Dissertation Synopsis for MD Paediatrics

Dissertation Synopsis for MD Paediatrics

Name: Dr.Joe Jose

Name of the Institution: St. John's Medical College and Hospital

Course: MD Paediatrics

Date of admission: 3rd JUNE 2013

Title of thesis:

To assess whether early positive fluid balance is associated with increased mortality and morbidity in critically ill children-A prospective observational study.

Brief resume of intended work

Introduction

Fluid management has a major impact on the duration, severity and outcome of critical illness. The overall strategy for the acutely ill child should be biphasic. Aggressive volume expansion to support tissue oxygen delivery as part of early managementof shock-especially septic shock-has been associated with dramatic improvements in outcome. Recent data suggest that the cost-benefit of aggressive fluid resuscitation may be more complex than previously thought, and may depend on clinical scenario and the availability of intensive care. After the resuscitation phase, critically ill children tend to retain free water while having reduced insensible losses. Fluid regimens that limit or avoid positive fluid balance are associated with a reduced length of hospital stay and fewer complications. Identifying the point at which patients change from the 'early shock' pattern to the later 'chronic critical illness' pattern remains a major challenge.

Need for the study

Positive fluid balance is very common in critically ill children,especially those requiring fluid resuscitation.It is however unclear whether positive fluid balance causes increased morbidity or is just an indicator of disease severity as the more critically ill children will require more fluids as compared to children with less severe illness. Studies done before have looked at relation between fluid overload and duration of ventilator support as well as the oxygenation parameters.A causal relationship between positive fluid balanceand respiratory morbidity has been postulated. A dose-response relationship between cardiopulmonary complications and increasing degrees of fluid overload(FO) was demonstrated in adult critical care patients; those with less fluid gain and lower lung water had more ventilator free days and shorter intensive care unit (ICU) and hospital length of stays (LOS).Few retrospective studies have looked at positive fluid balance and morbidity in paediatric population.However few studies have looked at degree of early positive fluid balance and the relation to morbidity and mortality as compared to those with no or lesser degree of positive fluid balance prospectively.This study compares the morbidity, assessed by duration of PICU and hospital stay and mortality, in critically ill children with early positive fluid balance as compared with those with lesser or no fluid overload. This study will also assess if liberal fluid management will result in a worse clinical outcome.

Review of literature

Various studies have been done in adult population correlating positive fluid balance and mortality.European survey of critically ill adult patients with sepsis showed a positive fluid balance wasassociated with increased mortality (1).Positive fluid balance also increased the time spent on mechanical ventilation and resulted in a trend toward increased mortality in a large randomized study of patients with acute lung injury (2).Large observational studies and post hoc analyses of randomized trials have found that positive fluid balance during thefirst days after development of ALI/ARDS is independently associated with a higher risk of death (3–6).In 2006, the ARDS Network published results of their Fluid and Catheter Treatment Trial (2). This trial demonstrated that a conservative fluid management strategy, aimed at achieving normal intravascular filling pressures after resolution of shock and resulting in relative even fluid balance over the first 7 days of the study, resulted in a shorter duration of mechanical ventilation and ICU stay.A dose-response relationship between cardiopulmonary complications and increasing degrees of fluid overload was demonstrated in adult critical care patients; those with less fluid gain and lower lung water had more ventilator free days and shorter intensive care unit (ICU) and hospitallength of stays (LOS) (8, 9). Additionally, diuresis with albumin-furosemide infusions has been shown to lead to rapid and persistent improvements in oxygenation(10).In the pediatric patient population,data on the impact of fluid balance on pulmonary mechanics and oxygenation is scarce. Randolph et al found that patients with the highest degree of cumulative FO at the time of weaning had a significantly longer period of time to extubation(11). Hence this study aims to look at fluid overload and its correlation with outcome.

Aim: To determine the impact of early fluid overload on mortality and morbidity in critically ill children.

Objectives of the study

To compare the maximum cumulative fluid accumulation and presence of fluid overload during the initial 7 days of ICU admission between survivors and nonsurvivors.
To determine the association between positive fluid balance with mortality and morbidity as assessed by length of PICU and hospital stay.
To determine the association between positive fluid balance and duration of ventilation and oxygenation index (OI).
To correlate the severity of fluid overload with severity and recovery of AKI

Materials and Methods

Design: Prospective, Cohort study

Study period- October 2013 to August 2015

Place of study-PICU, St. John’s Medical College, Bangalore.

Study population: All children admitted in PICU at St. John's Medical College Hospital will be considered for the study.

Inclusion criteria:

Age: all children aged between 1 month and 18 years at the time of hospital admission.
Critically ill children as defined below.

Exclusion criteria:

Children with chronic kidney disease, nephrotic syndrome, congestive cardiac failure.
PICU stay less than 24hours
Do Not Resuscitate consent or withdrawal of treatment

Method of collection of data:

A written and detailed consent will be obtained from parents/legal guardians of the child. Socio-demographic factors such as age, gender etc. will be noted. Provisional diagnosis at time of admission will be noted. Prism scoring will be done at admission and positive fluid balance will be calculated based on total fluid intake and urine output every day for the first 7 days of PICU stay.

Study definitions:

A) Critically ill child:These are children requiring, high dependency or intensive care, with fluid refractory shock requiring at least one inotrope or any child requiring mechanical ventilation.

B)Acute Kidney Injury defined according to AKIN criteria(12).

Stage Serum creatinine Urine Output

1 1.5–1.9 times baseline <0.5 ml/kg/h for 6–12hours

>0.3 mg/dl (X26.5mmol/l) increase

2 2.0–2.9 times baseline <0.5 ml/kg/h for >12 hours

3 3.0 times baseline <0.3 ml/kg/h for X24 hours

Anuria for >12 hours

Increase in serum creatinine to >4.0 mg/dl

Initiation of renal replacement therapy

OR, In patients <18 years, decrease in eGFR to

<35 ml/min per 1.73 m2

C)Oxygenation index- measured using the formula

OI=FiO2 xMAP/PaO2

D)Cumulative fluid balance-Cumulative fluid balance was defined as the sum of daily fluid balances.Daily fluid balance was calculated as a difference between fluid intake (oral and intravenous) and output (diuresis, discharge from nasogastric tube, and insensible losses).Insensible loses were assessed as 10 ml/kg/day in patients with mean daily temperature = 37º, in case of t > 37º insensible loses were increased by 13% for each Celsius higher 37º.Each defecation was estimated to add 100 ml fluid loss (13).

E)PRISM Score

a) PRISM score [PRISM III - 24]

Variable Age restrictions Score appointed a)Systolic blood pressure Neonate Infant Child Adolescent

40-55 45-65 55-75 65-85 3

<40 <45 <55 <65 7

b)Temperature All ages <33°C or >40°C 3

c)Mental status All ages: stupor or coma (GCS <8) 5

d)Heart rate Neonate Infant Child Adolescent

215-225 215-225 185-205 145-155 3

>225 >225 >205 >155 4

e)Pupillary reflexes All ages = One pupil fixed, pupil >3mm 7

All ages = Both fixed, pupil >3mm 11

f)Acidosis (pH) or All ages = pH 7.0-7.28 or total CO2 5-16.9 2 total CO2(mmol/l) All ages = pH <7.0 or total CO2 <5 6

All ages = pH 7.48-7.55 2

All ages=pH >7.55 3

g)PCO2 (mmhg) All ages = 50.0-75.0 1

All ages >75.0 3

h)Total CO2 (mmol/L) All ages >34.0 4

i)Arterial PaO2 (mmHg) All ages = 42.0-49.9 3

All ages <42.0 6

j)Glucose All ages >11.0 mmol/L 2

j)Potassium All ages >6.9 mmol/L 3

k)Creatinine (µmol/L) Neonate Infant Child Adolescent 2

>75 >80 >80 >115

l)Urea (mmol/L) Neonate All other ages 3

>4.3 >5.4

m)White blood cells All ages < 3000 cells/mm3 4

n)Prothrombin time (PT) or Neonate All other ages

PTT PT >22.0 sec or PT >22.0 sec or 3

PTT >85.0 sec PTT >57.0 sec

p)Platelets (cells/mm3) All ages = 100,000 to 200,000 2

All ages = 50,000 to 99,999

<50,000 5

Total PRISM III score 24

Sample size:100 critically ill children

Considering previous studies the minimum difference in mean fluid overload was taken as 5 between survivors and non survivors (3).The incidence of mortality being taken as 20%among critically ill children (7) and assuming an alpha of 0.5 and a power of 80%, our required sample size was a minimum of 30 survivors and 30 non survivors. Thus we have more than adequate numbers for this study if we recruit at least 100 critically ill children of which 50 will be survivors and 50 will benon survivors.

Primary outcome measures

Mortality at the end of PICU stay

Duration of PICU and hospital stay

Secondary outcome measures

Duration of ventilation

Oxygenation index

Acute kidney injury stage

Laboratory investigations

Based on clinical presentation, necessary investigations will be done as per protocol. Investigations required for Prism scoring will also be done.

Statistical analysis

Frequencies of different socio-demographic and clinical features of patients will be described.All continuous data will be expressed as mean+/- SD and all categorical data will be expressed as percentages.Statistical analysis of the data will include descriptive analysis and differences between groups (based on Prism scores) as analysed by Student’s t test. Univariate and multivariate regression analyses will be used to evaluate the relationship between positive fluid balance and parameters such as ventilator requirement,oxygen indices and length of stay in hospital. All p values will be two-sided, and a value of <0.05 will be considered as significant.

The two groups (survivors and non-survivors) will be compared with respect to other variables as described above and multivariable logistic regression analysis will be performed to determine factors associated with primary and secondary outcome measures.Cox proportional hazards analysis will be performed to compare survival between patients with fluid overload and those with no fluid overload.

Ethical clearance

Application for ethical clearance is submitted to the Institutional Ethical Review Board at St John’s Medical College Hospital.

References

1. Vincent JL, Sakr Y, Sprung CL, et al: Sepsis in European intensive care units: Results of the SOAP study. Crit Care Med 2006; 34:344–3532.

2. Wiedemann HP, Wheeler AP, Bernard GR, et al: Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354:2564–2575

3.Y. Sakr, J. L. Vincent, K. Reinhart et al., “High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury,” Chest, vol. 128, no. 5, pp. 3098–3108,2005.

4.R. S. Simmons, G. G. Berdine, J. J. Seidenfeld et al., “Fluid balance and the adult respiratory distress syndrome,” American Review of RespiratoryDisease, vol. 135, no. 4, pp. 924–929,1987.

5.A. L. Rosenberg, R. E. Dechert, P. K. Park, R. H. Bartlett, and N. N. A. Network, “Review of a large clinical series: association of cumulative fluid balance on outcome in acute lung injury:a retrospective review of the ARDSnet tidal volume study cohort,” Journal of Intensive Care Medicine, vol. 24, no. 1, pp.35–46, 2009.

6.C. V.Murphy, G. E. Schramm, J. A. Doherty et al., “The importance of fluid management in acute lung injury secondary to septic shock,” Chest, vol. 136, no. 1, pp. 102–109, 2009.

7.Ayse A. Arikan, MD; Michael Zappitelli, MD, MSc; Stuart L. Goldstein, MD; Amrita

Naipaul MD "Fluid overload is associated with impaired oxygenation and

morbidity in critically ill children"

8.Brandstrup B, Tønnesen H, Beier-Holgersen R, et al: Effects of intravenous fluid restriction on postoperative complications: Comparisonof two perioperative fluid regimens: A randomized assessor-blinded multicenter trial.Ann Surg 2003; 238:641–648

9.Schuller D, Mitchell JP, Calandrino FS, et al:Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome?Chest 1991; 100:1068–1075

10. Martin GS, Mangialardi RJ, Wheeler AP, et al:Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury. Crit Care Med 2002; 30:2175–2182

11.Randolph AG, Forbes PW, Gedeit RG, et al: Cumulative fluid intake minus output is not associated with ventilator weaning duration or extubation outcomes in children. Pediatr

Crit Care Med 2005; 6:642–647

12. Kidney International Supplements (2012) 2, 8–12; doi:10.1038/kisup.2012.7

13. R.V. Hakobyan1, D.L. Melkonyan2, H.N. Mangoyan3 1Yerevan State Medical University, Anesthesiology, Yerevan, Armenia, 2National Institute of Health, Anesthesiology, Yerevan, Armenia, 3Erebuni Medical Center, ICU, Yerevan.

Signature of the candidate

Remarks of the guide

This study will be useful in determining early prognosticating factors in critically children.

Name and designation of Guide Dr. Lalitha.A.V

Associate Professor

Department Of Pediatrics Signature

St. John’s Medical College Hospital,

Bangalore.

Co-guide:

Dr.Anil Vasudevan

Associate Professor

Department of Pediatric Nephrology

St.John’s Medical College Hospital Signature

Bangalore.

Head of the department

Dr.Sylvan John Rego

Professor and Head Signature

Department of Pediatrics

St.John’sMedical College Hospital

Bangalore.

Remarks of the chairman and principal

Signature

PROFORMA

NAME: AGE:

OP/IP No: SEX:

ADDRESS:

DOA: DOD:

PROVISIONAL DIAGNOSIS AT ADMISSION:

PRISM SCORE:

INVESTIGATIONS:

PCV

Blood urea

S.Creatinine

AST

ALT

PT/INR

APTT

Blood c/s

Urine c/s

ET tip c/s

ABG pH

pCO2

paO2

HCO3

Lactate

Oxygenation index

P/F ratio

Inotropes (duration)

Dopamine

Dobutamine

Noradrenaline

Fluid for resuscitation:

Type: Crystalloid-NS

-RL

Amount of fluid bolus:

Colloids used or not:

Blood products-Packed RBC

Platelet concentrate

Ventilation-Duration

Peak parameters

Weaning

Daily intake, output and cumulative positive balance

Day1

Day2

Day3

Day4

Day5

Day6

Day7

OUTCOME:

1. Recovery / death.

2. Duration