|Year : 2016 | Volume
| Issue : 1 | Page : 25-29
Study on the effect of dexmedetomidine in reducing hemodynamic responses to general anesthesia for elective cesarean section in patients with pre-eclampsia
Rabab S Mahrous
Department of Anaesthesia, Alexandria University, Alexandria, Egypt
|Date of Submission||19-Sep-2015|
|Date of Acceptance||22-Nov-2015|
|Date of Web Publication||15-Jun-2016|
Rabab S Mahrous
Anaesthesia Department, Alexandria University, 33 Bahaa El-Din El-Ghatwary St., Smouha, Alexandria
Source of Support: None, Conflict of Interest: None
Background Because of the effect of dexmedetomidine (DEX) in hemodynamic stability, it was started as a sedative before and during surgical and other procedures in nonintubated adult and pediatric patients. Since 2009 DEX has been successfully used in laboring parturients. It provides maternal hemodynamic stability, anxiolysis, and stimulation of uterine contractions. Studies have shown that DEX has high placental retention and does not cross the placenta, and there is lower incidence of fetal bradycardia. We hypothesized that dexmedetomidine would be effective in reducing the maternal hemodynamic responses to elective cesarean section in pre-eclamptic patients without adverse neonatal effects.
Patients and methods The present study included 40 parturients with pre-eclampsia who were planned for elective cesarean delivery for different indications under general anesthesia. The patients were divided in two groups and they were selected randomly to receive either fentanyl (control group) or 0.4 μg/kg/h intravenous DEX 10 min before induction (n = 20 per group). Changes in maternal heart rate, mean blood pressure, time from induction to delivery, the full anesthesia time, uterine contraction after placental delivery, umbilical blood gas parameters, and sedation scores were recorded.
Results The heart rate in the DEX group was lower than that in the fentanyl group. Patients in the dexmedetomidine group had statistically significantly lower change in mean arterial blood pressure, whereas patients taking fentanyl showed much higher mean arterial blood pressure from induction until 5 min after extubation. Further, the dexmedetomidine group showed greater uterine contraction, but there was no difference between the two groups in terms of Apgar score at 1 and 5 min, NACS below 35, and umbilical blood gas analysis.
Conclusion It can be concluded that DEX is effective in pre-eclamptic patients undergoing elective cesarean as it stabilizes the maternal hemodynamic parameters with negligible effect on the fetus.
Keywords: cesarean section, dexmedetomidine, pre-eclampsia
|How to cite this article:|
Mahrous RS. Study on the effect of dexmedetomidine in reducing hemodynamic responses to general anesthesia for elective cesarean section in patients with pre-eclampsia. Res Opin Anesth Intensive Care 2016;3:25-9
|How to cite this URL:|
Mahrous RS. Study on the effect of dexmedetomidine in reducing hemodynamic responses to general anesthesia for elective cesarean section in patients with pre-eclampsia. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2017 Aug 18];3:25-9. Available from: http://www.roaic.eg.net/text.asp?2016/3/1/25/184081
| Introduction|| |
The United States Food and Drug Administration (US FDA) approved the use of dexmedetomidine (DEX) in humans in 1999. It was approved to be used as a sedative and analgesic agent for a short duration in ICU patients and for less than 24 h.
DEX acts as a highly selective α-2 adrenergic receptor agonist and thus has many properties such as being a sedative and analgesic agent, decreasing intraoperative anesthetic requirements. It also preserves the respiratory function with smooth recovery when used as an adjunct to general anesthesia ,.
Because of the effect of DEX in hemodynamic stability it was started as a sedative before and during surgical and other procedures in nonintubated adult and pediatric patients in 2008 .
Since then DEX has been growing in popularity and expanding its role in anesthesia but with reluctancy to be used in parturients because of the possibility of uteroplacental transfer and untoward effects on the baby .
Since 2009 DEX has been successfully used in laboring parturients as an adjunct to epidural if pain relief was not satisfactory. Continuous intravenous DEX infusion has been successfully used as an adjuvant to systemic opioids in laboring parturients who do not benefit from epidural analgesia ,. It provides maternal hemodynamic stability, anxiolysis, and stimulation of uterine contractions. Studies report that DEX has a high placental retention and does not cross the placenta, and there is a lower incidence of fetal bradycardia ,.
The choice of anesthetic technique in severely pre-eclamptic women requiring cesarean section has been controversial for a number of years, with relative safety being attributed to epidural anesthesia . There is a high risk in performing cesarean section under general anesthesia in pre-eclampsia because of the increased risk of difficult airway and intubation and marked pressor response at laryngoscopy, intubation, and extubation resulting in dangerous surges in blood pressure. There is a significant risk for intracranial hemorrhage secondary to uncontrolled severe hypertension at induction of general anesthesia .
Successful use of DEX in laboring parturients who could not benefit from epidural analgesia, besides its effect in maternal hemodynamic stability, encourages us to use it in pre-eclampsia patients undergoing cesarean section under general anesthesia.
| Patients and Methods|| |
After obtaining approval from the local research ethics committee, informed consent was obtained from all patients participating in the study. This prospective, randomized, double blind study was carried out on 40 full-term parturients aged 20–35 years with pre-eclampsia who were planned for elective cesarean delivery for different indications under general anesthesia. The sample size was calculated according to the recommendation of the High Institute of Public Health, Biostatistics Department, Alexandria University. The patients were divided randomly into two groups: the control group received 1 μg/kg fentanyl at induction of anesthesia, and the patient group received 0.4 μg/kg/h intravenous DEX starting at 10 min before induction, which stopped after peritoneal closure (n = 20 per group). For randomization, patients drew a sealed opaque envelope from a shuffled deck containing a card representing one of the treatment groups. Patients were not informed of their treatment group.
Demographic data of the patients were recorded and included maternal age, parity, body weight, gestational age, and birth weight. The exclusion criteria were any medical illness other than pregnancy-induced hypertension (severe renal, hepatic, and cardiac illness, neurological or muscular disease, anemia), allergy to DEX, or evidence of any fetal compromise.
For prophylaxis against aspiration, all patients received 30 ml sodium citrate 30 min before induction. The patients were monitored using ECG, noninvasive blood pressure monitor, and pulse oximetry. Left uterine displacement was established, and denitrogenation was accomplished with 100% oxygen for 3 min. A rapid sequence induction was performed using propofol 2 mg/kg and suxamethonium 1 mg/kg. Anesthesia was maintained with 0.5–0.75 MAC isoflurane and cisatracurium 0.1 mg/kg. After the neonate and placenta had been delivered an infusion of 10 IU oxytocin in 500 ml Ringer lactate solution was given. Changes in maternal heart rate and mean blood pressure were recorded preoperatively and 1, 3, 5, 10, 20, and 30 min after the induction. Then after extubation by 1, 3, and 5 min, time from induction to delivery and the full anesthesia time were recorded. The uterine contraction after placental delivery was assessed by the obstetrician and scored from 0 to 10 according to the linear analogue scale , with 0 indicating compete uterine relaxation and 10 referring to the best contraction. Maternal sedation in the first postoperative hour was reported every 15 min. Apgar score of the neonates and neurologic adaptive capacity scores were assessed by the pediatrician. All neonates were observed for respiratory depression and bradycardia during the first hour after delivery. Umbilical blood samples were taken for blood gas analysis.
Sedation scores were recorded using a five-point scale (1 = completely awake, 2 = awake but drowsy, 3 = asleep but responsive to verbal commands, 4 = asleep but responsive to tactile stimulus, 5 = asleep and not responsive to any stimulus)  every 15 min during the first hour after the surgery.
Statistical analysis was undertaken using the Statistical Program for Social Sciences (SPSS) version 20.0 (IBM, Armonk, New York, USA). The paired t- test and comparison between means were used to analyze the relations between the obtained results in both groups. Statistical significance was set at P value of 0.05.
| Results|| |
The demographic data (age, weight, gestational age) and time to delivery were similar in both groups ([Table 1]).
On comparing the means of the two groups the preoperative heart rate and mean arterial blood pressure were found to be the same in both groups. The heart rate in the DEX group was lower than that in the fentanyl group and the difference was highly statistically significant (P = 0.001) ([Figure 1]).
|Figure 1: Comparison between heart rate changes in dexmedetomidine and fentanyl groups.|
Click here to view
Patients in the DEX group had statistically significantly lower change in mean arterial blood pressure, whereas patients taking fentanyl showed much higher mean arterial blood pressure from induction until 5 min after extubation. This relation proved to be highly significant (P = 0.001) ([Figure 2]). Also the DEX group showed greater uterine tone and less postoperative nausea and vomiting compared with the fentanyl group.
|Figure 2: Comparison between mean arterial blood pressure (MAP) changes in dexmedetomidine and fentanyl groups.|
Click here to view
As regards the neonatal parameters, there was no difference between the two groups in terms of Apgar score at 1 and 5 min, NACS below 35, and umbilical blood gas analysis ([Table 2]). In contrast, the DEX group showed a statistically significantly higher sedation score compared with the fentanyl group ([Figure 3]).
|Figure 3: Comparison of sedation score between dexmedetomidine group and fentanyl group.|
Click here to view
| Discussion|| |
Since the FDA approval of DEX for use in humans for short-term sedation and analgesia in 1999, it has been studied in several other perioperative settings. There are many studies on the efficacy of DEX in hemodynamical stability in patients on general anesthesia. Talke et al.  performed a placebo-controlled study in vascular surgery and reported that DEX-treated patients showed less increase in heart rate and noradrenaline levels when administered intravenously at a dose of 0.8 μg/kg.
Hall et al.  used DEX at a dose of 0.2 and 0.6 μg/kg intravenously and reported a reduction in heart rate without any change in mean arterial pressure.
Yildiz et al.  and Ozkose et al.  demonstrated a decrease in mean arterial pressure and heart rate after a single dose of 1 μg/kg DEX.
Gogus et al.  compared the effects of fentanyl, DEX, and esmolol in the prevention of hemodynamic response to intubation in 90 patients aged 2165 years undergoing elective surgery and who were in ASA I or II. They concluded that esmolol was more effective than DEX and fentanyl in preventing increases in systolic, diastolic, and mean arterial pressures following endotracheal intubation. In contrast, DEX was more effective than esmolol and fentanyl in preventing the increase in heart rate.
Our understanding of the existing literature is that there was a reluctance to use DEX in pregnant women because of the fear of passing the uteroplacental barrier and causing neonatal respiratory depression.
There have been many case reports on the use of DEX in parturients after proof of its retention in the placenta with negligible effect on the fetus ,.
All previous studies reported that DEX can be used in parturients safely without affecting the delivered babies, who were delivered with normal Apgar score ,,.
El-Tahan et al.  compared different concentrations of DEX and placebo in caesarian section and proved its effect in lowering the heart rate and mean arterial blood pressure. They concluded that preoperative administration of DEX at a dose of 0.4 and 0.6 μg/kg attenuates maternal hemodynamic and hormonal responses to cesarean section. However, they did not use DEX in pre-eclampsia and they excluded pre-eclamptic patients from their study.
In this study we attempted to apply the cardiovascular stabilizing effect of DEX in pre-eclamptic patients. To this end we randomly selected 40 patients with pre-eclampsia undergoing elective cesarean section. Twenty were given DEX preoperatively and the other 20 were given fentanyl as a premedication. Comparison of our results with that of the control group (fentanyl group) revealed that the preoperative infusion of DEX at a rate of 0.4 μg/kg/h led to a significant slowing down of heart rate and lowering of the mean arterial blood pressure during cesarean section in pre-eclamptic patients. In addition, it was noticed that babies were delivered with normal Apgar score and normal gas parameters.
Our results were, in fact, comparable to those of a previous study carried out by Abu-Halaweh et al.  who reported on the successful use of intravenous DEX infusion in pregnant women with diabetes mellitus and pregnancy-induced hypertension under general anesthesia without any untoward maternal and child adverse events
The limitation of this study is that we studied the effect of only a single dose of DEX and did not study the effect of increasing the dose on the hemodynamic parameters, as it is known that the effect of DEX on blood pressure and heart rate is dose dependent ,.
| Conclusion|| |
It can be concluded that this study supports the previous series in the literature that have proved the success of preoperative administration of DEX in attenuating the hemodynamic responses to caesarean section; in addition, this study also proved the effective use of DEX in pre-eclamptic patients undergoing elective cesarean as it stabilizes the maternal hemodynamic parameters with negligible effect on the fetus.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res 2011; 5:128–133.
Grewal A. Dexmedetomidine: new avenues. J Anaesthesiol Clin Pharmacol 2011; 27:297–302.
Shukry M, Miller JA. Update on dexmedetomidine: use in nonintubated patients requiring sedation for surgical procedures. Ther Clin Risk Manag 2010; 6:111–121.
Mattingly JE, D'Alessio J, Ramanathan J. Effects of obstetric analgesics and anesthetics on the neonate : a review. Paediatr Drugs 2003; 5: 615–627.
Abu-Halaweh SA, Al Oweidi AK, Abu-Malooh H, Zabalawi M, Alkazaleh F, Abu-Ali H, Ramsay MA. Intravenous dexmedetomidine infusion for labour analgesia in patient with preeclampsia. Eur J Anaesthesiol 2009; 26:86–87.
Grosu I, Lavand'homme P. Use of dexmedetomidine for pain control. F1000 Med Rep 2010; 2:90.
Galloway S, Lyons G. Preeclampsia complicated by placental abruption, HELLP, coagulopathy and renal failure-further lessons Int J Obstet Anesth 2003; 12:35–39.
Howell P. Spinal anaesthesia in severe preeclampsia: time for reappraisal, or time for caution?. Int J Obstet Anesth 1998; 7:217–219.
Hull J, Rucklidge M. Management of severe pre-eclampsia and eclampsia. Update Anaesth 2009; 25:50–54.
Ghaly RG, Flynn RJ, Moore J. Isoflurane as an alternative to halothane for caesarean section. Anaesthesia 1988; 43:5–7.
Memiş D, Turan A, Karamanlioğlu B, Pamukçu Z, Kurt I. Adding dexmedetomidine to lidocaine for intravenous regional anesthesia. Anesth Analg 2004; 98:835–840.
Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, et al
. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000; 90:834–839.
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.
Yildiz M, Tavlan A, Tuncer S, et al.
Effect of dexmedetomidine on haemodinamic responses to laryngoscopy and intubation: perioperative haemodynamics and anesthetic requirements. Drugs R D 2006; 7:43–52.
Ozkose Z, Demir FS, Pampal K, Yardim S. Hemodynamic and anesthetic advantages of dexmedetomidine, an alpha 2-agonist, for surgery in prone position. Tohoku J Exp Med 2006; 210:153–160.
Gogus N, Akan B, Serger N, Baydar M. The comparison of the effects of dexmedetomidine, fentanyl and esmolol on prevention of hemodynamic response to intubation. Rev Bras Anestesiol 2014; 64:314–319
Karaman S, Evren V, Firat V, Cankayali I. The effects of dexmedetomidine on spontaneous contractions of isolated gravid rat myometrium. Adv Ther 2006; 23:238–243.
Tariq M, Cerny V, Elfaki I, Khan HA. Effects of subchronic versus acute in utero
exposure to dexmedetomidine on foetal developments in rats. Basic Clin Pharmacol Toxicol 2008; 103:180–185.
Nair AS, Sriprakash K. Dexmedetomidine in pregnancy: review of literature and possible use. J Obstet Anaesth Crit Care 2013; 3:3–6.
Palanisamy A, Klickovich RJ, Ramsay M, Ouyang DW, Tsen LC. Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet Anesth 2009; 18:258–261.
Mendoza Villa JM. Dexmedetomidine as adjuvant for analgesia in labor: report of two cases. Rev Colomb Anestesiol 2012; 40:79–81.
El-Tahan MR, Mowafi HA, Al Sheikh IH, Khidr AM, Al-Juhaiman RA. Efficacy of dexmedetomidine in suppressing cardiovascular and hormonal responses to general anaesthesia for caesarean delivery: a dose-response study. Int J Obstet Anesth 2012; 21:222–229.
Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans. II. Hemodynamin changes. Anesthesiology 1992; 77:1134–1142.
Kallio A, Scheinin H. Effects of dexmedetomidine, a selective alpha2-adrenoceptor agonist, on hemodynamin control mechanisms. Cli Pharmacol Ther 1989; 46:33–42.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]