Hyperosmolar Treatment for Patients at Risk for Increased Intracranial Pressure: A Single-Center Cohort Study

Abstract

Treatment with osmoactive agents such as mannitol or hypertonic saline (HTS) solutions is widely used to manage or prevent the increase of intracranial pressure (ICP) in central nervous system (CNS) disorders. We sought to evaluate the variability and mean plasma concentrations of the water and electrolyte balance parameters in critically ill patients treated with osmotic therapy and their influence on mortality. This cohort study covered patients hospitalized in an intensive care unit (ICU) from January 2017 to June 2019 with presumed increased ICP or considered to be at risk of it, treated with 15% mannitol (G1, n = 27), a combination of 15% mannitol and 10% hypertonic saline (HTS) (G2, n = 33) or 10% HTS only (G3, n = 13). Coefficients of variation (Cv) and arithmetic means (mean) were calculated for the parameters reflecting the water and electrolyte balance, i.e., sodium (NaCv/NaMean), chloride (ClCv/ClMean) and osmolality (mOsmCv/mOsmMean). In-hospital mortality was also analyzed. The study group comprised 73 individuals (36 men, 49%). Mortality was 67% (n = 49). Median NaCv (G1: p = 0.002, G3: p = 0.03), ClCv (G1: p = 0.02, G3: p = 0.04) and mOsmCv (G1: p = 0.001, G3: p = 0.02) were higher in deceased patients. NaMean (p = 0.004), ClMean (p = 0.04), mOsmMean (p = 0.003) were higher in deceased patients in G3. In G1: NaCv (AUC = 0.929, p < 0.0001), ClCv (AUC = 0.817, p = 0.0005), mOsmCv (AUC = 0.937, p < 0.0001) and in G3: NaMean (AUC = 0.976, p < 0.001), mOsmCv (AUC = 0.881, p = 0.002), mOsmMean (AUC = 1.00, p < 0.001) were the best predictors of mortality. The overall mortality prediction for combined G1+G2+G3 was very good, with AUC = 0.886 (p = 0.0002). The mortality of critically ill patients treated with osmotic agents is high. Electrolyte disequilibrium is the independent predictor of mortality regardless of the treatment method used. Variations of plasma sodium, chloride and osmolality are the most deleterious factors regardless of the absolute values of these parameters

Distant Organ Damage in Acute Brain Injury

“…It’s vital to understand that critical care pathways used to treat TBI may also influence distant organ dysfunction. For example, osmotic therapy may cause serious abnormalities in water-electrolyte balance [ 175 ], which in turn would be detrimental to the kidneys and the gut. Acute respiratory failure promotes organ ischaemia and dysfunction.…”

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury

“…There is a dose–response relationship between the use of mannitol and the incidence and severity of AKI, with a cut-off of the daily dose at 1.34 g/kg body weight [ 73 ]. Interestingly, the combined therapy of ICH with mannitol and HTS did not increase the risk of AKI more than HTS alone, however several authors suggested to use HTS, demonstrating its superiority over mannitol [ 13 , 14 , 16 , 18 , 74 ]. In conclusion, it can be postulated that an increase in plasma hyperosmolality per se, as well as the use of osmotically active medications, may impair renal function, and that maintaining adequate renal perfusion may reduce the risk of AKI.…”