COMPLIANCE WITH THIS DOCUMENT IS MANDATORY

COVER SHEET NAME OF DOCUMENT Sepsis Pathway Emergency Department TYPE OF DOCUMENT Procedure DOCUMENT NUMBER ISLHD CLIN PROC 137 DATE OF PUBLICATION October 2016 RISK RATING Medium REVIEW DATE October 2018 FORMER REFERENCE(S) Nil EXECUTIVE SPONSOR or EXECUTIVE CLINICAL SPONSOR Director of Medical Services AUTHOR KEY TERMS SUMMARY Robert Marco - Inpatient Sepsis Project Manager Rob.marco@sesiahs.health.nsw.gov.au Sarah Dwyer - Senior Nurse Educator- Wollongong Hospital Sarah.Dwyer@SESIAHS.HEALTH.NSW.GOV.AU Emergency, sepsis, antibiotics, guideline, escalation, auditing This document is to act as a guideline for staff who suspect patients to have sepsis. The procedure includes the Clinical Excellence Commissions (CEC) sepsis pathway and antibiotics guidelines COMPLIANCE WITH THIS DOCUMENT IS MANDATORY Feedback about this document can be sent to ISLHDPolicies@sesiahs.health.nsw.gov.au

1. POLICY STATEMENT The Emergency Department (ED) Sepsis Pathway is based on the CEC Sepsis ED guidelines and aims to guide the recognition and management of emergency patients who are suspected of severe sepsis. Clinicians are required to refer to the Sepsis pathway when they recognise a patient s clinical condition is deteriorating. Where signs and/or symptoms of sepsis are identified the Sepsis Pathway must be followed until the AMO determines that sepsis is not the cause of deterioration. Quick administration of antibiotics and resuscitation fluids is vital in the management of the patient with sepsis. The goal is to commence antibiotic therapy within the first hour of recognition and diagnosis of sepsis. The guideline is based on the Therapeutic Guidelines: Antibiotic Version 15 and incorporates best available evidence and the principles of appropriate use of antibiotics. The selection of appropriate antimicrobial therapy in sepsis management is complex and this guideline is not intended to cover all possible scenarios. AIMS of the Sepsis Pathway Recognise sepsis early and escalate appropriately. Initiate appropriate management: Give IV antibiotics and fluids within one hour of identification. Provide appropriate follow up management to ensure sepsis is treated adequately or pathway is ceased if not required. 2. BACKGROUND Sepsis is a medical condition where the immune system goes into overdrive. This process releases chemicals into the blood to combat infection and trigger widespread inflammation. If the body is unable to control this immune response, it then overwhelms normal blood processes. This progression can lead to severe sepsis and septic shock which leads to organ dysfunction, hypotension, or hypoperfusion to one or more organs 1. Revision 0 Trim No. DT16/8628 October 2016 Page 1 of 16

3. RESPONSIBILITIES This guideline applies to all medical, nursing and allied health staff who attend to the care and treatment of hospital inpatients. 4. PROCEDURE 4.1 Procedure for Milton Hospital, Shellharbour Hospital, Shoalhaven District Hospital and Wollongong Hospital Consider Sepsis and refer to Sepsis Pathway when at triage, performing an A-G assessment or when asked to review a deteriorating patient. Sepsis pathway should be followed where: there are concerns that a patient has sepsis, there is a risk factor/s, sign or symptoms of infection (see pathway above) : Two Yellow Zone breaches or additional criteria: o Sepsis pathway model of care is to be activated on emr (FirstNet) o Obtain senior clinician review to confirm diagnosis o Commence treatment as per guidelines Any Red Zone breaches or additional criteria: o Sepsis pathway model of care is to be activated on emr (FirstNet) o Obtain immediate clinician review o Commence treatment as per guidelines 4.2 Sepsis Resuscitation Guidelines Clinicians are required to perform six key actions within 60 minutes (refer to Sepsis Resuscitation Guideline below) 1. Administer oxygen (M.O. approval if O 2 contraindicated) 2. Take blood cultures and other specimens Do not delay the administration of antibiotics or wait for the results of investigations 2. 3. IV antibiotics 4. IV fluid resuscitation 5. Measure serum lactate 6. Monitor input and urine output (Fluid Balance Chart), vital signs and reassess. Revision 0 Trim No. DT16/8628 October 2016 Page 2 of 16

Blood cultures: Take two sets of blood cultures before administering antibiotics. Obtain other clinical specimens as appropriate but do not delay administration of antibiotics or wait for results of investigations ISLHD Antibiotic Guidelines: Medical officers should follow the ISLHD Sepsis antibiotic guidelines (Appendix 5) unless otherwise indicated. Infectious disease should be contacted if there are any prescribing issues. Administration of antibiotics should be prioritized by the nurse and given as soon as possible once prescription is available, ensuring that bolus antibiotics are given prior to those requiring infusions. Before leaving the patient medical staff should ensure that: o Antibiotics are commenced. o A clear patient management plan is documented in the medical notes, with the CEC guidelines in mind. 4.3 After treatment has commenced: A sepsis data form must be completed by a clinician (a nurse in most instances) and the completed form placed in a collection tray. A detailed management plan should be written in the patient s progress notes. This will help to alert clinicians that the Sepsis Pathway was commenced and provide a management guide for their ongoing care. Sepsis Pathway sticker (NH700072) to be placed on the medication chart. If the patient is to remain in hospital, they are to be admitted to an appropriate ward. Patient status on the sepsis pathway is to be handed over to both medical and nursing staff. **If your emergency department is using the sepsis pathway patient form (NH700066), please fill this in and insert this into the patient notes before discharge from the ward** 5. DOCUMENTATION Staff are to use the appropriate sepsis pathway and medical records to document patient progress. 6. AUDIT Auditing ensures that clinical practice changes are carried out and provide a source of feedback and learning. We are currently measuring time taken to first antibiotics and IV fluid. Additional measures will be used by each facility to ascertain the effectiveness of the program Notification form data must be entered into the CEC sepsis database (http://sepsis.cec.health.nsw.gov.au/). Revision 0 Trim No. DT16/8628 October 2016 Page 3 of 16

7. REFERENCES Internal: ISLHD CLIN PD 86 Sepsis Management ISLHD CLIN PROC 136 Sepsis Pathway - Inpatient ISLHD CLIN PROC 95 - Transfer to Higher Level Care ISLHD CLIN PD 52- Between the Flags (BTF) - Patient with Acute Condition for Escalation (PACE) - Management of Clinical Deterioration: ISLHD CLIN PD 54 - Emergency Department Admission Process External: 1. Chang, H, Lynm, C & Glass, R, 2012, Sepsis, Journal of the American Medical Association, vol. 304, no. 16, pp.1813. Available from: http://jama.jamanetwork.com/data/journals/jama/4534/jpg1027_1856_1856.pdf 2. Australian Commission on Safety and Quality in Health Care. Antimicrobial Stewardship Clinical Care Standard. Sydney: ACSQHC, 2014 3. Antibiotic Expert Group. Therapeutic Guidelines: Antibiotic Version 15 Melbourne: Therapeutic Guidelines Limited; 2014 Accesses through etg complete (via CIAP) 4. Burridge N (ed). Australian Injectable Drugs Handbook (5 th Ed). The society of Hospital Pharmacists Australia; 2011 8. REVISION AND APPROVAL HISTORY Date Revision No. Author and Approval October 2016 0 Robert Marco - Inpatient Sepsis/VTE Project Manager Draft for comment February 2016 Endorsed ISLHD Drug & Therapeutics June 2016 IV Antibiotic Guideline Update and Pathway Updates August 2016 Distributed to Divisional Co-directors August 2016 Approved Clinical Governance Council October 2016 Revision 0 Trim No. DT16/8628 October 2016 Page 4 of 16

Sepsis pathways should not be printed from this procedure. For the most up to date pathway please check via the following link: http://cec.health.nsw.gov.au/patient-safety-programs/adult-patient-safety/sepsis-kills/sepsis-tools Appendix 1 Adult Sepsis Pathway Revision 0 Trim No. DT16/8628 October 2016 Page 5 of 16

Appendix 2 Paediatric Sepsis Pathway Revision 0 Trim No. DT16/8628 October 2016 Page 6 of 16

Appendix 3 Maternal Sepsis Pathway Revision 0 Trim No. DT16/8628 October 2016 Page 7 of 16

Appendix 4 Newborn Sepsis Pathway Revision 0 Trim No. DT16/8628 October 2016 Page 8 of 16

APPENDIX 5 Antibiotic Prescribing Guide ADULT SEVERE SEPSIS INTRAVENOUS ANTIBIOTIC GUIDELINE (Review after 24 hours) Sepsis = Infection + SIRS (Temp <36/ >38, RR > 24, HR >90, WCC < 4/ > 12) SEVERE SEPSIS= Sepsis + Deteriorating Organ Function ACTIONS (For ALL Sepsis) 1. Lactate 2. Blood cultures 3. IV antibiotics 4. Fluid Resus Follow the sepsis pathway in conjunction with your local BTF RED & YELLOW Zone escalation procedures. Source not covered below, recent travel, or HIGH risk of multi-resistant organisms? Antimicrobial stewardship (AMS) hotlines: 3838 (TWH, SHH, SDMH, CDH); #2828 (BDH, MUH); 3535 (PKH) For patients already on antibiotics: Contact AMO or ID (AMS hotline or switchboard) for advice. For sepsis in renal patients (e.g. PD peritonitis), contact the renal team via switchboard. Doses below are for SEVERE sepsis and SEPTIC SHOCK. For non-severe sepsis doses, refer to the Therapeutic Guidelines Likely source of SEVERE sepsis Preferred regimen Penicillin allergy (NOT anaphylaxis) Penicillin/cephalosporin allergy (anaphylaxis) Severe sepsis of unknown origin OR intravascular device source OR surgical site source Flucloxacillin 2g 6-hourly gentamicin 7mg/kg IDEAL body weight ACTUAL body weight If gentamicin contraindicated, use piperacillin/tazobactam 4.5g 6-hourly instead of flucloxacillin and gentamicin Cefazolin 2g 6-hourly gentamicin 7mg/kg IDEAL body weight ACTUAL body weight If gentamicin contraindicated, use meropenem 2g 8-hourly instead of cefazolin and gentamicin Gentamicin 7mg/kg IDEAL body weight ACTUAL body weight If gentamicin contraindicated, call AMS/ID for advice Severe sepsis due to community-acquired pneumonia Ceftriaxone 1g 12-hourly azithromycin 500mg daily Ceftriaxone 1g 12-hourly azithromycin 500mg daily Moxifloxacin 400mg daily Consider vancomycin if Staphylococcal pneumonia suspected (recent flu, cavitation, rapid progression) Severe sepsis due to hospital acquired pneumonia - low risk of MRO (no recent intubation) Ceftriaxone 1g 12-hourly metronidazole 500mg 12-hourly Ceftriaxone 1g 12-hourly metronidazole 500mg 12-hourly Moxifloxacin 400mg daily Severe sepsis due to hospital acquired pneumonia - high risk of MRO (recent intubation, prior infection, Piperacillin-tazobactam 4.5g 6-hourly If risk of MRSA, ADD Cefepime 2g 8-hourly If risk of MRSA, ADD Call AMS/ID for advice Revision 0 Trim No. DT16/8628 October 2016 Page 9 of 16

colonised) Severe sepsis with skin source Flucloxacillin 2g 6-hourly Cefazolin 2g 8-hourly Vancomycin 25-30mg/kg ACTUAL body weight Severe sepsis with urinary source (If recent TRUS biopsy, call AMS/ID for advice) Gentamicin 7mg/kg IDEAL bodyweight ^ampicillin 2g 6-hourly If gentamicin contraindicated, use ceftriaxone 1g 12-hourly Gentamicin 7mg/kg IDEAL bodyweight If gentamicin contraindicated, use ceftriaxone 1g 12-hourly Gentamicin 7mg/kg IDEAL bodyweight If gentamicin contraindicated, call AMS/ID for advice Biliary or gastrointestinal source Gentamicin 7mg/kg IDEAL bodyweight ^ampicillin 2g 6-hourly metronidazole 500mg 12-hourly Ceftriaxone 1g 12-hourly metronidazole 500mg 12-hourly Call AMS/ID for advice If gentamicin contraindicated, use piperacillin/tazobactam 4.5g 6-hourly Peri- or post-partum severe sepsis (See maternal sepsis pathway for ongoing therapy) Piperacillin-tazobactam 4.5g 6-hourly If patient meets toxic shock criteria, ADD clindamycin 600mg 8-hourly Ceftriaxone 1g 12-hourly metronidazole 500mg 12-hourly If patient meets toxic shock criteria, ADD clindamycin 600mg 8-hourly Call AMS/ID for advice Intravenous dexamethasone may be required before antibiotics refer to Therapeutic Guidelines Severe sepsis with neurological source (organism or susceptibility unknown) Ceftriaxone 2g 12-hourly If risk of listeria ADD benzylpenicillin 2.4g 4-hourly Moxifloxacin 400mg daily If risk of listeria, call AMS/ID for advice. Moxifloxacin 400mg daily If risk of listeria, call AMS/ID for advice. If post-neurosurgical, give meropenem 2g 8-hourly ACTUAL body weight Revision 0 Trim No. DT16/8628 October 2016 Page 10 of 16

Severe sepsis due to diabetic foot infection Piperacillin-tazobactam 4.5g 6-hourly Ciprofloxacin 400mg 12-hourly clindamycin 600mg 8-hourly Ciprofloxacin 400mg 12-hourly clindamycin 600mg 8-hourly Febrile neutropenia (refer to local protocol) Piperacillin-tazobactam 4.5g 6-hourly AND refer to local protocol Cefepime 2g 8-hourly AND refer to local protocol Call AMS/ID for advice Once prescribed, enter antibiotic approval/s in Guidance MS. ^If ampicillin unavailable use benzylpenicillin 2.4 grams 6-hourly. Revision 0 Trim No. DT16/8628 October 2016 Page 11 of 16

TABLE 2: ANTIBIOTIC ADMINISTRATION Reconstitute antibiotics with sterile water for injection (WFI) unless stated otherwise. If further dilution is required for IV injection or infusion, use sterile sodium chloride 0.9% or sterile glucose 5% unless stated otherwise. Where possible use separate dedicated lines for resuscitation fluid and for medications. When injecting antibiotics directly into an IV injection port which has resuscitation fluid running: - clamp the infusion fluid line and flush with 20 ml sterile sodium chloride 0.9% solution - administer antibiotic over the required time - flush the line with 20 ml sterile sodium chloride 0.9% solution and recommence resuscitation fluid. For detailed information refer to the SHPA injectable handbook via CIAP: http://aidh.hcn.com.au/index.php/section-one/drug-monographs-a-z?view=alphacontent Antibiotic Presentation (adult) Recon fluid /volume Final volume Minimum admin time Notes Ampicillin Vial 1g 10 ml NS 10-20 ml 3-5 min Penicillin class antibiotic Azithromycin Vial 500mg 4.8mL WFI 250mL 60 min 250mL sodium chloride 0.9% Benzylpenicillin Vial 1.2g 3.2mL WFI 10mL 5-10 min Penicillin class antibiotic. Do no inject faster than 300mg/min Cefepime Vial 1 g 10 ml NS 10 ml 3-5 min Cephalosporin class antibiotic Doses 2 g infused over 20 min Ceftriaxone Vial 1 g 10 ml WFI 10 ml 2 4 min Cephalosporin antibiotic incompatible with calcium containing solutions, flush before and after with sodium chloride 0.9% Cefazolin Vial 1 g 10 ml WFI 10 ml 3 5 min Cephalosporin class antibiotic Ciprofloxacin Infusion bag 400mg/200mL Flucloxacillin Vial 1 g 5 ml WFI 10 ml 3-5 min Gentamicin Ampoule 80 mg/2 ml N/A 200mL 60 min May induce seizures in epileptics (1 g) N/A 10-20 ml 240mg 50 ml or 100 ml 3 5 min > 240mg 30 min Penicillin class antibiotic Repeated doses of 2 g via a peripheral line should be further diluted and infused over 30 min Refer to notes for Gentamicin Clindamycin Amp 600mg N/A 50mL 20 min Do not give as bolus injection Metronidazole Infusion bag 500mg/100mL N/A 100mL 20 min Revision 0 Trim No. DT16/8628 October 2016 Page 12 of 16

Meropenem 1g vial 10 ml WFI 50-250 ml 30-60 min Moxifloxacin Piperacillintazobactam Infusion bag 400 mg/ 250 ml N/A 250mL 60 min May prolong QT interval and lead to ventricular arrhythmias. May induce seizures in epileptics Vial 4 g/0.5 g 20 ml WFI 50 ml 30 min Penicillin class antibiotic Vancomycin Vial 500 mg 10 ml WFI **5mg/mL peripheral Max 10 mg/min Infusion related effects are common, decrease infusion rate and monitor closely Revision 0 Trim No. DT16/8628 October 2016 Page 13 of 16

Sepsis = Infection + SIRS SEVERE SEPSIS= Sepsis + Deteriorating Organ Function ACTIONS: 1. Follow PAEDIATRIC Sepsis Pathway (Remember lactate/blood cultures/fluid resus/antibiotics) 2. Use local BTF RED & YELLOW Zone escalation procedures. 3. Contact PAEDIATRICIAN through switchboard for advice. PAEDIATRIC ANTIBIOTIC PRESCRIBING GUIDE FOR SEVERE SEPSIS (Review after 24 hours) Doses are for SEVERE sepsis and septic shock. For non-severe sepsis doses, refer to local guidelines. This guideline relates to intravenous and intraosseous administration. For intramuscular refer to full CEC guideline. Likely Source Preferred Regimen Penicillin Allergy (NOT immediate hypersensitivity) Penicillin/Cephalosporin Allergy (Immediate/anaphylaxis) SEVERE sepsis due to community-acquired pneumonia (CAP) OR hospital acquired pneumonia (HAP) + low risk of MRO* (eg. no recent intubation) Cefotaxime 50mg/kg ACTUAL bodyweight up to Cefotaxime 50mg/kg ACTUAL bodyweight up to Ciprofloxacin 10mg/kg up to 400mg, 8-hourly CAP: if atypical pneumonia suspected, ADD azithromycin 10mg/kg up to 500mg, IV daily SEVERE sepsis due to hospital acquired pneumonia (HAP) + high risk of MRO* (eg. recent intubation, prior infection, colonised) Piperacillin-tazobactam 100+12.5mg/kg up to 4 +0.5g, 6- hourly ACTUAL bodyweight up to Cefepime 50mg/kg up to 2g, 8-hourly ACTUAL bodyweight up to Ciprofloxacin 10mg/kg up to 400mg, 8-hourly SEVERE sepsis due to urinary tract source For known or suspected ESBLproducing organisms, see full CEC guideline Gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) ^ampicillin 50mg/kg Gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) Gentamicin 7.5mg/kg IDEAL bodyweight (1mth- 12yrs max dose 320mg, 12-16yrs max dose 560mg) SEVERE sepsis due to intra-abdominal source Gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) ^ampicillin 50mg/kg Gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) Gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) Revision 0 Trim No. DT16/8628 October 2016 Page 14 of 16

metronidazole 12.5mg/kg up to 500mg, 12-hourly metronidazole 12.5mg/kg up to 500mg, 12-hourly metronidazole 12.5mg/kg up to 500mg, 12-hourly Likely Source Preferred Regimen Penicillin Allergy (NOT immediate hypersensitivity) Penicillin/Cephalosporin Allergy (Immediate/anaphylaxis) SEVERE sepsis due to skin infection For water-related infections, see full CEC guideline) Flucloxacillin 50mg/kg ACTUAL bodyweight up to Cefazolin 50mg/kg up to 2 g, 8-hourly ACTUAL bodyweight up to Vancomycin 15mg/kg SEVERE sepsis due to intravascular device (eg. venous access device, permanent pacemaker or defib, endovascular prostheses such as stents) Flucloxacillin 50mg/kg gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) Cefazolin 50mg/kg up to 2 g, 8-hourly gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) Gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) SEVERE sepsis due to meningitis/ encephalitis Dexamethasone may be given before antibiotics: 0.15mg/kg up to 10mg, then 6-hourly for 4 days (If serious concern of encephalitis, do not give dexamethasone.) Cefotaxime 50mg/kg Cefotaxime 50mg/kg Vancomycin 15mg/kg ciprofloxacin 10mg/kg up to 400mg, 8-hourly If risk of Listeria, ADD ampicillin 50mg/kg If risk of Listeria, seek advice. If risk of Listeria, seek advice. If signs of encephalitis, ADD: 1mth - 5 yrs aciclovir 20mg/kg, 8-hourly; 5 years 15mg/kg, 8-hourly Revision 0 Trim No. DT16/8628 October 2016 Page 15 of 16

SEVERE sepsis due to unknown source (community OR healthcare associated) Cefotaxime 50mg/kg gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) ACTUAL bodyweight up to Cefotaxime 50mg/kg gentamicin 7.5mg/kg IDEAL bodyweight (1mth-12yrs max dose 320mg, 12-16yrs max dose 560mg) ACTUAL bodyweight up to Ciprofloxacin 10mg/kg up to 400mg, 8-hourly Fever OR Suspected Sepsis in oncology/ transplant patients REQUIRES IMMEDIATE REVIEW & TREATMENT: See NSW Health Guideline Initial management of fever/suspected sepsis in oncology/transplant patients ^If ampicillin unavailable use benzylpenicillin 60mg/kg up to 2.4g, 6-hourly. Ceftriaxone 50mg/kg up to 2g, 12-hourly, can be used in place of cefotaxime. Once prescribed, enter antibiotic approvals in Guidance MS. Revision 0 Trim No. DT16/8628 October 2016 Page 16 of 16