|Ahead of print publication
Comparison of prolongation of spinal anesthesia produced by intravenous dexmedetomidine and midazolam: A randomized control trial
Swetha N Sivachalam, Nitu Puthenveettil, Sunil Rajan, Jerry Paul, Lakshmi Kumar
Department of Anaesthesiology and Critical Care, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
Department of Anaesthesiology and Critical Care, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Various intravenous (i.v.) adjuvants have been used along with spinal anesthesia to delay the onset of postoperative pain. Aims: To compare effects of i.v. dexmedetomidine with midazolam on duration of spinal anesthesia. Settings and Design: This prospective randomized control trial was conducted in a tertiary care institution. Subjects and Methods: Forty-three patients presenting for elective infraumbilical surgery under spinal anesthesia were randomly allocated into two groups. Group A received a loading dose of 0.5 μg/kg followed by 0.5 μg/kg/h of i.v. dexmedetomidine. Group B received a loading dose of 0.03 mg/kg followed by 0.03 mg/kg/h of i.v. midazolam. Two dermatomal regressions, regression to S1level, and sedation score were noted. Statistical Analysis Used: To test the statistical significance of duration of sensory blockade, Mann–Whitney U-test was applied. The incidence of bradycardia and hypotension was analyzed using Pearson's correlation coefficient test. Results: The mean time for two dermatomal regressions was significantly prolonged in Group A (2.3 ± 0.4 h) than Group B (1.6 ± 0.5 h, P = 0.001). Mean time for sensory regression to S1dermatome was also prolonged in Group A (5.2 ± 0.83 h) than in Group B (4.4 ± 0.87 h, P = 0.01). Glycopyrrolate was administered in 45% of patients in Group A and 21% in Group B, which was statistically significant (P = 0.039). Conclusion: Conscious sedation with i.v. dexmedetomidine at a loading dose of 0.5 μg/kg followed by 0.5 μg/kg/h prolongs duration of spinal anesthesia than i.v. midazolam at a loading dose of 0.03 mg/kg followed by 0.03 mg/kg/h in patients undergoing infraumbilical surgeries. However, dexmedetomidine is associated with higher incidence of hemodynamic instability.
Keywords: Adjuvants, dexmedetomidine, midazolam, spinal anesthesia
|How to cite this URL:|
Sivachalam SN, Puthenveettil N, Rajan S, Paul J, Kumar L. Comparison of prolongation of spinal anesthesia produced by intravenous dexmedetomidine and midazolam: A randomized control trial. Anesth Essays Res [Epub ahead of print] [cited 2019 May 26]. Available from: http://www.aeronline.org/preprintarticle.asp?id=255881
| Introduction|| |
Various intravenous (i.v.) adjuvants have been used along with spinal anesthesia to delay the onset of postoperative pain and decrease the analgesic requirement. Midazolam is one of the frequently administered sedative agents during subarachnoid block for conscious sedation. Dexmedetomidine is a highly selective alpha agonist with sedative, analgesic, and anxiolytic properties. It is not associated with respiratory depression which makes it a safe drug for conscious sedation. i.v. dexmedetomidine and midazolam are known to prolong sensory and motor blockade of the subarachnoid block. This study was designed to compare the effects of these two drugs for conscious sedation on patients scheduled for infraumbilical surgery under spinal anesthesia. Previous studies have used higher bolus doses of dexmedetomidine and midazolam,,, but we have used lower bolus dose of the study drugs with a presumption that it would produce the same clinical effects with less hemodynamic instability. The primary objective of this study was to compare the effects of i.v. administered dexmedetomidine with midazolam on the duration of bupivacaine spinal anesthesia. The secondary objectives were to evaluate the hemodynamic changes caused by i.v. dexmedetomidine and midazolam.
| Subjects and Methods|| |
This prospective, single-blinded, parallel, randomized controlled study was conducted at the Anesthesiology Department of a tertiary care teaching hospital between June 2017 and February 2018. After approval from the institutional ethics committee and written informed consent from patients, American Society of Anesthesiologists (ASA) Physical Status Classes I and II patients age between 18 and 60 years presenting for elective infraumbilical surgery under spinal anesthesia were recruited. Patients on sedative medications, opioids, and antidepressants, pregnant women, and patients with baseline heart rate (HR) <50 beats per minute or systolic blood pressure (SBP) <90 mmHg and fall in HR <50/min or fall in mean arterial pressure (MAP) more than 20% from baseline within 5 min of spinal anesthesia were excluded from the study.
All patients received oral premedication of ranitidine 150 mg and metoclopramide 10 mg at night before and on the morning before surgery and alprazolam 0.25 mg at night before surgery. In the operation theater, preinduction monitors were placed. All the patients were preloaded with 10 mL/kg of lactated Ringer's solution. All patients received oxygen supplementation via facemask at 5 L/min subarachnoid block with 3 mL of 0.5% heavy bupivacaine being given using standard technique between L3 and L4 or L4 and L5 space in the lateral position. Patients were randomly allocated into Group A and Group B with the help of a random list generated by computer and opaque-sealed envelope method until both groups had 20 or more patients in it. If the patients were not excluded from study because of hypotension or bradycardia within 5 min of spinal anesthesia, study drugs were administered at 5 min. Group A patients received a loading dose of 0.5 μg/kg of i.v. dexmedetomidine over 10 min and immediately followed by a maintenance dose of 0.5 μg/kg/h. Group B patients received a loading dose of 0.03 mg/kg of i.v. midazolam over 10 min and immediately followed by a maintenance dose of 0.03 mg/kg/h till the end of surgery. The patients were not aware to which group they belonged. The anesthetist posted in the operating room prepared drug infusion. Sensory blockade was checked with loss of cold sensation in the midline with spirit-soaked cotton balls. Two-dermatomal regression from the maximum level of sensory blockade and regression to S1 dermatome were recorded. Sensory block was assessed in patients every 30 min. Vitals such as HR, SBP, MAP, and oxygen saturation were recorded immediately after the subarachnoid block and at 5-min intervals for first 15 min and thereafter at half hourly intervals till 2 h after the completion of surgery.
The management of blood pressure changes was according to standard protocol. If the MAP fell more than 20% from the baseline, ephedrine 3 mg i.v. bolus was used. Bradycardia is defined as HR <50 beats per min and was treated with i.v. glycopyrrolate 0.2 mg. If bradycardia persisted, it was treated with i.v. atropine 0.6 mg. The level of sedation was evaluated using Ramsay level of sedation scale (1 – anxious, agitated, or restless, 2 – cooperative, oriented, and tranquil alert, 3 – responds only to commands, 4 – asleep, but brisk response to light glabellar tap or loud, 5 – asleep, sluggish response to light glabellar tap or loud auditory stimulus, and 6 – no response) at half hourly intervals. The level of sedation between 3 and 4 was considered adequate for conscious sedation, but doses of drugs were fixed according to weight of the patient. Patients with a sedation score more than four at any point of time were considered to be excessively sedated and were excluded after discontinuation of the sedative infusion. At the end of the surgery, the patients were shifted to the recovery unit. Time to shift out from recovery to the ward was also noted.
Statistical analysis used
As there were no similar studies in the existing literature, comparing similar dosages of dexmedetomidine and midazolam that we used in our study, we conducted a pilot study to calculate sample size. Based on the mean and standard deviation of time taken for two dermatomal regression of sensory blockade in Group A (2.8 ± 0.27 h) and in Group B (1.8 ± 0.67 h) with 95% confidence and 80% power, the minimum sample size required to obtain statistically significant results with a P < 0.05 was estimated to be 5. However, we had recruited a minimum of 20 patients in each group.
Numerical variables were expressed as the mean and standard deviation, and categorical variables were expressed as frequency and percentages. To test the statistical significance of the differences in the mean duration of sensory blockade following spinal anesthesia between the two groups, Mann–Whitney U-test was applied. The incidence of bradycardia and hypotension between the two groups was analyzed using the Pearson's correlation coefficient test. The statistical analysis was done using IBM SPSS Statistics 20 for Windows 8 (SPSS Inc., Chicago, USA).
| Results|| |
In this prospective, single-blinded randomized control trial, a total of 43 patients were recruited and none of the cases were excluded during the study [Figure 1]. Distributions of patients in both groups were similar with respect to age, weight, sex, ASA physical status, and duration of surgery. Mean time for two dermatomal regressions was significantly prolonged in Group A (2.3 ± 0.4 h) than Group B (1.6 ± 0.5 h, P = 0.001). Mean time for sensory regression to S1 dermatome was also prolonged in Group A (5.2 ± 0.83 h) than in Group B (4.4 ± 0.87 h, P = 0.01) [Table 1]. Percentage of decrease in HR at 1 h after the subarachnoid block was not statistically significant between groups (27.9% ± 8.7% fall in Group A and 20.5% ± 8.7% fall in Group B). Percentage of SBP and MAP drop at 1 h after subarachnoid block was comparable [Table 2]. In both groups, none of the patients had blood loss more than 150 ml, which could have contributed to hypotension. Glycopyrrolate was administered in 45% of patients in Group A and 21% in Group B [Figure 2]. This was found to be statistically significant with a P = 0.039. Ephedrine was required for 30% of patients in Group A and 13% in Group B. This was not statistically significant. i.v. atropine was not used in any of the patients. There was no incidence of desaturation or excessive sedation observed in either of the group. The average time taken to shift patients out of recovery room was 2–2.5 h in both groups.
|Table 2: Percentage fall in heart rate and mean arterial pressure from baseline to 1 h|
Click here to view
| Discussion|| |
Spinal anesthesia is the most common choice of anesthesia for infraumbilical surgeries of short duration. Various i.v. agents such as midazolam,,, propofol, butorphanol, dexmedetomidine,,, and clonidine, have been used along with spinal anesthesia with the aim of prolonging the duration of the sensory block. Even with an adequate sensorimotor block of a desired dermatomal level, most patients would benefit from anxiolysis and sedation during the surgical period. Recently, i.v. dexmedetomidine has been frequently studied for its efficiency in prolonging the duration of the sensorimotor block. Some of the studies have emphasized caution while administering dexmedetomidine due to its association with bradycardia. In our study, we compared the efficacy of two i.v. drugs, midazolam and dexmedetomidine, in prolonging the duration of the sensory block of spinal anesthesia and in enhancing patient comfort. In our study, i.v. dexmedetomidine prolonged the time taken for two dermatomal sensory regression from the highest level and regression of blockade to S1 dermatome by 45 min. Similar observations were made by Kaya et al., Rekhi et al., Bisht and Prasad, and Patel and Patel. However, in the study by Kaya et al., there was no significant prolongation of time taken for regression to S1 dermatome between the two groups. This conflict could be explained by the fact that in our study bolus dose of i.v. dexmedetomidine was followed by an infusion till the end of surgery.
Dexmedetomidine provides analgesia through supraspinal effects which are mediated by activation of both presynaptic and postsynaptic sympathetic nerve terminal and central nervous system, resulting in suppression of noradrenergic neurons., This analgesic effect is obtained after dexmedetomidine administration irrespective of the route, whereas midazolam has no analgesic property following i.v. injection. This could be the reason for prolongation of sensory block in our patients in dexmedetomidine group.
In our study, the incidence of bradycardia was higher in the dexmedetomidine group than midazolam group even though we used a lower bolus dose than used in previous studies.,, Glycopyrrolate was required for 45% (9 of 20) patients in the dexmedetomidine group and 21% (5 of 23) patients in the midazolam group. Similar observations were made by Yoon et al., Rekhi et al., and Bisht and Prasad. However, in contrast, no bradycardia was noted in a study by Patel et al. Hall et al. stated that the initial bolus of dexmedetomidine results in a transient increase of blood pressure and reflex bradycardia. They attributed this to its action on α2B receptors and were mitigated by a slow infusion over 10 min.
Meta-analysis of seven randomized control trials analyzed a total of 364 patients, the initial bolus dose of i.v. dexmedetomidine varied between 0.5 and 1 μg/kg, and most trials included amaintenance dose between 0.2 and 0.5 μg/kg/h over 50 min to entire duration of surgery. The review showed that i.v. dexmedetomidine during spinal anesthesia prolonged sensory blockade by 34% and motor blockade by 17%. However, dexmedetomidine caused 3.7-fold increase in bradycardia, which responded to standard treatment.
The fall in blood pressure from the baseline at 1 h was statistically similar in both our groups. Ephedrine was required in 30% of our patients in the dexmedetomidine group and 13% in the midazolam group. Similar observations were made by Rekhi et al., Bisht and Prasad, and Patel and Patel. However, in a study by Sangma et al., higher incidence of hypotension was documented. The higher incidence of hypotension could be attributed to the higher bolus and infusion doses of dexmedetomidine used.
In a study by Talakoub et al., addition of 30 μg/kg of i.v. midazolam to lignocaine for spinal anesthesia improved duration of the motor block without causing any side effects. Various previous studies have shown,,,, prolongation of motor blockade when dexmedetomidine was given to patients under subarachnoid block. However, we have not looked into this because it was difficult to assess regaining of motor power intraoperatively and most of our patients were mobilized after 12 h postoperatively as per institutional policy. Similar to previous studies,,,, we did not encounter excessive sedation or desaturation or delay in shifting out of the recovery unit in any of our patients. In our study, a lower dexmedetomidine bolus dose followed by an infusion was used. However, we could provide an adequate level of sedation (Ramsay sedation score of 3–4) throughout the surgery without compromising the efficacy in prolonging the duration of sensory blockade of spinal anesthesia.
| Conclusion|| |
Conscious sedation with i.v. dexmedetomidine at a loading dose of 0.5 μg/kg followed by a maintenance dose of 0.5 μg/kg/h prolongs duration of spinal anesthesia than i.v. midazolam at a loading dose of 0.03 mg/kg followed by a maintenance dose of 0.03 mg/kg/h in patients undergoing infraumbilical surgeries. However, dexmedetomidine is associated with higher incidence of hemodynamic instability.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Annamalai A, Singh S, Singh A, Mahrous DE. Can intravenous dexmedetomidine prolong bupivacaine intrathecal spinal anesthesia? J Anesth Clin Res 2013;4:372.
Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs 2000;59:263-8.
Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699-705.
Yoon DK, Ban JS, Lee SG, Lee JH, Kim E, An J. Dexmedetomidine combined with midazolam vs. dexmedetomidine alone for sedation during spinal anesthesia. Korean J Anesthesiol 2016;69:446-52.
Rekhi BK, Kaur T, Arora D, Dugg P. Comparison of intravenous dexmedetomidine with midazolam in prolonging spinal anaesthesia with ropivacaine. J Clin Diagn Res 2017;11:UC01-4.
Patel VH, Patel HR. A comparison between dexmedetomidine and midazolam infusion on characteristic of spinal anesthesia. Int J Med Sci Public Health 2016;5:906-10.
Kaya FN, Yavascaoglu B, Turker G, Yildirim A, Gurbet A, Mogol EB, et al.
Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia. Can J Anaesth 2010;57:39-45.
Chikkahanumanthappa NB, Dasara SG, Pawar SD, Takkalki VV. A comparative study of sedation with dexmedetomidine or midazolam during spinal anesthesia. Anaesth Pain Intensive Care 2016;20:328-33.
AlOweidi AS, Al-Mustafa MM, Al Ajlouni JM, Mas'ad DF, Hamdan MQ, Alghanem SM, et al
. Intravenous dexmedetomidine or propofol adjuvant to spinal anesthesia in total knee replacement surgery. Jordan Med J 2011;45:174-83.
Bharti V, Gautam S, Das P, Chaudhary AK, Bogra J. Intravenous dexmedetomidine and butorphanol prolongs bupivacaine sensory analgesia in lower abdominal surgeries. IOSR J Dent Med Sci 2015;14:74-8.
Sangma SJN, Singh LK, Singh NR, Singh LC, Pongener AW, Bhutia D. Effect of intravenous dexmedetomidine on bupivacaine spinal analgesia. J Med Soc 2015;29:96-100. [Full text]
Dinesh CN, Sai Tej NA, Yatish B, Pujari VS, Mohan Kumar RM, Mohan CV. Effects of intravenous dexmedetomidine on hyperbaric bupivacaine spinal anesthesia: A randomized study. Saudi J Anaesth 2014;8:202-8.
] [Full text]
Agrawal A, Agrawal S, Payal YS. Comparison of block characteristics of spinal anesthesia following intravenous dexmedetomidine and clonidine. J Anaesthesiol Clin Pharmacol 2016;32:339-43.
] [Full text]
Reddy VS, Shaik NA, Donthu B, Reddy Sannala VK, Jangam V. Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine spinal anesthesia and analgesia: A randomized double-blind study. J Anaesthesiol Clin Pharmacol 2013;29:342-7.
] [Full text]
Kavya UR, Laxmi S, Ramkumar V. Effect of intravenous dexmedetomidine administered as bolus or as bolus-plus-infusion on subarachnoid anesthesia with hyperbaric bupivacaine. J Anaesthesiol Clin Pharmacol 2018;34:46-50.
] [Full text]
Bisht S, Prasad S. Intravenous dexmedetomidine prolongs bupivacaine spinal anesthesia. J Evol Med Dent Sci 2014;3:1745-52.
Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol 2011;27:297-302.
] [Full text]
Jaakola ML, Salonen M, Lehtinen R, Scheinin H. The analgesic action of dexmedetomidine – A novel alpha 2-adrenoceptor agonist – in healthy volunteers. Pain 1991;46:281-5.
Abdallah FW, Abrishami A, Brull R. The facilitatory effects of intravenous dexmedetomidine on the duration of spinal anesthesia: A systematic review and meta-analysis. Anesth Analg 2013;117:271-8.
Talakoub R, Rezvani M, Alikhani A, Golparvar M, Jabalameli M, Amini Z. The effect of intravenous midazolam on duration of spinal anesthesia. Shiraz E Med J 2015;16:e21586.
[Figure 1], [Figure 2]
[Table 1], [Table 2]