-
1.
Comparison of 1-day versus 3-day intravenous terlipressin in cirrhosis patients with variceal bleeding: A pilot randomised controlled trial
Vaishnav, M., Biswas, S., Shenoy, A., Pathak, P., Anand, A., Swaroop, S., Aggrawal, A., Arora, U., Elhence, A., Jagannath, S., et al
Alimentary pharmacology & therapeutics. 2024
Abstract
BACKGROUND In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).
-
2.
A randomized controlled trial of propranolol use during ligation program for secondary prophylaxis of esophageal variceal bleeding
Chen, W. C., Yang, T. C., Lee, P. C., Wang, Y. P., Hou, M. C., Lee, F. Y.
The American journal of gastroenterology. 2023
Abstract
INTRODUCTION Endoscopic variceal ligation (EVL) plus non-selective beta-blockers (NSBBs) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBBs till eradication of esophageal varices (EEV) and EVL plus long-term NSBBs. METHODS After control of acute EVB, patients with cirrhosis were randomized to two groups, with Group A patients receiving EVL plus propranolol till EEV, while Group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. RESULTS The median follow-up period was 23.0 months in Group A (n = 106) and 23.6 months in Group B (n = 106). Twelve patients (11.3%) in Group A and 11 (10.4%) in Group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5%, 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2% and the non-inferiority of Group A to Group B was established. Thirty-eight patients (35.8%) in Group A and 40 (37.7%) in Group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9%, 11.1%). Twenty-four patients (22.6%) in Group A and 26 (24.5%) in Group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3%, 9.5%). DISCUSSION EVL plus propranolol till EEV was non-inferior to EVL plus continuing propranolol in secondary prophylaxis of EVB but the impact on further decompensation and transplantation-free survival deserved further investigation.
-
3.
Proton pump inhibitor has no effect in the prevention of post-endoscopic sphincterotomy delayed bleeding: a prospective randomized controlled trial
Yu, Z., He, J., Cao, R., Yang, Z., Li, B., Hong, J., Chen, Y., Zhu, L.
Frontiers in medicine. 2023;10:1179512
Abstract
BACKGROUND AND AIMS Bleeding is one of the common adverse events of endoscopic retrograde cholangiopancreatography (ERCP), which is mainly caused by endoscopic sphincterotomy (EST). At present, it remains unclear whether proton pump inhibitor (PPI) should be used to prevent post-EST bleeding. Therefore, we performed a randomized controlled trial to investigate whether PPI is effective in the prevention of post-EST delayed bleeding. METHODS Consecutive eligible patients were randomly assigned (1:1) to experimental group (PPI group) or control group (normal saline, NS group). The patients in PPI group received intravenous esomeprazole 40 mg and normal saline 100 mL every 12 h for 2 days after ERCP immediately, and followed by oral esomeprazole (Nexium) 20 mg once a day for 7 days. Correspondingly, patients in the control group received intravenous normal saline 100 mL and did not take PPIs or any acid-suppressing drugs during hospitalization and after discharge. All patients were followed up for 30 days after ERCP. The primary endpoint was the incidence and severity of post-EST delayed bleeding. RESULTS Between July 2020 and July 2022, 290 patients were randomly assigned to PPI group (n = 146) or NS group (n = 144). 5 patients from each group were excluded from the final analysis. There were 6 patients with post-EST delayed bleeding, with an incidence rate of 2.14%. The median time of delayed bleeding was 2.5 days after ERCP. 3 cases (2.12%, 3/141) occurred in the PPI group, with 1 case of mild and 2 cases of moderate bleeding. 3 cases (2.16%, 3/139) occurred in the NS group, with 2 cases of mild and 1 case of moderate bleeding. There was no significant difference in the incidence and the severity of post-EST delayed bleeding between the two groups (p = 1.000). CONCLUSION Prophylactic use of PPI after EST does not reduce the incidence and severity of post-EST delayed bleeding in patients. CLINICAL TRIAL REGISTRATION https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2000034697.
-
4.
Efficacy of Vonoprazan vs. Pantoprazole or Non-acid Suppression in Prevention of Post-variceal Ligation Ulcer Bleeding in Portal Hypertension: A Multi-arm Randomized Controlled Trial
Lashen, S. A., Shamseya, M. M., Shamseya, A. M., Hablass, F. H.
Journal of clinical and experimental hepatology. 2023;13(6):962-971
Abstract
BACKGROUND Up-to-date data about the role of acid suppression therapy e.g. proton-pump inhibitors; to reduce post-endoscopic variceal ligation (EVL) ulcer-bleeding are conflicting. Vonoprazan; a recently introduced potassium-competitor acid blocker, has not been studied to prevent post-EVL ulcer/bleeding. The aim was to evaluate the efficacy of vonoprazan vs. pantoprazole or non-acid suppression to prevent post-EVL ulcer/bleeding in portal hypertension patients. MATERIAL AND METHODS We enrolled 275 portal hypertension patients undergoing EVL in a three-arm randomized, single-blind, controlled study. A clinico-laboratory baseline evaluation was performed. Following EVL, patients were randomly and equally assigned to receive vonoprazan 20mg once daily, pantoprazole 40 mg once daily, or no acid suppression therapy. Post-EVL ulcer bleeding, ulcer dimensions, odynophagia as well as vonoprazan safety were evaluated after 2 weeks of EVL. RESULTS Post-EVL ulcer bleeding occurred among 2.15% of vonoprazan, 8.7% of pantoprazole, and 14.2% of the non-acid suppression groups (P < 0.001). Post-ligation ulcer frequency and dimensions were higher among non-acid suppression and pantoprazole groups vs. vonoprazan (P < 0.05). Chest pain and odynophagia were encountered among 73.6% and 54.9% of the non-acid suppression group vs. 39.6% and 45.1% in pantoprazole, and 17.2% and 21.5% in vonoprazan groups, respectively (P < 0.05). There were no vonoprazan-related adverse events. Non-use of vonoprazan was the strongest independent predictor for post-EVL bleeding. CONCLUSION Short course of vonoprazan 20 mg/day is safe and superior to pantoprazole 40 mg/day in the reduction of post-EVL ulcer dimensions at 2 weeks post-EVL, and prevention of ulcer-related bleeding. Acid suppression is superior to no acid suppression to prevent post-EVL complications.
-
5.
Argipressin for prevention of blood loss during liver resection: a study protocol for a randomised, placebo-controlled, double-blinded trial (ARG-01)
Wisén, E., Kvarnström, A., Sand-Bown, L., Rizell, M., Pivodic, A., Ricksten, S. E., Svennerholm, K.
BMJ open. 2023;13(8):e073270
Abstract
INTRODUCTION Liver resection carries a high risk for extensive bleeding and need for blood transfusions, which is associated with significant negative impact on outcome. In malignant disease, the most common indication for surgery, it also includes increased risk for recurrence of cancer. Argipressin decreases liver and portal blood flow and may have the potential to reduce bleeding during liver surgery, although this has not been explored. METHOD AND ANALYSIS ARG-01 is a prospective, randomised, placebo-controlled, double-blinded study on 248 patients undergoing liver resection at Sahlgrenska University Hospital, Sweden. Patients will be randomised to one of two parallel groups, infusion of argipressin or normal saline administered peroperatively. The primary endpoint is peroperative blood loss. Secondary outcomes include need for blood transfusion, perioperative variables, length of hospital stay, the inflammatory response, organ damage markers and complications at 30 days. ETHICS AND DISSEMINATION The study is enrolling patients since March 2022. The trial is approved by the Swedish Ethical Review Authority (Dnr 2021-03557) and the Swedish Medical Product Agency (Dnr 5.1-2021-90115). Results will be announced at scientific meetings and in international peer-reviewed journals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT05293041 and EudraCT, 2021-001806-32.
-
6.
Rational for Continuing Terlipressin after Endoscopic Variceal Ligation in Acute Variceal Haemorrhage Needs Further Evidence: A Pilot Study
Poudel, R. C., Dhibar, D. P., Sharma, N., Sharma, V., Taneja, S., Prakash, A.
Arquivos De Gastroenterologia. 2022;59(1):89-96
Abstract
BACKGROUND Variceal hemorrhage (VH) is a medical emergency. Prompt endoscopic variceal ligation (EVL) is therapeutic. Terlipressin is used in VH and continued for 2-5 days even after EVL. As hemostasis is primarily achieved by EVL, the benefit of continuing trelipressin after EVL is unknown. OBJECTIVE To evaluate the efficacy of continuing terlipressin after EVL to prevent re-bleed and mortality. METHODS In this pilot study, after EVL 74 patients of VH were randomized into two treatment groups TG2 & TG5, received terlipressin (1 mg IV bolus q 4 hourly) for 2 days and 5 days respectively and one control group (TG0), received 0.9% normal saline (10 mL IV bolus q 4 hourly) and followed up for 8 weeks. RESULTS A total of 9 (12.6%) patients had re-bleed with maximum 4 (5.6%) patients in TG5 group followed by 3 (4.2%) in TG2 and 2 (2.8%) in TG0 groups (P=0.670). The overall mortality was 15 (21.1%) patients, 6 (8.5%) patients in TG0 group, followed by 5 (7.0%) in TG5 and 4 (5.6%) in TG2 group (P=0.691). Adverse drug reactions were significantly higher in treatment groups with maximum 18 (24.32%) patients in TG5, followed by 8 (10.8%) in TG2 and 2 (2.7%) in TG0 groups (P=0.00). Duration of hospital stay was also significantly higher in treatment group, 6.63 (±0.65) days in TG5 followed by 3.64 (±0.57) in TG2 and 2.40 (±0.50) days in TG0 groups (P=0.00). CONCLUSION The rational for continuing terlipressin after EVL is doubtful as it didn't have any benefit for the prevention of re-bleed or mortality; rather it increased the risk of adverse drug reactions and duration of hospital stay. Further randomized clinical trials are encouraged to generate more evidence in support or against continuing terlipressin after EVL.
-
7.
Desmopressin Acetate in Percutaneous Ultrasound-Guided Native Kidney Biopsy in Patients with Reduced Kidney Function: A Double-Blind Randomized Controlled Trial
Sattari SA, Shahoori A, Shahbazian H, Sabetnia L, Aref A, Sattari AR, Ghorbani A
Iranian journal of kidney diseases. 2022;16(4):238-245
-
-
-
Free full text
-
Editor's Choice
Abstract
INTRODUCTION Bleeding events are the most common complications after kidney biopsy. This study aims to evaluate the effect of desmopressin administration on bleeding complication, in native kidney biopsy candidates with reduced kidney function. METHODS This double-blind randomized clinical trial enrolled 18 to 80 years old patients with 15 < eGFR < 90 mL/min/ 1.73m² from July 2017 to August 2020. Patients were randomly assigned to receive either 3 µg/kg of intranasal desmopressin acetate or 1 mL/kg of intranasal sodium chloride 0.65%, one hour before ultrasound-guided, percutaneous native kidney biopsy. The primary outcome was the post-biopsy bleeding complications, and secondary outcomes were the volume of perirenal hematoma, and changes of post-biopsy hemoglobin and hematocrit level, plasma sodium and blood pressure (Clinical Trial Registration ID: IRCT20090701002112N3). RESULTS A total of 120 patients (58 men and 62 women), 60 patients in each group, were analyzed. The mean age and eGFR of the patients were 45.29 ± 15.95 years and 51.77 ± 18.02 ml/min/ 1.73m², respectively. Desmopressin administration significantly decreased post-biopsy perirenal hematoma compared to placebo (7/60 [11.6%]) vs. 33/60 [40%]; P < .05), and the hematoma volume was significantly smaller in the desmopressin group, in case of hematoma formation (2.31 ± 1.17 vs. 7.72 ± 5.45 mm³, P < .05). CONCLUSION Desmopressin administration before kidney biopsy is a safe and effective strategy to prevent bleeding complications. Considering absolute risk reduction of about 28%, the number needed to treat is about 4 procedures. We recommend considering desmopressin administration before percutaneous native kidney biopsy. DOI: 10.52547/ijkd.6966.
PICO Summary
Population
Adult patients with kidney disease, who were candidates for percutaneous native kidney biopsy (n= 120).
Intervention
Intranasal desmopressin acetate (n= 60).
Comparison
Placebo: intranasal sodium chloride (n= 60).
Outcome
Desmopressin administration significantly decreased post-biopsy perirenal haematoma compared to placebo (7/60 [11.6%]) vs. 33/60 [40%]), and the haematoma volume was significantly smaller in the desmopressin group, in case of haematoma formation (2.31 ± 1.17 vs. 7.72 ± 5.45 mm³).
-
8.
Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding
Kanno T, Yuan Y, Tse F, Howden CW, Moayyedi P, Leontiadis GI
The Cochrane database of systematic reviews. 2022;1:Cd005415
Abstract
BACKGROUND Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding. OBJECTIVES To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding. SEARCH METHODS We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials. SELECTION CRITERIA We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (H(2)RA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis. AUTHORS' CONCLUSIONS There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
-
9.
Can trajectory nor-epinephrine infiltration reduce blood loss during percutaneous nephrolithotomy? A double-blinded randomized controlled trial
El-Shaer W, Haggag MS, Elshaer A, Shaboob I, Kandeel W, Elmohamady B, Abdelmotaleb DS, Abdel-Lateef S
International journal of urology : official journal of the Japanese Urological Association. 2022
-
-
-
-
Editor's Choice
Abstract
PURPOSE To determine the efficacy and safety of trajectory infiltration with 1:150 000 Norepinephrine (NE) in reducing blood loss during percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS This is a prospective randomized double-blinded placebo-controlled trial. In all, 140 consecutive patients underwent PCNL for the management of large renal calculi. They were randomly assigned (1:1) to one of either study groups, the NE-PCNL group (70 patients whose PCNL-trajectory was infiltrated by NE) or the Placebo group (saline PCNL) (70 patients whose PCNL tracts were infiltrated by normal saline). Procedure-related blood loss (the primary outcome) was assessed and statistically analyzed. Also, all other procedure-related events and complications were recorded and compared. RESULTS The median blood loss was 378 ml (IQR: 252-504) in the NE-PCNL group versus 592 ml (IQR: 378-756) in the S-PCNL group (p < 0.0001). In addition, Hemoglobin and Hematocrit deficits were lower in NE-PCNL (p < 0.05). Patients who were randomized to the NE-PCNL group had a higher immediate stone-free rate (SFR) (80%) compared with those of the S-PCNL group (70%) (p = 0.034). However, no statistical differences were found in the final SFR. The reported overall complications between the 2 groups were similar (p > 0.05). Indeed, bleeding-related complications were 1 (1.4%) versus 10 (14.3%) for NE-PCNL and S-PCNL, respectively (p = 0.009). CONCLUSIONS Trajectory infiltration of PCNL tracts by NE was found to be effective and safe in mitigation of PCNL-related blood loss. This step is a timeless and cost-effective as NE is readily available in surgical theaters and of very low cost.
PICO Summary
Population
Patients undergoing percutaneous nephrolithotomy (PCNL) (n= 140).
Intervention
PCNL after tract infiltration with norepinephrine (NE) (NE-PCNL group, n= 70).
Comparison
PCNL after tract infiltration with normal saline (S-PCNL group, n= 70).
Outcome
The primary outcome was procedure-related blood loss. The median blood loss was 378 ml (IQR= 252, 504) in the NE-PCNL group versus 592 ml (IQR= 378, 756) in the S-PCNL group. Haemoglobin and haematocrit deficits were lower in NE-PCNL. Patients in the NE-PCNL group had a higher immediate stone-free rate (80%) compared with those of the S-PCNL group (70%). No statistical differences were found in the final stone free rate. The reported overall complications between the two groups were similar. Bleeding-related complications were 1 (1.4%) versus 10 (14.3%) for NE-PCNL and S-PCNL, respectively.
-
10.
Clinical characteristics and treatment of terlipressin-induced ischemic skin necrosis: A synthesis of 35 literature reported cases
Zhou Y, Zeng J, Song L, Wang C
Journal of clinical pharmacy and therapeutics. 2022
Abstract
WHAT IS KNOWN AND OBJECTIVE The clinical features of terlipressin-induced ischemic skin necrosis are unknown. The purpose of this study is to explore the clinical features of terlipressin-induced skin necrosis. METHODS We searched Chinese and English databases to collect case reports of terlipressin-induced skin necrosis for retrospective analysis. RESULTS AND DISCUSSION A total of 42 patients (31 males and 11 females) from 35 studies were included, with a median age of 54 years (range 0.17-84). The onset of skin ischemia ranged from a few hours to 21 days. The most common clinical manifestations were bulla (15 cases, 35.7%), cyanosis (12 cases, 28.6%), necrosis (11 cases, 26.2%), and purpura (10 cases, 23.8%). The following were often affected: the legs (26 cases), 61.9%), abdomen (13, 31.0%), scrotum (10 cases, 23.8%), feet (10 cases, 23.8%), upper extremities (8 cases, 19.0%), and hands (7 cases, 16.7%). Skin biopsy showed fibrin thrombus (7 cases, 38.9%), nonspecific inflammation (6 cases, 33.3%), and necrosis (10 cases, 55.6%). After discontinuation of terlipressin, skin symptoms improved in most patients. WHAT IS NEW AND CONCLUSION Ischemic skin necrosis is a rare and serious adverse effect of terlipressin. Patients receiving terlipressin therapy should be monitored closely for terlipressin-related ischemic complications. Terlipressin should be discontinued immediately if ischemic complications occur.