The Relationship between Serum Sodium, Serum Osmolality, and Intracranial Pressure in Patients with Traumatic Brain Injury Treated with Hyperosmolar Therapy

Background Treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI) is controversial. Hyperosmolar therapy is used to prevent cerebral edema in these patients. Many intensivists measure direct correlates of these agents—serum sodium and osmolality. We seek to provide context on the utility of using these measures to estimate ICP in TBI patients. Materials and Methods Patients admitted with TBI who required ICP monitoring from 2008 to 2012 were included. Intracranial pressure, serum sodium, and serum osmolality were assessed prior to hyperosmotic therapy then at 6, 12, 18, 24, 48, and 72 hours after admission. A linear regression was performed on sodium, osmolality, and ICP at baseline and serum sodium and osmolality that corresponded with ICP for 6-72-hour time points. Results 136 patients were identified. Patients with initial measures were included in the baseline analysis (n = 29). Patients who underwent a craniectomy were excluded from the 6-72-hour analysis (n = 53). Initial ICP and serum sodium were not significantly correlated (R2 .00367, P = .696). Initial ICP and serum osmolality were not significantly correlated (R2 .00734, P = .665). Intracranial pressure and serum sodium 6-72 hours after presentation were poorly correlated (R2 .104, P < .0001), as were ICP and serum osmolality at 6-72 hours after presentation (R2 .116, P < .0001). Discussion Our results indicate initial ICP is not correlated with serum sodium or osmolality suggesting these are not useful initial clinical markers for ICP estimation. The association between ICP and serum sodium and osmolality after hyperosmolar therapy was poor, thus may not be useful as surrogates for direct ICP measurements.

\"Balanced hyperosmolar therapy\" using 3% hypertonic saline - 20% mannitol versus an equiosmolar volume of either 3% hypertonic saline or mannitol 20% in supratentorial tumor resection: A new approach to achieve hemodynamic stability

Both 3% hypertonic saline (3% HTS) and 20% mannitol were proven to be effective in relaxing the brain during supratentorial surgeries. This work aimed to study the effect of consecutive use of both drugs on the brain relaxation score and hemodynamic status during such surgeries.Ninety patients scheduled for supratentorial brain surgeries included in this prospective, randomized and double-blind study. Patients were allocated in three groups; HTS group (n=30) received 3 ml/kg 3% NaCl infusion over 30 minutes, HTS/M group (n=30) received mannitol 20% (1.4 ml/kg) as an infusion over 15 minute followed by 1.5 ml/kg 3% NaCl infused over 15 minutes and M group (n=30) received 3.2 ml/kg mannitol 20% infusion over 30 minutes. Brain relaxation was estimated. MAP and serum Na level were recorded at baseline and then at 30, 90 and 150 min. Total fluid intake, total urine output and operative time were recorded. Fluid intake and urine output were the highest with 20% mannitol (p ˂ 0.001). HTS/M and HTS groups showed no significance when satisfactory and fairly brain relaxation scores were added (p=0.862). MAP and CVP were near to baseline in HTS/M group at 30 and 90 min, while at 150 min no significant difference between groups. Serum hyperosmolarity was noticed in all groups at all check points but maximally with HTS group at 30 min (321.1 mOsm/L). Balanced hyperosmolar therapy using 3% HTS and 20% mannitol consecutively resulted in a satisfactory brain relaxation and allowed more hemodynamic stability.

An Audit and Comparison of pH, Measured Concentration, and Particulate Matter in Mannitol and Hypertonic Saline Solutions

Background: The preferred hyperosmolar therapy remains controversial. Differences in physical properties such as pH and osmolality may be important considerations in hyperosmolar agent selection. We aimed to characterize important physical properties of commercially available hyperosmolar solutions.Methods: We measured pH and concentration in 37 commonly-used hyperosmolar solutions, including 20 and 25% mannitol and 3, 5, 14.6, and 23.4% hypertonic saline. pH was determined digitally and with litmus paper. Concentration was determined by freezing point and vapor pressure osmometry. Salinity/specific gravity was measured with portable refractometry. Particulate matter was analyzed with filtration and light microscopy and with dynamic light scattering nephelometry.Results: pH of all solutions was below physiological range (measured range 4.13–6.80); there was no correlation between pH and solution concentration (R2 = 0.005, p = 0.60). Mannitol (mean 5.65, sd 0.94) was less acidic than hypertonic saline (5.16, 0.60). 14/59 (24%) pH measurements and 85/111 concentration measurements were outside manufacturer standards. All 36/36 mannitol concentration measurements were outside standards vs. 48/72 (67%) hypertonic saline (p &lt; 0.0001). All solutions examined on light microscopy contained crystalline and/or non-crystalline particulate matter up to several hundred microns in diameter. From nephelometry, particulate matter was detected in 20/22 (91%) solutions.Conclusion: We present a novel characterization of mannitol and hypertonic saline. Further research should be undertaken, including research examining development of acidosis following hyperosmolar therapy, the relevance of our findings for dose-response, and the clinical relevance of particulate matter in solution.

Physiologic Characteristics of Hyperosmolar Therapy After Pediatric Traumatic Brain Injury

All work was performed at the Barrow Neurological Institute at Phoenix Children's Hospital.Objective: Investigate injury severity, neuroimaging, physiology, and outcomes with bolus hyperosmolar therapy (HT) of 3% hypertonic saline or mannitol.Methods: Retrospective cohort analysis was performed. Physiologic variables included intracranial pressure (ICP), arterial blood pressure (ABP), and heart rate (HR). Volume-pressure compensation (PVC) indices included ICP pulse amplitude (AMP) and correlation of AMP and ICP (RAP). Cerebrovascular pressure reactivity (CVPR) indices included pressure reactivity index (PRx), pulse amplitude index (PAx), wavelet PRx (wPRx), and correlation of AMP and cerebral perfusion pressure (RAC). Heart rate variability (HRV) indices included heart rate standard deviation (HRsd), heart rate root mean square of successive differences (HRrmssd) and low-high frequency ratio (LHF). Outcome was assessed using Glasgow Outcomes Scale Extended Pediatrics, 12-months post-injury. Generalized estimating equations was applied to investigate associations of physiologic changes and pre-treatment indices with HT efficacy. Repeated measures analysis of variance was applied to investigate changes after HT without intracranial hypertension (ICH). Wilcoxon rank-sum was applied to investigate HT responsiveness with age, injury severity, neuroimaging, and outcomes.Results: Thirty children received bolus HT. ICH reduction after HT was associated with reduced ICP (p = 0.0064), ABP (p = 0.0126), PRx (p = 0.0063), increased HRsd (p = 0.0408), and decreased pretreatment RAC (p = 0.0115) and wPRx (p = 0.0072). HT-responsive patients were older and had improved outcomes (p = 0.0394). HT without ICH was associated with increased ICP (P &lt; 0.0001) and ABP (P &lt; 0.0001), increases in all HRV indices and decreases in all PVC indices.Conclusion: After pediatric TBI, efficacious HT is associated with decreased ICP and ABP, pre-treatment indices suggesting efficient CVPR, and potentially improved outcomes.