Maternal Sepsis (572)

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NB Sepsis can kill mothers AND babies. If either of this pairing is infected ensure that those looking after the mother/baby know about this promptly to ensure risk evaluation of cross-infection is made.

Sepsis remains a significant cause of pregnancy and childbirth related deaths worldwide¹. The development of sepsis is often insidious and the physiological adaptations in normal pregnancy may mask developing sepsis or make it more difficult to identify. Once infection becomes systemic the woman’s condition can deteriorate extremely rapidly over the course of a few hours into septic shock, disseminated intravascular coagulation and multi-organ failure². A high index of suspicion should be maintained.

To reduce maternal death from sepsis requires high levels of vigilance and to “Think Sepsis” at an early stage with any unwell, pregnant or recently pregnant woman. Key actions are the importance of early diagnosis, the rapid initiation of broad spectrum antibiotics and the need for review by senior doctors and midwives and early involvement of relevant experts such as infection specialists and critical care, where appropriate. ²

Septic shock is now described as a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain an adequate blood pressure (MAP 65 mm Hg or more), alongside a persistent serum lactate (either venous or arterial) level more than 2 mmol/L despite adequate volume resuscitation. Using these criteria, hospital mortality is in excess of 40%. There are no widely agreed pregnancy specific adaptations to this definition.²

The purpose of this guideline is to provide a structured approach to investigation and management of these women. Observations should be documented as ‘MEOWS/MEWS’ on Badgernet and the digital MEWS chart reviewed with each entry via the charts section.

IT IS IMPORTANT TO NOTE THAT MOST LABOURING WOMEN WILL MEET NON-PREGNANT SEPSIS CRITERIA: see MODIFIED MATERNITY SEPSIS TOOL BELOW
SIMILARLY, NON-PREGNANT RISK ASSESSMENTS (eg CURBS 65) DO NOT PERFORM WELL IN THE PREGNANT POPULATION.
IF IN DOUBT MANAGE AS SEPSIS AND THEN REVIEW DIAGNOSIS.

All pregnant women and those who have recently given birth need to be informed of the signs and symptoms infection. Advice to all women should include information about Group A Strep (GAS) prevention, signs and symptoms and the need to seek advice early if concerned, as well as the importance of good personal hygiene being essential. This includes avoiding contamination of the perineum by washing hands before and after using the lavatory or changing sanitary towels. Such emphasis on hygiene is especially necessary when a woman or her family or close contacts have symptoms of GAS infection such as sore throat, impetigo or scarlet fever.

Risk factors for maternal sepsis in pregnancy and the puerperium

Maternal	Obstetric
Obesity	Prolonged rupture of membranes >18 hours
Diabetes in pregnancy	Has had invasive procedure in last 6 weeks (e.g. CB, VFB, ERPC, cerclage, CVs, Amniocentesis, miscarriage, termination)
Iron deficiency anaemia	Vaginal trauma
Maternal age >35 years	Retained pregnancy tissue
Impaired immunity/immunosuppressant medication (Steroids, chemotherapy)	Multiple pregnancy
Women of ethnic minority
Renal/cardiac/liver disease
History of pelvic infection
Close contact with Group A streptococcal infection e.g. Scarlet fever, impetigo
Intravenous drug use

The organisms most commonly implicated are²:

Organism	% of positive blood cultures
Escherichia coli	37.3%
Group B beta-haemolytic streptococcus (GBS)	20.6%
Anaerobes	8.3%
Staphylococcus aureus	7.6%
Group A beta-haemolytic streptococcus (GAS)	4.3% (10/12 women were post-partum )
Coliforms other than Escherichia coli	4.2%
Haemophilus influenzae	1.4%
Listeria monocytogenes	0.7%

Signs and symptoms

Modified Early Warning Scoring system charts should be used to aid timely recognition, treatment and referral of women. These do not take into account the physiological changes in pregnancy, however they allow a trend in the woman’s observations to be documented and acted upon. The screening tool below should include assessment against the MEWS and infection risk factors, as well as consideration of a possible source of sepsis (either suspicion of an infection or a known cause). You must also consider and investigate other non-infective causes that can masquerade as sepsis.

Considerations before implementing sepsis six

Suspicion of sepsis

Dysuria/frequency/loin pain
Generalised rash
Diarrhoea and vomiting
Fever or Rigors
Headache with neck stiffness
Sore throat/productive cough/sputum/SOB
Offensive liquor/ lochia/ discharge
Non-reassuring CTG/ fetal tachycardia > 160bpm
Signs of potential infection including cellulitis/ joint swelling/ redness, swelling or discharge at surgical site or breakdown of wound
Mastitis/breast engorgement/redness
Uterine tenderness
Severe pain
Perineal trauma
Hyperglycaemia, in absence of diabetes (Glucose >7mmol)

Women of Black, Asian and minority ethnic background are at higher risk of developing sepsis. Healthcare providers must be aware of this increased risk in ethnic minority groups and recognise that important signs of sepsis, such as skin rashes, may present differently.²

Non-response of symptoms to treatment for other causes of serious illness, e.g. treatment of haemorrhage, or deterioration should prompt a re-consideration of sepsis as a concurrent or alternative diagnosis.

MEWS observations

Full set of MEWS observation should be completed for all women with clinical signs suggestive of sepsis.
MEWS observations should be completed and documented as per GGC MEWS guidance.
Any concerns or deviations from normal should be escalated without delay.

Sepsis Triggers ^2,3

Red Flags: High Risk Criteria

Amber Flags: Moderate Risk Criteria

Objective evidence of newly altered mental state
Respiratory Rate ≥ 25 breaths per minute
Heart rate > 130bpm
Systolic blood pressure ≤90mmHg or >40mmHg below woman’s normal or MAP <65mmHg
New need for oxygen (40% or more) to maintain saturation > 92%
Catheter urine volumes of <0.5ml/kg/hour
Not passed urine in > 12 hours
Non-blanching petechial or purpuric rash, mottled/ ashen/ cyanotic
Lactate ≥2 mmol/l *

Intrapartum Only

Temperature ≥38°C or > 37.5 on 2 occasions, 1 hour apart **

*Note that lactate may be raised in and immediately after labour

History from patient, friend or relative of new onset of altered behaviour or mental state
History of acute deterioration of functional ability
Respiratory rate 21-24 breaths per minute
Heart rate 100 –130bpm or new dysrhythmia
Systolic blood pressure 91-100 mmHg
Temperature < 36°C or >38°C (see intrapartum amendments in high risk criteria)
Catheter urine volumes of 0.5ml/kg to 1ml/kg or urine per hour
Not passed urine ≤ 12 hours
Has had invasive procedure in last 6 weeks (e.g. CB, VFB, ERPC, cerclage, CVs, Amniocentesis, miscarriage, termination)
Impaired immune system (illness or medication, including oral steroids)
Current diabetes or gestational diabetes
Close contact with Group A Strep
Prolonged rupture of membranes 18 -24 hours
Prolonged vaginal bleeding and abdominal pain post birth
Abnormal CTG or significant rise in baseline e.g. > 20bpm
Signs of potential infection, including redness, swelling or discharge at surgical site or breakdown of wound
Offensive bleeding or vaginal discharge

If ONE criterion is present with suspicion of infection:

Commence Sepsis six now
Immediate Obstetric review (ST3 or above)
Broad spectrum antibiotics should be administered within 1 hour of identification
Stat IV fluid bolus for all women with lactate ≥2mmol/l
Transfer via 999 ambulance if in the community
Complete MEWS at least every 30 minutes
Escalate to consultant if no response to interventions within 1 hour
Women with lactate >4mmol/l or ongoing systolic blood pressure <90mmHg should be referred to critical care specialist or team

If ONE criterion is present with suspicion of infection:

Send bloods - FBC, CRP, U+E, LFT, Coag, Lactate, Blood cultures, venous blood gas
Arrange for ST3 or above to review within one hour
If antimicrobials are required, administer as soon as decision was made but always within 3 hours
If lactate if <2mmol/l and no evidence of acute kidney injury with no definitive condition identified, repeat assessment hourly.

**NICE (121) states that ‘Paracetamol is safe and can reduce discomfort when a woman has a raised temperature…. [although]… there is no evidence that this improves outcome for mother or baby. Because paracetamol may mask a worsening fever healthcare professionals should remember that paracetamol is not a treatment for sepsis and should not delay investigation and treatment when sepsis is suspected’.⁴

Sepsis 6 Management

Complete all actions within 1 hour

1	Ensure ST3 or above attends for immediate review	Not all women with red flags will require urgent sepsis 6 management. A senior decision maker may seek alternate diagnosis/ de-escalate care. Ensure time and name of member medical staff informed is documented in Badger notes
2	Oxygen if required	Commence high flow oxygen (15L) via non-rebreathe mask if O2 saturations are less than 92%. Aim for O2 saturations of 94-98%.
3	Send bloods, including cultures	Site 1-2 wide bore cannulas and obtain: Full Blood Count (FBC) +/- blood film Coagulation studies Urea and Electrolytes (U+E) CRP Liver function test (LFT) Lactate- A measure of tissue perfusion and prognostic indicator⁴. This can be performed on a venous or arterial blood gas. A lactate of >4 mmol/l is indicative of tissue hypo-perfusion. Elevated lactates should be monitored hourly. 2.1- 3.9 mmol/l Intermediate > 4 mmol/l Severe – consider discussion with critical care team Blood Cultures- should be obtained prior to antibiotic administration Blood Glucose Venous Blood Gas analysis Group and Save (X-match if appropriate : see separate MSBOS)
4	Give Antibiotics, consider delivery	Broad spectrum intravenous antibiotics can be life saving. Immediate aggressive treatment should be initiated as each hour of delay is associated with a measurable increase in mortality³. See the Antibiotics Policy for Obstetric Patients GG&C guideline. for required antibiotic and dosage. Microbiology advice should be sought in severe sepsis or septic shock. Breastfeeding may limit the use of some antimicrobials. Consider local policy, allergies and antivirals If no response after 24-48hrs of antibiotics consider change/addition of antibiotics under microbiology guidance. Evaluate need for imaging/ specialist review to assist in identifying the source.
5	Give IV Fluids	Loss of vasomotor tone, myocardial depression and increased vascular permeability contribute to the real risk of pulmonary oedema³. Fluid therapy should be titrated against the woman’s urine output, blood pressure and central venous pressure (if CVP line in place). With lactate <2mmol/l, consider administration of IV fluids Early fluid resuscitation should be administered with an immediate 500ml fluid bolus over 15 minutes in women with hypotension (systolic BP <90 mmHg) or lactate > 2 mmol/l. Exercise caution in PET. Vasopressors indicated if the MAP is <65mmHg after adequate fluid resuscitation (used in discussion with anaesthetics). Consideration of central venous monitoring. If CVP line in place aim for CVP 8-12 mmHg
6	Monitor	Use maternity early warning score (MEWS). All urine output should be measured and fluid balance documented. Consider catheterisation with hourly urine volumes. Hourly urine output >0.5mls/hr/kg Repeat lactate hourly if initial lactate is high or if clinical condition changes

Seek the source:

A through history should be obtained and should guide additional investigations such as:

Virological testing including SARS-Cov-2 and influenza
Midstream specimen of urine
Stool cultures
Vaginal swabs
Wound/perineal swabs
Placental swabs if delivered
Baby/fetal swabs if delivered
Chest X ray
Throat/ nose swabs
Imaging of the abdomen if suspected intra-abdominal sepsis
Breast examination
Wound examination
Consider the need for:

Lumbar puncture
Respiratory secretions culture

Also consider potential herpes simplex virus (HSV) infection in an unwell woman where an underlying diagnosis is not apparent. Refer to GGC Genital Herpes in Pregnancy RCOG (439) for further guidance.

Further considerations

Blood Products

Transfuse if Hb<70g/L until in the range 70 to 90g/L as per GGC Postpartum Blood Transfusion in Stable Patients (325)
Keep platelet >50 x10⁹/L if there is a significant risk of bleeding or if surgery or invasive procedures are planned
Be guided by haematological advice

Focus of infection

The focus of infection may need surgical evacuation, drainage or excision of necrotic tissue, e.g. uterine evacuation or breast, wound or pelvic abscess drainage

If either the woman or the baby is infected with invasive Group A streptococcus (iGAS) disease in the postpartum period, both should be treated with antibiotics and full infection control precautions adopted, including barrier nursing as per local guidelines.²

Thromboprophylaxsis

During and after pregnancy it should be noted that current systemic infection is an important risk factor for venous thromboembolism and should prompt reassessment for the correct thromboprophylaxis according to current guidelines

Low molecular weight heparin²

Prophylactic dose based on most recent weight
Once platelet count reviewed

The Fetus

Ensure a CTG is completed at point of sepsis diagnosis for all antenatal women ≥ 26+0 weeks. Duration and frequency of monitoring should be included in management plan. Please refer to GGC Antenatal Fetal Monitoring, Inpatients (641) and Fetal monitoring in labour - National Institute for Health and Care Excellence (NICE) (1143) for further guidance.
The decision regarding timing and mode of delivery will be made by a consultant obstetrician.
During the intrapartum period continuous electronic fetal monitoring should be employed in gestations from 26+0 weeks. Below this gestation, discuss fetal monitoring with the Consultant Obstetrician.
Caution is required when considering fetal blood sampling ²
If delivery is required the choice of anaesthesia will be made after discussion with a Consultant Anaesthetist.
The paediatric team must be informed of any neonate born to a mother with suspected sepsis
Babies of women treated for sepsis during labour or in the 24 hours before or after birth require assessment for risk factors and clinical indicators for infection.
The neonatal team must be informed of all positive maternal blood culture results regardless of when they are resulted and even if the baby has received treatment. If the baby is still an inpatient, the on-call neonatal team should be informed at the time of receiving result to allow review of the current treatment plan.
Ensure that if maternal HSV infection is suspected, the neonatal team are informed as soon as possible.

Multidisciplinary Team

Consultant Obstetrician
Consultant Anaesthetist
Intensive care specialists
Microbiology
Haematology
Appropriate specific specialty (e.g. Surgical, renal etc.)
Pharmacy

Indications for Referral to ITU²

Senior clinicians (obstetricians and obstetric anaesthetists) and a senior midwife should be directly involved in the decision to escalate care within one hour of any deterioration.

Expert multidisciplinary advice should be sought urgently at a senior level when sepsis is suspected and not responding to initial management.

There should be an urgent referral to the critical care team in severe or rapidly deteriorating case of sepsis where the facilities/skills to care for a woman are not available on the maternity unit.

Early consultation with an infection specialist (medical microbiologist or infectious disease clinician) is recommended to optimise microbiological diagnostic investigations and appropriate usage of antimicrobials. The decision to transfer a woman to the adult intensive care unit should be made by senior clinicians (obstetricians/anaesthetists). As soon as the need for an enhanced level of care/critical care is recognised that level of care should be provided, regardless of the setting. ²

Indications for critical care input:

Cardiovascular – Hypotension (< 90mmHg systolic) or raised serum lactate (>4mmol/l) persisting despite fluid resuscitation, suggesting the need for vasopressor and/or inotrope support
Respiratory - Pulmonary oedema/ Mechanical ventilation/ Airway protection
Renal - Renal dialysis
Neurological - Significantly decreased conscious level
Miscellaneous - Multi-organ failure/ Uncorrected acidosis/ Hypothermia

Once referral for ITU care has been made, the women should continue receiving at least level 2 care until transferred out of the Obstetric HDU. This includes maintaining CVP ≥ 8 mmHg, MAP >65mmHg (used in discussion with anaesthetics) and monitoring of appropriate bloods.

There is no place in this guideline for the use of high dose corticosteroids or recombinant human activated protein C

Risk factors for maternal sepsis in pregnancy and the puerperium

Signs and symptoms

Sepsis 6 Management

Further considerations

Editorial Information