RCOG updates its guidance on Pregnancy pain relief

It is important to prescribe the correct analgesic during pregnancy to optimize the maternal and neonatal outcome. Inadequate pain-relief in pregnancy leads to anxiety and psychological strain for mother and affects her ability to provide care for her newborn–note the recent Scientific Impact Paper published December 12, 2018, in the BJOG.

The paper was developed for the Royal College of Obstetricians and Gynaecologists (RCOG) by a group of eminent doctors and researchers following the advisory issued by the Medicines and Healthcare products Regulatory Authority (MHRA) and European Medicines Agency (EMA) on the use of codeine in pregnancy because of neonatal mishap and three other fatalities in children.

The findings reflect current NHS guidance on the use of medical pain relief options in pregnancy and during breastfeeding. However, the guidance does not address the concerns for Intrapartum analgesia.

Women often need analgesic during the antenatal period for a headache, backache, and pelvic pain. 

Non-pharmacological interventions like relaxation, adequate rest, heat, massage, acupuncture, posture training, physiotherapy, and exercise should be considered before starting any drugs. Notably, all drugs should be avoided during early pregnancy to prevent the teratogenic effects of drugs during the organogenesis period (4-10 weeks).

Paracetamol

Paracetamol remains the drug of choice for pain relief throughout pregnancy, although few studies have demonstrated an increased incidence of childhood asthma, behavioral problems, and a delay in gross motor and communication development in children with long‐term antenatal exposure.

NSAIDs 

Studies have failed to demonstrate any clear association between congenital malformations and the use of nonsteroidal anti-inflammatory drugs (NSAIDS) in early pregnancy.

However, there is conflicting evidence regarding the use of NSAIDs and risk of miscarriage in the first trimester.  Therefore, NSAIDs be avoided during pregnancy, especially during the first trimester. They should only be used when absolutely necessary in conditions such as a migraine or ankylosing spondylitis, that too in lowest possible dose and for the shortest duration of time.

Use of NSAIDs should be avoided after 30 weeks of gestation because it can cause neonatal pulmonary hypertension and premature closure of the ductus arteriosus. NSAIDs also reduce fetal renal blood flow leading to decreased urine production and causing oligohydramnios. 

Opioids (including codeine, dihydrocodeine, tramadol, and morphine)

The review says that opioid analgesic should only be used under the care of health professional in the lowest possible dose and shortest amount of time. It should be used when paracetamol has been ineffective. Limited data available does not point towards increased risk of fetal toxicity.

However, if used around the time of labor, it may lead to neonatal respiratory depression and if used for prolonged time cause neonatal withdrawal symptoms and maternal dependence.

The guidelines also highlighted the critical difference between the use of codeine and DHC during breastfeeding. If stronger analgesia is required, Dihydrocodeine (DHC) is much safer to use as compared to codeine which causes fetal toxicity.

Low doses of dihydrocodeine in combination with paracetamol can be bought over the counter but regular use of any opioid beyond 3 days should be under close medical supervision.

Gabapentin

Gabapentin is mostly used in chronic pain syndrome, and only a few studies have been done on the use of gabapentin in pregnancy. Evidence does not link the use of the drug to a particular birth defect; however, women are advised to take high doses of folic acid before conception and during the first trimester.

Gabapentin use in pregnancy after 30 weeks is very limited, and if used around the time of delivery it may lead to neonatal withdrawal syndrome.

Analgesics at the time of discharge

Majority of women who require analgesics at discharge should be prescribed paracetamol or ibuprofen. If stronger analgesics are required (cesarean delivery), women should be sent home with a limited supply of DHC. Tramadol is only given if a woman is intolerant to DHC.

Dr Dina Bisson, consultant obstetrician and gynecologist at the North Bristol NHS Trust and the lead authors of the guidance said: "It is absolutely essential that pain is managed appropriately during pregnancy and breastfeeding. Many women may develop headaches, lower back pain, and pelvic pain during pregnancy and breastfeeding, while others may have chronic conditions, where pain management is necessary.

"If pain is not adequately managed, this can have a negative impact on a woman's physical and mental wellbeing.

RCOG Scientific Impact Paper Full Text

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ACOG updates its recommendations for treatment of Dysmenorrhea and Endometriosis in the Adolescent

The American College of Obstetrics and Gynecology (ACOG) has issued new guidance on diagnosing and relieving dysmenorrhea in adolescents, published in December issue of Journal Obstetrics and Gynecology.

Obstetrician and gynecologists frequently come across adolescents with dysmenorrhea in their practice due to high prevalence ranging between 50% to 90%. It is also responsible for recurrent short-term school absenteeism and reduced quality of life.

Most of the adolescents suffering from dysmenorrhea have primary dysmenorrhea–– painful menstruation in the absence of pelvic pathology.

If the physician suspects it to be primary dysmenorrhea, no pelvic examination or ultrasound is indicated in the initial evaluation. The patient should be put on empirical therapy after a careful history and physical examination.

If the patient does not respond to empirical therapy with NSAIDs and hormonal treatment in 3-6 months, she should be investigated for secondary causes or irregular treatments.

The most common cause of secondary dysmenorrhea is endometriosis, the other being obstructive anomaly of the reproductive tract (hymenal, vaginal, or Mullerian), uterine fibroids and polyps, adenomyosis, cervical stenosis, and adhesions.

Patients who do not respond to treatment for primary dysmenorrhea should be investigated for secondary causes which include pelvic examination and pelvic ultrasound. If pathology is detected, treatment of the cause is warranted.

If no pathology is seen, suspect endometriosis and consider a diagnostic laparoscopy. About 75% of adolescents and young adults with dysmenorrhea who do not respond to NSAIDs and hormonal therapy have endometriosis as the primary pathology. 

Endometriotic lesions present a different appearance in adolescents as compared to a young woman and are typically transparent or red and are challenging to diagnose.   

If a young woman is diagnosed with endometriosis, treatment consists of biopsy of the lesions along with destruction, ablation, or excision of the visible lesions at the time of initial laparoscopy. The patient should also be started on suppressive medical therapy to prevent further endometrial proliferation.

Consideration should be given to placing a levonorgestrel-releasing intrauterine system (LNG-IUS) at the of diagnostic laparoscopy to minimize the pain of insertion later. 

If patients do not respond to conservative surgical therapy and suppressive hormonal therapy, they often benefit from at least six months of gonadotropin-releasing hormone (GnRH) agonist therapy with add-back medicine.

NSAIDs are the principal medications used for pain relief in endometriosis, and there is no role of long-term opioids in the management of endometriosis, besides being used by a specialized pain management team.

ACOG committee opinion No. 760

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Could perioperative NSAIDs treatment markedly reduce metastatic breast cancer recurrence?

Perioperative anti-inflammatory treatment could prevent or reduce the risk of secondary spread of breast cancer after the primary resection surgery according to a paper published April 11 in Journal of Science and Translational Medicine.

The study was conducted in mice but could offer an explanation for the resurgence of the tumor after primary surgery in humans too. It has been a long-known fact that after undergoing lumpectomy or mastectomy, there is metastatic recurrence elsewhere in the body after a year or two.

The cause of this is long been debated, some researchers taking it as the natural progression of disease while others propose that handling of the tumor during surgery release the cancerous cells in the circulation.

The researchers set up an experimental wound healing mice model who had breast cancer. They did not do any surgery or disturbed the primary tumor. The systemic inflammatory response to wound led to new tumor growth at the distant site, which was kept in check by the tumor-specific T cell response. Probably, the wound healing consumed all the T-cells that previously kept a check on tumor cells.

The researchers gave the mice NSAIDs for wound healing and noted that the growth of secondary metastasis was curbed considerably.

Earlier clinical studies have suggested that perioperative anti-inflammatory drugs reduce early metastatic recurrence in breast cancer patients, but no explanation was put forth for the cause.

A 2012 study particularly showed that breast cancer patients given the anti-inflammatory drug ketorolac during surgery were five times less likely to have their cancer spread than people who didn’t get the painkiller

“This represents the first causative evidence of surgery having this kind of systemic response,” Jordan Krall, the first author of the study and a researcher at the Massachusetts Institute of Technology's White Head Institute for Biomedical Research, said in a statement announcing the study's publication.

“Surgery is essential for treating a lot of tumors, especially breast cancer," Krall added. "But there are some side effects of surgery, just as there are side effects to any treatment. We’re starting to understand what appears to be one of those potential side effects, and this could lead to supportive treatment alongside surgery that could mitigate some of those effects.”

It’s not yet clear whether any specific NSAIDs will give more benefit than others, or what’s the best dose or timing to deliver the drug.

Professor Robert Weinberg, the new study’s senior author says, “Mice are not people and therefore this may not translate into clinical practice. Our paper is only intended to alert people to this possibility and to explore whether this mechanism operates as well in humans as we think it might.”

Scientist agrees that more research is needed to investigate an explanation as simple as this, as NSAIDs are routinely used in the peri and postoperative period to ease the pain.

Abstract

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Medical management of adenomyosis: current and future therapies

The current issue of Journal of Fertility and Sterility has focused exclusively on etiology, pathophysiology, and medical and surgical treatment of adenomyosis. Adenomyosis has long been the source of controversy and its only with the recent advent of Transvaginal sonography (TVS) and MRI that its etiology and pathophysiology been better understood.

Adenomyosis is a uterine pathology in which the endometrial glands and stroma invaginate within the uterine myometrium. This ectopic endometrium induces hypertrophy and hyperplasia of the myometrium resulting in the typical ‘globular” enlargement of the uterus.

It is also now known that endometriosis and adenomyosis are two different phenotypes of the disorder characterized by impaired cellular response to ovarian hormone. This concept has to lead to the use of common treatment modalities for both the diseases.

Transvaginal sonography (TVS) and MRI are now the gold standards for diagnosing adenomyosis. Adenomyosis requires a lifelong treatment plan that depends upon patient’s age, desire for children and symptoms. Medical management is the treatment of choice for women who want to preserve fertility, while hysterectomy is preferable in older women who have completed the childbearing.

No new drug has been developed in recent years for the treatment of adenomyosis although many new drugs are under development and undergoing clinical trials.  

Medical management includes minimally invasive procedures as well as medication to treat the symptoms.

Minimally invasive surgical procedures help preserve fertility as well as reduce the pain and abnormal uterine bleeding (AUB) and include endometrial ablation and resection, laparoscopic as well as open excision of adenomyosis and MRI-guided focused ultrasound. They are offered to patients who have not responded to medical drug treatments. 

The medical treatment is mainly aimed at easing the symptoms, improving quality of life and promote fertility. The rationale behind using these drugs is based on the pathophysiology of the disease which includes aberrant response to the ovarian hormone, inflammation, and impaired apoptosis.

http://journals.sagepub.com/doi/full/10.5301/je.5000261

The class of drugs includes:

Current Medical Treatments: 

GnRH agonist: These group of drugs cause a downregulation of GnRH activity and induce a reversible state of medical menopause. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice before fertility treatments to improve the chances of pregnancy in infertile women with adenomyosis.

Progestins: Drugs such as danazol, norethindrone acetate (NETA), Levonorgestrel-releasing intrauterine system (LNG-IUS), and Dienogest are mainly used because of anti-inflammatory properties to relieve pain and reduce the amount of abnormal uterine bleeding.

The Levonorgestrel-releasing intrauterine system (LNG-IUS) has been found extremely effective in reducing menorrhagia and decrease the uterine volume over a period of 12 months use.

Combined oral contraceptives (COC): They are effectively used to reduce pain and control bleeding with the additional advantage of long-term use with minimal side effects.

Future Medical treatments:

Selective estrogen receptor modulators (SERMs)

Aromatase inhibitors (AIs)

Selective progesterone receptor modulators (SPRMs)

Valproic acid

Anti-platelets therapy

NSAIDs

Thus, the medical treatment of adenomyosis comprises many current and future drugs. No double-blind, RCTs have yet been conducted in the management of adenomyosis and the drugs are solely used based on results of observational studies.

Abstract

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