Low Serum Creatinine as a Predictor of Prolonged Mechanical Ventilation and Weaning Failure

More than 95% of serum creatinine comes from skeletal muscles, where it is formed by non-enzymatic degradation of creatine. Therefore, in patients with normal kidney function, the serum creatinine value closely correlates with muscle mass volume. It is well documented that critically ill patients lose almost 20% of their muscle mass volume during the first 10 days of their stay in the intensive care unit (ICU). At the same time, it is clear that it is from this group of "longer-stay" patients that those who need subsequent intensive care come. From the above, it can be assumed that in some patients admitted to the post-ICU care unit, the admission serum creatinine value may be subnormal due to muscle devastation caused during the stay in the ICU. This assumption was verified by analysing the admission creatinine values in a group of chronically ventilated adult patients admitted to the post-ICU care unit on CHRONICARE GROUP a.s. over five consecutive months. Of the total number of 264 patients, 123 (47%) patients had an admission serum creatinine value in the subnormal range.

Subnormal serum creatinine levels in patients admitted to the post-ICU care unit may have a number of causes, most of which are related to the patient's pre-existing illness, medical interventions in the ICU, or the critical illness itself. It may be related to chronic liver disease (suppressed creatine synthesis) or kidney disease (suppressed creatine synthesis). It may also be a falsely low serum creatinine level caused by fluid overload. Critical illness itself leads to sarcopenia, as a result of which the total amount of creatinine produced in the muscles decreases, and therefore the serum creatinine concentration. Unfortunately, the development of sarcopenia induced by critical illness cannot be influenced therapeutically. Similarly, mitochondrial dysfunction in muscle cells induced by critical illness cannot be influenced therapeutically. This abnormality leads to a decrease in Adenosine Triphosphate (ATP) production and therefore to a decrease in the formation of creatine phosphate, which is the main source for creatinine formation (the conversion of creatine phosphate to creatinine is 3 times faster than the conversion of creatine to creatinine). It is also possible that the subnormal value of serum creatinine is a consequence of an insufficient supply of creatine during nutritional support of critically ill patients in the ICU. Parenteral nutrition does not contain creatine at all, and enteral nutrition are mostly made from milk, which contains only minimal amounts of creatine. This fact creates an environment for the transformation of critically ill patients into the "position of vegetarians", who have demonstrably lower serum creatinine concentrations and also lower muscle strength than "omnivores".

A number of clinical studies have shown that low serum creatinine on admission are associated with higher mortality in patients admitted to the ICU. However, it is not known whether this finding also apply to patients admitted to the post-ICU care unit. Similarly, it is not known whether nutritional support enriched with creatine can improve the outcome of patients admitted to the ICU or to the post-ICU care units. Creatine is a food supplement with significant ergogenic potential and its beneficial effect in these patients is generally expected. The aim of the study is to contribute to clarifying the above-described uncertainties in the knowledge of this issue. The relationship between subnormal serum creatinine od admission and weaning from mechanical ventilation will be investigated through prospective observation, with the assumption that patients with subnormal creatinine levels will have a prolonged weaning compared to patients with normal creatinine values. The methodology of a prospective double-blind, placebo-controlled, randomized clinical trial will be used to investigate the benefit of supplementing nutritional support with creatine in a group of patients with subnormal creatinine value on admission. It is assumed that this procedure will be associated with a reduction in the need for ventilatory support and a better outcome compared to patients who will not receive creatine.

Inclusion criteria

• Patients <18 years of age
• Patients admitted to post-ICU care units at Chronicare Group a.s. in the Czech Republic within 12 months

Exclusion criteria

• Patients who are unlikely to be weaned from ventilatory support.
• Patients in palliative care or with a survival probability of <3 months
• Patients with advanced malignancy
• Patients with a history of chronic kidney disease
• Patients with a history of chronic liver disease
• Patients with supranormal serum creatinine on admission to the post-ICU care unit
• Patients who refused to sign the Informed Consent with participation in the study.