Prevention and Correction of Dysnatremia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Dysnatremia occurs commonly in patients with aneurysmal subarachnoid hemorrhage (aSAH). The mechanisms for development of sodium dyshomeostasis are complex, including the cerebral salt-wasting syndrome, the syndrome of inappropriate secretion of antidiuretic hormone, diabetes insipidus. Iatrogenic occurrence of altered sodium levels plays a role, as sodium homeostasis is tightly linked to fluid and volume management. METHODS: Narrative review of the literature. RESULTS: Many studies have aimed to identify factors predictive of the development of dysnatremia, but data on associations between dysnatremia and demographic and clinical variables are variable. Furthermore, although a clear relationship between serum sodium serum concentrations and outcomes has not been established-poor outcomes have been associated with both hyponatremia and hypernatremia in the immediate period following aSAH and set the basis for seeking interventions to correct dysnatremia. While sodium supplementation and mineralocorticoids are frequently administered to prevent or counter natriuresis and hyponatremia, evidence to date is insufficient to gauge the effect of such treatment on outcomes. CONCLUSIONS: In this article, we reviewed available data and provide a practical interpretation of these data as a complement to the newly issued guidelines for management of aSAH. Gaps in knowledge and future directions are discussed.

The Impact of 2 Weight-Based Standard Parenteral Nutrition Formulations Compared With One Standard Formulation on the Incidence of Hyperglycemia and Hypernatremia in Low Birth-Weight Preterm Infants.

BACKGROUND: Standardized parenteral nutrition (PN) formulations are used in at-risk neonates to provide nutrition immediately following birth. However, evidence for the optimal formulation(s) to maximize growth while reducing the risks of glucose and electrolyte abnormalities is limited. PURPOSE: The purpose of this study was to compare the rates of hypernatremia and hyperglycemia with 2 weight-based standardized PN formulations versus one standard PN in low birth-weight preterm neonates. METHODS: This was a single-center observational study of infants less than 1800 g birth weight and less than 37 weeks' gestation who received standardized PN in the first 48 hours of life. Patients in the weight-based PN group were compared with a historical group of patients receiving single standard PN. Rates of hypernatremia and hyperglycemia were compared by χ2 analysis. RESULTS: There was a nonsignificant (P = .147) reduction in hypernatremia in the weight-based PN group (9 of 87; 10.3%) compared with the single PN group (16 of 89; 18.0%). However, hyperglycemia was significantly more frequent in the weight-based group than in the single PN group (24.1% vs 12.4%, P = .035). IMPLICATIONS FOR PRACTICE: The 2 weight-based PN standardized formulations studied did not significantly decrease the incidence of hypernatremia or hyperglycemia. IMPLICATIONS FOR RESEARCH: Future studies to determine optimal standardized PN to provide early nutrition in high-risk neonates are warranted.

Novel Risk Score Efficiently Prevents Tolvaptan-Induced Hypernatremic Events in Patients With Heart Failure.

BACKGROUND: It has been 7 years since tolvaptan was approved in Japan for the indication of heart failure in patients with volume overload; the drug can be used in patients with normonatremia. Hypernatremia was identified as a significant adverse event to be prevented.Methods and Results:We compiled and analyzed data from 3,349 patients over 5 years to identify patients at high risk of hypernatremia with tolvaptan treatment. The incidence of hypernatremia, defined as serum sodium ≥150 mEq/L, was 3.65%. Baseline serum sodium concentrations, serum potassium concentrations, blood urea nitrogen : creatinine ratio, initial tolvaptan dose, and age were identified as risk factors for hypernatremia. A hypernatremia risk score was developed using the odds ratios for these factors. The high-risk population was defined as patients with a risk score ≥17.80. CONCLUSIONS: To prevent the occurrence of hypernatremic events in patients taking tolvaptan, we recommend a very low starting dose (i.e., 3.75 mg/day) in patients identified as being at high risk of hypernatremia using our new scoring process.

Complications and management of hyponatremia.

PURPOSE OF REVIEW: Hyponatremia causes significant morbidity, mortality, and disability. This review considers the literature of the past 18 months to improve understanding of these complications and to identify therapeutic strategies to prevent them. RECENT FINDINGS: Acute hyponatremia causes serious brain swelling that can lead to permanent disability or death. A 4-6 mEq/l increase in serum sodium is sufficient to reverse impending herniation. Brain swelling is minimal in chronic hyponatremia, and to avoid osmotic demyelination, correction should not exceed 8 mEq/l/day. In high-risk patients, correction should not exceed 4-6 mEq/l/day. Inadvertent overcorrection of hyponatremia is common and preventable by controlling unwanted urinary water losses with desmopressin. Even mild chronic hyponatremia is associated with increased mortality, attention deficit, gait instability, osteoporosis, and fractures, but it is not known if the correction of mild hyponatremia improves outcomes. SUMMARY: Controlled trials are needed to identify affordable treatments for hyponatremia that reduce the need for hospitalization, decrease hospital length of stay, and decrease morbidity. Such trials could also help answer the question of whether hyponatremia causes excess mortality or whether it is simply a marker for severe, lethal, underlying disease.

[Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

OBJECTIVE: To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (P<0.05). There was high incidence of diabetes insipidus in patients with pituitary stalk excision and tumor close adhesion to the third ventricle floor at the early postoperation (P<0.05). Under such conditions, the incidence of diabetes insipidus in the vasopressin tannate group was decreased compared with the control group (P<0.05). Postoperative hypernatremia occurred in 37 patients (44.6%), and hyponatremia occurred in 60 patients (72.3%), the average time of the occurrence of hpernatremia and hyponatremia was 1.4 and 3.7 days after surgery. Postoperative high serum sodium and low serum sodium appeared alternately in 19 patients (22.9%). There was significant difference in the serum sodium distribution in the first day after surgery in both groups (P<0.05), and the percent of hpernatremia in the vasopressin tannate group was significantly less than that in the control group (P<0.05).
 Conclusion: Preventive use of vasopressin tannate can effectively reduce diabetes insipidus and hypernatremia incidence at the early postoperative stage after microsurgery for craniopharyngioma.

[Hyponatremia and tolvaptan : what is the situation 5 years after approval?]. / Hyponatriämie und Tolvaptan : Wo stehen wir 5 Jahre nach der Zulassung?

The diuretic tolvaptan has been approved for more than 5 years for the indications of euvolemic hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) secretion. In recent years many patients have been treated with tolvaptan and many physicians could gather practical experience. Other countries, such as the USA had already gained greater experience, also in the indications for hypervolemic hyponatremia. After approval was granted more than 5000 patients worldwide were included in the so-called hyponatremia register and 22 active centers in Germany with 317 patients participated. Although some details from this now concluded register have been published, the final publication of the multinational post-authorization safety study on tolvaptan in the treatment of SIADH has not yet been published. In the years 2012 and 2013 two warning letters were issued on tolvaptan. The first letter warned of the risk of a faster increase in serum sodium using tolvaptan and provided detailed information on how the risk of osmotic demeyelination can be minimized. So far only one proven case of osmotic demelination syndrome (ODS) is known; however, this occurred following incorrect use of tolvaptan in a monotherapy. The second warning letter provided information on the potential risk (reversible) of liver damage by tolvaptan, which resulted from the TEMPO 3:4 study. In this study tolvaptan was used in a higher dosage for therapy of autosomal dominant polycystic kidney disease. Although the European renal best practice (ERBP) guidelines from 2014 did not recommend tolvaptan for the indications of SIADH, other guidelines came to different conclusions. In summary, 5 years after the approval of tolvaptan there is still no consensus. At the current time many questions still remain unanswered. Initiation of therapy with tolvaptan remains reserved for experienced physicians in hospitals. Treatment must be adapted on the basis of a clinical estimation of the individual situation of each patient.

Sodium lactate for fluid resuscitation: the preferred solution for the coming decades?

In a recent issue of Critical Care, 0.5 M sodium lactate infusion for 24 hours was reported to increase cardiac output in patients with acute heart failure. This effect was associated with a concomitant metabolic alkalosis and a negative water balance. Growing data strongly support the role of lactate as a preferential oxidizable substrate to supply energy metabolism leading to improved organ function (heart and brain especially) in ischemic conditions. Due to its sodium/chloride imbalance, this solution prevents hyperchloremic acidosis and limits fluid overload despite the obligatory high sodium load. Sodium lactate solution therefore shows many advantages and appears a very promising means for resuscitation of critically ill patients. Further studies are needed to establish the most appropriate dose and indications for sodium lactate infusion in order to prevent the occurrence of severe hypernatremia and metabolic alkalosis.

A novel method for managing water and electrolyte balance after transsphenoidal surgery: preliminary study of moderate water intake restriction.

Hyponatremia is a common and potentially serious complication of transsphenoidal surgery (TSS). Since September 2009, we have implemented moderate water intake restriction (< 2500 mL/day) after TSS in an attempt to prevent this complication. The aim of this study was to investigate the efficacy of a combination of moderate restriction of water intake plus antidiuretic hormone (arginine vasopressin [AVP]) replacement therapy in patients with diabetes insipidus (DI) for reducing the incidence of delayed hyponatremia after TSS. Patients treated from September 2005 to August 2009 were allowed to drink water freely after surgery (the control group), while patients treated from September 2009 to June 2012 were restricted to less than 2500 mL water per day (the water restriction group). To reduce the occurrence of hypernatremia, AVP replacement therapy was provided immediately after the development of DI. We retrospectively analyzed the incidence of hyponatremia, DI, and hypernatremia in patients following TSS. Hyponatremia incidence was significantly lower in the water restriction group (P = 0.017); however, there were no significant differences in DI incidence and hypernatremia incidence between the 2 groups. Under DI control with AVP replacement therapy, the water restriction group showed no significant difference in the daily self-rated thirst level for the patients with and without DI. Moderate water intake restriction in addition to AVP replacement therapy significantly decreases the incidence of hyponatremia without patient discomfort (extreme thirst) and other complications. However, further studies are required to determine the most effective amount of water and the optimal duration of postoperative water restriction.

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial.

AIM: To compare the incidence of hyponatremia in full-term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). METHODS: In this double-blind, randomized, controlled trial, full-term newborns (≥37 weeks), appropriate for gestational age, with severe non-haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. RESULTS: Forty-two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. CONCLUSION: In full-term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.

Intravenous fluid management for the acutely ill child.

PURPOSE OF REVIEW: To review the principles of prescribing intravenous fluids (IVFs) to the acutely ill child and of adjusting sodium composition and fluid rate to prevent disorders in serum sodium or volume status from occurring. RECENT FINDINGS: Recent data have revealed that the historic approach of administering hypotonic IVFs results in a high incidence of hospital-acquired hyponatremia in children. The majority of hospitalized children requiring IVFs are at risk for developing hyponatremia from numerous stimuli for arginine vasopressin (AVP) production, such as volume depletion, pain, stress, nausea, vomiting, respiratory or central nervous system (CNS) disorders, or the postoperative state. Multiple recent prospective studies in over 600 children have demonstrated that hypotonic fluids cause acute hyponatremia, whereas 0.9% sodium chloride (NaCl) effectively prevents it. 0.9% NaCl is the most appropriate IVF for the majority of hospitalized children. Fluid and sodium restriction will be needed for children with edematous or oliguric states and hypotonic fluids needed for children with urinary or extra-renal free water losses or hypernatremia. SUMMARY: Hypotonic fluids should not be administered routinely in children due to the risk of hospital-acquired hyponatremia. 0.9% NaCl is the preferred IVF for the vast majority of hospitalized children.

Restoration of dysnatremia and acute kidney injury benefits outcomes of acute geriatric inpatients.

Dysnatremia and dyskalemia are common problems in acutely hospitalized elderly patients. These disorders are associated with an increased risk of mortality and functional complications that often occur concomitantly with acute kidney injury in addition to multiple comorbidities. In a single-center prospective observational study, we recruited 401 acute geriatric inpatients. In-hospital outcomes included all-cause mortality, length of stay, and changes in functional status as determined by the Activities of Daily Living (ADL) scale, Eastern Cooperative Oncology Group (ECOG) performance, and Clinical Frailty Scale (CFS). The prevalence of dysnatremia alone, dyskalemia alone, and dysnatremia plus dyskalemia during initial hospitalization were 28.4%, 14.7% and 32.4%, respectively. Patients with electrolyte imbalance exhibited higher mortality rates and longer hospital stays than those without electrolyte imbalance. Those with initial dysnatremia, or dysnatremia plus dyskalemia were associated with worse ADL scores, ECOG performance and CFS scores at discharge. Subgroup analyses showed that resolution of dysnatremia was related to reduced mortality risk and improved CFS score, whereas recovery of renal function was associated with decreased mortality and better ECOG and CFS ratings. Our data suggest that restoration of initial dysnatremia and acute kidney injury during acute geriatric care may benefit in-hospital survival and functional status at discharge.

Salt-Sensitive Hypertension of the Renal Tubular Cell-Specific NFAT5 (Nuclear Factor of Activated T-Cells 5) Knockout Mice.

[Figure: see text].

Fluids, pH, ions and electrolytes.

PURPOSE OF REVIEW: Significant attention has been recently focused on both maintenance fluid and resuscitation fluid use in critical care. Accordingly, a focused review of the properties of crystalloid and colloid fluids, their expected benefits, and potential deleterious side effects is appropriate and timely. RECENT FINDINGS: Despite their ubiquitous use, well described side effects, and ability to be titrated to a physiologic endpoint, fluids are rarely considered in a fashion similar to other pharmacologic agents. Understanding their physical and chemical properties allows the clinician to understand, anticipate and deliberately harness their expected impact on acid-base balance. Expanded insights into the pathogenesis of common acid-base disorders may be gleaned from utilizing a physicochemical approach that allows the precise quantification of the ionic species that impact pH. SUMMARY: This focused review further enables the clinician to appropriately investigate, modify, and optimize bedside clinical care related to fluid and acid-base management.

Management of sodium disorders during continuous haemofiltration.

In patients with acute kidney injury and concomitant severe hyponatraemia or hypernatraemia, rapid correction of the serum Na+ concentration needs to be avoided. The present paper outlines the principles of how to adjust the Na+ concentration in the replacement fluid during continuous renal replacement therapy to prevent rapid changes of the serum Na+ concentration.

100 cc 3% sodium chloride bolus: a novel treatment for hyponatremic encephalopathy.

Hyponatremic encephalopathy is a potentially lethal condition with numerous reports of death or permanent neurological injury. The optimal treatment for hyponatremic encephalopathy remains controversial. We have introduced a unified approach to the treatment of hyponatremic encephalopathy which uses 3% NaCl (513 mEq/L) bolus therapy. Any patient with suspected hyponatremic encephalopathy should receive a 2 cc/kg bolus of 3% NaCl with a maximum of 100 cc, which could be repeated 1-2 times if symptoms persist. The approach results in a controlled and immediate rise in serum sodium with little risk of inadvertent overcorrection.

[Hypernatremia as a predictor of poor outcomes in children with severe brain injury].

The aim of the study was to elucidate a relationship between the development of hypernatremia and the frequency of poor outcomes in children with severe brain injury (SBI). The retrospective study enrolled 77 children (54 boys and 23 girls) aged 1 month to 18 years, who had SBI in the period of January 2008 to September 2009, and were divided into 3 groups after treatment termination. The admission injury severity criterion was Glasgow coma scale (8 scores or less) rating. Group A comprised 51 children with SBI without hypernatremia; Group B included 14 children with SBI and hypernatremia. Group C consisted of 12 children with SBI, hypernatremia, and polyuremia. The latter group was appraised as a group with evolving central diabetes insipidus. A total of 26 (33.8%) patients had hypernatremia. Poor outcomes (Glasgow outcome scores of 1-3) at 30 days were noted in only Groups B and C: comparison of outcomes in Groups B and C showed the higher incidence of poor outcomes in 10 (84%) Group C patients (with hypernatremia and polyuria) and 4 (28%) children in Group B. Comparison of Groups B and C children indicated that the hazard ratio was 0.3. Therefore, the risk of poor outcomes is much higher in the development of central diabetes insipidous in the presence of hypernatremia.

Sodium and brain injury: do we know what we are doing?

There is mounting evidence, including the recent report by Maggiore and colleagues, of an association between hypernatremia and mortality in patients with traumatic brain injury. This mandates a re-evaluation of routine administration of agents such as hypertonic saline for the management of intracranial hypertension in those with traumatic brain injury.

Prevention of hypernatraemic dehydration in breastfed newborn infants by daily weighing.

UNLABELLED: Hypernatraemic dehydration, which predominantly appears in breastfed neonates, can cause serious complications, such as convulsions, permanent brain damage and death, if recognised late. Weight loss > or = 10% of birth weight could be an early indicator for this condition. In this prospective cohort study from October 2003 to June 2005 in the postnatal ward of the University Hospital Zurich, Switzerland, all term newborns with birth weight > or = 2,500 g were weighed daily until discharge. When the weight loss was > or = 10% of birth weight, serum sodium was measured from a heel prick. Infants with moderate hypernatraemia (serum sodium = 146-149 mmol/l) were fed supplementary formula milk or maltodextrose 10%. Infants with severe hypernatraemia (serum sodium > or = 150 mmol/l) were admitted to the neonatal unit and treated in the same way, with or without intravenous fluids, depending on the severity of the clinical signs of dehydration. A total of 2,788 breastfed healthy term newborns were enrolled. Sixty-seven (2.4%) newborns had a weight loss > or = 10% of birth weight; 24 (36%) of these had moderate and 18 (27%) severe hypernatraemia. Infants born by caesarean section had a 3.4 times higher risk for hypernatraemia than those born vaginally. All newborns regained weight 24 h after additional fluids. CONCLUSION: In our study, one out of 66 healthy exclusively breastfed term neonates developed hypernatraemic dehydration. Daily weight monitoring and supplemental fluids in the presence of weight loss > or = 10% of birth weight allows early detection and intervention, thereby preventing the severe sequellae of hypernatraemic dehydration.

[Experience in using normofundin and sterofundin solutions for the correction of hypernatremia].

The efficacy of Sterofundin, Normofundin, and physiological solutions in correcting hypernatremia and impaired acid-base balance was analyzed in patients with sellar region tumors. Twenty-one patients were enrolled in the study; three groups were formed. Physiological solution added by 4% of potassium chloride and 25% magnesium sulfate solution was used in Group 1 (n = 7). Normofundin was employed in Group 2 (n = 7). Sterofundin was applied to Group 3 (n = 7). The volume of administered fluid corresponded to the sum of volumes of basic needs and those of fluid losses. The study revealed that the most adequate correction of hypernatremia was seen with the use of Sterofundin. The use of Normofundin is associated with a risk of a rapid and significant reduction in the level of sodium and that of physiological solution fails to correct hypernatremia. Metabolic alkalosis was typical for all the patients included into the study. Its effective correction was noted only when Sterofundin was used.

Weight loss thresholds to detect early hypernatremia in newborns.

OBJECTIVE: The literature indicates a single universal cut-off point for weight loss after birth for the risk of hypernatremia, without considering other factors. The aim of this study was to construct and internally validate cut-off points for the percentage weight loss associated with the risk of hypernatremia, taking into account risk factors. METHODS: A prospective study with a three-day follow-up was conducted in 165 neonates with a gestational age ≥35 weeks. The main outcome variable was mild or moderate hypernatremia (serum sodium≥145mmol/L). Secondary variables (risk factors) were maternal and infant variables. A multivariate logistic regression model was constructed to predict hypernatremia, obtaining its probability and the optimal discriminant cut-off point for hypernatremia (receiver operating characteristic analysis). Based on this point, threshold weight loss values were obtained according to the other variables. These values were internally validated by bootstrapping. RESULTS: There were 51 cases (30.9%) of hypernatremia. The mean percentage weight loss for hypernatremic infants was 8.6% and 6.0% for the rest. Associated variables in the multivariate model included greater weight loss, male gender, higher education level, multiparity, and cesarean delivery. The model had an area under the receiver operating characteristic curve of 0.84 (sensitivity=77.6%; specificity=73.2%). Similar values were obtained in the bootstrapping validation. The lowest percentage weight loss was 4.77%, for cesarean delivery in male infants of mothers with a higher education level. CONCLUSIONS: The weight loss percentage values depended on the type of delivery, parity, newborn gender, and level of maternal education. External studies are required to validate these values.