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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 33-37

Dexmedetomidine versus clonidine as adjuvants in epidural analgesia in gynecological laparotomy: Case series


Department of Anesthesiology and Intensive Care, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia

Date of Submission02-Jul-2020
Date of Decision11-Sep-2020
Date of Acceptance24-Sep-2020
Date of Web Publication8-Feb-2021

Correspondence Address:
Dr. Tjokorda Gde Agung Senapathi
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Udayana University, Denpasar, Bali
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/BJOA.BJOA_129_20

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  Abstract 


Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. If the management of acute postoperative pain is not done properly, it can lead to the complication such as chronic pain. Epidural anesthesia reduces perioperative stress response in surgery, increasing the surgery outcome. Epidural analgesia is one of the potential acute postoperative pain treatments. The administration of α-2 agonists has analgesic and sedative effect when used as adjuvant in epidural analgesia. The administration of α-2 adrenergic agonists' adjuvant can increase the potential duration of analgesia and reduce the local anesthetic dose needed 30%–40% and can reduce the occurrence of the side effects. Dexmedetomidine is one of the most potent and high selective alpha-2 adrenergic receptor agonists. The use of dexmedetomidine during epidural anesthesia has faster onset and longer motor sensory blockade duration with hemodynamic stability that can be accepted. While clonidine acts as selective partial alpha-2 receptor agonists that cause the analgesic action of alpha-2 receptor in the dorsal of spinal cord. Clonidine has been shown its ability to reduce the local anesthesia needed and improve the pain scores when is combined with bupivacaine 0.125% with or without fentanyl opioid 1–2 μg/mL.

Keywords: Bupivacaine, clonidine, dexmedetomidine, epidural anesthesia, laparotomy gynecology


How to cite this article:
Isma Pratiwi DA, Kresna Sucandra I M, Agung Senapathi TG. Dexmedetomidine versus clonidine as adjuvants in epidural analgesia in gynecological laparotomy: Case series. Bali J Anaesthesiol 2021;5:33-7

How to cite this URL:
Isma Pratiwi DA, Kresna Sucandra I M, Agung Senapathi TG. Dexmedetomidine versus clonidine as adjuvants in epidural analgesia in gynecological laparotomy: Case series. Bali J Anaesthesiol [serial online] 2021 [cited 2021 Mar 1];5:33-7. Available from: https://www.bjoaonline.com/text.asp?2021/5/1/33/308879




  Introduction Top


Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage.[1] If the management of acute postoperative pain is not done properly, it can lead to the complication such as chronic pain.[2] There are some techniques to control postoperative pain, especially in the gynecological surgery. The use of systemic opioid such as morphine and fentanyl has been long recognized as one of the postoperative analgesia but has many unpleasant effects such as nausea, drowsiness, weakness, and longer mobilization and healing time. The use of systemic opioid can also result in the occurrence of ileus. Epidural analgesia becomes one of the most popular analgesia to control postoperative pain, especially in major abdominal surgery.[3]

Epidural anesthesia reduces perioperative stress response in surgery, increasing the surgery outcome.[4] Epidural analgesia is one of the potential acute postoperative pain treatment. The administration of α-2 agonists has analgesic and sedative effect when used as adjuvant in regional anesthesia. The administration of α-2 adrenergic agonists adjuvant can increase the potential duration of analgesia and reduce the local anesthetic dose needed 30%–40%, can reduce the occurrence of the side effects.[4],[5]

Dexmedetomidine is one of the most potent and high selective alpha-2 adrenergic receptor agonists.[6],[7] Dexmedetomidine can be potential as analgesic and contains sedative so it can cause minimal respiratory depression when used as an adjuvant in regional anesthesia.[8] Antinociceptive mechanism of this drugs when used in epidural anesthesia is mediated in the spinal because it does not have analgesic effect when given systemically. It is highly fat soluble and occurs rapidly in cerebrospinal fluid (CSF) and has high-binding affinity to the α-2 receptor in the spinal cord.[9] The use of dexmedetomidine during epidural anesthesia has faster onset and longer motor sensory blockade duration with hemodynamic stability that can be accepted.[10]

Clonidine acts as selective partial alpha-2 receptor agonists. Clonidine is an alpha-2 adrenergic agonist cause the analgesic action of alpha-2 receptor in the dorsal of spinal cord. Neuraxial clonidine has been proven effective as an analgesic for noncancer pain and chronic cancer pain. Clonidine has anti-hypertensive effect and has shown the potential as postoperative analgesia induced by local anesthetic. Clonidine is generally administered epidurally in doses between 75 and 150 μg. Clonidine can reduce the side effects such as chills, pruritus, nausea, vomiting or respiratory depression, and analgesia to patients. Clonidine has been shown its ability to reduce the local anesthesia needed and improve the pain scores when is combined with bupivacaine 0.125% with or without fentanyl opioid 1–2 μg/mL. Epidural with clonidine adjuvant has the saving effect of local anesthetic doses up to 30%–40% and can improve the quality of analgesia duration.[7]


  Case Reports Top


We recently managed ten patients aged 17–65 years old with American Society of Anesthesiology physical status I–II (ASA I–II) who were posted for elective gynecological laparotomy surgery. All participants were managed with general anesthesia in the combination with epidural anesthesia. In combination with bupivacaine 0.25% as an epidural medication, five patients received also dexmedetomidine 0.5 mcg/kg 15 mL and another five patients received clonidine 1 mcg/kg 15 mL as adjuvant. The observations are shown in [Table 1], [Table 2].
Table 1: Visual Analog Scale score and analgesic interventions needed in patients receiving dexmedetomidine

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Table 2: Visual Analog Scale score and analgesic interventions needed in patients receiving clonidine

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Case 1

A 57-year-old woman with cervical carcinoma Stage II A was planned a radical laparotomy hysterectomy bilateral salpingoophorectomy. Anesthesia was performed under general anesthesia with epidural combination and dexmedetomidine adjuvant 0.5 mcg/kg was given. After the epidural injection, blood pressure fluctuation was 105–111/63–75 mmHg, and heart rate fluctuation 62–78 times/min was obtained. There were no side effects of nausea, vomiting, dry mouth, or respiratory depression.

Case 2

A 65-year-old woman with suspected malignant ovarian cyst was planned a total laparotomy hysterectomy bilateral salpingooophorectomy surgery. After the epidural medication combined with dexmedetomidine 0.5 mcg/kg was injected, the blood pressure fluctuation was 92–125/56–70 mmHg, and heart rate fluctuation was 58–65 times/min. There were no side effects of nausea, vomiting, dry mouth, or respiratory depression. 6 h postoperative, patient felt pain with VAS 40 mm and was given ketorolac analgesic 30 mg intravenously and epidural 0.125% with morphine 1 mg.

Case 3

A 51-year-old woman with uterine myoma was planned a total hysterectomy bilateral salpingoophorectomy surgery. Ten minutes after giving the epidural injection with adjuvant 0.5 mcg/kg, blood pressure was drop in 88/54 mmHg and ephedrine was given to increase the blood pressure. The patient complained of having nausea while in the recovery room and then was given ondansetron 4 mg.

Case 4

A 58-year-old woman with suspected malignant ovarian cyst was planned a total laparotomy hysterectomy bilateral salpingoophorectomy surgery with frozen section. The anesthetic technique used was general anesthesia in combination with epidural with dexmedetomidine adjuvant 0.5 mcg/kg. After the epidural medication was injected, the hemodynamic tend to be stable with blood pressure fluctuation was 100–135/63–80 mmHg and heart rate fluctuation 68–75 times/min was obtained. There were no side effects of nausea, vomiting, dry mouth, or respiratory depression.

Case 5

A 56-year-old woman with suspected malignant ovarian cyst was planned a total abdominal laparotomy hysterectomy bilateral salpingoophorectomy with frozen section. 5 min after the epidural medications with dexmedetomidin adjuvant at 0.5 mcg/kgBB doses were injected, the blood pressure fluctuation was 92–105/58–70 mmHg and heart rate fluctuation were 54–65 times/min. 8 h postoperative, the patient complained of nausea and then was given ondansetron 4 mg while in the room.

Case 6

A 49-year-old woman with ovarian carcinoma postsuboptimal surgical staging was planned a surgical staging surgery. General anesthesia with epidural combination was performed and clonidine adjuvant was given 1 mcg/kg. Five minutes after the epidural medication was injected, hypotension with blood pressure of 78/45 mmHg was obtained and then ephedrine was given to increase the blood pressure. Heart rate fluctuation 45–57 times/min was obtained during the surgery. The patient complained of dry mouth 2 h after surgery.

Case 7

A 55-year-old woman with uterine prolapse Stage I + cystocele Stage II + rectocele Stage I + ovarian cysts dextra was planned a total abdominal hysterectomy and bilateral salpingoophorectomy. After the epidural medication was injected, hypotension with blood pressure 88/59 mmHg was obtained, and then, ephedrine 5 mg was given to increase blood pressure. Heart rate fluctuation was 55–62 times/min during surgery. It only needed one time of ephedrine administration to this patient, and then, the stable blood pressure was obtained during the surgery. There were no complaints of nausea or dry mouth in the patient, but 5 h after surgery, the patient felt pain with VAS 40 mm so the additional analgesic 30 mg was given intravenously.

Case 8

A 47-year-old woman with cervical carcinoma Stage IB was planned a radical hysterectomy and bilateral salpingoophorectomy surgery. After epidural medication was injected with clonidine adjuvant 1 mcg/kgB, stable hemodynamic with blood pressure fluctuation 92–102/50–62 mmHg and heart rate fluctuation 51–67 times/min were obtained. When in the recovery room, the patient felt pain in the surgical wound with VAS >30 mm and was given an additional ketorolac 30 mg intravenously. Complaint of dry mouth 6 h after surgery was obtained.

Case 9

A 55-year-old woman with suspected malignant ovarian cyst was planned a total abdominal hysterectomy and bilateral salpingoophorectomy surgery. General anesthesia with epidural combination was performed and clonidine adjuvant 1 mcg/kg was given. After epidural medication was injected, the blood pressure was 76/42 mmHg, and the heart rate was 47 times/min. Then, additional ephedrine was given to increase the blood pressure, and atropine sulfate was given to increase the heart rate. There were no postoperative side effects in this patient.

Case 10

A 50-year-old woman with ovarian cyst with an abdominal hernia was planned a cystetomy laparotomy sinistra with frozen section and herniotomy. The anesthetic techniques were general anesthesia and epidural anesthesia with clonidine adjuvant 1 mcg/kgBW. After epidural medication was injected, the blood pressure fluctuation was 90–117/65–75 mmHg, and the heart rate fluctuation was 55–78 times/min. 6 h after surgery the patient complained of pain with VAS 40 mm then was given an additional ketorolac analgesic 30 mg intravenously, and there was dry mouth side effect in this patient.


  Discussion Top


The use of neuraxial opioid is associated with some side effects, so the various options include alpha-2 agonists are evaluated widely as alternatives to suppress the opioid-related side effects such as respiratory depression, nausea, urinary retention, and pruritus.[6] Alpha-2 receptor agonists have been proven has anti-nociceptive action which is used for somatic and visceral pain.[8]

Dexmedetomidine is a selective α-2 adrenoceptor agonists with analgesic potential, that contains sedative and causes minimal respiratory depression when is used as an adjuvant in regional anesthesia.[8] The sedative effect of dexmedetomidine is believed to be mediated mainly by postsynaptic alpha-2 adrenoceptor that acts by inhibiting pertussis-toxin-sensitive G protein, so it increases the potassium canal flow. Then, the analgesic effect produced by dexmedetomidine is believed to be mediated by the same mechanism in the brain stem and spinal cord.[11],[12] Anti-nociceptive mechanism of this drug when used in epidural anesthesia is spinal mediated because it has not analgesic effect when is given systemically. It is very fat soluble and occurs rapidly in CSF and has high-binding affinity to the α-2 receptor in the spinal cord.[9] Dexmedetomidine does not have direct effect to the heart. A cardiovascular biphasic response is seen after dexmedetomidine is given. In loading dexmedetomidine 1 mcg/kg initially produces transient increases in blood pressure and decreases reflex in heart rate. Alpha-2 adrenoceptor stimulation in vascular smooth muscle seems to be responsible for the initial increase in blood pressure.[11]

Administration of alpha-2 agonists adjuvant in epidural is related to the effects of sedation, analgesia, anxiolytic, hypnosis, and sympatholysis.[12],[13] Alfa-2 agonists can provide an interested alternative in the use of anesthetic adjuvant agent because of the efficient anesthesia effect and stable hemodynamic.[14],[15],[16],[17] Alpha-2 adrenoceptor agonists produce analgesia by releasing C-fiber transmitters and hyperpolarization of post-synaptic dorsal horn neurons.[15],[16] Extension of motor block in local anesthesia results from the alpha-2 adrenoceptor agonists binding to motor neurons in dorsal horn.[17],[18],[19]

Clonidine has the effect of strengthening analgesia in neuraxial block technique by binding to the postsynaptic receptor alpha-2 adrenergic horn dorsalis spinal cord. The effect of clonidine 1–2 mcg/kg intrathecally to epidural bupivacaine can prolong the analgesic effect, but there are side effects of hypotension and bradycardia due to the suppression of central and peripheral sympathizers.

Dexmedetomidine is an alpha-2 adrenoceptor agonist which is high selective and eight times more specific than clonidine.[17] Additional of dexmedetomidine 1 mcg/kg or clonidine 2 mcg/kg as epidural bupivacaine adjuvant[10],[18],[19] can cause the onset of analgesia initially, the maximum level of faster sensory motor block. Not only the extension of analgesia duration but it can also provide an excellent level of sedation during the surgical procedure without any significant hemodynamic fluctuation. Previous research data support that the use of dexmedetomidine and clonidine can be used as an additional in regional anesthesia.[10],[18],[19]

We found that the decrease in heart rate and mean arterial pressure in clonidine group and hemodynamic in the dexmedetomidine group tended to be stable. The hypnotic and supraspinal analgesic effects of dexmedetomidine are mediated by hyperpolarization of the noradrenergic neurons, which suppress the act of neurons in locus coeruleus with the releasing of norepinephrine inhibition and activity in the nonadrenergic medulla spinalis descending pathway. Three patients in the group who received clonidine adjuvant and received additional ephedrine due to the decrease in blood pressure after epidural medication administration and one patient in the group who received dexmedetomidine adjuvant. However, this is different from the existing theory where dexmedetomidine has a greater affinity than clonidine so that dexmedetomidine can cause greater hemodynamic instability.

Avoiding the respiratory depression side effects in patients who received dexmedetomidine and clonidine adjuvants are according to the previous studies that in this case report there was no clinical event of respiratory depression because of the minimum dose of both adjuvants. This case report shows the differences between the two groups and suggest that adjuvant administration of dexmedetomidine in local anesthetic medication causes faster onset of sensory blockade compared to clonidine. The onset of motor block was also faster in the dexmedetomidine group compared to the clonidine group in accordance with the above theory that alpha-2 adrenoceptor agonists produce analgesia by releasing C-fiber transmitters and hyperpolarization of postsynaptic horned dorsal neurons. Increase duration motoric blockade due to binding of alpha-2 agonist adrenoreceptor in motoric neuron in the dorsal horn and dexmedetomidine has greater selectivity than clonidine.

The intensity of postoperative pain and the quality of the pain relief were assessed from the Verbal Rating Scale (VRS), and analgesia was given when VRS >4. We found a higher VAS in the clonidine group compared to the dexmedetomidine. In this case report, clonidine adjuvant group needed additional analgesic such as ketorolac on average at 4th h postoperative and in dexmedetomidine group needed additional analgesic at 6th h postoperative.

There were no side effects such as vomiting, headache, chills, and dizziness in the two groups. The occurrence of nausea was found in two patients with dexmedetomidine adjuvant administration, and the occurrence of dry mouth was found in four patients with clonidine adjuvant administration.


  Conclusion Top


Dexmedetomidine is a safe alternative for clonidine as an adjuvant in epidural analgesia in gynecological laparotomy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Nelson G, Altman AD, Nick A, Meyer LA, Ramirez PT, Achtari C, et al. Guidelines for postoperative care in gynecologic/oncology surgery: Enhanced recovery after surgery (ERAS®) Society recommendations-Part II. Gynecol Oncol 2016;140:323-32.  Back to cited text no. 3
    
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Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, et al. Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: A meta-analysis. Anesthesiology 2005;103:1079-88.  Back to cited text no. 5
    
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Gabriel JS, Gordin V. Alpha 2 agonist in regional anesthesia and analgesia. Curr Opin Anaesthesiol 2001;14:751-3.  Back to cited text no. 13
    
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Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddie MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7.  Back to cited text no. 15
    
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