Experience with Tolvaptan for Euvolemic and Hypervolemic Hyponatremia in the Acute Care Setting

Background:

Hyponatremia is a common electrolyte disorder and is associated with multiple comorbidities. Management strategies are varied and etiology-dependent. The use of tolvaptan, a vasopressin antagonist, outside of clinical trials has not been well characterized.

Objectives:

To quantify tolvaptan compliance with institutional guidelines and make recommendations concerning reasonable expectations for its role in hyponatremia management.

Methods:

This was a retrospective observational study in a 125-bed community hospital. Patients admitted in 2013 who received at least one dose of tolvaptan were included.

Results:

Thirty-seven patient encounters were evaluated. Tolvaptan was prescribed with 83.7% adherence to the institutional order set. Mean age was 71 ± 16.4 years with 20 (54%) females. Hyponatremia was a contributory cause of admission in 15 (40.5%) patients and offending medications were discontinued in 7 (19%). Causes of hyponatremia included syndrome of inappropriate antidiuretic hormone (SIADH), heart failure, and cirrhosis in 78.3%, 8.2%, and 13.5% of participants, respectively. Management included fluid restriction in 19 (51%) and furosemide in 5 (13.5%), with tolvaptan administration on average 3.2 days after admission. Most patients (78.4%) required ≤2 doses. Sodium concentration was elevated 8 mEq/L by the end of hospitalization. Discharge to palliative care or death occurred in 8 (21.6%). Postdischarge review revealed 3 (8%) maintained sodium concentration ≥130 mEq/dL.

Conclusion:

Tolvaptan was initiated after other interventions and with limited duration per institutional guidelines. This cohort had complicating underlying chronic diseases. These results will be used to refine recommendations with pharmacist input for risk/benefit stratification based on reasonable expectations.     

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

AIMS

Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.

METHODS

Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.

RESULTS

One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m⁻². Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.

CONCLUSIONS

Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.     

特利加压素导致低钠血症性脑病的病例分析并文献复习

目的： 提醒临床医师及药师在临床工作中应警惕特利加压素可能导致的低钠血症性脑病。方法： 报道1例使用特利加压素出现低钠血症性脑病最终导致患者死亡的案例,并复习国内外相关文献进行分析讨论。结果： 检索到3篇使用特利加压素至低钠血症性脑病的个案报道,但均未引起影像学改变且停药后神经系统症状得以恢复;在回顾性研究中,发现使用特利加压素发生低钠血症的危险因素可能有：年龄小、基线高血钠水平、长疗程（>5 d）以及较好的肝功能（低MELD或Child评分）。结论： 特利加压素引起的低钠血症可能导致不可逆的神经系统并发症,使用该药期间应严密监测血钠,尤其是有高危因素的患者。     

Hyponatremia in critically ill patients

Context:

Hyponatremia is a common electrolyte disturbance in critically ill hence understanding its implications is important.

Aims:

This study was carried out to ascertain frequency, predisposing conditions and outcome in critically ill patients with hyponatremia on intensive care unit (ICU) admission.

Settings and Design:

This was an observational, prospective study of a series of ICU patients during a 12-month period.

Materials and Methods:

The patients were divided into two groups: Hyponatremic (serum sodium < 135 mmol/L) and Eunatremic groups (135-145 mmol/L). Clinical examination included volume status and drug history, biochemistries, clinical diagnosis and cause of hyponatremia.

Statistical Analysis Used:

Fisher''s exact test, unpaired t-tests Wilcoxon ranksum tests, profile-likelihood method, log-rank test and Kaplan—Meier curves were used. P < 0.05 were considered to be statistically significant.

Results:

In the hyponatremic group, the frequency of hyponatremia on ICU admission was 34.3%, most were euvolumic, 58.96%. Females comprised of 36.5%. The mean age was 60.4 ± 17.2. The Syndrome of inappropriate Antidiuretic Hormone (SIADH) criteria was met in ninety-one patients (36.25%), peumonia being the leading cause of SIADH. Patients with severe sepsis, elective surgery patients, renal failure and heart failure, cirrhosis of liver and subarachnoid hemorrhage were other more likely etiologic causes (P < 0.05). The hyponatremic group spent a longer time in the ICU (P = 0.02), had longer mechanical ventilator days (P < 0.05) and had an increased mortality rate (P = 0.01).

Conclusions:

Hyponatremia present on admission to the ICU is independent risk factors for poor prognosis.     

Anesthesia for surgery related to craniosynostosis: a review. Part 2

The management of children with craniosynostosis is multidisciplinary and has evolved significantly over the past five decades. The treatment is primarily surgical. The anesthetic challenges continue to be the management of massive blood transfusion and prolonged anesthesia in small children, often further complicated by syndrome‐specific issues. This two‐part review aims to provide an overview of the anesthetic considerations for these children. The first part described the syndromes associated with craniosynostosis, the provision of services in the UK, surgical techniques, preoperative issues and induction and maintenance of anesthesia. This second part will explore hemorrhage control, the use of blood products, metabolic disturbance and postoperative issues.     

Adverse effects of voriconazole: Over a decade of use

Voriconazole use has increased since the drug's introduction in 2002, and new and unique adverse effects are emerging as patients undergo prolonged therapy. Most concerning is the increased risk of cutaneous malignancies, primarily squamous cell carcinoma (SCC); this risk is duration dependent and the associated malignancies tend to be more aggressive and multifocal. Voriconazole is also associated with phototoxicity (which may be a precursor to malignancy), periostitis, hallucinations and encephalopathy, peripheral neuropathy, alopecia, nail changes, hyponatremia, and other adverse effects. Some toxicities (neuropsychiatric and gastrointestinal including hepatic) are seen in clear association with supratherapeutic serum voriconazole levels; thus, careful monitoring of voriconazole levels is a critical component of safe drug use. Guidelines for screening for adverse effects after long‐term voriconazole use may be beneficial and need to be established.     

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3–CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.