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Comparative efficacy of terlipressin and norepinephrine for treatment of hepatorenal syndrome-acute kidney injury: A systematic review and meta-analysis
Olson, J. C., Subramanian, R. M.
PloS one. 2024;19(1):e0296690
Abstract
The treatment of choice for hepatorenal syndrome-acute kidney injury (HRS-AKI) is vasoconstrictor therapy in combination with albumin, preferably norepinephrine or terlipressin as recommended by recent guidelines. In the absence of larger head-to-head trials comparing the efficacy of terlipressin and norepinephrine, meta-analysis of smaller studies can provide insights needed to understand the comparative effects of these medications. Additionally, recent changes in the HRS diagnosis and treatment guidelines underscore the need for newer analyses comparing terlipressin and norepinephrine. In this systematic review, we aimed to assess reversal of hepatorenal syndrome (HRS) and 1-month mortality in subjects receiving terlipressin or norepinephrine for the management of HRS-AKI. We searched literature databases, including PubMed, Cochrane, Clinicaltrials.gov, International Clinical Trials Registry Platform, Embase, and ResearchGate, for randomized controlled trials (RCTs) published from January 2007 to June 2023 on June 26, 2023. Only trials comparing norepinephrine and albumin with terlipressin and albumin for the treatment of HRS-AKI in adults were included, and trials without HRS reversal as an endpoint or nonresponders were excluded. Pairwise meta-analyses with the random effects model were conducted to estimate odds ratios (ORs) for HRS reversal and 1-month mortality as primary outcomes. Additional outcomes assessed, included HRS recurrence, predictors of response, and incidence of adverse events (AEs). We used the Cochrane risk of bias assessment tool for quality assessment. We included 7 RCTs with a total of 376 subjects with HRS-AKI or HRS type 1. This meta-analysis showed numerically higher rates of HRS reversal (OR 1.33, 95% confidence interval [CI] [0.80-2.22]; P = 0.22) and short-term survival (OR 1.50, 95% CI [0.64-3.53]; P = 0.26) with terlipressin, though these results did not reach statistical significance. Terlipressin was associated with AEs such as abdominal pain and diarrhea, whereas norepinephrine was associated with cardiovascular AEs such as chest pain and ischemia. Most of the AEs were reversible with a reduction in dose or discontinuation of therapy across both arms. Of the terlipressin-treated subjects, 5.3% discontinued therapy due to serious AEs compared to 2.7% of the norepinephrine-treated subjects. Limitations of this analysis included small sample size and study differences in HRS-AKI diagnostic criteria. As more studies using the new HRS-AKI criteria comparing terlipressin and norepinephrine are completed, a clearer understanding of the comparability of these 2 therapies will emerge.
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Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis
Wang, T., Wang, J., Zhang, M., Zhang, H., Zhang, Q., Liu, G., Dong, W., Wang, Y., Ji, B.
BMC anesthesiology. 2024;24(1):26
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Editor's Choice
Abstract
BACKGROUND In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence. METHODS The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids. RESULTS The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid. CONCLUSION Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.
PICO Summary
Population
Adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (10 randomised controlled trials).
Intervention
Network meta-analysis (NMA) to perform direct comparisons, including albumin vs. artificial colloid and artificial colloid vs. crystalloid, and to obtain indirect evidence for the comparisons between albumin and crystalloid priming strategies.
Comparison
Outcome
Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative red blood cell (RBC) transfusions (MD -0.68U; 95% CI [-1.26, -0.09U]) and intraoperative RBC transfusions (MD -0.20U; 95% CI [-0.39, -0.01U]) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant (MD -0.16U; 95% CI: [-0.45, 0.14U]). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance.
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Role of albumin-induced volume expansion therapy for cerebral vasospasm in aneurysmal subarachnoid hemorrhage: A systematic review
Ali, A., Rajeswaran, A. B., Shaikh, N., Al-Rumaihi, G., Al-Sulaiti, G.
Journal of neurosciences in rural practice. 2023;14(4):582-590
Abstract
OBJECTIVES This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS Computer searches carried out from the Scopus, Medline, Embase, Web of Science, the Cochrane Library, and Internet documents; hand searching of medical journals; and review of reference lists. Randomized controlled trials (RCT) and observational studies (OSs) comparing albumin therapy in combination or alone with crystalloid therapy for the treatment of cerebral vasospasm in aSAH were included in the study. Risk-of-bias assessment was conducted using ROB2.0 and ROBINS-I tools for RCTs and Oss, respectively. RESULTS Out of a total of 1078 searches, one RCT (published in two articles) and one observational (retrospective) study were included for final analysis. In RCT, albumin was used for volume expansion therapy with a baseline crystalloid regime and comparison made between hypervolemic and normovolemic groups and it showed no beneficial effects on symptomatic vasospasm and clinical outcomes based on the Glasgow outcome scale. Furthermore, the use of albumin showed a tendency for sodium retention with lowering of glomerular filtration rate, limiting the amount of total fluid required for targeted central venous pressure values, and thereby avoiding fluid overload manifestations. The retrospective study results between albumin versus non-albumin groups (crystalloids only) supported improved outcomes in the former group with lower in-hospital mortality. Cardiorespiratory complications were equivocal in RCT and increased in non-albumin group in the retrospective study. Risk-of-bias assessment analyses revealed "some concerns" in RCT and "serious" limitation in OS due to its retrospective design. CONCLUSION Albumin-induced volume expansion therapy for cerebral vasospasm does not have substantiative evidence to improve cerebral vasospasm and clinical outcomes in aSAH. Studies with well-designed RCTs are required to compare the use of albumin for volume expansion therapy versus standard fluid management using crystalloids to mitigate the scarcity of published data.
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The Efficacy and Safety of Intra-articular Low Molecular Weight Fraction of Human Serum Albumin for the Management of Moderate to Moderately Severe Knee Osteoarthritis: A Systematic Review and Meta-Analysis
Nooh, M. H., Alshehri, M. S., Alzahrani, Z. S., Alsolami, H. M., Almutairi, A. O., AlOtaibi, A. S., Aljohani, A. N.
Cureus. 2023;15(6):e41240
Abstract
Osteoarthritis is a chronic degenerative joint disease that affects weight-bearing joints. Low molecular weight fraction of 5% (LMWF-5A) human serum albumin is an intra-articular injection that emerged for the treatment of knee osteoarthritis. The aim of this review is to assess the efficacy and safety of LMWF-5A versus placebo through a systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), EBSCO, and ClinicalTrials.gov registry databases were utilized to search for studies. Only randomized controlled trials (RCTs) that evaluated the efficacy of LMWF-5A versus placebo were included. Efficacy endpoints were represented by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A and C scores for pain and function, respectively. Serious adverse events (SAEs), non-serious adverse events (NSAEs), and mortality rates were used to evaluate the safety of the drug. The revised Cochrane risk of bias tool was used for the risk of bias assessment. Seven RCTs (n=2939) that met the inclusion criteria were included. The meta-analysis did not find significant improvement in pain (WOMAC A) (standardized mean difference (SMD)= -0.01, 95% confidence interval (CI) -0.10 - 0.09, P=0.87, I²=30%). Additionally, no significant change in function was noted (WOMAC C) (SMD=0.01, 95% CI -0.08 - 0.10, P=0.87, I²=22%). The pooled analysis did not find a significant difference between LMWF-5A and placebo regarding the incidence of joint swelling (P=0.84), joint stiffness (P=0.53), arthralgia (P=0.53), extremity pain (P=0.45), NSAEs (P=0.21), SAEs (P=0.92), or mortality (P=1.00). However, the subgroup analysis showed a significant reduction of 42% in NSAEs upon administration of 10 mL of LMWF-5A (risk ratio (RR)=0.58, 95% CI 0.35-0.97, P=0.04). In summary, our meta-analysis did not find significant differences between LMWF-5A and placebo regarding the incidence of NSAEs, SAEs, or mortality. On the other hand, LMWF-5A did not demonstrate superiority over saline in terms of efficacy. Therefore, it is not an effective drug for managing knee osteoarthritis.
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Human Albumin Infusion for the Management of Liver Cirrhosis and Its Complications: An Overview of Major Findings from Meta-analyses
Zheng X, Bai Z, Wang T, Romeiro FG, Mancuso A, Philips CA, Wong YJ, Nery FG, Qi X
Advances in therapy. 2023
Abstract
INTRODUCTION The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications. METHODS A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes. RESULTS Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100 g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate. CONCLUSIONS Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections.
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Intravenous albumin in cardiac and vascular surgery: a systematic review and meta-analysis
Skubas, N. J., Callum, J., Bathla, A., Keshavarz, H., Fergusson, D., Wu, B., Stanworth, S., Shehata, N.
British journal of anaesthesia. 2023
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Editor's Choice
Abstract
BACKGROUND Intravenous albumin is commonly utilised in cardiovascular surgery for priming of the cardiopulmonary bypass circuit, volume replacement, or both, although the evidence to support this practice is uncertain. The aim was to compare i.v. albumin with synthetic colloids and crystalloids for paediatric and adult patients undergoing cardiovascular surgery for all-cause mortality and other perioperative outcomes. METHODS A systematic review and meta-analysis of randomised controlled trials (RCTs) of i.v. albumin compared with synthetic colloids and crystalloids on the primary outcome of all-cause mortality was conducted. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use; subgroups were analysed by age, comparator fluid, and intended use (priming, volume, or both). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CCRT) from 1946 to November 23, 2022. RESULTS Of 42 RCTs, mortality was assessed in 15 trials (2711 cardiac surgery patients) and the risk difference was 0.00, 95% confidence interval (CI) -0.01 to 0.01, I(2)=0%. Among secondary outcomes, i.v. albumin resulted in smaller fluid balance, mean difference -0.55 L, 95% CI -1.06 to -0.4, I(2)=90% (nine studies, 1975 patients) and higher albumin concentrations, mean difference 7.77 g L(-1), 95% CI 3.73-11.8, I(2)=95% (six studies, 325 patients). CONCLUSIONS Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids. The lack of improvement in patient-important outcomes with albumin and its higher cost suggests it should be used restrictively. SYSTEMATIC REVIEW PROTOCOL PROSPERO; CRD42020171876.
PICO Summary
Population
Paediatric and adult patients undergoing cardiovascular surgery (42 randomised controlled trials).
Intervention
Intravenous albumin.
Comparison
Synthetic colloids and crystalloids.
Outcome
Primary outcome of all-cause mortality. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use. Mortality was assessed in 15 trials (n= 2,711) and the risk difference was 0.00; 95% confidence interval (CI) [-0.01, 0.01] I(2)= 0%. Among secondary outcomes, intravenous albumin resulted in smaller fluid balance, mean difference -0.55 L; 95% CI [-1.06, -0.4], I(2)= 90% (nine studies, n= 1,975) and higher albumin concentrations, mean difference 7.77 gL(-1); 95% CI [3.73, 11.8], I(2)= 95% (six studies, n= 325). Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids.
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Different Concentrations of Albumin Versus Crystalloid in Patients with Sepsis and Septic Shock: A Meta-Analysis of Randomized Clinical Trials
Geng L, Tian X, Gao Z, Mao A, Feng L, He C
Journal of intensive care medicine. 2023;:8850666231170778
Abstract
OBJECTIVE The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis. MATERIALS AND METHODS PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals. RESULTS Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; P = .11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; P = .04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; P = .03), which was better than 4% to 5% albumin and crystalloid. CONCLUSIONS Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation.
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Safety and Efficacy of Albumin for Pump Priming in Cardiac Surgery: A Meta-Analysis
Yin, J., Sun, M., Zeng, Y., Cai, M., Liu, H., Jin, Y.
Journal of cardiothoracic and vascular anesthesia. 2023
Abstract
OBJECTIVES To assess the efficacy and safety of albumin as pump priming fluid in cardiac surgery. DESIGN Meta-analysis of randomized controlled trials. SETTING Each study was conducted in a surgical center or intensive care unit. PARTICIPANTS Adult and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass who received circuit priming fluids. INTERVENTIONS Extracorporeal circuit priming with either albumin or crystalloid. MEASUREMENTS AND RESULTS Fourteen eligible randomized controlled trials with 741 patients were included in the present meta-analysis. Albumin prime had lower bleeding (CI -202.20 to -142.88 mL, p < 0.00001) and showed a greater advantage in preserving platelet counts (CI 14.85-21.48 × 10(3) mm(-3), p < 0.00001), maintaining colloid osmotic pressure and sustaining negative fluid balance. No significant differences were found in the remaining study outcomes. CONCLUSIONS Albumin was shown to be safe and efficacious in extracorporeal circulation perfusion. However, its clinical advantages were not clearly highlighted, as there were no significant differences in the number of deaths, length of hospital stay, or intensive care unit duration. The results should be interpreted cautiously, as most included studies were small in scale, and the total number of participants was limited.
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Furosemide and albumin for the treatment of nephrotic edema: a systematic review
Hedin E, Bijelić V, Barrowman N, Geier P
Pediatric nephrology (Berlin, Germany). 2022
Abstract
BACKGROUND Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS. OBJECTIVES (1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema. SEARCH METHODS The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface. ClinicalTrials.gov and the International Clinical Trials Registry Platform were also searched. SELECTION CRITERIA We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m(2) and patients with congenital NS. DATA COLLECTION AND ANALYSIS All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI = - 0.28 to 1.02). AUTHORS' CONCLUSIONS The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful. TRIAL REGISTRATION Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO A higher resolution version of the Graphical abstract is available as Supplementary information.
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Can albumin reduce the mortality of patients with cirrhosis and ascites? A meta-analysis of randomized controlled trials
Xu T, Liu W, Huang R
European journal of gastroenterology & hepatology. 2022
Abstract
BACKGROUND Albumin therapy in patients with decompensated liver cirrhosis has always been a controversial issue. This study aimed to investigate the efficacy and safety of albumin in reducing mortality and controlling complications in patients with liver cirrhosis and provide a reference for relevant decision-making. METHODS Databases such as PubMed, EMBASE, and Web of Science were searched to collect eligible articles published before January 2022, which were analyzed by Revman 5.3. RESULTS A total of 10 randomized controlled trials (2040 patients) were included. Based on the meta-analysis results, no significant difference in mortality was shown between the albumin administration group and the control group (HR = 1.01; 95% CI, 0.97-1.05; P = 0.62). Subgroup analysis showed that albumin administration had no significant short-term or long-term survival benefits in patients with decompensated liver cirrhosis and increased the risk of pulmonary edema adverse reactions (RR = 3.14; 95% CI, 1.48-6.65; P = 0.003). Subgroup analysis based on albumin administration time showed that short-term (HR = 0.93; 95% CI, 0.76-1.13; P = 0.47) or long-term (HR = 0.97; 95% CI: 0.87-1.08; P = 0.58) administration of albumin could not significantly reduce the mortality of patients with decompensated liver cirrhosis. In contrast, albumin administration could significantly reduce the recurrence rate of ascites (RR = 0.56; 95% CI, 0.46-0.68; P = 0.000). CONCLUSION Short-term(<1 month) or long-term (>1 month) administration of albumin can not significantly reduce the mortality of patients with decompensated liver cirrhosis, and a large amount of albumin infusion will increase the risk of pulmonary edema.