Dexmedetomidine with Low-dose Ketamine vs Dexmedetomidine Alone for Sedation and Hemodynamics in Otological Surgeries under Monitored Anesthesia Care
Corresponding Author: Pritee H Bhirud, Department of Anesthesia, Bhabha Atomic Research centre and Hospital, Navi Mumbai, Maharashtra, India, Phone: +91 9820669549, email: email@example.com
Aims and objectives: Dexmedetomidine a potent and highly selective α-2 adrenoceptor agonist with sympatholytic, sedative, amnestic and analgesic properties is ideal for monitored anesthesia care (MAC). When used with Ketamine, the bradycardia and hypotension associated with dexmedetomidine may be prevented. Whereas dexmedetomidine may prevent tachycardia, hypertension, salivation, and emergence phenomena of ketamine. There are few references in literature about this drug combination. Hence we studied and compared the effect of intravenous dexmedetomidine infusion with low-dose ketamine infusion on sedation and hemodynamics in ear surgeries under MAC.
Materials and methods: ASA 1 and 2 patients scheduled for elective ear surgeries were randomized in groups A and B. Patients in both groups were administered IV dexmedetomidine 0.5 μg/kg as a bolus over 10 minutes followed by the 0.5 μg/kg/hr as maintenance infusion in group A, whereas low-dose IV Ketamine 0.2 mg/kg/hr was added in group B in addition to dexmedetomidine infusion.
Local block using 2% lignocaine with adrenaline was performed by the ENT surgeon. Sedation (MOAA/S) hemodynamics, respiratory rate and oxygen saturation were recorded. Patient satisfaction was assessed using Likert scale. Mann-Whitney test was used to compare sedation between the two groups. Hemodynamic variables were analyzed by Student’s t -test. The Association of parameters among study group was assessed with the help of Chi-square test. Qualitative data was presented with the help of Frequency and Percentage table.
Results: There was a statistically significant difference (p < 0.05) in sedation score between the groups (group A-3, group B-2) from 5 minutes interval onwards. There was significant difference in hemodynamics between the two groups from 5 minutes interval onwards with the values being higher in group B. Patient satisfaction score was better in group B compared to group A. Group A, i.e., only exmedetomidine needed more interventions to maintain sedation and to correct hypotension.
Conclusion: Dexmedetomidine with low-dose ketamine infusion provides early onset and adequate sedation, better hemodynamic profile, and patient satisfaction than dexmedetomidine alone for ENT surgeries under MAC.
Clinical significance: ‘Synergistic’ combination of dexmedetomidine with low-dose ketamine provides early and better sedation while maintaining hemodynamics as compared to dexmedetomidine infusion alone for ENT surgeries under MAC.
How to cite this article: Bhirud PH, Kate JA, Toal PV, et al. Dexmedetomidine with Low-dose Ketamine vs Dexmedetomidine Alone for Sedation and Hemodynamics in Otological Surgeries under Monitored Anesthesia Care. J Res and Innov Anesth 2022;7(1):14-18.
Source of support: Nil
Conflict of interest: None
Keywords: Dexmedetomidine, Ketamine, Monitored anesthesia care, Otological surgery
Dexmedetomidine is a potent and highly selective α-2 adrenoceptor agonist with sympatholytic, sedative, amnestic and analgesic properties. It provides unique “conscious sedation” and analgesia, without respiratory depression.1 This has facilitated its use for surgeries of the ear such as tympanoplasty, stapedectomy, ossiculoplasty, mastoid surgery, etc., under MAC. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist has sedative, analgesic and sympathomimetic effects.2 When used together, dexmedetomidine may prevent tachycardia, hypertension, salivation, and emergence phenomena of ketamine, whereas ketamine may prevent bradycardia and hypotension associated with dexmedetomidine.3 Combination of ketamine with dexmedetomidine has been used for sedation particularly in pediatric patients as well as for procedural sedation in adults.4-11 Hence we conducted this prospective, randomized, double blind, comparative study to elucidate the effects of dexmedetomidine with or without low-dose on sedation and hemodynamics in ear surgeries done under MAC. Our primary aim was to compare intraoperative sedation and study the effect on hemodynamics.
MATERIALS AND METHODS
After institutional ethics committee approval, written, informed consent was taken from adult ASA I and II patients posted for elective ear surgeries under MAC. Patients with a history of atrioventricular block or conduction block, heart failure, liver cirrhosis, concurrent beta blocker therapy, existing bradycardia (HR <50 per minute), psychiatric disorders on medications and respiratory disorder were excluded from the study.
Consecutive patients who participated in the study were randomized based on computer generated random numbers (www.randomizer.org) into two groups, A and B. The patients were blinded to group allocation.
Drug loading and administration were done by two different anesthetists to ensure blinding. Dexmedetomidine was prepared 5 μg/mL strength in syringe 1 (20 mL) and ketamine as 5 mg/mL in syringe 2 (20 mL).To ensure blinding in group A, a syringe with 20 mL normal saline was labeled as Syringe 2.
Baseline monitoring included electrocardiogram (ECG), heart rate (HR), respiratory rate (RR), noninvasive blood pressure (NIBP), mean arterial pressure (MAP) and oxygen saturation (SpO2). Supplemental oxygen was administered via nasal prongs at 2l/minute. RR was monitored using a side stream EtCO2, by attaching the tip of the cannula near the nostril of the patient. An intravenous (IV) access was established with 20 G cannula and Ringer lactate infusion was started.
Patients in both groups were administered inj. Dexmedetomidine (syringe 1) at 0.5 μg/kg infusion as a bolus dose over 10 mintues. The surgeon performed the local block using 2% lignocaine with 1:200000 Adrenaline (4-6 mg/kg). In group A the bolus was followed by inj. Dexmedetomidine 0.5 μg/kg/hr as maintenance infusion along with normal saline (syringe 2) infusion throughout the duration of surgery to ensure blinding. In group B bolus was followed by inj. Dexmedetomidine 0.5 μg/kg/hr infusion with low-dose inj. Ketamine 0.2 mg/kg/hr (syringe 2) infusion throughout the duration of surgery.
The level of sedation Modified Observer Assessment of Alertness/Sedation Scale (MOAA/S), HR, BP- MAP, SBP, DBP, were assessed at the start and end of bolus infusion, and every 5 minutes thereafter for 15 minutes and every 15 minutes till the completion of surgery.
Bradycardia was defined as HR <50 beats/min and was treated with inj. Glycopyrrolate 0.2 mg IV. If bradycardia persisted even after inj. Glycopyrrolate, Inj. Atropine 0.6 mg IV was given.
Hypotension was defined as more than 25% fall in MAP compared to MAP recorded at end of dexmedetomidine bolus or MAP less than 60 mm Hg, whichever was lower. Hypotension was treated with inj. Ephedrine 6 mg (E6).
Adequate sedation was defined as MOAA/S score of 2-3, whereas a score of 4-5 or 1 was defined as inadequate and excess sedation respectively. In case of inadequate sedation, infusion in syringe 1 was titrated from 0.5 ug/kg/hr to 0.75 μg/kg/hr. If sedation level was still inadequate, infusion in syringe 2 was titrated from 0.2 mg/kg/hr to 0.5 mg/kg/hr. In case of excess sedation, infusion in syringe 1 was titrated from 0.5 μg/kg/hr to 0.25 μg/kg/hr. If the patient became uncooperative or complained of discomfort, infusion in syringe two was stopped.
Injection Fentanyl 20 ug IV bolus was administered as a rescue analgesic. In spite of sedation and hemodynamic stability if there was impairment in the visibility of the surgical field due to bleeding injection nitroglycerin 0.05 μg/kg/min was started.
In the postoperative period, after 24 hours the patient was asked about the recall of perioperative events and patient satisfaction with sedation during surgery was assessed using Likert scale.12
Confidence interval 90%, Power of 80% (type II error) Margin of error (type I error) 5%, (population size 150) sample size 97 was derived. 100 patients were assessed for eligibility, of which 4 patients were excluded as per the exclusion criteria. 96 patients were enrolled in the study of which 2 were excluded due conversion to general anesthesia. Finally, a total of 94 patients were studied.
Data analysis was done with the help of SPSS software version 23. Quantitative data was presented with the help of Mean, Standard deviation, Median and median interquartile range (IQR). Comparison among study groups was done with the help of student t -test. Intraoperative sedation by MOAA/S was compared between groups with the help of Mann-Whitney test. Hemodynamics were analyzed by student’s t -test. Qualitative data was presented with the help of the Frequency and Percentage table, Association among the study group was assessed with the help of the Chi-square test. p-value < 0.05 was taken as significant.
The demographic details such as age, weight, gender and ASA status were comparable in both the groups. There was a statistically significant difference (p < 0.05) in sedation levels between both the groups from 5 minutes interval onwards. In group A sedation score remained 3 for most of the surgery duration whereas in group B it was 2 (Fig. 1).
Baseline hemodynamic parameters were comparable in both groups. There was significant difference in MAP between the two groups from 5 minutes interval onwards (p < 0.05). MAP was higher in group B compared to group A but did not affect the surgical field. MAP decreased from baseline 104.57 ± 10.68 mm hg to lowest MAP of 75.00 ± 6.00 mm hg at 3 hours interval in group A (p -0.012) and from baseline MAP of 103.72 ± 8.37mm hg to lowest MAP of 81.88 ± 3.96 mm hg at 2 hours 15 minutes interval in group B (p -0.000) (Fig. 2).
There was a significant difference in HR between groups A and B from 30 minutes interval onwards (p < 0.05). Within the group, HR showed decreasing trend from baseline HR 79.26 ± 6.12 per minute to lowest HR of 53.75 ± 1.26 per minute at 2 hours 30 minutes in group A (p -0.011) and from baseline HR 77.85 ± 8.52 per minute to lowest HR of 62.71 ± 7.11 per min at 2 hours 45 minute in group B (p -0.001) (Fig. 3).
Patient satisfaction score was significantly more in group B 4.5 ± 0.6 compared to group A 4.2 ± 0.6 (p -0.007).
Considering interventions, in group A, 4 patients required dexmedetomidine infusion to be increased to 0.75 μg/kg/hr to achieve adequate sedation, whereas none of the patients in group B needed change in Infusion rate (8.5%). Inj. Ephedrine as a single IV bolus 6 mg for hypotension was required by 6 patients (12.8%) of group A as compared to 1 patient (2.1%) in group B.
Inj. Fentanyl single IV bolus 20 μg as a rescue analgesic was required by 7 patients (14.9%) in group A whereas in group B it was required by 6 patients (12.8%). Inj. Glycopyrrolate 0.2 mg IV was required by 5 patients (10.6%) of group A and 1 patient (2.1%) of group B for bradycardia. None of the patients required further inj Atropine for bradycardia. NTG infusion was started for 1 patient (2.1%) in group A whereas for 3 patients (6.4%) in group B for hypertension. The number of interventions needed was significantly more in group A as compared to group B for maintaining adequate sedation and treating hypotension (Table 1). Two patients needed conversion to GA due to the increased extent of surgery intraoperatively.
|Group A||Group B||Chi-square||p-value|
This study aimed to compare sedation and hemodynamic profile of dexmedetomidine infusion alone and in combination with low-dose ketamine infusion in ear surgeries. A statistically significant difference was seen in sedation, MAP and HR between the two groups. Low-dose ketamine infusion (0.2 mg/kg/hr) in group B ensured early onset sedation and stable hemodynamics with higher intraoperative MAP as compared to group A. Despite the higher MAP in group B, the surgical field was unaffected.
In our study, adequate sedation score (MOAA/S 2-3) was achieved in both groups, with none of the patients having inadequate or excess sedation. Patients in group B achieved a sedation score of 3 at 5 minutes (after infusion) and score 2 at 15 minutes which was earlier than group A. Sinha S.K et al. found sedation scores in dexmedetomidine-ketamine group was 3.43 whereas in dexmedetomidine group 3.97 for awake fibreoptic intubation. These findings are similar to our study, but Sinha SK et al. noted observations only for 2 minutes postintubation.11 Chun E.H. et al. in their study for chemoport insertion under MAC found lowest MOAA/S score 2 in dexmedetomidine-ketamine (group DK). But they needed more rescue sedative, which could be due to the single bolus of ketamine used rather than infusion.6 Bali B K et al. used Ramsay sedation Score (RSS) to evaluate sedation in upper gastrointestinal scopy and noted mean time to achieve the score of 3-4 was 3.7 ± 0.4 minute.5 The time needed to achieve MOAA/S 3 in our study was 5 minutes from the end of bolus. The sedation score used in our study was MOAA/S whereas Bali et al. used the RSS score.
Although hemodynamics stayed within normal physiological limits there was a statistically significant fall in MAP from baseline in both groups in our study. In group B, low-dose ketamine infusion (0.2 mg/kg/hr) was attributed to higher intraoperative MAP. Despite the higher MAP, the surgical field was unaffected. Similar to our results Sinha S.K. et al. compared the fall in MAP between the two groups and found a significant difference. In their dexmedetomidine Ketamine group (group I) the fall in MAP from baseline was significant only at 2 minutes interval whereas in the dexmedetomidine group (group II) there was a significant fall in MAP from baseline at all intervals.11 However Sinha et al. found no significant fall in MAP compared to baseline in dexmedetomidine-Ketamine group which could be due to the fact that they used a higher bolus followed by infusion of ketamine and also recorded their finding only for 2 minutes postintubation.11 In contrast, Bali BK et al. found insignificant change in hemodynamics compared to baseline in their groups. This could be due to the use of ketamine as a single bolus along with a smaller duration of the procedure, i.e., 20 minutes.9
We found a significant difference in HR from baseline between the two groups from 30 minutes interval onwards which was maintained throughout the duration of surgery (p < 0.05). Further, the HR was lower in group A compared to group B. Sinha S.K. et al. in their study found that mean HR decreased persistently in both their groups (dexmedetomidine plus Ketamine vs dexmedetomidine alone) with no significant difference in HR between groups.11 But they studied HR only till 2 minutes after the intubation was completed. Bali B.K. et al. used dexmedetomidine and ketamine combination for upper gastrointestinal endoscopy and found no statistically significant difference in the HR from baseline during the procedure and recovery (p > 0.001).5 This difference could be because of different dose of dexmedetomidine and ketamine used in their study. Also we continued the infusion of ketamine along with dexmedetomidine whereas Bali B.K et al. gave a bolus of ketamine and continued a maintenance dose of dexmedetomidine alone. Another factor for the difference could be the time at which we appreciated significant reduction in HR from baseline which was 2 hours 45 minutes, whereas Bali BK et al. recorded readings only till 20 minutes in their study.
In our study to achieve adequate sedation (MOAA/S 2-3), in group A dexmedetomidine infusion needed titration from 0.5 μg/kg/hr to 0.75 μg/kg/hr in 4 patients (8.5%), whereas in group B none of the patients (0%) required titration (p -0.04). Thus significantly more patients required adjustment of dexmedetomidine infusion to 0.75 μg/kg/hr in group A. This also confirms better sedation characteristics in group B as compared to group A. Bali BK et al.5 as well as Rasheed MA et al., needed rescue boluses of ketamine for sedation which may be due to the use of initial bolus of ketamine rather than infusion as used in our study.5,13
LIMITATION OF STUDY
Assessment of sedation using bispectral index or entropy was not done due to difficulty in attaching and maintaining under drapes for ENT surgery. Hence, subjective assessment of sedation using modified observer assessment of alertness/sedation score was done.
We conclude that dexmedetomidine bolus 0.5 μg/kg followed by addition of low-dose ketamine infusion 0.2 mg/kg/hr along with dexmedetomidine infusion 0.5 μg/kg/hr provides earlier onset of sedation, better hemodynamic profile and patient satisfaction as compared to dexmedetomidine bolus 0.5 μg/kg followed by dexmedetomidine infusion 0.5 μg/kg/hr in otological surgeries under monitored anesthesia care.
We would like to term a combination of dexmedetomidine with low-dose ketamine “synergistic” for sedation. Dexmedetomidine prevents undesired effects of ketamine such as tachycardia, hypertension, salivation, and emergence phenomena, whereas ketamine reduces side effects of dexmedetomidine such as bradycardia and hypotension. This study shows that the combination not only gives early onset and better quality of sedation but also a better hemodynamic profile. Thus, the combination of dexmedetomidine with low-dose ketamine is beneficial for ENT surgeries done under MAC.
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