Pediatric Premedication: A Double-blind Randomized Trial of Dexmedetomidine or Ketamine Alone Versus a Combination of Dexmedetomidine and Ketamine

Hui Qiao; Zhi Xie; Jie Jia

Disclosures

BMC Anesthesiol. 2017;17(158) 

In This Article

Methods

This trial was approved by the institutional review board of the Eye and ENT hospital affiliated with Fudan University and registered at the Chinese Clinical Trial Registry with registration number ChiCTR-TRC-14004475. The parents of all children in the study provided written, informed consent. A total of 135 children scheduled for eye surgery under general anesthesia, who were 2 to 6 years old with an American Society of Anesthesiologists' status of I–II and a body mass index of 15–18 kg/m2, were enrolled in the study. The exclusion criteria included a recent respiratory tract infection, mental disorder, severe dysfunction of the central nervous system, increased intracranial pressure, or a history of dexmedetomidine allergy. Using a simple randomization procedure with computer-generated allocation, patients were randomly assigned to 1 of 3 treatment groups: group D (intranasal dexmedetomidine 2.5 μg/kg), group DK (intranasal dexmedetomidine 2 μg/kg and oral ketamine 3 mg/kg), or group K (oral ketamine 6 mg/kg). The allocation sequence was concealed from the investigator enrolling and assessing participants by using sequentially-numbered, opaque, sealed, and stapled envelopes.

Pre-anesthetic visits and communications with patients and their parents were conducted the day before surgery. Solid food was allowed until 8 h prior to the scheduled surgery time, and clear liquids were permitted until 3 h before this time. The investigator who prepared the concealed allocation envelopes was responsible for informing the nurse premedicating the children of the allocation group; this investigator was not involved with patient management or assessment during the trial. At 30 min before the induction of anesthesia, while the patient was still in the waiting room, a full-time nurse not involved in study measurements or evaluation administered intranasal dexmedetomidine, an oral ketamine syrup mixture (racemic ketamine and 5% glucose in a 1:2 ratio), or both to each patient, depending on the group assignment. Given that the concentration of the undiluted dexmedetomidine solution was 100 μg/ml, the volume administered with a 1-ml syringe was 0.02 ml/kg, which was sprayed evenly into both nostrils. The timing of premedication 30 min before induction was chosen based on the results of a previous clinical trial, which reported a sedation onset time of approximately 20–30 min.[7]

The heart rate (HR) and pulse oxygen saturation (SpO2) were recorded before drug administration (T0) and 10 min (T10), 20 min (T20), and 30 min (T30) after drug administration. The pulse oximeter was decorated with cartoon stickers and the children were distracted with stuffed toys to minimize stress associated with this monitoring. Sedation scores were assessed according to the Sedation Scale (SS-5, Table 1) at T10, T20, and T30. The time of sedation onset, defined as the time from drug administration to the time when the SS-5 score reached three points, was also recorded. Separation state was assessed at 30 min after premedication and designated as satisfactory separation if the Emotional State Scale (ESS-4, Table 1) score was no more than two points.

A trained nurse anesthetist with at least 5 years clinical experience performed venous cannulation; this person was blinded to the patient's group assignment. Successful venous cannulation was defined as an ESS-4 ≤ 2 at the time of attempted cannulation, regardless of whether the vein was actually cannulated on the first attempt. Children whose vein was cannulated were induced with intravenous propofol 3 mg/kg, fentanyl 3 μg/kg, and mivacurium chloride 0.2 mg/kg. Children for whom intravenous cannulation was not possible on the first attempt and those with an ESS-4 score ≥ 3 points were induced with sevoflurane.

After induction, an appropriately-sized laryngeal mask airway (LMA™, The Laryngeal Mask Company Limited, Singapore) was inserted. Ophthalmic 0.4% oxybuprocaine drops were instilled into the affected eye to provide topical anesthesia. Anesthesia was maintained with a combination of remifentanil 0.15 μg/kg/min and sevoflurane 1.0 minimum alveolar concentration. The attending anesthetists were unaware of the type of premedication administered. At the conclusion of the surgical procedure, the children were transferred to the recovery room with the LMA in place. The time of LMA removal (from the end of surgery to the time of removal) and the time of resumption of mental orientation (from the end of surgery to the time when the child opened his or her eyes and became oriented) were recorded. The children were discharged to the ward when their Aldrete score was at least 9. Follow-up evaluations were performed at 4, 8, 12, and 24 h after surgery, and adverse events were recorded by an observer who was blinded to the child's group assignment and did not participate in patient care.

Based on preliminary experiments, the rate of success of venous cannulation with dexmedetomidine alone was approximately 47%. Prospective power analysis revealed that 39 patients per group offered a 90% likelihood of detecting a clinically relevant (30%) increase in the successful venous cannulation rate, with a type I error of 5%. Estimating a loss of 10–15% of subjects during the trial, the number of patients in each group was tentatively set at approximately 45.

The results were analyzed with SPSS 15.0 software (SPSS Inc., Chicago, IL, USA). Parametric data are presented as mean ± standard deviation, and one-way analysis of variance (ANOVA) was used to compare mean differences between groups for demographic data, time of sedation onset, time of LMA removal, and time of resumption of mental orientation. Two-way ANOVA, followed by post hoc tests, was used to analyze heart rates, considering treatment and time as two independent factors. Tukey-corrected post hoc test was used to adjust the observed significance level for the multiple comparisons performed. Chi-square test was used to compare qualitative data: rate of successful intravenous cannulation, type of diagnosis, and rate of postoperative adverse events. Wilcoxon's rank sum test was to compare ranked data (sedation scores). P < 0.05 was considered statistically significant.

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