Abstract
BackgroundMannitol and hypertonic saline are used to ameliorate brain edema and intracranial hypertension during and after craniotomy. We hypothesized that the agreement of measured and calculated serum osmolality during the infusion of hypertonic saline would be better than mannitol. The objective was to determine the accuracy of serum osmolality estimation by different formulas during the administration of hyperosmolar agent.MethodsA prospective, randomized, double-blinded, controlled trial was conducted in a 30-bed neurosurgical intensive care unit at a university hospital. Thirty-five adult patients requiring the use of hyperosmolar agents for prevention or treatment of brain edema after elective craniotomy were enrolled, and randomly assigned 1:1 to receive 125 mL of either 20 % mannitol (mannitol group) or 3.1 % sodium chloride solution (hypertonic saline group) in 15 min. Serum osmolality, serum sodium and potassium concentration, blood urea nitrogen and blood glucose concentration were measured during the study period. The primary outcome was the agreement of measured and estimated serum osmolality during the infusion of the two experimental agents. We used Bland and Altman’s limits of agreement analysis to clarify the accuracy of estimated serum osmolality. Bias and upper and lower limits of agreement of bias were calculated.ResultsFor each formula, the bias was statistically lower in hypertonic saline group than mannitol group (p < 0.001). Within group comparison showed that the lowest bias (6.0 [limits of agreement: −18.2 to 30.2] and 0.8 [−12.9 to 14.5] mOsml/kg in mannitol group and hypertonic saline group, respectively) was derived from the formula ‘2 × ([serum sodium] + [serum potassium]) + [blood urea nitrogen] + [blood glucose]’.ConclusionsCompared to mannitol, a better agreement between measured and estimated serum osmolality was found during the infusion of hypertonic saline. This result indicates that, if hypertonic saline is chosen to prevent or treat brain edema, calculated serum osmolality can be used as a reliable surrogate for osmolality measurement.Trial registrationClinicalTrials.gov identifier: NCT02037815
Highlights
Mannitol and hypertonic saline are used to ameliorate brain edema and intracranial hypertension during and after craniotomy
The main findings of our study are that, (1) calculation by using the formula ‘2 × ([Na+] + [K+]) + blood urea nitrogen (BUN) + Blood glucose concentration (BG)’ provides the most accurate estimation of serum osmolality after the infusion of hypertonic saline (HS); (2) an increase of serum osmolality is observed after the infusion of either 20 % mannitol or 3.1 % HS, and with the latter this is associated with the increase in serum sodium concentration; and (3) compared with HS, mannitol results in an abrupt and significant increase in osmolal gap during the early stage after the infusion
If HS is chosen to prevent or treat brain edema during post-operative period, calculated serum osmolality can be used as a reliable surrogate for osmolality measurement
Summary
Mannitol and hypertonic saline are used to ameliorate brain edema and intracranial hypertension during and after craniotomy. Hyperosmolar agents have been used to ameliorate brain edema and intracranial hypertension during and after craniotomy, where mannitol and hypertonic saline (HS) are the two most extensively studied and most frequently used in the clinical practice [6,7,8,9,10,11,12]. The primary mechanism of hyperosmolar agents to control brain edema is based on the increased osmotic gradient across blood–brain barrier during drug infusion, and this helps in the removal of water from brain tissue to the intravascular space [17]. Clinical studies showed that an osmotic gradient between blood and brain of just above 10 mOsmol/kg was effective in reducing ICP [18]. Measurement of serum osmolality during hyperosmolar agent infusion is of clinical importance to determine clinical efficacy, adjust dosage and avoid side effects
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