Hypernatremia, is a high concentration of sodium in the blood. Normal serum sodium levels are 135 – 145 mmol/L (135 – 145 mEq/L). Hypernatremia is generally defined as a serum sodium level of more than 145 mmol/L.

Hypernatremia is one of the most common electrolyte disturbances following aneurysmal subarachnoid hemorrhage (aSAH) and has been correlated with increased mortality in single institution studies. Both hyponatremia and hypernatremia during ICU management were significantly associated with unfavorable neurologic outcomes 1).

In neurosurgical patients, this is most often seen in the setting of diabetes insipidus (DI). Since normal total body water (TBW) is ≈ 60% of the patient’s normal body weight, the patient’s current TBW may be estimated by Eq.

Mild and moderate hypernatremia were significantly associated with increased early mortality in patients with severe TBI 2). Hypernatremia was associated also with poorer outcomes in patients with severe TBI. This finding warrants further investigation in a prospective, randomized study 3).

Electrolyte imbalances are common in traumatic brain injury. In a study Hypokalemia was the most common electrolyte imbalance at 65.5%. The results of the use of a multivariable logistic regression model showed that the odds of postoperative death in TBI patients were increased with high levels of blood glucose, hypernatremia, and acidosis.Hypokalemia was the most common electrolyte imbalance in TBI patients. Hypernatremia, acidosis, and hyperglycemia significantly increased the odds ratio of death in the first 24  hours post TBI 4).

Clinical features

Early symptoms may include a strong feeling of thirstweaknessnausea, and loss of appetite.

Severe symptoms include confusion, muscle twitching, and bleeding in or around the brain.

Severe symptoms typically only occur when levels are above 160 mmol/L.


The free water deficit to be replaced is given by a Eq. Correction must be made slowly to avoid exacerbating cerebral edema. One half the water deficit is replaced over 24 hours, and the remainder is given over 1–2 additional days. Judicious replacement of deficient ADH in cases of true DI must also be made.

The aim of a work of Vassilyev was to evaluate the effectiveness of Sterofundin in the framework of complex therapy of hypernatremia in neurosurgical patients after removal of brain tumors. They analyzed the dynamics of the concentrations of sodium, potassium, chorus of the plasma, anion gap and buffer bases in the postoperative period of these patients. For obtaining reliable results, the patients were divided into groups according to the nature of the treatment: Sterofundin and symptomatic correction of hypotonic solution of sodium chloride, saluretic and Spironolactone respectively. In a comparison between the groups, a distinct difference in the speed of regression of hypernatremia and durability of the achieved effect was observed. In case of treatment with Sterofundin there was a significant decrease of hypernatremia by the end of the second day of the postoperative period without tendency to re-raise. The prevalence of hypotonic solutions of sodium chloride and potassium-sparing saluretics in intensive care allowed reducing the sodium concentration non-persistently to the fourth day on the background of significant fluctuations in its concentration. The use of Sterofundin in complex therapy of electrolyte disturbances, particularly of hypernatremia in neurosurgical patients after removal of brain tumors, is reflected in the form of significant regression of increased sodium concentration in plasmacompared with the method of use “hypotonic” hemodilution, saluretics and potassium-sparing diuretics 5).



Pulmonary complications and acute kidney injury were more common in hypernatremia 6).

Hoffman et al., from the Upstate Medical University performed a retrospective analysis of adults between 2002 and 2011 with a primary diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) using the Nationwide Inpatient Sample (NIS). Patients were grouped according to whether or not an inpatient diagnosis of hypernatremia was present. The primary outcome was the NIS-SAH outcome measure. Secondary outcomes included in-hospital mortalitylength of stay (LOS), and non-routine hospital discharge. Outcomes analyses adjusted for SAH severity using the NIS-SAH Severity Score, Charlson Comorbidity Index, and the presence of cerebral edema.

A total of 18,377 patients were included in the study. The incidence of a poor outcome as defined by the NIS-SAH outcome measure was 65.9% in the hypernatremia group and 33.4% in the normonatremia group (OR 1.96, 95% CI 1.68 – 2.27). There was higher mortality in the hypernatremia group (OR 1.60, 95% CI 1.37 – 1.87). Patients with hypernatremia had a significantly higher rate of non-routine hospital discharge and gastrostomy. The incidences of poor outcome, in-hospital mortality, and non-routine disposition were higher in the hypernatremia group regardless of treatment type (clipping vs. endovascular embolization). Pulmonary complications and acute kidney injury were more common in the hypernatremia group as well.

In patients with aSAH, hypernatremia is associated with poorer functional outcomes regardless of SAH severity 7).



Okazaki T, Hifumi T, Kawakita K, Shishido H, Ogawa D, Okauchi M, Shindo A, Kawanishi M, Tamiya T, Kuroda Y. Target Serum Sodium Levels During Intensive Care Unit Management of Aneurysmal Subarachnoid Hemorrhage. Shock. 2017 Nov;48(5):558-563. doi: 10.1097/SHK.0000000000000897. PubMed PMID: 28498294.

Vedantam A, Robertson CS, Gopinath SP. Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus. 2017 Nov;43(5):E2. doi: 10.3171/2017.7.FOCUS17418. PubMed PMID: 29088954.

Hoffman H, Jalal MS, Chin LS. Effect of Hypernatremia on Outcomes After severe Traumatic Brain Injury: A Nationwide Inpatient Sample analysis. World Neurosurg. 2018 Oct;118:e880-e886. doi: 10.1016/j.wneu.2018.07.089. Epub 2018 Jul 18. PubMed PMID: 30031178.

Pin-On P, Saringkarinkul A, Punjasawadwong Y, Kacha S, Wilairat D. Serum electrolyte imbalance and prognostic factors of postoperative death in adult traumatic brain injury patients: A prospective cohort study. Medicine (Baltimore). 2018 Nov;97(45):e13081. doi: 10.1097/MD.0000000000013081. PubMed PMID: 30407307; PubMed Central PMCID: PMC6250545.

Vassilyev D. [MODERN APPROACHES TO CORRECTION OF HYPERNATREMIA IN NEUROSURGICAL PATIENTS]. Georgian Med News. 2016 Nov;(Issue):12-16. Russian. PubMed PMID: 28009309.
6) , 7)

Hoffman H, Verhave B, Chin LS. Hypernatremia is associated with poorer outcomes following aneurysmal subarachnoid hemorrhage: a nationwide inpatient sample analysis. J Neurosurg Sci. 2018 Dec 5. doi: 10.23736/S0390-5616.18.04611-8. [Epub ahead of print] PubMed PMID: 30514071.

Traumatic spinal cord injury treatment

Early decompression surgery post-SCI can enhance patient outcomes, but does not directly facilitate neural repair and regeneration. Currently, there are no U.S. Food and Drug Administration-approved pharmacological therapies to augment motor function and functional recovery in individuals with traumatic SCI.

Acute traumatic spinal cord injury (SCI) is a devastating event with far-reaching physical, emotional, and economic consequences for patients, families, and society at large. Timely delivery of specialized care has reduced mortality; however, long-term neurological recovery continues to be limited. In recent years, a number of exciting neuroprotective and regenerative strategies have emerged and have come under active investigation in clinical trials, and several more are coming down the translational pipeline. Among ongoing trials are RISCIS (riluzole), INSPIRE study (Neuro-Spinal Scaffold), MASC (minocycline), and SPRING (VX-210). Microstructural MRI techniques have improved our ability to image the injured spinal cord at high resolution. This innovation, combined with serum and cerebrospinal fluid (CSF) analysis, holds the promise of providing a quantitative biomarker readout of spinal cord neural tissue injury, which may improve prognostication and facilitate stratification of patients for enrollment into clinical trials. Given evidence of the effectiveness of early surgical decompression and growing recognition of the concept that “time is spine,” infrastructural changes at a systems level are being implemented in many regions around the world to provide a streamlined process for transfer of patients with acute SCI to a specialized unit. With the continued aging of the population, central cord syndrome is soon expected to become the most common form of acute traumatic SCI; characterization of the pathophysiologynatural history, and optimal treatment of these injuries is hence a key public health priority. Collaborative international efforts have led to the development of clinical practice guidelines for traumatic SCI based on robust evaluation of current evidence 1).


Badhiwala JH, Ahuja CS, Fehlings MG. Time is spine: a review of translational advances in spinal cord injury. J Neurosurg Spine. 2018 Dec 20;30(1):1-18. doi: 10.3171/2018.9.SPINE18682. Review. PubMed PMID: 30611186.

Biodegradable wafer

One of the therapeutic options for Glioblastoma multiforme includes placing biodegradable wafers releasing BCNU (Gliadel®) into the tumor bed at the time of surgical removal of the tumor. Due to the significant benefit this polymer technology has had clinically, Shapira-Furman et al., from Johns Hopkins Hospital have prepared wafers releasing Temozolomide (TMZ), TMZ delivered via polymer wafer could be used as a complementary treatment with or as an alternative to Gliadel®. TMZ is an alkylating agent which is water soluble. To remain comparable with the preclinical studies that led to Gliadel® the same size of wafers were formulated with TMZ. Wafers were loaded with 50% w/w TMZ in poly(lactic acid-glycolic acid) (PLGA) and showed reliable release of high dose TMZ for a period of 4 weeks. To achieve this 30-day release of the highly water soluble drug, they developed an encapsulation method, where the drug powder was first coated with the polymer to form core-shell particles in which the coating shell served as a rate controlling membrane for the drug particles. Wafers were also made with a co-loading of TMZ and BCNU. All wafers were tested in vivo by treating an intracranial 9L gliosarcoma model in F344 rats. Rats that were either untreated or treated with blank wafer died within 11 days while the median survival for rats treated with systemic TMZ was 18 days. The group that received the BCNU alone wafer had a median survival of 15 days, the group that received the TMZ wafer alone had a median survival of 19 days, and the group treated with the BCNU-TMZ wafer had a median survival of 28 days with 25% of the animals living long term (p < .0038 vs. Control; p < .001 vs. Blank Polymer). These findings demonstrate the potential of this newly designed wafer for treating GBM. Moreover, this concept, can pave the way for other drug combinations that may improve the clinical application of numerous agents to treat solid tumors 1).


Shapira-Furman T, Serra R, Gorelick N, Doglioli M, Tagliaferri V, Cecia A, Peters M, Kumar A, Rottenberg Y, Langer R, Brem H, Tyler B, Domb AJ. Biodegradable wafers releasing Temozolomide and Carmustine for the treatment of brain cancer. J Control Release. 2018 Dec 31. pii: S0168-3659(18)30753-3. doi: 10.1016/j.jconrel.2018.12.048. [Epub ahead of print] PubMed PMID: 30605703.
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