In metabolic acidosis due to TA, plasma Cl concentration decreases relative to sodium. The Cl:Na ratio is a simple alternative to the AG for detecting TA in this setting.

End-of-life care (ELC) on a paediatric intensive care unit (PICU) is a fundamental aspect of clinical practice and yet often remains a highly emotive and challenging issue. Every year, many children die in PICU often following the withdrawal of life-sustaining treatment, and as health professionals we have a duty to provide ELC that meets the needs of the dying child and their family. To achieve this, there is a growing emphasis on incorporating parental views on withdrawal of intensive care especially in time and place. Home care of the dying child enables the child to die at home in familiar surroundings and with the people who love them the most. This service is essentially child centred and acknowledges the unique and pivotal position that parents have in their child's life by empowering them to have control over the time and place of death. This is a vitally important aspect of end-of-life in PICU and underpins the ethos of this area of practice. We present a series of case reviews of patients cared for within a 12-month period, where intensive care was withdrawn distant from the PICU environment and address the challenges and considerations surrounding this area of practice.

Base deficit is a parameter often used to guide further treatment in acidotic children and is taken as a measure of how "sick" they are. Five children with septic shock are presented who had persisting base deficit after large volume resuscitation with 0.9% saline. Stewart's strong ion theory of acid-base balance is able to quantify the causes of metabolic acidosis and is used to show that our patients had a hyperchloraemic metabolic acidosis. We show how the chloride content of the saline loads given to our patients caused this hyperchloraemia. It is concluded that 0.9% saline and other chloride rich fluids may not be ideal resuscitation fluids; if used, clinicians must be aware of their potential to cause a persistent base deficit. (Arch Dis Child 2000;83:514-516)

The use of gastric residual volumes to define feed intolerance is justified in critically ill children. High serum amylin levels are associated with delayed gastric emptying in these patients. The correlation between serum amylin and insulin levels indicates a degree of preservation of pancreatic hormonal co-release.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).