Ray, Samiran; (2020) The impact of fever and its treatment in critically ill children. Doctoral thesis (Ph.D), UCL (Univeristy College London).

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Abstract

Abstract Background: Fever is associated with improved mortality in critically ill adults with infection. Although infection is common in critically ill children, fever is treated, often with the aim to reduce oxygen consumption or improve oxygen delivery. This work tests the hypothesis that in critically ill children, fever impacts on outcomes by significantly imbalancing oxygen consumption and delivery. Methods: (i) A retrospective study of fever epidemiology in an unselected population of children admitted to the paediatric intensive care unit (PICU); (ii) A prospective study of fever epidemiology in children admitted to PICU with infection; (ii) A prospective study of the use of anti-pyretic interventions in children with infection and fever; (iv) A retrospective study exploring the effectiveness of paracetamol in reducing temperature; (v) A prospective study using indirect calorimetry to measure the changes in oxygen consumption with fever; (vi) Retrospective studies using high-resolution data and pulse-contour analysis to explore haemodynamic changes in children with fever and paracetamol; (vii) An observational study of the association between temperature and mortality in children admitted to PICU and children recruited to the FEAST study in sub-Saharan Africa. Results: (i) Fever occurred in 4066/10379 (40.1%) children in the first 48-hours of PICU admission. (ii) Seventy-seven of 140 children admitted with infection (55.0%) had a fever within the first 5-days of admission. (iii) 101/140 (72.1%) children were treated with anti-pyretic interventions, with paracetamol used in 99/101 (98.0%). The use of anti-pyretic interventions was correlated with temperature. (iv) Paracetamol was associated with a temperature decrease by 0.78oC (95% CI 074-0.82oC) in febrile children following the analysis of 4849 doses. (v) Changes in oxygen consumption with fever were variable, although the data could not be interpreted due to small numbers. (vi) A 1oC rise in temperature was associated with an 8.31/min (95% CI 8.30-8.33) rise in heart rate following an analysis of 7,39,466 data pairs from 170 children; and a 0.11 mmHg (95% CI 0.09-0.12) rise in mean arterial pressure following analysis of 5,212,439 pairs from 123 children. Rise in temperature was associated with a rise in the cardiac index but fall in the systemic vascular resistance. Paracetamol was associated with a drop in mean blood pressure by 3.02 mmHg (95% CI 1.56-4.47) following multi-variable analysis of 148 doses in 31 children. (vii) Maximum temperature in the first 24-hours of admission had a U-shaped relationship with mortality in 10125 PICU patients. The optimum temperature for survival was 38oC in those with unplanned admissions. Fever was similarly associated with improved survival in children with infection in sub-Saharan Africa without ICU provision. Conclusions: Fever is common in critically ill children. It is associated with near-equal increases in oxygen delivery and consumption. Given this, it is unlikely that an imbalance between oxygen consumption and delivery impacts on outcomes; fever was associated with a lower mortality compared to those with a maximum temperature of 36.5oC or below.

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