|Year : 2020 | Volume
| Issue : 1 | Page : 70-74
Comparison of the use of nebulized dexmedetomidine, ketamine, and a mixture thereof as premedication in pediatric patients undergoing tonsillectomy: a double-blind randomized study
Mohammad Hazem I Ahmad Sabry, Nader A El Gamal, Nourhan Elhelw, Ramadan A Ammar
Department of Anesthesiology and Surgical Intensive Care, Faculty of Medicine, Alexandria University, Alexandria, Egypt
|Date of Submission||14-Oct-2018|
|Date of Acceptance||19-Jun-2019|
|Date of Web Publication||16-Apr-2020|
MBChB, MSc, FRCPC, MD, ABPM Nader A El Gamal
Department of Anesthesiology and Surgical Intensive Care, Alexandria Faculty of Medicine, Khartoum Square, Shalalat, Alexandria 2111
Source of Support: None, Conflict of Interest: None
Purpose To compare the use of nebulized dexmedetomidine, nebulized ketamine, and a mixture thereof as premedication in children aged 3–6 years undergoing tonsillectomy.
Patients and methods Seventy-five patients were assigned randomly to three groups (n=25/group) that received nebulized dexmedetomidine (3 μg/kg; group A), nebulized ketamine (3 mg/kg; group B), and nebulized dexmedetomidine (1.5 μg/kg) plus nebulized ketamine (1.5 mg/kg; group C). The drugs were prepared in 0.9% normal saline, and the children underwent nebulizer sessions 30 min before surgery. The primary end point was the level of sedation, measured 30 min after nebulization using Ramsay scale. We also measured ease of parental separation, face mask acceptance, hemodynamic stability, postoperative analgesia requirement (using a visual analog scale), and recovery and discharge times.
Results The three groups did not differ in terms of age, sex, or weight. The level of sedation (in 15 and 30 min) was higher in group A than in group B (P=0.039), but no significant difference in sedation score was detected among the three groups. Ease of parental separation and face mask acceptance were better in group A than in group B (P=0.037). The groups did not differ in terms of analgesia requirement, recovery time, or discharge time.
Conclusion Nebulized dexmedetomidine achieves better sedation and facilitates parental separation and face mask acceptance during inhalational induction compared with nebulized ketamine and a mixture of nebulized ketamine and dexmedetomidine, with no effect on hemodynamic stability or recovery or discharge time.
Keywords: clinical practice guidelines, dexmedetomidine, ketamine, nebulized, pediatric general, premedication, preoperative workup, sedation, tonsillectomy
|How to cite this article:|
Ahmad Sabry MI, El Gamal NA, Elhelw N, Ammar RA. Comparison of the use of nebulized dexmedetomidine, ketamine, and a mixture thereof as premedication in pediatric patients undergoing tonsillectomy: a double-blind randomized study. Res Opin Anesth Intensive Care 2020;7:70-4
|How to cite this URL:|
Ahmad Sabry MI, El Gamal NA, Elhelw N, Ammar RA. Comparison of the use of nebulized dexmedetomidine, ketamine, and a mixture thereof as premedication in pediatric patients undergoing tonsillectomy: a double-blind randomized study. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 Jun 2];7:70-4. Available from: http://www.roaic.eg.net/text.asp?2020/7/1/70/282593
| Introduction|| |
In pediatric patients, preoperative anxiety and parental deprivation remain challenges to anesthesiologists that must be managed in many ways, most importantly by premedication . Premedication should reduce preoperative anxiety, fear, emotional stress, and tension; ease child–parent separation; and facilitate the induction and maintenance of anesthesia . Drugs can be administered by many routes, including oral, intramuscular, intravenous, intranasal, rectal, transdermal, and nebulized routes . Nebulized drugs may enable better absorption through the nasal, buccal, and respiratory mucosa, with better patient acceptance .
Dexmedetomidine is an α-adrenoceptor agonist with dose-dependent α2-adrenoceptor selectivity. Its primary site of action in the central nervous system is the locus coeruleus, where it induces electroencephalographic activity similar to that of natural sleep, with easy arousal by external stimulation . Ketamine induces dissociative anesthesia, a totally different state from those provided by other anesthetic drugs (e.g. barbiturates, propofol, benzodiazepines, and halogenated volatile anesthetics). In this cataleptic state, the patient’s eyes remain open, with typical nystagmus and conservation of the laryngeal, corneal, and pupillary reflexes . In this study, we compared the use of nebulized dexmedetomidine, nebulized ketamine, and a mixture of the two drugs as premedication in children aged 3–6 years who were undergoing tonsillectomy. We examined the sedating effects of these premedications as the primary end point. We also measured ease of parental separation, face mask acceptance, analgesia, hemodynamic stability, and sedation at emergence. The purpose of this study is to compare the use of nebulized dexmedetomidine, nebulized ketamine, and a mixture thereof as premedication in children aged 3–6 years undergoing tonsillectomy.
| Patients and methods|| |
This double-blind randomized study was approved by the Ethics Committee of the Faculty of Medicine, Alexandria Main University Hospital, Alexandria, Egypt, and registered in the pan-African clinical trial registry (http://www.pactr.org) before patient enrollment (PACTR #201610001691412, 23 June 2016). The first patient was enrolled on 25 June 2016. Written informed consent was obtained from all participants’ parents. The primary outcome of sedation (Ramsey sedation score, [Table 1]) was examined.
The study included 75 children aged 3–6 years with American Society of Anesthesiologists physical statuses I and II who were scheduled for tonsillectomy [performed in the hospital’s Ambulatory Surgery operating rooms (ORs)]. Sample size was calculated by our statistic department of Alexandria University Research Institute. Exclusion criteria were chest infection or respiratory disease, cardiac disease, mental or physical disability, treatment with sedatives or anticonvulsants, and parental refusal of participation. We determined that a sample of 25 patients per group would yield 81% power to detect a one-point difference in sedation.
Using sealed envelopes, patients were assigned randomly to three groups (n=25/group) that received nebulized dexmedetomidine (3 μg/kg; group A) (Precedex Pfizer, NY, USA), nebulized ketamine (3 mg/kg; group B) (Ketlar), and nebulized dexmedetomidine (1.5 μg/kg) plus ketamine (1.5 mg/kg; group C) (Ketalar Hameln; Hameln, Germany). The drugs were prepared in 0.9% normal saline to a final volume of 3 ml. Nebulization was performed using a wall nebulizer and wall oxygen source on 4 l/min (disposable nebulizer face mask, Alimed, Alexandria, Egypt). A researcher who did not participate in the evaluation of sedation administered the drugs to all children in nebulizer sessions ∼30 min before transfer to the OR. Parents were not allowed to accompany the patients to the OR, per hospital protocol.
In the OR, children received standard monitoring, including ECG, noninvasive arterial blood pressure measurement, and pulse oximetry (Penlon-PM9000 express). An anesthesiologist not involved in the evaluation of sedation induced anesthesia by inhalation of sevoflurane, followed by the establishment of an intravenous peripheral line and muscle relaxation using cisatracurium (Nimbex, Abimol; GSK Egypt, Cairo, Egypt, 0.1 mg/kg) and fentanyl (1 μg/kg) (fentanyl Hameln). After tracheal intubation, anesthesia was maintained using isoflurane. Extubation was performed after the completion of surgery when patients met the extubation criteria as awake , followed by discharge to a recovery room.
Data collection and measures
Demographic data (age, weight, and sex) was collected at the beginning of the study. Vital signs (heart rate and mean arterial blood pressure) and oxygen saturation (%) were recorded before sedation, before the induction of anesthesia (30 min after sedation), every 10 min after induction, and every 30 min in the recovery room for the first postoperative hour. Ramsay sedation scale  scores were recorded 15 and 30 min after sedation by an anesthesiologist blinded to the study medication. The ease of parental separation and face mask acceptance were evaluated using a four-point scale ([Table 2]) . The need for postoperative analgesia was measured using a visual analog scale (scale from 0 to 10) every 30 min postoperatively until discharge .
Patients with scores more than or equal to 4 received rescue analgesia in the form of paracetamol suppositories, with doses determined according to weight as 15 mg/kg . We used paracetamol suppositories 300 mg (Abimol) cut to approximate dose maximum 300 mg. All patients received it except two patients in group A and one patient in group C. Fast-track criteria were used to determine whether outpatients could be transferred directly from the OR to the step-down unit . A modified postanesthetic discharge scoring system was used to determine when patients were ready to be discharged home .
Data were fed to the computer and analyzed using IBM SPSS software package, version 20.0 (IBM). The primary outcome of sedation (nonparametric Ramsey sedation score) was examined using the Monte-Carlo method. The secondary outcomes were assessed using the χ2 test and analysis of variance in the form of ease of parental separation and face mask acceptance, analgesia, hemodynamic stability, and sedation at emergence.
| Results|| |
The three groups did not differ in terms of age, sex, or body weight. The heart rate, mean arterial blood pressure, and oxygen saturation did not differ among groups before sedation, 30 min after the nebulizer session, or at 40, 50, and 60 min after sedation (intraoperatively and postoperatively).
At 15 and 30 min after nebulization ([Figure 1]), 24% of patients in group A had Ramsey sedation scores of 1, 64% had scores of 2, and 12% of patients had scores of 3. In group B, 48% of patients had scores of 1, 52% had scores of 2, and no patient had a score of 3 at these time points. In group C, 24% of patients had scores of 1, 72% had scores of 2, and 4% of patients had scores of 3 at these time points. These values differed significantly between groups A and B (P=0.039), but not among the three groups.
|Figure 1 Comparison between the three studied groups according to Ramsay sedation score.|
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Regarding parental separation and face mask acceptance ([Figure 2]), 20% of patients in group A had excellent scores and 32% had good scores. In group B, no patient had an excellent score and 20% of patients had good scores. In group C, 4% of patients had excellent scores and 28% had good scores.
Visual analog scale scores at 30 min postoperatively were 2–8±1.63 in group A, 4–8±1.41 in group B, and 2–8±1.43 in group C. Recovery and discharge times had no significant difference among the three groups.
Regarding respiratory complications, five patients who received nebulized ketamine in group C had productive cough with excessive mucus secretion immediately after the nebulizer session, and two of them vomited several minutes thereafter.
| Discussion|| |
Premedication remains an important issue in pediatric anesthesia. Drugs that have been used as premedication have shown variable degrees of effectiveness, acceptance, and safety . In this study, we compared the effects of nebulized dexmedetomidine, nebulized ketamine, and a nebulized mixture of these drugs when used as premedication in pediatric patients undergoing tonsillectomy. Sedation scores was higher using Nebulized dexmedetomidine with less respiratory complications than ketamine (productive cough, excessive mucus secretion, and vomiting).
The lack of a difference in heart rate, mean arterial blood pressure, and oxygen saturation among the three groups in this study likely reflects the use of doses smaller than those that produce adverse effects (e.g. dexmedetomidine-associated bradycardia and hypotension and ketamine-associated tachycardia and hypertension). Administration by nebulization requires the use of larger doses than does administration by other routes . In contrast to our findings, Zanaty and Elmetainy  reported significantly lower heart rate and mean blood pressure at 30 min after premedication administration in pediatric dental restoration patients receiving dexmedetomidine compared with baseline values and values from those receiving ketamine and a mixture of ketamine and dexmedetomidine.
Ketamine has been reported to cause excessive secretion, which provokes cough and then vomiting , as observed in five cases in this study; this was attributed to the difference in patient population.
Ramsay sedation scores were the same at 15 and 30 min after nebulization in all patients in this study, probably because sedation by this method is effective within less than 15 min. Group A had the highest sedation scores, which differed significantly from those in group B. Group A also had the highest parental separation and face mask acceptance scores, whereas these scores were lowest in group B. In contrast, Zanaty and Elmetainy  used the Modified Observer’s Assessment of Alertness/Sedation Scale and reported higher sedation scores at 30 min after nebulization for patients who received a mixture of ketamine and dexmedetomidine than for those who received ketamine or dexmedetomidine alone, and higher scores for ease of parental separation and face mask acceptance in patients who received ketamine and dexmedetomidine mixture group compared with the other two groups. These differences could be owing to differences in patient population as it was done in pediatrics undergoing dental restoration and possible small sample size. Jia et al.  studied the premedication effects of various combinations of intranasal dexmedetomidine and oral ketamine in children and found that the administration of 2 µg/kg intranasal dexmedetomidine and 3 mg/kg oral ketamine was optimal to facilitate separation from parents and intravenous line placement or face mask acceptance .
In this study, no difference among groups in analgesia requirement was observed 30 min postoperatively, with most patients receiving rescue analgesia based on visual analog scale scores. In contrast, Zanaty and Elmetainy  reported that analgesia was better in patients who received dexmedetomidine/ketamine with lower pain score compared with ketamine alone, possibly owing to differences in patient population as it was done in pediatrics undergoing dental restoration. Fast track and discharge times did not differ among groups in this study (P=0.234 and 0.849, respectively). Limitations of the study include the sample size was small, postoperative follow-up was short, and patient/parents satisfaction was not assessed.
| Conclusion|| |
Nebulized dexmedetomidine (3 μg/kg), nebulized ketamine (3 mg/kg), and a mixture of dexmedetomidine (1.5 μg/kg) and ketamine (1.5 mg/kg) can be used as premedication in pediatric patients. Nebulized dexmedetomidine achieves better sedation and facilitates parental separation and face mask acceptance during inhalational induction compared with nebulized ketamine, with neither drug affecting hemodynamic stability nor recovery or discharge time.
The work was carried out in Alexandria University Hospitals.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]