The burden of sepsis in critically ill patients with multiple sclerosis: A population-based cohort study

Abstract Background Lactate is a robust prognostic marker for the outcome of critically ill patients. Several small studies reported that metformin users have higher lactate levels at ICU admission without a concomitant increase in mortality. However, this has not been investigated in a larger cohort. We aimed to determine whether the association between lactate levels around ICU admission and mortality is different in metformin users compared to metformin nonusers. Methods This cohort study included patients admitted to ICUs in northern Denmark between January 2010 and August 2017 with any circulating lactate measured around ICU admission, which was defined as 12 h before until 6 h after admission. The association between the mean of the lactate levels measured during this period and 30-day mortality was determined for metformin users and nonusers by modelling restricted cubic splines obtained from a Cox regression model. Results Of 37,293 included patients, 3183 (9%) used metformin. The median (interquartile range) lactate level was 1.8 (1.2–3.2) in metformin users and 1.6 (1.0–2.7) mmol/L in metformin nonusers. Lactate levels were strongly associated with mortality for both metformin users and nonusers. However, the association of lactate with mortality was different for metformin users, with a lower mortality rate in metformin users than in nonusers when admitted with similar lactate levels. This was observed over the whole range of lactate levels, and consequently, the relation of lactate with mortality was shifted rightwards for metformin users. Conclusion In this large observational cohort of critically ill patients, early lactate levels were strongly associated with mortality. Irrespective of the degree of hyperlactataemia, similar lactate levels were associated with a lower mortality rate in metformin users compared with metformin nonusers. Therefore, lactate levels around ICU admission should be interpreted according to metformin use.

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Prediction of blood lactate values in critically ill patients: a retrospective multi-center cohort study

Journal of Clinical Monitoring and Computing ◽

10.1007/s10877-021-00739-4 ◽

2021 ◽

Author(s):

Behrooz Mamandipoor ◽

Wesley Yeung ◽

Louis Agha-Mir-Salim ◽

David J. Stone ◽

Venet Osmani ◽

...

Keyword(s):

Cohort Study ◽

Blood Lactate ◽

Critically Ill ◽

Critically Ill Patients

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Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured Versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study

Antibiotics ◽

10.3390/antibiotics10050557 ◽

2021 ◽

Vol 10 (5) ◽

pp. 557

Author(s):

Matthias Gijsen ◽

Erwin Dreesen ◽

Ruth Van Daele ◽

Pieter Annaert ◽

Yves Debaveye ◽

...

Keyword(s):

Renal Function ◽

Cohort Study ◽

Protein Binding ◽

Critically Ill ◽

Critically Ill Patients ◽

Observational Cohort Study ◽

Target Attainment ◽

Binding Model ◽

Observational Cohort ◽

The Impact

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

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