Intravenous dexmedetomidine use in obstetric anesthesia: A focused review

Yang M., Li S., Drzymalski D., Chen X.

Sun J., Wang H., Tang L., Jiang H., Liu X.

Highlights•Postoperative gastrointestinal dysfunction commonly occurs cesarean section.•Delayed recovery in gastrointestinal function can lead to many complications.•Intravenous dexmedetomidine could accelerate gastrointestinal function recovery.•This method can shorten the postoperative hospital stay and reduce medical costs.AbstractObjectiveGastrointestinal dysfunction after cesarean section negatively affects postoperative recovery. Dexmedetomidine has been shown to improve postoperative gastrointestinal function in patients undergoing lumbar spinal fusion surgery and laparoscopic gastrectomy, but its role in cesarean section has not been fully elucidated. The study aimed to investigate the effect of dexmedetomidine on gastrointestinal function after cesarean section.Study Design220 pregnant women who underwent elective cesarean section were randomized into group D and group S. Group D patients received a loading dose of 0.5 μg/kg of dexmedetomidine for 10 mins followed by a maintenance dose of 0.5 μg/kg/h intravenously immediately after the umbilical cord was cut intraoperatively, whereas the other group (group S) received an equivalent quantity of normal saline as loading and maintenance dose IV by infusion pump. The primary outcome was time to first flatus after surgery (hours). Secondary outcomes included time to first feces and first bowel sounds (hours), incidence rates of postoperative gastrointestinal complications, and the length of postoperative hospital stay (days).ResultsModified intention-to-treat analysis showed that patients in Group D had a significantly shorter time to first flatus (21 [16 to 28.25] vs. 25 [18 to 32.25] h; P = 0.014), time to first feces (45.5 [35.75 to 55.25] vs. 53 [40 to 60] h; P = 0.019), and time to first bowel sounds (P = 0.010), a lower incidence of abdominal distension (21[20.6 %] vs. 36[34.3 %], P = 0.027), shorter length of postoperative hospital stay (P = 0.010) compared to patients in Group S.ConclusionIntraoperative dexmedetomidine infusion reduces the time to first flatus, the incidence of abdominal distension, and shortens the length of hospital stay, promoting gastrointestinal function after cesarean section.

Xu S., Zhou Y., Wang S., Li Q., Feng Y., Chen L., Duan K.

Abstract The efficacy of perioperative dexmedetomidine (DEX) infusion as a precaution against postpartum depression (PPD) in women undergoing cesarean section has not been substantiated systematically. A literature search for RCTs on DEX against PPD was retrieved in the following databases from inception to January 3, 2024: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, CBM, VIP, etc. A total of 13 RCTs with 1711 participants were included. Meta-analysis was performed by RevMan5.3 and Stata16 using a random-effects model. EPDS scores were significantly decreased in the DEX group within one week or over one week postpartum compared to the control group (SMD = −1.25, 95 %CI: −1.73 to −0.77; SMD = −1.08, 95 %CI: −1.43 to −0.73). The prevalence of PPD was significantly inferior to the control at both time points (RR = 0.36, 95 %CI: 0.24 to 0.54; RR = 0.39, 95 %CI: 0.26 to 0.57). Univariate meta-regression suggested that age influenced the heterogeneity of the EPDS scores (P = 0.039), and DEX infusion dose was a potential moderator (P = 0.074). The subgroup analysis results of PPD scores at both time points were consistent, showing that: ① Mothers younger than 30 years old had better sensitivity to DEX for treating PPD. ② The anti-PPD efficacy of continuous infusion of DEX by PCIA was superior to both single infusion and combined infusion. ③ DEX showed a better anti-PPD effect when the total infusion dose was ≤ 2 μg/kg. Moreover, DEX improved analgesia and sleep quality, provided appropriate sedation, and reduced the incidence of nausea, vomiting, and chills. The current evidence confirmed the prophylaxis and superiority of DEX for PPD. More high-quality, large-scale RCTs are required for verifying the reliability and formulating administration methods.

Mohammed S., Biyani G., Kalagara R., Kumar M., Baidya D.K., Chhabra S., Metta R., Eeshwar M., Goel A.D., Yalla B., Fakiris K.

Background and Aims: Dexmedetomidine has been used as an anti-shivering agent in the perioperative period in pregnant patients undergoing caesarean section (CS), but its effectiveness remains inconclusive. This systematic review and meta-analysis aimed to assess the efficacy of intravenous Dexmedetomidine in the management of shivering. Methods: PubMed, MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and Google Scholar were explored for the randomised controlled trials (RCTs), which compared intravenous administration of Dexmedetomidine with normal saline (placebo) or other anti-shivering agents for the prevention or treatment of shivering in pregnant patients undergoing CS under central neuraxial blockade. The primary outcome was either incidence and/or severity (for prevention) and duration and/or success rate (for treatment) of shivering between the two groups. The secondary outcome measures were adverse effects (bradycardia, hypotension, sedation, nausea and vomiting, and effect on the APGAR scores of the baby) if observed. Data were synthesised using a random effect model. We calculated the odds ratio (95% CI) for presenting the categorical outcome and standardized mean difference (95% CI) for continuous outcomes. Heterogeneity was assessed using I2 statistics and was investigated using sensitivity analysis. Results: A total of 15 RCTs were included in the present systematic review and data from 10 RCTs comparing Dexmedetomidine with normal saline were pooled into the meta-analysis for primary outcome measure. The incidence and severity of shivering at 30 and 60 minutes weresignificantly less in the Dexmedetomidine group compared to the normal saline group [OR = 0.30, 95% CI: 0.19 to 0.47, P < 0.0001; MD = -0.54, 95% CI: -0.81 to -0.26, Z = 3.78, P = 0.0002 and MD = -1.06, 95% CI: -1.46 to -0.66, Z = 5.23, P < 0.0001 respectively]. Similarly, the time to reduce shivering was significantly lower and the success rate of treatment was higher in the Dexmedetomidine group compared to the normal saline group [MD = -13.55, 95% CI: −17.78 to -9.12, Z = 6.0, P < 0.0001 and OR = 0.03, 95% CI: 0.02 to 0.07, P < 0.0001 respectively]. There was no heterogeneity among the studies for incidence, severity at 60 minutes, and success rate of treatment outcome, while the severity of shivering at 30 minutes and time to reduce shivering demonstrated moderate heterogeneity. The side effect profile was comparable between the Dexmedetomidine and control (active and passive) group. Conclusion: This meta-analysis shows that intravenous administration of Dexmedetomidine for both prophylaxis and treatment is superior to normal saline in the management of perioperative shivering during CS, but is comparable to other most commonly used anti-shivering agents. There is no statistically significant difference in the incidence of side effects between the two groups.

Yu Y., Li Y., Han D., Gong C., Wang L., Li B., Yao R., Zhu Y.

ImportancePosttraumatic stress disorder (PTSD) is common in people who have experienced trauma, especially those hospitalized for surgery. Dexmedetomidine may reduce or reverse the early consolidation and formation of conditioned fear memory and prevent the occurrence of postoperative PTSD.ObjectiveTo evaluate the effects of intraoperative and postoperative low-dose intravenous pumping dexmedetomidine on PTSD among patients with trauma undergoing emergency surgery.Design, Setting, and ParticipantsThis double-blind, randomized clinical trial was conducted from January 22 to October 20, 2022, with follow-up 1 month postoperatively, in patients with trauma undergoing emergency surgery at 4 hospital centers in Jiangsu Province, China. A total of 477 participants were screened. The observers were blinded to patient groupings, particularly for subjective measurements.InterventionsDexmedetomidine or placebo (normal saline) was administered at a maintenance dose of 0.1 μg/kg hourly from the start of anesthesia until the end of surgery and at the same rate after surgery from 9 pm to 7 am on days 1 to 3.Main Outcomes and MeasuresThe primary outcome was the difference in the incidence of PTSD 1 month after surgery in the 2 groups. This outcome was assessed with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (CAPS-5). The secondary outcomes were the pain score within 48 hours and 1 month postoperatively; incidence of postoperative delirium, nausea, and pruritus; subjective sleep quality; anxiety; and occurrence of adverse events.ResultsA total of 310 patients (154 in the normal saline group and 156 in the dexmedetomidine group) were included in the modified intention-to-treat analysis (mean [SD] age, 40.2 [10.3] years; 179 men [57.7%]). The incidence of PTSD was significantly lower in the dexmedetomidine group than in the control group 1 month postoperatively (14.1% vs 24.0%; P = .03). The participants in the dexmedetomidine group had a significantly lower CAPS-5 score than those in the control group (17.3 [5.3] vs 18.9 [6.6]; mean difference, 1.65; 95% CI, 0.31-2.99; P = .02). After adjusting for potential confounders, the patients in the dexmedetomidine group were less likely to develop PTSD than those in the control group 1 month postoperatively (adjusted odds ratio, 0.51; 95% CI, 0.27-0.94; P = .03).Conclusions and RelevanceIn this randomized clinical trial, the administration of intraoperative and postoperative dexmedetomidine reduced the incidence of PTSD among patients with trauma. The findings of this trial support the use of dexmedetomidine in emergency trauma surgery.Trial RegistrationChinese Clinical Trial Register Identifier: ChiCTR2200056162

Davis P.R., Sviggum H.P., Delaney D.J., Arendt K.W., Jacob A.K., Sharpe E.E.

Background. Dexmedetomidine is a selective α-2 agonist commonly used for sedation that has been used in obstetric anesthesia for multimodal labor analgesia, postcesarean delivery analgesia, and perioperative shivering. This study evaluated the role of intravenous dexmedetomidine to provide rescue analgesia and/or sedation during cesarean delivery under neuraxial anesthesia. Methods. We conducted a single-center, retrospective cohort study of all parturients undergoing cesarean delivery under neuraxial anesthesia between December 1, 2018, and November 30, 2019, who required supplemental analgesia during the procedure. Patients were divided into two groups: patients who received intravenous dexmedetomidine (Dexmed group) and patients who received adjunct medications such as fentanyl, midazolam, ketamine, and nitrous oxide (Standard group). Primary outcome was incidence of conversion to general anesthesia. Results. During the study period, 107 patients received adjunct medications. There was no difference in conversion to general anesthesia between the Dexmed group and the Standard group (6% (4/62) vs. 9% (4/45); p = 0.718 ). In the Dexmed group, the mean dexmedetomidine dose received was 37 μg (range 10 to 140 μg). While the use of inotropic/vasopressor medications was common and similar in both groups, there was an increase in the incidence of bradycardia (Dexmed 15% vs. Standard 2%; p = 0.042 ) but not hypotension (Dexmed 24% vs. Standard 24%; p = 1.00 ) in the Dexmed group. Conclusion. In patients who required supplemental analgesia for cesarean delivery, those who received dexmedetomidine versus other medications had a similar rate of conversion to general anesthesia, a statistically significant increase in bradycardia, but no difference in the incidence of hypotension.

Lee M., Kim H., Lee C., Kang H.

BACKGROUND Various strategies have been used to mitigate haemodynamic instability during general anaesthesia for caesarean section. However, the safety of these strategies for neonates remains controversial. OBJECTIVE To investigate the effects of intravenous dexmedetomidine and remifentanil on neonatal outcomes during caesarean section under general anaesthesia. DESIGN Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES Databases of PubMed, EMBASE and CENTRAL were searched until March 2020 and updated in February 2021. ELIGIBILITY CRITERIA Randomised controlled trials were included if they compared dexmedetomidine and remifentanil infusion on neonatal outcomes after elective caesarean section under general anaesthesia. Primary outcomes were 1 and 5 min Apgar scores. Secondary outcomes were the incidence of neonatal mask ventilation or endotracheal intubation, and pH of the umbilical artery and vein. Studies that did not report primary outcomes were excluded. RESULTS Five studies with 258 patients in total were included. The Apgar score at 1 min in the remifentanil group was lower than that in the dexmedetomidine group for both quantitative [weighted mean difference (WMD): 0.75; 95% CI, 0.44 to 1.07; τ2 = 0.00] and categorical outcomes (≥Apgar 7 vs.

Sween L.K., Xu S., Li C., O'Donoghue M.A., Ciampa E.J., Kowalczyk J.J., Li Y., Hess P.E.

Intravenous dexmedetomidine 30 µg reduces shivering after cesarean delivery but can result in sedation and dry mouth. We hypothesized that prophylactic administration of 10 µg of IV dexmedetomidine would reduce the patient-reported severity of shivering after cesarean delivery, without an increased incidence of side effects.After institutional review board approval and informed written consent, women undergoing scheduled cesarean delivery with spinal or combined spinal-epidural anesthesia were randomized to receive either intravenous normal saline or dexmedetomidine 10 µg immediately after delivery. The primary outcome was a patient-rated subjective shivering score using a 10-cm visual analog scale at 30 and 60 min after arrival in the Post-Anesthesia Care Unit. Secondary outcomes included subjective scores for pain, nausea, itching, dry mouth, and sedation, as well as 24-h medication administration and investigator-rated observations of shivering, vomiting, pruritus, and sedation. Repeated measures ANOVA with Tukey-Kramer multiple-comparison test was applied for primary outcomes.One hundred patients were enrolled, and 85 completed the study and were included in analysis. The mean ± SD shivering score in the dexmedetomidine group was significantly lower by repeated measures analysis than among controls across the first 60 min (P=0.0002), and individually at both 30 and 60 min (placebo 1.8 ± 2.6 vs. dexmedetomidine 0.6 ± 1.4 at 30 min; 1.2 ± 2.1 vs. 0.3 ± 0.6 at 60 min; both P

Kim D.J., Ki Y.J., Jang B.H., Kim S., Kim S.H., Jung K.T.

Background: Recently, there have been some trials to use dexmedetomidine in the obstetric field but concerns regarding the drug include changes in uterine contractions after labor. We aimed to evaluate the effects of dexmedetomidine on the myometrial contractions of pregnant rats.Methods: In a pilot study, the contraction of the myometrial strips of pregnant Sprague-Dawley rats in an organ bath with oxytocin at 1 mU/ml was assessed by adding dexmedetomidine from 10-6 to 10-2 M accumulatively every 20 min, and active tension and the number of contractions were evaluated. Then, changes in myometrial contractions were evaluated from high doses of dexmedetomidine (1.0 × 10−4 to 1.2 × 10−3 M). The effective concentrations (EC) for changes in uterine contractions were calculated using a probit model.Results: Active tension and the number of contractions were significantly decreased at 10-3 M and 10-4 M dexmedetomidine, respectively (P < 0.05). A complete loss of contractions was seen at 10-2 M. Dexmedetomidine (1.0 × 10−4 to 1.2 × 10−3 M) decreased active tension and the number of contractions in a concentration-dependent manner. The EC95 of dexmedetomidine for inhibiting active tension and the number of contractions was 5.16 × 10-2 M and 2.55 × 10-5 M, respectively.Conclusions: Active tension of the myometrium showed a significant decrease at concentrations of dexmedetomidine higher than 10-3 M. Thus, clinical concentrations of dexmedetomidine may inhibit uterine contractions. Further research is needed for the safe use of dexmedetomidine in the obstetrics field.

Kimizuka M., Tokinaga Y., Azumaguchi R., Hamada K., Kazuma S., Yamakage M.

Several anesthetic agents are used in cesarean sections for both regional and general anesthesia purposes. However, there are no data comparing the in vivo effects of propofol, sevoflurane, and dexmedetomidine on the contraction of the myometrium in pregnant rats. The aim of this study was to investigate the effect of these anesthetic agents on myometrial contraction and elucidate the underlying mechanisms. Contraction force and frequency changes in response to propofol, dexmedetomidine, or sevoflurane were evaluated in vivo and in vitro. To test the effect of arachidonic acid on myometrial contraction enhanced by dexmedetomidine, changes in myometrial contraction with dexmedetomidine after administration of indomethacin were evaluated. The amount of phosphorylated myosin phosphatase target subunit 1 (MYPT1) in the membrane fraction was expressed as a percentage of the total fraction by Western blot analysis. This study demonstrated that dexmedetomidine enhances oxytocin-induced contraction in the myometrium of pregnant rats, whereas propofol and sevoflurane attenuate these contractions. The dexmedetomidine-induced enhancement of myometrial contraction force was abolished by the administration of indomethacin. Propofol did not affect oxytocin-induced MYPT1 phosphorylation, whereas sevoflurane attenuated oxytocin-induced MYPT1 phosphorylation. Inhibition of myofilament calcium sensitivity may underlie the inhibition of myometrial contraction induced by sevoflurane. Arachidonic acid may play an important role in the enhancement of myometrial contraction induced by dexmedetomidine by increasing myofilament calcium sensitivity. Dexmedetomidine may be used as a sedative agent to promote uterine muscle contraction and suppress bleeding after fetal delivery.

Hu B., Zhou H., Zou X., Shi J., Li X., Tan L.

To compare the efficacy of dexmedetomidine and midazolam in the prevention of postoperative nausea and vomiting (PONV) caused by hemabate in postpartum hemorrhage during cesarean delivery.One hundred and five parturients with American Society of Anesthesiology (ASA) physical status I and II, aged 20-40 years, undergoing elective cesarean delivery under epidural anesthesia were randomly allocated into dexmedetomidine group (group D, n=35), midazolam group (group M, n=35) and control group (group C, n=35). Patients received an intrauterine injection of 250 μg hemabate and continuous intravenous infusion of 5 units oxytocin immediately following the delivery of the infant. At the same time, patients in group D received 1μg/kg intravenous dexmedetomidine, group M received 0.02 mg/kg intravenous midazolam and group C received 20 mL intravenous saline. Parameters such as the PONV, other adverse reactions (chest distress, flush, etc.) caused by hemabate, patient satisfaction, the sedation (OAA/S) scores, and the hemodynamic parameters were recorded in both groups.The PONV incidence in group D and group M was significantly lower compared with group C (6%, 17%, and 71% for group D, group M, and group C, respectively, P

Wang Y., Fang X., Liu C., Ma X., Song Y., Yan M.

Objective Few studies have investigated the effects of dexmedetomidine (DEX) on breastfeeding after cesarean delivery. A randomized double-blind controlled trial was conducted to investigate whether the administration of DEX, immediately after delivery and for patient-controlled intravenous analgesia (PCIA), can be beneficial for breastfeeding. Patients and Methods One hundred sixty parturients scheduled for elective cesarean section under spinal anesthesia were randomly allocated to the DEX group (a loading dose of DEX was pumped at 0.5 μg/kg within 10 min, followed by a further infusion of DEX at 0.5 μg/kg/h until the end of the surgery and PCIA for 2 days with DEX plus sufentanil) or the standard care group (infusion saline intraoperatively, and PCIA for 2 days with sufentanil). The number of days required to switch to exclusive breastfeeding within six weeks of delivery, the time to first lactation and breast milk volume on day 1 and day 2 after delivery were recorded. Recovery quality, comfort, anxiety, depression, postoperative analgesia, and adverse reactions of parturients were also assessed. Results Compared with the standard care group, parturients in the DEX group could be converted to exclusive breastfeeding earlier (11 [14] vs 8 [10] days, log-rank P=0.025), the first lactation time was sooner (28.38 [13.82] vs 33.79 [14.85] hrs, P=0.024), and the amount of breast milk on the second day after delivery increased (P=0.012). There was no difference between the two groups in postpartum uterine contraction pain, but postpartum rest and movement VAS scores and recovery quality score in the DEX group were better than those in the standard care group (all P

Orovou E., Dagla M., Iatrakis G., Lykeridou A., Tzavara C., Antoniou E.

A birth experience with cesarean section (CS) can be a cause of the development of post-traumatic stress disorder after a cesarean (PTSD-AC) or profile PTSD, for a percentage of women. So far, there is no data on the frequency of PTSD-AC in Greece and this syndrome is often associated with other mental disorders of the postpartum period. The purpose of this research is to associate the kind of CS with PTSD-AC for Greek mothers and the combination of factors that make them less resistant to trauma. A sample of ahundred and sixty-six mothers who gave birth with emergency cesarean section (EMCS) and elective cesarean section (ELCS) at a Greek University hospital have consented to participate in the two phases of the survey, in the 2nd day postpartum and a follow-up in the 6th week postpartum. Medical/demographic data and a life events checklist (LEC-5) with Criterion A and post-traumatic stress checklist (PCL-5) were used to diagnose PTSD and PTSD Profile. Out of166 mothers enrolled, 160 replied to the follow-up (96.4%), ELCS 97 (97%) and EMCS 63 (95%). Twenty (31.7%) EMCS had PTSD and nine (14.3%) had Profile. One (1%) ELCS had PTSD and 4 (4.1%) had Profile. This survey shows a high prevalence rate of PTSD after EMCS with additional risk factors of preterm labor, inclusion in the Neonatal Intensive Care Unit (NICU), a lack of breastfeeding, and a lack of support from the partner.

Chen Y., Yang X., Guo C., Liao Y., Guo L., Chen W., Chen I., Krewski D., Wen S.W., Xie R.

Background: While caesarean section (CS) can be a lifesaving intervention when performed in a timely manner to overcome dystocia or other complications, it is a traumatic event and may increase the risk of post-traumatic stress disorder (PTSD). No attempt has been made to assess prevalence of PTSD after CS specifically. This study aimed to quantify pooled prevalence of PTSD after CS through a systematic review and meta-analysis. Methods: MEDLINE, PsycINFO, EMBASE, and CINAHL were searched using PTSD terms crossed with CS terms. Studies were included if they reported the prevalence of PTSD after CS using an instrument based on Diagnostic and Statistical Manual of Mental Disorders-criteria to identify PTSD. The pooled prevalence was then estimated by meta-analysis in overall eligible studies and in subgroups. Results: Nine studies were included with a total of 1,134 postpartum women, of which 136 were identified as having PTSD. Pooled prevalence of PTSD after CS was 10.7% (95% confidence interval [CI]: 4.0-20.2). Pooled prevalence of PTSD after emergency CS (10.3% [95% CI: 1.7-24.9]) was higher than that after elective CS (7.1% [95% CI: 0.7-19.4]), but the difference was not statistically significant. Subgroup analysis showed that pooled prevalence of PTSD after CS differed according to study setting, time interval of PTSD assessment, and type of participants. Meta-regression analysis showed that study setting and type of study participants were significant sources of heterogeneity. Conclusions: Women with CS apparently have higher rates of PTSD as compared with women without CS. However, the susceptibility to PTSD appears to vary based on emergency/elective CS, study methodology, self-perceived traumatic birth, and country of study. Further targeted research is needed to elucidate the role of these factors in relationship between CS and PTSD.

Yu H., Wang S., Quan C., Fang C., Luo S., Li D., Zhen S., Ma J., Duan K.

Few studies have investigated the prophylactic efficacy of dexmedetomidine (DEX) in postpartum depressive symptoms (PDS). A randomized double-blind placebo-controlled trial was conducted to investigate whether the administration of DEX, immediately after delivery and for patient-controlled intravenous analgesia (PCIA), can attenuate PDS.A total of 600 parturients scheduled for elective cesarean delivery under spinal anesthesia were randomly allocated into the control group (infusion with 0.9% normal saline after delivery and PCIA with sufentanil) and the DEX group (DEX infusion 0.5 μg/kg after delivery and PCIA with DEX plus sufentanil). The prevalence of postpartum depressive disorders was indicated by the Edinburgh Postnatal Depression Scale (EPDS). Postoperative analgesia, sedation, and sleep quality of parturients were also assessed.Postpartum blues and PDS prevalence in the DEX, versus control, group were significantly lower (5.0% vs 14.1%, p