Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology of Chinese Medical Association and Hepatology Committee of Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis related complications.
Electrolytes ; Esophageal and Gastric Varices/drug therapy* ; Gastrointestinal Hemorrhage/etiology* ; Hepatorenal Syndrome/etiology* ; Humans ; Liver Cirrhosis/drug therapy* ; Lypressin/adverse effects* ; Terlipressin/adverse effects* ; Vasoconstrictor Agents/adverse effects*

BACKGROUND: Norepinephrine infusion decreases hypotension after spinal anesthesia during cesarean section. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus against post-spinal hypotension in parturients. METHODS: In this double-blinded, randomized controlled clinical trial, parturients scheduled for elective cesarean section were randomly allocated to receive norepinephrine infusion (0.05 μg·kg-1·min-1) just before spinal anesthesia continuing for 30 min or ephedrine bolus (0.15 mg/kg) just before spinal anesthesia. A rescue bolus (5 μg norepinephrine for the norepinephrine group, and 5 mg ephedrine for the ephedrine group) was administered whenever hypotension occurred. Our primary outcome was the incidence of hypotension within 30 min of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 min after spinal block, and neonatal cerebral oxygenation 10 min after birth. RESULTS: In total, 190 patients were enrolled; of these patients, 177 were included in the final analysis. Fewer patients suffered hypotension in the norepinephrine group than in the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28-0.95, P = 0.034). Moreover, the tachycardia frequency was lower in the norepinephrine group than in the ephedrine group (OR: 0.22, 95% CI: 0.11-0.44, P < 0.001), and patients suffered less nausea and vomiting (OR: 0.28, 95% CI: 0.11-0.70, P = 0.004). There was no difference in Apgar scores and umbilical arterial blood gas analysis between the two groups. However, neonatal cerebral regional saturations were significantly higher after birth in the norepinephrine group than in the ephedrine group (mean difference: 2.0%, 95% CI: 0.55%-3.45%, P = 0.008). CONCLUSION: In patients undergoing elective cesarean section with spinal anesthesia, norepinephrine infusion compared to ephedrine bolus resulted in less hypotension and tachycardia, and exhibited potential neonatal benefits. TRIAL REGISTRATION ClinicalTrials.gov, NCT02542748; https://clinicaltrials.gov/ct2/show/record/NCT02542748.
Anesthesia, Spinal/adverse effects* ; Cesarean Section/adverse effects* ; Double-Blind Method ; Female ; Humans ; Hypotension/prevention & control* ; Infant, Newborn ; Phenylephrine ; Pregnancy ; Randomized Controlled Trials as Topic ; Vasoconstrictor Agents/therapeutic use*

BACKGROUND: Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section. METHODS: Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis. RESULTS: Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH. CONCLUSION This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.
Anesthesia, Spinal/adverse effects* ; Cesarean Section/adverse effects* ; Colloids ; Female ; Humans ; Hypotension/etiology* ; Incidence ; Infant, Newborn ; Pregnancy ; Vasoconstrictor Agents/therapeutic use*

Hepatorenal syndrome is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin is a nonselective V1 vasopressin agonist. When comparing with ornipressin, it is known to have a similar vasoconstricting potency, but much less ischemic complication. We report a case of gangrene on toes and necrosis on the infusion site of left hand which developed after the use of terlipressin due to hepatorenal syndrome in a 41-year-old-man with liver cirrhosis. Ischemic complication of terlipressin is rare and there has been no case report in Korea. Although it is rare, we must pay attention to the peripheral ischemic complication of terlipressin.
Adult ; Hand/*blood supply ; Hepatorenal Syndrome/drug therapy ; Humans ; Ischemia/*chemically induced ; Lysine Vasopressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Toes/*blood supply ; Vasoconstrictor Agents/*adverse effects/therapeutic use

PURPOSE: Although penile duplex Doppler ultrasonography (PDDU) is a common and integral procedure in a Peyronie's disease workup, the intracavernosal injection of vasoactive agents can carry a serious risk of priapism. Risk factors include young age, good baseline erectile function, and no coronary artery disease. In addition, patients with Peyronie's disease undergoing PDDU in an outpatient setting are at increased risk given the inability to predict optimal dosing. The present study was conducted to provide support for a standard protocol of early administration of phenylephrine in patients with a sustained erection after diagnostic intracavernosal injection of vasoactive agents to prevent the deleterious effects of iatrogenic priapism. MATERIALS AND METHODS: This was a retrospective review of Peyronie's disease patients who received phenylephrine reversal after intracavernosal alprostadil (prostaglandin E1) administration to look at the priapism rate. Safety was determined on the basis of adverse events reported by subjects and efficacy was determined on the basis of the rate of priapism following intervention. RESULTS: Patients with Peyronie's disease only had better hemodynamic values on PDDU than did patients with Peyronie's disease and erectile dysfunction. All of the patients receiving prophylactic phenylephrine had complete detumescence of erections without adverse events, including no priapism cases. CONCLUSIONS: The reversal of erections with phenylephrine after intracavernosal injections of alprostadil to prevent iatrogenic priapism can be effective without increased adverse effects.
Alprostadil/adverse effects/diagnostic use ; Drug Evaluation/methods ; Humans ; Male ; Middle Aged ; Penile Erection ; Penile Induration/*ultrasonography ; Phenylephrine/*therapeutic use ; Pilot Projects ; Priapism/chemically induced/*prevention & control ; Retrospective Studies ; Ultrasonography, Doppler, Duplex/adverse effects/methods ; Vasoconstrictor Agents/*therapeutic use ; Vasodilator Agents/adverse effects/diagnostic use

This study is to investigate protective effect of safflor yellow B (SYB) against vascular endothelial cells (VECs) injury induced by angiotensin-II (Ang-II). VECs were cultured and divided into six groups: control group, Ang-II group, Ang-II + SYB (1 micromolL(-1)) group, Ang-II + SYB (10 micromolL(-1)) group, Ang-II + SYB (100 micromolL(-1)) group and Ang- II + verapamil (10 micromolL(-1)) group. Except control group, all of VECs in other groups were treated with Ang- II at the final concentration of 0.1 micromolL(-1). Mitochondria membrane potential (MMP) and free calcium concentration ([Ca2+]i) were measured by laser scanning confocal microscopy, and mitochondria complex IV activity was detected by BCA method. The levels of reactive oxygen species (ROS) in VECs were analyzed by fluorescence detector and apoptosis of VECs was observed by flow cytometer. Caspase 3 was determined by Western blotting method. Comparing with control group, Ang-II was able to increase [Ca2+]i and ROS level, decrease MMP level, inhibit complex IV activity and enhance caspase 3 activity in VECs, as a result, enhance apoptosis of VECs. But SYB could significantly reduce the result induced by Ang- II relying on different dosages (P < 0.05 or P < 0.01). SYB was able to eliminate the effect of Ang-II on VECs via regulating [Ca2+]i, mitochondrial structure and function and inhibiting apoptosis.
Angiotensin II ; adverse effects ; Antioxidants ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Carthamus tinctorius ; chemistry ; Caspase 3 ; metabolism ; Cells, Cultured ; Chalcone ; analogs & derivatives ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Electron Transport Complex IV ; metabolism ; Endothelial Cells ; cytology ; metabolism ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondrial Proton-Translocating ATPases ; metabolism ; Plants, Medicinal ; chemistry ; Reactive Oxygen Species ; metabolism ; Vasoconstrictor Agents ; adverse effects

Terlipressin is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion. Thus, it has a less adverse reaction than vasopressin. We report a case of ischemic skin complication in a cirrhotic patient treated with terlipressin. A 71-year-old man with liver cirrhosis was admitted because of hematemesis and melena. He was commenced on terlipressin at a dose 1 mg every 6 hours for the treatment of varicieal bleeding. After 36 hours of treatment, skin blistering and ecchymosis was noted on the skin of his upper thigh, scrotal area and trunk. We found that terlipressin was a possible cause of ischemic skin complication based on the skin biopsy finding. Terlipressin may induce a complication of the ischemic event. In spite of rarity, special attention needs to paid on the peripheral ischemic complication of terlipressin.
Aged ; Fatal Outcome ; Hematemesis/diagnosis ; Hemorrhage/drug therapy ; Humans ; Ischemia/*chemically induced/*pathology ; Liver Cirrhosis/*complications ; Lysine Vasopressin/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Melena/diagnosis ; Necrosis ; Skin/*blood supply/drug effects/*pathology ; Vasoconstrictor Agents/administration & dosage/*adverse effects/therapeutic use

This is a report on a case of severe skin necrosis in a vasodilatory septic shock patient after the infusion of low-dose vasopressin through a central venous catheter. An 84-year-old male was hospitalized for edema on both legs at Asan Medical Center, Seoul, Korea. On hospital day 8, the patient began to complain of dyspnea and he subsequently developed severe septic shock caused by E. coli. After being transferred to the medical intensive care unit, his hypotension, which was refractory to norepinephrine, was controlled by an infusion of low-dose vasopressin (0.02 unit/min) through a central venous catheter into the right subclavian vein. After the infusion of low-dose vasopressin, severe skin necrosis with bullous changes developed, necessitating discontinuation of the low-dose vasopressin infusion. The patient expired from refractory septic shock. Although low-dose vasopressin can control hypotension in septic shock patients, low-dose vasopressin must be used with caution because ischemic complications such as skin necrosis can develop even with administration through a central venous catheter.
Vasopressins/administration & dosage/*adverse effects/therapeutic use ; Vasoconstrictor Agents/administration & dosage/*adverse effects/therapeutic use ; Skin/*drug effects/*pathology ; Shock, Septic/*drug therapy ; Necrosis/chemically induced/pathology ; Male ; Infusions, Intravenous ; Humans ; Fatal Outcome ; Dose-Response Relationship, Drug ; Catheterization, Central Venous ; Aged, 80 and over

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.
Aged ; Creatinine/blood ; Foot/pathology ; Gangrene/*etiology ; Hepatitis C, Chronic/complications ; Humans ; Liver Cirrhosis/complications/diagnosis ; Liver Diseases/*diagnosis/drug therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Osteomyelitis/*etiology ; Severity of Illness Index ; Toe Phalanges/radiography ; Vasoconstrictor Agents/*adverse effects/therapeutic use

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.
Bilirubin/blood ; Creatinine/blood ; Electrocardiography ; Fatal Outcome ; Hepatorenal Syndrome/*drug therapy ; Humans ; Intestinal Mucosa/pathology ; Intestines/surgery ; Liver Cirrhosis/diagnosis/therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Necrosis/*chemically induced/surgery ; Tomography, X-Ray Computed ; Vasoconstrictor Agents/*adverse effects/*therapeutic use