|Year : 2017 | Volume
| Issue : 4 | Page : 220-225
Dexmedetomidine in preeclamptic patients undergoing caesarean section under general anesthesia
Nosaiba K Ezz El-Arab, Salama I El-Hawary, Ashraf E El-Zeftawy, Rabab M Mohammed
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||16-Mar-2017|
|Date of Acceptance||03-Sep-2017|
|Date of Web Publication||12-Mar-2018|
Nosaiba K Ezz El-Arab
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Tanta University, Botross street, El-Gharbia, Tanta
Background Dexmedetomidine is used as a sedative in surgical and other procedures in nonintubated adult and pediatric patients. It has been successfully used in laboring parturients as it provides maternal hemodynamic stability and anxiolysis.
Aim The aim of this study is to assess the effects of dexmedetomidine in preeclampsia patients under general anesthesia as regards: pressor response to laryngoscopy and intubation, doses of anesthetic agents, muscle relaxants and narcotics, uterine contractility and neonatal effect, postoperative recovery, and postoperative analgesic requirements.
Patients and methods This study was carried out on 60 parturients with preeclampsia who were scheduled for elective caesarean delivery. Patients were divided randomly into two groups: DEX group, patients received 1 µg/kg intravenous dexmedetomidine 10 min before induction and a maintenance dose with 0.4 µg/kg/h during surgery, and the control group: patients did not receive dexmedetomidine (n=30/group). Changes in maternal heart rate, mean arterial blood pressure, time from induction to delivery, full anesthesia time (especially during stress of intubation), and depth of anesthesia were monitored by bispectral index. The total dose of propofol, rocuronium and fentanyl consumption, uterine contraction after placental delivery, Apgar score, postoperative recovery profile, postoperative pain, and postoperative analgesia were also assessed.
Results Heart rate was significantly lower in the DEX group than in the control group. The mean arterial blood pressure was significantly lower in the DEX group than in the control group from the induction till after extubation. Also there was significant decrease in the total consumption of propofol, fentanyl, and muscle relaxant in the DEX group than in the control group, while both groups were comparable in uterine contraction, Apgar score, and awareness.
Conclusion This study suggests the effective use of dexmedetomidine in pre-eclamptic patients undergoing elective cesarean as it stabilizes the maternal hemodynamic parameters during intubation and after intubation with negligible effect on the fetus.
Keywords: cesarean section, dexmedetomidine, preeclampsia
|How to cite this article:|
Ezz El-Arab NK, El-Hawary SI, El-Zeftawy AE, Mohammed RM. Dexmedetomidine in preeclamptic patients undergoing caesarean section under general anesthesia. Tanta Med J 2017;45:220-5
|How to cite this URL:|
Ezz El-Arab NK, El-Hawary SI, El-Zeftawy AE, Mohammed RM. Dexmedetomidine in preeclamptic patients undergoing caesarean section under general anesthesia. Tanta Med J [serial online] 2017 [cited 2018 Nov 12];45:220-5. Available from: http://www.tdj.eg.net/text.asp?2017/45/4/220/227119
| Introduction|| |
Pre-eclampsia is a disease which has a great impact on maternal and neonatal health. It is one of the leading causes of maternal and perinatal mortality and morbidity. It is accepted that the onset of a new episode of hypertension during pregnancy (with persistent diastolic blood pressure >90 mmHg) with the substantial proteinuria (>0.3 g/24 h) can be considered as criteria for pre-eclampsia diagnosis. Although pathophysiological changes (e.g. inadequate placentation) exist from very early stages of the pregnancy, hypertension and proteinuria usually become apparent after 20th week of pregnancy and are present in 2–8% of all pregnancies overall .
Complications for the mother may include eclampsia (seizures), stroke, liver or kidney failure, abnormal coagulation, and problems for the baby may include poor growth and preterm birth .
The stress response results from the increase in sympathetic and sympathoadrenal activity, as evidenced by increased plasma catecholamine concentrations in patients undergoing surgery under general anesthesia ,. Many drug regimens and techniques have been used for attenuating the stress response to laryngoscopy and intubation, including opioids, barbiturates, benzodiazepines, beta blockers, calcium channel blockers, vasodilators, lidocaine, etc. ,.
An α2 adrenergic agonist has been shown to decrease the stress responses to noxious stimulation and to prevent the overall hemodynamic changes ,. It also reduces the need for anesthetics and therefore can be used as an adjuvant for general anesthetics (7, 9, 10].
Pharmacologically, dexmedetomidine is an active d-isomer of medetomidine, and a highly selective α2-adrenoceptor agonist . It is more potent than clonidine as it is 16 times more specific for α2-receptors. Dexmedetomidine (by its central sympatholytic action) enhances hemodynamic stability when used as an adjuvant during general anesthesia. It has analgesic- and anesthetic-sparing property . Dexmedetomidine has potent sedative properties ,. However, because of its sedative property, it is unknown if the recovery from anesthesia would be delayed or not .
| Aim|| |
The aim of this study is to assess the effects of dexmedetomidine in pre-eclampsia patients under general anesthesia as regards: the pressor response to laryngoscopy and intubation as the primary end point, doses of anesthetic agents, muscle relaxants and narcotics, uterine contractility and neonatal effect, postoperative recovery, and postoperative analgesic requirements as secondary end points.
| Patients and methods|| |
After approval from the ethics committee, an informed consent was obtained from all participants in this research. All data of patients was confidential with secret codes and private file for each patient, and the photographs applied only to the parts of body linked to the research. Each patient received an explanation to the purpose of the study. All given data were used for the current medical research only. Any unexpected risks appeared during the course of the research was clarified to the participants and the ethics committee in time.
The series of the present study included 60 full-term parturients aged 20–40 years with preeclampsia who were planned for elective caesarean delivery for different indications under general anesthesia.
The patients were divided into two groups and they were selected randomly to receive either 1 µg/kg intravenous dexmedetomidine 10 min before induction and maintenance dose with 0.4 µg/kg/h during surgery till 15 min before the end of surgery (DEX group) or to not receive dexmedetomidine (control group) (n=30/group). Demographic data of the patients were recorded including: the maternal age and body weight. The exclusion criteria were parturients with any medical illness rather than the pregnancy-induced hypertension (sever renal, hepatic and cardiac illness, neurological or muscular disease, anemia), allergy to dexmedetomidine, or with evidence of any fetal compromise. For prophylaxis against aspiration, all patients were received 30 ml sodium citrate 30 min before induction. Monitoring of the patients was done using ECG, noninvasive blood pressure, and pulse oximetry. Left uterine displacement was established, preoxygenation with 100% O2 was performed from the start of the infusion of the drug. Anesthesia was induced by propofol which was injected slowly till loss of eye lash reflex and the time and dose was calculated followed by rocuronium (1 mg/kg); Sellick’s maneuver was done; the patients were intubated with a properly sized cuffed tube. Tidal volume and respiratory rate were adjusted to a maintain end tidal CO2 of between 32 and 35 mmHg measured by capnography. Maintenance of anesthesia by isoflurane which was adjusted to below 0.75 minimum alveolar concentration for the patients to maintain the heart rate (HR) and arterial blood pressure within 20% from baseline with monitoring of awareness by bispectral index helped to control minimum alveolar concentration. Increments of rocuronium 0.3 mg/kg were given to two groups.
After the neonate and placenta were delivered an infusion of oxytocin 5–10 IU was given. Changes in maternal heart rate, mean arterial blood pressure (MAP) at baseline, immediately after intubation, 5, 15, 30 min after intubation, and immediately before and after extubation were monitored. The total dose of propofol, rocuronium, and fentanyl were calculated. Intraoperative and postoperative uterine relaxation was assessed by the obstetrician and doses of oxytocin were calculated. Awareness of the patient was assessed by bispectral index (BIS) , Apgar score was assessed ; postoperative recovery profile  and postoperative pain were assessed using visual analogue scale (VAS)  at 30 min after extubation (when the patient becomes fully awake), 1, 2, 4, 6 h postoperatively, postoperative analgesia was given according to the VAS value.
- If the VAS was less than 4, nonsteroidal anti-inflammatory drugs ketorolac 0.75 mg/kg was given intravenously.
- If the VAS was at least 4, morphine of dose 0.1 mg/kg was given intravenously.
Postoperative sedation was assessed by Ramsay Sedation Scale  at 30 min after extubation, 1, 2, 4, 6 h, postoperatively.
The collected data were organized, tabulated, and statistically analyzed using the SPSS software statistical computer package, version 16 (SPSS Inc., Chicago, Illinois, USA). For quantitative data, the range, mean, and SD were calculated. For qualitative data, comparison between two groups and more was done using χ2-test. For comparison between the means of two groups of parametric data, Student’s t-test was used. Intragroup comparison was performed using repeated measures of t-test. We used Mann–Whitney U-test for analyzing the VAS score.
| Results|| |
The demographic data (age and weight) showed no significant difference between both groups ([Table 1]).
Preoperative hemodynamics (HR, blood pressure) were comparable between the two studied groups. The heart rate in the DEX group was significantly lower than that in the control group at all measured times (P=0.001) as in [Table 2].
Patients in the DEX group had statistically significant lower change in MAP, whereas patients of the control group showed significant elevation of arterial blood pressure from the induction till after extubation (P=0.001) as in [Table 3].
|Table 3 Comparison between mean arterial blood pressure changes in both groups|
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As regards consumption of propofol, rocuroniume, and fentanyl, there was significantly lower change in the DEX group (P=0.001).
As regards awareness this study showed that in the DEX group the percentage of deeply anesthetized patients (BIS<40) was 30% and the percentage of adequately anesthetized patients (BIS=40–60) was 70% and in the control group the percentage of deeply anesthetized patients was 3.33% and the adequately anesthetized patients was 83.33%, and in the lightly anesthetized patients (BIS>60) it was 10%, so there was significant difference between both groups (P=0.006).
There were no significant differences between both groups as regards uterine contraction, oxytocin consumption, and Apgar score of the baby.
As regards postoperative recovery profile it showed that there was significant decrease in the DEX group than in the control group (P<0.001) as in [Table 4].
|Table 4 Comparison between postoperative recovery profile changes in both groups|
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As regards VAS there was a significant decrease in the DEX group than the other group (control) at 30 min, 2 h, and 6 h after extubation, other than that times there was no significant difference as shown in [Table 5].
As regards the time of rescue analgesia it was significantly shorter in the control group than in the DEX group.
Also the total consumption of ketorolac was insignificant between both groups unlike morphine consumption which was significantly lower in the DEX group than in the control group.
As regards Ramsy Sedation Scale there was no significante difference between both groups as in [Table 6].
| Discussion|| |
In this study, it was found that dexmedetomidine succeded significantly in reducing the stress response presented by tachycardia and hypertention in preeclamptic patient making good option for less complicated general anesthesia in preeclamptic patients.
Since the FDA approval of dexmedetomidine for use in humans for short-term sedation and analgesia in 1999, it has been studied in several other perioperative settings. There are many series reported in the literature about the efficacy of dexmedetomidine in the hemodynamical stability of patients on general anesthesia.
The mean value of postoperative HR and MAP was significantly lower in the DEX group as compared with the control group. Concerning the total dose of propofol, rocuronium, and fentanyl, there was significant decrease in group I (DEX) than in group II (control). According to the comparison of intraoperative and postoperative uterine relaxation in both groups there was an insignificant difference between both groups.
Oxytocin consumption (IU) in both groups was also insignificant between both groups.
Awareness of patients in both groups using BIS, it was found that there was significant difference between both groups, as in group I (DEX) the percentage of deep anesthesia was 30% and the percentage of adequate anesthesia was 70% and in group II (control) the percentage of deep anesthesia was 3.33% and adequate anesthesia was 83.33% and light anesthesia was 10%, which was significant.
A comparison of Apgar score in both groups shows an insignificant difference between both groups. Concerning postoperative recovery profile (time of extubation, eye opening, orientation, and mobility) was shorter and highly significant in group I (DEX) when compared with group II (control). The VAS score was significantly lower in group I (DEX) than in group II (control) at 30 min, 1, 2, 4, and 6 h after extubation. The onset of postoperative analgesic requirement was significantly lower in group II (control) than in group I (DEX). There was no significant difference between both groups as regards postoperative requirement of NSAIDS (ketorolac). The total dose of postoperative morphine requirement was significantly lower in group I (DEX) than in group II control. There was no significant difference between both groups as regards Ramsay Sedation Scale.
As regards the study by Gandhiand colleagues, which is about the comparison between dexmedetomidine with fentanyl in attenuation of pressor response during laryngoscopy and intubation, the study concluded that dexmedetomidine when used intravenous premedicant at a dose of 0.6 µg/kg provides beneficial effect in attenuation of pressor response to laryngoscopy and endotracheal intubation in patients undergoing elective surgical procedures under general anesthesia .
Also the study by Keniya and colleagues, which about that dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anesthetic requirement concluded that dexmedetomidine as a preanesthetic medication 1 µg/kg and intraoperative infusion 0.2–0.7 µg/kg/h significantly attenuates sympathoadrenal response to tracheal intubation. In addition, continuous intraoperative administration of dexmedetomidine maintains intraoperative cardiovascular stability .
Also the study by Patel et al.  concluded that dexmedetomidine, when administered as a preanaesthetic medication 1 µg/kg and intraoperative infusion 0.2–0.8 µg/kg, attenuates stress response to various noxious stimuli and maintains hemodynamic stability. This study nearly has the same outcome in attenuation of pressor response to laryngoscopy and endotracheal intubation, but the present study is better because of the use of lower, fixed doses of intraoperative dexmedetomidine infusion 0.4 µg/kg.
Guen and colleagues concluded that giving dexmedetomedine in 1 µg/kg as a loading dose over 10 min, followed by continuous infusion of 0.5 µg/kg/h till the skin closure significantly reduced the total propofol dosage and remifentanyl, the same in our study but we used fentanyl instead of remifentanyl.
Also the study by Memis et al.  showed that dexmedetomidine reduces rocuronium requirements during sevoflurane anesthesia, by altering the pharmacokinetic profile of rocuronium. This effect may decrease muscle relaxant requirements during surgery, thereby potentially reducing the risk of residual muscle weakness during emergence. Dexmedetomidine significantly attenuates postoperative pain and reduces opioid and volatile anesthetic requirements in morbidly obese patients and our study showed a significant decrease in doses needed of rocuronium for optimal relaxation.
Also Schnabel et al. , concluded in their meta-analysis of randomized controlled trials that intravenous DEX administration leads to lower postoperative pain, reduced opioid consumption, and a lower risk for opioid-related adverse events.
Blaudszun et al.  concluded in their systematic review and meta-analysis of randomized controlled trials that dexmedetomidine was statistically significantly lower in opioid consumption, which was observed from the second postoperative hour until the 24th hour. The present study showed the delayed onset of requirement of postoperative analgesia in the dexmedetomidine group.
In contrast to our study Patel et al.  concluded that sedative property of dexmedetomidine delays postoperative recovery. This controversy may be due to the use of high doses of dexmedetomidine infusion (0.8 µg/kg), while in our study we used lower doses of dexmedetomidine (0.4 µg/kg) and sedation was assessed in both groups by Ramsay Sedation Scale, at 30 min after extubation, 1, 2, 4, 6 h, postoperatively, which showed no significant difference between both groups (P>0.05). Also in their study they did not define the duration of the operation which may be prolonged and interfere the recovery period.
Nair and Sriprakash concluded that dexmedetomidine does not cross the uteroplacental barrier due to its high placental extraction which because of its different and unique pharmacokinetics do not cross the placenta significantly. Dexmedetomidine has a high placental retention of 0.77 maternal/fetal index .
Also Abu-Halaweh and colleagues reported a case of an obese diabetic patient with severe eclampsia who received only dexmedetomidine, achieving mild pain scores and superficial sedation during the infusion, with no other side effects. The patient eventually underwent C-section under general anesthesia due to late persistent decelerations .
Obstetric patients are liable to awareness intra operative, so Patel and colleagues showed that using dexmedetomidine during surgery permit adequate depth of anesthesia with response and state entropy being maintained between 40 and 60, and this study showed that in comparison between both groups using dexmetomedine in group I (DEX) affects significantly in decreasing intraoperative awareness (P=0.006) .
| Conclusion|| |
The study concluded that a loading dose of intravenous 1 µg/kg dexmedetomidine and intraoperative 0.4 µg/kg/h infusion as a maintenance dose is effective in the attenuation of the pressor response to laryngoscopy and endotracheal intubation in pre-eclamptic patients undergoing cesarean section, decreasing muscle relaxant, anesthetics and narcotics requirement, improving postoperative recovery profile, and providing postoperative analgesia which reduces the demand of opioid and delays the onset of rescue analgesia.
All authors had equal role in the design, work, statistical analysis, and in manuscript writing.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010; 376:631–644.
Meher S, Duley L. Nitric oxide for preventing pre‐eclampsia and its complications. Cochrane Database Syst Rev 2007; 18:CD006490.
Sturaitis M, Kroin J, Swamidoss CP, Moric M. Effects of intraoperative dexmedetomidine infusion on hemodynamic stability during brain tumor resection. Anesthesiology 2002; 97(3A):A310.
Yildiz M, Tavlan A, Tuncer S, Reisli R, Yosunkaya A, Otelcioglu S. Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and intubation. Drugs in R & D 2006; 7:43–52.
Charuluxananan S, Kyokong O, Somboonviboon W, Balmongkon B, Chaisomboonpan S. Nicardipine versus lidocaine for attenuating the cardiovascular response to endotracheal intubation. J Anesth 2000; 14:77–81.
Abou-Arab M, Heier T, Caldwell J. Dose of alfentanil needed to obtain optimal intubation conditions during rapid-sequence induction of anaesthesia with thiopentone and rocuronium. Br J Anaesth 2007; 98:604–610.
Flacke JW, Bloor BC, Flacke WE, Wong D, Dazza S, Stead SW, Laksh A. Reduced narcotic requirement by clonidine with improved hemodynamic and adrenergic stability in patients undergoing coronary bypass surgery. Anesthesiology 1987; 67:11–19.
Quintin L, Bonnet F, Macquin I, Szekely B, Becquemin J, Ghignone M. Aortic surgery: effect of clonidine on intraoperative catecholaminergic and circulatory stability. Acta Anaesthesiol Scand 1990; 34:132–137.
Kaukinen S, Pyykkö K. The potentiation of halothane anaesthesia by clonidine. Acta Anaesthesiol Scand 1979; 23:107–111.
Bloor BC, Flacke WE. Reduction in halothane anesthetic requirement by clonidine, an alpha-adrenergic agonist. Anesth Analg 1982; 61:741–745.
Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya N, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anesth 2006; 53:646–652.
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. J Am Soc Anesthesiol 2000; 93:382–394.
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.
Patel CR, Engineer SR, Shah BJ, Madhu S. Effect of intravenous infusion of dexmedetomidine on perioperative haemodynamic changes and postoperative recovery: a study with entropy analysis. Indian J Anaesth 2012; 56:542.
] [Full text]
Lee JH, Kim H, Kim H-T, Kim M-H, Cho K, Lim SH, Lee KM et al.
Comparison of dexmedetomidine and remifentanil for attenuation of hemodynamic responses to laryngoscopy and tracheal intubation. Korean J Anesthesiol 2012; 63:124–129.
Myles P, Leslie K, McNeil J, Forbes A, Chan M et al.
Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet 2004; 363:1757–1763.
Aly H, Hassanein S, Nada A, Mohamed MH, Atef SH, Atiea W. Vascular endothelial growth factor in neonates with perinatal asphyxia. Brain Dev 2009; 31:600–604.
Singh SK, Kumar A, Mahajan R, Katyal S, Mann S. Comparison of recovery profile for propofol and sevoflurane anesthesia in cases of open cholecystectomy. Anesth Essays Res 2013; 7:386. [Full text]
Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. Ann Emerg Med 2001; 38:639–643.
Keniya VM, Ladi S, Naphade R. Dexmedetomidine attenuates sympathoadrenal response to tracheal intubation and reduces perioperative anaesthetic requirement. Indian J Anaesth 2011; 55:352.
] [Full text]
Gandhi S, Goyal V, Radhakrishnan K, Balakrishnan M. Comparison of dexmedetomidine with fentanyl in attenuation of pressor response during laryngoscopy and intubation. IOSR J Pharm 2014; 2:28–38.
Woudstra DM, Chandra S, Hofmeyr GJ, Dowswell T. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy. Cochrane Database Syst Rev 2010; 8:CD008148.
Schnabel A, Meyer-Friessem C, Reichl S, Zahn P, Pogatzki-Zahn E. Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials. Pain 2013; 154:1140–1149.
Blaudszun G, Lysakowski C, Elia N, Tramèr MR. Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensitysystematic review and meta-analysis of randomized controlled trials. J Am Soc Anesthesiol 2012; 116:1312–1322.
Nair AS, Sriprakash K. Dexmedetomidine in pregnancy: review of literature and possible use. J Obstetr Anaesth Crit Care 2013; 3:3.
Abu-Halaweh SA, Al Oweidi A-KS, Abu-Malooh H, Zabalawi M, Alkazaleh F, Abu-Ali H, Ramsay M. Intravenous dexmedetomidine infusion for labour analgesia in patient with preeclampsia. Eur J Anaesthesiol 2009; 26:86–87.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]