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  Table of Contents 
Year : 2022  |  Volume : 23  |  Issue : 2  |  Page : 138-143

Preemptive analgosedation with ketamine-dexmedetomidine versus ketamine-propofol in upper limb surgeries under supraclavicular brachial plexus block: A randomized controlled trial

1 Department of Anesthesia, Pramukhswami Medical College, Bhaikaka University, Anand, Gujarat, India
2 Central Research Services, Bhaikaka University, Karamsad, Anand, Gujarat, India

Date of Submission31-Mar-2022
Date of Decision03-Aug-2022
Date of Acceptance10-Aug-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Dr. Madhavi Sanjay Chaudhari
No. 3, Radhakutir C/o Parthkutir, Oppsite Sarshawati Prajapati Chhatralaya, Karamsad-Vidyanagar Road, Vallabh Vidyanagar, Anand, Karamsad - 388 120, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/TheIAForum.TheIAForum_42_22

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Background and Aims: Analgosedation before and during regional anesthesia provides analgesia, anxiolysis, and amnesia. This study has been conducted to compare ketamine-dexmedetomidine (KD) versus ketamine-propofol (KP) for sedation, pain on needle prick while giving block, hemodynamics, and their side effects under supraclavicular brachial plexus block.
Materials and Methods: After obtaining ethics committee approval, CTRI registration and patient consent, 75 patients were recruited who satisfy inclusion and exclusion criteria. Patients were divided into two groups. Group KP received a loading dose of ketamine 0.5 mg/kg, propofol 1 mg/kg over 10 min, followed by a maintenance dose of ketamine 0.3 mg/kg/h and propofol 10 μg/kg/min. Group KD received loading dose of ketamine 0.5 mg/kg, dexmedetomidine 0.5 μg/kg over 10 min, followed by maintenance dose of ketamine 0.3 mg/kg/h and dexmedetomidine 0.3 μg/kg/h. Patients were monitored for sedation, pain on needle prick while performing block, side effects of study drugs, hemodynamic and respiratory parameters. An independent sample t-test was used to compare continuous outcomes, descriptive statistics were used to depict the baseline profile of the study participants, Chi-square test was used to compare the categorical outcomes. A value of P < 0.05 was considered statistically significant.
Results: Pain on needle prick was experienced in 5.7% and 42.9% in Group KD and Group KP, respectively. In Group KD, 28.6% and Group KP 5.7% of patients experienced nausea.
Conclusion: In this study, group KD has adequate sedation as compared to group KP with less pain on needle prick while performing supraclavicular block. Group KD has higher incidence of nausea than gruop KP.

Keywords: Analgosedation, ketamine-dexmedetomidine, ketamine-propofol, Ramsay sedation scale

How to cite this article:
Makwana MD, Pathak BP, Panchal NN, Chaudhari MS, Phatak AG. Preemptive analgosedation with ketamine-dexmedetomidine versus ketamine-propofol in upper limb surgeries under supraclavicular brachial plexus block: A randomized controlled trial. Indian Anaesth Forum 2022;23:138-43

How to cite this URL:
Makwana MD, Pathak BP, Panchal NN, Chaudhari MS, Phatak AG. Preemptive analgosedation with ketamine-dexmedetomidine versus ketamine-propofol in upper limb surgeries under supraclavicular brachial plexus block: A randomized controlled trial. Indian Anaesth Forum [serial online] 2022 [cited 2023 Jun 1];23:138-43. Available from: http://www.theiaforum.org/text.asp?2022/23/2/138/359855

  Introduction Top

Regional anesthesia is the most commonly used technique for upper limb fractures. It provides benefits to the patients such as staying awake during surgery, early food intake, and more patient satisfaction and for the anesthesiologist; it offers preservation of protective airway reflexes, cardiovascular and respiratory stability, and early recovery.[1] There are some limitations with this technique such as pain at the needle puncture site, fear of needles, recall of perioperative events, apprehension due to surgical procedure, and unfamiliar surroundings. To overcome these inadequacies, analgosedation is a must. This can be achieved with the combination of various groups of analgesics and sedative drugs.[2],[3] For analgosedation, two such popular combinations are ketamine-propofol (KP) and ketamine-dexmedetomidine (KD).[3] Many previous studies have used either ketofol or KD and compared the same with propofol, ketamine, or a combination like dexmedetomidine-propofol or propofol-ketamine for analgosedation in procedures such as cardiac catheterization, dentoalveolar surgeries, upper gastrointestinal endoscopy, burns dressing, laparoscopic cholecystectomy, and procedures in the emergency department in both adult and pediatric patients.[4],[5],[6],[7],[8],[9] Combination of KD and KP same as ours were used only in the pediatric population so far.[10],[11] Analgosedation with KD and KP is yet to be studied in the adult population. This is why we have decided to study these drugs. When ketamine and propofol are used in combination, dense analgesic and sedative effects can be achieved at lesser doses with minimal side effects. Bradycardia, hypotensive, and respiratory depressive effect of propofol neutralized by the sympathomimetic effect of ketamine.[12],[13] Dexmedetomidine antagonizes the sympathomimetic effect of ketamine and the emergence phenomenon caused by ketamine and also it has antinociceptive synergistic interaction with ketamine. Hence, when both the drugs are used in combination, they provide intense analgesia and sedation with minimal side effects. [5,14] Primary objective of this study was to assess sedation using the Ramsay sedation score (RSS). Secondary objectives were to assess pain on needle prick while giving block, hemodynamic parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], heart rate [HR]), and respiratory parameters (respiratory rate [RR], SPO2).

  Materials and Methods Top

A prospective randomized double-blinded controlled trial was conducted from September 2020 to June 2021 in patients undergoing upper limb surgeries under supraclavicular block after Institutional Ethics Committee and Clinical Trial Registry (CTRI/2020/09/027976) approval.

After obtaining the patient's written informed consent, 75 patients of either gender, aged 18–70 years, American Society of Anesthesiologists (ASA) I–III physical status with body mass index (BMI) of 18–40 kg/m2, posted for elective and emergency upper limb surgeries were included in this study. Patients with a history of hypersensitivity to local anesthetics, allergy to study drugs, altered mental status, sedative and hypnotic medication, chronic pain on the operated limb, severe hepatic or kidney impairment, thyrotoxicosis, uncontrolled hypertension, neurological diseases, pregnant or breastfeeding female, failure or unsatisfactory action of the block were excluded from the study.

Assuming a moderate effect size of 0.7 with respect to the Ramsay sedation score (RSS), a sample size of 32 (/group) was required to achieve 80% power and allowing for 5% Type 1 (Alpha) error. Considering 10% lost to follow-up and feasibility, a sample size of 35/group was decided. Participants were randomly allocated to Group KD (38 patients) and Group KP (37 patients) via computer-generated balanced randomization process. Opaque envelopes containing treatment codes with serial numbers were kept with the in-charge sister of the operation theater. Each envelope was open after confirming the eligibility and consent of the participant. Junior resident who was not aware of studying prepared the drugs. The participants as well as the assessor were not aware of the drug injected.

After a thorough preanesthetic checkup and confirming adequate nil by mouth, all patients were prehydrated with Ringer's lactate solution 5 ml/kg over 15 min. In the operative room, electrocardiogram, pulse oximeter, and noninvasive blood pressure were attached. Sedation was started according to group allocation 10 min before placement of supraclavicular block either peripheral nerve stimulator (PNS) or Ultrasound (USG) guided. Oxygen supplementation was given using a face mask. The infusion was continued with the same rate targeting Ramsay's sedation score (RSS) of 4 during the procedure. If RSS was increased more than 4, the infusion was stopped.

Group KD: Infusion of 100 mg (2 ml) of ketamine and 100 μg (1 ml) of dexmedetomidine diluted in normal saline (NS) was prepared. Patient received a loading dose of ketamine 0.5 mg/kg, dexmedetomidine 0.5 μg/kg over 10 min, followed by a maintenance dose of ketamine 0.3 mg/kg/h and dexmedetomidine 0.3 μg/kg/h.[15]

Group KP: Infusion of 100 mg (2 ml) of ketamine and 200 mg (20 ml) of propofol diluted in NS was prepared. The patient received a loading dose of ketamine 0.5 mg/kg, propofol 1 mg/kg over 10 min, followed by a maintenance dose of ketamine 0.3 mg/kg/h and propofol 10 μg/kg/min.[8]

The primary objective was assessed using the Ramsay sedation score (1 = Nervous, agitated, and/or restless, 2 = cooperative, oriented, quite patient, 3 = only obeying the orders, 4 = sleeping, hitting the glabella and responding to high voice suddenly, 5 = sleeping, hitting the glabella and responding to high voice slowly, 6 = No response to any of these stimulations). The secondary objective, pain on needle prick while giving PNS and USG-guided block was assessed by change in patient's facial expression (Relax 1, partially tightened-blow lowering 2, fully tightened-eyelid closing 3, Grimacing 4) and body movement (No movement 1, partially bent 2, fully bent with finger flexion 3, permanently retracted 4) (Components of Behavioral pain scale [BPS]).[16] In both the groups, hemodynamic parameters (HR, SBP, and DBP), respiratory parameters (RR, SPO2), and side effects were assessed. If SBP decreased 20% from the baseline, considered hypotension and treated with injection Mephentermine 6 mg. If HR was <60/min, that was considered bradycardia and treated with injection glycopyrolate 0.2 mg. Once the surgery was over, patients were observed in the postanesthesia care unit for 30 min.

Independent sample t-test was used to compare continuous outcomes, descriptive statistics (mean(standard deviations), frequency (%)) was used to depict the baseline profile of study participants; Chi-square test was used to compare the categorical outcomes. A value of P < 0.05 was considered statistically significant. Analysis was performed using STATA (14.2).

  Results Top

This study included total of 75 patients who met the inclusion criteria were randomly allocated into two groups, Group KD 38 patients and Group KP 37 patients. In five patients intervention was discontinued as supplementary GA was given so 35 patients in each group were analyzed [Figure 1].
Figure 1: Consort flow diagram. KD: Ketamine-dexmedetomidine, KP: Ketamine-propofol

Click here to view

Both the groups were comparable with respect to demographic characteristics (age, weight, height and BMI distribution, ASA grading, and type of surgery) [Table 1]. The level of sedation was assessed using the Ramsay Sedation Score (RSS). The mean of sedation score in Group KD was higher than Group KP throughout the intraoperative period with P values statistically significant at 30 min (P = 0.001), 40 min (P = 0.047), 70 min (P = 0.030), 80 min (P = 0.024), 90 min (P = 0.004), and 100 min (P = 0.003) as shown in [Graph 1]. Out of 70 patients, a total of 17 patients had experienced pain on needle prick while giving block. In Group KD 5.7% and Group KP 42.9% experienced pain on needle prick (P < 0.001) [Graph 2]. Intraoperative parameters such as HR, SBP [Graph 3] and [Graph 4], DBP, RR, and SpO2 showed no statistically significant difference between the two groups with P values for all these parameters being >0.05. Out of 70 patients, nausea was seen in 12 patients. In Group KD 28.6% and in Group KP 5.7% experienced nausea (P = 0.001).

Table 1: Demographic data

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  Discussion Top

Regional anesthesia is a time-honored procedure for producing surgical anesthesia. In order to improve patient's acceptability to regional anesthesia, it is necessary to provide moderate procedural sedation with sedative and/or analgesic drugs.[ 17] Neither systematic review nor clinical trials in the adult population for this combination of analgosedation in orthopedic intervention with the supraclavicular block are available at present in the literature.

The medications used during analgosedation should provide analgesia, anxiolysis, and amnesia. In our study, we have used continuous intravenous (IV) infusion of analgosedation as it leads to steady plasma concentration of the drugs with less side effects and less total drug requirement when compared to intermittent IV bolus administration of the same drugs.[18] Ketamine was described as safe, effective, and simple and was firstly hoped to be used as the sole anesthetic medication causing loss of consciousness, amnesia, and analgesia. Combination of ketamine with either propofol or dexmedetomidine allows usage of lower doses and adds synergism and decreases side effects.[19]

Various reliable sedation assessment tools such as Observer's Assessment of Alertness/Sedation Scale, Ramsay sedation score (RSS), ASA's continuum of sedation are equally effective, and previous multiple studies have suggested their correlation with electroencephalogram indices.[20] We decided to use the Ramsay sedation score in the current study because it is easy to apply and reliable.[21],[22]

The sedation score mean in Group KD was higher than Group KP and P value was statistically significant at 30 min (P = 0.001), 40 min (P = 0.047), 70 min (P = 0.030), 80 min (P = 0.024), 90 min (P = 0.004), and 100 min (P = 0.003). In Group KD 71.4% and in Group KD, 85.75% of patients had RSS of 3. In comparison to Group KP, group KD has a higher number of patients with RSS of 4 (KP8.5% vs. KD 28.5%). These results are probably due to the use of continuous infusion of a combination of analgesic and sedative drugs which has significantly reduced the dose required to achieve the desired effect. Tosun et al.[10] did study on pediatric patients and found no significant difference in terms of RSS between KD and KP group. However, in Group D, a higher sedation score was found at 30, 45, and 60 min from the baseline and in Group P higher sedation score was achieved early at 15 min. Canpolat et al.[11] found no statistically significant difference in RSS with the same combination of analgosedation in pediatric tooth extraction study, but they gave medication IV bolus and intermittent.

In our study, as patients were sedated, we could not use conventional pain assessment tools. Instead, we have assessed the incidence of pain on needle prick using the subscale of BPS. This scale includes facial expressions, upper limb movement, and compliance with ventilation. In our study, patients were only sedated and not ventilated, that is why we have used only the first two components of BPS. The incidence of pain on needle prick while performing block was lower in Group KD (5.7%) than in Group KP (42.9%) with statistical significance (P < 0.001). In a study performed by Yağan Ö et al., pain during retrobulbar block for cataract surgery was evaluated with visual Analog scale. They compared dexmedetomidine with Ketofol and found that the visual analog scale (VAS) was statistically nonsignificant in both groups. This study result was deferred from our results as we have used a combination of ketamine and dexmedetomidine.[23] The synergistic analgesic action of dexmedetomidine with ketamine is probably responsible for less incidence of pain on needle prick.[5]

The hemodynamic parameters such as HR, SBP, DBP, RR, and SpO2 showed no statistically significant difference between the two groups with P values for all these parameters being > 0.05 as we used a combination of analgosedation with continuous infusion. In the study performed by Algharabawy W et al., they concluded that the KD group had lower MAP and HR in comparison to the KP group, but the results were not statistically significant.[24] They used higher doses of KD and KP in comparison to our study. That may be the cause for the difference in both study results. Kumar et al.[1] compared the effect of propofol and dexmedetomidine bolus, followed by continuous infusion in the brachial plexus block. They found that propofol group had significantly low MAP, whereas dexmedetomidine group had a significantly low HR. These results differed from our study as they had used a single drug in infusion and bolus. Canpolat et al. and Tosun et al. had similar results as ours and they found no statistically significant difference in hemodynamic and respiratory parameters.[10],[11]

The incidence of nausea was lower in Group KP than in Group KD with a statistical significance of P = 0.001. In Group KD, 10 patients and in Group KP, two patients experienced nausea. In the KP group, nausea was less as propofol has antiemetic action. Canpolat et al.[11] had a similar finding, six pediatric patients had nausea in Group KD. El Mourad et al.[25] found no nausea, or vomiting in the study as they used Propofol in both the groups which itself has antiemetic properties. Other side effects such as shivering, vomiting, pruritus, hypotension, hypertension, bradycardia, tachycardia, and desaturation were not seen in either group.

We did not use bispectral index (BIS) monitor for objective sedation and used only the RSS score, which is subjective, and the correlation between the two that is BIS and RSS for sedation was not done due to the nonavailability of BIS monitor in our institute.

  Conclusion Top

Preemptive analgosedation with KD and KP can be used safely and effectively in upper limb orthopedic surgeries under the supraclavicular brachial block. KD provides better sedation and analgesia compared to KP. Both the groups ensured hemodynamic and respiratory stability.

Scope of the study

  1. Combination of drugs can be used in the future for various procedures such as fiberoptic bronchoscopy and endoscopic procedures wherever analgosedation is required
  2. Other combinations of analgesics and sedatives such as ketamine with midazolam, fentanyl with ketamine, fentanyl with etomidate, and fentanyl with propofol can be studied and compared
  3. Onset time of targeted BIS sedation score and regression of sedative effect along with VAS score and requirement of rescue analgesics can be studied with such combination of drugs in future.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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