SEPSIS KILLS program Paediatric Inpatients

Learning Objectives Recognise that sepsis is a medical emergency Identify the risk factors, signs and symptoms Outline the escalation of the septic patient Define the initial A-G management actions Discuss the requirements for 48 hour sepsis management including referral Apply the pathway to a case study

Paediatric Sepsis Many paediatric sepsis related deaths are preventable Sepsis is one of the leading causes of death in children Mortality rates are as high as 10% Mortality rates are as high as 10% (data from the US). Some recent articles have suggested this figure to be 8-9%. The majority of these are preventable.

Systemic Inflammatory Response Syndrome Sepsis continuum Severe Sepsis Infection Systemic Inflammatory Response Syndrome Sepsis Septic Shock Sepsis is a whole of body syndrome Sepsis is infection plus SIRS (systemic inflammatory response syndrome) Severe sepsis is sepsis + organ dysfunction, hypotension and/or hypoperfusion Signs of hypoperfusion include lactic acidosis, oliguria, or an acute alteration in mental status Septic shock is severe sepsis + a BP unresponsive to fluid bolus Note the increasing mortality as you move along the continuum. Keep in mind a patient can present at any stage of the continuum. Increasing Mortality

Sepsis recognition & management …..is there a problem in your facility? This is a problem in our LHD/ hospital. Provide a de-identified example of a late recognition of sepsis in your hospital/ LHD.

Sepsis program linkages with other paediatric resources The Inpatient SEPSIS KILLS program is linked to the NSW Between the Flags system. These links have been strongly established to ensure an integrated and comprehensive approach:

Surviving Sepsis Campaign Infuse 20ml/kg 0.9% sodium chloride bolus over no more than 10 minutes Rapid administration of antibiotic therapy BP is not a reliable target. Treatment should be titrated to clinical signs of adequate cardiac output -Heart rate in normal range -Improved capillary refill time -Improved LOC -Urine output ≥ 1ml/kg/hr Early intubation recommended The Surviving Sepsis Campaign is a global initiative to improve sepsis recognition and treatment. There are a number of Surviving Sepsis Campaign recommendations which have been incorporated into the CEC SEPSIS KILLS program. In children BP is not a reliable end point for assessing the adequacy of treatment. We know that children are able to maintain their BP despite significant compromise. Children can prevent reduction in their BP by vasoconstriction and increasing their HR. Children cannot change their stroke volume so they increase their heart rate to improve cardiac output. Tachycardia is a valuable indicator in identifying sepsis. Treatment should be titrated to clinical signs of adequate cardiac output.

Pitfalls……. Sepsis is a difficult diagnosis to make Often under appreciate the mortality Do not see sepsis as time critical The challenge is selecting the septic children from the other sick children. It is often a difficult diagnosis and the pathway is not an exact science. We do know however, that the risks of missing these children early on can be catastrophic. An important component of the pathway working involves a senior clinician review to determine if the child could be septic and therefore to continue using the pathway. Clinicians under-appreciate the mortality and don’t see sepsis as time critical like some of the other well known presentations: Trauma-the golden hour, AMI time is muscle, stroke time is brain, We need to change our way of thinking - sepsis kills -time is life

You can make a difference for patients in this hospital Sepsis is a medical emergency You can make a difference for patients in this hospital Sepsis is as important as other medical emergencies. Early treatment with antibiotics and fluid resuscitation are life saving. Need to think of sepsis as a time critical illness just like trauma, AMI and acute stroke.......TIME IS LIFE

Sepsis Pathway aims to: Provide clear guidelines regarding sepsis notification escalation and initial management Early involvement of senior clinicians in diagnosis and management of sepsis Prompt administration of resuscitation fluids Prompt administration of antibiotics (goal is within one hour of recognition) Timely referral, clinical supervision and escalation

Broken down into recognise and respond and escalate 1st page The inpatient sepsis pathway should be reviewed and considered for all activations of the Clinical Emergency Response System The sepsis pathway provides clear guidelines for sepsis recognition, notification, escalation and initial management. ‘Between the Flags’ criteria are used instead of classic SIRS (systemic inflammatory response syndrome) as the pathway needs to integrate with the Between the Flags system and the Recognition and Management of Patients who are Clinically Deteriorating Policy. Recognition of sepsis risk factors, signs and symptoms may be facilitated via any of the following systems:   Observations in the red or yellow zone on a Standard Adult General Observation Chart (SAGO)  or Standard Paediatric Observation Chart (SPOC) A patient may be identified as being at risk of or having sepsis during a ward round. REACH (Recognise, Engage, Act, Call, Help is on its way) patient and family activated Rapid Response program.   Important note: The sepsis pathway is not intended for patients at risk of febrile neutropenia. Patients with a recent haematological or oncology diagnosis should be managed using relevant local guidelines for febrile neutropenia.

Resuscitate and refer on the back page.

During a Clinical Review, Rapid Response or during a routine ward round or patient review Ask – First Click - Does your patient have a known or suspected infection? If the answer is NO – don’t use the pathway If Yes – Click 2 - assess if they have any risk factors or signs or symptoms Remember “clinician concern” can be a valuable risk factor when your patient has no other obvious risk factors signs or symptoms when you still may have concerns of sepsis. This allows you to keep the patient on the pathway. If sepsis is not a concern of the clinician and there is no risk factors, signs or symptoms are present Stop using the pathway and assess for other causes of deterioration – but continue to monitor for signs of sepsis They then must have at least one risk factor sign or symptom PLUS….

Either a Red Zone criteria = Rapid Response or 2 or more Yellow Zone criteria Note: 3 simultaneous Yellow Zone criteria = Rapid Response If your are reviewing the patient following a Clinical Review call or Rapid Response call, review the observation (repeat if required) and identify If the patient has any Red Zone observation or additional criteria or serious clinician concern? Yes = ENSURE SENIOR CLINICAN REVIEW TO CONFIRM THE LIKLIHOOD OF SEPSIS. Follow “yes“ arrow to next red box – “This patient has severe sepsis or septic shock until proven otherwise.” Call for a Rapid Response unless already made. A decision will be made as to whether the patient is to continue on the pathway by the senior clinician. There must be a clear alternative diagnosis and management plan for the patient who is “taken off” the pathway and this must be clearly documented in the patient's notes. Follow “yes” red arrow -Commence Sepsis Resuscitation Guideline – ensure Attending Medical Officer (AMO) is aware this child has sepsis. Your patient has no Red Zone observation or additional criteria – Do they have two or more Yellow Zone observations or additional criteria or clinician concern? If “yes” follow yellow arrow to next yellow box. Obtain a senior clinician review within 30 minutes. Consider bloods gas and gather more information - these values for lactate, base excess and procalcitonin are significant for sepsis. If senior clinician considers that the patient is septic…. Follow red “yes” arrow to bottom red box and “Commence Sepsis Resuscitation Guideline – ensure AMO is aware.” If they do not have either 2 or more Yellow Zone criteria OR after obtaining more information (with blood test etc.) the senior clinician doesn’t believe the child is septic then follow the blue arrow into the blue box at the bottom of the 1st page “Look for other causes of deterioration.” Keep in mind these patient's may later deteriorate and have abnormal observations which would place them in one of the adjacent red or yellow boxes. A patient can activate the pathway at any stage in their journey on the ward. Use ISBAR to structure communication.

 Follow the A through to G highlighting urgent IV access and bloods (blood culture crucial). Consider intraosseous insertion if patient acutely unwell and unable to obtain IV access. Fluid bolus to be given as a 20ml/kg bolus which can be repeated if nil improvement in HR, cap refill or colour. It is vital that antibiotics are given within 60 minutes - do not delay for investigations or results. It is important the patient is in fact on the correct antibiotic when considering alternate source of infection and/ or resistance. This must be reviewed by the AMO.

Continue monitoring and assess for signs of deterioration: Persistent tachycardia, slow capillary refill and hypotension Colour pale and mottled Drowsiness or abnormal LOC Urine output < 1mL/kg/hr Acidosis, increasing serum lactate or procalcitonin Hypoglycaemia, leukopenia or abnormal coagulation

Early escalation of care is important in managing these patients not only by the most appropriate people but also the most appropriate place. Patients with sepsis are at high risk of further deterioration and should be monitored closely for at least 48 hours. The CEC 48 hour sepsis management plan provides a useful guide.

Case Study Note: this is a case study taken from a de-identified RCA which occurred prior to the development of the pathway and a well defined escalation process.

Transferred to the ward 20:09 22:00 7 year old girl admitted via the Emergency department with 3 day history of flu-like symptoms Increasing shortness of breath in last 8 hours according to mother. Transferred to the paediatric ward for observations. 7 year old girl Admitted via the Emergency Department with 3 day history of flu-like symptoms Preliminary diagnosis of asthma

Lactate 3.4mmol/L; CO2 48mmHg 21 21 A FD RA Bloods VBG: pH 7.31; BE -5.3mmol/L Lactate 3.4mmol/L; CO2 48mmHg RR 28 HR 103 BP 130/78 Temp 37.2 SPO2 ≥95% RA (nil oxygen requirement in ED) Was prescribed 4/24 ventolin on ward and was given a dose of prednisalone in Emergency. Click 1 Bloods done in ED VBG: pH 7.31; BE -5.3mmol/L Lactate 3.4mmol/L; CO2 48mmHg CXR NAD So the lactate and BE are already concerning (relate back to the pathway) FD

Given analgesia +  ventolin 2/24 Oral antibiotics ordered Arrive on ward Observations stable 22:00 23:10 00:42 Arrive on ward 22:00 observations stable. Alert slightly pale, SPO2 95% RA, mild WOB, RR 32 (blue zone) , HR 103 At 23:10 she complained of tummy pain and was reviewed by RMO Given analgesia +  ventolin 2/24 Oral antibiotics ordered however not given Lets look at her obs at this time…. C/O “tummy pain” Reviewed by RMO Given analgesia +  ventolin 2/24 Oral antibiotics ordered

21 22 2340  21 22 2340        Sepsis pathway activated with obs in Yellow Zone and deterioration despite treatment     RARA RA    Reviewed by RMO 2310 for tummy pain 3/10 Obs at 23:40 RR 38 (Yellow Zone), HR 138 (Blue Zone), SPO2 93% RA (Yellow Zone), pain in Blue Zone

CO2 52mmHg; BE -7.1mmol/L; Lactate 5.6mmol/L; 2nd Clinical Review Obs in Yellow Zone and “looks tired” Bloods 01:46 Repeat VBG pH 7. 35; CO2 52mmHg; BE -7.1mmol/L; Lactate 5.6mmol/L; 22:00 00:42 01:30 01:46 At 00:42 2nd review by RMO with the following obs: Alert, RR 42 (Yellow Zone), HR 142 (Yellow Zone), WOB mod (Yellow Zone), SPO2 92% RA – oxygen applied via NP improved SPO2 to 96%, Temp 37.8, pain mild 3/10, CERS : x3 Yellow Zone observations or additional criteria= Rapid Response She looks “very tired” however couldn’t sleep despite the pain resolving. At 01:30 SPO2 dropped with NP O2 Reviewed by RMO for the 3rd time, reported to have nil wheeze however ordered IV antibiotics and repeated the VBG As you can see there are a number of concerning values SPO2 drop to 91% with NP O2 3rd review by RMO Ordered IV antibiotics

                     21 22 2340130  21 22 2340130                 RARA RA6LH     Here you can see those obs at 01: 30 charted on the SPOC chart Documented as: Looking very tired however still answering questions appropriately, RR42 (Yellow Zone), HR 142 (Yellow Zone), WOB mod (Yellow Zone), SPO2 95% RA with 6L oxygen applied via Hudson mask, Temp 37.8, pain mild 3/10,

IVAB administered Bloods 02:30 Repeat VBG pH 7.19 CO2 57mmHg; BE -7.1mmol, Lactate 6.3mmol/L IVAB administered 01:30 02:10 02:20 02:40 02:10 IV antibiotics administered. This is 5 hrs from time of abnormal VBG in ED and 3 hrs from time of abnormal observations and effectively activating the pathway on the ward. 02:20 she refuses to keep the Hudson mask however tolerates the nasal prongs achieving SPO2 of 91% however that too is pulled off after approx. 10 mins. 02:40 She is grunting as Hudson mask held on by RN Administered ventolin nebuliser and IV hydrocortisone Note the worsening VBG Refusing to keep Hudson mask on SPO2 91% with NP oxygen Becomes irritable Now grunting as Hudson mask held on by RN Administered ventolin nebuliser and IV hydrocortisone

Paediatrician contacted 10ml/kg 0.9% sodium chloride bolus and IV ceftriaxone and fluclox Nil improvement Paediatrician contacted 03:05 04:10 04:26 03:05 Nil improvement and paediatrician contacted. This is the first time the patient's care was escalated. At 04:10 Reviewed by paediatrician Requested repeat CXR. Contacts NETS requesting transfer to tertiary hospital. Repeat CXR reveals significant changes to the one completed in emergency and was looking like a rapidly progressive pneumonic infection It is at this stage that the paediatrician raises concerns over possible sepsis for the first time (6hrs into the admission to the ward). 10ml/kg sodium chloride 0.9% bolus ordered and administered (this is the first bolus prescribed despite her persistent tachycardia). IV ceftriaxone and flucloxacillin ordered and administered Reviewed by paediatrician Requested repeat CXR Contacts NETS requesting transfer to tertiary hospital

                             21 22 2340130 03  21 22 2340130 03                       RARA RA6L 6L      Here you can see the last set of obs at 0300 RR 48, HR 145, moderate work of breathing with grunting, SPO2 91-93% with 6L O2 via Hudson mask 

Significant deterioration Difficulty keeping SPO2>88% (NRB) Rapid Response call made Decision to intubate NETS arrive Adrenaline infusion commenced Arrested while transferring on to equipment 04:26 05:00 06:00 Asystole CPR 07:20 2nd arrest Between 05:00-06:00 she had a further deterioration: Difficulty keeping SPO2 > 88% with 10-15L O2 via non-rebreather mask Now difficult to rouse HR never less than 152 BP not obtainable Rapid Response call was made and a decision to intubate using rapid sequence induction Patient noted to be asystolic during preparation for intubation and CPR commenced Team were able to get a rhythm and was intubated and ventilated with great difficulty 07:20 NETS arrive commenced inotropes and administered further 20ml/kg bolus and while attempting to transfer onto their equipment the patient's HR dropped requiring CPR again Significant deterioration Difficulty keeping SPO2>88% (NRB)

Aystole CPR 07:20 2nd arrest Post mortem Sadly she did not make it out of the hospital and post mortem reported the death to be from staphylococcal septicemia with a fulminating bronchopneumonia.

The patient demonstrated signs of deterioration despite treatment at 23:40. As she deteriorated over the proceeding hours she definitely demonstrated new or persistent signs of toxicity as well. She activated the pathway with the deterioration despite treatment and the x2 Yellow Zone observations relatively early on. One could also argue that clinician concern in the yellow box was warranted. As she deteriorated over the proceeding hours her 3 simultaneous Yellow Zone observations would have resulted in a Rapid Response using current BTF escalation.

Using the pathway a senior clinician would be involved early escalating her care. Her VBG from ED and certainly worsening numbers on the ward would highlight concern placing the patient in the red box at the bottom “Commence treatment as per Sepsis Resuscitation Guideline”

Follow the A through to G highlighting urgent IV access and bloods (blood culture crucial) Consider intraosseous insertion if patient acutely unwell and unable to obtain IV access Fluid bolus to be given as a 20ml/kg bolus which can be repeated if no improvement in HR, cap refill or colour

What is the evidence for urgent delivery of first dose antibiotics and aggressive fluid resuscitation?

Antibiotics For each hour of delay to administration of antibiotics, after the onset of hypotension, there is a 7.6% increase in mortality (in adults) Kumar Crit Care Med 2006 Kumar's study showing After the onset of hypotension-for each hour of delay to administration of antibiotics there was a 7.6% increased risk of mortality (in adults)

Time - and Fluid - Sensitive Resuscitation for Hemodynamic Support of Children in Septic Shock This study was in San Paolo Brazil in 2008 with 90 children presenting with septic shock. As you can see the mortality rate was extremely high however again you can see there was a 73% mortality with < 20ml/kg compared with 33% with > 40ml/kg. Similarly you can see the high mortality rate 73% when appropriate fluid resuscitation took more than 60 minutes compared to 40% when they received fluid resuscitation in less than 30 minutes. Oliveira et al Time-and fluid- sensitive resuscitation for haemodynamic support of children in septic shock. Pediatr Emerg Care 2008

“For every hour a child remains in shock their mortality rate doubles” 91 children retrieved to Pittsburgh 1993-2001 for “septic shock” For every hour a child remains in shock their mortality rate doubles. That is why early recognition is so vital. This US study was conducted of 91 infants and children who presented to local community hospitals with septic shock and required transport to the Children’s Hospital of Pittsburgh in the US. Community physicians successfully achieved shock reversal in (26%) patients at a median time of 75 minutes (when the transport team arrived at the patient’s bedside), which was associated with 96% survival and >9-fold increase in odds of survival. So it was not their equivalent of NETS who arrived and saved the day- it was the clinicians at these smaller sites that recognised sepsis early and treated appropriately. Keep in mind it is a bundle of care that results in these good outcomes. That is a number of actions all put together including oxygen, respiratory support, fluid bolus, antibiotics, all done in a timely fashion that gets good results. “For every hour a child remains in shock their mortality rate doubles”

Points to remember Senior clinician review is crucial Beware of a lactate over 2mmol/L Not all children with sepsis will be febrile Persistent tachycardia is often consistent with sepsis For every hour a child remains in shock their mortality rate doubles Sepsis is an emergency Rapid antibiotic therapy and early aggressive fluid resuscitation improves survival Senior clinician review is a crucial component of the pathway in decision making around management. Children won't always have an elevated lactate – beware of a lactate over 2mmol/L. Persistent tachycardia is often consistent with sepsis- particularly when children/infants remain tachycardic despite fluid therapy e.g. 10ml/kg bolus or antipyretics. Sepsis is an emergency- if treated in the 1st 4 hours chances of survival are over 50%. After 12 hours chances of survival sinks below 15% (US adult data) The evidence for management of sepsis in paediatric patients is limited and not comprehensive (mostly adult). Limited data however suggests rapid antibiotic therapy and early aggressive fluid resuscitation improves survival.

SEPSIS KILLS TIME IS LIFE Recognise Resuscitate Refer Recognise risk factors, signs, symptoms of sepsis and have early involvement of senior clinicians Resuscitate with rapid IV fluids and administer intravenous antibiotics Refer to appropriate in-hospital teams or retrieval Simple treatment saves lives!