# Abstract

 

## Background Preemptive analgesia is the blocking of pain perception afferent pathways before noxious painful stimuli. Clonidine is an alpha agonist drug that is partially selective for α-2 adrenoreceptors. Clonidine is used as anti-anxiety medication and an, analgesic, and it prolongs the duration of the block in the brachial plexus block. 

## Objectives To compare the effect of preemptive clonidine with midazolam on intraoperative sedation, duration of block, and postoperative pain scores\*\*.\*\* 

## Patients and Methods In a randomized clinical trial, 80 patients with orthopedic fractures of an upper extremity who underwent supraclavicular nerve block were randomly assigned to receive 0.2 mg oral clonidine or 2 mg oral midazolam. Intraoperative sedation was measured at one hour after the start of urgery and again in the PACU (Post-Anesthesia Care Unit) using the Ramsay scale. The duration of sensory blockade was measured. Postoperative pain scores were measured using the VAS (Visual Analogue Scale) after entrance to recovery up to 2 hours. 

## Results The percentages of patients in the calm and sedated scale were significantly higher in clonidine group (35 and 42.5%, respectively), compared to the midazolam group (17.5 and 17.5%, respectively) (P = 0.042, 0.029; respectively). Those administered fentanyl in the clonidine group 105 ± 30.8 was significantly lower than that for the midazolam group 165 ± 34.5 (P = 0.0018). The percentages of patients in the calm scale were significantly higher in the clonidine group (52.5), compared to the midazolam group (17.5) (P = 0.001) in the post-operative period. VAS scores were significantly lower at one (P = 0.01) and two hours (P = 0.001) after operation in the clonidine group, compared to the midazolam group. 

## Conclusions Preemptive clonidine has many marvelous advantages over midazolam, including better sedation inside the operating room and then in the post-operative care unit, lower fentanyl doses are required during surgery, more stable heart rate and blood pressure are observed during the procedure, and patients report lower post-operative pain scores. # 4. Results In a randomized clinical, trial 80 patients enrolled in the study, 40 in the clonidine group and 40 in the midazolam group. All demographic variables, including age, gender, and BMI (body mass index) were not significantly different between the clonidine and midazolam groups ([Table 1](#)). ::::table-wrap

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## Demographic and Block Characteristics^[a](#)^

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Variables Clonidine Midazolam P value

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**Age** 35.6 (14.5) 37.4 (18.3) 0.33
**Gender** 0.25
Female 13 (33) 15 (38)\
Male 27 (67) 25 (62)\
**BMI, kg/m^2^** 22.1 (4.8) 22.9 (3.4) 0.65
**Onset of block** 5.8 (3.9) 5.5 (4.8) 0.41
**Duration of block** 176.5 (77.3) 158.5 (72.6) 0.059
**Duration of surgery** 152.7 (55.8) 158.3 (59.6) 0.28

^a^Data are expressed as No. (%) or mean ± SD:::: Patients' sedation scales, as measured by the Ramsay sedation scale, were compared during surgery (right 60 minutes after the initiation of surgery). Patients in the clonidine group had significantly better sedation scale ratings than the other group. The percentages of patients in the calm and sedated scale were significantly higher in the clonidine group (35 and 42.5%, respectively), compared to the midazolam group (17.5 and 17.5%, respectively) (P = 0.042, 0.029; respectively). In addition, the percentages of patients in the agitated and heavily sedated group were significantly higher in the midazolam group, compared to this in the clonidine group (P = 0.002 and 0.014; respectively) ([Figure 1](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Sedation Scale at 60 Minutes After the Start of Surgery in the Clonidine and Midazolam Groups</figcaption> </figure> Total intraoperative fentanyl requirements were compared between the two groups of the study. The mean ± SD of intraoperatively administered fentanyl in the clonidine group (105 ± 30.8) was significantly lower than in the midazolam group (165 ± 34.5) (P = 0.0018) ([Figure 2](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Total Doses of Fentanyl Administered During Surgery in the Clonidine and Midazolam Groups</figcaption> </figure> Heart rates during the operations were compared between the two groups of the study. Mean ± SD of heart rate in the clonidine group was lower than that for the midazolam group, at 0 (P = 0.51), 30 (P = 0.24), 60 (P = 0.32), 90 (P = 0.088), 120 (P = 0.072), and 180 (P = 0.095) minutes, but it was not significant at these time points ([Figure 3](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Heart Rates During Operation in the Clonidine and Midazolam Groups</figcaption> </figure> Systolic blood pressures during operation were compared between the two groups of the study. mean ± SD of systolic blood pressure in the clonidine group were was not significantly lower than that for the midazolam group, at 0 (P = 0.73), 30 (P = 0.064), 120 (P = 0.33), and 180 (P = 0.17) minutes, but it was significantly lower at 60 (P = 0.011) and 90 (P = 0.008) minutes in the clonidine group, compared to the midazolam group ([Figure 4](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Systolic Blood Pressures During Operation in the Clonidine and Midazolam Groups</figcaption> </figure> Diastolic blood pressures during operation were compared between the two groups of the study. Mean ± SD of diastolic blood pressure in the clonidine group was not significantly lower than that for the midazolam group at 0 (P = 0.60), 30 (P = 0.46), 60 (P = 0.41), 120 (P = 0.065), and 180 (P = 0.068) minutes, but it was significantly lower at 90 (P = 0.019) minutes in the clonidine group, compared to the midazolam group ([Figure 5](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Diastolic Blood Pressures During Operation in the Clonidine and Midazolam Groups</figcaption> </figure> Patients' sedation scales were measured again using the Ramsay sedation scale at the end of surgery in the PACU (30 minute after entrance to recovery). The percentages of patients in calm scale were significantly higher in the clonidine group (52.5), compared to the midazolam group (17.5) (P = 0.001) in the post-operative period. Further, the percentages of patients in the agitated and very agitated group were significantly higher in the midazolam group (20 and 25%, respectively), compared to the clonidine group (2.5 and 7.5%, respectively) (P = 0.02 and P = 0.006, respectively) ([Figure 6](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Sedation Scales After Surgery in the PACU in the Clonidine and Midazolam Groups</figcaption> </figure> Pain scores measured by VAS during two hours post operation were compared between the two groups. VAS scores at 0 hour (entrance to recovery) were not significantly different between the two groups; however, VAS scores were significantly lower at one (P = 0.01) and two hours (P = 0.001) after operation in the clonidine group, compared to the midazolam group ([Figure 7](#)). <figure> <p><img src="" /></p> <figcaption>Comparison of Pain Scales Visual Analogue Scale (VAS) in the Postoperative Period</figcaption> </figure> The total dose of administered morphine (mg) was measured during the 24 hours after surgery. Total morphine requirements were not significantly different between the clonidine (8.5 ± 5.3) and midazolam (9.3 ± 7.2) groups (P = 0.077).


Extracted trial result:
Outcome: The percentages of patients in the calm (binary)
Intervention: 0.2 mg oral clonidine
Comparator: 2 mg oral midazolam
Intervention events: 14
Intervention group size: 40
Comparator events: 7
Comparator group size: 40
Notes: Even though the outcome says percentage, the way that the results are reported in the table makes it easier to calculate as binary outcome.