Sepsis and Pregnancy

Infection, sepsis and septic shock are a spectrum of disease from “mild” to severe, from a diagnosis that we have all had at different times of our lives, if even only due to the common cold, to severe disease. Take these challenges – common conditions, range in severity from mild to severe, and multiple different presentations – and then add in pregnancy, where we must think of both an adult and a baby, and where sepsis may be masked by the common symptoms of pregnancy, making the diagnosis and treatment potentially more difficult. The aim of this review is to support healthcare professionals and educate regarding sepsis in pregnancy. As with the clinical care that we provide, this review was written with the input of a multidisciplinary team. Here we have included nurses, midwives, obstetricians, microbiologists and anaesthesiologists, but we also recognise that other specialities may be required to provide care when pregnant people have sepsis, including pharmacy, infectious diseases, neonatology, general medical physicians and the medical specialities, surgery and the surgical specialities, allied health including physiotherapists, occupational therapists and dietetics; high dependency, intensive care, peri-operative teams and (as always) the wonderful medical scientists that help us make these diagnoses.

Firstly, to review the difference between infection, sepsis and septic shock. Infection is defined as the invasion and multiplication of microorganisms such as bacteria, viruses, fungi or parasites that are not normally present within the body.

An infection may cause no symptoms and be subclinical, only recognised years later or not at all – we sometimes see this when testing for toxoplasmosis or cytomegalovirus, when we tell people they have had it in the past and they had no memory of this. Infections may cause symptoms and be clinically apparent – people may say “I have a cold” or “I have COVID”. An infection may remain localized, or it may spread through the blood or lymphatic vessels to become systemic.

Microorganisms that live naturally in the body are not considered infections. For example, bacteria that normally live within the mouth and intestine are not infections, they are the commensal microbiota. If normal flora migrate to another part of the body, they may cause infection e.g. E. coli is normally resident in the bowel and it is the commonest cause of urinary tract infection.

Sepsis is defined as new organ dysfunction due to infection. Here the diagnosis becomes more technical, relying on vital sign changes or blood test results. Sepsis may be based on vital signs (high temperature, heart rate or respiratory rate, low blood pressure or low temperature, low oxygen saturations) or tests (glucose, white cell counts). It should be noted for pregnancy that the upper limit of normal for heart rate is 100 beats per minute rather than 90 beats per minute in the non-pregnant population due to the physiological changes of pregnancy.

In pregnancy and the postpartum period (six weeks after the birth) the monitoring system of IMEWS (Irish Maternity Early Warning System) is recommended. The presence of two persistent abnormal vital signs necessitates a review to consider sepsis; if this is suspected then use of the “Sepsis Six + 1” should be used; this will be discussed in more detail later in the review.

Septic Shock is a subset of sepsis defined as a requirement for vasopressors/ inotropes to achieve a mean arterial pressure of ≥ 65mmHg AND a lactate > 2mmols/l despite adequate fluid resuscitation. The diagnosis of septic shock mandates an escalation of care – if not already done- to consultant level, multidisciplinary care and immediate consult to critical care and anaesthesia.

Morbidity and mortality

While infections are reasonably common in pregnancy, sepsis is less common and septic shock is incredibly rare. All women who experience a severe maternal morbidity in the Republic of Ireland must be reported anonymously to the National Perinatal Epidemiology Centre in Cork. They produce an annual report of this audit, which are freely available on line. In 2020, for example, in the first few waves of the SARS COV2 pandemic, sixteen women were diagnosed with septic shock, in comparison to 329 women who had a major obstetric haemorrhage (the most common cause of maternal morbidity in Ireland). These may seem like small numbers, but if the degree of morbidity is considered, this is significant. In addition, it was noted that pregnant women were disproportionally represented in intensive care admissions due to SARS COV2 infection.

A second mandatory reporting audit in the UK, the United Kingdom Obstetric Surveillance System (UKOSS) report, showed common themes for maternal admission to ICU and maternal deaths in the United Kingdom (there have thankfully been no maternal deaths due to SARS CoV2 in the Republic of Ireland). From February to September 2021, when the COVID vaccines became available, 1,714 pregnant women were admitted to hospital in the UK with symptomatic COVID infection, of which 235 (14%) required intensive care admission. The vast majority (98%) were unvaccinated against COVID. Thirty three women died in pregnancy or the postnatal period – thirteen of these women died between July to September 2021 died during the “Delta” wave, when vaccination was recommended to all adults; of these eleven were known to be unvaccinated. UKOSS also showed the risk factors for more severe infection, sepsis and shock in pregnancy, including higher BMI, age over 35 years, diabetes and co-existing medical disease.

A third mandatory reporting audit, for both the UK and Republic of Ireland, is the MBRAACE report (Mothers and Babies: reducing risk though audits and confidential enquires across the UK). The 2021 report reviewed cases from 2017- 2019, so did not include the SARS CoV2 pandemic, and concentrated on specific causes of mortality: cancer, adversity, older mothers, venous thromboembolism and mental health. Previous reports which focused on sepsis (again, prior to the SARS CoV2 pandemic, but with learning from the influenza pandemic) highlight the importance of suspecting sepsis, early diagnosis and treatment, multidisciplinary care, early antibiotics and ongoing education. One study showed that for “each maternal sepsis death, approximately 50 women have life threatening morbidity from sepsis” and that “follow-up to ensure infection is eradicated is important”.

What are the most common causes of maternal septic shock?

Chorioamnionitis

Chorioamnionitis is an infection of the chorion and amnion, the two layers of the placenta, which can occur after spontaneous rupture of the membranes (SROM, or “waters breaking”). After 37 weeks’ gestation women will usually go into labour themselves, or induction of labour will be recommended if they have prolonged SROM or risk factors for vertical infection, such as infection with HIV, Hepatitis B or C, or Group B Strep colonisation.

When SROM occurs at a preterm gestation – under 36-37 weeks’ gestation – then the risk of infection needs to be balanced against the risk of prematurity.

Chronic renal/liver/heart failureWomen are usually recommended to be admitted to hospital for support and intensive surveillance for complications. Treatment for chorioamnionitis is the same as treatment for any infection: it starts with recognition (which can be hard in the early stages), source control (starting intravenous antibiotics while making rapid plans for birth) and then monitoring for further complications. Even after the birth there can be some complications, including for endometritis (infection of the lining of the womb) which may present with heavier vaginal bleeding than normal or a malodorous discharge. If pre-viable the decision to deliver can be difficult to make but the principles of source control remain.

Pyelonephritis

Pyelonephritis is an infection of the kidneys or upper urinary tract. Pyelonephritis can arise from cystitis (infection of the bladder). It may surprise clinicians that pyelonephritis can cause septic shock in pregnancy, but nearly every year in our hospital one or two women will need High Dependency care with pyelonephritis or urogenic (“from the urinary tract”) septic shock. Treatment starts with recognition, then source control (high dose intravenous antibiotics, ultrasound for renal abscess is occasionally required if no response) and referral to urology may be required. Remember that pyelonephritis can cause preterm labour so the aim is to treat early and hard!

SARS CoV2

Multitudes have been written about COVID infection in pregnancy. While vaccination has undoubtedly reduced maternal and fetal complications, there are still many pregnant women who get a COVID infection in pregnancy.

There are also pregnant women who have chosen not to get a COVID vaccine. The advice remains that non vaccination confers risks of increased severity of infection and maternal and fetal complications, including requiring oxygen care, admission to critical/ intensive care and preterm birth.

It is now recommended that women consider a second COVID booster vaccine during pregnancy and this programme is currently rolling out. There is minimal safety information currently available for use of antiviral treatment against COVID in pregnancy.

Influenza

Infection, sepsis and septic shock due to maternal influenza infection usually occurs during the Flu season. Pregnant woman, particularly those in the third trimester, are at increased risk of developing Influenza-related sepsis. While most people can self-care at home with infection, as per the normal practice we would recommend admission if there are symptoms or signs suggestive of more severe infection (for example, an abnormal respiratory rate, O2 saturations) or any maternal or fetal concerns. Oseltamivir is commonly prescribed for influenza infection with pregnancy.

Puerperal Sepsis

The puerperium is the six weeks postnatal period after the birth, where there are risks of complications such as infection, deep venous thrombosis and mental health issues. With regard to infections, Group A Streptococcus (GAS) most commonly occurs postnatally. Infection usually occurs in patients delivered vaginally. Onset of symptoms and deterioration can be rapid. Group A Strep is generally the most virulent maternal infection with a high rate of critical care admission. It is the most common cause of maternal death due to infection. In a recent maternal mortality report, women who died from GAS sepsis were often in a caring role for children (suggesting GAS infection in the child, passed onto the mother). After this report, maternity antenatal and postnatal education recommended that women should wash their hands both before and after using the bathroom.

Listeria monocytogenes

Listeria is uncommon in Ireland with <20 cases occurring per annum. Pregnant women and new-born infants are more likely to develop serious infection if they come into contact with Listeria. Listeria is a foodborne illness in the mother and can spread via the blood stream and placenta, from mother to her unborn baby. Listeria may cause meningitis in the baby.

No organism identified

Sepsis and septic shock can occur if infection is clinically diagnosed, even if no organism is identified in blood cultures, other cultures or PCR tests.

Prevention: vaccination

Three vaccines are currently recommended in pregnancy in the Republic of Ireland. These are based on the principles of reduction in severity of maternal complications, and thus fetal complications, as well as neonatal protection against infection. As per the HSE: “The immunity developed by a mother after vaccination during pregnancy is passed on to her baby in the womb. This immunity helps protect the baby during the first few months of life.

The flu vaccine is inactive and can be given safely at any time during pregnancy. A pregnant woman who gets the flu is at risk for serious respiratory illness and complications. Getting flu in pregnancy can also so lead to premature birth and smaller babies. Flu vaccination during pregnancy provides immunity against influenza infection to babies in the first six months of life.”

For the COVID vaccines, the HSE state that if a woman “has not had any COVID-19 vaccines then you can get your first round of COVID-19 vaccination or first booster at any stage of pregnancy. If you had a booster done during your current pregnancy then a second booster is not required. If you had a booster done before this pregnancy, you can get your second booster after 16 weeks of your pregnancy” (All above as of September 2022, please refer to HSE website for more current guidance).

Pertussis vaccine is also recommended during pregnancy, from 16 weeks gestation onwards and maternal immunity helps protect the newborn baby against severe whooping cough during the early months of life.

Principles of sepsis management

Timely recognition and appropriate treatment by the right team in the right place are the key principles for sepsis management.

A favourable clinical outcome is dependent upon early recognition and a rapid response to changes in the clinical picture or triggers on the IMEWS. This should prompt a clinical review with history and examination focused on trying to identify a likely source.

The Sepsis Six (“take three” and “give three”) has widely been adopted as a framework for sepsis management. This should be commenced as soon as possible. Blood is taken to include a full blood count, urea and electrolytes, c reactive protein, liver function and lactate, the urine output is monitored and samples (including viral swabs) are taken to help determine the cause (“take three”). Fluids should be given in accordance with weight (30mls/ kg) to ensure adequate volume resuscitation (with the exception of maternal pre-eclampsia); oxygen is given if required and appropriate antibiotics are commenced (“give three”). These should be specific to the presumed source and given within one hour. If no source is identified, antibiotics suitable for pyrexia of unknown origin are commenced.

Antibiotic therapy should be guided by local guidelines and microbiology input. Most hospitals or hospital groups have consolidated their antimicrobial guidelines in an app format, and these should be used as routine. A sepsis decision tool should be used to guide care and management, and this should be included within the patient notes or electronic chart.

If there is not sufficient improvement with antimicrobial therapy, other avenues for source control should be considered e.g., imaging to help identify a focus amenable to drainage.

Sepsis should be managed by appropriately trained personnel. A multidisciplinary team approach is needed and early escalation to senior level is essential. Care at ward level may not be appropriate and an assessment should be made to determine if the patient requires transfer to a high dependency unit (HDU) or intensive care (ICU) with the escalated nursing, midwifery and medical care inherent to level two/ three care.

The documentation of sepsis should include a sepsis-specific form. This serves as an aide de memoir, ensuring that essential elements do not get forgotten. It also allows for de-escalation of care when appropriate. In hospitals using an electronic chart this has been embedded in the electronic health record.

Sepsis and Infection Prevention and Control

As with all patients, please don’t forget the basics. Standard precautions are a series of routine measures that should be used for all patients regardless of the perceived risk of infection. These measures include hand hygiene, use of personal protective equipment (PPE), respiratory etiquette, aseptic technique, sharps & safe injection practices, environmental hygiene and appropriate waste disposal. You must assess the risk for each patient and decide what level of PPE is required. If there is likely to be contact with blood or body fluids but there is a low risk of splashing, you should wear an apron and gloves; if there is a high risk of splashing, you should wear a gown, gloves and eye protection. Some patients require isolation in a single room with an en-suite e.g., patients with gastro-enteritis or if the patient is at risk of having a multi-drug resistant organism (MDRO) such as MRSA, VRE, CPE, etc. Other patients require airborne precautions and isolation in a negative pressure room or a room with a positive pressure ventilated lobby (PPVL) e.g., COVID, open pulmonary TB. An FFP-2 or FFP-3 mask should be worn if airborne isolation is required.

Education in sepsis

Ongoing education in infection, sepsis and septic shock is crucial for all healthcare professionals. This education needs to be evidence based, appropriate, meaningful and relevant. In September 2022, the NMH ran a “Sepsis Education” week for all healthcare workers and for women and families attending the hospital. Daily emails were sent out, highlighting the issues reported in this review, with daily posters and reminders of key learning points for sepsis in pregnancy. Sepsis was highlighted at daily multidisciplinary huddles, multidisciplinary team meetings and team/ward handovers. At grand rounds we reviewed case reports of relevance to sepsis in maternity care,.

We ran face to face practical drill training in the Emergency Department, the Labour and Birthing Unit, Operating theatre, Antenatal and Postnatal wards and Antenatal clinics. Sepsis is always included in our core training for practical emergency skills. As with other maternity units and departments, multiple staff members have been trained as PROMPT (Obstetrics Emergency) trainers, which includes sepsis training, and we are grateful to the support of the National Women and Infants Health Programme for their support in this. Ongoing training in infection, infection control, sepsis and septic shock is provided to staff at all levels of training and speciality.

Written by Farren M 1 , Houlihan E 2 , Kiafar S 3 , O’Reilly D 4 , Knowles S 2 , MacColgain S 4 , Higgins MF 1

1. Obstetrics and Gynaecology 2. Microbiology 3. Infection Control, Nursing and Midwifery 4. Anaesthesiology

The National Maternity Hospital, Holles Street, Centre of Excellence for Maternal, Neonatal and Women’s Health.

For further information, please visit www.nmh.ie

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