[CG] Maternal sepsis

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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 an important cause of maternal death (1). 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.

Briefly learn that SIRS > sepsis > septic shock unless appropriate action taken

 SIRS (systemic inflammatory response syndrome) -  a  clinical state consisting of two or more coexisting conditions: fever or hypothermia, tachycardia, tachypnoea, and an abnormally high leukocyte count.

Severe sepsis with acute organ dysfunction has a mortality rate of 20-30%, rising to 40-50% if septic shock (sepsis with hypotension refractory to fluid resuscitation) develops. Severe Sepsis with multi-organ failure carries a mortality rate >60%3.

The purpose of this guideline is to provide a structured approach to investigation and management of these women. The screening tool is to be filed in the patient notes and completed goals documented.

  • IT IS IMPORTANT TO NOTE THAT MOST LABOURING WOMEN WILL MEET NON-PREGNANT “SIRS” 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.

Signs and symptoms

Modified Early Warning Scoring System charts should be used to aid timely recognition, treatment and referral of women who have or who are developing a critical condition. These do not take into account the physiological changes in pregnancy, however, they allow a trend in the patients’ observations to be documented and acted upon. SEE SEPSIS SCREENING TOOL BELOW

In labour changes in some parameters are highlighted in red and should be considered. Err on overdiagnosis / response if in doubt

Temperature <36°C or >38°C 4

In labour a temperature of ≥ 37.5°C on 2 separate occasions at least 2 hours apart  

Persistent tachycardia > 100bpm5
Or

>110bpm in labour

Tachypnoea >20 breaths per minute4
Or

>22 in labour

WCC <4 or >16 x 109 /L  4

WCC in labour >20 x 109 /L  (although WCC of up to 30 have been seen in labour, a WCC of 20 is the generally recommended threshold for investigation in the literature)3,5

Oliguria <0.5mls/hour4

Arterial Hypoxaemia <8k Pa on air and/or metabolic acidosis pH <7.35 / H+ >45nmol/l  

(pregnancy results in a relative respiratory alkalosis)4

Hypotension MAP <65mmHg or systolic BP <90mmHg4

Abnormal U&Es, LFTs , Coagulation 

CRP – However a normal CRP may be falsely reassuring and does not rule out systemic sepsis.  There is often a delay in CRP increase in acute sepsis.

Fetal tachycardia and/or non reassuring CTG

  • this can be evidence of intrauterine infection / choriomamnioitis
  • these changes may serve as an early warning sign for derangements in maternal end-organ systems  

Hyperglycaemia in the absence of diabetes


The Common Organisms

The organisms most commonly implicated are2:

  • Streptococcus pyogenes ( Group A strep)
  • Group B streptococcus 
  • Escherichia coli
  • Staphylococcus aureus
  • Gram- positive and gram – negative mixed infections
  • Streptococcus pneumoniae
  • Klebsiella
  • Enterococcus faecalis
  • MRSA

Investigations

Seek the organism

This should ideally be guided by the history and take place before administration of antibiotics – HOWEVER, do not delay starting antibiotic therapy.

  • Take a History and examine the patient
  • Blood cultures
  • Midstream specimen of urine
  • Stool cultures
  • Vaginal swabs
  • Wound/perineal swabs
  • Placental swabs if delivered
  • Baby/fetal swabs if delivered
  • Chest X ray
  • Throat swabs
  • Imaging of the abdomen if suspected intra-abdominal sepsis
  • Breast examination
  • Wound examination
  • Consider the need for:
    • Lumbar puncture
    • Respiratory secretions culture

Bloods

  • FBC +/- blood film
  • COAGULATION STUDIES
  • UREA AND ELECTROLYTES
  • CRP
  • LFT
  • LACTATE
  • Group and Save (X-match if appropriate : see separate MSBOS)
  • Consider Blood Gas analysis (NOT ROUTINE)

Serum 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 hypoperfusion.

  • 2.1- 3.9 Intermediate
  • > 4 Severe

Management

Antibiotics

  • 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
  • Microbiology advice should be sought in severe sepsis or septic shock.
  • Breastfeeding may limit the use of some antimicrobials.
  • If no response after 24-48hrs of antibiotics consider change/addition of antibiotics under microbiology guidance.

See the Antibiotics Policy for Obstetric Patients GG&C guideline. The following table summarises GGC Antibiotic guidance in SEPSIS only. 

Suspected source of sepsis

 Antibiotic if no history of penicillin allergy

Antibiotic if penicillin allergy

Group B streptococcus prophylaxis where there is suspected chorioamnionitis or

sustained intrapartum pyrexia (>38.0°C once 
OR ≥37.5°C twice at least 1 hour apart). 

Broad spectrum antibiotics and Group B streptococcus prophylaxis are required.

 

 

 

 

IV Benzyl penicillin 3g 

followed by

IV Benzyl penicillin 1.8 g 4 hourly AND 

IV Co-amoxiclav 1.2 g 8 hourly 

AND

IV Gentamicin* (Dose per GGC gentamicin dose calculator) Review post-delivery then daily.

 

 

IV Clindamycin 900 mg  8 hourly 

AND

 IV Gentamicin* (Dose per GGC gentamicin dose calculator)

 Review post-delivery then daily.

Effective prophylaxis

 Prophylaxis has the greatest chance of being effective if the first dose is completed >2hrs before delivery and continued at the correct intervals.

Prophylaxis is considered to have lapsed if a dose is > 1hr late. If prophylaxis with Benzylpenicillin has lapsed a further loading dose is required.

Suspected chorioamnionitis or sustained intrapartum pyrexia
(>38.0°C once 
OR ≥37.5°C twice at least 1 hour apart)

IV Co-amoxiclav 1.2 g 8 hourly  AND

IV Gentamicin* (Dose per GGC gentamicin dose calculator) Review daily.

IV Clindamycin 900 mg  8 hourly 

AND

IV Gentamicin* (Dose per GGC gentamicin dose calculator)   Review daily.

Group A streptococcus infection - confirmed

IV Benzylpenicillin 2.4g 6 hourly

AND

IV Clindamycin 600mg 6 hourly Review daily.

Total course duration 7-10 days (IV/oral).

IV Vancomycin** (see GGC vancomycin dose calculator)

AND 

IV Clindamycin 600mg 6 hourly Review daily.

Total course duration 10 days (IV/oral).

Necrotizing fasciitis

IV Clindamycin 600mg 6hourly

AND

 IV Flucloxacillin 2g 4hourly

AND

IV Benzyl penicillin 2.4g 6hourly

AND

IV Metronidazole 500mg 8hourly

AND

 IV Gentamicin ( See GGC gentamicin dose calculator)

 

Replace IV Flucloxacillin and IV Benzyl penicillin  with  IV Vancomycin** (see GGC vancomycin dose calculator)

Consider siting 2 cannulas to aid speed of administration of all antibiotics.

Seek urgent surgical / orthopaedic review. Urgent DEBRIDEMENT / EXPLORATION may be required.

Severe systemic infection – source unknown

IV Flucloxacillin 2g 6hourly 

AND

 IV Gentamicin* ( See GGC gentamicin dose calculator)

AND 

IV Clindamycin 600mg 6hourly Review daily.

Replace IV Flucloxacillin with IV Vancomycin** (see GGC vancomycin dose calculator) Review daily.

See definition of sepsis above.

 

Postnatal CS wound infection, systemically unwell

IV Flucloxacillin 1 to 2 g 6 hourly

If severe sepsis, consider ADDING IV Gentamicin* (See GGC Gentamicin

dose calculator)

If  anaerobes suspected

ADD

PR Metronidazole 1 g  8 hourly  or 

IV Metronidazole 500 mg 8 hourly. 

Total course duration 10 days (IV/oral).

IV Clarithromycin***  500 mg 12 hourly

If severe sepsis, consider ADDING 

IV Gentamicin* (See GGC Gentamicin dose calculator)

If  anaerobes suspected, 

ADD

PR Metronidazole 1 g  8 hourly  or 

IV Metronidazole 500 mg 8 hourly. 

Total course duration 10 days (IV/Oral). Clarithromycin*** serious drug interactions (see BNF appendix 1) and QTc prolongation.

Pyelonephritis with sepsis, antenatal or postnatal

IV Co-amoxiclav 1.2 g 8 hourly 

AND

IV Gentamicin* (See GGC gentamicin dose calculator)  Review daily.

 

Oral switch co-amoxiclav 625mg 8 hourly 

Total course duration (IV/oral) 14 days

IV Gentamicin* (See GGC gentamicin dose calculator). Do not continue gentamicin beyond 96 hours.

Contact microbiology for oral or alternative IV options within 96 hours of commencing IV gentamicin.

Total course duration (IV/oral) 14 days IV antibiotic administration in sepsis – see note on introduction. Culture prior to treatment and daily review on basis of results. Re-culture 7 days after completion of course.

Postnatal genital tract sepsis

IV Co-amoxiclav 1.2g  8 hourly  +/- I V

Gentamicin* if severe

Total course duration 5 days

IV Clindamycin 900mg  8 hourly  +/- gentamicin* IV if severe Total course duration 5 days

Antenatal or Postnatal Infection - Severe community acquired pneumonia (CAP) or CAP PLUS sepsis syndrome

 

 

 

 

 

 

CAP (See above) PLUS Staphyloccoccal pneumonia suspected e.g. complicating influenza

IV/ Oral Clarithromycin*** 500 mg  12 hourly AND Either

IV Amoxicillin 1 g 8 hourly

OR 

IV Co-amoxiclav 1.2g 8 hourly.  Total Course duration (IV and oral): if rapid clinical improvement by day 3, then 5 days of treatment otherwise 7-10 days (as per response). Confirmed legionella 10-14 days

 

Add to CAP schedule 
IV Flucloxacillin 2 g 6 hourly. 

Total course duration 14-21 days

IV/ Oral Clarithromycin*** 500 mg  12 hourly

AND

Vancomycin (See GGC Vancomycin dosing guidelines)

Total Course duration (IV and oral): if rapid clinical improvement by day 3, then 5 days of treatment otherwise 7-10 days (as per response). Confirmed legionella 10-14 days

 

 

IV/Oral Clarithromycin*** 500mg 12 hourly

AND

IV Vancomycin** (see GGC Vancomycin

dosing guidelines)

Total course duration 14-21 days ***Clarithromycin serious drug interactions (see BNF appendix 1) and QTc prolongation.

Mastitis

IV Flucloxacillin 1-2 g 6 hourly Or (depending on severity)

Oral flucloxacillin 1 g 6 hourly

Total course duration 5 days

IV Clarithromycin*** 500mg IV twice Daily

Total course duration 5 days 
Clarithromycin*** serious drug interactions (see BNF appendix 1) and QTc prolongation 

Post-partum endometritis (with fever/unwell)

IV Clindamycin 900mg 8hourly

AND

IV Gentamicin* ( See GGC gentamicin dosing guidelines)  

IVOST Co- amoxiclav 625 mg oral 8 hourly. 

Total course duration (IV/oral) 7 days.   AND

 Azithromycin 1 g oral once only

IV  Clindamycin 900 mg  8 hourly

AND

IV Gentamicin* (See GGC Gentamicin dosing calculator)

IVOST Oral Clindamycin
<70 kg booking weight
450 mg 8 hourly 
≥ 70 kg booking weight
600 mg  8 hourly 

AND

Oral ciprofloxacin 500 mg 12 hourly. 

Total course duration (IV/oral) 7 days.  AND 

Azithromycin 1 g oral once only

If already received azithromycin postabortion do not redose.

* Gentamicin- dose in accordance with NHS GGC Gentamicin Dosage and Monitoring Guidelines.

** Vancomycin dose in accordance with NHS GGC Vancomycin Dosage and Monitoring Guidelines. Care if renal function compromised.

All gentamicin or vancomycin prescriptions that continue beyond 3-4 days of treatment must be discussed with microbiology/ infectious diseases unit.

*** Clarithromycin- serious drug interactions (see BNF appendix 1) and QTc prolongation

Haemodynamic Management

  • 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 womans urine output, blood pressure and central venous pressure (if CVP line in place).
  • Initial fluid bolus of 500mls Hartmanns over 30 mins (caution in PET)
  • Hourly urine output >25mls/hr
  • Mean arterial pressure >65mmHg (used in discussion with anaesthetics)
    • Vasopressors indicated if the MAP is <65mmHg after adequate fluid resuscitation 
  • Consideration of central venous monitoring
    • if CVP line in place aim for CVP 8-12 mmHg 

 

Blood Products

  • Transfuse if Hb<70g/L until in the range 70 to 90g/L2
  • 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 

 

Thromboprophylaxsis

  • TEDS
  • Low molecular weight heparin2 
    • Prophylactic dose based on most recent weight
    • Once platelet count reviewed

 

The Fetus

  • 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. 
  • 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

 

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

  • Cardiovascular - Hypotension or raised serum lactate persisting despite fluid resuscitation, suggesting the need for inotrope support
  • Respiratory - Pulmonary oedema/ Mechanical ventilation/ Airway protection
  • Renal - Renal dialysis
  • Neurological - Significantly decreased conscious level
  • Miscellaneous - Multi-organ failure/ Uncorrected acidosis/ Hypothermia

Referral to ITU should be from a discussion with the consultant obstetrician and consultant anaesthetist.

Once referral for ITU care has been made, the patient 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

 

Last reviewed: 17 September 2019

Next review: 30 September 2022

Author(s): Julie Murphy; Dr. Brian Jones, Head of Service, Microbiology, GRI, GG&C; Ysobel Gourlay Lead Pharmacist GG&C Antimicrobial Management Team; Mrs June Grant, Lead Clinical Pharmacist, W & C, GG&C

Version: 2

Approved By: GONEC

Document Id: 572