In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Classification of evidence levels (1++ to 4) and grades of recommendations (A-D) are defined at the end of the "Major Recommendations" field.
Which Women Are at Risk of Sepsis in Pregnancy?
D - Multiple risk factors for severe sepsis have been identified by the Confidential Enquiries into Maternal Deaths (CEMD) (see table 1 in the full guideline document).
What Should Prompt Recognition of Sepsis in the Pregnant Woman?
D - All healthcare professionals should be aware of the symptoms and signs of maternal sepsis and critical illness and of the rapid, potentially lethal course of severe sepsis and septic shock. Suspicion of significant sepsis should trigger an urgent referral to secondary care.
D - Clinical signs suggestive of sepsis include one or more of the following: pyrexia, hypothermia, tachycardia, tachypnoea, hypoxia, hypotension, oliguria, impaired consciousness and failure to respond to treatment. These signs, including pyrexia, may not always be present and are not necessarily related to the severity of sepsis.
Clinical features suggestive of sepsis are shown in table 2 of the original guideline document. Diagnostic criteria for sepsis and severe sepsis are provided in appendix 1 and features of toxic shock syndrome are listed in appendix 2 of the original guideline.
What Are the Appropriate Investigations When Sepsis Is Suspected?
D - Blood cultures are the key investigation and should be obtained prior to antibiotic administration; however, antibiotic treatment should be started without waiting for microbiology results.
D - Serum lactate should be measured within six hours of the suspicion of severe sepsis in order to guide management. Serum lactate ≥4 mmol/l is indicative of tissue hypoperfusion.
D - Any relevant imaging studies should be performed promptly in an attempt to confirm the source of infection.
Blood cultures and other samples as guided by clinical suspicion of the focus of infection (e.g., throat swabs, mid-stream urine, high vaginal swab, or cerebrospinal fluid) should be obtained prior to starting antibiotic therapy as they may become uninformative within a few hours of commencing antibiotics but must not delay antibiotic therapy. If the methicillin-resistant Staphylococcus aureus (MRSA) status is unknown, a pre-moistened nose swab may be sent for rapid MRSA screening where such testing is available. The results of these tests should be reviewed when they become available to allow subsequent optimisation of the antibiotic regime. Similarly, prompt imaging may identify the source of the infection, allowing early definitive treatment, and should not be deferred on the grounds of pregnancy. Use of the resuscitation 'bundle' developed as part of the Surviving Sepsis Campaign is recommended (see table 3 in the original guideline document) and includes measurement of serum lactate within six hours of suspicion of severe sepsis with the result being used to guide management. Arterial blood gas measurement should be undertaken to assess for hypoxia. Laboratory findings suggestive of a diagnosis of sepsis are outlined in appendix 1 of the original guideline document. [Evidence level 4]
Who Should Be Involved in the Collaborative Care of Women with Sepsis?
D - If sepsis is suspected, regular frequent observations should be made. The use of a Modified Early Obstetric Warning Score (MEOWS) chart is recommended. There should be an urgent referral to the critical care team in severe or rapidly deteriorating cases, and the involvement of a consultant obstetrician.
D - The expert advice of a consultant microbiologist or infectious disease physician should be sought urgently when serious sepsis is suspected.
The decision to transfer to intensive care should be decided by the critical care team in conjunction with the obstetric consultant and the consultant obstetric anaesthetist. Cardiac output monitoring, ventilatory support requiring intubation, and renal support would all require transfer to ICU in the majority of units (see table 4 in the original guideline document).
What Empirical and Specific Antimicrobial Therapy Should Be Used to Treat the Woman?
D - Administration of intravenous broad-spectrum antibiotics is recommended within one hour of suspicion of severe sepsis, with or without septic shock.
D - If genital tract sepsis is suspected, prompt early treatment with a combination of high-dose broad-spectrum intravenous antibiotics may be lifesaving.
Information on antimicrobials which may aid in guiding choice is provided in table 5 of the original guideline document; however, hospital guidelines differ, and local guidance should be followed as the incidence of resistant organisms varies throughout the UK.
In addition to antimicrobial therapy, the source of sepsis should be sought and dealt with if possible: for example, by delivery of the baby. [Evidence level 3]
What Is the Role of Intravenous Immunoglobulin (IVIG)?
D - IVIG is recommended for severe invasive streptococcal or staphylococcal infection if other therapies have failed.
Classification of Evidence Levels
1++ High-quality meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias
1– Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies or high-quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal
2- Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal
3 Non-analytical studies, e.g. case reports, case series
4 Expert opinion
Grades of Recommendations
A - At least one meta-analysis, systematic review or randomised controlled trial rated as 1++ and directly applicable to the target population; or
A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results
B - A body of evidence including studies rated as 2++ directly applicable to the target population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D - Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group