Surviving Sepsis in Pregnancy
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- Sepsis and septic shock during pregnancy is a medical emergency that requires specific considerations due to the unique physiological changes of pregnancy. - A "Sepsis Six" bundle is recommended which includes obtaining cultures, measuring blood lactate, monitoring hourly urine output, providing oxygen, intravenous fluids, and administering antibiotics. - Management consists of two approaches: resuscitation including fluid resuscitation and source control through removal of infected materials and use of appropriate antibiotics. Scoring systems can help identify at-risk pregnant patients.
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Surviving Sepsis in Pregnancy
- 1. Helen V. Madamba, MD MPH-TM DHPEd February 9-11, 2021
- 2. https://jamanetwork.com/journals/jama/article-abstract/2598893 The initial SSC guidelines were first published in 2004, and revised in 2008 and 2012. The recommendations are intended to provide guidance for the clinician caring for adult patients with sepsis or septic shock. Recommendations from these guidelines cannot replace the clinician’s decision-making capability when presented with a patient’s unique set of clinical variables. These guidelines are appropriate for the sepsis patient in a hospital setting.
- 3. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality. Rhodes, Evans, et al. 2017 Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 https://pubmed.ncbi.nlm.nih.gov/28101605/
- 6. Sepsis-3 DEFINITION OF SEPSIS life-threatening organ dysfunction caused by a dysregulated host response to infection
- 7. IDENTIFICATION OF PATIENTS WITH SEPSIS The quick Sequential Organ Failure Assessment (qSOFA) is a mortality prediction score that is based on the degree of dysfunction of six organ systems. PSMID Clinical Practice Guideline for Sepsis and Septic Shock in Adults in the Philippines 2020
- 8. INITIAL MANAGEMENT OF PATIENTS WITH SEPSIS AND IDENTIFICATION OF PATIENTS WITH SEPSIS-INDUCED HYPOPERFUSION PSMID Clinical Practice Guideline for Sepsis and Septic Shock in Adults in the Philippines 2020
- 9. INITIAL MANAGEMENT OF PATIENTS WITH SEPSIS-INDUCED HYPOPERFUSION AND IDENTIFICATION OF PATIENTS WITH SEPTIC SHOCK PSMID Clinical Practice Guideline for Sepsis and Septic Shock in Adults in the Philippines 2020
- 10. CLINICAL ALGORITHM FOR ASSESSMENT OF FLUID RESPONSIVENESS PSMID Clinical Practice Guideline for Sepsis and Septic Shock in Adults in the Philippines 2020
- 11. MANAGEMENT OF PATIENTS WITH SEPTIC SHOCK PSMID Clinical Practice Guideline for Sepsis and Septic Shock in Adults in the Philippines 2020
- 12. Greer O, Shah NM, Johnson MR. Maternal sepsis update: current management and controversies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 13. Greer O, Shah NM, Johnson MR. Maternal sepsis update: current management and controversies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ SEPSIS CARDINAL SIGNS OF INFLAMMATION RUBOR TUMOR CALOR DOLOR FUNCTIO LAESA
- 14. Greer O, Shah NM, Johnson MR. Maternal sepsis update: current management and controversies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ DAMP = danger associated molecular pattern
- 15. Resuscitation • 20 mL/kg crystalloids Source control • empirical antibiotics are started to cover Gram-positive, Gram- negative and anaerobic organisms • Removal of infected material Greer O, Shah NM, Johnson MR. Maternal sepsis update: current management and controversies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 16. PREGNANCY-SPECIFIC SEPSIS BUNDLE: SEPSIS SIX • to have a low index of suspicion to aid early recognition, perform essential investigations and monitoring 1. cultures 2. blood lactate 3. hourly urine output • to commence essential treatment 1. oxygen 2. intravenous fluids 3. antibiotics Greer O, Shah NM, Johnson MR. Maternal sepsis update: current management and controversies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 17. • This narrative review evaluates the presentation, scoring systems for risk stratification, diagnosis, and management of sepsis in pregnancy. • Pregnant septic patients require specific considerations and treatment goals to provide optimal care for this particular population. Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ modified obstetric early warning scoring system (MOEWS) Sepsis in Obstetrics Score (SOS)
- 18. PHYSIOLOGIC CHANGES DURING PREGNANCY Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 19. modified obstetric early warning scoring system (MOEWS) Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ “to help detect the early signs of illness and trigger timely medical review with appropriate intervention” These variables were scored according to variance from normal, and a composite score of ≥6 would predict ICU admission.
- 20. Sepsis in Obstetrics Score (SOS) Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 21. Presentation of sepsis etiologies and recommended antibiotics Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 22. Presentation of sepsis etiologies and recommended antibiotics Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ Genital tract infections are often polymicrobial, and group A streptococcus and E. coli are commonly associated with severe infections, hence the need for empirical broad-spectrum antibiotics that cover Gram-positive, Gram- negative and anaerobic organisms before culture results are available.
- 23. Presentation of sepsis etiologies and recommended antibiotics Bridwell et.al 2019 Sepsis in Pregnancy: Recognition and Resuscitation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ Prophylactic antibiotics prior to operative obstetric intervention should be considered mandatory, results in a significant reduction in the incidence of postoperative infections, endometritis and wound infection.
- 24. https://jamanetwork.com/journals/jama/article-abstract/2598893 • Sepsis and septic shock from different obstetric infections is a medical emergency. • Pregnancy presents a unique physiological picture, which will result in unique responses to disease processes. • PREGNANCY-SPECIFIC BUNDLE “SEPSIS SIX”: Cultures, blood lactate , hourly urine output, oxygen, intravenous fluids, antibiotics. • Management consists of two key approaches: resuscitation and source control. IN PREGNANCY
- 25. #HealthXPH tweetchat Healthcare Conversations on Twitter Saturdays 9:00 p.m. to 10:00 p.m. @helenvmadamba https://www.facebook.com/helenvmadamba http://helenvmadamba.blogspot.com http://www.slideshare.net/HelenMadamba
- 26. References • Rachel E. Bridwell, MD Brandon M. Carius, MPAS, PA-C Brit Long, MD Joshua J. Oliver, MD Gillian Schmitz, MD. Sepsis in Pregnancy: Recognition and Resuscitation. Western Journal of Emergency Medicine. Volume 20, no. 5: September 2019. pp 822-832. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/ • Greer O, Shah NM, Johnson MR. Maternal sepsis update: current management and controversies. The Obstetrician & Gynaecologist 2020;22:45–55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754194/
- 27. References • Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med (2017) 43:304–377 accessed on February 9, 2021 at https://pubmed.ncbi.nlm.nih.gov/28101605/ • PSMID Clinical Practice Guideline for Sepsis and Septic Shock in Adults in the Philippines 2020 at https://www.psmid.org/wp-content/uploads/2020/03/2020- CPG-for-Sepsis-in-Adults-Full-Manuscript.pdf
- 28. Helen V. Madamba, MD MPH-TM DHPEd February 9-11, 2021
Editor's Notes
- Pathophysiology of sepsis. The pathophysiology of sepsis is complex and involves the interaction of multiple biological pathways via positive and negative feedback loops. When communication between these pathways becomes uncontrolled, widespread tissue injury can lead to organ dysfunction and sepsis. On breaching the tissue epithelium/mucosal barrier, pathogens are first identified for clearance by immune cells of the innate system, monocytes and neutrophils. Invading pathogens have conserved surface molecular regions that act as danger signals (pathogen associated molecular patterns [PAMPs]) which are recognised by monocyte pathogen recognition receptors (PRRs) such as the toll-like receptor 4 (TLR-4). Simplified, interaction between the two triggers monocyte intracellular gene transcription of pro-inflammatory intracellular cytokines and chemokines via NFKB; resulting in recruitment of more immune cells to the site of infection and activation of inducible nitric oxide synthase (iNOS), which causes nitric oxide overproduction that functions to aid pathogen clearance but is also a potent vasodilator contributing to systemic hypotension and attenuated cardiac function. Neutrophils clear bacteria by phagocytosis or enzymatic degradation, which may cause tissue injury. This releases danger associated molecular patterns (DAMPs) such as heat shock protein (hsp) or high-mobility group box-1 (HMGB-1) which can result in rapid escalation of cell recruitment, cytokine release and tissue injury. Cells of the adaptive system, T cell and B cells, can recognise specific bacterial associated antigens. T cells target the pathogen via cytotoxic activity (CD8) or by the production of cytokines (CD4). Adaptive responses from T regulatory cells and other immune suppressive leukocytes, in turn, produce immuno-modulatory molecules (IL-10, TGF-b) during the contraction phase of the immune response, alongside T-helper CD4 production of ‘anti-inflammatory’ cytokines (IL-4). B cells produce antigenspecific antibodies which opsonise to pathogens together with complement to facilitate neutrophil phagocytosis. Pathogens can trigger the complement cascade, which interacts with the coagulation system. In severe sepsis this is associated with disseminated intravascular coagulation (DIC), a mixed clinical picture of microthrombus formation and haemorrhage. Adapted with permission from the text of Conway-Morris et al. characterised inflammation by five cardinal signs, namely redness (rubor), swelling (tumour), heat (calor; only applicable to the body' extremities), pain (dolor) and loss of function (functio laesa)
- The pathophysiology of septic shock. Interaction between a PAMP on bacteria and the pathogen recognition receptor on innate cells triggers release of nitric oxide and cytokines. Nitric oxide is associated with reduced vascular tone and vasodilatation. When this is severe, hypotension and septic shock occurs. Cytokine release causes tissue injury and release of DAMPs. These can cause recruitment of more innate cells and can cause tissue injury (e.g. of the heart). Cardiomyocyte death may lead to reversible reduced cardiac function. Adapted with permission from Kakihana et al.13 PRR = pattern recognition receptor; PAMP = pathogen associated molecular pattern; DAMP = danger associated molecular pattern.
- The effects of pregnancy physiology on the clinical presentation of sepsis. The modified early warning score (MEWS) observation chart of key physiological characteristics modified for obstetrics is a helpful tool to identify the ill patient, but is notoriously nonspecific. A validation study published in 201232 demonstrated an all cause obstetric morbidity sensitivity of 89% and specificity of 79%. Albright et al.33 developed a prognostic tool to identify the obstetric patient with sepsis requiring admission to the intensive care unit (ICU). The mainstay of management is supportive with a significant onus on early recognition of sepsis. Management consists of two key approaches: resuscitation and source control. The SSC recommends initial intravenous fluid resuscitation at a rate of 30 ml/kg.40This recommendationismodified to 20 ml/kg by the RCOG,1,2 due to an increased risk of pulmonary oedema in pregnancy caused by decreased colloid oncotic pressure. Source control requires initiation of antibiotics. The SSC recommends combining two classes of antibiotics only for the treatment of septic shock.40 However, in maternal sepsis, Escherichia coli and group B streptococcus are the most common bacterial pathogens, but the most severe outcomes are associated with E. coli and group A streptococcus.51 Therefore, the choice of antibiotic is guided by clinical assessment and the presumed site of infection. In reality, empirical antibiotics are started to cover Gram-positive, Gram-negative and anaerobic organisms, as per local microbial susceptibility patterns. De-escalation is then implemented in accordance with culture results.
- Pregnancy is an exclusion criterion in all major sepsis trials to date, relinquishing clinical decisions to provider preference and expert opinion. Similar to preceding trials, pregnancy was an exclusion criterion in these studies that established and validated the SOFA and qSOFA scores, thereby minimizing their utility in the pregnant population
- Working in parallel to the Surviving Sepsis Campaign, other parties presented criteria aimed at identifying maternal sepsis. The World Health Organization (WHO) modified the definition of maternal sepsis to “puerperal sepsis.”36 This narrow definition limited pregnant or postpartum sepsis to genitourinary tract infections between the time of rupture of membranes and six-weeks postpartum.37,38 The WHO provided a definition for septic abortion, which likewise remained isolated to genitourinary tract infections.36,38 As a result, many early maternal sepsis studies focused solely on the diagnosis and treatment of only these infections. The lone major MOEWS validation study analyzed 913 cases of chorioamnionitis, but only five cases met the definition of severe sepsis.48 Intended to predict severe sepsis by 2.0 guidelines, MOEWS restricts its utility not only by using a recently redefined term, but also by generating a myopic view of sepsis in pregnancy by focusing on chorioamnionitis and not the broader scope of sepsis sources.
- The anatomic and physiologic changes of pregnancy pose a challenge in early recognition and management of sepsis. Current sepsis guidelines were extrapolated from randomized control trials that specifically excluded pregnant patients. Although new guidelines have been created to risk stratify pregnant patients, they are without significant validation. Further research and validation are needed to help properly recognize and treat this small but critically ill population to improve outcomes for both mother and fetus.
- The anatomic and physiologic changes of pregnancy pose a challenge in early recognition and management of sepsis. Current sepsis guidelines were extrapolated from randomized control trials that specifically excluded pregnant patients. Although new guidelines have been created to risk stratify pregnant patients, they are without significant validation. Further research and validation are needed to help properly recognize and treat this small but critically ill population to improve outcomes for both mother and fetus.
- The anatomic and physiologic changes of pregnancy pose a challenge in early recognition and management of sepsis. Current sepsis guidelines were extrapolated from randomized control trials that specifically excluded pregnant patients. Although new guidelines have been created to risk stratify pregnant patients, they are without significant validation. Further research and validation are needed to help properly recognize and treat this small but critically ill population to improve outcomes for both mother and fetus.
- The anatomic and physiologic changes of pregnancy pose a challenge in early recognition and management of sepsis. Current sepsis guidelines were extrapolated from randomized control trials that specifically excluded pregnant patients. Although new guidelines have been created to risk stratify pregnant patients, they are without significant validation. Further research and validation are needed to help properly recognize and treat this small but critically ill population to improve outcomes for both mother and fetus.