Empressin (Argipressin)
Synthetic vasopressin analogue for catecholamine-refractory septic shock
Empressin contains argipressin, a synthetic form of the naturally occurring hormone vasopressin. It is used exclusively in hospital intensive care settings for the treatment of septic shock when conventional vasopressor therapy with catecholamines has failed to maintain adequate blood pressure. Empressin must be administered as a continuous intravenous infusion under strict hemodynamic monitoring.
Quick Facts
Key Takeaways
- Empressin (argipressin) is a synthetic vasopressin used as adjunctive vasopressor therapy in septic shock when catecholamines alone are insufficient.
- It must be administered as a continuous intravenous infusion, typically starting at 0.01 IU/min and titrated up to a maximum of 0.03 IU/min in non-emergency situations.
- Treatment should ideally begin within the first 6 hours of septic shock onset and must never be discontinued abruptly — gradual tapering is essential.
- Common side effects include cardiac arrhythmias, peripheral vasoconstriction, tissue necrosis, and gastrointestinal disturbances.
- Empressin is not recommended for use in children, neonates, or during pregnancy unless absolutely necessary, and requires continuous hemodynamic monitoring throughout treatment.
What Is Empressin and What Is It Used For?
Empressin contains the active substance argipressin, which is chemically identical to the naturally occurring hormone arginine vasopressin (AVP), also known as antidiuretic hormone (ADH). This hormone plays a fundamental role in the body's regulation of fluid balance, blood pressure homeostasis, and vascular tone. In healthy individuals, vasopressin is produced by the hypothalamus and released from the posterior pituitary gland in response to changes in plasma osmolality and blood volume.
In the context of septic shock, the body's endogenous vasopressin stores become rapidly depleted. During the early phases of sepsis, vasopressin levels may initially rise as a compensatory response, but as shock progresses, plasma vasopressin concentrations drop significantly — a phenomenon known as relative vasopressin deficiency. This deficiency contributes to the refractory hypotension that characterizes advanced septic shock and makes it particularly difficult to manage with catecholamines alone.
Empressin is specifically indicated for the treatment of catecholamine-refractory hypotension in septic shock. This means it is used when standard first-line vasopressors such as norepinephrine (noradrenaline) have failed to achieve or maintain the target mean arterial pressure (MAP) of 65–75 mmHg despite adequate volume resuscitation. According to the Surviving Sepsis Campaign guidelines, vasopressin can be added to norepinephrine to raise MAP to target or to decrease norepinephrine requirements.
The drug exerts its vasoconstrictive effects primarily through V1 receptors (V1a) located on vascular smooth muscle cells. Unlike catecholamines, which act through adrenergic receptors, vasopressin's mechanism of action remains effective even in the acidotic and catecholamine-desensitized environment that characterizes advanced septic shock. This complementary mechanism of action is what makes argipressin a valuable adjunct to catecholamine therapy. Additionally, argipressin acts on V2 receptors in the renal collecting ducts, promoting water reabsorption and decreasing urine output.
Empressin is authorized for use in multiple European countries under various brand names, including Empesin, Reverpleg, Embesyn, and Empressine, among others. It is manufactured by AOP Orphan Pharmaceuticals GmbH, based in Vienna, Austria. The marketing authorization holder is Orpha-Devel Handels und Vertriebs GmbH, based in Purkersdorf, Austria.
What Should You Know Before Taking Empressin?
Before Empressin is administered, healthcare professionals must carefully evaluate the patient's medical history, current medications, and overall clinical status. Because argipressin is a potent vasoconstrictive agent, its use carries significant risks that must be weighed against the potential benefits in each individual case. The decision to initiate vasopressin therapy should only be made by experienced intensive care physicians in settings with full hemodynamic monitoring capabilities.
Contraindications
The only absolute contraindication to Empressin is known hypersensitivity to argipressin or any of the excipients contained in the formulation. The excipients include sodium chloride, glacial acetic acid (for pH adjustment), and water for injections. Patients with a documented history of allergic reactions to vasopressin or its analogues should not receive this medication.
Empressin must not be administered as a bolus injection for the treatment of catecholamine-refractory shock. It must only be given as a continuous intravenous infusion using a precision infusion pump or syringe pump. Bolus administration can cause severe cardiovascular adverse events including cardiac arrest.
Warnings and Precautions
Empressin must be administered with extreme caution and under continuous monitoring of hemodynamic and organ-specific parameters. The following conditions require special vigilance during argipressin therapy:
- Cardiovascular disease: Patients with pre-existing cardiac or vascular conditions are at increased risk of myocardial ischemia, intestinal ischemia, intestinal infarction, and impaired limb perfusion. High-dose argipressin has been associated with these complications.
- Epilepsy: Vasopressin can lower the seizure threshold and may exacerbate epileptic conditions, particularly if water intoxication develops.
- Migraine: The vasoconstrictive effects of argipressin may trigger or worsen migraine episodes.
- Asthma: Argipressin may contribute to bronchospasm in susceptible patients.
- Heart failure: Patients with heart failure or conditions where a rapid increase in extracellular fluid volume poses a risk to an already overloaded system require careful fluid balance monitoring.
- Chronic nephritis: Patients with chronic kidney inflammation should be monitored closely for changes in renal function and fluid balance.
Argipressin can in rare cases cause water intoxication due to its antidiuretic effect. Early warning signs include drowsiness, lethargy, and headache. These symptoms must be recognized promptly to prevent potentially fatal coma and convulsions. Serum sodium levels should be monitored regularly during treatment.
Treatment with argipressin should only be initiated when adequate perfusion pressure cannot be maintained despite appropriate volume replacement and the use of catecholaminergic vasopressors. Ideally, treatment should begin within the first 6 hours of septic shock onset, or within 3 hours if the patient is already on high doses of catecholamines.
It is critical that this product is not used interchangeably with other argipressin-containing medications whose potency is expressed in different units (for example, pressor units [P.U.]). Dose conversion errors between different unit systems could lead to life-threatening overdosing or underdosing.
Pregnancy and Breastfeeding
Empressin is not recommended for use during pregnancy unless the clinical situation is life-threatening and no safer alternatives are available. Argipressin can cause uterine contractions and increase intrauterine pressure during pregnancy, which may lead to adverse outcomes for both the mother and the fetus. Additionally, the drug may reduce uterine blood flow, potentially compromising fetal perfusion and oxygenation.
It is currently unknown whether argipressin is excreted in human breast milk. Given the pharmacological properties of the drug and its potential effects on the nursing infant, breastfeeding is not recommended during Empressin treatment. Healthcare providers should carefully consider the risk-benefit ratio before administering this medication to pregnant or lactating women.
Children and Adolescents
The use of Empressin in children and neonates is generally not recommended. Although argipressin has been used in clinical practice for treating vasodilatory shock in infants, young children, and older pediatric patients in intensive care and perioperative settings, clinical evidence has not demonstrated improved survival outcomes compared to standard treatment. Furthermore, the frequency of adverse events was higher in the pediatric population. Consequently, a positive benefit-risk ratio has not been established for pediatric use.
Sodium Content
Empressin contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets, though in the context of critical care, sodium intake from the infusion vehicle (0.9% sodium chloride solution) will be the more significant contributor.
How Does Empressin Interact with Other Drugs?
Drug interactions are of critical importance when managing patients in septic shock, as these patients are typically receiving multiple concurrent medications. The interactions with argipressin can broadly be categorized into those that potentiate its effects and those that diminish them. Understanding these interactions is essential for appropriate dose titration and patient safety.
Drugs That Enhance Empressin's Effects
The following medications can increase the antidiuretic and vasopressive effects of argipressin, potentially leading to excessive vasoconstriction, water retention, or hyponatremia. Dose adjustments and increased monitoring may be necessary when these drugs are used concurrently:
| Drug | Mechanism | Clinical Significance |
|---|---|---|
| Carbamazepine | Enhances antidiuretic effect of vasopressin | Increased risk of water intoxication and hyponatremia |
| Chlorpropamide | Potentiates renal action of vasopressin | Enhanced water retention and hypoglycemia risk |
| Clofibrate | Stimulates vasopressin release and sensitizes renal tubules | Additive antidiuretic effect |
| Fludrocortisone | Synergistic effect on fluid retention | Increased fluid overload risk |
| Tricyclic antidepressants | Enhance vasopressin-mediated antidiuresis | Risk of hyponatremia and water intoxication |
| Urea | Synergistic antidiuretic effect | Enhanced water reabsorption |
Drugs That Reduce Empressin's Effects
The following substances may diminish the therapeutic efficacy of argipressin, potentially requiring dose adjustments to maintain adequate hemodynamic targets:
| Drug / Substance | Mechanism | Clinical Significance |
|---|---|---|
| Demeclocycline | Blocks vasopressin V2 receptor action in renal tubules | Reduced antidiuretic effect; commonly used to treat SIADH |
| Lithium | Interferes with vasopressin signaling in collecting duct | Decreased antidiuretic response; may cause nephrogenic diabetes insipidus |
| Heparin | Reduces vasopressin-mediated effects through unclear mechanisms | Potentially decreased vasopressive efficacy |
| Norepinephrine | Complex interaction; may alter vasopressin receptor sensitivity | Dose titration of both agents required; used together in clinical practice |
| Alcohol | Inhibits vasopressin release from the pituitary gland | Reduced antidiuretic and vasopressive effects |
Antihypertensive Medications
Concurrent use of antihypertensive medications with Empressin can have variable effects on the blood pressure response induced by argipressin. Some antihypertensive agents may enhance the vasopressor effect, while others may attenuate it, depending on their specific mechanism of action and the patient's hemodynamic status. Close monitoring of blood pressure and careful titration of all vasoactive agents is essential in this setting.
In the intensive care setting, patients receiving Empressin will typically be on multiple concurrent medications. A comprehensive review of all current medications should be performed before initiating argipressin therapy, and continuous hemodynamic monitoring should guide dose adjustments. Pharmacist consultation is recommended for complex drug interaction assessments.
What Is the Correct Dosage of Empressin?
Empressin is exclusively administered as a continuous intravenous infusion using a precision infusion pump or syringe pump. It must never be given as a bolus injection. The medication should only be administered by qualified healthcare professionals in an intensive care setting with continuous hemodynamic monitoring capabilities.
Adults
Standard Adult Dosing
Preparation: Dilute 2 ml of Empressin concentrate (40 IU) with 48 ml of 0.9% sodium chloride solution (normal saline). This produces a solution containing 0.8 IU argipressin per ml with a total volume of 50 ml.
Initial dose: 0.01 IU per minute (equivalent to 0.6 IU per hour, infusion rate 0.75 ml/hour)
Dose titration: The dose may be increased every 15–20 minutes based on clinical response
Maximum recommended dose: 0.03 IU per minute (equivalent to 1.8 IU per hour, infusion rate 2.25 ml/hour)
Target MAP: 65–75 mmHg for patients in intensive care
| Dose (IU/min) | Dose (IU/hour) | Infusion Rate (ml/hour) |
|---|---|---|
| 0.01 | 0.6 | 0.75 |
| 0.02 | 1.2 | 1.50 |
| 0.03 | 1.8 | 2.25 |
Doses exceeding 0.03 IU per minute should only be used as emergency rescue therapy. Higher doses significantly increase the risk of intestinal necrosis, skin necrosis, and cardiac arrest. The decision to exceed the recommended maximum dose must be made by an experienced intensivist and requires even more intensive monitoring.
Treatment Timing and Duration
Treatment with argipressin should ideally be initiated within the first 6 hours of septic shock onset. For patients already receiving high doses of catecholamine vasopressors, treatment should begin within 3 hours of shock onset. Early initiation has been associated with better outcomes in clinical studies.
The minimum recommended treatment duration is 48 hours, though the total duration is determined by the treating physician based on the individual clinical course. It is essential that Empressin treatment is never discontinued abruptly. The drug must be tapered gradually, with dose reductions made based on the patient's hemodynamic response and overall clinical trajectory. Abrupt discontinuation can lead to rebound hypotension and hemodynamic instability.
Children and Neonates
Although argipressin has been used in clinical practice for the treatment of vasodilatory shock in pediatric intensive care and perioperative settings, its use in children and neonates is generally not recommended. Clinical trials in the pediatric population did not demonstrate improved survival compared to standard vasopressor therapy, and adverse event rates were higher. There are no established pediatric dosing guidelines for Empressin.
Elderly Patients
No specific dose adjustments are recommended for elderly patients. However, elderly patients may be more susceptible to the cardiovascular effects of argipressin due to pre-existing vascular disease, reduced cardiac reserve, and altered fluid balance. Close hemodynamic monitoring and cautious dose titration are advisable in this population.
Overdose
Empressin is administered by healthcare professionals in a controlled intensive care environment, which significantly reduces the risk of accidental overdose. However, if an overdose is suspected, treatment should be symptomatic and supportive. Signs of overdose may include severe hypertension, bradycardia, myocardial ischemia, intestinal ischemia, peripheral ischemia (blanching of fingers and toes), and water intoxication with hyponatremia. The infusion should be stopped immediately, and standard intensive care supportive measures should be initiated.
Missed Dose or Interrupted Treatment
Because Empressin is administered as a continuous infusion in an intensive care setting, the concept of a "missed dose" does not apply in the traditional sense. However, if the infusion is inadvertently interrupted, it should be restarted promptly at the previously established rate, as any interruption may lead to rapid hemodynamic deterioration. The treating physician should be notified immediately of any interruption in the infusion. If the patient believes the medication was stopped prematurely, they should inform their physician immediately.
What Are the Side Effects of Empressin?
Like all medications, Empressin can cause side effects, although not everyone receiving the drug will experience them. The side effects of argipressin are largely related to its vasoconstrictive mechanism of action and its effects on water balance. In the context of septic shock, distinguishing drug-related adverse effects from manifestations of the underlying disease can be challenging. Healthcare professionals must maintain vigilant monitoring throughout treatment.
Common Side Effects
- Abnormal heart rhythms (cardiac arrhythmias)
- Chest tightness or chest pressure
- Circulatory disturbances affecting the heart muscle (myocardial ischemia)
- Circulatory disturbances in the intestines (mesenteric ischemia)
- Circulatory disturbances in fingertips and toes (digital ischemia)
- Peripheral vasoconstriction
- Tissue necrosis (gangrene)
- Abdominal cramps
- Pallor around the mouth (circumoral pallor)
- Skin necrosis
Uncommon Side Effects
- Low blood sodium levels (hyponatremia)
- Tremor and shaking
- Dizziness
- Headache
- Decreased circulating blood volume (hypovolemia)
- Life-threatening changes in heart rhythm (ventricular arrhythmias)
- Cardiac arrest
- Breathing difficulties due to airway constriction (bronchospasm)
- Nausea and vomiting
- Flatulence
- Intestinal necrosis (bowel infarction)
- Excessive sweating
- Skin rash
- Changes in laboratory blood values (elevated liver enzymes, thrombocytopenia)
Rare Side Effects
- Severe and life-threatening allergic reaction (anaphylaxis)
Frequency Not Known
- Water intoxication (dilutional hyponatremia with cerebral edema)
- Diabetes insipidus (paradoxical response after discontinuation)
Many of the side effects listed above are directly related to the vasoconstrictive properties of argipressin. The risk of ischemic complications (tissue necrosis, intestinal necrosis, myocardial ischemia) is dose-dependent and increases significantly at doses exceeding 0.03 IU per minute. Patients with pre-existing cardiovascular disease are at higher risk for these complications.
Water intoxication, though rare, is a potentially fatal complication. It occurs due to the antidiuretic action of vasopressin, which promotes excessive water reabsorption in the kidneys. Early signs include drowsiness, lethargy, and headache, which can progress to convulsions and coma if not recognized and treated promptly. Regular monitoring of serum sodium levels and fluid balance is essential during treatment.
Healthcare professionals and patients are encouraged to report suspected adverse reactions to their national pharmacovigilance authority. Reporting helps ensure the continued monitoring of the drug's benefit-risk balance. In the EU, reports can be submitted through national reporting systems. In the UK, reports can be made via the Yellow Card Scheme.
How Should You Store Empressin?
Proper storage of Empressin is essential to maintain the stability and efficacy of the argipressin concentrate. As a peptide hormone, argipressin is sensitive to temperature extremes and improper storage conditions can lead to degradation of the active substance, potentially rendering the medication less effective or unsafe for use.
- Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
- Light protection: Keep the ampoules in the outer carton to protect from light.
- After opening: Once the ampoule is opened, the concentrate should be diluted and used immediately. Any unused portion should be discarded.
- Diluted solution: The prepared infusion solution should be used promptly. Chemical and physical stability after dilution has been demonstrated for up to 24 hours at room temperature, but from a microbiological perspective, immediate use is recommended.
- Expiry date: Do not use Empressin after the expiry date stated on the label and carton. The expiry date refers to the last day of the stated month.
- Disposal: Do not dispose of Empressin through household waste or wastewater. Return unused medications to your pharmacy or follow local regulations for the disposal of pharmaceutical waste to protect the environment.
The appearance of Empressin concentrate should be clear and colorless. Before use, visually inspect the solution for particulate matter or discoloration. Do not use if the solution appears cloudy, discolored, or contains visible particles. Each package contains either 5 or 10 ampoules of 2 ml concentrate; not all pack sizes may be marketed in every country.
What Does Empressin Contain?
Empressin is formulated as a sterile concentrate for solution for infusion. Understanding the full composition is important for healthcare professionals to identify potential hypersensitivity risks and ensure compatibility with other intravenous solutions and medications.
Active Ingredient
The active substance is argipressin, supplied in the form of argipressin acetate. Each ampoule contains 2 ml of concentrate with argipressin acetate equivalent to 40 International Units (IU) of argipressin. This corresponds to approximately 133 micrograms of the active peptide. Argipressin is a synthetic nonapeptide that is structurally identical to the endogenous human hormone arginine vasopressin (AVP).
Inactive Ingredients (Excipients)
- Sodium chloride: Used as a tonicity agent to make the solution isotonic
- Glacial acetic acid (concentrated): Used for pH adjustment to ensure stability of the active substance
- Water for injections: Pharmaceutical-grade purified water serving as the solvent
Physical Properties
Empressin concentrate is a clear, colorless solution. It is presented in glass ampoules, each containing 2 ml of concentrate. The solution should be free of visible particles and show no discoloration. If any abnormalities are observed upon visual inspection, the ampoule should not be used.
Frequently Asked Questions About Empressin
Empressin (argipressin) is used in the treatment of catecholamine-refractory septic shock. It is administered as a continuous intravenous infusion in intensive care settings when conventional vasopressor therapy with catecholamines (such as norepinephrine) fails to maintain adequate blood pressure. Argipressin works through a different receptor pathway (V1 receptors) than catecholamines, making it effective even when adrenergic receptors have become desensitized.
Empressin contains argipressin, which is a synthetic form that is chemically identical to the naturally occurring hormone arginine vasopressin (AVP). The term "argipressin" specifically refers to the arginine-containing form of vasopressin, which is the form found in humans. While the active substance is the same as endogenous vasopressin, Empressin is produced synthetically to ensure pharmaceutical purity and standardized dosing. It is specifically formulated and approved for use in septic shock.
No, Empressin must never be discontinued abruptly. Treatment should be tapered gradually based on the patient's clinical course and hemodynamic parameters. Sudden discontinuation can lead to rebound vasodilatory hypotension and hemodynamic collapse. The treating intensivist will determine the appropriate tapering schedule based on the patient's overall clinical trajectory and response to concurrent vasopressor therapy.
Empressin is not recommended during pregnancy unless the situation is life-threatening and no safer alternatives exist. Argipressin can cause uterine contractions, increase intrauterine pressure, and reduce uterine blood flow, all of which could adversely affect the pregnancy and fetal well-being. It is also unknown whether argipressin passes into breast milk, so breastfeeding is not recommended during treatment. Any use during pregnancy requires careful risk-benefit assessment by the treating physician.
Empressin requires continuous and comprehensive hemodynamic monitoring throughout treatment. This includes continuous arterial blood pressure monitoring (typically via an arterial line), heart rate and rhythm monitoring, central venous pressure measurement, cardiac output monitoring, urine output measurement, serum sodium and electrolyte levels, lactate levels as a marker of tissue perfusion, and regular assessment of peripheral perfusion (skin color, capillary refill, temperature). Organ-specific parameters including liver function, renal function, and intestinal perfusion markers should also be monitored regularly.
The use of Empressin in children and neonates is generally not recommended. While argipressin has been used off-label in pediatric intensive care for vasodilatory shock, clinical evidence has not shown improved survival outcomes compared to standard treatment. Additionally, adverse event rates were higher in the pediatric population. A positive benefit-risk ratio has not been established for pediatric use, and there are no established pediatric dosing guidelines for Empressin.
References
This article is based on the following peer-reviewed sources and international clinical guidelines:
- European Medicines Agency (EMA). Empressin Summary of Product Characteristics (SmPC). Last updated 2023. Available at: www.ema.europa.eu
- Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine. 2021;49(11):e1063–e1143. doi:10.1097/CCM.0000000000005337
- Russell JA, Walley KR, Singer J, et al. Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (VASST trial). New England Journal of Medicine. 2008;358(9):877–887. doi:10.1056/NEJMoa067373
- Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock (VANISH trial). JAMA. 2016;316(5):509–518. doi:10.1001/jama.2016.10485
- World Health Organization (WHO). Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Critical Care Medicine. 2013;41(2):580–637.
- Holmes CL, Walley KR. Vasopressin in the ICU. Current Opinion in Critical Care. 2004;10(6):442–448.
- British National Formulary (BNF). Argipressin (vasopressin). National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk
- Russell JA. Vasopressin in vasodilatory and septic shock. Current Opinion in Critical Care. 2007;13(4):383–391.
- Tsuneyoshi I, Yamada H, Kakihana Y, et al. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Critical Care Medicine. 2001;29(3):487–493.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in critical care medicine, clinical pharmacology, and intensive care therapeutics.
Written by medical professionals with clinical experience in intensive care medicine and vasopressor pharmacology, following the GRADE evidence framework for systematic evaluation of medical literature.
Independently reviewed by the iMedic Medical Review Board. All claims verified against current international guidelines including the Surviving Sepsis Campaign 2021 and EMA product information.
Conflict of Interest Statement: The iMedic Medical Editorial Team has no financial relationships with pharmaceutical companies or commercial interests in the medications described. All content is independently produced without commercial sponsorship.
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