|Year : 2015 | Volume
| Issue : 2 | Page : 183-188
The hemodynamic and analgesic profile of dexmedetomidine against fentanyl in preeclamptic parturients undergoing Cesarean section under general anesthesia
Nadia Helmy, Jehan Helmy, Ahmed El-Sakka MD , Heba Rafaat
Department of Anesthesia, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||28-Aug-2014|
|Date of Acceptance||29-Dec-2014|
|Date of Web Publication||8-May-2015|
Department of Anesthesia, Faculty of Medicine, Cairo University, Cairo 11223
Source of Support: None, Conflict of Interest: None
The aim of the study was to evaluate the effect of dexmedetomidine against fentanyl infusions on stabilizing intraoperative and postoperative hemodynamic parameters; the study also aimed to detect the effect of dexmedetomidine on postoperative pain and analgesic requirements and the neonatal outcome in preeclamptic parturients undergoing Cesarean section under general anesthesia.
Patients and methods
The study was conducted on 100 female preeclamptic parturients scheduled for elective Cesarean section under general anesthesia in the Kasr Elainy school of medicine. Patients were allocated randomly into two groups: group F, fentanyl group (n = 50); group D, dexmedetomidine group (n = 50). During surgery, the blood pressure and the heart rate were traced, and the ventilation time, the extubation time, the postoperative visual analogue score, the time for the first analgesic, the total analgesic requirements, postoperative nausea and vomiting, maternal satisfaction, and the neonatal outcome for each group were observed and recorded.
Regarding hemodynamic parameters, the mean arterial blood pressure and the heart rate were significantly lower in group D in comparison with group F. There was a significant difference between the two study groups in the neurologic adaptive capacity score in favor of group D. Group D showed significantly longer spontaneous ventilation and extubation times compared with group F. The visual analogue score was significantly lower in group D than in group F at all times. Maternal satisfaction was higher in group D than in group F. Both study groups were comparable with regard to the quality of extubation and maternal complications.
The present study demonstrates the benefits of dexmedetomidine in augmenting the hemodynamic stability and the analgesic quality in preeclamptic patients undergoing Cesarean section under general anesthesia without any apparent deleterious maternal or fetal effects. This favors the use of dexmedetomidine as an adjuvant to general anesthesia in preeclamptic parturients in the future.
Keywords: dexmedetomidine, fentanyl, postoperative pain, preeclampsia
|How to cite this article:|
Helmy N, Helmy J, El-Sakka A, Rafaat H. The hemodynamic and analgesic profile of dexmedetomidine against fentanyl in preeclamptic parturients undergoing Cesarean section under general anesthesia. Ain-Shams J Anaesthesiol 2015;8:183-8
|How to cite this URL:|
Helmy N, Helmy J, El-Sakka A, Rafaat H. The hemodynamic and analgesic profile of dexmedetomidine against fentanyl in preeclamptic parturients undergoing Cesarean section under general anesthesia. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2021 Apr 17];8:183-8. Available from: http://www.asja.eg.net/text.asp?2015/8/2/183/156675
| Introduction|| |
Normal pregnancy is associated with significant physiological and anatomical maternal organ adaptation. Preeclampsia is a multisystem disorder unique to human pregnancy. The syndrome is characterized by hypertension, proteinuria, and intrauterine growth restriction starting from 20 weeks of gestation. The disease is characterized by platelets and endothelial dysfunction with severe vasoconstriction, capillary leak, and intravascular volume contraction causing multiorgan hypoperfusion.  .
Dexmedetomidine is a highly selective α2 agonist. The perioperative uses of dexmedetomidine include premedication, prevention of delirium, and postoperative pain management  . Premedication with dexmedetomidine causes anxiolysis, sedation, and analgesia and also helps in decreasing stress responses to tracheal intubation, extubation, and recovery from anesthesia  . As an adjunct to general anesthesia, it helps to decrease the minimum alveolar concentration (MAC) and has opioid-sparing properties, which helps decrease inhalational and opioid requirements and can be of considerable value in situations where a high anesthetic concentration is undesirable or not tolerated, and also under conditions in which hemodynamic alterations are expected  . Perioperatively, dexmedetomidine infusion is associated with a significant reduction in nausea and vomiting, thus causing a reduction in postoperative morbidity  . Dexmedetomidine use in obstetric analgesia is being studied in the view of its high lipophilic properties. It is retained in the placenta, thus resulting in lower fetal transfer and a lower incidence of fetal bradycardia. Continuous dexmedetomidine infusion was used successfully in conjunction with systemic opioids in laboring parturients  . Dexmedetomidine is associated with a decreased hemodynamic response to extubation after surgery  . Intravenous dexmedetomidine reduces opioid-induced muscle rigidity, postoperative shivering, and also possesses hemodynamic stabilizing effects  . Because of all the above advantages, the use of dexmedetomidine is recommended in high-risk pregnancies such as in preeclamptic parturients in whom blood pressure control, hemodynamic stability, and pain control are of significant value. Fentanyl is a synthetic opioid. Its analgesic potency is 50-100 times more than that of morphine  . Intravenous administration of fentanyl causes a short-onset analgesic effect lasting for about 30-60 min. Fentanyl metabolism is not associated with the production of active metabolites  . The lack of prolonged effects on neonates is a characteristic of fentanyl, making it a suitable opioid in Cesarean sections when general anesthesia is provided  . The aim of this study was to determine whether the dexmedetomidine infusion was superior to fentanyl in stabilizing intraoperative hemodynamics and reducing postoperative pain and analgesic requirements, and hence maintaining hemodynamic stability in preeclamptic parturients. The study also aimed to observe the neonatal outcome in the two groups.
| Patients and methods|| |
After approval by local ethical committee and obtaining written consents from the patients included in this study, this prospective randomized controlled double-blinded study was conducted on 100 full-term, 18-45-year-old parturients suffering from mild to moderate preeclampsia with a singleton fetus in vertex presentation. They were scheduled for elective Ceserean section under general anesthesia after refusal to undergo regional anesthesia, which is considered as a contraindication to regional anesthesia. The study was performed in the Kasr Alainy university hospital over a period of 6 months starting from January 2014. Emergency cases, patients with evidence of intrauterine growth restriction or fetal compromise, patients with severe preeclampsia, or BMI greater than 30 were excluded from the study.
Preoperative assessment: All patients were assessed clinically and investigated for exclusion of any of the above-mentioned contraindications. All patients were instructed regarding the visual analogue score (VAS). The laboratory work needed included a complete blood count, the prothrombin time and concentration, liver function tests, and kidney function tests. Preoperative vital signs were recorded including heart rate (HR), arterial blood pressure (ABP), and oxygen saturation on room air. All patients received preoperative medications in the form of H 2 -blocking drug, ranitidine 150 mg and ondansetron 4 mg intravenously. Upon arrival to the operating theatre, standard monitors were applied to the patients including ECG, pulse oximetry, and noninvasive blood pressure monitors. Patients were allocated randomly into two equal groups each of 50 patients using a computer-generated number and concealed using the sequentially numbered, sealed opaque envelope technique. The injection fluid was prepared by the operation theatre nurses, according to a closed envelope data. All staff members inside the theater were blinded to the prepared study drugs and it was disclosed only in case of an emergency situation.
Group F: the fentanyl group received an intravenous bolus of 1 μg/kg fentanyl immediately before the induction of anesthesia, followed by an infusion of 1 μg/kg/h until the beginning of skin closure.
Group D: the dexmedetomidine group received a loading dose of 1 μg/kg intravenous infusion over 10 min before the induction of anesthesia. Intraoperatively, the dexmedetomidine intravenous infusion was continued at a rate of 0.4 μg/kg/h until the beginning of skin closure.
All patients received general anesthesia after preoxygenation for 5 min, and rapid-sequence induction was performed with thiopental 3-5 mg/kg and suxamethonium 1.5 mg/kg. Cricoid pressure was applied, laryngoscopy was performed, and tracheal intubation was performed. Anesthesia was maintained with 0.5-1 MAC of isoflurane in 100% oxygen. Atracurium 0.5 mg/kg was given for muscle relaxation after suxamethonium action faded, with the last dose given with peritonial closure. Patients were ventilated to maintain an EtCO 2 of 30-35 mmHg. After clamping of the umbilical cord, an infusion of 10 U oxytocin in 200 ml saline was given. The dexmedetomidine or fentanyl infusion was stopped at the beginning of skin closure. At the end of the surgery, isoflurane was discontinued and residual neuromuscular block was antagonized with neostigmine 50 μg/kg and atropine 20 μg/kg, and then the trachea was extubated.
- Hemodynamic parameters [HR and systolic and diastolic arterial blood pressures (SBP and DBP)] were recorded preoperatively and every 5 min till the end of surgery.
- All neonates were assessed regarding neonatal apgar scores at birth and then after 1 and 5 min, the neurologic adaptive capacity, and the umbilical pH.
- The time from the discontinuation of isoflurane to regaining spontaneous ventilation was recorded (ventilation time), the time from discontinuation of isoflurane to extubation was recorded (extubation time), and the quality of extubation was observed.
- Postoperative pain was assessed using the pain VAS (0-10 cm) 20 min, 1, and 4 h after extubation. Time for the first analgesic (analgesic rescue time) was recorded and the total analgesic requirements for each group were observed and recorded for the first 24 h postoperatively.
- Postoperative complications such as nausea and vomiting were recorded.
- Maternal satisfaction was recorded.
Data were analyzed using the SPSS statistical program (version 13, SPSS, Inc, Chicago, IL, USA). The sample size was calculated on the basis of the assumption of a difference of 10 mmHg in SBP between the two study groups and a SD within 10% difference; the α value was 0.05 and the power (1−α) of the study was 0.95. Thus, the minimum calculated sample size for each group was 42 patients. This number was increased to 50 patients per group to compensate for possible dropouts. Continuous data were presented as mean ± SD and analyzed using the unpaired Student t-test and the Mann-Whitney U-test. Repeated measures (ABP, HR, etc.) were analyzed by two-way analysis of variance. Categorical data (incidence of complications, VAS, etc.) were presented as the number (frequency) and were analyzed using the χ2 or the Fisher exact test when appropriate. The ventilation time and the extubation time were compared using the log-rank test using a Kaplan-Meier survival analysis. Data were considered significant if the P value was less than 0.05.
| Results|| |
Regarding the demographic data, no significant difference was found between the two study groups with respect to their age, weight, gestational age, and baseline laboratory investigations ([Table 1]).
Regarding hemodynamic parameters, group D showed a significantly lower HR compared with group F at intubation (101 vs. 113, P = 0), skin incision (106 vs. 118, P = 0), delivery time (89 vs. 99, P = 0), and at extubation (97 vs. 112, P = 0). Group D showed a significant decrease in the HR at delivery and extubation compared with the baseline reading ([Table 2]).
Group D showed significantly lower SBP and DBP compared with group F at intubation (systolic 145 vs. 156, P = 0.001) (diastolic 84 vs. 90, P = 0.001), significantly lower blood pressures at skin incision (systolic 145 vs. 154, P = 0.001) (diastolic 84 vs. 88, P = 0.02), at the delivery time (systolic 129 vs. 133, P = 0.01), and at the extubation time (systolic 139 vs. 145, P = 0.01) (diastolic 81 vs. 85, P = 0.02). Group D showed significantly lower SBP and DBP when compared with the baseline reading ([Table 3] and [Table 4]).
Regarding the time to regaining spontaneous ventilation, group D showed a significantly longer time than group F (5 ± 1 vs. 4 ± 1, P = 0.001). Regarding the time to extubation, group D showed a significantly longer time to extubation than group F (11 ± 2 vs. 8 ± 2, P = 0.001). There was a significant difference between the two study groups in ventilation and extubation times ([Table 5]).
Regarding the neonatal outcome, the Apgar score was significantly higher in group D than in group F at birth [5 (0-6) vs. 3 (0-6), P = 0.001] and after 5 min [10 (9-10) vs. 8 (9-10), P = 0.001]. The Apgar score was comparable in both groups at 3 min after birth. Group D showed a higher neurologic adaptive capacity than group F (38.8 ± 0.4 vs. 33.6 ± 3.6 P = 0.001). There was no significant difference between the two study groups in the umbilical pH ([Table 6]).
Regarding postoperative analgesia, the VAS was significantly lower in group D than in group F after 20 min [1 (1-2) vs. 3 (2-5), P = 0.01], after 1 h [3 (2-5) vs. 6 (5-8), P = 0.01], and after 4 h [2 (1-4) vs. 4 (3-6) P = 0.01] ([Table 7]).
The number of patients who requested a rescue postoperative analgesic was significantly lower in group D than in group F [23 (46%) patients vs. 50 (100%) P = 0.001]. The analgesic rescue time was significantly longer in group D postoperatively than in group F [189 ± 94 vs. 55 ± 24, P = 0.001]. The number of patients who received NSAIDs after 1 h was significantly lower in group D than in group F [23 (46%) patients vs. 50 (100%) P = 0.001] ([Table 8]).
Regarding complications, two patients in group D suffered from mild headache and one patient developed delerium. In group F, four patients suffered from vomiting after extubation in comparison with three patients in group D. Both study groups were comparable regarding maternal complications. Maternal satisfaction was significantly higher in group D than in group F (P = 0.03) ([Table 9]).
| Discussion|| |
This double-blinded, prospective, randomized study was performed to compare the effect of intraoperative dexmedetomidine infusion in comparison with fentanyl infusion on intraoperative hemodynamics, the neonatal outcome, postoperative analgesic requirements, maternal complications, and maternal satisfaction in preeclamptic parturients undergoing Cesarean sections under general anesthesia. Regional anesthesia is the anesthetic of choice in preeclamptic women undergoing Cesarean section; however, some women prefer general anesthesia or have contraindications for regional techniques. General anesthesia in preeclamptic parturients may be associated with severe hemodynamic changes during induction and intubation, and severe fluctuations in HR and blood pressure can occur, leading to increased risk of cerebral events, and hence result in double jeopardy for the mother and the fetus. There is an increased risk of aspiration, airway control loss, and transient neonatal depression. Using sedatives and narcotics in parturients have been always controversial as these drugs have a tendency to cross the uteroplacental barrier and might have deleterious effects on the fetus. Dexmedetomidine is an imidazole compound and is the pharmacologically active dextro-isomer of medetomidine, which displays selective α2 -adrenoceptor agonism. Dexmedetomidine has a high placental retention (0.77 maternal/fetal index). Also, it is highly lipophilic, which is why it is retained in the placental tissue  . The mechanism of action is peculiar and differs from the currently used sedatives including clonidine. Activation of the cerebral and the spinal cord receptors inhibits neuronal firing, thus causing bradycardia, hypotension, sedation, and analgesia  . To our knowledge, there is no previous study using dexmedetomidine during Cesarean section for preeclamptic parturients.
Dexmedetomidine was used successfully to attenuate the hemodynamic responses to intubation; Yildiz et al.  demonstrated that perioperative dexmedetomidine use was associated with blunting of the hemodynamic response during laryngoscopy. Neumann et al.  used dexmedetomidine to facilitate awake fiberoptic intubation in patients with spinal muscular atrophy before Cesarean delivery and found no serious neonatal outcome. Klickovich et al.  used intravenous dexmedetomidine successfully in conjunction with opioid-based patient controlled analgesia (PCA) with general anesthesia for Cesarean section in a parturient with tethered spinal cord and they also obtained a favorable maternal and neonatal outcome. Abu-Halaweh et al.  used dexmedetomidine infusion for labor analgesia in preeclamptic patients without any significant neonatal side effects.
In our study, administration of dexmedetomidine was associated with significant reduction in SBP and DBP at intubation, which resembles the results in the study conducted by Saπύroπlu et al.  , in which a comparison of two different doses of dexmedetomidine (0.5 and 1 μg/kg) to suppress hemodynamic responses to tracheal intubation was made. In the present study, the hemodynamic parameters in the dexmedetomidine group were significantly stable during extubation when compared with the fentanyl group. These results are in accordance with the study conducted by Turan et al.  in which dexmedetomidine 0.5 mcg/kg administered 5 min before the end of the surgical procedure was shown to maintain hemodynamic stability, allow easy extubation, provide a more smooth recovery, and allow early neurological assessment after intracranial operations. In our study, the dexmedetomidine group showed better postoperative analgesia as compared with the fentanyl group; the analgesic rescue time was longer in the dexomedetomidine group. It was observed that the dexmedetomidine group had a VAS between 1 and 3 after 20 min, 1, and 4 h, which was lower than that in the fentanyl group, in which the VAS was between 3 and 6; in contrast to our results, Park et al.  in their study to determine the effect of dexmedetomidine in laparoscopic cholecystectomy patients, concluded that the administration of dexmedetomidine in conjunction with multimodal analgesia has minimal effects on the reduction of the postoperative VAS score. The safety of the use of dexmedetomidine on neonates and infants is an important issue. In the present study, the Apgar score was lower in the dexmedetomidine group at 1 min and was comparable at 3 min to the fentanyl group; however, a significantly higher Apgar score was found after 5 min, together with a significantly higher neurologic adaptive capacity score in the dexmedetomidine group compared with the fentanyl group. These results are in line with the case reports by Ala-kokko et al.  , who described dexmedetomidine use in parturients, wherein the delivered babies were within the normal Apgar scores, thus proving that even if there was any uteroplacental transfer, it did not affect the neonatal outcome. Jeong et al.  suggested that invasive diagnostic procedures can be conducted successfully in spontaneously breathing infants having congenital heart disease with either dexmedetomidine 1-3 μg/kg alone or combined with low-dose ketamine. In our study, patients in the dexmedetomidine group showed significantly longer ventilation and extubation times as compared with the fentanyl group; contradictory findings were reported by Belleville et al.  as dexmedetomidine seemed to have minimal respiratory side effects in their study. Postoperative nausea and vomiting (PONV) decrease the patients' recovery quality and also slow its speed and thus decreases patients' satisfaction and prolongs hospitalization; a study conducted by Guo et al.  indicated that dexmedetomidine injection into the locus ceruleus reduced the occurrence of PONV significantly; our results showed that the incidence of PONV was lower in the dexmedetomedine group than in the fentanyl group; however, the difference between the two groups was not significant.
The current study showed many advantages of using dexmedetomidine as an adjunct to general anesthesia in preeclamptic patients, which favors its future use; also, the use of dexmedetomidine as an adjuvant sedative agent to subarachnoid block in preeclamptic patients should be considered in the future. A recent systematic review conducted by Abdallah et al. showed that dexmedetomidine increases the duration of sensory and motor block and the analgesic rescue time associated with spinal anesthesia  .
Our study had some limitations that can be modified in future research; the study was carried out in a surgical procedure of short duration; more studies are required to establish the effects of dexmedetomidine in surgeries of longer duration; also, our study was conducted on mild and moderate preeclamptic patients only, and not in severe preeclampsia, which should also be considered.
| Conclusion|| |
Dexmedetomidine used as a preanesthetic medication and an intraoperative infusion drug in preeclamptic parturients undergoing elective Cesarean section under general anesthesia reduces sympathoadrenal responses to tracheal intubation and extubation significantly, causes significant hemodynamic stability, has significant anesthetic and opioid-sparing properties, and reduces postoperative analgesic requirements and thus postoperative adverse reactions without causing significant adverse neonatal outcome.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Turner JA. Severe preeclampsia: anesthetic implications of the disease and its management. Am J Therapeut 2009; 16: 284-288.
Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol 2008; 21:457-461.
Antilla M, Penttila J, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects Br J Clin Pharmacol 2003; 56:691-693.
Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000; 93:1345-1349.
Grosu I, Lavand'homme P. Use of dexmedetomidine for pain control. Med Rep 2010; 2:90.
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.
Guler G, Akin A, Tosun Z, Eskitascoglu E, Mizrak A, Boyaci A. Single-dose dexmedetomidine attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol Scand 2005; 49:1088-1091.
Weinbroum AA, Ben-Abraham R. Dextromethorphan and dexmedetomidine: new agents for the control of perioperative pain. Eur J Surg 2001; 167:563-569.
Jaslow D, Klimke A, Cunnius P, Neubert D. Prehospital pharmacology: is fentanyl a 21st century replacement for morphine? JEMS 2007; 36:105-109.
Craft JB Jr, Coaldrake LA, Bolan JC, Mondino M, Mazel P, Gilman RM, et al
. Placental passage and uterine effects of fentanyl. Anesth Analg 1983; 62:894-898.
Koehntop DE, Rodman JH, Brundage DM, Hegland MG, Buckley JJ. Pharmacokinetics of fentanyl in neonates. Anesth Analg 1986; 65:227-232.
Evren V, Firat V, Cankayali I. Th effects of dexmedetomidine on spontaneous contractions of isolated gravid rat myometrium. Adv Ther 2006; 23:238-243.
Metz SA, Halter JB, Robertson RP. Induction of defective insulin secretion and impaired glucose tolerance by clonidine. Selective stimulation of metabolic alpha-adrenergic pathways. Diabetes 1978; 27:554-562.
Yildiz M, Tavlan A, Tuncer S, Reisli R, Yosunkaya A, Otelcioglu S. Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and intubation: perioperative haemodynamics and anaesthetic requirements. Drugs R D 2006; 7:43-52.
Neumann MM, Davio MB, Macknet MR, Applegate RL. 2nd. Dexmedetomidine for awake fiberoptic intubation in a parturient with spinal muscular atrophy type III for cesarean delivery. Int J Obstet Anesth 2009; 18:403-407.
Klickovich RJ, Ramsay M, Ouyang DW, Tsen LC. Intravenous dexmedetomidine as an adjunct for labor analgesia and caesarean delivery anesthesia in a parturient with a tethered spinal cord. Int J Obstet Anesth 2009; 18:258-261.
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.
Saðýroðlu A, Celik M, Orhon Z, Yüzer S, Sen B. Different doses of dexmedetomidine on controlling haemodynamic responses to tracheal intubation. Internet J Anesthesiol 2010; 27:2.
Turan G, Ozgultekin A, Turan C, Dincer E, Yuksel G. Advantageous effects of dexmedetomidine on haemodynamic and recovery responses during extubation for intracranial surgery. Eur J Anaesthesiol 2008; 25:816-820.
Park JK, Cheong SH, Lee KM, Lim SH, Lee JH, Cho K, et al
. Does dexmedetomidine reduce postoperative pain after laparoscopic cholecystectomy with multimodal analgesia? Korean J Anesthesiol 2012; 63:436-440.
Ala-Kokko TI, Pienimäki P, Lampela E, Hollmén AI, Pelkonen O, Vähäkangas K. Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta. Acta Anaesthesiol Scand 1997; 41:313-319.
Lee JS, Park SJ, Min KT. Dexmedetomidine for rigid bronchoscopy in an infant with tracheal web after ventricular septal defect patch repair. Yonsei Med J 2014; 55:539-541.
Belleville JP, Ward DS, Bloor BC, Maze M. Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 1992; 77:1125-1133.
Guo TZ, Jiang JY, Buttermann AE, Maze M. Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology 1996; 84:873-881.
Abdallah FW, Abrishami A, Brull R. The facilitatory effects of intravenous dexmedetomidine on the duration of spinal anesthesia: a systematic review and meta-analysis. Anesth Analg 2013; 117:271-278.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]