terlipressin
Regulatory sources consulted
Approved indications
- Gastrointestinal bleeding from ruptured esophagogastric varices and urgent treatment of type 1 hepatorenal syndrome.
Contraindications
Absolute
- Pregnancy or hypersensitivity.
Clinical warnings
- Major warning · May cause serious or fatal respiratory failure, pulmonary edema, and hypoxia. Monitor oxygen saturation, respiratory rate, and fluid-overload signs; avoid with hypoxia or worsening respiratory status. — CIMA/AEMPS, ficha técnica 72359
- Major warning · Vasoconstriction may cause myocardial, intestinal, peripheral, or skin ischemia, arrhythmias, and necrosis. Monitor blood pressure, heart rate, ECG, electrolytes, and perfusion; use IV only and avoid extravasation. — CIMA/AEMPS, ficha técnica 72359
- Major warning · In hepatorenal syndrome, avoid when baseline creatinine is ≥5 mg/dL, acute-on-chronic liver failure grade 3, or MELD ≥39, unless benefit clearly outweighs risk. — CIMA/AEMPS, ficha técnica 72359
Drug interactions
- HighDrugs that cause bradycardia
Mechanism: Propofol, sufentanil, and others may cause additive acute bradycardia.
Recommendation: Monitor heart rate and ECG; avoid high-risk combinations.
CIMA/AEMPS, ficha técnica 72359https://cima.aemps.es/cima/dochtml/ft/72359/FT_72359.html
- HighQT-prolonging or potassium/magnesium-lowering drugs
Mechanism: They increase ventricular arrhythmia and torsade de pointes risk.
Recommendation: Correct electrolytes, monitor ECG, and avoid when possible.
CIMA/AEMPS, ficha técnica 72359https://cima.aemps.es/cima/dochtml/ft/72359/FT_72359.html
Adverse events
Common (≥1%)
Abdominal pain · Nausea, vomiting, or diarrhea · Pallor · Dyspnea · Bradycardia · Hyponatremia
Rare but serious
Respiratory failure or pulmonary edema · Myocardial or intestinal ischemia · Torsades de pointes ventricular arrhythmia · Skin or injection-site necrosis
Pregnancy and lactation
Contraindicated during pregnancy because of uterine contractions, reduced uterine blood flow, and fetal harm. During breastfeeding, decide whether to stop breastfeeding or treatment based on benefits and risks.
Recent literature (PubMed)
Cirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people. The most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective β-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent ov
Inotropes and vasopressors frequently are administered in critically ill and perioperative patients. However, clinical practice is highly variable across clinicians and institutions. The inotropic score and its upgrade "vasoactive-inotropic score" (VIS) can be used to objectively quantify the degree of hemodynamic support. Several studies demonstrated a correlation between high VIS and poor outcome. Furthermore, VIS can help compare different clinical and research experiences. Several recently developed scores include VIS in their model, although they still require independent validation. Conversely, VIS has several pitfalls, including the fact that a universally recognized version that includes all commonly used vasoactive drugs does not exist. In this review, the authors summarize all the VIS, VIS-related, and VIS-validating manuscripts, and suggest a new updated version of VIS that also includes terlipressin, methylene blue, and angiotensin II.
Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
Hepatorenal syndrome-acute kidney injury (HRS-AKI) occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites. HRS-AKI is found in ∼20% of patients presenting to the hospital with AKI, but it may coexist with other causes of AKI and/or with preexisting chronic kidney disease, thereby making the diagnosis challenging. Novel biomarkers such as urinary neutrophil gelatinase-associated lipocalin may be useful. While HRS-AKI is a functional form of AKI related to circulatory and neurohormonal dysfunction, there is increasing recognition of the importance of systemic inflammation and the renal microenvironment. Early diagnosis and initiation of HRS-AKI-specific treatment can improve outcomes. The mainstay of therapy is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases. Liver transplantation is the only option for patients failing to respond to medical therapies.
Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.