|Year : 2017 | Volume
| Issue : 1 | Page : 23-28
Effect of intrathecal dexmedetomidine on the quality of combined spinal epidural analgesia and obstetric outcome during vaginal delivery
Gehan F Ezz1, Heba M Fathi MD 1, Hussein M Abd Eldayem2
1 Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Zagazig University Hospitals, Zagazig University, Zagazig, Egypt
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Zagazig University Hospitals, Zagazig University, Zagazig, Egypt
|Date of Submission||31-May-2016|
|Date of Acceptance||22-Oct-2016|
|Date of Web Publication||22-Mar-2017|
Heba M Fathi
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Zagazig University Hospitals, Zagazig University, Zagazig, 44519
Source of Support: None, Conflict of Interest: None
A prospective double-blind randomized controlled study was conducted to evaluate the efficacy and safety of intrathecal (IT) dexmedetomidine when used combined spinal epidural analgesia on maternal and neonatal outcomes during vaginal delivery.
Patients and methods
A total of 60 patients were randomly divided into two groups: group B comprised 30 patients who received IT 2.5 mg hyperbaric bupivacaine+0.05 ml normal saline and group D comprised 30 patients who received IT 2.5 mg hyperbaric bupivacaine+0.05 ml (5 µg) dexmedetomidine. Epidural catheter was inserted in both groups. Epidural analgesia of 10–12 ml of 0.125% bupivacaine in repeated doses was given when visual analog scale (VAS) greater than 3 until delivery. If emergency Cesarean section was indicated, epidural 10–15 ml of 0.5% bupivacaine was administered. The characters of analgesia, VAS, progress of labor, maternal side effects, and neonatal outcomes in terms of mode of delivery and neonatal Apgar score and umbilical artery pH were recorded.
There was a significant shorter onset, longer duration of analgesia and lower number of patients who requested epidural analgesia in group D than in group B. VAS was lower in group D from 10 min until 4 h after spinal injection. Duration of second stage and number of instrumental deliveries was lower in group D. There were no maternal or neonatal complications in both groups, but first Apgar score was higher in group D (P<0.05).
The addition of IT dexmedetomidine to combined spinal epidural improves the quality of analgesia and is considered safe during vaginal delivery.
Keywords: analgesia, bupivacaine, combined spinal epidural, dexmedetomidine, labor
|How to cite this article:|
Ezz GF, Fathi HM, Abd Eldayem HM. Effect of intrathecal dexmedetomidine on the quality of combined spinal epidural analgesia and obstetric outcome during vaginal delivery. Res Opin Anesth Intensive Care 2017;4:23-8
|How to cite this URL:|
Ezz GF, Fathi HM, Abd Eldayem HM. Effect of intrathecal dexmedetomidine on the quality of combined spinal epidural analgesia and obstetric outcome during vaginal delivery. Res Opin Anesth Intensive Care [serial online] 2017 [cited 2021 May 18];4:23-8. Available from: http://www.roaic.eg.net/text.asp?2017/4/1/23/202696
| Introduction|| |
Labor pain is the result of many complex physiological and psychological interactions, both excitatory and inhibitory. The first stage of labor is associated with diffuse pain, which originates from the dilation and stretching of lower uterine segment and cervix . Greater dilation of the vagina and pressure on the perineum are responsible for the more intense somatic pain during the second stage of labor .
Labor pain and painful uterine contractions cause hyperventilation and release high amounts of catecholamine, resulting in maternal and fetal hypoxemia .
Pain relief provides patients comfort and attenuates the release of stress hormones . During labor, combined spinal epidural (CSE) analgesia involves the administration of spinal analgesia through epidural needle and results in rapid onset and profound analgesia from subarachnoid injection and later prolongation of analgesia through epidural catheter .
Dexmedetomidine is a highly selective α2 adrenergic agonist that has both analgesic and sedative properties when used in combination with regional anesthesia .
Dexmedetomidine acts by binding to G-protein that coupled α2 adrenergic receptors, which are found in peripheral, central, and autonomic nervous systems, various vital organs, and blood vessels throughout the body .
There are three subtypes of these receptors, namely α2A, α2B, and α2C, each having different functions and activities. When compared with clonidine, dexmedetomidine is considered to have more affinity for α2A and α2C receptors .
Dexmedetomidine significantly reduces opioid requirements and has sympatholytic effect that can attenuate the stress response to surgery .
Dexmedetomidine is used in pregnancy, as it does not significantly cross the placenta because of its high placental retention . In addition, it has no adverse effect on the mother or fetus in many studies .
This study aimed to evaluate the analgesic effect and safety of intrathecal (IT) dexmedetomidine when added to low-dose bupivacaine in CSE analgesia during vaginal delivery.
| Patients and methods|| |
A prospective double-blind randomized controlled study was done in Department of Anesthesia and Surgical Intensive Care and Department of Obstetrics and Gynecology, Zagazig University Hospitals from January 2015 to September 2015 after approval of the Local Institutional Ethical Committee of Zagazig University Hospitals. This study included 60 patients aged 20–39 years old, with American Society of Anesthesiologists classification I–II, scheduled for normal vaginal delivery with uncomplicated pregnancy, cephalic presentation, not in fetal distress, single fetus, in active labor (had four uterine contractions in 10 min, each contraction lasted for 40–60 s), and cervical dilation 3 cm or more with head engaged.
Patients with cardiac, liver, kidney disease, allergy to local anesthetics or study drugs, contraindications of regional anesthesia, patient refusal, intrauterine growth retardation, fetal distress, past history of sedative drug abuse or failed spinal or epidural, patients with international normalized ratio greater than 1.3, or platelet count less than 100 000 were excluded from this study.
A written informed consent was taken from all patients, and then they were randomly divided into two groups via computer-generated random numbers.
Both groups received CSE analgesia.
Group B: 30 patients received intrathecal (IT) 2.5 mg hyperbaric bupivacaine+0.05 ml of normal saline.
Group D: 30 patients received IT 2.5 mg hyperbaric bupivacaine+0.05 ml (5 µg) of dexmedetomidine.
Test solution was diluted with normal saline to a total volume of 2 ml.
In all patients, an intravenous line was secured with an 18-G cannula. Standard monitoring devices including noninvasive blood pressure cuff, ECG leads, and pulse oximetry probe were attached to the patient and respiratory rate was recorded.
Preloading was done with Ringer’s lactate solution at a dose of 15 ml/kg/body weight over 15 min. The obstetrician showed the cervical dilation, stage and progress of labor, and fetal heart rate (HR).
The onset of administration of IT analgesia was considered when the patient was in active labor.
Aseptic precautions were taken and all instruments of general anesthesia were present during the procedure.
Using CSE set at L3–L4 intervertebral space, with the patient in the sitting position, an IT injection of the study drugs was done and epidural catheter was inserted 5 cm into the epidural space and secured for future administration of 10–12 ml of 0.125% bupivacaine when visual analog scale (VAS) was recorded above 3. If emergency Cesarean section (CS) was indicated, epidural 10–15 ml of 0.5% bupivacaine was administered.
The baseline was defined as time before IT injection of drugs.
Analgesia onset was the time of recording VAS less than 3 after IT injection.
Afterward, VAS was recorded every 10 min for 1 h, and then every 1 h until delivery of the baby.
The analgesia time was calculated from IT injection until the time of first rescue of epidural analgesia.
The number of patients who needed additional epidural analgesia was recorded in each group.
The progress, duration of first and second stage, and modes of labor (vaginal delivery or CS) were recorded by the gynecologist and maternal side effects were observed, recorded, and treated.
There was a decrease in blood pressure more than 20% from baseline treated with intravenous fluids and ephedrine. Maternal bradycardia (decrease in HR<60) was treated with atropine. Fetal bradycardia was monitored by cardiotocography and treated with oxygen to the mother, ensuring lateral position to avoid aortocaval compression. Occurrence of nausea and vomiting were treated with ondansetron 4 mg. Pruritus was treated with intravenous diphenhydramine 50 mg. Occurrence of shivering was also recorded in all patients.
Neonatal Apgar score was recorded together with umbilical cord pH, PaCO2, and HCO3.
The sample size was calculated to detect an increase of 30 min difference in the duration of analgesia between the two groups . It was 30 patients in each group to achieve 80% power and 95% confidence interval with permitting type-1 error rate of 0.05.
Data collected were coded, entered, and analyzed using Microsoft Excel software, and then imported into statistical package for the social sciences (SPSS, version 18.0, SPSS Inc., Chicago, IL, USA). Differences between frequencies (qualitative variables) in groups were compared by Fisher’s exact test. Differences between means (quantitative variables) in groups were compared by Student’s t-test. P-value was set at less than 0.05 for significant results ([Figure 1]).
| Results|| |
A total of 60 women in two equal groups participated in the study. The two groups (group B: bupivacaine +saline and group D: bupivacaine +5 μg dexmedetomidine) were comparable in terms of demographic variables ([Table 1]).
The onset of analgesia was faster, and the time of analgesia was longer in group D than in group B. The number of patients in group B who needed top-ups of epidural analgesia (11 women) was significantly higher when compared with those in group D (three women), as shown in [Table 2].
The baseline VAS was comparable in the two groups, but the subsequent records showed significantly higher VAS in group B than in group D until the end of the fourth hour. After 4 h, no significant difference was found between the two groups ([Table 3]).
The gynecologist recorded that there was no significant difference as regards progress of cervical dilation, duration of the first stage of labor, and the incidence of CS, whereas there was a significant prolongation in the second stage of labor and a significant higher incidence of instrumental delivery was shown in group B as compared with group D ([Table 4]).
Apgar scores (at 1 and 5 min) and umbilical artery pH, PCO2, and HCO3 in the two groups were within normal values. First minute Apgar score was significantly higher in group D than in the other group, but other neonatal parameters showed no significant differences between the two groups ([Table 5]).
The maternal side effects were controllable in the two groups. [Table 6] showed that there was a higher incidence of motor blockade in group B as compared with group D. Other side effects did not differ significantly between the two groups.
| Discussion|| |
In this study, dexmedetomidine provided longer duration of spinal analgesia and lower VAS when added to bupivacaine in the spinal component of CSE analgesia during vaginal delivery.
Dexmedetomidine is a highly selective α2 adrenoceptor agonist that has been used in spinal and epidural anesthesia, as an adjuvant to local anesthetics, with the advantage of increasing the duration of analgesia without adverse neurological effects .
IT dexmedetomidine depresses the release of C-fiber transmitters through binding to presynaptic C-fibers and hyperpolarization of postsynaptic dorsal horn neurons .
Consistent with our result, Kanazi et al.  showed that dexmedetomidine when added to IT bupivacaine resulted in prolongation of the duration of spinal anesthesia.
Gupta et al.  reported that single injection of dexmedetomidine as a local anesthetic adjuvant has been shown to extend the duration of both motor and sensory blockade, in neuraxial and peripheral nerve block.
Clinical studies have demonstrated the safety of IT dexmedetomidine in humans . However, it has been shown that dexmedetomidine in relatively high doses can lead to hypotension when administered either neuraxially or intravenously .
Dexmedetomidine when used in pregnancy does not significantly cross the placenta because of its high placental retention .
In the current study, we found that addition of dexmedetomidine to IT bupivacaine decreased the demand of epidural bupivacaine in compound spinal epidural analgesia and associated with significant decrease in the duration of the second stage of labor and the incidence of instrumental delivery.
Previous studies demonstrated that high concentration of neuraxial local anesthetic might relax pelvic floor musculature, interfere with fetal rotation during descent , and prolong the second stage of labor ,,,.
Many studies demonstrated that neuraxial analgesia is associated with increased risk of instrumental vaginal delivery ,,.
In the current study, the duration of first stage of labor was not affected by increasing epidural demand. This is supported by 2005 Cochrane review  and another systematic review done by Halpern and Leighton  that demonstrated no difference in the duration of first stage of labor among women who received epidural analgesia, systemic opioid analgesia, or no analgesia.
In the current study, although the number of patients who needed additional epidural analgesia was higher in group B, no significant difference in the rate of CS was found between the two groups. Consistent with our result, Dipti et al.  found no relation between epidural analgesia and CS This was also supported by Segal et al.  in their meta-analysis that included nine studies involving 37 000 parturients who found no association between Cesarean delivery rates and the rates of epidural administration.
We found no significant adverse effects of dexmedetomidine, which goes along with results of a meta-analysis conducted by Niu et al.  and showed that IT dexmedetomidine prolonged the duration of spinal anesthesia and improved postoperative analgesia without increasing the incidence of adverse events such as nausea, headache, vomiting, shivering, and hypotension.
With regard to neonatal outcomes, Apgar scores (at 1 and 5 min) and mean umbilical artery pH and blood gases showed normal values with no significant differences between the two groups, except first minute Apgar score, which was significantly higher in group D (P<0.001).
Fyneface-Ogan et al.  found no significant differences in the Apgar score, pH of umbilical venous blood, and fetal HR when compared with the three groups given IT bupivacaine alone, bupivacaine with dexmedetomidine, or bupivacaine with fentanyl.
Many case reports and studies that described the use of dexmedetomidine in parturients have mentioned that babies were delivered with normal Apgar scores, and thus dexmedetomidine does not affect the fetal well-being .
| Conclusion|| |
In CSE analgesia during vaginal delivery, the addition of IT dexmedetomidine to bupivacaine improves the quality of intraoperative analgesia and decreases the requested epidural doses with safe outcomes for mothers and babies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pan P, Eisenach JC. The pain of childbirth and its effect on the mother and fetus. In: Chestnut DH, Pollay LS, Tsen LC, Wong CA, editors. Obstetric anesthesia principles and practice. 4th ed. Philadelphia, PA: Elsevier Mosby; 2009. 387–404.
Ward ME. Acute pain and obstetric patient: recent developments in analgesia for labour and delivery. Int Anaesthesiol Clin 1997; 35:83–103.
Dilesh PK, Eapen S, Kiran S, Chopra V. A comparison of intrathecal dexmedetomidine versus intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labour analgesia. J Obstet Anaesth Crit Care 2014; 4:69–74. [Full text]
Onah HE, Obi SN, Oguanuo TC, Ezike HA, Ogbuokiri CM, Ezugworie JO. Pain perception among parturients in Enugu, South-Eastern Nigeria. J Obstet Gynaecol 2007; 27:585–588.
Macarthur AJ, Ostheimer GW. What is new in obstetric anaesthesia? Lecture. Anesthesiology 2008; 108:777–785.
Mauro VA, Brandao ST. Clonidine and dexmedetomidine through epidural route for postoperative analgesia and sedation in a colecistectomy. Rev Bras Anesthesiol 2004; 4:1–10.
Afsani N. Clinical application of dexmedetomidine. S Afr J Anaesthesiol Analg 2010; 16:50–56.
Fairbanks CA, Stone LS, Wilcox GL. Pharmacological profile of alpha-2 adrenergic receptor agonists identified using genetically altered mice and isotolographic analysis. Pharmacol Ther 2009; 123:224–238.
Taghinia AH, Shapiro FE, Slavin SA. Dexmedetomidine in anesthetic facial surgery: improving anesthetic safety and efficacy. Plast Reconstr Surg 2008; 121:269–276.
Nair AS, Sriprakash K. Dexmedetomidine in pregnancy: review of literature and possible use. J Obstet Anaesth Crit Care 2013; 3:3–6. [Full text]
Hanowra SE, Hassanin R, Sigh R. Intraoperative conditions and quality of postoperative analgesia after adding dexmedetomidine to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anaesthesia. Anesth Essays Res 2013; 7:168–172.
Gupta R, Bogra J, Verma R, Kohli M, Kushwaha JK, Kumar S. Dexmedetomidine as an intrathecal adjuvant for postoperative analgesia. Indian J Anaesth 2011; 55:347–351.
] [Full text]
Mahendru V, Tewari A, Katyal S, Grewal A, Singh MR, Katyal R., A comparison of intrathecal dexmedetomidine, clonidine and fentanyl as adjuvants to hyperbaric bupivacaine for lower limb surgery: a double-blind controlled study. J Anaesthesiol Clin Pharmacol 2013; 29:496–502.
] [Full text]
Elsenach JC, DeKock M, Klimscha W. Alpha-2-adrenergic agonists for regional anaesthesia: a clinical review of clonidine (1984-1995). Anesthesiology 1996; 85:655–674.
Kanazi GE, Aouad MT, Jabbour-Khowry SI, Al Jazzar MD, Alameddine MM, Al-Yaman R et al.
Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anesthesiol Scand 2006; 50:222–227.
Weinbroum AA, Ben-Abraham R. Dextromethorphan and dexmedetomidine: new agents for the control of perioperative pain. Eur J Surg 2001; 167:563–569.
Al-Ghanem SM, Massad IM, Al-Mustafa MM, Al-Zaben KR, Qudaisat IY, Qatawneh IY, Abu-Ali HM. Effect of adding dexmedetomidine versus fentanyl to intrathecal bupivacaine on spinal block characteristics in gynecological procedures: a double-blind controlled study. Am J Appl Sci 2009; 6:882–887.
Cambic CR, Wong CA. Labour analgesia and obstetric outcomes. Br J Anaesth 2010; 105:i50–i60
Halpern SH, Leighton BL. Epidural analgesia and the progress of labor. In: Halpern SH, Douglas MJ, editors. Evidence-based obstetric anesthesia. Oxford: Blackwell; 2005. 10–22.
Sharma SK, Leveno KJ. Update: epidural analgesia does not increase cesarean births. Curr Anesthesiol Rep 2000; 2:18–24.
Sharma SK, Alexander JM, Messick G, Bloom SL, McIntire DD, Wiley J, Leveno KJ. Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women. Anesthesiology 2002; 96:546–551.
Sharma SK, McIntire DD, Wiley J, Leveno KJ. Labor analgesia and cesarean delivery: an individual patient meta-analysis of nulliparous women. Anesthesiology 2004; 100:142–148.
Liu EH, Sia AT, Liu EHC, Sia ATH. Rates of caesarean section and instrumental vaginal delivery in nulliparous women after low concentration epidural infusions or opioid analgesia: systematic review. Br Med J 2004; 328:1410–1412.
Anim-Somuah M, Smyth R, Howell C. Epidural versus non-epidural or no analgesia in labor. Cochrane Database Syst Rev 2005; 4:CD000331.
Dipti A, Bela M, Manjeet A, Arpana H, Pavan G. The effect of epidural analgesia on labor, mode of delivery and neonatal outcome in nullipara of India, 2011-2014. J Clin Diagn Res 2014; 8:OC03–OC06.
Segal S, Su M, Gilbert P. The effect of a rapid change in availability of epidural analgesia on the cesarean delivery rate: a meta-analysis. Am J Obstet Gynecol 2000; 183:974–978.
Niu XY, Ding XB, Guo T, Chen MH, Fu SK, Li Q. Effects of intravenous and intrathecal dexmedetomidine in spinal anaesthesia: a meta-analysis. CNS Neurosci Ther 2013; 19:897–904.
Fyneface-Ogan S, Job OG, Enyindah CE. Comparative effects of single shot intrathecal bupivacaine with dexmedetomidine and bupivacaine with fentanyl on labor outcome. ISRN Anesthesiol 2012; 2012:1–6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]