Measuring and reporting glycemic control in clinical trials: building a path to consensus

Clinical trials over time have used a variety of approaches for both measuring tight glycemic control and reporting results. The review by Finfer and colleagues in this issue of Critical Care is a step toward consensus within the research community to standardize the way blood glucose is measured and reported in clinical trials. The authors propose using specific measures of central tendency and dispersion for reporting glucose, advocate the use of blood gas analyzers and elimination of point-of-care glucose monitors in the intensive care unit, and comment on performance of continuous glucose monitors. As we await the release of updated rules from the International Standards Organization and process the new rules from the Clinical Laboratory and Standards Institute to regulate glucose monitoring, these recommendations should trigger many more conversations within the field as we strive for uniformity. However, we need to be cautious in prematurely proposing and adopting standards of care that fail to account for newer technology and data in this rapidly growing area of research

Critical illness hyperglycemia: is failure of the beta-cell to meet extreme insulin demand indicative of dysfunction?

In the recent study by Preissig and Rigby in Critical Care, the authors argue that critical illness hyperglycemia in children with both respiratory failure and cardiovascular failure is due to a primary failure of the beta-cell. However, alternative explanations that the failure is secondary to an increase in insulin resistance leading to beta-cell exhaustion, or a negative impact of exogenous glucocorticoid therapy, may be equally likely

The correlation and level of agreement between end-tidal and blood gas pCO2 in children with respiratory distress: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>To investigate the correlation and level of agreement between end-tidal carbon dioxide (EtCO₂) and blood gas pCO₂in non-intubated children with moderate to severe respiratory distress.</p> <p>Methods</p> <p>Retrospective study of patients admitted to an intermediate care unit (InCU) at a tertiary care center over a 20-month period with moderate to severe respiratory distress secondary to asthma, bronchiolitis, or pneumonia. Patients with venous pCO₂(vpCO₂) and EtCO₂measurements within 10 minutes of each other were eligible for inclusion. Patients with cardiac disease, chronic pulmonary disease, poor tissue perfusion, or metabolic abnormalities were excluded.</p> <p>Results</p> <p>Eighty EtCO₂-vpCO₂paired values were available from 62 patients. The mean ± <smcaps>SD</smcaps> for EtCO₂and vpCO₂was 35.7 ± 10.1 mmHg and 39.4 ± 10.9 mmHg respectively. EtCO₂and vpCO₂values were highly correlated (r = 0.90, p < 0.0001). The correlations for asthma, bronchiolitis and pneumonia were 0.74 (p < 0.0001), 0.83 (p = 0.0002) and 0.98 (p < 0.0001) respectively. The mean bias ± <smcaps>SD</smcaps> between EtCO₂and vpCO₂was -3.68 ± 4.70 mmHg. The 95% level of agreement ranged from -12.88 to +5.53 mmHg. EtCO₂was found to be more accurate when vpCO₂was 35 mmHg or lower.</p> <p>Conclusion</p> <p>EtCO₂is correlated highly with vpCO₂in non-intubated pediatric patients with moderate to severe respiratory distress across respiratory illnesses. Although the level of agreement between the two methods precludes the overall replacement of blood gas evaluation, EtCO₂monitoring remains a useful, continuous, non-invasive measure in the management of non-intubated children with moderate to severe respiratory distress.</p

Plasma Soluble Intercellular Adhesion Molecule-1 Has a Central Role in Biomarker Network Analysis and Is Associated With Poor Outcomes in Two Distinct Pediatric Cohorts of Acute Respiratory Distress Syndrome and Acute Respiratory Failure

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on immune, endothelial, and epithelial cells. In the setting of inflammation, it becomes upregulated and spliced into a soluble form (soluble ICAM-1 [sICAM-1]). This study examined the association of sICAM-1 with clinical outcomes in two large pediatric cohorts with acute respiratory distress syndrome (ARDS) and acute respiratory failure (ARF) and examined the relationships between sICAM-1 and other protein biomarkers utilizing network analysis to contextualize its role in ARDS pathophysiology. DESIGN: Secondary analysis of prospective cohort studies. SETTING: Multicenter PICUs. PATIENTS OR SUBJECTS: Critically ill children with ARDS (Pediatric Acute Lung Injury [PALI], 2008-2014) and ARF (Coagulation and Fibrinolysis in Pediatric Insulin Titration Trial [CAF-PINT], 2012-2016). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: sICAM-1 levels were measured from plasma collected within 72 hours of diagnosis. The primary outcome was in-hospital mortality, and secondary outcomes included multiple organ dysfunction and ventilator-free days. We constructed a biomarker correlation-based network that included sICAM-1 and 32 plasma biomarkers reflective of inflammation, endothelial and epithelial injury, and extracellular matrix degradation. Key biomarkers with centrality metrics in the top 10% (≥ 90th percentile) were defined as critical hubs within the network. The study included 214 children from PALI and 251 from CAF-PINT. In-hospital mortality was 18% and 14%, respectively. Baseline median oxygenation index ratios were 10 (interquartile range [IQR], 5.6-19.7) and 8.5 (IQR, 3.5-17.7). Higher plasma sICAM-1 was associated with in-hospital mortality, multiple organ dysfunction, and fewer ventilator-free days in each of the two cohorts (all p &lt; 0.05). Tissue inhibitor of metalloproteinase-1 (composite centrality, 0.99), tumor necrosis factor receptor-1 (0.83), sICAM-1 (0.74), and interleukin-8 (0.74) were identified as network hubs. CONCLUSIONS: Elevated sICAM-1 levels were associated with poor outcomes in two separate cohorts of ARDS and ARF patients. Network analysis revealed sICAM-1 as a central hub, characterized by high centrality metrics. These findings underscore the multifaceted role of sICAM-1 in leukocyte transmigration, inflammation, and endothelial dysfunction and highlight its critical role in ARDS pathophysiology

Tight glycemic control in the ICU - is the earth flat?

Tight glycemic control in the ICU has been shown to reduce mortality in some but not all prospective randomized control trials. Confounding the interpretation of these studies are differences in how the control was achieved and underlying incidence of hypoglycemia, which can be expected to be affected by the introduction of continuous glucose monitoring (CGM). In this issue of Critical Care, a consensus panel provides a list of the research priorities they believe are needed for CGM to become routine practice in the ICU. We reflect on these recommendations and consider the implications for using CGM today

Pediatric intermediate care and pediatric intensive care units: PICU metrics and an analysis of patients that use both

PurposeTo examine how intermediate care units (IMCUs) are used in relation to pediatric intensive care units (PICUs), characterize PICU patients that utilize IMCUs, and estimate the impact of IMCUs on PICU metrics.Materials &amp; methodsRetrospective study of PICU patients discharged from 108 hospitals from 2009 to 2011. Patients admitted from or discharged to IMCUs were characterized. We explored the relationships between having an IMCU and several PICU metrics: physical length-of-stay (LOS), medical LOS, discharge wait time, admission severity of illness, unplanned PICU admissions from wards, and early PICU readmissions.ResultsThirty-three percent of sites had an IMCU. After adjusting for known confounders, there was no association between having an IMCU and PICU LOS, mean severity of illness of PICU patients admitted from general wards, or proportion of PICU readmissions or unplanned ward admissions. At sites with an IMCU, patients waited 3.1h longer for transfer from the PICU once medically cleared (p&lt;0.001).ConclusionsThere was no association between having an IMCU and most measures of PICU efficiency. At hospitals with an IMCU, patients spent more time in the PICU once they were cleared for discharge. Other ways that IMCUs might affect PICU efficiency or particular patient populations should be investigated