Publications by authors named "Hari Ravindranathan"

9 Publications

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Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017.

BMC Pediatr 2020 02 8;20(1):59. Epub 2020 Feb 8.

University of New South Wales, Sydney, Australia.

Background: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines.

Methods: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed.

Results: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed.

Conclusions: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.
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http://dx.doi.org/10.1186/s12887-020-1958-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007668PMC
February 2020

Epidemiology of childhood death in Australian and New Zealand intensive care units.

Intensive Care Med 2019 09 3;45(9):1262-1271. Epub 2019 Jul 3.

Royal Children's Hospital and Murdoch Children's Research Institute, Melbourne, Australia.

Purpose: Data on childhood intensive care unit (ICU) deaths are needed to identify changing patterns of intensive care resource utilization. We sought to determine the epidemiology and mode of pediatric ICU deaths in Australia and New Zealand (ANZ).

Methods: This was a retrospective, descriptive study of multicenter data from pediatric and mixed ICUs reported to the ANZ Pediatric Intensive Care Registry and binational Government census. All patients < 16 years admitted to an ICU between 1 January 2006 and 31 December 2016 were included. Primary outcome was ICU mortality. Subject characteristics and trends over time were evaluated.

Results: Of 103,367 ICU admissions, there were 2672 (2.6%) deaths, with 87.6% of deaths occurring in specialized pediatric ICUs. The proportion of ANZ childhood deaths occurring in ICU was 12%, increasing by 43% over the study period. Unadjusted (0.1% per year, 95% CI 0.096-0.104; p < 0.001) and risk-adjusted (0.1%/year, 95% CI 0.07-0.13; p < 0.001) ICU mortality rates fell. Across all admission sources and diagnostic groups, mortality declined except following pre-ICU cardiopulmonary arrest where increased mortality was observed. Half of the deaths followed withdrawal of life-sustaining therapy (51%), remaining constant throughout the study. Deaths despite maximal resuscitation declined (0.92%/year, 95% CI 0.89-0.95%; p < 0.001) and brain death diagnoses increased (0.72%/year, 95% CI 0.69-0.75%; p = 0.001).

Conclusions: Unadjusted and risk-adjusted mortality for children admitted to ANZ ICUs is declining. Half of pediatric ICU deaths follow withdrawal of life-sustaining therapy. Epidemiology and mode of pediatric ICU death are changing. Further investigation at an international level will inform benchmarking, resource allocation and training requirements for pediatric critical care.
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http://dx.doi.org/10.1007/s00134-019-05675-1DOI Listing
September 2019

Admission Hyperoxia Is a Risk Factor for Mortality in Pediatric Intensive Care.

Pediatr Crit Care Med 2018 08;19(8):699-704

Intensive Care Unit, Sydney Children's Hospital, Randwick, NSW, Australia.

Objectives: To determine whether the association between hyperoxia and increased risk-adjusted mortality in adult intensive care patients is also observed in a pediatric intensive care population.

Design: Single-center retrospective analysis of admissions to ICU over a 5-year period commencing January 1, 2012, examining the relationship between PaO2 measured within the first hour of admission and risk-adjusted mortality. Standardized mortality rates were calculated using the Pediatric Index of Mortality-3, and patients were grouped into 50 mm Hg (6.67 kPa) PaO2 bands to assess the relationship between initial PaO2 and risk-adjusted mortality.

Setting: Tertiary PICU with 17 beds and 1,100 annual admissions located in metropolitan Sydney, Australia.

Patients: A total of 1,447 patients 0-18 years old with PaO2 recorded at admission to the ICU.

Interventions: None.

Measurements And Main Results: There were 5,176 patients admitted to the ICU during the study period and 1,447 (28%) with PaO2 recorded at admission. A U-shaped relationship between raw mortality and admission PaO2 was observed, with lowest mortality (2.3% and 2.6%, respectively) observed in the 101-150 (13.5-20.0 kPa) and 151-200 mm Hg (20.1-26.7 kPa) bands and the highest mortality observed in patients with PaO2 less than 50 mm Hg (6.67 kPa) with mortality of 5.3%, or greater than 350 mm Hg (46.7 kPa) with mortality of 18.2%. Hyperoxia at admission was associated with an increase in risk-adjusted mortality, with polynomial regression indicating a strong correlation between PaO2 band and risk-adjusted outcome (r = 0.845). When included in a multivariate model that included the Pediatric Index of Mortality-3 variables, the odds ratio for hyperoxia (defined as PaO2 > 250 mm Hg [33.3 kPa]) predicting death was 2.66 (p = 0.047).

Conclusions: In this single-center study, hyperoxia at admission to the PICU was highly correlated with increased risk-adjusted mortality. Further investigation of these observations in a large multicenter cohort is warranted.
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http://dx.doi.org/10.1097/PCC.0000000000001630DOI Listing
August 2018

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

Hum Mutat 2013 Jun 12;34(6):801-11. Epub 2013 Apr 12.

Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.
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http://dx.doi.org/10.1002/humu.22313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663886PMC
June 2013

Barotrauma as aetiological cascade of fatal intrapulmonary plastic bronchitis in a post-Fontan child.

Interact Cardiovasc Thorac Surg 2012 Oct 12;15(4):805-7. Epub 2012 Jul 12.

Department of Cardiothoracic Surgery, Sydney Children's Hospital, Randwick, NSW, Australia.

The role of barotrauma in the exaggeration of plastic bronchitis after Fontan circulation has yet to be examined. We aim to describe a case of a 4-year old post-Fontan circulation girl where barotrauma suffered during commercial air travel played a role in the aetiological cascade of plastic bronchitis.
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http://dx.doi.org/10.1093/icvts/ivs308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445384PMC
October 2012

Extracorporeal membrane oxygenation support in a situation of diagnostic dilemma.

Heart Lung Circ 2012 Dec 18;21(12):821-3. Epub 2012 May 18.

Department of Cardiothoracic Surgery, Sydney Children's Hospital, High Street, Randwick, NSW, Australia.

Severe acute respiratory distress syndrome (ARDS) in children carries a high morbidity and mortality. High frequency ventilation and extracorporeal membrane oxygenation (ECMO) are used as rescue modes of support in difficult situations. Malignancy may be considered to be a relative contraindication to ECMO support. We report a case where the decision was made to support the patient with ECMO for fulminant Epstein-Barr (EBV) infection while investigations were being done to exclude an underlying malignancy.
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http://dx.doi.org/10.1016/j.hlc.2012.04.014DOI Listing
December 2012

Extremes of weight centile are associated with increased risk of mortality in pediatric intensive care.

Crit Care 2011 31;15(2):R106. Epub 2011 Mar 31.

Intensive Care Unit, Sydney Children's Hospital, High Street, Randwick 2031, Australia.

Introduction: Although numerous studies have linked extremes of weight with poor outcome in adult intensive care patients, the effect of weight on intensive care outcome has not previously been reported in the pediatric population. The aim of this study was to investigate the relationship between admission weight centile and risk-adjusted mortality in pediatric intensive care patients.

Methods: Data were collected on 6337 consecutively admitted patients over an 8.5 year period in a 15 bed pediatric intensive care unit (ICU) located in a university-affiliated tertiary referral children's hospital. A weight centile variable was entered into a multivariate logistic regression model that included all other pediatric index of mortality (PIM-2) variables, in order to determine whether weight centile was an independent risk factor for mortality.

Results: Weight centile was associated with mortality in both univariate and multivariate analysis, with the lowest mortality being associated with weights on the 75th centile and increasing symmetrically around this nadir. A transformed weight centile variable (absolute value of weight centile-75) was independently associated with mortality (odds ratio 1.02, P = 0.000) when entered into a multivariate logistic regression model that included the PIM-2 variables.

Conclusions: In this single-center cohort, weight centile was an independent risk factor for mortality in the ICU, with mortality increasing for patients at either end of the weight spectrum. These observations suggest that the accuracy of mortality prediction algorithms may be improved by inclusion of weight centile in the models. A prospective multicenter study should be undertaken to confirm our findings.
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http://dx.doi.org/10.1186/cc10127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219384PMC
December 2011

Intensive care experience with sclerotherapy for cervicofacial lymphatic malformations.

Pediatr Crit Care Med 2008 May;9(3):304-9

Paediatric Intensive Care Unit, The Children's Hospital at Westmead, Sydney, Australia.

Objective: To describe a cohort of patients needing intensive care support after sclerotherapy for cervicofacial lymphatic malformations.

Design: Retrospective review of case records of patients undergoing sclerotherapy between January 2004 and November 2006.

Setting: A tertiary, university-affiliated, pediatric teaching hospital.

Patients: Five patients needing admission to a pediatric intensive care unit (PICU) following sclerotherapy with OK432.

Interventions: None.

Measurements And Main Results: Five patients needed a total of 13 PICU admissions. Ages ranged from 4 months to 19 months. All patients had extensive lesions that involved the airways, mediastinum, or floor of the mouth, documented by magnetic resonance imaging. Nine admissions involved elective intubation and ventilation following sclerotherapy due to the extent of lesions. There were four urgent admissions to the PICU with respiratory distress ranging from 3 to 18 days after sclerotherapy. The mean duration of admission was 7 days (total 93 days, range 2-22 days). Total ventilated hours were 1656 hrs with a range of 16.5-370 hrs per admission. Multiple procedures, such as drainage of cysts and further sclerotherapy procedures, were performed before extubation on the PICU.

Conclusions: Children with extensive disease and airway involvement need multiple PICU admissions. The potential for life-threatening respiratory embarrassment is unpredictable following sclerotherapy. Consideration should be given to performing further sclerotherapy while the patients are intubated in the PICU. The PICU provides a safe and secure environment for such procedures.
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http://dx.doi.org/10.1097/PCC.0b013e31817287deDOI Listing
May 2008

Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial.

Pediatrics 2007 Jun 7;119(6):e1248-55. Epub 2007 May 7.

Department of Newborn Care, Royal Hospital for Women, Barker Street, Randwick, New South Wales 2031, Australia.

Objectives: The purpose of this work was to compare the efficacy of propofol, a hypnotic agent, to the regimen of morphine, atropine, and suxamethonium as an induction agent for nonemergency neonatal endotracheal intubation. We hypothesized that propofol aids intubation by allowing the continuation of spontaneous breathing.

Patients And Methods: We conducted a randomized, open-label, controlled trial of infants who required nonemergency endotracheal intubation. Primary outcome was successful intubation confirmed by chest auscultation and clinical examination of the infant.

Results: Infants randomly assigned to propofol (n = 33) and the morphine, atropine, and suxamethonium regimen (n = 30) were comparable in median gestational age (27 vs 28 weeks), birth weight (1020 vs 1095 g), weight at intubation (1068 vs 1275 g), and age at intubation (4 vs 3 days). Sleep or muscle relaxation were achieved within 60 seconds in both groups, but time to achieve successful intubation was more than twice as fast with propofol (120 vs 260 seconds). Blood pressure and heart rates were not different, but intraprocedural oxygen saturations were significantly lower in infants on the morphine, atropine, and suxamethonium regimen (trough arterial oxygen saturation: 60% vs 80%). Nasal/oral trauma was less common, and recovery time was shorter (780 vs 1425 seconds) in the propofol group. No significant adverse effects were seen in either group.

Conclusions: Propofol is more effective than the morphine, atropine, and suxamethonium regimen as an induction agent to facilitate neonatal nasal endotracheal intubation. Importantly, hypoxemia was less severe, probably because of the maintenance of spontaneous breathing. A controlled environment may have promoted the ease of intubation, resulting in less trauma. The shorter duration of action would be advantageous in a compromised infant.
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http://dx.doi.org/10.1542/peds.2006-2708DOI Listing
June 2007