Efficacy and Safety of Esketamine for Supplemental Analgesia During Elective Cesarean Delivery

Xu, Lili; Wang, Chun; Deng, Chonghai; Dai, Shaobing; Zhou, Qun; Peng, Yong-Bao; Shou, Hong-Yan; Han, Yinqiu; Jing, Yu; Liu, Chaohui; Xing, Feng; Zhang, Suqin; Wang, Dong‐Xin; Chen, Xinzhong

doi:10.1001/jamanetworkopen.2023.9321

Cited by 33 publications

(17 citation statements)

References 40 publications

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“…However, further studies are required to confirm the role of antihyperalgesics in the preventive effect of esketamine on PPD. In addition, there were no notable neurologic symptoms observed during the postoperative period in the esketamine group, in line with previous reports …”

Section: Discussionsupporting

confidence: 92%

“…Numerous studies have found that an esketamine nasal spray could rapidly induce and sustain beneficial effects for patients with a diagnosis of treatment-resistant depression and risk of suicides . Previous studies have also found that, for women who have undergone cesarean deliveries, a preventive administration of esketamine, either by the intrathecal or intravenous route, could yield both safe and efficacious analgesic effects . Given its bidirectional efficacy as an analgesic and antidepressant, we performed a double-blind, randomized clinical trial to investigate the effects of perioperative adjunctive esketamine administration during cesarean delivery on patients with PPD.…”

Section: Introductionmentioning

confidence: 99%

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Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery

Chen,

Guo,

et al. 2024

JAMA Netw Open

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ImportancePostpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant.ObjectiveTo investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD.Design, Setting, and ParticipantsA single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis.InterventionsPatients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients.Main Outcomes and MeasuresThe primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42.ResultsA total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], −1.17 [0.44]; 95% CI, −2.04 to −0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03).Conclusions and RelevanceThese results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2100054199

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery

Chen,

Guo,

et al. 2024

JAMA Netw Open

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“…In China, Esketamine, the enantiomer of ketamine has also been widely used in recent years. Some researchers have investigated the safety of supplemental use of Esketamine in cesarean delivery for pregnancy and neonates but focused on its short‐term effects 53,54 . It is also of great importance to compare the long‐term effects of these two enantiomers in our model in the future.…”

Section: Discussionmentioning

confidence: 99%

Impaired synaptic plasticity and decreased excitability of hippocampal glutamatergic neurons mediated by BDNF downregulation contribute to cognitive dysfunction in mice induced by repeated neonatal exposure to ketamine

Wan,

Ma,

Jiao

et al. 2024

CNS Neurosci Ther

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AimRepeated exposure to ketamine during the neonatal period in mice leads to cognitive impairments in adulthood. These impairments are likely caused by synaptic plasticity and excitability damage. We investigated the precise role of brain‐derived neurotrophic factor (BDNF) in the cognitive impairments induced by repeated ketamine exposure during the neonatal period.MethodsWe evaluated the cognitive function of mice using the Morris water maze test and novel object recognition test. Western blotting and immunofluorescence were used to detect the protein levels of BDNF. Western blotting, Golgi‐Cox staining, transmission electron microscopy, and long‐term potentiation (LTP) recordings were used to assess synaptic plasticity in the hippocampus. The excitability of neurons was evaluated using c‐Fos. In the intervention experiment, pAdeno‐CaMKIIα‐BDNF‐mNeuronGreen was injected into the hippocampal CA1 region of mice to increase the level of BDNF. The excitability of neurons was enhanced using a chemogenetic approach.ResultsOur findings suggest that cognitive impairments in mice repeatedly exposed to ketamine during the neonatal period are associated with downregulated BDNF protein level, synaptic plasticity damage, and decreased excitability of glutamatergic neurons in the hippocampal CA1 region. Furthermore, the specific upregulation of BDNF in glutamatergic neurons of the hippocampal CA1 region and the enhancement of excitability can improve impaired synaptic plasticity and cognitive function in mice.ConclusionBDNF downregulation mediates synaptic plasticity and excitability damage, leading to cognitive impairments in adulthood following repeated ketamine exposure during the neonatal period.

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“…One promising alternative is esketamine, an N -methyl- d -aspartate receptor antagonist and the dextrorotatory isomer of ketamine. Esketamine possesses twice the potency of ketamine in terms of hypnotic and analgesic effects, with fewer psychiatric adverse effects . Previous studies have also indicated that a subanesthetic dose of esketamine can maintain hemodynamic stability and reduce respiratory depression in surgical patients .…”

Section: Introductionmentioning

confidence: 99%

Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy

Song,

Yang,

Zheng

et al. 2023

JAMA Netw Open

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ImportancePropofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events.ObjectiveTo evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo).InterventionsAfter induction of sedation with 0.1 μg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration.Main Outcomes and MeasuresThe primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction.ResultsAmong the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, −12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P &lt; .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q &lt; .001) and reduced propofol requirements (difference, −58.9 mg; 95% CI, −65.7 to −52.2 mg; q &lt; .001), without significant effects on other secondary outcomes.Conclusions and RelevanceIn this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2200055938

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Efficacy and Safety of Esketamine for Supplemental Analgesia During Elective Cesarean Delivery

Cited by 33 publications

References 40 publications

Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery

Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery

Impaired synaptic plasticity and decreased excitability of hippocampal glutamatergic neurons mediated by BDNF downregulation contribute to cognitive dysfunction in mice induced by repeated neonatal exposure to ketamine

Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy

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