Acute intermittent porphyria: A rare cause of syndrome of inappropriate antidiuretic hormone secretion.

A 31-year-old female presented to the emergency department with abdominal pain, vomiting and constipation. Serum sodium levels were recorded at 110 mmol/L on admission, dropping to 96 mmol/L despite fluid restriction. The patient developed hallucinations and required hypertonic saline administration in critical care. Urinary sodium was detected at 149 mmol/L, consistent with syndrome of inappropriate antidiuretic hormone secretion (SiADH). Urinary porphyrins were also raised, consistent with a diagnosis of acute intermittent porphyria with SiADH as a complication.

Transient diabetes insipidus in critically ill COVID19 patients.

PURPOSE: Vasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon. METHODS: We retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not. RESULTS: Out of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium. CONCLUSIONS: Temporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

Adjusting vasopressin availability and formulation: A cost-savings initiative.

PURPOSE: The increase in vasopressin price has required many healthcare systems to consider cost-saving strategies. To combat rising medication costs, our institution changed formulations from 50 units/250 mL to 20 units/100 mL and removed vasopressin from automated dispensing cabinets (ADCs). METHODS: This retrospective review occurred at a 545-bed academic medical center with 97 adult intensive care unit beds. Adult patients receiving a continuous vasopressin infusion were included with no exclusion criteria. A 1-month period was assessed before and after changing the formulation (pre and post groups, respectively). Duplicate bags compounded by pharmacy and bedside teams were also assessed in the pre group. The primary outcome was the estimated annual cost savings due to formulation change with a secondary outcome of estimated annual cost savings due to removal of vasopressin from ADCs. Each 20-unit vial of vasopressin cost $183.21 (wholesale acquisition cost) at the time of the study. RESULTS: In the pre group, 39 patients requiring a vasopressin infusion were allocated an average of 2 bags each costing $1,099.26 per patient. In the post group, 41 patients required an average of 4 bags each costing $732.84 per patient. With respect to the primary outcome, a savings of $366.42 per patient and an average of 40 patients per month would lead to an annual cost savings of $175,881.60. Secondary outcome analysis identified 9 duplicate bags prepared in the pre group; therefore, removal of vasopressin from ADCs is estimated to provide additional cost savings of $59,360.04. The estimated annual cost savings from both initiatives is $235,241.64. CONCLUSION: Changing the vasopressin formulation and removing it from ADCs resulted in a significant cost savings to the health system.

Kidney Transplant Recipient with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Secondary to COVID-19 Pneumonia: A Case Report.

BACKGROUND: Currently, COVID-19 is becoming one of the most common causes of viral pneumonia worldwide. In the medical literature, very few case reports describe the association between COVID-19 and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in kidney transplant patients. METHODS: A 74-year-old immunocompromised man post-kidney transplant presented with nonspecific symptoms consisting of fatigue, malaise, and anorexia. He was also found to have hyponatremia in the context of pulmonary insults. SIADH in the setting of COVID-19 pneumonia was diagnosed after exclusion of other causes of hyponatremia. He was treated for COVID-19 pneumonia with antiviral therapy, secondary bacterial infection prophylaxis, dexamethasone and ventilatory support in addition to modification of antirejection medications. RESULTS: The patient has improved and his serum sodium normalized with management of primary insult. CONCLUSIONS: SIADH should be suspected in transplant patients with COVID-19 pneumonia once they develops hyponatremia. The decision of intravenous fluid administration should be taken carefully in these settings.

Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides.

Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.

A single-center cost analysis assessing a change in vasopressin formulation.

PURPOSE: Cost savings achieved at an academic medical center by reformulating the institution's standard vasopressin infusions to reduce waste are described. SUMMARY: After a retrospective review of vasopressin utilization over a 4-month period revealed that only approximately 40% of dispensed vasopressin units were actually administered to patients, pharmacy leaders determined that the institution's standard vasopressin concentration for continuous infusions (100 units in 100 mL of sodium chloride 0.9% injection) was resulting in substantial waste, as many infusion preparations were not needed within the 18- to 24-hour expiration window. A concentration of 20 units/100 mL was adopted as the new standard formulation for vasopressin continuous infusions, with use of alternative concentrations allowed on a restricted basis. A pre-post study to assess the impact of the formulation change indicated a 38.7% decrease in vasopressin utilization (from 21,900 to 8,480 units) relative to utilization in a retrospective sample of patients who received vasopressin infusions prior to the formulation change. This reduced utilization equated to a cost decrease of $55,656.20 (as calculated on the basis of 2017 cost estimates) or $77,214.23 (as calculated on the basis of 2019 cost estimates) for the time period collected. It was estimated that the new formulations could yield annual cost savings ranging from $222,625 to $308,857. CONCLUSION: To our knowledge, this is the first description of cost savings following a change in formulation of vasopressin for continuous infusions. Other institutions could consider employing a similar approach in addition to the previously reported cost-saving interventions, such as lower vasopressin starting doses and vasopressin restriction policies.

Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute respiratory disease and multiorgan failure. Finding human host factors that are essential for SARS-CoV-2 infection could facilitate the formulation of treatment strategies. Using a human kidney cell line-HK-2-that is highly susceptible to SARS-CoV-2, we performed a genome-wide RNAi screen and identified virus dependency factors (VDFs), which play regulatory roles in biological pathways linked to clinical manifestations of SARS-CoV-2 infection. We found a role for a secretory form of SARS-CoV-2 receptor, soluble angiotensin converting enzyme 2 (sACE2), in SARS-CoV-2 infection. Further investigation revealed that SARS-CoV-2 exploits receptor-mediated endocytosis through interaction between its spike with sACE2 or sACE2-vasopressin via AT1 or AVPR1B, respectively. Our identification of VDFs and the regulatory effect of sACE2 on SARS-CoV-2 infection shed insight into pathogenesis and cell entry mechanisms of SARS-CoV-2 as well as potential treatment strategies for COVID-19.