IV fluid administration in sepsis

Dr David Inwald Consultant in PICU

St Mary’s Hospital, London CATS, London

The talk

• What is septic shock?

• What are the recommendations?

• What is the evidence?

• Do we follow them?

• What should we do next?

Not included (but probably more important)

• Vaccination

• Early warning scores and tools

• Antibiotic resistance

• Education

• Genetic determinants of disease severity

A definition of shock

• A clinical syndrome of inadequate tissue perfusion

• DO2 < VO2

Septic shock

• Increased capillary permeability

• Dysregulation of vascular tone

• Depression of myocardial function

• Disseminated intravascular thrombosis

Increased capillary permeability

Dysregulation of vascular tone

Carcillo JA et al, Crit Care Med. 2002;30:1365-78

Sepsis

Warm shock High CO

vasodilation

Cold shock Low CO

vasoconstriction

Depression of myocardial contractility

Children – individual physiology

• Relative hypovolaemia

• Pump failure (variable)

• Vascular tone (variable)

• All unquantified

Management – one size fits all

• A & B management

• “Optimise” preload

• 20 mls/kg aliquots isotonic saline/colloid

• At 40-60 mls/kg reassess and consider inotropic support

• If developing pulmonary oedema consider “elective” ventilation

…in the first hour

Crit Care Med 2009; 37:666–688

isotonic crystalloid or colloid

Frank-Starling curve

inotrope

fluids

J Physiol. 1914 Sep 8;48(5):357-79

RAP

Car

dia

c o

utp

ut

..it is possible to overfill the heart…

…and the system is very complex

Lungs = black box

Pressure Flow

Sympathetic stimulation Parasympathetic stimulation

Shim EB et al, Phil. Trans. R. Soc. A (2006) 364, 1483–1500

Somatic influences

What is the evidence for the guidelines?

Carcillo JA et al, JAMA, 1991

Fluid in early septic shock • Retrospective review of 34 pediatric

patients with culture positive septic shock, from 1982-1989

• Hypovolemia determined by PCWP, urine output and hypotension. All on pressors.

• Three groups: • 1: received up to 20 mls/kg in 1st 1 hour

• 2: received 20-40 mls/kg in 1st hour

• 3: received greater than 40 mls/kg in 1st hour

• No difference in ARDS between the 3 groups

Early fluid and inotrope resuscitation 10 - fold reduction in mortality rate

Booy R et al, Arch Dis Child 2001;85:386-90

Early reversal of shock • Retrospective study of 91 children with septic

shock. Shock reversal, adherence to ACCM-PALS Guidelines, hospital mortality.

• 26 (29%) patients died.

• >9 x increased odds of survival (96%) in 24 (26%) patients in whom shock reversal was achieved by 75 minutes

• ACCM-PALS guidelines followed in 27 (30%) patients; in these patients, a lower mortality was observed (8% vs 38%)

Han YY et al Pediatrics. 2003;112:793-9

Fluid resuscitation of hypovolemic shock: acute medicine's great triumph for

children

Carcillo JA and Tasker RC, ICM 2006;32:958-61

Brierley J et al, Crit Care Med 2009; 37:666–688

Up to and over 60 ml/kg by 15 minutes

Do we follow the recommendations?

Arch Dis Child. 2009;94:348-53

PICS sepsis audit

• 200 patients with sepsis accepted to UK PICUs over 6 months 2006-7

• Median age 1.13 yrs (IQR 0.24 – 3.17)

• PIM2 predicted mortality 10% (5-16)

• 184 (92%) ventilated

• 138 (69%) required inotropes

• 24 (12%) required RRT

PICS sepsis audit

• 34 (17%) died

• 139 (70%) shocked on referral to PICU – 83/139 (60%) failed to reverse shock – 22 (26%)

died

– 53/139 (40%) reversed shock – 3 (6%) died

– p=0.02, Chi square, 3 patients not classified

PICS sepsis audit

• 107 (53%) shocked on arrival to PICU

• risk of death – OR=3.7 (95% CI 1.4-10.2), p=0.008

• ACCM-PALS guideline NOT followed in relation to – > 60 mls/kg fluid in 21/107 (20%)

– > 60 mls/kg + inotrope in only 68/107 (62%)

“The reasons for clinicians failing to follow simple algorithms for resuscitation are unclear and need further investigation”.

• African children with severe febrile illness with either impaired consciousness or respiratory distress, and impaired perfusion - Albumin bolus

- Saline bolus 20 ml/kg over 1 hour

- No bolus

• 48 hour mortality - Albumin group – 10.6% (111/1050)

- Saline group – 10.5% (110/1047)

- Control group – 7.3% (76/1044), p=0.003

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• Definitions unusual

- Severity = impaired consciousness OR respiratory distress

• African epidemiology

- High incidence of malaria, malnutrition, malaria

• No ICU treatments available (and in many centres no oxygen)

• Cause of death in bolus groups not known

Recent PICU studies (2011–2015)

Flori et al (2011). Acute lung injury, n=320. Increased ventilation days and mortality.

Arikan et al (2012). General PICU population, n=80. Oxygenation index, ventilation days, and LOS

Valentine et al (2012). Acute lung injury, n=168. Fewer ventilator-free-days at 28 days

Sinitsky et al (2015). General PICU population, n=636. Oxygenation index and ventilation days

Bhaskar et al (2015). General PICU, n=114. Mortality

How much fluid?

What fluid?

What fluid? • Hydroxyethyl starch associated with mortality

and RRT in critically ill adults, particularly those with sepsis

• Albumin associated with increased mortality in adults with severe traumatic brain injury

• 0.9% saline may be associated with adverse outcomes due to hyperchloraemic metabolic acidosis

What is the paediatric data?

Goal directed therapy

Early goal-directed therapy in the treatment of severe sepsis and septic

shock

NEJM 2001;345:1368-77

Rivers E et al.

Goal directed therapy

• RCT in 263 adult patients with severe sepsis

• Goals: – CVP 8-12 mm Hg

– mean arterial pressure ≥65 mm Hg

– urine output of ≥0.5 mls/kg/h

– central venous (superior vena cava) (Scvo2) or mixed venous oxygen (Svo2) saturation of ≥70%.

• In-hospital mortality 30.5 percent in the group assigned to early goal-directed therapy, 46.5 percent in the group assigned to standard therapy (p = 0.009)

Systematic review

• Five RCTs (n = 4735 patients); no effect on mortality (EGDT: 23.2% mortality [495/2134] versus control: 22.4% mortality [582/2601], p=0.9

• The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) showed no difference [OR 0.99 (95 % CI 0.86-1.15), p = 0.93]

Conclusion?

• We don’t know how much fluid to give – and when

• We don’t know what fluid to give

• We don’t know whether EGDT works in kids or not

Current management

• A - Airway

• B - Breathing

• C - Circulation

ACCM-PALS goals

• HR

• BP

• CRT

• Conscious level

• Peripheral skin temperature

• Urine output

November 2011 - Manchester United 1-0 Sunderland Wes Brown gifts three points to Sir Alex Ferguson as 25th

anniversary present with own goal

ACCM-PALS goals

• HR – effect of pain, fever, distress

• BP – 5th centile? 50th centile?

• CRT – ambient temp? methodology?

• Conscious level

• Peripheral skin temperature

• Urine output

Paediatric sepsis management – Levels of evidence for anecdote-based

medicine

• Level I: Beardy old gent from Royal College

• Level II: Doctor with air of credibility and honest face

• Level III: Academic with mad stare

• Level IV: NHS manager with Trust in financial crisis

Conclusion

• Early aggressive fluid therapy current “gold standard”

• Lack of trial evidence

• Concerns raised by FEAST

• Need a paediatric fluid bolus trial in developed world