Predictors of adverse events with intramuscular ketamine sedation in children

doi:10.1016/S0196-0644(00)70102-8

Annals of Emergency Medicine

Volume 35, Issue 1, January 2000, Pages 35-42

https://doi.org/10.1016/S0196-0644(00)70102-8 Get rights and content

Abstract

Study Objective: Ketamine is a safe and effective sedative for emergency department procedures in children. However, the use of ketamine sometimes is associated with airway complications, emesis, and recovery agitation. We wished to identify predictors of these adverse events that clinicians might use to risk-stratify children who are candidates for ketamine sedation. Methods: We analyzed data from 1,021 ED intramuscular ketamine sedations in children 15 years of age or younger at a university medical center and an affiliated county hospital over a 9-year period. Five potential predictor variables (age, gender, American Society of Anesthesiologists’ [ASA] risk classification, quantity of first ketamine dose, and number of ketamine doses administered) were compared between children with and without complications. We used multiple logistic regression analyses to determine the association of these 5 variables with emesis and recovery agitation, and validated these analyses with bootstrap resampling techniques. We compared children with and without airway complications using univariate statistics alone, as there were too few patients with airway complications to support a multivariate analysis. Results: No study variables had significant univariate associations with airway complications (all P values >.40). We found emesis to be associated with increasing age in multivariate analysis (odds ratio [OR] 1.25 per year, bias-corrected 95% confidence interval [CI] 1.17 to 1.34, P <.001). The incidence of emesis was 12.1% in children aged 5 years or older, and 3.5% in those younger than 5 years (Δ8.6%, 95% CI 4.9% to 12.1%). Recovery agitation was associated with the presence of an underlying medical condition (ie, ASA class ≥2, OR 3.05, bias-corrected 95% CI 1.65 to 7.30, P =.004) and inversely associated with increasing age (OR 0.79 per year, bias-corrected 95% CI 0.69 to 0.89, P <.001). The incidence of recovery agitation was 17.9% in ASA class 1 children and 33.3% in children in ASA class 2 or greater (Δ–15.4%, 95% CI 0.0% to –30.7%). The incidence of recovery agitation was 12.1% in children aged 5 years or older, and 22.5% in those younger than 5 years (Δ–10.4%, 95% CI –3.0% to –17.7%). Bootstrap resampling techniques validated the importance of the significant variables identified in the regression analyses. Conclusion: No study variable was predictive of ketamine-associated airway complications. Emesis that occurred after ketamine administration was modestly associated with increasing age. Recovery agitation was modestly associated with decreasing age and the presence of an underlying medical condition. The discriminatory power of these variables was low enough as to be unlikely to alter clinical decisions regarding patient selection for ketamine administration. No evidence of a significant ketamine dose relationship was noted for airway complications, emesis, or recovery agitation. [Green SM, Kuppermann N, Rothrock SG, Hummel CB, Ho M. Predictors of adverse events with intramuscular ketamine sedation in children. Ann Emerg Med. January 2000;35:35-42.]

Introduction

The dissociative agent ketamine is a safe and effective sedative used to facilitate the performance of painful or emotionally disturbing emergency department procedures in children.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 We recently reported a prospective case series of 1,022 consecutive intramuscular ketamine administrations.¹ Although there were no complications with sequelae in this sample, 3 types of adverse events were observed: transient airway complications (1.4%), emesis (6.7%), and generally mild recovery agitation (19.2%).

We hypothesized that demographic or other clinical factors might be predictive of these 3 types of adverse events, and that emergency physicians could then use such factors to risk-stratify children when ketamine sedation is considered. Accordingly, we analyzed our 9-year experience with ketamine to identify predictors of airway complications, emesis, and recovery agitation.

Section snippets

Materials and methods

We previously published our ketamine protocol and the sedation characteristics of the study sample, which included 1,022 consecutive children 15 years or younger given intramuscular ketamine. This prospective study was performed in the EDs of a university medical center and an affiliated county hospital over a 9-year period.¹ The study was approved by the institutional review board at each institution.

Ketamine was administered according to a specific protocol that delineated inclusion criteria,

Results

No predictor variable had significant univariate associations with airway complications (Table 1).

. Univariate analysis of airway complications (n=1,021).

Variable	Airway Complication (n=14)	No Airway Complication (n=1,007)	Difference in Mean or Percentage (95% CI)	P Value
Mean age (y±SD)	4.56±2.96	4.54±2.80	0.02 (–1.46 to 1.50)	.982
Gender (male, %)	50.0	59.7	–9.7 (–36.0 to 16.7)	.464
ASA risk classification ≥2 (%)	21.4	12.5	8.9 (–12.7 to 30.1)	.405
Mean quantity of first dose (mg/kg±SD)	3.87±0.85	3.96±0.68	–0.09

Discussion

In this study, we report the largest analysis of predictors of ketamine adverse events ever reported in any setting. Importantly, we found that no variable could predict the adverse event of greatest concern—airway complications. We found certain parameters to be associated with emesis and recovery agitation, although the discriminatory power of these variables was relatively modest.

We found no variable to be predictive of airway complications, and observed no trends to suggest any effect that

Acknowledgements

We thank Sean P Bush, MD, for his review of the manuscript and many helpful suggestions.

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Advantages of Sedation With Remimazolam Compared to Midazolam for the Removal of Impacted Tooth in Patients With Dental Anxiety
2023, Journal of Oral and Maxillofacial Surgery
Although midazolam is commonly used to sedate patients with dental anxiety, it has shortcomings that reduce the satisfaction of patients and doctors. The aim of this study was therefore to explore the advantages of remimazolam as a sedative.
The study design was a prospective randomized controlled trial. Patients with dental anxiety and who were to undergo impacted tooth removal were randomized into remimazolam and midazolam groups. They were sedated with remimazolam or midazolam prior to receiving nerve blocker. The predictor variable was the type of sedative, while the primary outcome variables were the onset time, awakening time, recovery time, and postoperative side effects. Secondary outcome variables were the Modified Dental Anxiety Scale score before and after surgery, patient satisfaction and comfort levels scores, and doctor satisfaction level scores. Other variables included the patient demographics and the operation time. Data were analyzed using the Student's t-test, Mann-Whitney test, χ² test, and two-way repeated measurement ANOVA test (SPSS Version 25.0).
A total of 83 patients were included in this study, with 42 randomized to the remimazolam group and 41 to the midazolam group. There were no significant differences between the two groups in terms of demographic features and operation time. Patients in the remimazolam group had significantly shorter onset time, awakening time, and recovery time compared to those in the midazolam group (each P < .001). Postoperative side effects were more frequent in the midazolam group (P < .001). Following surgery, the Modified Dental Anxiety Scale scores in both groups were significantly lower than prior to surgery (P < .001). Satisfaction levels scores for the patients and doctor were higher in the remimazolam group than in the midazolam group (P < .001).
The use of remimazolam results in faster onset, more rapid recovery, and lower incidence of postoperative side effects compared to midazolam, leading to improved satisfaction for patients and doctors. Remimazolam therefore appears to have several advantages over midazolam for the sedation of patients with dental anxiety associated with the removal of impacted teeth.
Opioids Safety in Pediatric Procedural Sedation with Ketamine
2022, Journal of Pediatrics
To evaluate the effects of pre- and intraprocedural opioids on adverse events in children undergoing procedural sedation with ketamine in the emergency department (ED).
We conducted a retrospective cohort study of all children aged 0-18 years who underwent procedural sedation with intravenous ketamine alone, or in combination with an opioid, at a tertiary-care pediatric ED between June 1, 2018, and August 31, 2020. We explored predictors of serious adverse events (SAEs), desaturation or respiratory intervention, and vomiting.
Of 1164 included children (694 male, 59.6%; median age 5.0 years [IQR 2.0-8.0]), 80 (6.8%) vomited, 63 (5.4%) had a desaturation or required respiratory interventions, and 6 (0.5%) had SAEs. Pre- and intraprocedural opioids were not independent predictors of sedation-related adverse events. A concurrent respiratory illness (aOR 3.73; 95% CI 1.31-10.60, P = .01), dental procedure (aOR 3.05; 95% CI 1.25-7.21, P = .01), and a greater total ketamine dose (aOR 1.75; 95% CI 1.21-2.54, P = .003) were independent predictors of desaturation or respiratory interventions. A greater total ketamine dose (aOR 1.86; 95% CI 1.16-2.98, P = .01) and older age (aOR 1.15; 95% CI 1.07-1.24, P < .001), were independent predictors of vomiting.
Pre- and intraprocedural opioids do not increase the likelihood of sedation-related adverse events. SAEs are rare during pediatric procedural sedation with ketamine in the ED.
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.
Optimal dosing of intravenous ketamine for procedural sedation in children in the ED—a randomized controlled trial
2016, American Journal of Emergency Medicine
Citation Excerpt :
This study did not describe the infusion time of IV ketamine. Current recommendations support administration of IV ketamine over 30 to 60 seconds to prevent respiratory depression [9,20]. Recent studies have investigated the administration of lower doses of IV ketamine (< 1 mg/kg) over much shorter time period (≤ 5 seconds) for brief procedures as well as lower initial doses of IV ketamine with subsequent “top-up” doses and have demonstrated adequate sedation with shorter sedation times [21,22].
The objective of the study is to compare need for redosing, sedation efficacy, duration, and adverse events between 3 commonly administered doses of parenteral ketamine in the emergency department (ED).
We conducted a prospective, double-blind, randomized controlled trial on a convenience sample of children 3 to 18 years who received intravenous ketamine for procedural sedation. Children from each age group (3-6, 7-12, and 13-18 years) were assigned in equal numbers to 3 dosing groups (1, 1.5, and 2 mg/kg) using random permuted blocks. The primary outcome measure was need for ketamine redosing to ensure adequate sedation. Secondary outcome measures were sedation efficacy, sedation duration, and sedation-related adverse events.
A total of 171 children were enrolled of whom 125 (1 mg/kg, 50; 1.5 mg/kg, 35; 2 mg/kg, 40) received the randomized dose and were analyzed. The need for ketamine redosing was higher in the 1 mg/kg group (8/50; 16.0% vs 1/35; 2.9% vs 2/40; 5.0%). There was no significant difference in the median Ramsay sedation scores (5.5 [interquartile range {IQR}, 4-6] vs 6 [IQR, 4-6] vs 6 [IQR, 5-6]), FACES-R score (0 [IQR, 0-4] vs 0 [IQR, 0-0] vs 0 [IQR, 0-0]), sedation duration in minutes (23 [IQR, 19-38] vs 24.5 [IQR, 17.5-34.5] vs 23 [IQR, 19-29]), and adverse events (10.0% vs 14.3% vs 10.0%) between the 3 dosing groups. Physician satisfaction was lower in the 1 mg/kg group (79.6% vs 94.1% vs 97.3%).
Adequate sedation was achieved with all 3 doses of ketamine. Higher doses did not increase the risk of adverse events or prolong sedation. Ketamine administered at 1.5 or 2.0 mg/kg intravenous required less redosing and resulted in greater physician satisfaction.
Paediatric procedural sedation using ketamine in a UK emergency department: A 7 year review of practice
2016, British Journal of Anaesthesia
Citation Excerpt :
No drug is without side-effects, and ketamine is no exception. Experience from North America has identified a number of predictors of airway complications, including age (<2 yr or >13 yr old), high doses, and co-administration of anticholinergics or benzodiazepines.37 Likewise, patterns of postemergence agitation and emesis have been identified.38
Ketamine is growing in popularity for procedural sedation in the paediatric population, yet safety concerns remain. We performed a retrospective review of practice and outcomes of paediatric ketamine sedation using the World SIVA International Sedation Task Force reporting tool.
A retrospective inspection of the dedicated emergency department electronic sedation database and subsequent note and sedation chart review was performed for all paediatric sedations throughout a 7 yr period from September 2006. All adverse events were stratified.
During the study period, procedural sedation was provided for a total of 243 children, of whom 215 were sedated with ketamine, most commonly for wound management (n+131). The median patient age was 4 yr (14 months to 15 yr), and 63.7% were male. Of the total, 76.7% were discharged home either directly (n+101) or after brief observation (n+64). One patient required subsequent general anaesthesia after a failed sedation with paradoxical agitation. Of the total, 9.8% of patients had an adverse event, the most severe risk stratification being ‘minor risk’. All interventions were ‘minimal risk’. There were no ‘sentinel risk’ outcomes.
These data support the ongoing use of ketamine for paediatric procedural sedation in the emergency department by emergency physicians. Relatively high resource requirements mean that ensuring adequate numbers of procedures may prove challenging.
Remifentanil–ketamine vs. propofol–ketamine for sedation in pediatric patients undergoing colonoscopy: A randomized clinical trial
2018, Brazilian Journal of Anesthesiology
Os pacientes pediátricos com frequência precisam de sedação profunda ou anestesia geral para colonoscopia. Este estudo foi desenhado para comparar a eficácia sedativa da combinação de remifentanil‐cetamina e de propofol‐cetamina em crianças submetidas à colonoscopia.
Setenta pacientes, entre 2–16 anos, programados para colonoscopia diagnóstica foram alocados randomicamente em dois grupos. O grupo remifentanil‐cetamina recebeu a combinação de 2 mg.kg⁻¹ de cetamina por via intravenosa e 0,25 μg.kg⁻¹ de remifentanil; seguido de infusão de remifentanil (0,1 μg.kg⁻¹.min⁻¹). O grupo propofol‐cetamina recebeu a combinação de 1 mg.kg⁻¹ de propofol e 2 mg.kg⁻¹ de cetamina; seguido de infusão de propofol (1 mg.kg⁻¹.h⁻¹). Em caso de desconforto das crianças (choro, movimento e tosse), remifentanil (0,1 μg.kg⁻¹) seria administrado ao grupo remifentanil‐cetamina ou propofol (0,5 mg.kg⁻¹) ao grupo propofol‐cetamina. A despeito da terapia acima citada, caso as crianças ainda sentissem desconforto, cetamina (1 mg.kg⁻¹) seria administrada como fármaco de resgate, independentemente do grupo. Escore de sedação de Ramsay, variáveis hemodinâmicas, necessidade de medicamentos, satisfação dos gastroenterologistas, duração da colonoscopia, tempo de recuperação e efeitos colaterais foram registrados durante o procedimento e o período de recuperação.
O percentual de pacientes com escore 4 ou mais na escala de sedação de Ramsay durante o procedimento foi de 73,5% e 37,1% nos grupos remifentanil‐cetamina e propofol‐cetamina, respectivamente, (p = 0,02). As variáveis, pressão arterial sistólica e diastólica, foram significativamente maiores no grupo remifentanil‐cetamina do que no grupo propofol‐cetamina, mas somente após a indução (p = 0,015).
A coadministração de cetamina com remifentanil ou propofol fornece sedação e analgesia de forma eficaz e segura em crianças submetidas à colonoscopia. Os escores de sedação foram significativamente melhores no grupo remifentanil‐cetamina do que no grupo propofol‐cetamina.
Pediatric patients frequently require deep sedation or general anesthesia for colonoscopy. This study was designed to compare the sedative efficacy of remifentanil–ketamine combination with propofol–ketamine combination in children undergoing colonoscopy.
Seventy patients, between 2 and 16 years of age, scheduled for diagnostic colonoscopy were randomly allocated into two groups. Remifentanil–ketamine group received intravenous ketamine 2 mg.kg⁻¹ and remifentanil 0.25 μg.kg⁻¹ combination, followed by 0.1 μg.kg⁻¹.min⁻¹ remifentanil infusion. Propofol–ketamine group received intravenous propofol 1 and 2 mg.kg⁻¹ ketamine combination, followed by 1 mg.kg⁻¹.h⁻¹ propofol infusion. In the case of children discomfort (cry, movement, and cough), remifentanil 0.1 μg.kg⁻¹ in the remifentanil–ketamine group or propofol 0.5 mg.kg⁻¹ in the propofol–ketamine group were administered to improve children discomfort. Despite the therapy given above, if children still experience discomfort, 1 mg.kg⁻¹ of ketamine was administered as a rescue drug, regardless of the group. Ramsay sedation score, hemodynamic variables, drug requirements, gastroenterologists’ satisfaction, colonoscopy duration, recovery time, and side effects were recorded throughout the procedure and the recovery period.
The percentage of patients with a Ramsay sedation score of 4 or higher during the procedure was 73.5 and 37.1% in remifentanil–ketamine and propofol–ketamine groups, respectively (p = 0.02). Systolic and diastolic blood pressure variables were significantly higher only after induction in the remifentanil–ketamine group than in the propofol–ketamine group (p = 0.015).
Coadministration of ketamine with either remifentanil or propofol effectively and safely provides sedation and analgesia in children undergoing colonoscopy. Sedation scores were significantly better in remifentanil–ketamine group than in propofol–ketamine group.

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Predictors of adverse events with intramuscular ketamine sedation in children☆,☆☆,★

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Ann Emerg Med

Ann Emerg Med

Ann Emerg Med

Ann Emerg Med

J Oral Maxillofac Surg

Ann Emerg Med

Am J Emerg Med

Br J Anaesth

Br J Anaesth

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

Acad Emerg Med

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

Arch Pediatr Adolesc Med

Efficacy of oral ketamine for providing sedation and analgesia to children requiring laceration repair

Pediatr Emerg Care

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

Pediatrics

The role of anesthesia in surgical mortality

JAMA