receiving atropine had reduced hypersalivation and increased rash and tachycardia; no differences were observed in nausea, vomiting, desaturation, agitation and laryngospasm between the two groups. Given that some of the studies were of low quality, additional high-quality randomized controlled trials should be conducted to further verify these findings.

View all citing articles on Scopus

Supervising editor: Steven M. Green, MD

Author contributions: MGR, JEW, and TM conceived the study. MGR and JEW oversaw data collection. MGR, JEW, and LB managed the data, including quality control. TM provided statistical advice on study design. TM and LB analyzed the data. MGR drafted the manuscript, and all authors contributed substantially to its revision. MGR takes responsibility for the paper as a whole.

Reprints not available from the authors.

Funding and support: Grant support was from The Children’s Hospital Research Institute.

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Pain management/original researchA Randomized, Controlled Trial of IV Versus IM Ketamine for Sedation of Pediatric Patients Receiving Emergency Department Orthopedic Procedures

Study objective

Methods

Results

Conclusion

Introduction

Section snippets

Study Design

Setting

Results

Limitations

Discussion

Intravenous ketamine sedation of pediatric patients in the emergency department

Ann Emerg Med

Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children

Pediatrics

Intravenous ketamine for pediatric sedation in the emergency department: safety profile with 156 cases

Acad Emerg Med

Ketamine sedation for the reduction of children’s fractures in the emergency department

J Bone Joint Surg

Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases

Ann Emerg Med

Intramuscular ketamine, midazolam, and glycopyrrolate for pediatric sedation in the emergency department

J Oral Maxillofac Surg

Intramuscular ketamine is superior to meperidine, promethazine, and chlorpromazine for pediatric emergency department sedation

Arch Pediatr Adolesc Med

Predictors of adverse events with intramuscular ketamine sedation in children

Ann Emerg Med

Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic procedures

Pediatrics

Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures?a randomized, double-blind, placebo-controlled trial

Ann Emerg Med

Does midazolam alter the clinical effects of intravenous ketamine sedation in children?a double-blind, randomized, controlled emergency department trial

Ann Emerg Med

Adverse events associated with procedural sedation and analgesia in a pediatric emergency department: a comparison of common parenteral drugs

Acad Emerg Med

Safe and efficacious use of procedural sedation and analgesia by nonanesthesiologists in a pediatric emergency department

Arch Pediatr Adolesc Med

Pain management/original research
A Randomized, Controlled Trial of IV Versus IM Ketamine for Sedation of Pediatric Patients Receiving Emergency Department Orthopedic Procedures