Vasopressin (ADH)

Vasopressin, also known as antidiuretic hormone (ADH), is a nine-amino acid peptide hormone that exerts its physiological effects through two primary receptor pathways. The hormone binds to V2 receptors located in the basolateral membrane of principal cells in the kidney's collecting ducts, triggering a cAMP-mediated signaling cascade. This activation leads to the phosphorylation and translocation of aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane, dramatically increasing water permeability and reabsorption. This mechanism allows the kidneys to concentrate urine and conserve body water, making vasopressin essential for maintaining proper fluid balance and osmolality. Additionally, vasopressin binds to V1a receptors found in vascular smooth muscle cells, activating phospholipase C and increasing intracellular calcium levels. This pathway triggers smooth muscle contraction, resulting in vasoconstriction and increased peripheral vascular resistance, which elevates blood pressure. The hormone also interacts with V1b receptors in the anterior pituitary, modulating ACTH release and stress responses. Vasopressin's dual action on water retention and vascular tone makes it a critical regulator of cardiovascular homeostasis and fluid balance, with its release being stimulated by increased plasma osmolality, decreased blood volume, and various stress conditions.

Vasopressin therapy provides significant clinical benefits for patients with specific endocrine and cardiovascular conditions. In diabetes insipidus, whether central (neurogenic) or nephrogenic in origin, vasopressin replacement therapy effectively restores the body's ability to concentrate urine and maintain proper fluid balance. Patients experience dramatic reduction in polyuria and polydipsia, with urine output decreasing from potentially 10-15 liters per day to normal levels of 1-2 liters. This restoration of normal water homeostasis prevents dangerous dehydration, electrolyte imbalances, and the associated complications such as hypernatremia and cardiovascular instability. The improvement in quality of life is substantial, as patients regain normal sleep patterns and daily functioning without the constant need for water intake and frequent urination. In critical care settings, vasopressin demonstrates remarkable efficacy in treating vasodilatory shock, particularly septic shock and post-cardiac surgery hypotension. Unlike traditional vasopressors that may lose effectiveness due to receptor desensitization, vasopressin works through different mechanisms and often remains effective when catecholamine vasopressors fail. Clinical studies have shown that vasopressin can restore blood pressure and reduce the need for high-dose norepinephrine, potentially reducing the risk of arrhythmias and other catecholamine-related side effects. The hormone's ability to maintain organ perfusion while reducing overall vasopressor requirements has been associated with improved outcomes in critically ill patients, including better renal function preservation and reduced mortality in certain patient populations.

Vasopressin dosing requires careful individualization based on the specific condition, patient characteristics, and clinical response. For central diabetes insipidus, treatment typically begins with intranasal desmopressin at 10 mcg once or twice daily, with dose titration based on urine output and serum sodium monitoring. The goal is to reduce urine output to 1.5-2 liters per day while maintaining serum sodium between 135-145 mEq/L. If intranasal administration is unsuitable, subcutaneous vasopressin can be initiated at 5 units every 8-12 hours, with adjustments based on clinical response. In vasodilatory shock, intravenous vasopressin infusion starts at 0.01-0.04 units per minute, typically added when norepinephrine requirements exceed 15 mcg/minute. The infusion rate rarely exceeds 0.04 units/minute to minimize adverse effects, with careful monitoring of blood pressure, heart rate, and organ perfusion. Dose adjustments should occur gradually, with reassessment every 15-30 minutes initially, then hourly once stable. Pediatric dosing follows weight-based calculations, typically 0.0005-0.002 units/kg/minute for shock states, with more frequent monitoring due to increased sensitivity. Duration of therapy varies: diabetes insipidus often requires long-term treatment, while vasodilatory shock typically involves 24-72 hours of therapy with gradual weaning as hemodynamic stability improves. Regular monitoring of electrolytes, kidney function, and cardiovascular parameters guides dosing decisions throughout treatment.

Clinical research on vasopressin spans several decades, with robust evidence supporting its therapeutic applications. The landmark VASST trial (Vasopressin and Septic Shock Trial) published in the New England Journal of Medicine demonstrated that low-dose vasopressin infusion (0.01-0.03 units/minute) in septic shock patients reduced mortality compared to norepinephrine alone, particularly in patients with less severe shock. A systematic review by Polito et al. (2012) analyzing 23 studies found that vasopressin as adjunctive therapy in septic shock significantly reduced norepinephrine requirements and improved hemodynamic parameters without increasing adverse events. In diabetes insipidus management, multiple studies have confirmed the efficacy of vasopressin replacement therapy, with desmopressin showing superior outcomes due to its longer duration of action and reduced pressor effects. The VANISH trial (2016) further validated vasopressin's role in septic shock, showing improved kidney failure-free days when used early in treatment. Recent meta-analyses have consistently demonstrated that vasopressin reduces catecholamine requirements in distributive shock states, potentially reducing associated complications like arrhythmias and digital ischemia. Pediatric studies have established safety and efficacy profiles for younger patients, though with more stringent monitoring requirements. Current research focuses on optimal timing of initiation, combination therapies, and identification of patient populations most likely to benefit from vasopressin therapy.