Fluids and Solutions in Septic

Shock: Crystalloids, Colloids and

Blood Product - When to Use?
Joe Brierley
Paediatric Intensivist, Great Ormond St, London

Welcome to London!
Welcome to the North of the River to my colleagues from the South
 Fluids and Solutions in
Septic Shock: Crystalloids,
Colloids and Blood Product -
whether to Use?

Joe Brierley
Paediatric Intensivist Great Ormond St, London
 Galen c.AD 129c.216
discussing fluids in septic shock
All who drink of this
remedy recover in a short
time, except those whom
it does not help, who all
die

Therefore, it is obvious
that it fails only in
incurable cases
Marik PE. Iatrogenic salt water drowning and hazards of high CVP
Annals of Intensive Care. 2014;4:21

Aggressive fluid resuscitation fluid overload associated increased morbidity &

mortality in diverse groups- severe sepsis, elective surgical & trauma

Excessive fluid administration increased interstitial fluid in vital organs impairing

renal, hepatic & cardiac function

Increased extra-vascular lung water is particularly lethal, leading to iatrogenic salt

water drowning

EGDT & Surviving Sepsis Campaign Guidelines recommend CVP > 8 mmHg
CVP > 8 mmHg decreases microcirculatory flow, renal blood flow & associated renal failure & death

Normal saline (0.9% salt solution) as compared to balanced electrolyte solutions

associated with greater risk of acute kidney injury & death
 Fluid bad for children?
Bhaskar P et al. Early fluid accumulation in children with shock
and ICU mortality: a matched casecontrol study. Intensive Care
Medicine. 2015 :3851

Sinitsky L, Walls D, Nadel S, Inwald DP. Fluid overload at 48 hours

is associated with respiratory morbidity but not mortality in a
general PICU: retrospective cohort study. Pediatr Crit Care Med.
2015 Mar;16(3):205-9
 How did we get here?
APLS, EPLS 20ml/kg and
repeat
 How did we get here?

Those who cannot remember the past are condemned

to repeat it.

George Santayana, The Life of Reason, 1905

Lancet
She had apparently reached the last moments
of her earthly existence.I feared I should be
unable to get my apparatus ready ere she expired.

Having inserted a tube into the basilic vein; ounce

after ounce was injected, but no visible change
was produced

. she began to breath less laboriously; soon the ..

sunken eye and fallen jaw, pale and cold, bearing
the manifest impress of deaths signet, began to
glow with returning animation;
the pulse which had long ceased, returned to the
wrist.

and in a short space of half an hour, when six

pints had been injected,

she expressed in a firm voice that she was free

from all uneasiness, actually became jocular, and
fancied all she needed was a little sleep;

her extremities were warm, and every feature

bore the aspect of comfort and health.
This being my first case, I fancied my
patient secure, and left her in charge of
the hospital surgeon;

but I had not been long gone, ere the vomiting

and purging recurring, soon reduced her to her
former state of debility. I was not apprised of the
event, and she sunk in five and a half hours
after I left her.

I have no doubt the case would have issued

in complete reaction, had the remedy
been repeated
Role of early fluid resuscitation in pediatric (sic) septic shock.
Carcillo JA, Davis AL, Zaritsky A. JAMA 1991 4;266(9):1242-5

All children with septic shock to ER over 6 yrs PA catheter by 6 hrs

3 groups based on fluid volume in first hour:

group 1, less than 20 mL/kg
group 2, 20 to 40 mL/kg
group 3, more than 40 mL/kg

RESULTS: 34 patients (median age 13.5 months)

mL/kg (mean +/- SD)
1 hour 6 hours

group 1 (n =14) 11 +/-6 71 +/-29

group 2 (n=11) 32 +/-5 108 +/-54

group 3 (n=9) 69 +/-19 117 +/-29

Role of early fluid resuscitation in pediatric (sic) septic shock.
Carcillo JA, Davis AL, Zaritsky A. JAMA 1991 4;266(9):1242-5

All children with septic shock to ER over 6 yrs PA catheter by 6 hrs

3 groups based on fluid volume in first hour:

group 1, less than 20 mL/kg
group 2, 20 to 40 mL/kg
group 3, more than 40 mL/kg

RESULTS: 34 patients (median age 13.5 months)

mL/kg (mean +/- SD)
Death 1 hour 6 hours

group 1 (n =14) (6/14) 57% 11 +/-6 71 +/-29

group 2 (n=11) (7/11) 63% 32 +/-5 108 +/-54

group 3 (n=9) (1/9) 11%* 69 +/-19 117 +/-29

* Less organ dysfunction, including CVS, failure group 3

Amount of Fluid given in first hour
(C Oliveira et al 2006)
P = 0.03 chi square for trend

80% 73%

70%
60% 52%
50%

40% 33%
Mortality
30%
20%

10%
0%
> 40 ml/kg 20-40 ml/kg < 20 ml/kg
Shock should be clinically diagnosed,
before hypotension occurs, by:

hypothermia or hyperthermia,
altered mental status,
with peripheral vasodilation
or cool extremities with capillary refill > 2 seconds
Han Y, Carcillo J, Dragotta M, et al. Early Reversal of Pediatric-Neonatal Septic Shock by
Community Physicians Is Associated With Improved Outcome. Pediatrics, Oct 2003; 112: 793 -
799
Algorithm for time sensitive, goal-directed stepwise
management of hemodynamic support in infants & children:
Proceed to next step if shock persists

1) First hour goals

Restore & maintain heart rate thresholds, capillary
refill < 2 sec & normal BP

Support oxygenation & ventilation as appropriate

2) Subsequent (ICU) goals

shock not reversed?

- Intervene to restore & maintain

normal perfusion pressure: MAP-CVP for age

central venous O2 saturation > 70%

CI 3.3-6.0 L/min/m

Hgb, hemoglobin, PICCO, pulse contour cardiac output;

FATD,femoral arterial thermodilution;ECMO, extracorporeal
membrane oxygenation; CI, cardiac index; CRRT, continuous renal
replacement therapy; IV, intravenous; IO, interosseous; IM,
intramuscular
Clinical practice parameters for hemodynamic support of pediatric &
neonatal septic shock: 2007 update from the ACCM. Brierley J,
Carcillo J, Choong K et al. Crit Care Med 2009 Vol. 37
 102 Septic Shock
Patients

Goal normal perfusion Goal CV O2 sat > 70%

28 day Mortality 28 day Mortality

20/51 (39.2%) 6/51(11.8%)

OR 0.2 95% CI 0.07-0.57 p=0.002

 Stop fluid
When shock reversed
ACCM: When rales or hepatomegaly.
Static parameters
CVP, HR fall, Global end diastolic volume index
Dynamic parameters
Arterial pressure variations with ventilation, SV change with
passive leg raising or fluid bolus

Extravascular lung water

When ? Not clear!

 Septic Shock
UK mortality 17% from referral to PICU

odds ratio for death, if shocked at PICU admission 3.8

(95% CI 1.4-10.2, p=0.008)
(<1% GOSH after been admitted 4 hours)

International consensus guidelines ACCM-PALS not followed

Inadequate recognition, fluid, senior review & antibiotics < 1 hr

Every hour child stays shocked DOUBLES mortality (Han)

Inwald DP et al. Emergency management of children with severe sepsis in the
United Kingdom: the results of the Paediatric Intensive Care Society sepsis audit.
Arch Dis Child 2009;94:348-53.
 Take home message
From hemodynamic work by lead author in similar cohort
Fluid negatively inotropic (KM personal communication)

In FEAST ACCM Hemodynamic parameter guidance not followed

No inotrope, ? FiO2, no CPAP
Protein malnutrition affects on myocardium?

Are these children already at the top of their Starling curve?

Is there an adaptive response at work in this population?
Chronic shock

Later analysis shock reversed, death not due to fluid overload but
cardiovascular collapse: Maitland K, George E, Evans J, et al. Exploring
mechanisms of excess mortality with early fluid resuscitation: insights from the
FEAST trial. BMC Medicine 2013, 11:68.
Faddan N, Sayh K, Badrawy H. Myocardial dysfunction in
malnourished children. Ann Pediatr Cardiol. 2010 Jul;3(2):113

45 malnourished infants/young children v 25 apparently healthy controls

Malnourished children significantly lower LV mass,

LV systolic functions significantly impaired with severe malnutrition

cTnT level > upper reference limits -11 (24%) malnourished children (all severe malnutrition)

cTnT level significantly higher with anemia, sepsis & electrolyte abnormalities & correlated
negatively with LV ejection fraction

6 with high cTnT levels (54.5%) died within 21 days vs. 1 (2.9%) with normal cTn
Surviving Sepsis Campaign: International Guidelines
for Management of Severe Sepsis and Septic Shock,
2012. ICM Volume 39, Issue 2 / February , 2013

Key fluid recommendations and suggestions:

initial fluid resuscitation with crystalloid (1B) and consideration of addition of
albumin in patients who continue to require substantial amounts of crystalloid to
maintain adequate mean arterial pressure (2C)
& avoidance of hetastarch formulations (1B)
initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and
suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids
(more rapid administration and greater amounts of fluid may be needed in
some patients (1C)
fluid challenge technique continued as long as hemodynamic improvement is
based on either dynamic or static variables (UG)
 What do we do?
Give less or fewer fluids?
How
Numbers - e.g. 10 vs 20ml/kg, repeat or not
Parameters
Starling curve - measure CI change with volume?

Give no fluid?
Which fluid?
Gan H, Cannesson M, Chandler J, Ansermino J. Predicting fluid
responsiveness in children: systematic review. Anesth Analg. 2013;117(6)

PubMed (1947-2013) & EMBASE (1974-2013): CONCLUSIONS:

Search terms: Infant, child, & adolescent; fluid, volume, response,
respond, challenge, bolus, load, predict & guide
Respiratory variation in ABF-PV only
Independent data extraction predefined data fields
variable shown to predict fluid
Variables with area under ROC curve significantly > 0.5 responsiveness in children
considered predictive
Static variables did not predict fluid
12 studies - 501 fluid boluses in 438 pts (1/7-17.8 yrs)
responsiveness - consistent with adult
evidence
24 variables investigated: 1 predictive multiple (5) studies
Respiratory variation in aortic blood flow peak velocity (ABF-PV) Dynamic variables based on arterial BP did
not predict fluid responsiveness, evidence
Stroke volume index, stroke distance variation, & cardiac index
for dynamic variables based on
(& stroke volume) from passive leg-raising predictive single
studies only plethysmography inconclusive
Static variables: based heart rate, systolic arterial BP, preload (CVP,
PA occlusion pressure), thermodilution (global EDV index), ultrasound
dilution (active circulation volume, central blood volume, total EDV, total
ejection fraction), echo (LV end diastolic area), & Doppler (stroke volume
index, corrected flow time) not predictive Dynamic variables: based
arterial BP (variation in systolic pressure or pulse pressure or stroke
volume; difference between maximal or minimal systolic arterial BP &
systolic pressure at end-expiratory pause) & plethysmography (pulse
oximeter plethys amplitude variation) not predictive
Plethysmograph variation index & IVC diameter variation
contradictory results
Ketharanathan N, McCulloch M, Wilson C, Rossouw B, Salie S, Ahrens J,
Morrow BM, Argent AC. Fluid overload in South African PICU. J Trop Pediatr.
2014 Dec;60(6):428-33

OBJECTIVE: Fluid resuscitation integral to resus guidelines & critical care. But, fluid overload (FO) yields
increased morbidity

METHODS: Prospective observational study Red Cross PICU admissions (February -March 2013)

FO % = (fluid in minus fluid out) [liters]/weight [kg] 100%

PRIMARY OUTCOMES: FO 10%, 28 day mortality

RESULTS:
Median IQR age: 9.5 (2.0-39.0)months, IQR admission weight: 7.9 (3.6-13.7)kg. Median IQR FO with admission weight: 3.5
(2.1-4.9)%
28 day mortality 10% (n = 10), those who died had higher mean (IQR) FO using admission weight [4.9 (2.9-9.3)% vs. 3.4 (1.9-
4.8)%; p = 0.04]

CONCLUSIONS: Low FO 10% prevalence with 28 day mortality 10%; higher FO% with admission weight
associated with mortality (p = 0.04)

Advocate further investigation of FO% as simple bedside tool

 Which fluid to choose
Time to give
Expense
Volume expansion
Time remains in intravascular space
Toxicity

Studies/data
Lira A, Pinsky M. Choices in fluid type & volume during
resuscitation: impact on patient outcomes. Annals of
Intensive Care 2014, 4:38
Lira A, Pinsky M. Choices in fluid type and volume during
resuscitation: impact on patient outcomes. Annals of
Intensive Care 2014, 4:38

1. Colloids at large: no clear benefit associated with use of expensive colloids over
inexpensive crystalloids. Colloids increase TBI mortality. No indications exist for routine
colloids over crystalloids

2. Albumin: No evidence supports unique benefit of albumin as resuscitation fluid.

With inclusion of ALBIOS trial (NEJM 2015 20% albumin and crystalloid solution vs.
crystalloid solution in severe sepsis)mortality benefit in sepsis unproven. With cost &
limited shelf-life, albumin as resus fluid not supported

3. HES: Associated with harm, not clearly mortality. Evidence increased AKI & RRT,
coagulopathy & blood transfusion. Effects dose dependent, but no consensus re safe
dose: AVOID

4. Dextran and gelatins: Other synthetic colloids poorly studied. No evidence harm or
benefit vs. other colloids & theoretical potential for adverse effects: AVOID
Lira A, Pinsky M. Choices in fluid type and volume during
resuscitation: impact on patient outcomes. Annals of
Intensive Care 2014, 4:38

5. 0.9% saline: Associated with development hyperchloremic metabolic acidosis &

increased risk AKI in susceptible pts, especially DKA. Risk decreased if balanced salt
solutions used. Balanced crystalloid solutions rather then NS should be considered in
these populations

6. Balanced crystalloid solutions: No harmful effects in any particular population.

Evidence benefit over NS as above. No head-to-head study comparing different balanced
crystalloids, therefore no consensus on preferred solution. Literature supports balanced
crystalloids especially where NS may cause adverse effects

7. Volume: Fluid resuscitation should be applied in goal-directed manner, targeted to

physiological needs of individual patients. Evidence supports fluid use in volume-
responsive patients whose end-organ perfusion parameters not met. Studies show
improved outcomes of goal-directed therapy over fluid-liberal approach
 Blood use in sepsis
No

Holst L, Haase N, Wetterslev J et al. Lower vs Higher Hemoglobin Threshold for Transfusion in
Septic Shock. N Engl J Med 2014; 371:1381-1391.
Restrictive 7g/dl vs 9 no difference (c.f. TRIPICU)

Vs. Transfuse as part of Rivers original protocol

Yes

Strong Recommendation: WHO ETAT 4B Children with shock & severe anaemia
(defined by WHO Handbook) should receive blood transfusion as early as possible
and only receive fluids to maintain normal hydration status
(likely) WHO ETAT 2015
4a. Children who have shock i.e. all the following: cold
extremities & weak & fast pulse & capillary refill >3 sec,
should receive IV fluids as follows:

10-20 ml/kg isotonic crystalloid fluids over 30-60

minutes

Should be reassessed at completion of infusion

and over subsequent hrs to check for
deterioration:
If still in shock consider further 10 ml/kg
over 30 mins
If shock resolved provide maintenance only
fluids to maintain normal hydration
If at any time signs of neurological
deterioration, fluid overload or cardiac
failure then fluid infusion should be stopped
and no further IV fluid infusions given until
signs resolve
 Fluids and Solutions inWhen
Septic the facts
Shock:
change,
Crystalloids, Colloids and I change
Blood Product - my
mind. What do you
Yes: 10-20 ml/kg balanced crystalloid
do, Sir?
No: to colloid John Maynard
Keynes
No: to blood unless severe anaemia leading to shock

New (last) ACCM guidelines soon

Evidence.

Yes we could do with need some in our population