|Year : 2018 | Volume
| Issue : 3 | Page : 255-261
Dexmedetomidine-ketamine versus magnesium sulfate-ketamine for sedating children undergoing bronchoscopic fiberoptic intubation
Mostafa M Sabra
Department of Anesthesia and Intensive Care, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||06-Jul-2018|
|Date of Acceptance||10-Jan-2019|
|Date of Web Publication||15-Apr-2019|
Mostafa M Sabra
Department of Anesthesia, Faculty of Medicine, Al-Azhar University, Cairo 112273
Source of Support: None, Conflict of Interest: None
Background and aims Meticulous airway management, with the support of satisfactory sedation while keeping up a patent airway and guaranteeing ventilation, is an integral part for conscious sedation for bronchoscopic fiberoptic intubation in pediatric patients. This randomized double-blinded, prospective, comparative, clinical study aimed to compare the effects of dexmedetomidine-ketamine versus magnesium sulfate-ketamine for sedating children experiencing bronchoscopic fiberoptic intubation. The primary outcome was intubation scores as assessed by (a) vocal cord movement, (b) coughing, and (c) limb movement. Secondary outcomes were intubation time and patient tolerance using fiberoptic intubation comfort score.
Patients and methods A total of 60 patients having American Society of Anesthesiologist grade I aged between 7 and 14 years undergoing elective minor infraumbilical surgeries were included in the study. Patients were randomly allocated to one of two groups: group DK patients (n=30) received intravenous loading dose of dexmedetomidine (2 µg/kg) in 20 min, and then were maintained by 0.5 µg/kg/h infusion until successful placement of the tube in the trachea, and intravenous ketamine (0.5 mg/kg/h) after finishing the loading dose, and just before fiberoptic intubation, and group MK patients (n=30) received intravenous loading dose of magnesium sulfate (40 mg/kg) in 20 min, and then were maintained by 10 mg/kg/h until successful placement of the tube in the trachea, and ketamine (0.5 mg/kg) after finishing the loading dose, and just before fiberoptic intubation. Continuous data were summarized as mean±SD, whereas discrete (categorical) in percentage. The groups were compared by independent Student’s ‘t’ test. The discrete (categorical) variables were compared by χ2-test.
Results Intubation scores were better in group DK than group MK for vocal cord movement (P=0.009) and limb movement (P=0.0016), but there was no statistically significant difference in coughing (P=0.89). Time required for intubation was significantly less in group DK, as compared with the group MK (76.4±13.25 and 89.83±20.069 s, P=0.043). There was better fiberoptic intubation comfort score in group DK (P=0.0032). All patients were successfully intubated through fiberoptic bronchoscope in both groups. There were no significant hemodynamic changes between the two groups.
Conclusion Intravenous dexmedetomidine/ketamine improved awaken bronchoscopic fiberoptic intubation in children with better intubation scores, intubation tolerance, and less intubation time when compared with magnesium sulfate-ketamine.
Keywords: dexmedetomidine, fiberoptic bronchoscopy, ketamine, magnesium sulfate, pediatrics
|How to cite this article:|
Sabra MM. Dexmedetomidine-ketamine versus magnesium sulfate-ketamine for sedating children undergoing bronchoscopic fiberoptic intubation. Al-Azhar Assiut Med J 2018;16:255-61
|How to cite this URL:|
Sabra MM. Dexmedetomidine-ketamine versus magnesium sulfate-ketamine for sedating children undergoing bronchoscopic fiberoptic intubation. Al-Azhar Assiut Med J [serial online] 2018 [cited 2020 Jul 6];16:255-61. Available from: http://www.azmj.eg.net/text.asp?2018/16/3/255/255859
| Introduction|| |
Intubation strategies with high first-pass achievement rates may diminish complications of multiple attempts, such as cardiovascular arrest in children . One challenge related with this method is to give satisfactory sedation while keeping up a patent airway and guaranteeing ventilation. A perfect sedation regimen would provide patient comfort, blunting of airway reflex hemodynamic steadiness, amnesia, and maintenance of a patent airway with spontaneous ventilation ,.
Dexmedetomidine is an α2-adrenoceptor agonist that has antisialagogue effects, so it has a valuable role during bronchoscopy for intubation as it induces sedation and analgesia without respiratory depression ,.
Magnesium sulfate is used to treat hyperactive airway owing to smooth muscle relaxation of the bronchi , and also magnesium appears to diminish the occurrence of laryngospasm in pediatric patients .
Fibreoptic-guided tracheal intubation remains the ‘gold standard’ for pediatric difficult airways and is a basic skill in pediatric anesthesia .
The present study was designed to compare the effects of dexmedetomidine-ketamine versus magnesium sulfate-ketamine combinations for sedating children undergoing awake fiberoptic intubation regarding blunting of airway reflexes. The primary outcome measurements were intubation scores as assessed by (a) vocal cord movement, (b) coughing, and (c) limb movement. Secondary outcomes were intubation time and patient tolerance using fiberoptic intubation comfort score.
| Patients and methods|| |
After approval of the ethical and scientific committee, an informed written consent was obtained from the child’s parent or legal guardian on the day of surgery. This prospective, randomized, double-blind study was conducted in young cooperative 60 patients aged 7–14 years scheduled for minor infraumbilical surgeries, over a period of 6 months (from mars to August 2017) at Al-Hussein University hospital. All patients were American Society of Anesthesiologist class I. Exclusion criteria included refusal for consenting, patients with allergy to study drugs, bleeding disorder, predict difficult intubation cases, or patients with personality disorder.
Preprocedural evaluation included history taking, physical examination, and laboratory investigations (complete blood picture, liver and kidney function tests, and coagulation profile).
All patients fasted for at least 6 h before surgery; received EMLA cream to the dorsum of both hands, 1 h before induction; and were premedicated with intramuscular midazolam 0.05 mg/kg and atropine 0.01 mg/kg 30 min before admission to the operating room.
On arrival to the operating room, an intravenous line was secured with a 22 G cannula, and then standard monitoring was applied: ECG, blood pressure monitoring, pulse oximetry (S5, Patient Monitor; Datex Ohmeda-GE, Chicago, USA), and bispectral index (BIS) (Aspect Bis A-2000TM, Maryland, USA). Baseline mean arterial blood pressure (MAP1) and heart rate (HR1) were recorded.
Lactated ringer’s solution was infused (5–6 ml/kg/h). Children were preoxygenated with 100% oxygen insufflation through nasal prong (3–4 1/min).
Randomization was done by using computer-produced randomization chart (http://www.randomization.comhttp://www.randomization.com). Patients were divided into two groups of 30 patients each, that is, dexmedetomidine/ketamine (group DK) or magnesium sulfate/ketamine group (group MK). Random group assigned was enclosed in a sealed envelope to guarantee concealment of the assignment sequence. After transferring the patient to the operation theater, sealed envelope was opened by an anesthesiologist, who was not engaged in the study.
The study drugs were prepared in identical 50 ml infusion syringes:
- Dexmedetomidine infusion syringe contained 100 µg dexmedetomidine (precedex; United Pharmaceutical Group Company, CA, USA) diluted by normal saline to have 50 ml filled syringe (2 µg/ml).
- The magnesium sulfate infusion syringe contained 2000 mg magnesium sulfate (1% Misr Gmbh, 20 ml, Egypt) diluted by normal saline to have 50 ml filled syringe (40 mg/ml).
Ketamine: 20 mg ketamine (Ketamine; Sigma Company, Egypt) diluted with normal saline in a 10-ml syringe (2 mg/ml).
Group DK (n=30) received intravenous (iv) loading dose of dexmedetomidine (2 μg/kg=1 ml/kg/h) in 20 min, using B-Braun infusion pump (Perfusor compact 5, B. Braun, Germany), then maintained by (0.5 μg/kg/h infusion) until the tube is in the proper position, and iv ketamine (0.5 mg/kg=0.25 ml/kg) is given after finishing the bolus dose of dexmedetomidine, and just before fiberoptic intubation.
Group MK (n=30) received iv loading dose of magnesium sulfate (40 mg/kg=1 ml/kg/h) in 20 min, then maintained by (10 mg/kg/h infusion=0.25 ml/kg/h) until the tube is in the proper position, and iv ketamine (0.5 mg/kg=0.25 ml/kg) is given after finishing the bolus dose of magnesium sulfate, and just before fiberoptic intubation.
Following infusion of loading dose in each group, assessment of sedation level of the patient was done by using BIS. If BIS value less than 80 was achieved, airway manipulation was started through oral approach by placing an oral airway, and chin left was maintained to prevent possible airway obstruction.
If the patient remained inadequately sedated (BIS >80), propofol was given, and the patient was excluded from the study.
The fiberscopes were prepared by using an antifogging solution. Appropriate-sized endotracheal tubes were loaded onto the fiberscope with the Murphy eye up (bevel facing down); this orientation was maintained during passage of the endotracheal tube orally to facilitate successful placement into the trachea.
Blinding of the study was ensured for the patients receiving the treatment drugs and the investigators assessing the outcomes. The study medications were prepared by an independent observer who did not participate in any other part of the study, and the study drugs were administered by an anesthesiologist who was blind to the study drug.
The primary outcome measurements were as follows:
Intubation scores  were assessed as follows:
- Vocal movement: 1=open, 2=moving, 3=closing, and 4=closed.
- Coughing: 1=none, 2=slight, 3=moderate, and 4=severe.
- Limb movement: 1=none, 2=slight, 3=moderate, and 4=severe.
Secondary outcomes were as follows:
- Patient tolerance was assessed by a five-point fiberoptic intubation comfort score as follows :
- 1 = no reaction, 2=slight grimacing, 3=heavy grimacing, 4=verbal objection, and 5 = defensive movement of head and hands.
- The intubation time is recorded, which is defined as the time from mask removal to confirmation of endotracheal tube placement by end-tidal carbon dioxide detection, and auscultation for bilateral equal air entry. This time is measured by stopwatch.
The number of attempts required for successful intubation was recorded. If three attempts of intubation were unsuccessful, the attending anesthesiologist intubated the child and a failure was recorded. Intubation attempt was aborted if there was a decrease in oxygen saturation to 95% before completion of intubation, or if the attempt took longer than 3 min. Failure rate between groups was also compared.
After successful intubation and after identification of the carina, the cuff was inflated, the tube was secured, and general anesthesia was induced. Fentanyl (1 µg/kg) and atracurium (0.45 mg/kg) were administered to facilitate mechanical ventilation. MAP and HR were recorded at the end of infusion (MAP2 and HR2), just before intubation (MAP3 and HR3), and 1 min after intubation (MAP4 and HR4).
Mechanical ventilation was adjusted to maintain Et-CO2 at 30–35 mmHg. Anesthesia was maintained by sevoflurane, and top-up doses of atracurium were administered when indicated by muscle relaxation monitoring with a nerve stimulator (model NS252; Fisher and Paykill, USA). Blood pressure and HR were calculated every 5 min through the procedure until extubation was done.
At the end of the surgery, reversal of neuromuscular block was done by 0.05 mg/kg prostigmine and 0.01 mg/kg atropine followed by suctioning of secretions. Tracheal extubation was performed after confirming sufficient recovery (patient is conscious, hemodynamic stability, spontaneous breathing and oxygen saturation >95%), finally patients were transferred to recovery room.
The recovery time (time from extubation to spontaneous eye opening) and incidence of adverse effects (hoarseness and xerostomia) were also recorded. Postoperative nausea and vomiting were managed by giving intravenously 4-mg ondansetron. Any respiratory complications such as labored breathing, respiratory depression (RR <10 bpm), or oxygen desaturation (SpaO2<92%) were recorded. Oxygen mask was applied to improve oxygen saturation.
Sample size calculation was based on the data of a similar study  which indicated that a total sample size of 60 patients (after exclusion of the dropout) randomly allocated into two equal groups (30 patients in each group) is sufficient to ensure power 80% and type-1 error of 0.05, for difference in intubation scores by 10–20%, before intubation.
Continuous data were summarized as mean±SD, whereas discrete (categorical) in percentage. The groups were compared by independent Student’s ‘t’ test. The discrete (categorical) variables were compared by χ2-test. Collected data were organized, tabulated, and statistically analyzed using statistical package for the social sciences, version 22 (SPSS; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
A total of 60 children aged 7–14 years having American Society of Anesthesiologist I scheduled for minor infraumbilical surgeries were enrolled for the study, and all patients underwent successful orotracheal intubation. The patients were assigned to dexmedetomidine-ketamine group (group DK) (n=30) and magnesium sulfate-ketamine (group MK) (n=30). Both the groups were similar with respect to demographic characteristics such as age, sex, and Mallampati classification in cooperative patients [Table 1] and [Table 2]. No patients were excluded from the study.
There was a statistically significant decrease regarding BIS (P=0.009) in group DK, compared with group DM ([Figure 1]).
The intubation scores for vocal cord movement and limb movement differ significantly between the groups. Poor scores were seen in group DM. Seventeen patients in group MK had moderate movements during the procedure, whereas only three in group DK, but there was no statistically significant difference in coughing scores. With respect to fiberoptic intubation comfort score, there was better intubation comfort score in group DK, as heavy grimacing was observed in eight patients in group MK, whereas it was observed only in one patient in group DK. This difference was also statistically significant (P<0.0032). No patient had verbal objection, or defensive movements in both groups, as shown in [Table 3].
|Table 3 Intubation time and number of intubation attempts among the two groups|
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There was a statistically significant decrease (P=0.0433) in intubation time in group DK than group DM, but there was no statistically significant difference in the number of intubation attempts between the two groups (1.2±0.48 in group DK vs. 1.3±0. 59 group MK). There was no record of attempt failure in both groups.
There were no recorded cases of decreased oxygen saturation below 95% in both groups. In addition, no apneic episodes occurred and no rescue maneuvers were required in either group. No airway obstruction in spontaneously breathing patients has been reported owing to maintained chin lift.
Hemodynamic parameters (HR and MAP) did not differ significantly between the groups at all time intervals, and these variables did not differ significantly from baseline values ([Figure 2] and [Figure 3]).
|Figure 2 Mean heart rate changes in both groups: four time points were used for analyzing heart rate changes: HR1=baseline (preinfusion); HR2=end of infusion; HR3=immediately before tracheal intubation, and HR4=1 min after tracheal intubation.|
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|Figure 3 Mean arterial pressures in the groups: four time points were used for analyzing heart rate changes: MAP1=baseline (preinfusion preparation); MAP2=end infusion; MAP3=immediately before tracheal intubation, and MAP4=1 min tracheal intubation.|
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There were no statically significant differences in blood pressure or HR in both groups throughout the surgical procedure until extubation was done.
No serious complications occurred in either groups throughout the fiberoptic intubation procedures. Three cases in group DK cases complained of xerostomia.
Moreover, there was no statistically significant difference in the recovery time in both groups (130.2±30.48 s in group DK vs. 125.3±24. 59 s group MK, P=0.68), likely owing to the time of administration of drugs (20 min before induction). In the postoperative period, no patients in both groups remembered that the fiberscope was in their mouth.
| Discussion|| |
Spontaneous breathing during fiberoptic intubation in pediatric patients is required, especially in difficult airways, as pediatric patients desaturate very quickly if ventilation is interrupted, mainly owing to high metabolic rate and increased oxygen consumption. Patients at that age usually are uncooperative, which is an another challenge.
Anesthesiologists use different methods to provide enough sedation for pediatric patients to perform nonapneic fiberoptic intubation, while at the same time staying away from compromising airway with too much sedation. The ideal sedation regimen should provide patient acceptable sedation level and maintain spontaneous respiration without altering airway function.
In this study, the use of dexmedetomidine-ketamine provides optimum sedation without compromising airway with lower intubation time and less intubation attempts during awake bronchoscopic fiberoptic intubation in comparison with magnesium sulfate-ketamine.
The use of infusion method in this study exerts a choice to control the level of sedation, so there was a margin of safety enough to prevent unintended deep sedation. This technique is not difficult and can be appropriate for pediatric patients expected to have intubation difficulty. Children in both groups showed helpful amnesia, as it would be expected owing to the use of midazolam. Group DK showed statistically significant decrease in BIS value, indicating more sedation level at the intubation time, which was clinically important.
Over the most recent of years, dexmedetomidine has been used as a result of its sedative, anxiolytic, and antisialagogue properties, while keeping spontaneous respiration; it has prodded the term cooperative sedation .
Ketamine was used in this study to counteract sympatholytic effects of dexmedetomidine, its analgesic effects, and maintaining airway reflexes .
Dexmedetomidine dose used in this study was obtained from a synthesis of the current literature that used high doses of dexmedetomidine versus different studies that used lower doses .
Mason et al.  describe increased success rate with a higher dosage of dexmedetomidine (3 μg/kg for loading dose and 2 μg/kg for infusion) for noninvasive procedures such as magnetic resonance imaging. Dexmedetomidine at a lower dose used for noninvasive techniques has brought about a requirement for adjuvant such as fentanyl and midazolam. In this study, ketamine was used as adjuvant which allowed the use of low-dose regimen with minimal effect on ventilatory drive. Moreover, the use of ketamine also compensates for bradycardia, hypotension, and dry mouth induced by dexmedetomidine .
Matthew Green et al.  recorded similar results in managing difficult pediatric airways, through case reports. One of them was a 6-year-old female child with Pierre Robin syndrome sequence, with difficult intubation and mask ventilation, and the patient was successfully intubated through GlideScope video laryngoscope after infusion of dexmedetomidine bolus dose of 2 μg/kg intravenously over 10 min, followed by an infusion of 1 μg/kg/h, and then ketamine bolus of 1 mg/kg intravenously was administered .
This study used magnesium sulfate (40 mg/kg) as per Elgebaly and Eldabaa , who described fiberoptic bronchoscopy for tracheal intubation in magnesium sulfate at that dose was simpler, quicker, and without hemodynamic or respiratory adverse effects. Many studies showed that magnesium sulfate infusion with similar doses was well tolerated, with no complications, and the dose did not reach toxic levels ,.
Magnesium sulfate has anesthetic, analgesic, and sedative effects , as it has antagonistic effects for NMDA glutamate receptors, so magnesium sulfate appears to have multifactorial mechanisms of action .
In this study, both dexmedetomidine/ketamine and magnesium sulfate-ketamine provided adequate and satisfactory sedation for fiberoptic intubation as shown by primary and secondary outcomes, but dexmedetomidine-ketamine combination was found to have superior effect.
| Conclusion|| |
Fiberoptic bronchoscopic tracheal intubation in dexmedetomidine-ketamine provides favorable conditions for bronchoscopic fiberoptic intubation including, excellent intubation conditions and hemodynamical stability, as compared with magnesium sulfate-ketamine group. Hence, this study recommends dexmedetomidine-ketamine to facilitate awaken bronchoscopic fiberoptic intubations in children.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]