Management of paediatric
shock – fluids and inotropes
Allan Wardhaugh
Paediatric Intensivist
UHW Cardiff
Management of shock
Physiology
Basic clinical assessment
Laboratory and invasive clinical
assessment
Management


Fluid choice
Inotropes and vasopressors
Definition of Shock
Definition of Shock
Inadequate oxygen delivery to
tissues to meet demand because
of circulatory failure
Cause of shock
Not enough fluid in circuit
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Sepsis
Haemorrhage
Dehydration
Maldistribution – ‘third spacing’ – many causes
Pump failure

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Sepsis
Cardiomyopathy/ myocarditis
Arrythmia
Inadequate oxygen carrying capacity
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Anaemia
CO poisoning
Very low circuit resistance
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AVM
Sepsis
Physiological aims of treatment
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure

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Maintain pump pressure
Optimise circuit resistance
Physiology – oxygen delivery
O2 delivery =[(1.34  Hb  O2 sats) + (PO2  0.023)]  CO
CO = HR  SV
Oxygen supply – dependence in
critically ill
Physiology – fluid filled circuit and
Ohm’s Law
I = V/R
Flow = Perfusion pressure/
Resistance
Cardiac Output = MAP-CVP/ SVR
Perfusion pressure = CO 
SVR
Aim of treatment – prevent perfusion
pressure dropping below critical
point
Critical point
Clinical assessment
Recognition - clinical
Tachycardia
Tachypnoea
Energy conservation

Relative inactivity
Vasoconstriction

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CRT
Core–peripheral temperature gap
Organ hypoperfusion

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Oliguria
Irritability, diminished consciousness
Hypotension
Distribution of cardiac output
Brain
13%
Skeletal Muscle
20%
Abdominal viscera
25%
Skin
10%
Kidneys
20%
Kidneys receive high proportion CO – if urine is
flowing >0.5 – 1ml/kg/hr, cardiac output is
probably adequate
Has enough fluid been given?
Distribution of blood in circulation
Heart
Systemic


Arteries
Veins
Pulmonary
5%
80%
10%
65%
15%
Venous reservoir
‘Window’ on venous reservoir


Liver in neonates/ infants
Jugular venous pulse in older children
Response to hepatic pressure – simulates
venoconstriction and fluid bolus

beware cardiogenic shock
Recognition - bloods
Base deficit > -4

Hyperchloraemia confounds after volume
resuscitation
Lactate >2.5 mmol/l

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May signify poor tissue oxygen delivery
Beware other causes (metabolic, liver failure)
Mixed venous oxygen saturations
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Venous PO2 reflects tissue oxygenation
Low values probably more reliable than high
Mixed venous sats > 70% imply adequate tissue
oxygenation
More invasive monitoring?
Once in ICU, clinical
parameters correlate
less well to cardiac
output
Cardiac output
estimation


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TOE
PiCCO
Li dilution
et al
Tibby et al. Clinicians’ abilities to estimate cardiac index in
ventilated children and infants. Archives of Disease in Childhood 1997;77:516–518
Management
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure


Maintain pump pressure
Optimise circuit resistance
ABC
Oxygen
A also stands for antibiotics

Ceftriaxone 80mg/kg
Management
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure


Maintain pump pressure
Optimise circuit resistance
Volume Volume Volume
Sepsis - >40ml/kg fluid volume in first hour –
should almost certainly be ventilated
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Early intubation and ventilation easier and safer
Prevents hypoxia
Facilitates line placement for adequate monitoring,
inotrope delivery
Restoring circulating volume
Blood volume 65ml/kg adult, 80-90ml/kg infant
40ml/kg corrects volume in most cases if
ongoing losses have stopped
Ongoing losses hidden in
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Intra-abdominal/ intra-thoracic haemorrhage
IVH in neonates
Sepsis
Gut obstruction
Which fluid?
0.9% Saline or 4.5% Albumin
Meta-analysis 1998 flawed
Units reporting improving outcomes in sepsis
use 4.5% albumin routinely
More recent meta-analyses show no increased
mortality with albumin
0.9% saline cheaper
Albumin produces greater expansion in ECF and
plasma volume

Individual responses to this vary
SAFE study
MCRCT of 4% human albumin vs 0.9% saline 16 ICUs
Australia/ New Zealand.
Patients aged >18years and needed fluid resuscitation.
Randomised to have saline or albumin for duration of
stay in ICU, or 28/7.
Burns, liver transplant and cardiac surgery excluded.
Death at 28 days primary outcome.
3499 HAS, 3501 Saline.
Baseline characteristics of both groups similar.
SAFE – fluid volume given
Which crystalloid?
Normal saline
Hartmann’s solution
Crystalloid electrolyte composition
Na
K
Cl
Other
0.9% saline
150
0
150
0.45% saline/ 5%
dextrose
75
0
75
0.18% saline/ 4%
dextrose
30
0
30
286
Dextrose 5%
0
0
0
252
Hartmann’s
131
5
111
Tonicity
308
lactate
280
Which colloid?
Albumin
Gelatins
Starches
Dextrans  hypertonic
saline
Colloids
Fluid
Notes
Half life in
circulation
Gelofusine
Made from horses. Anaphylaxis
4h
Dextran 70/
Saline 0.9%
Relatively high risk of anaphylaxis compared to 12h
starch.
Tetratsarch
(Voluven)
Associated with coagulopathy (reduces factor
VIII and vWF activity)
Hyperchloraemic acidosis.
Accumulates in RES – long term effects
uncertain.
May reduce systemic inflammation, but it
needs to be given with additional free water.
17 days
Pentastarch
(HemoHes)
Less effect on coagulation
18hr
Management
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure
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
Maintain pump pressure
Optimise circuit resistance
Haemodilution
Keep Hb > 10g/dL in resuscitation phase
Clotting factors – FFP
Platelets
X Match at presentation
Haemorrhagic shock - lose blood
 give blood?
Less O2 carrying capacity, but better than
clear fluid
3 for 1 rule using crystalloid to correct ECF
fluid shifts
Animal models suggest aggressive volume
resuscitation may be harmful
One RCT in adults promoted delayed fluid
resuscitation (Houston 1994)
Houston penetrating trauma study
Survive to
discharge
Hospital stay
(days)
Immediate
volume
resuscitation
Delayed volume
resuscitation
p-value
193/309 (62%)
203/289 (70%)
0.04
14  24
11  19
0.006
8% in DR violated protocol (received volume)
Severity of shock varied from pulse barely palpable to systolic bp
90mmHg

Arrival bp higher in DR group
Deaths before theatre removed ( destined to die) – no difference in
outcome
Times from injury to theatre short
NNT 12.5 ( 6.4 – 230) – very wide confidence intervals
Bickell et al.Immediate versus Delayed Fluid Resuscitation for Hypotensive
Patients with Penetrating Torso Injuries. N Engl J Med 1994; 331:1105-1109
Hypotensive resuscitation cannot
presently be recommended in
paediatric trauma
How much fluid?
Aggressive volume resuscitation associated
with improved survival in septic children
Only study to show a beneficial intervention in paediatric
septic shock – observational study
Recruited all paediatric sepsis patients to ER in
Washington DC Childrens Hospital – PA catheter in situ
by 6 hours
34 patients – mean age 13.5 months
Divided into 3 groups by volume received in first hour
(post hoc)
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Group 1
<20ml/kg
Group 2 20 – 40ml/kg
Group 3
>40ml/kg
Carcillo et al.
Carcillo et al. Role of early fluid resuscitation in pediatric
septic shock. JAMA. 1991;266:1242-1245
Mortality
Totals in each group
14
11
9
70%
60%
50%
40%
30%
20%
10%
0%
<20ml/kg
20 -
>40ml/kg
ARDS
40%
35%
30%
25%
20%
15%
10%
5%
0%
<20ml/kg
20-40ml/kg
>40ml/kg
Hypovolaemia at 6 hours
50%
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%
<20ml/kg
20 >40ml/kg
40ml/kg
Management
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure


Maintain pump pressure
Optimise circuit resistance
Inotropes (and pressors)
Inotropes and pressors
Advantages
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Improve pump function
Increase SVR
improving perfusion
pressure
Increase diastolic BP
improving coronary
artery perfusion
Disadvantages
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May increase afterload
Increase myocardial
oxygen demand
Arrythmia
Extravasation danger
– should go centrally
When to start inotropes
Sepsis – failure to respond to 40ml/kg fluid
in first hour
Mortality in paediatric septic shock
strongly associated with low cardiac output
Will need adequate monitoring
Invasive BP if possible
Available inotropes and pressors
Natural catecholamines
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Adrenaline
Noradrenaline
Dopamine
Synthetic catecholamines
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Dobutamine
Phosphodiesterase inhibitors
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Milrinone
Pure pressors
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Vasopressin, terlipressin
Which inotrope?
Choice of inotrope
Personal preference prejudices common

remember this is ‘class 4 evidence’
No RCTs to rely on
‘Warm’ shock with good CO and low SVR
less common in children
‘Cold’ shock with low CO and normal or
high SVR more common – some use
vasodilators
Management
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure


Maintain pump pressure
Optimise circuit resistance
Dopamine
Precursor of noradrenaline.
1, 1, 2, DA1, DA2 receptors.
5 – 15 mcg/kg/min
1 effects dominate
> 15
1 become important
> 25
1 dominates
Renal dose – no such thing
Adrenaline
 1 , 1 , 2 .
0.05 – 0.3 g/kg/min

1, 2 > 1,
2 effects may cause balanced effect on SVR.
0.3 – 1 g/kg/min
> 1 g/kg/min
1, 2 = 1
1, 2 < 1
Disadvantage - increase in myocardial O2
demand and arrythmias
Dobutamine
Synthetic mixture of two stereo-isomers.
One isomer has  effects, the other 1.
5 – 20 g/kg/min
1,2
Increases contractility, increases HR
May ‘unmask’ hypovolaemia
SVR decreases. Direct coronary vasodilatory
effect.
>20 g/kg/min 1 dominates
Management
Get oxygen into the fluid
Get fluid in the circuit

Make sure the fluid can carry oxygen
Maintain adequate perfusion pressure


Maintain pump pressure
Optimise circuit resistance
Noradrenaline
1 and 1, with dominant 1 effects.
<0.5 g/kg/min
1 = 1
0.5 - 4g/kg/min 1 > 1
Use to maintain MAP improves urine
output and creatinine clearance in
paediatric hyperdynamic septic shock.
Milrinone
PDE III inhibitor
Small X-over trial showed benefit in
catecholamine resistant septic shock
Inotrope, improves diastolic function,
vasodilates
Long half-life, but loading dose usually
avoided by me
Vasopressin
Vasopressin deficiency in vasodilatory
shock
Adult trial showed reduced catecholamine
requirement with vasopressin
May have beneficial effects on coronary
circulation
Putting it all together goal directed treatment
Goal directed treatment in sepsis –
first hour
Resuscitation goals
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Maintain oxygenation
Maintain normal perfusion pressure (MAP – CVP)
Maintain threshold heart rates
Therapeutic end points
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CRT < 2 secs
Urine output > 1ml/kg/hr
Normal conscious level
Normal bp for age
Threshold values
Age (years)
Heart rate
MAP – CVP
(Carcillo)
MAP –CVP
(ESICM)
Term newborn
120-180
55
40
≤1
120-180
60
45
≤2
120-160
65
50
≤7
100-140
65
55
≤ 15
90-140
65
60
Goal directed treatment in sepsis –
beyond first hour
Goals
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Normal perfusion
Appropriate MAP-CVP (CVP 8 – 12mmHg)
SVC sats > 70%
CI >3.3 < 6.0 L/min/m2
0 – 5 mins
Recognise shock
Airway support
20ml/kg colloid or 0.9% saline
Correct glucose, calcium
15 mins
Central venous access
Start Dopamine
Titrate Adrenaline (cold shock)
Titrate noradrenaline (warm shock)
60 mins
Hydrocortisone if risk of adrenal
insufficiency
Normal BP cold shock
SVC O2 sat < 70%
Low BP Cold shock
SVC O2 sat < 70%
Low BP Warm shock
More volume
Vasodilator or PDE III inhibitor
More volume plus adrenaline
More volume plus noradrenaline
Consider vasopressin
Cardiac output monitoring – direct therapy to
Cardiac Index and MAP-CVP
ECMO
Does goal directed treatment work?
Goal directed treatment in sepsis –
evidence of benefit
Detroit, RCT – 263 adults
Randomised on arrival A + E and managed first 6 hours
standard vs goal directed
Targets for CVP, MAP, UO, SVC sats
In hospital mortality 46% standard vs 30% goal directed
NNT 4.8 (3 – 11)
Rivers E, Nguyen B, Havstad S et al. Early Goal-Directed Therapy in the
Treatment of Severe Sepsis and Septic Shock. N Eng J Med 2001; 345:13681377
Goal directed treatment in sepsis –
evidence of benefit children
100 consecutive paediatric septic shock (3
different hospitals) patients with PA
catheter by 6 hours
Goals targeted – CI, SVR
Overall 80% 28 day survival.
Outcomes improved compared to
historical controls
Ceneviva G, Paschall JA, Maffei F, Carcillo J. Hemodynamic support in
fluid refractory pediatric septic shock. Pediatrics 1998; 102:e19.
Ceneviva G et al – survival less
likely in low cardiac output group
100%
90%
28 day survival
80%
70%
60%
50%
Low CI
High CI, low SVR
CI and SVR
abnormal
Early management influences
outcome
9 year retrospective cohort 91 children
septic shock
Audited against ‘standard’ ACCM septic
shock management guidelines
Han YY, Carcillo JA, Dragotta MA, et al. Early Reversal of Pediatric-Neonatal
Septic Shock by Community Physicians Is Associated With Improved Outcome.
Pediatrics 2003;112 793-799.
Case control study of fatal vs. non-fatal
meningococcal disease 1997-1999
145 cases; 355 controls
Factors associated with death

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Not under care of paediatrician
Failure of supervision by a consultant
Failure in administration of inotropes
Ninis N, Phillips C, Bailey L et al. The role of healthcare delivery in
the outcome of meningococcal disease in children: case-control
study of fatal and non-fatal cases. BMJ 2005;330:1475
Practical advice – septic shock
Volume paramount following basic ABC
Give 20ml/kg saline or albumin 4.5%,
reassess, repeat as often as needed.
If no response to 40ml/kg in first hour,
prepare to intubate and ventilate, start
dopamine 10mcg/kg/min (centrally if
possible)
Refer PICU
Practical advice
No response to dopamine – start
adrenaline at 0.1mcg/kg/min centrally
If low diastolic and bounding peripheries
start noradrenaline – echo may help if
available
Keep giving fluid boluses
Haemodilution and clotting factor depletion
will occur – have blood, FFP,
cryoprecipitate available