BJA Education, 21(2): 51e58 (2021)
doi: 10.1016/j.bjae.2020.09.004
Matrix codes: 1A02,
2C03, 2D01, 2D01,
3D00
Sepsis in paediatrics
H.D. O’Reilly* and K. Menon
Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada
*Corresponding author. hdoreilly@gmail.com
Keywords: anaesthesia; critical care; paediatric; sepsis; sepsis syndromes
Learning objectives
By reading this article, you should be able to:

Describe the clinical signs of septic shock in
paediatrics.

Explain the initial management of septic shock in
children.

Discuss the considerations of providing anaes-
thetic care to a child with sepsis.
Sepsis and septic shock continue to be a major cause of
morbidity and mortality in infants and children worldwide.
Mortality can be over 10%, and influenced by the child’s age
and comorbidities, source of infection, causative organism
and management.1 There are persisting disparities between
high- and low-to-middle-income areas, with mortality rates
exceeding 30% in some countries.2 In developed areas, septic
shock requiring paediatric intensive care admission is asso-
ciated with a mortality rate as high as 17%.3 Despite this global
burden of disease, uncertainties persist in diagnosis and
Heather O’Reilly MD FRCPC is a consultant paediatric anaesthesi-
ologist at Children’s Hospital of Eastern Ontario (CHEO) and a
lecturer at the University of Ottawa. She completed fellowships in
paediatric anaesthesia and critical care. Currently, she is a member
of the Ottawa University anaesthesia and paediatric critical care
competence committees, and faculty mentor and member of the
anaesthesia simulation faculty at CHEO.
Kusum Menon MD MSc FRCPC is a consultant paediatric intensivist
and Senior Scientist at Children’s Hospital of Eastern Ontario. Her
research interests include adrenal insufficiency in critical care and
paediatric sepsis. She is a member of the Society of Critical Care
Medicine task force for the development of a new definition for
paediatric sepsis and of PODIUM for the new definition of MODS.
Accepted: 23 September 2020
© 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com
Advance Access Publication Date: 7 December 2020
Key points

Early signs of septic shock include tachycardia
and derangements in temperature, mental status
and peripheral perfusion.

In younger children, intraosseous (i.o.) access is
often easier and achieved more quickly than i. v.
access.

Broad-spectrum antibiotics should be given
within 1 h of presentation.

Children in septic shock are often extremely
dehydrated and respond favourably to initial
resuscitation with fluids.

Infusions of inotropic drugs can be started
through either the peripheral i.v. or i.o. routes.
management, and sepsis remains a hot topic of research in
paediatric intensive care medicine.
In this article, we review the diagnosis and management of
sepsis in paediatrics. We focus on recognition and initial
management, special considerations for the child presenting
with sepsis in the community and those requiring emergency
anaesthesia and surgery.
Definitions
The pathophysiology of sepsis is complex, involving an
altered inflammatory response to infection, paired with de-
rangements in coagulation, cardiovascular, immune, meta-
bolic, hormonal and neuronal responses.4
The Third International Consensus Definitions for Sepsis
and Septic Shock in adults were published in 2016.5 Several
concepts were altered significantly to reflect contemporary
understanding of pathophysiology and management, and
sepsis in adults is now defined as a ‘life-threatening organ
dysfunction caused by a dysregulated host response to
infection’.5 A subset of sepsis, septic shock, is associated with
51
Sepsis in paediatrics

higher mortality and can be defined as sepsis accompanied by
significant circulatory, cellular and metabolic abnormalities.5
The most recent consensus statement concerning paedi-
atric sepsis was published in 2005.6 Age-adapted sequential
organ failure assessment (SOFA) scales have recently been
validated, and the Society of Critical Care Medicine has
commissioned a task force to update the definition of paedi-
atric sepsis.7 In the meantime, paediatric sepsis continues to
be discussed in terms of the systemic inflammatory response
syndrome (SIRS) criteria, defined as the presence of at least
two of the following four criteria, one of which must be
abnormal temperature or leucocyte count6:
(i) Core temperature of >38.5 C or <36 C
(ii) Tachycardia, defined as a mean HR >2 standard de-
viations (SD) above normal for age in the absence of
external stimulus, chronic drugs or painful stimuli; or
otherwise unexplained persistent increase in HR over a
0.5e4 h time period; or for children <1 yr old: brady-
cardia, defined as a mean HR <10th percentile for age in
the absence of external vagal stimulus, beta-blocker
drugs or congenital heart disease; or otherwise unex-
plained persistent decrease in HR over a 0.5 h time period
(iii) Mean ventilatory frequency >2 SD above normal for age
or mechanical ventilation for an acute process not
related to underlying neuromuscular disease or the
receipt of general anaesthesia
(iv) Leucocyte count increased or decreased for age (not
secondary to chemotherapy-induced leucopenia) or
>10% immature neutrophils
Systemic inflammatory response syndrome in the pres-
ence of a known or suspected infection is considered diag-
nostic of sepsis.6 When cardiovascular organ dysfunction
exists in the presence of sepsis, the child is considered to be in
septic shock.6
The consensus criteria define cardiovascular organ
dysfunction as despite giving isotonic i. v. fluid bolus 40 ml
kg1 in 1 h6:
(i) Decrease in BP (hypotension) <5th percentile for age or
systolic BP <2 SD below normal for age, or
(ii) Need for vasoactive drug to maintain BP in normal range
(dopamine >5 kg1 min1, or dobutamine, adrenaline
[epinephrine] or noradrenaline [norepinephrine] at any
dose), or
(iii) Two of the following:
(a) Unexplained metabolic acidosis: base deficit >5.0
mEq L1
(b) Increased arterial lactate >2 times upper limit of
normal
(c) Oliguria: urine output <0.5 ml kg1 min1
(d) Prolonged capillary refill: >5 s
(e) Core to peripheral temperature gap >3 C
The SIRS criteria may underidentify children with infection
at the highest risk of mortality; research validating an age-
adapted SOFA scale demonstrates that this scale may more
accurately identify those children most at risk.7,8 Although
definitions are important for prognostication, benchmarking
and research endeavours, in clinical practice, the strategies
that improve early recognition and initial management of

Recognition of sepsis in paediatrics

Abnormal vital signs
Suspicion of Age HR MAP Or SBP VF
infection? (mmHg) (mmHg)
0 days–1 week >205 <100 <46 < 60 >50
Yes >1 week–1 >205 <100 <55 < 60 >40
month
>1 month–1 yr >190 <90 <55 <70 >34
Yes Begin
Hypotensive? 2–5 yrs >140 <60 <62 <70 + (age in yr × 2) >22
resuscitation
6–12 yrs >130 NA <65 <70 + (age in yr × 2) >18
13–18 yrs >110 NA <67 <90 >14
No Worrisome features
Heightened concern if >2 features or 1 feature with comorbid condition*
Worrisome Yes Core temperature <36°C or >38.5°C
features? Altered mental status ↓ conscious level, irritable,
confused, lethargic,
inappropriate cry
No Altered peripheral perfusion Flash capillary refill <1 s
Prolonged capillary refill >3 s
Inappropriate tachycardia
Routine care
Strong clinical suspicion Begin resuscitation

*Immunocompromised, recent surgery, indwelling central line, neonate <3

months, underlying chronic disease

Fig 1 Paediatric sepsis recognition algorithm.6,8e10 LOC, level of consciousness; SBP, systolic BP; VF, ventilatory frequency.

52 BJA Education - Volume 21, Number 2, 2021

 Sepsis in paediatrics

patients with possible sepsis have been shown to decrease
morbidity and mortality the most.
Recognition
The American College of Critical Care Medicine recommends
the use of bundles for the recognition, resuscitation and sta-
bilisation of children with septic shock.9 These bundles pro-
mote an institutional approach to septic shock, encouraging
the use of a recognition bundle, in which a trigger tool is used
to rapidly identify children at risk of septic shock, and a
resuscitation bundle, which delineates initial management
and promotes evidence-based best practice.9
Practitioners need a high index of suspicion to quickly and
appropriately recognise the signs of septic shock. If an infec-
tion is suspected, then one must play close attention to the
child’s core temperature, level of consciousness and haemo-
dynamic status, including peripheral perfusion.9 In the
absence of an institutional specific bundle, the algorithms in
Figs. 1 and 2 may be used to guide recognition and manage-
ment of children with potential sepsis.
Initial management
Monitors and oxygen therapy
Children with suspected septic shock should be monitored
continuously and given O2 100% via a non-rebreather mask or
high-flow oxygen device. Essential monitoring includes oxy-
gen saturation (SpO2) probe, three-lead ECG with rhythm strip,
appropriately sized non-invasive BP cuff, respiratory monitor
with ventilatory frequency and thermometer to measure core
temperature. When continuous monitors are not available,
these vital signs should be rechecked regularly at a minimum
interval of 5 min. Urine output and point-of-care glucose
concentration should also be monitored, and level of con-
sciousness and capillary refill should be assessed at the
beginning of resuscitation and after every intervention.
Early clinical signs that indicate septic shock include
tachycardia, derangement in temperature (hypothermia or
hyperthermia), alteration in mental status and peripheral
vasoconstriction (cold shock) or vasodilation (warm shock). In
children, these signs usually occur before significant changes
in arterial BP.9,10 Age-specific guidelines will help guide diag-
nosis and management. However, in general, critically ill in-
fants with an HR <90 or >160 beats min1 or a child with an HR
<70 or >150 beats min1 have higher mortality risk.9,11 Teen-
agers with sepsis are often tachycardic, and an HR of >110
beats min1 in an adolescent is also a cause for concern.6
Initial management should focus on attaining the thera-
peutic endpoints of capillary refill <3 s and threshold HR and
BP for age with palpable distal pulses.9 Mortality increases
when capillary refill is prolonged (>3 s), especially when
associated with hypotension. However, appropriate resusci-
tation can dramatically improve survival.9,12
In children with sepsis, a reduction in oxygen delivery (D_ O2)
is the major determinant of derangement in oxygen con-
sumption (V_ O2). Providing adequate oxygenation may improve
outcomes and is essential to the resuscitation process.9,11
Escalation of respiratory support should be dictated by the

Paediatric sepsis resuscitation

Begin
resuscitation Monitoring Fluid-refractory shock?

Reassess every 5 min and after every intervention Cold shock

Monitors
Begin high-flow O2 and Pulse oximetry
place on monitors ECG, HR with rhythm strip
BP
Core temperature
Ventilatory frequency
Urine output
Secure i.v. or i.o. × 2
send blood tests Fluids, antibiotics and blood tests
First hour
Clinical examination
Airway patency
WOB, crackles, rales
Pulse, capillary refill
Cardiac gallop, hepatomegaly
GCS/LOC
Peripheral skin temperature
Cool extremities
Prolonged capillary refill
(>2 s) narrow pulse
pressure
Weak peripheral pulses
Low cardiac output, high
SVR state.
Warm shock
Adrenaline
0.05–0.3 µ kg–1 min–1
Add noradrenaline*
0.05–0.3 µ kg–1 min–1
Add milrinone†
0.25–1 µ kg–1 min–1

Fluids Antibiotics Warm extremities Noradrenaline

–1 –1
Ringer’s lactate Ceftriaxone Flash cap refill (<1 s) 0.05–0.3 µ kg min
Fluids and • 20 ml kg–1 × 3 PUSH • 50 mg kg–1; maximum 2g Wide pulse pressure Add vasopressin*
Vancomycin Low diastolic pressure 0.002–0.2 units kg–1 min–1
antibiotics Sepsis panel –1
• 15 mg kg ; maximum 1g (<1/2 SBP); bounding pulses
CBC with differential Metronidazole High cardiac output, low
Blood culture • Add if intra-abdominal source SVR state.
Blood gas and lactate suspected
–1
Fluid-refractory POC glucose and electrolytes • 10 mg kg ; maximum 500mg †
*continued hypotension; continued cold shock with normal BP
shock? Metabolic and DIC screen
Catecholamine-resistant shock?
Type and screen
Therapeutic endpoints Rule out Pneumothorax, tamponade,
increased intra-abdominal
Catecholamine- Cap refill ≤2 s Normal pulses pressure >12 mmHg, blood loss
Warm extremities Normal mental status
resistant shock? Normal BP for Age Urine output >1ml kg–1 h–1 Adrenal suppression? Consider steroid replacement
Normal glucose Normal ionised calcium Hypothyroid? Consider thyroid replacement
Refractory shock? Consider ECMO

Fig 2 Paediatric sepsis resuscitation algorithm.6,9,10 CBC, complete blood count; DIC, disseminated intravascular coagulation; ECMO, extracorporeal membrane
oxygenation; GCS, Glasgow Coma Scale; LOC, level of consciousness; POC, point of care; SBP, systolic BP; SVR, systemic vascular resistance; WOB, work of
breathing.

BJA Education - Volume 21, Number 2, 2021 53

Sepsis in paediatrics
clinical situation. Apart from the child that presents with a
profoundly decreased level of consciousness or inadequate
respiratory drive, oxygen therapy alone is usually tolerated
during the initial resuscitation process; if shock worsens or is
fluid refractory, escalation of respiratory support should be
considered.8 Non-invasive methods, such as high-flow nasal
cannulae, CPAP and BiPAP can be tried in the child with an
adequate level of consciousness and respiratory drive. For
children with worsening shock, tracheal intubation and
invasive ventilation can decrease oxygen demand and
potentially improve oxygen delivery.9,13 Children with sepsis
are at risk of pulmonary oedema secondary to fluid resusci-
tation, SIRS-induced capillary leak and sepsis-related
myocardial depression. Other factors that worsen respira-
tory status include a pneumonic source of infection and
sepsis-related acute respiratory distress syndrome. If escala-
tion in respiratory support is needed, appropriate fluid
resuscitation and vasopressor support before intubation can
improve cardiovascular instability during intubation and
mechanical ventilation; high-flow oxygen or CPAP may be
used as a bridge to allow for intravascular access and fluid
resuscitation before intubation.9
Vascular access and blood tests
I.V. or i. o. access should be attained within 5 min of sepsis
recognition.9 It is often difficult to attain i.v. access in critically
ill infants and young children. It is recommended to avoid
perseverating on attaining i.v. access if difficult and quickly
move to i.o. access in these situations.14 Intraosseous access is
often easier and more quickly attained than i.v. access,
especially in younger children, allowing for earlier blood tests
and infusion of fluids and medications.14,15 The exception to
this practice are children under 3 kg, in whom the use of i.o.
access is contraindicated.9
All i.v. medications can be safely given through the i.o.
route, including emergency medications, such as adrenaline,
antibiotics and all blood products.14 An i.o. cannula functions
similarly to an i.v., so the onset of action of medications is
similar, and it can be used as an access for blood tests.14 All
medications should be flushed with saline to ensure access to
the vascular system, and fluids should be given continuously
through the i.o. cannula via an infusion pump to avoid clotting
and loss of access.14
Once i.v. or i.o. access has been attained, blood work
should be sent immediately, ideally before other medications,
including antibiotics. Difficulty in attaining blood work from
an i.o. access can occur when marrow fat occludes the needle
tip; if this occurs, consider attaining blood work through a
femoral artery stab. Antibiotics should not be delayed if blood
sampling proves difficult or time consuming. A sepsis panel
(see Fig. 2), including blood culture, and urinalysis and culture
should be obtained as quickly as possible. Depending on the
child’s haemodynamic and respiratory stability and coagula-
tion status, consideration should also be given to a lumbar
puncture if meningitis is suspected.
Fluids
Resuscitation with fluids should begin as soon as an initial
examination of the patient has been performed and i.v. access
is attained. An initial fluid bolus of 20 ml kg1 should be given
by rapid infusion or manual push.9 In children with signs of
cardiogenic shock, such as hepatomegaly, rales, crackles,
54 BJA Education - Volume 21, Number 2, 2021
cardiac gallop or increased work of breathing, consider giving
a smaller initial fluid bolus of 5e10 ml kg1.9 Reassess after
each fluid bolus for fluid overload or attainment of therapeutic
endpoints. Unless the child demonstrates signs of fluid over-
load, anticipate giving 40e60 ml kg1 fluids in the first hour of
resuscitation before normal BP and perfusion are attained or if
fluid-refractory shock is suspected.9
The American College of Critical Care Medicine recom-
mends isotonic crystalloid or albumin 5% as the preferred
fluid for fluid resuscitation.9 In paediatric sepsis, resuscitation
with high chloride-containing solutions, such as NaCl 0.9%, is
potentially associated with worse outcomes compared with
more balanced solutions, such as lactated Ringer’s.16 This
concept remains controversial, as a recent systematic review
did not support the use of lactated Ringer’s over saline 0.9% in
critically ill adults and children.17 A potentially modifiable
factor, hyperchloraemia, is common in children with sepsis
and is independently associated with worse outcomes.18
Within the first 72 h of paediatric sepsis resuscitation,
balanced solutions, such as lactated Ringer’s, may confer a
survival benefit, decrease acute kidney injury and are associ-
ated with a shorter duration of vasoactive infusions.16
Infants in septic shock are prone to hypoglycaemia and
hypocalcaemia. An early point-of-care glucose test can help
dictate therapy. Both hypoglycaemia and hypocalcaemia
should be addressed early in resuscitation efforts. Children
who are profoundly hypoglycaemic can be given dextrose
solution 10% (10 ml kg1) rapidly through an i.v. or i.o. can-
nula.9 Hyper-osmolar dextrose solutions may cause irritation
and sclerosis of small and fragile veins; in these situations,
consider diluting dextrose solutions with normal saline. If
access is available, an isotonic solution of dextrose 10% can be
given at maintenance rate to prevent hypoglycaemia.9 In older
children and teenagers, sepsis is more likely to cause a stress-
induced hyperglycaemia.6 In the ongoing management of
sepsis, maintaining a plasma glucose concentration of <10
mmol L1 has been shown to confer a survival benefit.6,9
Hypocalcaemia should be treated to normalise ionised cal-
cium concentrations.9 Both calcium chloride (10 mg kg1) or
calcium gluconate (30 mg kg1) may be used, and although
calcium chloride is more hypertonic and therefore irritating to
peripheral veins, its onset of action is quicker than calcium
gluconate, especially in the setting of liver dysfunction.
Antibiotics
Broad-spectrum antibiotics should be given to the child with
sepsis within 1 h of presentation.10 Ideally, blood cultures
should be sent before giving antibiotics. However, attaining
i.v. access can be difficult in children and should not delay
antibiotics that can be given by i.m. injection.10 Appropriate
and timely treatment with antibiotics is critical to the effec-
tive management of septic shock, and a delay in antibiotic
therapy may increase morbidity and mortality.13 In critically
ill children, the duration of organ dysfunction and risk of
mortality increases with each hour after recognition of sepsis
until appropriate initial antibiotics are given.19
Choice of antibiotics may vary by location. However, in
general, the initial antibiotics should be broad spectrum and
cover endemic and suspected Gram-negative and Gram-
positive organisms, based on source and suspected site of
infection.13 Combination therapy of at least two antibiotics
should be used in septic shock.13 Children are more suscep-
tible to toxic shock if clinical symptoms, such as
 Sepsis in paediatrics

Anaesthesia sepsis algorithm

Preoperative optimisation
Suspect infection?
• I.V. access × 2, or central access
• I.O. inappropriate for surgery because of high risk of dislodgement
• Consider placing central venous catheter under sedation, before induction, especially if
Yes receiving peripheral catecholamine infusions
• Review sepsis panel
• Transfuse Hb >100 mg dl–1, correct coagulopathy (platelets, FFP, cryoprecipitate as needed)
• Correct hypoglycaemia (D10W 10 ml kg–1)
Refer to sepsis • Correct electrolyte and acid–base abnormalities (hypocalcaemia, hyperkalaemia, consider
recognition algorithm sodium bicarbonate if pH <7.2)
• Appropriate antibiotic coverage?

Induction
• Preoxygenate the lungs
• Before induction
• Consider fluid bolus
Has child received • Vasopressor infusion and boluses prepared, consider giving pre-emptively before
Yes induction medications
appropriate
• Consider invasive monitoring (arterial and, central venous access)
resuscitation? • Prioritise titration of medications on induction (haemodynamics) over potential risk of aspiration

Intraoperative management
No • Titrate anaesthetic and haemodynamic medications to achieve:
• Adequate depth of anaesthesia and pain control
• Scvo2 >70%, lactate <2, Hb >100 mg dl–1, normal pH, electrolytes
• Normal BP, HR, temperature, capillary refill
Refer to sepsis • Repeat antibiotics:
resuscitation algorithm • Every 2 half-lives (~every 4 h)
• Lung-protective ventilation strategy

Postoperative considerations
• Continued Intubation with lung-protective ventilation strategy
• Pain control and continued haemodynamic monitoring
• Transfer to paediatric ICU
• Involvement of intensivist and infection disease specialists, if not already involved in care

Fig 3 Anaesthesia sepsis algorithm.6,9,10 ECMO, extracorporeal membrane oxygenation; FFP, fresh frozen plasma; Hb, haemoglobin; ScvO2, central venous oxygen
saturation.

erythroderma, indicate the possibility of toxic shock. Anti-
biotic coverage should be broadened to include clindamycin
because of its anti-toxin properties.13 Once an organism has
been identified, antibiotics should be narrowed in consulta-
tion with your infectious disease (ID) service.
Source control
Although an obvious source of infection is often not apparent
in up to 50% of children with sepsis, in those children with an
identifiable source, early and aggressive source control is
fundamental to their management.10 Once intravascular or
i.o. access has been attained, indwelling lines, if present,
should be removed.10,13 Debridement and drainage of wounds
should occur expediently, and intraperitoneal sources, such
as a perforated viscus, should be repaired with peritoneal
washout as soon as medically and logistically possible.10,13
Fluid-refractory shock
Children in septic shock are often extremely dehydrated and
respond favourably to initial fluid resuscitation.9 It can
reasonably be expected that a child with sepsis will require
40e60 ml kg1 fluids within the first hour of resuscitation.9
However, fluids should be given with caution because there
is emerging evidence that liberal use of fluids may be associ-
ated with worse outcomes in paediatric sepsis.20,21 If resus-
citation has been ongoing for more than 15 min and a child is
not responding to rapid fluid boluses, consider fluid refractory
shock and the need for support with vasoactive drugs.9,10
Inotrope infusions can be initiated peripherally through
either the i.v. or i.o. route.9 Although practices vary globally,
the American College of Critical Care Medicine recommends
adrenaline as the initial inotrope in paediatric cold shock.9,22
As children usually present in cold shock, adrenaline is the
preferred choice for peripheral use and can be initiated at
0.05e0.3 kg1 min1 until central access is attained.23 It is
advisable to dilute peripheral adrenaline by a factor of 10 to
that given centrally.9 The limb, in which adrenaline is
infusing, should be monitored closely for signs of infiltration
and ischaemia.9 Noradrenaline can also be given peripherally,
similarly to adrenaline, and is the inotrope of choice in vaso-
dilatory or warm shock. Dopamine is an option if adrenaline is
not available, but it is no longer considered first line in infants
and children.9,23 Once central i.v. access has been attained,
inotropic and vasopressor drugs can be further tailored to the
shock phenotype.

BJA Education - Volume 21, Number 2, 2021 55

Sepsis in paediatrics
Clinical examination does not always accurately deter-
mine the underlying shock phenotype, but during initial
resuscitation efforts and in the absence of invasive moni-
toring, delineating between cold and warm shock can help
guide management choices.
The shock phenotype can also change over time. Practi-
tioners must remain vigilant, frequently re-evaluating the
child, and adjusting doses of inotropes and vasopressors as
the underlying pathophysiology dictates.
Catecholamine-resistant shock
Septic shock that responds poorly to both fluids and
increasing doses of initial inotropic or vasopressor support is
termed catecholamine-resistant shock. If the child with sepsis
is not responding favourably to your efforts at resuscitation,
escalation in therapies should be matched with investigations
into other potential causes of shock. Ensure source control
and broad and appropriate antibiotics. A haemodynamically
unstable child may need emergency surgery to address a
localised source of infection. Clindamycin and i.v. immuno-
globulin should be added for suspected toxic shock. Drugs that
treat anaerobic organisms, such as metronidazole, should be
added for a suspected gastrointestinal source, and doses of
antibiotics for use in meningitis should be used if meningitis
is suspected. Other causes of shock, such as pericardial effu-
sion, pneumothorax, increased intra-abdominal pressure,
blood loss, adrenal suppression or hypothyroidism, should be
actively investigated and managed.9,10 The use of steroids in
septic shock is debated in the literature. Practice varies
widely, and although clinical guidelines continue to recom-
mend considering steroids in catecholamine-resistant shock,
recent research points towards worsening outcomes in pae-
diatric sepsis.9,24 Risk of adrenal suppression should be
considered in children with catecholamine-resistant shock.
However, reserve exogenous steroids for children with
laboratory-confirmed adrenal suppression, or those who have
received recent high-dose or long-term steroid therapy.
Special considerations for the anaesthetist
Up to a quarter of children hospitalised with severe sepsis will
undergo surgery during their management.1 Sepsis and multi-
organ failure in children account for 47% of perioperative
cardiac arrests.8 It is important that the anaesthetist remains
vigilant when caring for a patient with, or at risk for, sepsis or
septic shock. Sepsis should remain high on the differential
diagnosis of any child with worrisome features, especially if
the child has a known infection (see Figs. 1 and 3).
It is important to note that sepsis can dramatically alter
drug pharmacokinetics, potentially affecting pharmacody-
namics, and care must be taken to adjust medication choice
and dosage to avoid unexpected effects and iatrogenic harm.25
It is critical that the anaesthetist has a thorough under-
standing of how sepsis affects the pharmacokinetics and
subsequent pharmacodynamics of commonly used anaes-
thetic medications. Even in the absence of signs of organ
failure, sepsis can alter the absorption, distribution, meta-
bolism and excretion of medications.25 Drug absorption from
both enteral and non-enteral routes may be unpredictable in
sepsis. Medications are best given i.v., as altered blood flow to
the gut, skin and muscles resulting from changes in circula-
tory status can impair oral and subcutaneous absorption.26
Distribution may be affected by changes in tissue perfusion,
56 BJA Education - Volume 21, Number 2, 2021
tissue membrane permeability, protein binding, body water,
tissue mass and pH.26 Metabolism of most commonly used
anaesthetic medications primarily occurs in the liver, but may
also occur in the kidney and lung.26 Sepsis is associated with
hepatic dysfunction, with metabolism affected by altered
hepatic blood flow, free unbound drug fraction and hepato-
cyte intrinsic activity.25,26 Clearance of medications with high
hepatic extraction ratios, the fraction of drug cleared from the
circulation after one pass through the liver, is altered pri-
marily by hepatic blood flow.25 Clearance of medications with
low extraction ratios is altered by drug protein binding and
hepatocyte function.25 Renal excretion of medications and
their metabolites may also be altered by sepsis-induced renal
injury, which may be pre-, renal and post-renal in aetiology.26
Anaesthetic medications and sepsis
Ketamine25,26
(i) Induction dose should be reduced (0.25e0.5 mg kg1),
given slowly and titrated to effect.
(ii) Ketamine is a direct myocardial depressant. (In a child
with sepsis and who is ‘adrenergically deplete’, keta-
mine may cause profound cardiovascular depression.)
(iii) Hepatic impairment may prolong the effects of
ketamine.
(iv) Consider giving both inotropic and vasopressor drugs or
fluids to counteract cardiovascular depressant effects.
Benzodiazepines25,26
(i) Induction dose should be reduced (i.e. midazolam
0.05e0.1 mg kg1), titrated to effect, and infusions should
be given with caution.
(ii) Hepatic and renal dysfunction prolongs the effects.
(iii) Decreased serum albumin concentrations may enhance
the response.
(iv) Consider giving both inotropic and vasopressor drugs or
fluids to counteract cardiovascular depressant effects.
Opioids25
(i) Dose should be reduced and titrated to effect (i.e. fenta-
nyl 0.5e2 mcg kg1 or morphine 0.025e0.05 mg kg1).
(ii) Consider using opioids in combination with other agents
(i.e. fentanylþmidazolam).
(iii) Sepsis-related decreased volume of distribution pro-
longs the effects.
(iv) Hepatic hypoperfusion causes decreased clearance of
morphine and fentanyl.
(v) Metabolism of remifentanil is unchanged in sepsis.
(vi) Consider giving both inotropic and vasopressor drugs or
fluids to counteract cardiovascular depressant effects.
Propofol25,26
(i) Caution use in patients with sepsis who have cardio-
vascular instability.
(ii) Induction dose should be reduced (0.5e1 mg kg1), given
slowly and titrated to effect.
(iii) Propofol can cause profound cardiovascular depression.
(iv) Induction may be prolonged secondary to sepsis-
induced cardiomyopathy.

(v) Higher risk of propofol infusion syndrome, dose and
duration of infusion should not exceed 4 mg kg1 h1.
(vi) Consider giving both inotropic and vasopressor drugs or
fluids to counteract cardiovascular depressant effects.
Rocuronium25,26
(i) Hepatic dysfunction, hypoalbuminaemia, electrolyte ab-
normalities, acidosis and hypothermia prolong the
effects.
(ii) Unpredictable duration of action in sepsis necessitates
neuromuscular monitoring.
Suxamethonium25,26
(i) Avoid use in children with sepsis, underlying hypotonia,
renal injury associated with hyperkalaemia, rhabdo-
myolysis or prolonged immobility.
(ii) Sepsis may result in an acquired plasma cholinesterase
deficiency.
(iii) Unpredictable duration of action necessitates neuro-
muscular monitoring.
Special considerations for the community
physician
Regardless of whether a critically ill child presents to a com-
munity or tertiary care hospital, initial management strate-
gies remain unchanged. In the absence of hospital-specific
sepsis recognition and resuscitation bundles, the algorithms
in Figs 1 and 2 can help guide initial management. Further
considerations for the community physician include timely
consultation with tertiary care services, including paediatric
intensive care, ID and surgical specialties. If surgical and
intensive care services are not available at a local centre,
organising urgent transport of a child with sepsis must be
considered early. Decisions regarding care do not need to be
made in isolation; consulting services can help guide man-
agement and provide support until transfer is organised.
Declaration of interests
The authors declare that they have no conflicts of interest.
MCQs
The associated MCQs (to support CME/CPD activity) are
accessible at www.bjaed.org/cme/home by subscribers to BJA
Education.
References
1. Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS.
Trends in the epidemiology of pediatric severe sepsis.
Pediatr Crit Care Med 2013; 14: 686e93
2. Tan B, Wong JJM, Sultana R et al. Global case-fatality rates
in pediatric severe sepsis and septic shock: a systematic
review and meta-analysis. JAMA Pediatr 2019; 173: 352e61
3. Schlapbach LJ, Straney L, Alexander J et al. Mortality
related to invasive infections, sepsis and septic shock in
critically ill children in Australia and New Zealand,
2002e13: a multicentre retrospective cohort study. Lancet
Infect Dis 2015; 15: 46e54
Sepsis in paediatrics
4. Wynn J, Cornell TT, Wong HR, Shanley TP, Wheeler DS.
The host response to sepsis and developmental impact.
Pediatrics 2010; 125: 1031e41
5. Singer M, Deutschman CS, Seymour CW et al. The Third
international consensus definitions for sepsis and septic
shock (Sepsis-3). JAMA 2016; 315: 801e10
6. Goldstein B, Giroir B, Randolph A et al. International pe-
diatric sepsis consensus conference: definitions for sepsis
and organ dysfunction in pediatrics. Pediatr Crit Care Med
2005; 6: 2e8
7. Matics TJ, Sanchez-Pinto N. Adaptation and validation of
a pediatric sequential organ failure assessment score and
evaluation of the Sepsis-3 definitions in critically ill chil-
dren. JAMA Pediatr 2017; 171, e172352
8. Schlapbach LJ, Straney L, Bellomo R, MacLaren G,
Pilcher D. Prognostic accuracy of age-adapted SOFA, SIRS,
PELOD-2, and qSOFA for in-hospital mortality among
children with suspected infection admitted to the inten-
sive care unit. Intensive Care Med 2018; 44: 179e88
9. Davis AL, Carcillo JA, Aneja RK et al. The American College
of Critical Care Medicine clinical practice parameters for
hemodynamic support of pediatric and neonatal septic
shock: executive summary. Pediatr Crit Care Med 2017; 18:
884e90
10. Dellinger RP, Levy MM, Rhodes A et al. Surviving sepsis
campaign: international guidelines for management of
severe sepsis and septic shock: 2012. Crit Care Med 2013;
41: 580e637
11. Pollack MM, Fields AI, Ruttimann UE. Distributions of
cardiopulmonary variables in pediatric survivors and
non-survivors of septic shock. Crit Care Med 1985; 13:
454e9
12. Carcillo JA, Kuch BA, Han YY et al. Mortality and func-
tional morbidity after use of PALS/APLS by community
physicians. Pediatrics 2009; 124: 500e8
13. Rhodes A, Evans LE, Alhazzani W et al. Surviving sepsis
campaign: international guidelines for management of
sepsis and septic shock: 2016. Intensive Care Med 2017; 43:
304e77
14. Kleinman ME, Chameides CL, Schexnayder SM et al. Part
14: pediatric advanced cardiovascular life support: 2010
American Heart Association guidelines for cardiopulmo-
nary resuscitation and emergency cardiovascular care.
Circulation 2010; 122: S876e908
15. El-Nawawy AA, Omar OM, Khalil M. Intraosseous versus
i.v. access in pediatric septic shock patients admitted to
Alexandria University pediatric intensive care unit. J Trop
Pediatr 2018; 64: 132e40
16. Emrath ET, Fortenberry JD, Travers C, McCracken CE,
Hebbar KB. Resuscitation with balanced fluids in associ-
ated with improved survival in pediatric sepsis. Crit Care
Med 2017; 45: 1177e83
17. Antequera Martı́n AM, Barea Mendoza JA, Muriel A et al.
Buffered solutions versus 0.9% saline for resuscitation in
critically ill adults and children. Cochrane Database Syst
Rev 2019; 7: CD012247
18. Stenson EK, Cvijanovich NZ, Anas N et al. Hyperchloremia
is associated with complicated course and mortality in
pediatric patients with septic shock. Pediatr Crit Care 2018;
19: 155e60
19. Weiss SL, Fitzgerald JC, Balamuth F et al. Delayed anti-
microbial therapy increases mortality and organ
dysfunction duration in pediatric sepsis. Crit Care Med
2014; 42: 2409e17
BJA Education - Volume 21, Number 2, 2021 57
Sepsis in paediatrics
20. Li D, Li X, Cui W, Shen H, Zhu H, Xia Y. Liberal versus
conservative fluid therapy in adults and children with
sepsis or septic shock. Cochrane Database Syst Rev 2018; 12:
CD010593
21. Wong JJ, Ho SX, Lee AOC et al. Positive fluid balance is
associated with poor clinical outcomes in paediatric se-
vere sepsis and septic shock. Ann Acad Med Singapore 2019;
48: 290e7
22. Morin L, Kneyber M, Jansen NJG et al. Translational gap in
pediatric septic shock management: an ESPNIC perspec-
tive. Ann Intensive Care 2019; 9: 73
23. Ventura AM, Shieh HH, Bousso A et al. Double-blind pro-
spective randomized controlled trial of dopamine versus
58 BJA Education - Volume 21, Number 2, 2021
epinephrine as first-line vasoactive drugs in pediatric
septic shock. Crit Care Med 2015; 43: 2292e302
24. Menon K, McNally JD, Choong K et al. A cohort study of
pediatric shock: frequency of corticosteroid use and as-
sociation with clinical outcomes. Shock 2015; 44: 402e9
25. Charlton M, Thompson JP. Pharmacokinetics in sepsis.
BJA Educ 2019; 19: 7e13
26. Paepe PD, Belpaire FM, Buylaert WA. Pharmacokinetic
and pharmacodynamic considerations when treating
patients with sepsis and septic shock. Clin Pharmacokinet
2002; 41: 1135e51