Low serum levels of magnesium, phosphate, and zinc in ICU patients. Prevalence, management, characteristics, and outcomes. Protocol and statistical analysis plan for The WhyTrace cohort study

BackgroundPatients admitted to the intensive care unit often have low serum levels of magnesium, phosphate, and zinc. We aim to describe the prevalence, management, characteristics, and outcomes of patients with low levels of these minerals in a large cohort of Danish ICU patients. MethodsIn this multicenter cohort, we will include all adult ICU patients admitted to one of 10 ICUs during a six years period. Patients will be excluded if the ICU admission is post-operative after planned surgery, length of stay is <24 hours, they are transferred from ICUs not participating in the study, or are without measurements of neither magnesium, phosphate nor zinc. First, we will do a descriptive assessment of the prevalence of low serum levels and management of supplementation according to different patient characteristics. Second, we will conduct a cohort study using prospectively registered outcome data, to assess associations between serum levels of magnesium, phosphate, and zinc respectively, and each of two principal outcomes: time to successful extubation and incident tachyarrhythmia. We will use a joint modelling approach for estimating the strengths of associations, combining time to event data and longitudinal data from repeated measurements of serum levels. DiscussionThis study will provide information from a very large cohort of Danish ICU patients. Strengths of the study will be the large number of patients, the interconnection of data from several registers, and for the association analysis the use of a statistical approach making the optimal use of the repeated measures of serum levels. Limitations will be the risk of bias from unmeasured or unregistered confounding factors, and the lack of randomization in the observational design, which will prevent us from interpreting possible associations between serum levels and outcomes as definite effects on the outcome.