1. Sepsis in Obstetrics Dr Lay-Kok Tan MBBS FRCOG MMED(OG) FAMS
Senior Consultant, Department of OBGYN
Singapore General Hospital
Adjunct Associate Professor, Duke-NUS Graduate School of Medicine

2. Overview Size of the problem Risk factors
Concept of the continuum of sepsis
Pitfalls in diagnosis
Management of sepsis in obstetrics

3. Why this interest in sepsis?
Why this interest? Sepsis as cause of maternal mortality is a problem of THE PAST and stastistics show its DRAMATIC decline over last DECADES

4. Why this interest in sepsis?
18th and 19th centuries, puerperal fever >50% of maternal deaths in Europe
Today accounts for up to 15% of maternal deaths worldwide
Global burden of maternal sepsis >6.9 million / year (WHO)
75k maternal deaths /year in low income countries
Health disparity: low versus high income countries >3:1
But sepsis CONCERNS the developed world

5. Why this interest in sepsis?
UK: sepsis leading cause of direct maternal deaths
29 cases: rate up from 0.85 to 1.13/100,000 maternities
From EARLY 2000s, leading cause was sepsis

6. Why this interest in Sepsis?
Increase in maternal deaths in UK
Tripled in last 25 years
CEMD: lack of recognition of signs, lack of guidelines on management
“Urgent need for national clinical guideline to cover identification & management of sepsis in pregnancy, labour and postnatal period”

7. RCOG issued two guidelines for sepsi IN and AFTER pregnancy

8. In USA, sepsis is NOT a small player and shares same freq as hypertnsive disorders

9. Maternal Sepsis in USA
4th leading case of maternal mortality (USA), 13%
MMWR Surveillance Summ 2003
5% of maternal admissions to ICU
Pollock W et al. Intensive Care Med 2010
Frequency increasing 1:15,385 (1998) to 1:7246 (2008)
10% increase sepsis-related maternal death
Bauer MET et al Anesth Analg 2013

10. BURDEN is particuarly CONCENTRATED in Asia, Africa, Central and South America,
SIGNIFICANT missing data

11. Over 6.9 million / year (WHO)
75k maternal deaths /year in low income countries

12. Over 6.9 million / year (WHO)
75k maternal deaths /year in low income countries
High income countries: / 1000 deliveries (2.1% of all maternal deaths)
Low income – 11.6% of maternal deaths

13. Maternal deaths from Sepsis are largely
PREVENTABLE
The CONSTANT REFRAIN we hear is that …

14. A NZ study looking at PREVENTABILITY of severe maternal morbidity…

15. That the most common causes of preventable morbidiy was HAEMORRHAGE which all obstetric units are fully aware of and significant RESOURCES dedicated for this, and SEPTICAEMIA, which arguably has not received the same ATTENTION

16. Low incidence of bacteremia (0.2%) (54/37584)
No maternal deaths
Sepsis occurs at all gestational ages
URINARY TRACT – most common route for Prenatal bacteraemia
GENITAL TRACT – most common route for Intrapartum & Postpartum bacteraemia
E coli the most common organism
38% pre and intrapartum bacteraemia & 79% postpartum bacteraemia had raised WBC
Obstetric settlings – abortion, miscarriage, PPROM, stillbirth
AN Irish study reviewing maternal bactermia found… LOW incidence of … SEPSIS occuts at ALL gestation ages, the URINARY trach for PRENATAL and GENITAL TRACT for intraprtum and postpartum, E coli
Not all baecteremia elicited a leucocytosis, and the commonest obstetric settings were …

17. The same centre studied maternal and fetal outcomes…

18. Sepsis rate of 1.8 per k, E coli and GBS commonest, Strep A postpartum sepsis,, preterm lidevery, increased perinatal MR

19. Fetal Outcome & Maternal Sepsis
Pregnancy looses significant in 1st and second trimester

20. Obstetric interventions & Sepsis
They found BOTH CS and INSTRUMENTAL were INTERVENTIONS a/w sepsis

21. So causes can be divided into obstetric, genital and non genital, and non obstetric causes, which obstetricians in particular should not forget

22. Among the risk factors identified, the PREVALENT ones include obesity, diabetes…wary of those who have stitches inesrted, and ROM

23. These can be perhaps better organised, divided into obsetric and patient factors

24. The single most important risk factor for post-partum infection is caesarean section
van Dillen J, Zwart J, Schutte J, et al. Maternal sepsis: epidemiology, etiology and outcome.
Current Opinion in Infectious Diseases 2010;23(3):249–54.
CS carries 5-20 fold increase in infectious morbidity compared with vaginal birth

25. Sepsis Syndrome reflecting patient’s systemic response to infection
=SIRS + Infection

26. Satisfies 2 or more

27. Challenges in Obstetrics
Overlap between physiological changes in vital signs and inflammatory response
Immune modulation leading to differential response to infection
By these criteria …Pregnancy associated immune modulation leads to

28. Other challenges
…decreased vigiliance and complaisance…

29. Other problems
Source of infection was not apparent in 44% of their patients with septic shock.
Mabie WC, Barton JR, Sibai B. Septic shock in pregnancy. Obstet Gynecol. 1997;90:553–61.
Time from the first symptom of infection to ‘‘full-blown sepsis’’ was <24 h in 39% of patients
Time from the onset of infection to death < 24 h in 50% of patients.
Kramer HMC, Schuttle JM, Zwart JJ, et al. Maternal mortality and severe morbidity from sepsis in the Netherlands.
Acta Obstet Gynecol Scand. 2009; 88:647–53.

30. Maternal deaths relating to sepsis are often associated with failure to recognise the severity of illness
The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG: 2011;118(Suppl. 1):1–203.
This is a statement that BEARS REPEATING

31. The continuum of Sepsis
Systemic Inflammatory Response syndrome (SIRS)
Sepsis
Severe Sepsis
Septic shock
Sepsis IS A CONTIUUM, progressing from SIRS to shock with increasing organ dysfunction and hypotension

32. The continuum of Sepsis (stepwise rise in mortality rate)
Systemic Inflammatory Response syndrome (SIRS) (7%)
Sepsis (16%)
Severe Sepsis (20%)
Septic shock (46%)
This advancement across the spectrum is a/w stepwise increase in MR

33. The continuum of Sepsis (stepwise rise in mortality rate)
Systemic Inflammatory Response syndrome (SIRS) (7%)
Sepsis (16%)
Severe Sepsis (20%)
Septic shock (46%)
Onset of sepsis is insidious, progression can be rapid
Onset

34. Suboptimal care stems from unfamiliaroty with , we only recognise something is wrong in advanced stages down the SEPSIS continuum

35. Early Warning Scores
Early recognition and response to patient deterioration
MODIFIED EARLY OBSTETRIC WARNING SYSTEMS
Not validated for maternal sepsis
There are early warning scores deisgned in criticial medicinefor early recognition and response and modified for obstetric use but not maternal sepsis

36. MEWS
This is an example THE MODIFIED EARLY WATNING SCORE

37. For SEPSIS, But unfortunately failed to perform as a predictor for spesis
Am J Obstet Gynecol 2010

38. While it improved specificity, the PPV remained poor, due to low prevalence

39. Primary outcome: ICU admission within 48 h
Combines and modifies elements from REMS (Rapid Emergency Medicine Score) & SIRS/Sepsis criteria (Surviving Sepsis Campaign)
Score of 0=normal
Primary outcome: ICU admission within 48 h
Hypothesis: SOS identifies women at risk for ICU for sepsis
Retrospective, single institution
More recently another scoring system the SOS was developed to REPICT ICU admission
Am J Obstet Gynecol 2014:211:39.e7-8

40. ROC curve showed promise as a screening tool

41. With better PPV but this is retrospective data and not validated prospectively

42. RELY on HIGH index of suspicion
Ray Powrie

43. SKIP the Common symtoms

44. Clinical “red flags” MOVE to the clinical RED flags
Postpartum think of GAS

45. Surviving Sepsis Campaign
Protocolised ‘care bundles’ in the management of severe sepsis and septic shock
The protocolised care of patients with severe sepsis and septic shock is associated with a significant decrease in mortality
The management of the patient is divided into
initial resuscitation phase,
antimicrobial therapy (including obtaining blood cultures and source control) and
subsequent supportive therapies.
Guidelines do not specifically address maternal sepsis
emphasis of these guidelines on
institution of early aggressive treatment
multidisciplinary approach.
The SURVUUNG SEPSI campaign was born out of protoclised care bundles which showed decrease in…
NOT based on pregnancy data
Essential points was divided into intiial resus…Unclear whether this is directly related to the protocol per se or simply due to earlier recognition and intervention.
Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, Intensive care medicine 2013;39(2):165–228
Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-basedperformance improvement program targeting severe sepsis. Intensive Care Medicine 2010;36(2):222–31.

46. Management
Promptly restore adequate organ perfusion with fluid resuscitation and, if needed, drug support.
In critically ill patients, lactate is used as a surrogate marker of inadequate tissue oxygenation.
Good relationship between hyperlactaemia and mortality
Lactate is a target in goal directed therapy for early sepsis.
Progressive sepsis leads to circulatory compromise, important to

47. Management

48. Sepsis Bundle
One of the key points is prompt administration of BS antibiotic

49. When to start antibiotics
High dose IV broad spectrum antibiotics should be started immediately
Early treatment may be crucial in determining outcome
Do not wait for results of investigations
Rapid deterioration of woman’s condition if infection becomes systemic
Death within few hours if untreated

50. Let’s remind ourselves of the bugs associated with maternal sepsis
Ray Powrie

51. Ray Powrie

52. Antimicrobials
Maternal sepsis is commonly associated with polymicrobial infections, reflecting colonisation of the genital tract
The prevalence of resistant organisms, including MRSA and resistant Gram-negative bacteria (extended spectrum beta-lactamases (ESBL)), is increasing
Points to note are…POLYMICROBIAL…. RISING PREVALENCE OF MRSA and RESISTANCE of G-ve

53. This CHART show ANTIBIOTIC SPECTRA, from ANEROBES on LEFT thorugh MRSA, G+VE to G-ve LEFTWARDS, and the coverage by various anitbiotics

55. This combi covers the entire spectrum

56. Empiric Antibiotics
Complement each other in completing coverage

57. A combination … MRSA may be resistant to clindamycin, important to engage ID

58. A combination … MRSA may be resistant to clindamycin, important to engage ID

59. Other Considerations Is surgery needed in addition to antibiotics?
Consider surgery in draining abscesses, empty uterus in chorioamnionitis

60. Other considerations

62. This is a nice poster I saw at the RCOG conference in Indai and presents audit of maternal sepsis in Bolton

63. N Katakam, S Patel, S Worton. Bolton NHS Foundation Trust, UK
Protocol for clinical observations, tests, interventsion (called Sepsis 6) and relevant expertise to be involved, AT DIAGNOSIS, WITHIN 1st hour, and within THREE hours
N Katakam, S Patel, S Worton. Bolton NHS Foundation Trust, UK

64. N Katakam, S Patel, S Worton. Bolton NHS Foundation Trust, UK
Found that NONE of ases had tests and interventions done in first hour and only 40% reviewed within 3 hours
N Katakam, S Patel, S Worton. Bolton NHS Foundation Trust, UK

65. POINT 2: ACTIVATION of SEPSIS CARE BUNDLE inadequate

66. Action plan in promoting AWARENESS, updating areas of WEAKNESS and ingeniously made a sticker

67. Strong emphasis that sepsis has to be suspected and is potentially fatal

68. Conclusion Sepsis is potentially deadly
Morbidity/mortality from sepsis can be preventable
Sepsis is easily missed
Suspect sepsis, do not forget puerperium
Aggressive approach, early antibiotics
Measure lactate
Protocolised care and Audit
Systems issue

69. Thank you