IV fluid administration in sepsis. Dr David Inwald Consultant in PICU St Mary s Hospital, London CATS, London
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1 IV fluid administration in sepsis Dr David Inwald Consultant in PICU St Mary s Hospital, London CATS, London
2 The talk What is septic shock? What are the recommendations? What is the evidence? Do we follow them? What should we do next?
3 Not included (but probably more important) Vaccination Early warning scores and tools Antibiotic resistance Education Genetic determinants of disease severity
4 A definition of shock A clinical syndrome of inadequate tissue perfusion DO 2 < VO 2
5 Septic shock Increased capillary permeability Dysregulation of vascular tone Depression of myocardial function Disseminated intravascular thrombosis
6 Increased capillary permeability
7
8 Dysregulation of vascular tone
9 Sepsis Warm shock High CO vasodilation Cold shock Low CO vasoconstriction Carcillo JA et al, Crit Care Med. 2002;30:
10 Depression of myocardial contractility
11
12 Children individual physiology Relative hypovolaemia Pump failure (variable) Vascular tone (variable) All unquantified
13 Management one size fits all A & B management Optimise preload 20 mls/kg aliquots isotonic saline/colloid At mls/kg reassess and consider inotropic support If developing pulmonary oedema consider elective ventilation
14 isotonic crystalloid or colloid in the first hour Crit Care Med 2009; 37:
15 Frank-Starling curve fluids inotrope
16 J Physiol Sep 8;48(5):357-79
17 Cardiac output RAP
18 ..it is possible to overfill the heart
19 and the system is very complex
20 Lungs = black box Pressure Flow
21 Somatic influences Sympathetic stimulation Parasympathetic stimulation Shim EB et al, Phil. Trans. R. Soc. A (2006) 364,
22
23 What is the evidence for the guidelines?
24 Carcillo JA et al, JAMA, 1991
25 Fluid in early septic shock Retrospective review of 34 pediatric patients with culture positive septic shock, from Hypovolemia determined by PCWP, urine output and hypotension. All on pressors. Three groups: 1: received up to 20 mls/kg in 1 st 1 hour 2: received mls/kg in 1 st hour 3: received greater than 40 mls/kg in 1 st hour No difference in ARDS between the 3 groups
26
27 Early fluid and inotrope resuscitation 10 - fold reduction in mortality rate Booy R et al, Arch Dis Child 2001;85:386-90
28 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
29 Fluid resuscitation of hypovolemic shock: acute medicine's great triumph for children Carcillo JA and Tasker RC, ICM 2006;32:958-61
30 Up to and over 60 ml/kg by 15 minutes Brierley J et al, Crit Care Med 2009; 37:
31 Do we follow the recommendations?
32 Arch Dis Child. 2009;94:348-53
33 PICS sepsis audit 200 patients with sepsis accepted to UK PICUs over 6 months Median age 1.13 yrs (IQR ) PIM2 predicted mortality 10% (5-16) 184 (92%) ventilated 138 (69%) required inotropes 24 (12%) required RRT
34 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
35 PICS sepsis audit 107 (53%) shocked on arrival to PICU risk of death OR=3.7 (95% CI ), 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%)
36 The reasons for clinicians failing to follow simple algorithms for resuscitation are unclear and need further investigation.
37
38
39 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
40
41 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
42 Recent PICU studies ( ) 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
43 How much fluid?
44 What fluid?
45 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
46 What is the paediatric data?
47 Goal directed therapy
48 Early goal-directed therapy in the treatment of severe sepsis and septic shock NEJM 2001;345: Rivers E et al.
49 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) (Scvo 2 ) or mixed venous oxygen (Svo 2 ) 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)
50
51
52 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 ), p = 0.93]
53
54 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
55 Current management A - Airway B - Breathing C - Circulation
56 ACCM-PALS goals HR BP CRT Conscious level Peripheral skin temperature Urine output
57 November Manchester United 1-0 Sunderland Wes Brown gifts three points to Sir Alex Ferguson as 25th anniversary present with own goal
58 ACCM-PALS goals HR effect of pain, fever, distress BP 5 th centile? 50 th centile? CRT ambient temp? methodology? Conscious level Peripheral skin temperature Urine output
59 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
60 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
61
towards early goal directed therapy
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