Womens Health Conference 2014 Chicago Dr. Lovina Machado

Womens Health Conference 2014 Chicago Dr. Lovina Machado

Womens Health Conference 2014 Chicago Dr. Lovina Machado PUERPERAL SEPSIS DUE TO GROUP A STREPTOCOCCUS KEY MANAGEMENT ISSUES DR. LOVINA MACHADO MBBS,DGO,MD,FRCOG,FRCPI Senior Consultant, Dept. of Obs & Gyn Sultan Qaboos University Hospital, Muscat, Oman Associate Program Director, OBGYN Residency Program, Oman Medical Specialty Board

Dr. Lovina Machado Outline Historically .. UN Millenium goals sepsis related MMR The client About GAS, Why is it so virulent? Typical features Key Management Issues Take home messages Dr. Lovina Machado Historically speaking 1500 BC ancient Hindus ---childbed fever hygiene- cut nails 500 BC Hippocrates postpartum fever due to suppression of lochia resulting from accumulation of humors

1530-1606 Hieronymous Mercurialis failure of lactation among affected women milk instead of flowing to the breast, localised in the uterus purulent discharge milk fever UK, Scotland 1800s..J. Bundell, T. Watson, R. Collins cleanliness, hand hygiene, chlorination 1844- Ignaz Semmelweis Vienna transmission route & hand hygiene. Reduced MMR from18% to 2.4% Dr. Lovina Machado Global, regional, and national levels and causes of maternal mortality during 19902013: a systematic analysis for the Global Burden of Disease Study 2013 The Lancet, Online, 2 May 2014. doi:10.1016/S01406736(14)60696-6 No. of maternal deaths from all causes in 188 countries between 1990 & 2013. Dr. Lovina Machado

Global Causes of maternal death: a WHO systematic analysis Estimated 287,000 maternal deaths worldwide in 2010 most in lower & middle income countries- most avoidable Reduction of maternal mortality global health priority & is a target in the UN Millenium Devpt. Goals launched in Sept 2010 To achieve this, a 75% decrease in MMR between 1990 & 2015 is needed Key is to understand the causes & report data accurately Dr. Lovina Machado The Lancet, May 2014. http://dx.doi.org/10.1016/S2214-109X(14)70227-X

Global Maternity Deaths Rate of change in MMR 1990-2013 Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015 Dr. Lovina Machado Distribution of causes of death by Millenium Devpt. Goal regions Sepsis 10.7% Global Causes of Maternal Death: A WHO systematic analysis. Lancet May 2014

Dr. Lovina Machado Causes of Maternal deaths in 1990-2013 (A) Mean proportion (left) and total number (right) of maternal deaths due to different causes in 1990 and 2013. Error bars Dr. Lovina Machado show 95% uncertainty intervals. WHO Estimated causes of maternal deaths worldwide. Sepsis 4.7% - 10.7% Developing & developed countries Dr. Lovina Machado Sepsis related maternal

deaths Point estimates shown by bars & 95% CI by horizontal lines Dr. Lovina Machado Risk factors for maternal sepsis in pregnancy2005-2008 Obesity Diabetes Immuno-compromised Anemia Vaginal discharge H/o pevic infection Dr. Lovina Machado Confidential

Enquiries into Maternal Deaths : UK H/o GBS infection Amniocentesis/ inv. procedures Cervical cerclage Prolonged SROM GAS inf. in close contacts/ family The client. 27 year old Omani lady, Para3 Presented to ER 36 hrs after a normal vaginal delivery with intact perineum

c/o generalized pain abdomen, colicky, giddiness, shortness of breath. No associated nausea, vomiting, diarrhea or chest pain. History of one spike of temp 38 degrees c. 18 hrs after delivery. Intermittent lower abd.pain after pains. Uterus well contracted, lochia Dr. Lovina Machado normal, Hb 12.9 gm/dl Examination Findings Conscious, anxious, in pain, sweating Temp 36.5, Pulse- 170/mt, BP: 101/59 mm Hg, RR 22/mt, Maintaining 100% saturation on room air. BP dropped to 80/40, resuscitated with 2 L fluids, BP settled to 97/66 - 110/65mmhg. Chest - clear , normal breath sounds.

Abdominal examination - generalized distension , diffuse tenderness all over abdomen. Uterus 18 weeks size, well contracted . Lochia normal. Dr. Lovina Machado Initial investigations CBC: HB 13.8 g/dl ( postdelivery - d/c Hb 12.9 g/dl),WBC,PLT normal, VPG: normal, pH 7.3 Troponin: -ve RFT: raised urea 13,Cr normal, ECG: sinus tachycardia Chest Xray USG pelvis and abdomen CT pelvis and abdomen Dr. Lovina Machado

Distressed, dehydrated despite aggressive fluid resuscitation BP 90/50 to 110/60 mmHg Plt 130, coag deranged-APTT 55, INR 1.4, K+ 3.1 ABG- compensated metabolic acidosis Morphine, cross match PRBC & FFP , NPO, Tazocin IV Imaging, HDU, CVP line Dr. Lovina Machado Imaging Studies XR chest: normal. XR abdomen: Normal gaseous distribution of bowels in abdomen. Gasless lower abdomen and ? pelvic mass/fluid. Colon loaded with fecal matter. Air is seen in rectum. No evidence of dilated bowel loops.

No evidence of pneumoperitoneum. Dr. Lovina Machado USG Pelvis 21/03/2014 Fluid streaks in myometrium Dr. Lovina Machado Dr. Lovina Machado Grossly enlarged uterus, showing diffuse hypo and hyper echoic non vascular areas, more pronounced in lower uterine segment associated with scattered areas of fluid streaks within. No endometrial mass or fluid. Uterus integrity intact, no signs of rupture

USG Pelvis 21/03/2014 Diffusely enlarged uterus with altered echoes Diffuse hypoechoic area Dr. Lovina Machado No fluid in POD, haematoma 8x8 cms, appeared to be in the lower part of the uterus.organised Dr. Lovina Machado HB not dropping, one spike of fever, no heavy vaginal bleeding, coagulation impaired ??? Infected haematoma ?Perforation

Plan: Conservative manangement at this stage, Tazocin IV, urinary catheter involve haematologist re imapired coagulation NPO for the next 24 hrs until her condition is stable Follow up imaging HDU check HB and Coag screen at 4 pm Dr. Lovina Machado Coronal CE CT Abdomen 21/03/2014 Sagittal

Hypo-attenuated enlarged uterus Distorted ovaries & adnexa Dr. Lovina Machado CE CT Abdomen 21/03/2014 - Axial Dr. Lovina Machado Dr. Lovina Machado Moderate free fluid abdomen and pelvis. Grossly enlarged uterus with complete loss of its normal attenuation, being replaced by non enhancing hypo/low attenuation areas, more in lower uterine segment involving cervix too Bilateral ill defined / distorted ovaries and parametria.

CT Abdomen + pelvis with IV contrast: Impression:- Findings are suggestive of post partum status uterus with likely lower segment uterine hematoma with moderate free fluid in abdomen and pelvis. No evidence of bowel perforation. Dr. Lovina Machado Investi 18/3 g 21/3 05.00

20.00 22/3 13.00 Hb 12.5 13.8 11.4 10.9

WBC 8.2 3.5 1.7 3.3 Neutro 2.9 3.2 1.1

2.6 PLT 224 153 95 69 Coag PT 10

15.7 14.8 15.7 INR 0.92 1.4 1.32 1.4 APTT

37.2 55.2 56.5 51.3 Fibrinogen 7.2 3.9 4.7

Creatinin 75 109 99 Urea 13 16.5 15.7 Bilirubin

54 44 AST 65 44 ALT 11 12

22 19 Albumin 30 Lactate 2.5 281 CRP Dr. Lovina Machado

296 8 u FFP + Prothrombin concentrate Labs ICU Deteriorating Looked toxic Severe Postpartum Sepsis DIC, Ac. Kidney injury ?infected pelvic haematoma Meropenem +

Clindamyciin + Vancomycin added Meropenem + Clindamyciin + Vancomycin added Labs ICU DeterioratingLooked toxic Severe Postpartum Sepsis DIC, Ac. Kidney injury. Liver impairment ?? infected pelvic haematoma Prothrombin complex concentrate 3 vials over 5 min each PT improved

Taken for surgery with very high risk consent- hysterectomy, massive haemorrhage, death Surgeons also to scrub in NGT, Norepinephrine infusion, pneumatic compression device Dr. Lovina Machado Operative findings Midline incision 1.8 L pus in peritoneal cavity. White flabby uterus Necrotic ovaries Dr. Lovina Machado Uterus 17 x 11.5 x 11 cms, Myometrial wall thickness 4 cms, serosal

surface greenish, haemorrhagic Dr. Lovina Machado Postoperative course ICU intubated -mechanical ventilation Ionotropic support Noradrenaline BP 88/54, pulse 130/mt Plt 54- 34, TC 4.1, PT 11.9, Hb 12.1, CRP 296 Continued to spike temperature, multiorgan failure Vanco/Mero/Clinda/Anidulofungin Hypocalcemic, hypokalemia, generalised edema Atrial fibrillation x 2 Amidiarone bolus & infusion Coagulation deranged 4 u PRBC, 4 U platelets Dr. Lovina Machado Investi

g Hb WBC Neutro PLT Coag PT INR APTT Fib Creatinine Urea Bilirubin AST ALT Albumin Lactate CRP

23/3 24/3 05.0 0 05.00 11.7 11.8 8.3 13.4 7.2

11.5 54 34 11.6 11.4 1.06 1.04 42.6 49.4

5.4 5.2 79 55 13.1 10.2 42 13

34 39 13 13 22 18 Dr. Lovina Machado 296 Labs

HR 130-140/mt Spiking temp BP maintained 100/70 off ionotropes Platelets low, coag deranged 4u Plt Weaned off ventilator D3 Micro result preliminary Colonies on Blood Agar Blood c/s Pus c/s Gray colonies with clear zone of surrounding haemolysis Dr. Lovina Machado

Day 2 postop - Group A Streptococcus IV Clindamycin + IV Penicillin G IVIG 1 gm/kg that day, then 0.5 mg/kg x 2 days after Further platelet transfusions Still spiking fever but less Histopathology results Dr. Lovina Machado Dr. Lovina Machado Necrosis and inflammation of myometrium Widespread microthrombi & microabscesses

Dr. Lovina Machado All resected tissues bacteriology- heavy growth of strep. pyogenes Day 6 Diarrhoea, abdominal cramps, nausea, abd tenderness. ?pseudomembranous colitis C. difficile sent, Clindamycin stopped, Metro + oral vanco added CT imaging Hypertension- oral Labetalol Still febrile intermittently, c/o flank pain Dr. Lovina Machado Invest 25/3 ig 050

0 Hb WBC Neutro PLT Coag PT INR APTT Fib Creatinine Urea Bilirubin AST ALT Albumin CRP

26/3 D4 27/3 28/3 29/3 D7 7/4 D16 10.7 10.7

12 11.5 10.7 9.5 12 10.1 13.2 16.3 15.4

8.9 10 8.2 9.7 11.9 10.2 4.9 34

55 146 299 418 719 11.4 16.1 14 13

13.4 13.5 1.04 1.43 1.26 1.18 1.21 1.22

42.5 46 41.9 45.8 45.9 37 4.4 3.7 3.9

4.2 4.1 4 49 38 29 30 29

33 9.1 7.4 4.1 2 1.5 1.2 47 131

139 13 39 13 18 116 Dr. Lovina Machado 86 24 Labs Afebrile since D8

Perioral ulcers Tinnitus Peeling of skin Postop CE CT ABDOMEN D1608/04/2014 Moderate right pleural effusion and minimal pericardial effusion Pericardial effusion PE Dr. Lovina Machado Postop CE CT ABDOMEN 08/04/2014

Loculated fluid collection Scattered mildly distended small bowel loops with surrounding fat stranding, min. free fluid Dr. Lovina Machado Small focal areas of fluid collections with enhancing wall in pelvis Discharged Discharged on 10/4. 19 days post surgery Dr. Lovina Machado Readmitted 14/5/2014 Acute abdominal pain Severe vomiting bilious Constipation

Low grade fever Dr. Lovina Machado CE CT Abdomen Coronal14/05/2014 Dilated prox. small bowel loops With thickened walls & fat stranding Obstruction site Transition narrowing distal jejunum (sub acute bowel obstruction-Closed loop pattern) Dr. Lovina Machado

At surgery Imp: Small bowel vovlulus with ? Ac. Bowel ischemia Emergency Laparotomy Volvulus, release of adhesive band Findings: Hemorrhagic fluid within the peritoneal cavity - 20cm segment of proximal Ileum incarcerated by an adhesive band at approx. 200cm from the DJ flexure - the knotted small bowel loop was congested with small dusky patch , but was viable with good peristalsis and good colour. Pelvic findings: cervical stump neither felt nor seen, round ligaments and infundibulopelvic ligaments identified and ovaries -very small and nodular about 1 cm Dr. Lovina Machado The fulminant nature of GAS poses impressive challenges from diagnostic & therapeutic perspectives. Most present early with mild symptoms- sent home-return to

ER with full blown sepsis in 12-24 hrs Shock occurs early in severe GAS infection - STSS Early diagnosis imperative requires a high index of suspicion Diagnosis often established only after aggressive interventional management has begun. Dr. Lovina Machado Incidence of invasive GAS Incidence of invasive GAS infections is 1 to 5 cases per 100,000 population per year. Approx. 20% of these are STSS Most cases- primary & sporadic in nature Epidemics of invasive GAS have been reported health care workers, family contacts Dr. Lovina Machado

Group A Streptococcus Streptococcus pyogenes Gram-positive, nonmotile, non-spore forming coccus Occurs in chains or in pairs of cells. Individual cells - round-to-ovoid cocci, 0.6-1.0 m in diameter Dr. Lovina Machado Group A Streptococcus Catalase-negative facultative anaerobe, requires blood enriched medium to grow. GAS typically have a capsule composed of hyaluronic acid & exhibit beta (clear) hemolysis on blood agar. Dr. Lovina Machado

Cell surface structure of strep pyogenes & virulence factors Dr. Lovina Machado Pathophysiology Pyrogenic exotoxins SPE A,B and C - Superantigens A & B induce human mononuclear cells to synthesize TNF-, IL-1 and IL-6 fever, shock, tissue injury, TSS. C - mild , scarlet fever SSA and MF Proteins M protein responsible for invasiveness by impeding phagocytosis of streptococcus by human PMN Leucocytes + Pro-inflammatory M type 1 and 3 strains common isolates

Others DNAse Sda1, cysteine protease SpeB, hyaluronic acid capsule, serum opacity factor, IL-8 peptidase, & the cell wall group A carbohydrate Dr. Lovina Machado Dr. Lovina Machado Net effect- T cell stimulation Cytokine production contributes to the genesis of shock & organ failure Peptidoglycan, lipoteichoic acid, killed organisms induce TNF- production by mononuclear cells Exotoxin - Streptolysin O - potent inducer of TNF- & IL- 1. Exotoxin A, B, SLO - additive effects inducing cytokines Dr. Lovina Machado

Dr. Lovina Machado SpeB and Ska/ Plasmin directly damage the host tissues, degrade the extracellular matrix proteins, and induce vascular dissemination via their enzymatic pathway Exotoxins Streptococci elaborate surface proteins M-1 and M-3, exotoxins A, B, C, streptolysin O, and superantigen. The M proteins increase the microbes' ability to adhere to tissue and escape phagocytosis. Toxins A and B, damage endothelium, cause loss of microvascular integrity, and escape of plasma, that results in tissue oedema and impaired blood flow. In addition, these toxins, together with streptolysin O, stimulate CD4 cells and macrophages to produce large amounts of TNF, interleukin-1 and 6. Systemic release of cytokines produces the systemic inflammatory response then progress to septic shock, multi-organ failure and death. TNF also induces additional injury to the vascular endothelium by stimulating neutrophil degranulation. These in turn activate the complement system, and the coagulation cascade, and worsening small vessel thrombosis and tissue ischaemia. The tissue ischaemia

impedes the oxidative destruction of bacteria by PMNs and prevents adequate delivery of antibiotics. Thus, surgical debridement is the mainstay therapy of NF and antibiotics alone are not useful Dr. Lovina Machado Dr. Lovina Machado Clinical isolates M types 1,2,12 & 28 most common isolates in pts. With shock & multiorgan failure Sweden-80% of strains- M type 1 with pyrogenic exotoxin B mainly USA- pyrogenic exotoxin A Streptococcal superantigen (SSA) a novel pyrogenic exotoxin from an M3 strain Mitogenic factor in many M types

Dr. Lovina Machado Portal of entry of GAS Dr. Lovina Machado Routes of maternal infection 1. Colonization in vagina/rectum Rare 0.03% 2. Asymptomatic carriers-throat, skin 5-30% of population 3. Recent h/o sore throat in mum 4. Children at home/work who are carriers 5. Nosocomial infections- health care workers 6. Cesarean sections invasive surgery. 7. Can follow normal deliveries

Regardless of the type of delivery, postpartum patients have a 20 fold increased incidence of GAS as compared to nonbpregnant women. Dr. Lovina Machado Risk determinants for GAS to cause puerperal sepsis 1. Disrupted mucosal barriers 2. Altered immune status 3. Delayed diagnosis 4. Specific virulence of the GAS strain 5. Environmental exposure Dr. Lovina Machado D/D of GAS puerperal sepsis Sepsis due to other pathogens

Postpartum endometritis Retained infected POCs Pelvic abscess Hypotensive shock secondary to PPH Endocarditis Pulmonary embolism Urosepsis/ pneumonia Dr. Lovina Machado Other sepsis causing microbes GBS- less severe disease Staphylococcus Mycoplasma Chlamydia Clostridium Coliforms

Bacterial vaginosis organisms Dr. Lovina Machado Dr. Lovina Machado Case definition of STSS 1. Isolation of GAS ( strep. Pyogenes) from a A. Normally sterile site blood, CSF, tissuebiopsy, surgical wound RCOG JAMA 1993 B. Non-sterile site throat, vagina, sputum 11. Clinical signs of severity

A. Hypotension: Systolic 90 mm Hg in adults AND B. 2 of the following signs 1. Renal impairment: Cr 177mol/L ( 2 mg/dl) or 2 fold elevation 2. Coagulopathy: Plt 100 x 109/L or DIC (prolonged APTT,fibrinogen,FDP 3. Liver impairment: ASAT, ALAT, Bili 2 fold from baseline or 2ce normal values 4. ARDS, hypoxemia in absence of cardiac failure, diffuse cap. Leak manifested by acute onset generalised edema, pleural effusion, peritoneal fluid, hypoalbuminemia 5. Generalised erythematous macular rash may desquamate 6. Soft tissue necrosis, necrotising fasciitis, myositis, gangrene Probable case- meets clinical case definition + isolation from non-sterile site Dr. Lovina Machado Definite case - meets clinical case definition + isolation from normally sterile

Defining STSS Dr. Lovina Machado Dr. Lovina Machado Clinical course of strep. sepsis Fulminant process that can progress to shock & organ failure within 48-96 hours after acquisition of virulent strains of GAS Initial signs & symptoms are mild & non-specific. 20% have flu like symptoms- fever, chills, myalgia, nausea, vomiting, diarrhoea Pain- most common feature Dr. Lovina Machado

STSS PAIN most common initial symptom of STSS abrupt in onset, severe involving extremity, mimic peritonitis, PID, pulm embolism, acute MI FEVER- common sign early in course of disease STSS frequently misdiagnosed at this stage -food poisoning, viral gastroenteritis, DVT, cellulitis, muscle spasm Confusion in 55% of pts. Coma Dr. Lovina Machado STSS 80% devp. signs of soft tissue infection swelling, erythema Necrotising fasciitis, myositis requiring surgical intervention

20% - variety of presentationsendophthalmitis, perihepatitis, peritonitis, overwhelming sepsis 10% - diffuse scarlatina-like erythema Later hypotension, profound shock Dr. Lovina Machado Dr. Lovina Machado Systematic Review 55 cases with symptomatic GAS in pregnancy English 20 cases, French 2, Japanese 33 cases Symptom Percentage Concurrent/ preceding fever >38

94 % Respiratory sore throat 40% GIT diarrhoea, nausea, vomiting 49% Non-reassuring CTG fetal demise/NND 66% Decreased consciousness

31% Skin rash 15% ) 5 5 / 3 2 ( 91% Early onset of shock/ hypotension % 2 4

l ) a 9 v i 5 / v r 0 u 2 ( 75% l s contractions a Unusually strong

uterine % n 4 r 3 e l t iva Ma v r u s l ta

a n o e N(purulent uterine myometritis) Dr. Lovina Yamada T etMachado al. Invasive GAS infection in pregnancy. J of Infection 2010, 60,412-24 Complications of GAS soft tissue infection Complication Shock ARDS Renal impairment

Irreversible Reversible Bacteremia Death Dr. Lovina Machado % of patients 95 55 80 10 70 60 30 Lab evaluation - STSS Serum CPK level Elevated or rising

correlates with necrotising fasciitis or myositis Initially- only mild leucocytosis Striking-40-50% of immature neutrophils (band forms, metamyelocytes, myelocytes) Blood culture +ve in 60% Haemoglobinuria & elevated CPK renal involvement Renal impairment precedes hypotension in 40 -50% Hypoalbuminemia & hypocalcemia occur early & become profound Dr. Lovina Machado 24-48 hours after admission LRINEC (Lab Risk Factor Indicator for NF) Score Developed by Wong et al in 2004 - scoring system using CRP, total WBC, Hb, serum sodium, creatinine & glucose levels Value CRP (mg/L)

<150 >150 WBC <15,000 15,000-25,000 >25,000 Hg (g/dL) >13.5 11-13.5 <11 Na (mmol/L) >135 <135 Cr (mg/dL) <1.6 >1.6 Glucose (mg/dL)

<180 >180 Dr. Lovina Machado Score 0 4 0 1 2 0 1 2 0 2 0 2

0 1 Score 6 -7 probability of NF 5075% Score 8 - probability of NF > 75% Positive predictive value 92% Negative predictive value 96% Score validated in a number of studies. Standard of investigation to diagnose NF in early clinical settings

Management of streptococcal sepsis Aggressive fluid resuscitation Appropriate IV antibiotics within 1 hour of suspicion of sepsis Source Control Dr. Lovina Machado Dr. Lovina Machado Source control Identify site of infection Surgical intervention to remove necrotic infected foci paramount importance Multidisciplinary team ICU, ID, haemat CT/MRI- helpful but GAS does not form gas or frank abscess,

so radiologist interpretation often not definitive Swelling/edema in deep tissues may indicate deep-seated infection Dr. Lovina Machado Surgical intervention If labs marked left shift, elevated creatinine, high CPK further impetus to prompt surgery Stakes higher & surgery more difficult when GAS involves abdomen, thorax, head or neck Clost. Perfringens causes extensive gas in uterus- easy diagnosis & surgery With GAS, uterus only modestly enlarged & edematousmistaken for postpartum uterus Shock or anatomic location of infection may make surgical intervention risky/ not possible Dr. Lovina Machado

Antibiotic choice Initial antibiotic management for necrotizing fascitis. Gram Stain Result Initial Empiric Gram-positive Gram-positive PolymicrobialTherapy Cocci in Clusters Cocci in Pairs or Gram+ve cocci Chains + Gram-ve Bacilli Clindamycin plus Clindamycin plus Clindamycin plus Clindamycin plus any of following: vancomycin, or any of following: any of the imipenem,

monotherapy with piperacillin/tazoba following: meropenem, linezolid ctam, amplicillin/ imipenem, amplicillin/sulbact sulbactam, or meropenem, am, high-dose amplicillin/ piperacillin/tazob penicillin sulbactam, actam piperacillin/tazoba ctam

Dr. Lovina Machado Antibiotic therapy Strep. Pyogenes exquisitely susceptible to -lactam antibiotics. Penicillin has excellent efficacy but if started late mortality may be high despite treatment high colony count of GAS and loss of Penicillin binding protein(PBP) in stationary growth phase Dr. Lovina Machado Clindamycin Better efficacy- modulates immune response to GAS infection Efficacy unaffected by inoculum size/stage of growth

Suppresses bacterial toxin synthesis Facilitates phagocytosis of S. pyogenes by inhibiting M protein synthesis Suppresses synthesis of PBPs which are also involved in cell wall synthesis & degradation Longer postantibiotic effect Suppresses lipopolysaccharide-induced monocyte synthesis of TNF- Dr. Lovina Machado How to choose the antibiotics Dr. Lovina Machado RCOG GTG 64a Bacterial sepsis in pregnancy Dr. Lovina Machado

Fluid resuscitation Aggressive IV fluid replacement with crystalloids to achieve MAP > 60 mm Hg & tissue perfusion Invasive monitoring Maintain pulm artery occlusion pressure of 12-16 mm Hg . If hypotension persists,S. albumin conc & Hct checked. Profoundly low levels of albumin are common, haemolysins produced by GAS cause dramatic drops in circulating red cell mass. PRBC Albumin may be useful. Dr. Lovina Machado Dr. Lovina Machado Indications for transfer to ICU

Surviving Sepsis Campaign Resuscitation Bundle RCOG System Indication Cardiovascular Hypotension or raised serum lactate persisting despite fluid resuscitation, need for ionotropic support Respiratory Pulmonary edema, mechanical ventilation, airway

protection Renal Renal dialysis Neurological Significantly decreased consciousness level Miscellaneous Multiorgan failure, uncorrected acidosis, hypothermia Adapted from Plaat and Wray 2008. Dr. Lovina Machado

Management in ICU Monitoring Cardiac output mandatory in pts. With persistent hypotension Mechanical ventilation generally needed- high incidence of ARDS Intractable hypotension + diffuse capillary leak massive amounts of IV fluids (10-20L/day) may be needed. 10% rapidly improve Pressors Dopamine Dr. Lovina Machado Strategies to neutralise toxins IVIG has antibodies against some toxins such as SpeA, SpeB & opsonic antibody against

some M types of gas Dialysis & haemoperfusion reduce toxins + renal failure common in 50% of STSS pts. Sweden- Stegmayr et al Hemofiltration assoc with lowest recorded mortality rates- 14% Dr. Lovina Machado Do we have any prophylaxis? Cluster infections- nursing homes, health care workers. 50-200 times greater risk.Strict infection control practices Vaccines centred on M protein as the immunogen hypervariable regions are the primary immunologic determinant for the M type.Optimalnot yet available Screening for vaginal carriage of GAS. Rare inf, not cost effective Latest technology to develop high titre humanized monoclonal antibodies that neutralise a variety of streptococcal virulence factors is ready but

awaits production. CDC single case..enhanced surveillance of contacts 2 postpartum/postsurgical cases..demands full epidemiologic investig & cultures of involved health care team Dr. Lovina Machado In conclusion . Virulent strains of GAS causing life threatening sepsis have reemerged in the last 25 years Must be recognized & treated early & aggressively to prevent severe morbidity & mortality Be alert when postpartum women present with unstable vital signs, high fever or an unexpected toxic appearance Most report an onset within the first few days postpartum in previously healthy women with rapid progress from fever & abdominal/ pelvic pain to ICU care for refractory vasopressor dependant shock & mulitorgan failure Dr. Lovina Machado

In conclusion . Key management issues Early recognition Send labs, cultures, start broad spectrum IV antibiotics Aggressive fluid resuscitation

Early source control- surgical intervention Multidisciplinary team from the start ICU care Dr. Lovina Machado Tasks to be performed within the first 6 hours of identification of severe sepsis. Surviving Sepsis campaign Resuscitation Bundle Obtain blood cultures prior to antibiotic administration

Adminster broad spectrum antibiotic within 1 hour of severe sepsis Measure serum lactate within 6 hrs. 4 tissue hypoperfusion In the event of hypotension &/or serum lactate > 4 mmol/L, deliver an initial minimum 20 ml/kg crystalloid. Start vasopressors for hypotension not responding to initial fluid resuscitation to maintain MAP > 65 mm Hg If persisting hypotension (septic shock) &/or lacate > 4 mmol/L - Achieve CVP of 8 mm Hg - Achieve central venous O2 sat. 70% or mixed venous O2 sat 65% Dr. Lovina Machado Red flag signs/symptoms for tertiary care referral Pyrexia > 38oC Sustained tachycardia > 90 b/minute Breathlessness RR > 20/min serious Abdominal or chest pain

Diarrhoea/ vomiting Uterine or renal angle pain and tenderness Generally unwell, unduly anxious or distressed Dr. Lovina Machado Infection Control issues Isolate single room Contact precautions Waterproof dressing for breaks in skin of woman/care giver Fluid repellant surgical masks with visors during surgery/ dressing change Neonate to be given antibiotics Dr. Lovina Machado References

Stevens Dennis L. Group A Streptococcal sepsis. Current Infectious Disease Reports 2003,5:379-386 Busowski MT et al. Puerperal Group A Streptococcal infections: Case series & discussion. Case Reports in Medicine. Vol 2013/Article ID 751329. Hindawi RCOG Green top guidelines No.64A, April 2012 RCOG Green top guidelines No.64B, April 2012 Global, regional, and national levels and causes of maternal mortality during 19902013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet, Online, 2 May 2014. doi:10.1016/S0140-6736(14)60696-6 Yamada T. et al. Invasive GAS infections in pregnancy. J of Inf 2010; 60: 417-424. Dr. Lovina Machado RCOG

Dr. Lovina Machado RCOG Dr. Lovina Machado Dr. Lovina Machado

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