SOMANZ Guidelines for the investigation and management of ... · women with sepsis in pregnancy and post-partum •All encompassing multidisciplinary guidance in one location –a

SOMANZ Guidelines for the investigation and management of

sepsis in pregnancy 2017Bowyer L, Robinson H, Barrett H, Crozier T, Giles M, Idel I, Lowe S,

Lust K, Marnoch C, Morton M, Said J, Wong M, Makris A

http://onlinelibrary.wiley.com/doi/10.1111/ajo.12646/pdf

http://onlinelibrary.wiley.com/doi/10.1111/ajo.12646/pdf

Why Write Guidelines?

• Evidence based guidance for the investigation and care of women with sepsis in pregnancy and post-partum

• All encompassing multidisciplinary guidance in one location – a ‘one stop shop’ for investigation and management

• Maternal mortality rate (sepsis) has increased from 0.6/100,000 to 0.8/100,000 (2003-5 to 2008-15)

• Sepsis accounted for 11.4% of all maternal deaths

• Facilitate research in the field with a uniform diagnosis

Other Guidelines

• Sepsis Kills

• NICE

• Surviving Sepsis

Methods

• Recommendations made by a multidisciplinary team

– obstetric, physician, microbiology, anesthetics and intensive care

– Australia and New Zealand represented

• Current literature was reviewed

• Evidence for the guideline recommendations was graded using the GRADE system

• Financial support for administration from SOMANZ

Definition of sepsis

• Sepsis- life threatening organ dysfunction caused by a deregulated host response to infection

• Early detection and management are pivotal to ensure best outcomes for mother and baby

• Septic shock- subset of sepsis where profound circulatory , cellular and metabolic abnormalities substantially increase mortality

Definition of sepsis

• Sequential (sepsis-related) Organ Failure Assessment (SOFA) score is useful in identifying patients with a suspected infection who are likely to need ICU or die

• Scoring of many parameters including the use of laboratory results

• q(quick) SOFA score can be used at the bedside to identify patients using clinical information only

Flowchart

Flowchart – for assessment and management of sepsis

ALWAYS USE MATERNITY

OBS CHART

Orange = action

Blue = steps to perform

Green = comments

SOMANZ Sepsis Checklist

SOMANZ Definition of Sepsis

• Data based on general population with paucity of data in the obstetric population

• Important to modify the criteria for the definition of sepsis for the obstetric population

• qSOFA obstetric modified qSOFA (omqSOFA) score

• Score of >2 – predicts in-hospital mortality






Parameter omqSOFA Score

0 1

Systolic Blood Pressure (SBP)

Respiratory Rate

Altered mentation







0 1

Systolic Blood Pressure (SBP) >90mmHg <90mmHg

Respiratory Rate

Altered mentation







0 1


Respiratory Rate Less than 25 breaths/min 25 breath/min or greater

Altered mentation







0 1



Altered mentation Alert Not alert


• Respiratory rate doesn’t change in pregnancy –aligned with cut off on the maternity observation charts (evidence=22resp/min)

• SBP – reduced in pregnancy- 15% of pregnant women have usual BP below cut off -> so reduced to 90mmHg (evidence= 100mmHg)


0 1



Altered mentation Alert Not alert


• If sepsis suspected with the omqSOFA, then assessment for end organ dysfunction should be undertaken

• Use SOFA score omSOFA to account for physiology of pregnancy

• Sepsis is defined if the score increases by >2

• Associated with a 10% mortality

– Not yet validated in obstetric population


System Parameter omSOFA Score0 1 2

RespirationPaO2/FIO2

>400 300 - <400 <300

CoagulationPlatelets,x106/L

>150 100-150 <100

LiverBilirubin (µmol/L)

<20 20-32 >32

CardiovascularMean Arterial Pressure

(mm Hg) MAP>70 MAP<70

Vasopressors required

Central Nervous SystemAlert

Rousable by voice

Rousable by pain

RenalCreatinine (µmol/L)

<90 90-120 >120




>400 300 - <400 <300


>150 100-150 <100


<20 20-32 >32





Rousable by voice

Rousable by pain


<90 90-120 >120

To demonstrate end organ dysfunction >2 is

needed.

So categories 3 and 4 condensed




>400 300 - <400 <300


>150 100-150 <100


<20 20-32 >32





Rousable by voice

Rousable by pain


<90 90-120 >120

Adjustment in the serum

creatinine cut off for each

category that are pregnancy

appropriate




>400 300 - <400 <300


>150 100-150 <100


<20 20-32 >32





Rousable by voice

Rousable by pain


<90 90-120 >120

GCS not routinely

assessed on maternity

wards. Any score other than 0 should trigger GCS to be performed

SOMANZ Definition of Septic Shock

• No alteration for obstetric patients

• Clinical criteria (not validated for obstetric population):

– Hypotension requiring vasopressor therapy to maintain MAP 65mmHg

and

– Serum lactate greater than 2mmol/L

………After adequate fluid resuscitation

Fever in Pregnancy

• Fever in the first trimester has been associated with congenital abnormalities– Neural tube defects OR 2.9 (2.2-3.8)

– Oral clefts OR 1.9 (1.4-2.8)

– Congenital heart defects OR 1.5 (1.4-1.7)

• High dose aspirin and non-steroidal anti-inflammatory agents used with caution in 3rd

trimester- risk of premature closure of the ductusarteriosus

Etiology of Sepsis

• Sepsis-related maternal death is most commonly caused by GAS

• E Coli is the commonest bacterial infectionInfection Pathogens

Bacterial - common Group A- beta-hemolytic Streptococcus (GAS) pyogenes

Escherichia Coli

Group B Streptococcus

Klebsiella pneumoniae

Staphylococcus aureus

Streptococcus pneumonia

Proteus mirabilus

Anaerobic organisms

Bacterial – less common Haemophilus influenza

Listeria monocytogenes

Clostridium species

MycobacteriumTuberculosis

Viral Influenza

Varicella zoster virus

Herpes Simplex virus

Cytomegalovirus

Etiology of Sepsis

Condition Common Maternal Clinical FeaturesAcute pulmonary embolism Hypotension, tachypnoea, tachycardia, low grade fever

Amniotic fluid embolism Hypotension, tachycardia, haemorrhageAcute pancreatitis Fever, nausea, vomiting, abdominal painAcute Fatty Liver of Pregnancy Fatigue, nausea, vomiting, abdominal pain, jaundice, impaired level of

consciousnessAdverse drug reactions, drug fever Hypotension, relative bradycardia, fever, rash, angio-oedema

Acute liver failure-drug related, viral Jaundice, nausea, vomiting, abdominal pain impaired level of consciousness

Acute adrenal insufficiency Weakness, fatigue, nausea, anorexia, weight loss, hypotension, fever

Acute pituitary insufficiency Failure to lactate, hypotension, relative bradycardia, polyuria, polydipsia

Autoimmune conditions Low grade fever, rash (eg.malar rash), arthritis, dry eyes or mouth, mouth ulcers, diagnostic serology

Concealed haemorrhage including ectopic pregnancy

Hypotension, tachycardia, low grade fever

Disseminated Malignancy Low grade fever, weight lossPelvic Thrombosis Pelvic pain, fever, Transfusion reactions High fever, rigors, dysrhythmia, tachypnoea, hypotension, rash, bleeding,

haematuria

• Non- infective causes should be considered

Investigations in sepsis

• Blood cultures ideally should be obtained BEFORE antibiotics but SHOULD NOT DELAY therapy

• Pregnancy specific reference ranges should be used for interpretation

• Imaging should not be withheld due to pregnancy and breastfeeding

• Arterial (or venous) blood gas for a serum lactate should be performedindicate tissue hypoperfusion

Investigations in sepsisInvestigation Obstetric reference range (if relevant)

Blood cultures– At least 2 sets, prior to antibiotic commencement as long as there is no delay. - Obtain samples from different sites - Cultures should also be obtained from IV access devices Other Cultures– Obtain cultures of additional sites as clinically indicated and as soon as possible

Eg. urine MCS, wound swab - episiotomy, caesarean, placental swabs, amniotic fluid, sputum culture, naso-pharyngeal aspirate/swab, cerebrospinal fluid, vaginal swabs, stool culture

Arterial blood gases –detect acidosis, hypoxaemia, lactate as below

PaO2: 1st trimester: 93-100 mmHg, 2nd trimester: 90-98mmHg, 3rd trimester: 92-107mmHgPaCO2: 25-33mmHg, Arterial pH: 7.4-7.47, HCO3 16-22mmol/L

Lactate- elevated levels in sepsis relate to tissue hypoperfusion and are associated with

an increased sepsis mortality risk

0.6-1.8 mmol/L

Full blood count White cell count :6-17 X 109 /L (may increase to 9-15 X 109/L immediately post-delivery). Steroids also increase white cell countPlatelets – lower limit of normal 150-420 x109/L

Coagulation studies No change

Creatinine urea and electrolytes- Measure at baseline and until the patient improves, elevated creatinine is a sign

of severe sepsis

Creatinine Varies with Gestation (reference ranges) :1st

trimester:35-62µmol/L, 2nd trimester: 35-71µmol/L, 3rd

trimester: 35-80µmol/LLiver function tests- Baseline test, may be elevated if sepsis source is from hepatic or perihepatic

infections- May be elevated due to septic shock affecting hepatic blood flow

AST 3-33 U/L, ALT 2-33 U/L, Alkaline Phosphatase 17-229 U/L GGT 2-26 U/L, Total Bilirubin 1.7-19 µmol/L

CXR

Fetal Assessment – CTG and /or fetal ultrasound A non-reassuring CTG suggests inadequate uteroplacental perfusion and may reflect maternal organ hypoperfusion or intrauterine sepsis

Treatment of sepsis

• Treatment should be immediate and antibiotics should be administered within the first hour -> every hour delay increases maternal mortality by 8%

• Empiric treatment

– Fluid resuscitation

• 2L crystalloid and if not better-> escalate

– Correction of hypoxia

– Antimicrobials

– Thromboprophylaxis

Treatment of sepsis

• Source control may be important

• Delivery of fetus may be required

• In treating immunosuppressed women a physician should be involved soon:– Solid organ transplant, malignancy or autoimmune disease

– Chronic infection/conditions eg HIV and diabetes

• Treatment based on sepsis source- unknown or known source (latter detailed in full guidelines on the SOMANZ website)

Treatment of Sepsis

Australian and New Zealand Antibiotic Regimen

Alternative for penicillin hypersensitivity

Community-acquired sepsis (source not apparent)+

Aus : amoxicillin/ampicillin 2g IV 6-hourly PLUS gentamicin 4-7mg/kg (first dose) IV* PLUS metronidazole 500mg IV 12-hourlyNZ: cefuroxime 1.5g IV 8-hourly PLUS gentamicin 4-7mg/kg (first dose) IV * PLUS metronidazole 500mg IV 12-hourly

At risk of MRSA sepsis (based on previous swabs/cultures and local epidemiology): ADD vancomycin 25-30mg/kg (loading dose) IV *

At risk of Group A Streptococcal (GAS) sepsis: ADD clindamycin 600mg IV 8-hourly, PLUS consider normal immunoglobulin 1-2g/kg IV, for up to 2 doses during the first 72 hours

Clindamycin 600mg IV 8-hourly PLUS gentamicin 4-7mg/kg (first dose) IV (severe hypersensitivity)

Cefazolin 2g IV 6-hourly PLUS gentamicin 4-7mg/kg (first dose) IV* PLUS metronidazole 500mg IV 12-hourly (mild-moderate hypersensitivity)

Hospital-acquired sepsis (source not apparent)

Aus: piperacillin 4 g + tazobactam 0.5g IV 8-hourly AND consider gentamicin 4-7mg/kg (first dose) IV* (if local epidemiology suggests Gram negative aminoglycoside susceptibility)NZ: cefuroxime 1.5g IV 8-hourly PLUS gentamicin 4-7mg/kg (first dose) IV * PLUS metronidazole 500mg IV 12-hourly

At risk of MRSA sepsis (based on previous swabs/cultures and local epidemiology or if line sepsis) ADD vancomycin 25-30mg/kg (loading dose) IV *

At risk of multidrug-resistant Gram-negative organisms: use as a SINGLE AGENT meropenem 1g IV 8-houly

At risk of Group A Streptococcal (GAS) sepsis: ADD clindamycin 600mg IV 8-hourly PLUS consider normal immunoglobulin 1-2g/kg IV, for up to 2 doses during the first 72 hours

Severe: ciprofloxacin 400mg IV 8-hourly PLUS vancomycin 25-30mg/kg IV*

Consider influenzaOseltamivir 75mg BD or Zanamivir 2 inhalations (each 5mg) twice daily for 5 days

* Use local protocols for gentamicin and vancomycin dosing and monitoring. Once daily dosing of gentamicin in pregnancy and postpartum can be used and in pregnancy results in levels below the toxicity threshold for more hours per day than in 8-hourly dosing. + NZ regime does not cover listeria – if suspected use a penicillin as per Australian regime. #NZ has increasing Group B strep resistance to clindamycin and macrolides – if penicillin hypersensitivity seek expert advice for best agent. IV- intravenous, MRSA- methicillin resistant staphylococcus aureas, mg/kg- milligrams per kilogram, BD- twice daily, mg- milligrams.

• Unknown source guidance for initial therapy

Timing and mode of delivery

• 3 important factors to be considered

– Presence of intrauterine sepsis

• Delivery should always be considered

• Consider steroids but balance against urgency

– Maternal response to resuscitation efforts

• Fetal wellbeing to be monitored

– Gestation of the pregnancy and fetal status

Anesthetic considerations in managing maternal sepsis

• Initial stabilisation

• Patient transfer– Hand over and level of care expected on transfers

• Anaesthesia– Spinal anaesthesia

• Not performed in patients untreated systemic infection• Antibiotics initiated BEFORE dural puncture• Safe in patients at low risk for bacteraemia after dural

puncture

• General anesthesia in women with sepsis

Intensive Care Issues

• Assist with resuscitation

• Indications for ICU admission will vary based on local resources

• Evidence of organ dysfunction ->indication for ICU involvement

Indications for ICU involvement Signs or observationsCardiorespiratory compromise hypotension, circulatory instability, worsening tachypnoea,

worsening hypoxia, increasing supplemental oxygenrequirements

Evidence of organ dysfunction altered mental status, oliguria, worsening urea and creatinine,other e.g. coagulation failure, cytopenias, worsening hepaticdysfunction

Other evidence of hypoperfusion metabolic/lactic acidosis, signs of poor tissue perfusion, signs ofinadequate placental perfusion

Other serious clinical concern

Breastfeeding

• Breastfeeding

– Small amount of antibiotic is present in breast milk

– Infants should be monitored for side effects egdiarrhoea, skin rash

– More specific details: https://tgldcdp.tg.org.au.acs.hcn.com.au/quicklinks?type=Pregnancyandbreastfeeding

Post partum

• These ‘pregnancy specific’ guidelines recommended for the first week

• Given a woman’s physiology slowly returns to non-gravid state, beyond the first week- the usual sepsis guidelines should be followed

Guideline Implementation

• Implementation

– Publishing

– Educating -> discussing/ disseminating

• Audit of implementation

– Audit points for local/centre based implementation assessment

Guideline Implementation

Guideline to be assessed Measure of implementation

Assessment of sepsis What is the Incidence of sepsis as a proportion of all births ?

What proportion of patients diagnosed with sepsis where screened using qSOFA?

Fever in pregnancy What proportion of pregnant women presenting with fever were administered anti-pyretics?

Aetiology of sepsis What is the prevalence of the different microorganisms causing sepsis?

What proportion of all infections are caused by GAS?

Investigations in sepsis What proportion of women with sepsis had blood cultures taken?.............

Thank you

Michelle Giles

Sandra Lowe

Lucy Bowyer

Mark MortonJoanne Said

Karin Lust

Helen Robinson

Catherine Marnoch

Irena Idel

Timothy Crozier

Helen Barrett

Angela Makris

Maggie Wong

Documents

SOMANZ Guidelines for the investigation and management of ... · women with sepsis in pregnancy and post-partum •All encompassing multidisciplinary guidance in one location –a