Sepsis- an update Maternal Critical Care Symposium 2016 Dr Judith Joss MRCP, FRCA, DICM, FICM Consultant in Anaesthesia and Intensive Care Medicine Ninewells Hospital and Medical School, Dundee Maternal Critical Care Symposium 2016

‘SEPSIS 3’ The Third International Consensus Definitions for Sepsis and Septic Shock SCCM, ESICM taskforce JAMA. 2016;315(8):801-810

Areas to cover Changes in Sepsis definitions Old vs New Why?, How? The Implications for clinicians and healthcare systems Brief review of the treatments The Surviving Sepsis Campaign guidelines and bundles Sepsis in the Obstetric patient The unique challenges Local initiatives and successes (and a small bit about PCT)

Have we ever known what sepsis is? “Advances in the treatment of fever … have not kept pace with the rapid progress in our knowledge of the etiology. In the present condition of bacteriology we may expect great things in the near future, but meanwhile we jog along without any fixed aim, too often carried away by winds of doctrines and wild theories”. William Osler, The study of the Fevers of the South. JAMA 21, 999–1004 (1896)

Back in the days when we thought knew what ‘sepsis’ was SIRS Sepsis Septic Shock SCCP/SCCM consensus definitions 1991, 2001 Severe Sepsis Severe sepsis + hypotension Sepsis + acute organ dysfunction SIRS + infection Temp> 38 °C or < 36°C, HR>90, RR>20/min, PaCO2 < 4.2kPa, WCC>12 or <4 Non-specific clinical response

Did we need a new definition? SIRS Overly non specific 4:5 patients with SIRS dont have infection 1:8 with infection causing organ dysfunction dont have SIRS New knowledge Greater understanding of science of infection, cell biology and organ dysfunction Research We had a research problem!! With good evidence of inconsistencies in terminology

How were the new definitions derived? SCCM and ESICM convened a panel of 19 experts (2014) Literature review, Analysis of huge electronic databases Delphi process Peer review Endorsement by international societies SEPSIS 3

SEPSIS - 3 The new definition of sepsis is: ‘Infection with an increase of two or more SOFA points’ “Life threatening organ dysfunction caused by a dysregulated host response to infection”

SEPSIS - 3 The new definition of septic shock is: “Infection with hypotension requiring vasopressors to maintain MAP >65mmHg PLUS a Lactate of >2mmol/l” “A subset of sepsis with particularly profound circulatory, cellular and metabolic abnormalities associated with an increased mortality than sepsis alone”

SOFA SCORE

Quick SOFA Patients with suspected infection that are likely to have a prolonged ICU stay or to die in the hospital can be promptly identified at bedside with qSOFA The qSOFA score is less robust than a SOFA score of 2 or greater, but it does not require laboratory tests and can be assessed quickly and repeatedly.

Comparison of terminology SEPSIS 2 SIRS SEPSIS SIRS plus Infection SEVERE SEPSIS SEPSIS Plus Organ Dysfunction SEPTIC SHOCK SEPSIS 3 ? Infection + SOFA increase 2 Vasopressor + Lactate >2

How does this work clinically? all patients with suspected INFECTION SEPSIS SOFA >2 or qSOFA≥2 (10% Mortality) SEPTIC SHOCK (40% mortality) These patients are sick They must be identified and treatment started These patients are very sick require increased frequency of review And may require an increased level of care These patients are on vasopressors and should be in a critical care area

May 2016 Scottish Patient Safety Programme May 2016 Scottish Patient Safety Programme consensus definition of sepsis. Recommendations The National Early Warning Score will continue to be the recommended method of identifying deteriorating patients, including those with sepsis. Early Warning Scoring System trigger points for sepsis screening and management will continue to be locally defined. Screening for sepsis should be undertaken with the question – ‘could this deterioration be due to infection’. Systemic Inflammatory Response (SIRS) criteria will continue to aid in the general diagnosis of infection. The qSOFA criteria may be used as an adjunct to identify patients at increased risk of death and support decisions about treatment escalation. All monitoring and screening tools should be viewed as an adjunct to clinical judgement. Further studies on qSOFA will inform decisions about their potential use as a screening tool for sepsis.

SSC statement in response to SEPSIS 3 Step 1: Screening and Management of Infection Hospitals should continue to use signs and symptoms of infection to promote the early identification of patients with suspected or confirmed infection. management should begin by obtaining blood and other cultures administering tailored antibiotics as appropriate, and simultaneously obtaining laboratory results to Evaluate the patient for infection-related organ dysfunction. Step 2: Screening for Organ Dysfunction and Management of Sepsis (formerly called Severe Sepsis) Patients with sepsis (formerly called severe sepsis) should still be identified by the same organ dysfunction Criteria (including lactate level greater than 2 mmol/L). Organ dysfunction may also be identified in the future using the quick Sepsis-Related Organ Failure Assessment (qSOFA) Practitioners should strongly consider closer monitoring of these at-risk patients. If organ dysfunction is identified, ensuring that the three-hour bundle elements have been initiated continues to be a priority.

Step 3: Identification and Management of Initial Hypotension In those patients who have infection and hypotension or a lactate level greater than or equal to 4 mmol/L, providing 30 mL/kg crystalloid with reassessment of volume responsiveness or tissue perfusion should be implemented. The six-hour elements of care should be completed. For the six-hour bundle, repeat lactate level is also recommended if initial lactate level was greater than 2 mmol/L. Note that: qSOFA does not define sepsis (but the presence of two qSOFA criteria is a predictor of both increased mortality and ICU stays of more than three days in non-ICU patients) Prepare for Change Hospitals should develop detailed plans and educate their physician and nursing staff hospitals should also create detailed plans and educate quality department staff to abstract charts and translate the new nomenclature into language compatible with the national quality measure, which typically uses the older terminology. Conclusion Once hospitals have adequately prepared for change, sepsis team leaders should reinforce the message that the new definitions Do not change the primary focus of early sepsis identification and initiation of timely treatment in the management of this Vulnerable patient population

SSC Guidelines (2012) 3 Hour Target 6 Hour Target Key Recommendations Lactate Blood Cultures Antibiotics 30ml/kg crystalloid If ↓BP or lactate>4 6 Hour Target Vasopressors for ↓BP MAP>65mmHg CVP &Scv02 Key Recommendations FLUIDS VASOPRESSORS INOTROPES STEROIDS (APC) ANTIBIOTICS PCT Supportive Treatments Blood Immunoglobulin Selenium Mechanical ventilation Glucose Sedation RRT Bicarbonate DVT and stress ulcer Nutrition Goal setting

Maternal Mortality in the UK

CMACE EMERGENT THEME BRIEFING #1: Genital Tract Sepsis September 2010 SAVING MOTHERS’ LIVES 2006-08: Briefing on genital tract sepsis During the 2006 – 2008 triennium, sepsis was the leading cause of direct maternal deaths, accounting for 26 direct deaths and a further 3 deaths classified as ‘Late Direct’ Whilst maternal mortality is declining overall, maternal deaths due to sepsis have risen in recent triennia, particularly those associated with Group A streptococcal infection (GAS) 2000-2002 2003-2005 2006-2008 Rate per 100000 maternities 0.65 0.85 1.13 Numbers (all organisms) 13 21 29 Numbers (GAS) 3 8

Causes of maternal death 2011-13

Maternal Deaths – definitions DIRECT As a consequence of a disorder specific to pregnancy (Haemorrhage, Pre eclampsia, Genital tract Sepsis) INDIRECT Deaths not directly associated with pregnancy state but may be exacerbated by pregnancy (cardiac disease, psychiatric disease, sepsis (pneumonia, flu etc) COINCIDENTAL Incidental or accidental deaths not related to pregnancy LATE Deaths occurring after 42days but before 1yr following pregnancy

Sepsis in the Obstetric Patient Complex Antenatal decision making Pregnancy and labour may make detection more difficult All trials exclude pregnancy Is Sepsis more challenging in the obstetric patient? Lack of validation of early warning scores

National Maternity Modified SIRS Criteria Any 2 or more: - Temp < 36 or > 38 oC - HR > 100 bpm - WCC <4 or > 16 x 109/L - RR > 20 bpm - Altered mental state  

Are we ‘over treating’ infection? Not infected ‘Over’ treatment group Could we safely stop treatment? Infection Appropriate Treatment How do we monitor for deterioration? Sepsis Escalation of treatment Early identification? All patients on Sepsis 6

The role of biomarkers Procalcitonin Secreted by most cells in response to bacterial Infection More specific than most commonly used biomarkers Rises rapidly (6-12hr), correlates with severity PCT in Ninewells Introduced into clinical use 2012 (ICU/sHDU) Evidence of decreased antibiotic duration in ICU PCT in Obstetrics No current evidence base Novel preliminary work being carried out

PCT Algorithm to stop Antibiotics

Summary INFECTION Is still a clinical diagnosis We may still screen with SIRS/EWS SEPSIS Is what was previously ‘severe sepsis’ Screen with qSOFA SEPTIC SHOCK Vasopressors + Lactate >2mmol/l 40% mortality

j.joss@nhs.net Acknowledgements Dr Pamela Johnston Consultant Anaesthetist Dr Pauline Lynch Consultant Obstetrician Dr Katy Orr O&G registrar, j.joss@nhs.net