Ketamine to Prevent PPD After Cesarean
关键词
抽象
描述
Postpartum depression (PPD)
PPD is one of the most common perinatal medical complications and can have a detrimental effect on both mother and baby. Suicide exceeds hemorrhage and hypertensive disorders as a cause of maternal mortality and maternal psychopathology interferes with the parent-infant relationship. It has been estimated to have a period prevalence of 19.2% in the first 3 postpartum months. The rapid decline in reproductive hormones is thought to contribute to the development of PPD in susceptible women, although the specific pathogenesis is unknown. The American College of Obstetricians and Gynecologists recommend that all women should be routinely screened for depressive symptoms in the perinatal period.
Risk factors for PPD include:
- Depression during pregnancy • Breastfeeding problems
- Preterm birth/infant admission to neonatal intensive care (NICU)
- Traumatic birth experience
- History of depression
- Anxiety during pregnancy
Ketamine's anti-depressant effect
Ketamine, a phencyclidine derivative, is a non-competitive antagonist at the N-methyl-D-aspartic acid (NMDA) receptor that is commonly used as an anesthetic or sedative agent and has proven analgesic effect after a variety of surgeries including CD, where it has also been shown to reduce shivering. It has been demonstrated to have a rapid anti-depressant effect in treatment-resistant depression outside of pregnancy. The most commonly employed intravenous (IV) dose for this purpose is 0.5 mg/kg over 40 minutes, as single or repeated infusions. It has been postulated that prolonged blockade of NMDA receptors causes long-term changes in signal transduction leading to sustained clinical improvement, some investigators have explored longer term infusions such as those used to treat chronic pain. A recent pilot study assessing the feasibility of a 96-hour (~0.5mg/kg/hr) infusion compared with a single 40-minute (0.5 mg/kg) infusion suggested a trend toward greater efficacy in the prolonged infusion but confirmation of a statistically significant result is awaited.
Ketamine and PPD
This promising anti-depressant effect has prompted investigation of ketamine as a preventative measure in patients undergoing CD. There have been 2 studies to date, one which failed to demonstrate any benefit from a bolus dose of 0.25 mg/kg and one which documented a large reduction (1 and 22% in the treatment and control, respectively) in the (6 week) period prevalence of postpartum depression after a 4 mg/kg dose of ketamine over 50 hours (~0.08 mg/kg/hr).
The prolonged IV infusion, was achieved by adding the ketamine to a sufentanil patient-controlled analgesic (PCA) pump with a background infusion. This PCA pump is a standard part of their post-cesarean analgesic regimen. In our institution, it is standard practice to discontinue IV infusions and to remove IV cannulae as early as it is safe to do so. This practice is essential to the attempts to enhance postoperative recovery and aid mother's bonding with their babies and facilitate their early-life care. This reflects patients' expectations and preferences and is in line with other maternity units across North America and Europe.
The natural course of PPD varies and, although it may resolve spontaneously within weeks, approximately 20% of women with PPD still have depression at 12 months and beyond. As many as 13% will still have depressive symptoms at 2 years and 40% will have a relapse. Considering the maternal suffering, disruption to the family, potential impairment of the social, emotional, and cognitive development of the child, and the rare cases of infanticide and suicide caused by PPD, the impact on families and society as a whole is difficult to overemphasize. An intervention that promises such a large reduction in this devastating disease warrants extensive research. In an attempt to achieve the benefit whilst employing methods more acceptable to our patients we have designed a pilot study to assess the feasibility of our study design and collect preliminary tolerability and efficacy data on ketamine administered by two alternative routes: 40-minute IV infusion (i.v.) and subcutaneous (s.c.) injection.
日期
最后验证: | 06/30/2020 |
首次提交: | 11/19/2019 |
提交的预估入学人数: | 01/12/2020 |
首次发布: | 01/13/2020 |
上次提交的更新: | 07/20/2020 |
最近更新发布: | 07/21/2020 |
实际学习开始日期: | 07/31/2020 |
预计主要完成日期: | 08/31/2021 |
预计完成日期: | 08/31/2021 |
状况或疾病
干预/治疗
Drug: Ketamine 50 MG/ML
Drug: Control
相
手臂组
臂 | 干预/治疗 |
---|---|
Placebo Comparator: Control Shortly after cesarean delivery of their baby, participants will receive a subcutaneous injection and 40-minute intravenous infusion of 0.9% sodium chloride. | |
Experimental: Ketamine SC Shortly after cesarean delivery of their baby, participants will receive a subcutaneous injection of 0.5 mg/kg of ketamine and a 40-minute intravenous infusion of 0.9% sodium chloride. | |
Experimental: Ketamine IVI Shortly after cesarean delivery of their baby, participants will receive a subcutaneous injection of 0.9% sodium chloride and a 40-minute intravenous infusion of 0.5 mg/kg ketamine. |
资格标准
有资格学习的年龄 | 18 Years 至 18 Years |
有资格学习的性别 | Female |
接受健康志愿者 | 是 |
标准 | Inclusion criteria: - Term pregnancy - Age 18-45 years of age - Scheduled cesarean delivery under neuraxial anesthesia Exclusion criteria: - ASA classification IV or V - History of psychotic episodes - History of allergy to ketamine - Inability to communicate in English or any other barrier to providing informed consent |
结果
主要结果指标
1. The incidence of PPD, as defined as EPDS greater than 10 out of 30 [42 days postpartum]
2. Percentage of eligible patients consenting to participation [Through study completion, an average of 1 year]
3. Percentage of patients with a complete dataset [Through study completion, an average of 1 year]
4. Number of patients in study arms experiencing one or more severe side effects [Through study completion, an average of 1 year]
次要成果指标
1. Dose of opiate analgesics administered [Intraoperative phase]
2. Dose of ketorolac administered [Intraoperative phase]
3. Incidence of intraoperative hypotension of a systolic BP of less than 90 [Intraoperative phase]
4. Maximum intraoperative pain (NRS) [Intraoperative phase]
5. Adverse effects [Intraoperative and 2 and 6 hours postoperatively]
6. Plasma concentrations of ketamine [At baseline and approximately 20, 40 and 100 minutes postpartum]
7. Total opiate consumption in morphine equivalents [In the first 2 days postpartum]
8. Surgical site pain: numerical rating scale (NRS 0-10) [At 2, 6, 24 and 48 hours after delivery and on postpartum days 21 and 42]
9. Edinburgh Postpartum Depression Scale (0 - 30, a higher score represents greater depressive symptomatology) [On postpartum days 1, 2, 21 and 42]
10. Apgar scores [At 1 and 5 minutes after delivery]
11. Admission to NICU [Postpartum day 1]
12. Breastfeeding success [Postpartum days 1 and 2]
13. Incidence of intraoperative hypertension of a systolic BP greater than 140 mmHg [Intraoperative phase]
14. Incidence of intraoperative bradycardia of less than 40 bpm [Intraoperative phase]
15. Incidence of intraoperative tachycardia of greater than 110 bpm [Intraoperative phase]
16. Incidence of Anxiety on the Generalized Anxiety Disorder- 7 item scaleGAD-7 [On day of surgery, and postpartum days 1, 2, 21 and 42]