SIRS, Sepsis and Shock Module

Things to consider in septic neonates and infants < 2months

These groups are at increased risk of invasive bacterial infections which include Group B Streptococcal disease (GBS), Listeria monocytogenes or Listeriosis and Escherichia Coli. An overgrowth of the yeast candida usually shows as a diaper rash or oral thrush.

Congenital infections are transmitted from mother to infant, either during pregnancy or delivery and are most often caused by viruses and parasites namely HIV; rubella; chickenpox; syphilis; herpes; toxoplasmosis; and cytomegalovirus (CMV). Some early signs of a possible congenital infection include: a large or small head, small body size, seizures, problems with the eyes, skin rashes, jaundice, enlarged abdominal organs, and a heart murmur.

Bacterial infections in the neonate present with one or more non-specific clinical signs such as feeding problems, lethargy, abdominal distension, diarrhoea, jaundice, apnoea, tachycardia to name a few.

Ensure a neutral thermal environment (and monitor temperature) and ensure adequate nutrition. Enteral feeding where possible, via oro/nasogastric tube after ileus obstruction, apnoea or other contraindications to enteral feeding have been excluded. Give IV fluids if enteral feeding is not possible.

Antibiotics: always refer to your local guideline or consult with the Microbiologist on call if you are unsure. General approach in this age group:

• <1 month of age give Cefotaxime and Ampicillin and Aciclovir
• >1 month give Ceftriaxone

Vascular access

In a resuscitation setting, umbilical vein access continues to be the preferred route in neonates. However, umbilical veins can only be accessed up to 2 weeks and at this stage they are dry and require approximately 1 hour of saline gauze soaking before attempting access.

Ultrasound-guided peripheral intravenous (PIV) access for the external jugular vein; ultrasound-guided central venous access of femoral vein (for temporary use until definitive femoral catheter can be inserted). If two x failed PIV attempts then go straight to the intra-osseous route

Sepsis management

Once suspected or recognised then early goal directed therapy or ‘bundles of therapy’ can be administered: aggressively manage sepsis and patients get better, it’s been proven. The SEPSIS 6 is a set of interventions which can be delivered by any junior healthcare professional working as part of a team. Sepsis 6 uses objective physiological measures from PEWS, emphasises importance of tachycardia, identifies high risk groups and includes early interventions all within the first hour.

Further management discussion points:

Discuss early with (local) or regional intensive care services who offer decision making support and retrieval if necessary.

Airway and breathing:

Indications for immediate endotracheal intubation and mechanical ventilation are hypoxia, with severe respiratory distress indicating a progression of pulmonary oedema; severe persistent shock; fluctuating or decreasing conscious level (Glasgow Coma Score 8 or less, or a decrease of 3 points within 1hr) or signs of raised ICP. When possible the cardiovascular system should be stabilised before intubation, and the potential for acute decompensation should be anticipated. Inotropes, when indicated, should be started before intubation.

It is important that infants are reassessed clinically after commencing on High Flow Nasal Cannula (HFNC) oxygen in order to judiciously intervene in those who do not respond and may require escalation of respiratory support especially in settings where HFNC oxygen is used outside of an intensive care setting.

There was no need for urgent intubation, but because Zach remained lethargic after the first hour or resuscitation and was at increased risk of recurrent seizures and apnoea (hypoxia) he was intubated and ventilated once admitted to PICU.

Circulation:

Rapidly administered 10% dextrose containing fluid was initially required to help correct Zach’s hypoglycaemia. Guidance suggests that if a glucose bolus is given it should be followed by a maintenance infusion. Further slower infusions to optimise
and sustain an increased intravascular volume can also be administered watching HR, perfusion and liver edge closely or by more sophisticated means (if available) like echocardiography and central venous monitoring. These could be given as 10mL/kg crystalloid boluses over a 20-30minute period. The patient should be catheterised at this stage to monitor urine output as this is a marker of end organ perfusion.

Zach is septic with Group B Streptococcus meningitis complicated by seizures. He is hypoglycaemic because he has not fed well and is mildly dehydrated. He has shown clinical improvement after the first hour of resuscitation. He is less tachycardic, not mottled anymore but he is still lethargic. He is transferred to PICU for further care and intubated because of recurrent seizure and apnoea risk.

Is this septic shock?

Yes, Martin could have septic shock. He is functionally asplenic and therefore at increased risk of infections with encapsulated organisms (streptococcus pneumoniae, Klebsiella pneumoniae, group B streptococci, Escherichia coli, Neisseria meningitides and Haemophilus influenzae). He should have blood cultures taken and receive early antibiotics (Ceftriaxone).

Shock is multifactorial and we need to identify the primary cause. Remember there are also other causes of shock: cardiogenic, obstructive, hypovolaemic and distributive. Read more with PEM Playbook for a practical approach on shock.

Fluid assessment in septic children (from DFTB: Fluid Assessment in Sepsis)

There is no volume loss in sepsis and shock. There is an imbalance between oxygen demand and oxygen delivery. The main goal is to improve perfusion. Oxygen delivery (D02) is determined by cardiac output (CO), Haemoglobin concentration (Hb), how much oxygen is bound to haemoglobin (Sa02) and the partial pressure of oxygen (Pa02).

Note: BP is not part of the equation.

Note: the main aim is to increase CO.

The equation:

DO2 = (cardiac output) x [(haemoglobin concentration) x SaO2 x 1.39] + (PaO2 x 0.003)

Practically, in order to decrease oxygen demand you can bring down the fever, sedate and use mechanical ventilation. Increase oxygen delivery by administering oxygen, transfuse blood or red cells. By giving fluids, you increase CO, but not all patients benefit from fluid therapy particularly if they are already in a compensated state or show signs of fluid overload or have other elements of obstructive or cardiogenic causes of shock. In these instances, there is a dose effect: more fluid equals more harm (=mortality).

Frank Starlings in Fluid Responsiveness

3 steps to a fluid assessment:

1. Patient history – ask about input and output (feeds, fluids, urine, diarrhoea, vomiting) and do a risk stratification i.e. young, central indwelling device, immunocompromised etc.
2. Examination – look for signs of shock: inadequate perfusion, tachycardia out of proportion to the exam, normal or low BP, tachypnoea, normal or altered level of consciousness, persistently abnormal or multiple abnormal vital signs or individual sign that is extremely abnormal. Assess for signs of fluid overload: i.e. no physiological improvement with fluid, worsening respiratory status, increased FiO2 requirement, large liver, muffled heart sounds or gallop, raised jugular venous pressure (JVP).
3. Extended examination using POCUS – put the patient on the frank starling curve. Is the patient on the steep part of the curve? Fluid will increase CO. Or on the flat part of the curve? Here the cardiac myocytes are maximally stretched. Giving fluid here will increase right atrial pressures (RAP) which do not lead to increases in CO. The patient is no longer ‘fluid responsive’.
   
   

3 US views:

• Lung US: presence of B-lines = pulmonary oedema = will not benefit from fluid
• IVC: collapsing and small diameter = give fluid
  Dilated and fixed IVC = no fluid
• Heart: hyperdynamic = give fluid
  Poor function, poorly contracting heart = no fluid

How much fluid? (DFTB: FEAST trial analysis)

We hesitate to administer fluid because of randomised evidence that fluid in sepsis is harmful in some settings i.e. FEAST study 2011. FEAST taught us that fluid can kill. Important points to note about the FEAST trial include:

• Poor resource setting where children are more likely to present late therefore negating the positive effects early fluid resuscitation.
• Many children presented with severe anaemia, a situation where haemodilution with intravenous fluids would further worsen oxygen carriage and tissue hypoxia.
• Approximately half the children in the study presented obtunded with cerebral malaria, a situation which may be exacerbated by excess fluid administration.
  

So, if you’re going to give fluid, ensure the patient needs it first and always reassess before giving more.

Surviving Sepsis suggests giving 10mL/kg boluses up to 40-60mL/kg in total if an ICU facility is available over the first hour. Discontinue if signs of fluid overload develop.

In healthcare systems with no availability of intensive care, if hypotension is present, it is suggested to administer up to a total of 40 mL/kg.

Which fluid?

Balanced/buffered crystalloids are preferred (i.e. Plasmalyte-148 and compound sodium lactate (CSL)) over isotonic saline as their tonicity and electrolyte content matches closely to that of blood plasma.

There is inconclusive evidence in paediatric practice for the use of colloids vs crystalloids as resuscitation fluids. Surviving sepsis campaign guidelines suggest the use of crystalloids over albumin and there is little pooled meta-analysis to suggest a benefit to using colloids vs crystalloids except in one specific situation: the use of albumin for resuscitation in septic shock associated with dengue fever.

Blood products are highly effective volume expanders due to their high oncotic load. They are commonly used to replace losses such as in acute trauma, disseminated intravascular coagulation and consumptive thrombocytopaenia.

Keep an eye out for the PRoMPT BOLUS study results – a large multi-centre randomised control trial comparing outcomes in septic children resuscitated with balanced crystalloids vs 0.9% saline fluid.

How fast?

Surviving sepsis suggests fluid therapy administration over the first hour, titrated to clinical markers of cardiac output and dis-continued if signs of fluid overload develop for the initial resuscitation of sepsis or septic shock.

Before giving fluid, a member of the team brings the ultrasound (US) machine and performs a Point-of-Care-Ultrasound (POCUS) and notices that Martin in fact has a large pericardial effusion impeding his heart contractility. The team decides not to give fluids or blood products intravenously as this would further reduce his cardiac output. The team have prepared to intubate in case there is further deterioration but luckily the PICU team arrived to take over management. They are organising an urgent CT Chest for Martin. He remains on high-flow nasal cannula oxygen and is commenced on peripheral adrenalin to optimise him for intubation. and pericardiocentesis.

Cause for fever is more important than treating it

Fever is a physiological response to infections; pyrogens stimulate the hypothalamus to increase the body temperature which inhibits pathogen replication thereby protecting the body. The fever itself is of less importance than the cause for the fever and the main issue is to exclude an underlying dangerous infection rather than treating the fever with antipyretic interventions.

Approximately 15-20% of children present to the emergency department with a fever and only 0.5-1% will be due to sepsis. When managing a child with fever, focus on the clinical assessment to determine the risk of a serious illness such as pallor or cyanosis, depressed level of consciousness, grunting, tachypnoea, reduced skin turgor and bulging fontanelle. Treat fever in febrile convulsions and in situations such as shock with reduced output.

Use PEWS as a guideline

The term PEWS covers a multitude of scores and systems which were initially designed to detect deterioration in inpatient settings. The use of PEWS in Emergency Departments have always been shown to be poorly specific and no studies have shown adequate ability to determine need for hospitalisation. High scores are associated with need for Intensive care so should never be ignored but a low PEWS score is poor at ruling out a serious underlying condition.

Over-investigating and chasing numbers (gppaedstips)

NICE guidelines are safe however if followed closely, staff are more likely to over-investigate. This is because sepsis is difficult to diagnose. There is no mathematical equation to define sepsis. All the features of sepsis are non-specific and you cannot rely on any one feature to be present all of the time“ Sepsis doesn’t appear, it develops“. There is a misconception that the point where sepsis began can always be identified. This is simply not the case. A viral illness bringing you to hospital one day, may well still have been a viral illness regardless of whether you present to the hospital the next day with sepsis. Clinical suspicion is better used to identify sepsis than a blood test. In practice, decisions often rely on the experience of the clinicians involved so if sepsis is a possibility it is wise to involve a clinician who has had significant exposure to seriously ill children in an ED setting. Ask for senior advice.

CRP and Procalcitonin (PCT) (10.1136/archdischild-2011-300178)

No marker of infection can rule in or rule out sepsis in all children and inflammatory markers should not be relied on to decide whether a child has an acute bacterial infection or sepsis. PCT is better able to discriminate against severe bacterial infection than CRP and PCT is particularly useful in the early stages of infection. PCT is able to differentiate between SIRS and sepsis while CRP is not. CRP is not a good predictor of sepsis.

Management discussion points:

Diagnosing sepsis in children is not easy. There is no right or wrong answer here. You will see many of these kinds of patients in your career, many even in one shift. Realistically, you cannot do septic screens and admit every single child who comes in with a fever. So, be an advocate for this patient and use your greatest skill: the clinical examination. Be like Sherlock Holmes, look for the abnormal and try find the source of the fever.

Management outcome discussion:

Your registrar is available, so you discuss Ellie’s case, you re-examine Ellie together with your registrar and conclude that this is probably a viral upper respiratory infection (URTI). You explain the course of the illness and support the parents on how to look after Ellie at home, safety net and discharge Ellie home.

Match the following columns:

Staphylococcus aureus – Endocarditis, Osteomyelitis, Septic Arthritis

Staphylococcus aureus is a gram positive, bacterium (looks like clusters of grapes under a microscope). Approximately 30% of the population are asymptomatic carriers; and can be found as part of normal flora of the upper respiratory tract and skin. Complications are included above as well as abscesses and pneumonias. Cloxacillin is the recommended antibiotic choice for sensitive staph (MSSA) and Vancomycin for resistant staph (MRSA).

Pneumococcus – Bacterial Meningitis (invasive disease decreased with vaccine)

Invasive disease of Haemophilus influenzae and Streptococcus pneumoniae are less commonly seen due to vaccinations.

Haemophilus – Sinusitis, Orbital Cellulitis, Epiglottitis (less common due to vaccine)

Group A Streptococcus – Toxic Shock Syndrome, Scarlet fever

Group A Streptococcus (GAS) is a gram positive, beta-haemolytic coccus in chains. It is responsible for diseases such as strep throat, impetigo and cellulitis. Complications include post strep glomerulonephritis, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), rheumatic fever, scarlet fever and toxic shock syndrome (TSS). Treatment should include penicillin, and clindamycin added for TSS.

Neisseria Meningitidis – Sepsis, Meningitis

Meningococcaemia caused by the virulent gram-negative Neisseria meningitidis is relatively rare. Fever and petechial rash/purpura and poor perfusion can equate to meningococcaemia but not always. Leg pain and refusal to walk, cold hands and feet and abnormal skin colour are also important, subtle signs to be vigilant about when assessing a child with suspected meningococcaemia.

Group B Streptococcus – Meningitis, Sepsis in < 3months

Group B streptococcus (GBS), Listeria monocytogenes and Escherichia Coli (E.Coli) are 3 important bacteria to remember in sick neonates. Early-onset GBS (<7days) presents commonly as acute respiratory distress or septicaemia. Late-onset GBS (7- 89days) present with meningitis, seizures. Intrapartum screening and antibiotic programs have not reduced incidence in late-onset GBS.

Gram negative sepsis – UTI, Appendicitis, Hospital-Acquired

Which of the following statements are true?

A. The meningococcal serum PCR result is affected by antibiotics therefore it is important to do this test prior to the administration of antibiotics in suspected meningococcal sepsis.

B. Balanced/buffered crystalloids are preferred (i.e. Plasma Lyte-148, Hartmanns’s solution and Ringer’s Lactate) over isotonic saline for resuscitation in septic shock.

C. Blood lactate levels provide a valuable indirect marker of tissue hypoperfusion and are not spuriously increased by squeezing of a limb, use of a tourniquet or stored for a prolonged period of time.

D. A Haemoglobin level (Hb), CRP and Blood Culture are investigations you can reliably interpret from bone marrow blood following intraosseous access (IO).

The correct answer is B & D

The pre-hospitalisation administration of parenteral benzylpenicillin normally renders blood cultures sterile, and lumbar puncture is undertaken less frequently, especially in young children. Sensitivity to meningococcal serum PCR is unaffected by prior antibiotic treatment. PCR is a rapid, sensitive test that may be used to confirm a diagnosis of meningococcal disease by using peripheral blood samples. Introduction of this test into clinical laboratories may in some cases obviate the need for lumbar puncture to be performed on patients with suspected meningococcal disease.

Squeezing of a limb when acquiring a blood sample can spuriously increase lactate by venous stasis, impaired local perfusion and distress/exertion of the
child. Haemolysis does not affect lactate. Prolonged sample storage will spuriously increase lactate unless sent in an oxalate tube or on ice. ILCOR guidelines and Surviving Sepsis suggest the use of balanced or buffered crystalloids over isotonic saline as a resuscitation fluid in sepsis as their tonicity and electrolyte content matches closely to that of blood plasma. Saline may be associated with decreased renal blood flow and promote inflammation.

Most laboratory tests cannot be performed on aspirated bone marrow blood as the particulate matter may block and damage laboratory equipment. Aspirated IO blood is suitable for blood culture bottles, bedside glucometers, handheld I-STAT instruments (pH, glucose, and lactate) and haematological and biochemistry testing. Sodium, potassium, CO(2), and calcium levels from IO blood should be interpreted cautiously as well as white cell counts (WCC appear elevated) and platelets (which tend to be lower).

Which groups of patients are at increased risk of sepsis?

A. Children under 1 year of age
B. Patients with (functional) asplenia (sickle cell, SLE, splenectomy)
C. Patients with a breach to skin barrier function (burns)
D. Patients with congenital/acquired immunodeficiency (CVID, HIV,diabetes)
E. All of the above

The correct answer is E.

Always be aware of certain groups who may be predisposed to sepsis, for example neonates or oncology patients (undergoing chemotherapy), who display less profound features. These individuals may maintain normothermia and also have diminished physiological responses e.g. less tachycardia.