Fluid Boluses in Preterm Babies with Poor Perfusion: A Hot Potato. Win Tin The James Cook University Hospital University of Durham

Transcription

1 Fluid Boluses in Preterm Babies with Poor Perfusion: A Hot Potato Win Tin The James Cook University Hospital University of Durham

2 Introduction Fluid Bolus/es (Intravascular Volume Expansion) - One of the most widely used non-evidence based therapy in NICUs Can be live saving Can also be harmful Lack of good evidence; hence rationalised approach at best Difficulty in ascertaining its role in sick newborns

3 A Hot Potato Definition (Cambridge English Dictionaries) A problem, situation, etc. that is difficult to deal with and causes a lot of disagreement

4 Outline Why do we use fluid bolus/es (volume expansion)? Physiology & Pathophysiology Definition and Assessment of Perfusion Effect of volume expansion on: blood pressure systemic blood flow metabolic acidosis Fluid bolus therapy in preterm infants Why should we be cautious? Discussion future directions

5 Why do we use fluid bolus in NICU? CLINICAL SIUATIONS Acute blood volume loss (true hypovolemia) Septic shock (relative hypovol.) Low blood pressure Poor capillary refill Metabolic acidosis Pale and mottled Low O2 saturation Fluid challenge (acute renal dysfunction) Neuroprotection in preterm Resuscitation WHY FLUID BOLUS/VOLUME EXPANSION Hypovolemic Cultural (derived from acute paediatric practice) Saw my senior colleague/s doing it Suggested by my senior nurse Felt that I need something to do Easier to give compared to setting up infusion of inotropes I am in a desperate situation I like it! (Pumping up the volume)

6 Pump up the volume? The routine early use of colloid (fluid bolus) in very preterm infants Arch Dis Child Fetal Neonatal Ed 1998;78:F163-F165 Rarely does a very low birth weight infant escape at least 10 ml/kg of colloid (fluid bolus) in the first few hours of life. Most units do not give volume routinely on admission, in the same way that most units don t prescribe routine antibiotics, yet almost every very preterm baby gets both, as routinely as vitamin K or a photograph for the mother. In the case of antibiotics there is usually some feature of the history or examination that can be invoked to suggest a risk of infection... In the case of colloid there is always a slight metabolic acidosis, or a lowish temperature on arrival from labour ward, or a casual tweak of the big toe..., provides conclusive proof of hypovolaemia. Peter Hope

7 Physiology (The Frank-Starling Law) the stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (the end diastolic volume) when all other factors remain constant.

8 Pathophysiology of Hypovolemia Absolute Hypovolemia (loss of IV volume) preload Cardiac Output Tissue perfusion Oxygenation Relative Hypovolemia (vasodilatation) Response in Absolute Hypovolaemia Corticosteroid, adrenalin, nor-adrenalin heart rate, contractility

9 What is Shock? A pathological state in which tissue oxygen delivery is inadequate to meet demand. Systemic blood flow Oxygen content of blood Oxygen demand of tissue Difficult to measure

10 Perfusion: Definition and Assessment Normal or adequate perfusion enough oxygen delivery to the tissues to maintain all their vital functions and to avoid long term consequences Assessment Clinical: - capillary refill - warmth of extremities - colour - urine output Biochemical: Lactate, ph Near Infra Red Spectroscopy

11 Assessment of shock CRT > or = 3 seconds had 55% sensitivity and 81% specificity Mean BP < 30 mm Hg had 59% sensitivity and 77% specificity Systolic BP < 40 mm Hg had 76% sensitivity and 68% specificity Combining mean BP < 30 mm Hg and central CRT > or = 3 seconds increases the sensitivity to 78% Core peripheral temperature difference did not detect patients with low CO BP and CRT are imperfect bedside tests for detecting low blood flow in the first day after birth. Osborn D A, Evans N, Kluckow M. Arch Dis Child 2004;89(2):F168-F173

12 How do we define hypotension? Mean BP< 30 mmhg Mean BP Gestational Age Mean BP Gestational Age plus clinical signs Mean BP Gestational Age plus echocardiographic signs Systolic BP less than 3 rd centile Systolic BP less than 3 rd centile plus echocardiographic signs

13 Blood Pressure Trend in the Early Hours in Preterm Infants Spontaneous elevation in arterial blood pressure during the first hours of life in the VLBW infants (Moscoso P, Goldberg RN, Jamieson J, Bancalari E), J Pediatr 1983 Period A 2 nd and 3 rd hours Period B 7 th and 8 th hours

14 Blood Pressure versus Age in Preterm Babies Fanaroff et al. Pediatrics 2006;117(4): Tin W et al. Arch Dis Child 1999;80(1): F38-42

15 Blood Pressure versus Gestation in Preterm Babies Tin W et al.arch Dis Child 1999;80(1): F38-42

16 ELGAN Study 1 Pediatrics 2007;119; Identify the blood pressures of extremely low gestational age newborns (ELGANS) [23-27 weeks gestation] that prompt intervention. Identify characteristics associated with receipt of therapies intended to raise blood pressure. Assess inter-institutional variability in the use of these therapies

17 N = 1507 ELGAN Study (1) Results 1387 survived first post natal week Gestational Age % Treated in the first 24 h % Treated on day

18 Conclusions: ELGAN Study (1) Blood pressures increase with gestational and postnatal age Lower gestational age, birth weight, male gender and illness severity were associated with treatment There was a large inter-centre variability of proportion of infants treated (29%-98%) WE HAVE NO CLEAR IDEA WHAT WE ARE DOING!

19 The ELGAN (2) Study Logan et al. Early postnatal hypotension and developmental delay at 24 months of age among extremely low gestational age newborns (Arch Dis Child 2011; 96: F321-28) Prospective study, <28 weeks : n=945 78% received volume expansion or vasopressor All who received vasopressor were treated with volume expansion WHAT THIS STUDY ADDS We found little support for the concept that early postnatal hypotension indicators are associated with developmental delay, or that vasopressor therapy decreases that risk. Inferences from this study are most pertinent to populations in which volume expansion is used frequently, as the majority of infants received volume expansion.

20 Effect of volume expansion on blood pressure Most hypotensive babies are not hypovolaemic Median gest: 29 weeks (n=11) 10 ml/kg fluid bolus Rennie JM, 1989 Preterm (n=43) 10 ml/kg fluid bolus Osborn et al, 2002

21 Assessing Hypovolemia Normal Hypovolemia

22 Effect of volume expansion on systemic blood flow Study (year) Population Intervention Result Pladys et al (1997) Lundstrom et al (2000) Osborn et al (2002) preterm, <7 days (n=12) Low CO, no dysfunction 20 ml/kg Median CO increased 177 to 283 ml/kg/m Preterm (RCT, n=36) 15 ml/kg Mean LVO increased by 19% Preterm, low systemic flow 10 ml/kg SVC flow increased by 55%

23 Effect of volume expansion on systemic blood flow Towards logical treatment of hypotension (Early Human Dev 1996) (Wyllie JP, Hunter S, Hey E) Preterm: n= 26 BP (mean/systolic) of less than 10 th centile, No acidosis Fluid bolus 10 ml/kg (colloid) Left Ventricular Output, Fractional Shortening, LV End Diastolic Diameter measured before, 1 hr and 2 hrs after fluid bolus Results Increased in LVO >10% in 17, BUT sustained to 2 hrs in only 3 All with sustained effect had LVEDD:Ao <2 LVEDD:Ao <2 LVEDD:Ao>2 P value LVO increased 88% 33% <0.005 Conclusion To increase LVO in babies with low BP (<10 C), colloid should be logistically considered only if LVEDD:Ao is <2. The colloid effect is likely to be transient

24 Effect of volume expansion on metabolic acidosis Least evidence-based No evidence that ph and base excess are good markers of circulatory compromise - no correlation with SBF measurements (Kluckow M, Evans N. Pediatr Res 1998) Available data suggests volume expansion is not a good therapy for metabolic acidosis - Dixon et al. Eur J Pediatr Dimitriou et al. J Perinat Med 2001 No data to support volume expansion as a first line treatment - Evans N. Semin Neonatol 2004

25 Early Intravascular Volume Expansion in preterm infants Reduced perfusion to major organs may lead to acute dysfunction and be associated with permanent injury Blood pressure (as surrogate for tissue perfusion) Hypotension is associated with haemorrhagic/ ischaemic brain injuries and poor developmental outcomes Strategies to provide cardiovascular support - intravascular volume expansion - inotropes - corticosteroids One small study (1985) reported reduced P/IVH by early volume expansion (FFP)

26 The Volume Expansion Trial (NNNI Trial Group) < 32 weeks N = 776 FFP (N=257) 20 ml/kg, then 10 ml/kg 24 h later Gelatin (N=261) 20 ml/kg, then 10 ml/kg 24 h later Control Assessment at two years of age (N=604) - Medical history & Clinical Examination - Griffiths Mental Developmental Scales - Vision & Hearing - Anthropometry (N=258) Glucose infusion as routine Minimisation before 2 h of age 84% of eligible infants enrolled Primary outcome: Survival without major disability Follow up rate: 100% All eligible (but not enrolled) children also had same assessments

27 RCT of prophylactic early FFP or gelatin or glucose in preterm babies Outcome Volume n/n Control n/n Risk Ratio (95% CI) Severe P/IVH 26/266 14/ (0.55, 1.90) NEC 18/518 14/ (0.32, 1.27) Sepsis 93/518 36/ (0.90, 1.83) Death (before 2 yrs) 107/518 47/ (0.83, 1.54) Severe Disability 45/399 29/ (0.52, 1.23) Death/ severe disability 164/518 82/ (0.80, 1.24) Favours treatment Favours control Tin et al Lancet 1996

28 Conclusion: This trial provides no evidence that the routine use of FFP, or some other form of intravascular volume expansion, affects the risk of death or disability in babies born more than 8 weeks before term. Tin et al Lancet 1996

29 Early Intravascular Volume Expansion in preterm infants Systematic Review 4 RCTs, N=940 Only NNNI trial (n=776) provided neurodevelopmental outcome NO evidence to support routine use of early volume expansion in preterm infants Insufficient evidence whether infants with cardiovascular compromise benefit from volume expansion Cochrane Database of Systematic Reviews 2009

30 Fluid Bolus for infants with cardiovascular compromise Most commonly used intervention as first line (for hypotension ) Hypovolaemia is NOT common Associated with: - IVH (Goldberg RN et al. J Pediatr 1980) - Adverse Neurological outcome (Greenough A et al. Eur J Pediatr 2002) - Increased mortality (Ewer AK et al. Pediatr Perinat Epidemiol 2003) - Sodium increases BPD (Costarino AT et al. J Pediatr 1992) (Hartnoll G et al. Arch Dis Child F&N 2000)

31 Excessive volume expansion and neonatal death in preterm infants born at weeks gestation Anonymised regional data from Project Case controlled study: 22 deaths matched with 29 survivors Primary outcome: death within 28 days No differences in lowest BP, base deficits Babies who died received twice as much of VE in first 48 h compared with survivors (38ml v 18 ml/kg) Babies who received 30 ml/kg VE are more likely to die than those who received < 30 ml/kg [OR 4.5, 95%CI ] Ewer AK et al. Paediatr Perinat Epidemiol 2003; 17 (2): 180-6

32 Primum non nocere First, do no harm Thomas Inman Foundation for a New Theory and Practice of Medicine (1860)

33 Fluid Bolus (Volume Expansion) in Preterm Babies with Poor Perfusion Summary Fluid Bolus (Intravascular Volume Expansion) commonly used therapy in preterms with poor perfusion Most preterms with poor perfusion are NOT hypovolemic Poor perfusion state, assessed clinically correlates poorly with systemic blood flow Available observation data suggest association of fluid bolus therapy and harm NO observation data to suggest any association fluid bolus and benefit

34 Fluid Bolus (Volume Expansion) in Preterm Babies with Poor Perfusion Summary Echocardiography assessment of haemodynamic status will reduce the irrational use of fluid bolus Avoid the use of repeated fluid boluses on the basis of unreliable clinical assessment parameters No data to support fluid boluses maintain intravascular blood volume

35 Future Directions... Neonatologist performed echocardiography: Education, Training and accreditation New development of non invasive assessment of perfusion Exploring the knowledge gaps Develop research agenda to bridge the gaps Collaboration to accomplish the research agenda

36 THANK YOU FOR LISTENING!!