A comparative study of dexmedetomidine and propofol to prevent recovery agitation in adults undergoing procedural sedation with ketamine: A randomized double-blind clinical trial

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Abstract

Background

The present study was designed to evaluate the effect of dexmedetomidine and propofol on ketamine-induced recovery agitation in adults when used as co-administration with ketamine.

Methods

In this prospective, randomized, and double-blind clinical trial, 93 patients aged 18 years or older who were candidates for painful procedures in the emergency department (ED) were enrolled and assigned into three equal groups to receive either ketadex (dexmedetomidine 0.7 μg/kg and ketamine 1 mg/kg), ketofol (propofol 0.5 mg/kg and ketamine 0.5 mg/kg) or ketamine alone (1 mg/kg) intravenously. Incidence and severity of recovery agitation were evaluated using the Richmond Agitation-Sedation Scale and compared between groups.

Results

There were no significant differences in demographic characteristics, procedures, pain scores, pre-sedation agitation, and duration of procedure between the three groups. The incidence of recovery agitation was 26% in the Ketadex group, 29% in the Ketofol group, and 58% in the Ketamine group. The difference in incidence of recovery agitation between Ketadex group and Ketamine group was 32% (95% confidence interval (CI), 9 to 56]) and between Ketofol group and Ketamine group was 29% (95% CI, 6 to 53). The severe agitation was significantly higher in Ketamine group, with a difference between Ketamine and Ketadex group of 19% (95% CI, 6 to 33), and a difference between Ketamine and Ketofol group of 16% (95% CI, 1 to 31).

Conclusions

In this study, a combination of ketamine–dexmedetomidine and ketamine–propofol reduced the incidence and severity of ketamine-induced recovery agitation in adults undergoing procedural sedation in the ED.

Introduction

Ketamine is a safe and effective sedative agent commonly used for painful procedures in the emergency department (ED) [1,2]. This dissociative agent causes rapid induction, profound sedation, good analgesia, and amnesia with a short recovery period [2,3]. However, ketamine can induce emergence delirium, unpleasant dreams, excitement, and hallucinations during recovery, and these are the main drawback of ketamine use [[2], [3], [4]]. Its use has traditionally been limited in adults because of concern in regard to more frequent recovery agitation [2,5]. Recovery agitation (so-called emergence phenomenon) has been reported in up to 30% of adults receiving ketamine [6]. One review of 70 adult cases showed that, although 25% remembered dreaming, less than a third described their dreams as unpleasant [7].

Recovery agitation was not dose-related. The accepted risk factor to influence the nature and severity of emergence reactions in adults is previous psychosis, but ketamine use is not an additional risk of psychotic precipitation in adults [6]. Patients with psychotic traits or evidence of personality disorders on psychological inventories, those who normally dream frequently, excessive noise or stimulation during recovery, and female patients relative to male patients appear at greater risk for recovery agitation [2,8].

Co-administration of other drugs has been investigated in reducing the incidence of recovery agitation. Benzodiazepines have been used as premedication in decreasing emergent reactions [9]. However, some problems such as prolonged impairment of mental activity, amnesia, slower onset of action, and delay in recovery with benzodiazepines have been reported [4]. Some studies demonstrated that haloperidol can reduce the incidence of recovery agitation [5,10]. Other drugs such as opium, neuroleptics, physostigmine, and α2 adrenoceptor agonists have been used with varying success to prevent stimulation of recovery [11].

Propofol with the formulation of 2,6-diisopropyl phenol is a short-acting intravenous anesthetic drug used in ED procedural sedation [12]. Propofol is known to be an anxiolytic. The opposing physiologic effects of ketamine and propofol suggest the potential for synergy, and a reduction in ketamine-associated recovery agitation [13]. Dexmedetomidine is a potent α2 adrenergic agonist, used to induce sedation, reduce the dose of anesthetic agent and improve hemodynamic stability, which suggests that it can be a suitable adjuvant to ketamine anesthesia [9,14].

The potential advantage of Ketofol (ketamine–propofol combination) and Ketadex (ketamine–dexmedetomidine combination) over ketamine-alone procedural sedation is a lower incidence of ketamine-associated recovery agitation. Therefore, the present study was designed to evaluate the effect of dexmedetomidine and propofol when used as co-administration with ketamine in ketamine-induced recovery agitation in adults.

Section snippets

Study design and setting

This prospective, randomized and double-blind study was conducted at Al-Zahra and Kashani hospitals, two educational hospitals affiliated with Isfahan University of Medical Sciences in central Iran, from March 2017 to Feb 2019. The study was approved by the Research Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.REC.1396.3.356) and registered in the Iranian Registry of Clinical Trials (IRCT20190422043340N1). The researchers adhered to the Declaration of Helsinki Principles

Results

A total of 103 patients were initially enrolled in the study. Of them, 10 were excluded; finally, 93 cases were included (Fig. 1). Baseline characteristics of patients are shown in Table 2. The mean ages of patients were 39 ± 16 years and male patients were predominant (82%). There were no significant differences in demographic characteristics, pain scores, procedures, and ASA classifications. The pre-sedation agitation and duration of procedure were similar between the three groups (Table 3).

Discussion

The use of ketamine in adults for procedural sedation is likely to be complicated by unpleasant recovery reactions. Most adult patients who receive ketamine alone experience dreams or hallucinations. Hence, several adjuncts have been used before or in combination with ketamine to prevent or attenuate these undesirable emergence reactions. In this study, co-administration of dexmedetomidine with ketamine and co-administration of propofol with ketamine significantly reduced the incidence and

Conclusion

In this study, a combination of ketamine–dexmedetomidine and ketamine–propofol reduced the incidence and severity of ketamine-induced recovery agitation in adults undergoing procedural sedation in the ED. These findings suggest administration of dexmedetomidine or propofol with ketamine may form an effective combination for procedural sedation in adults and prevention of recovery agitation due to ketamine in the ED.

Funding

This study was funded by Isfahan University of Medical Sciences.

Author contributions

R.A., S.K., F.H., S.M.; Contributed to conception, study design and data collection and evaluation. R.A., S.K., F.H.; Contributed to statistical analysis, and interpretation of data. R.A., F.H.; Were responsible for overall supervision. S.K.; Drafted the manuscript, which was revised by R.A., F.H. and S.M. All authors performed editing and approving the final version of this paper for submission, also participated in the finalization of the manuscript and approved the final draft.

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgements

The authors appreciate the staff of the emergency departments of Kashani and Al‑Zahra hospitals for their kind contributions.

References (26)

  • C.R. Chudnofsky et al.

    A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients

    Acad Emerg Med

    (2000 Mar)
  • S.M. Green et al.

    The taming of ketamine-40 years later

    Ann Emerg Med

    (2010 Nov 2)
  • S. Trivedi et al.

    A comparative study of dexmedetomidine and midazolam in reducing delirium caused by ketamine

    J Clin Diagn Res

    (2016 Aug)
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