Sainath Raman

Survey of Oxygen Delivery Practices in UK Paediatric Intensive Care Units

Purpose. Administration of supplemental oxygen is common in paediatric intensive care. We explored the current practice of oxygen administration using a case vignette in paediatric intensive care units (PICU) in the united kingdom. Methods. We conducted an online survey of Paediatric Intensive Care Society members in the UK. The survey outlined a clinical scenario followed by questions on oxygenation targets for 5 common diagnoses seen in critically ill children. Results. Fifty-three paediatric intensive care unit members from 10 institutions completed the survey. In a child with moderate ventilatory requirements, 21 respondents (42%) did not follow arterial partial pressure of oxygen (PaO2) targets. In acute respiratory distress syndrome, cardiac arrest, and sepsis, there was a trend to aim for lower PaO2 as the fraction of inspired oxygen (FiO2) increased. Conversely, in traumatic brain injury and pulmonary hypertension, respondents aimed for normal PaO2 even as the FiO2 increased. Conclusions. In this sample of clinicians PaO2 targets were not commonly used. Clinicians target lower PaO2 as FiO2 increases in acute respiratory distress syndrome, cardiac arrest, and sepsis whilst targeting normal range irrespective of FiO2 in traumatic brain injury and pulmonary hypertension.

Pao2/fio2 Ratio Derived From the Spo2/fio2 Ratio to Improve Mortality Prediction Using the Pediatric Index of Mortality-3 Score in Transported Intensive Care Admissions*

Objectives: To derive a relationship between the SpO2/FIO2 ratio and PaO2/FIO2 ratio across the entire range of SpO2 values (0–100%) and to evaluate whether mortality prediction using the Pediatric Index of Mortality-3 can be improved by the use of PaO2/FIO2 values derived from SpO2/FIO2. Design: Retrospective analysis of prospectively collected data. Setting: A regional PICU transport service. Patients: Children transported to a PICU. Interventions: None. Measurements and Main Results: The relationship between SpO2/FIO2 and PaO2/FIO2 across the entire range of SpO2 values was first studied using several mathematical models in a derivation cohort (n = 1,235) and then validated in a separate cohort (n = 306). The best SpO2/FIO2-PaO2/FIO2 relationship was chosen according to the ability to detect respiratory failure (PaO2/FIO2 ⩽ 200). The discrimination of the original Pediatric Index of Mortality-3 score and a derived Pediatric Index of Mortality-3 score (where SpO2/FIO2-derived PaO2/FIO2 values were used in place of missing PaO2/FIO2 values) were compared in a different cohort (n = 1,205). The best SpO2/FIO2-PaO2/FIO2 relationship in 1,703 SpO2/FIO2-to-PaO2/FIO2 data pairs was a linear regression equation of ln[PF] regressed on ln[SF]. This equation identified children with a PaO2/FIO2 less than or equal to 200 with a specificity of 73% and sensitivity of 61% in children with SpO2 less than 97% (92% and 33%, respectively, when SpO2 ≥ 97%) in the validation cohort. PaO2/FIO2 derived from SpO2/FIO2 (derived PaO2/FIO2) was better at predicting PICU mortality (area under receiver operating characteristic curve, 0.64; 95% CI, 0.55–0.73) compared with the original PaO2/FIO2 (area under receiver operating characteristic curve, 0.54; 95% CI, 0.49–0.59; p = 0.02). However, there was no difference in the original and derived Pediatric Index of Mortality-3 scores and their discriminatory ability for mortality. Conclusions: SpO2-based metrics perform no worse than arterial blood gas–based metrics in mortality prediction models. Future Pediatric Index of Mortality score versions may be improved by the inclusion of risk factors based on oxygen saturation values, especially in settings where PaO2 values are missing in a significant proportion of cases.

Fluid management in the critically ill child

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 goal-directed resuscitation algorithms for 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 case-mix 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. Very little data are available on the choice of fluids, and most of the information that is available arises from studies of critically ill adults. There is therefore an urgent need for high-quality trials of both resuscitation and maintenance fluid regimens in critically ill children.

Protocol for a randomised pilot multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU)

Introduction Optimal targets for systemic oxygenation in paediatric critical illness are unknown. Observational data indicate that high levels of arterial oxygenation are associated with poor outcomes in resuscitation of the newborn and in adult critical illness. Within paediatric intensive care units (PICUs), staff prevent severe hypoxia wherever possible, but beyond this there is no consensus. Practice varies widely with age, diagnosis, treating doctor and local or national guidelines followed, though peripheral blood oxygen saturations (SpO2) of >95% are often targeted. The overall aim of this pilot study is to determine the feasibility of performing a randomised trial in critically ill children comparing current practice of liberal SpO2 targets with a more conservative target. Methods and analysis Oxy-PICU is a pragmatic, open, pilot randomised controlled trial in infants and children requiring mechanical ventilation and receiving supplemental oxygen for abnormal gas exchange accepted for emergency admission to one of three participating UK PICUs. The study groups will be either a conservative SpO2 target of 88%–92% (inclusive) or a liberal SpO2 target of >94%. Infants and children who fulfil all inclusion criteria and none of the exclusion criteria will be randomised 1:1 by a secure web-based system to one of the two groups. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support. Discharge outcomes will also be recorded. In addition to observational data, blood and urine samples will be taken to identify biochemical markers of oxidative stress. Outcomes are targeted at assessing study feasibility with a primary outcome of adequate study recruitment (target: 120 participants). Ethics and dissemination The trial received Health Research Authority approval on 1 June 2017 (16/SC/0617). Study findings will be disseminated in national and international conferences and peer-reviewed journals. Trial registration number NCT03040570.

Admission PaO2 and Mortality in Critically Ill Children: A Cohort Study and Systematic Review.

Objective: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. Design: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: “hyperoxia,” “hypoxia,” “critically ill children,” “pediatric intensive care,” “mortality,” and/or “survival.” Setting: Tertiary PICU. Patients: Patients younger than 18 years of age. Interventions: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, Measurements and Main Results: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group ( 40 kPa). Nonlinear regression displayed a “U-shaped” relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79–5.48; p Conclusions: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.Objective: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. Design: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: “hyperoxia,” “hypoxia,” “critically ill children,” “pediatric intensive care,” “mortality,” and/or “survival.” Setting: Tertiary PICU. Patients: Patients younger than 18 years of age. Interventions: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, < 60 torr [8 kPa] or peripheral oxygen saturations, < 90%) to mortality in critically ill children was explored. Measurements and Main Results: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group (< 8 kPa) to 5.3% (287/5,385) with normoxia and 9.1% (64/701) in the hyperoxic group (> 40 kPa). Nonlinear regression displayed a “U-shaped” relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79–5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42–3.17; p = 0.77). Conclusions: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.

Near infrared spectroscopy with a vascular occlusion test as a biomarker in children with mitochondrial and other neuro-genetic disorders

Background Mitochondrial and neurogenetic diseases can present diagnostic challenges. We investigated if near infrared spectroscopy with the vascular occlusion test is able to differentiate between children with mitochondrial disease and children with neurogenetic disease or healthy controls. Methods Prospective observational study conducted in a tertiary children’s hospital. Results Forty-three children with mitochondrial disease (including both genetically confirmed primary mitochondrial disease and cases with biochemical evidence of mitochondrial dysfunction), 19 children with non-mitochondrial neurogenetic disease and 13 healthy controls were recruited. The delta tissue oxygen index (ΔTOI) values showed greater variability amongst children with mitochondrial disease and neurogenetic disease than healthy controls despite the median ΔTOI being similar (median 14.1 and 18.8, t-test, p = 0.16). A low ΔTOI identifies cases with a higher probability of mitochondrial disease or neurogenetic disease compared to healthy controls (positive likelihood ratio: 3.67; 95%CI:1.01–13). A high ΔTOI with the near infrared spectroscopy with vascular occlusion test identifies cases with a lower probability of having a disease (negative likelihood ratio: 0.51; 95%CI:0.36–0.74). Conclusion Near infrared spectroscopy with vascular occlusion test might be able to discriminate children with mitochondrial disease and neurogenetic disease from healthy controls.

Haemodynamic changes with paracetamol in critically-ill children

Purpose Paracetamol has been associated with a reduction in blood pressure, especially in febrile, critically‐ill adults. We hypothesised that blood pressure would fall following administration of paracetamol in critically‐ill children and this effect would be greater during fever and among children with a high body surface area to weight ratio. Methods A 12‐month prospective observational study of children (0–16 years) admitted to paediatric intensive care, who underwent pulse contour analysis and received paracetamol concurrently. Results Mean arterial blood pressure decreased significantly by 4.7% from baseline (95% CI 1.75–8.07%) in 31 children following 148 doses of paracetamol. The nadir was 2‐hour post‐dose. The effect was pronounced in children with fever at baseline (6.4%, 95% CI 2.8–10%), although this was not statistically significant. There was no simple relationship between this effect and body surface area to weight ratio. The association between a change in blood pressure and changes in heart rate or measured stroke volume was poor; therefore it was likely that a change in the systemic vascular resistance contributes most to this effect. Conclusion There is a significant but modest reduction in blood pressure post‐paracetamol in critically‐ill children. This is likely related to a change in systemic vascular resistance. HighlightsChildren have a significant drop in blood pressure after paracetamol administrationThis is smaller and later than the described change in adultsThe drop is primarily explained by a change in systemic vascular resistance

Admission Pao: A Cohort Study and Systematic Review2: A Cohort Study and Systematic Review and Mortality in Critically Ill Children: A Cohort Study and Systematic Review

Objective: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. Design: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: “hyperoxia,” “hypoxia,” “critically ill children,” “pediatric intensive care,” “mortality,” and/or “survival.” Setting: Tertiary PICU. Patients: Patients younger than 18 years of age. Interventions: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, Measurements and Main Results: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group ( 40 kPa). Nonlinear regression displayed a “U-shaped” relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79–5.48; p Conclusions: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.Objective: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. Design: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: “hyperoxia,” “hypoxia,” “critically ill children,” “pediatric intensive care,” “mortality,” and/or “survival.” Setting: Tertiary PICU. Patients: Patients younger than 18 years of age. Interventions: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, < 60 torr [8 kPa] or peripheral oxygen saturations, < 90%) to mortality in critically ill children was explored. Measurements and Main Results: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group (< 8 kPa) to 5.3% (287/5,385) with normoxia and 9.1% (64/701) in the hyperoxic group (> 40 kPa). Nonlinear regression displayed a “U-shaped” relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79–5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42–3.17; p = 0.77). Conclusions: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.

Admission Pao: A Cohort Study and Systematic Review and Mortality in Critically Ill Children: A Cohort Study and Systematic Review

Objective: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. Design: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: “hyperoxia,” “hypoxia,” “critically ill children,” “pediatric intensive care,” “mortality,” and/or “survival.” Setting: Tertiary PICU. Patients: Patients younger than 18 years of age. Interventions: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, Measurements and Main Results: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group ( 40 kPa). Nonlinear regression displayed a “U-shaped” relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79–5.48; p Conclusions: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.Objective: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. Design: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: “hyperoxia,” “hypoxia,” “critically ill children,” “pediatric intensive care,” “mortality,” and/or “survival.” Setting: Tertiary PICU. Patients: Patients younger than 18 years of age. Interventions: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, < 60 torr [8 kPa] or peripheral oxygen saturations, < 90%) to mortality in critically ill children was explored. Measurements and Main Results: Cohort study: Of 14,321 admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4% (204/1,324) in the hypoxia group (< 8 kPa) to 5.3% (287/5,385) with normoxia and 9.1% (64/701) in the hyperoxic group (> 40 kPa). Nonlinear regression displayed a “U-shaped” relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79–5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42–3.17; p = 0.77). Conclusions: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy.

Impact of stops for road traffic accidents on the inter-hospital transport of critically ill children

Transport of critically ill children has become necessary following centralisation of paediatric specialist services. Childrens Acute Transport Service (CATS) retrieves critically ill children in the Greater London area. Our teams have had to stop during these journeys to assist in road traffic accidents or ill passers-by. We undertook a review of our practice over a 3.5-year period. Our teams had to stop on 12 occasions over this period amounting to an incidence rate of 1 per 959 ambulance journeys. Although this is an infrequent occurrence, the impact on the retrieved patient and service delivery could be significant. We would like to direct the attention of transport services to this problem.