A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients
Critical care (London, England). 2021;25(1):18
BACKGROUND Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients. METHODS A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded. RESULTS Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011]. CONCLUSION In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.
Patient Preferences for Subcutaneous versus Intravenous Administration of Treatment for Chronic Immune System Disorders: A Systematic Review
Patient preference and adherence. 2021;15:811-834
BACKGROUND For many chronic immune system disorders, the available treatments provide several options for route of administration. The objective of this systematic literature review is to inform discussions about therapy choices for individual patients by summarizing the available evidence regarding the preferences of patients with chronic immune system disorders for intravenous (IV) or subcutaneous (SC) administration. METHODS Searches of the MEDLINE, Embase and Cochrane Library databases were conducted using terms designed to capture studies reporting patient preferences between IV and SC therapy published in English. Relevant studies were limited to those in which mode of administration, including treatment frequency and setting, was the main difference between comparators. RESULTS In total, 49 studies were included in the review. Among 18 studies that compared IV and SC immunoglobulin therapy, 16 found patients to prefer the SC administration route. The results of the 31 studies comparing IV infusion and SC injection of non-immunoglobulin therapies were mixed, with patients favoring SC administration in 20, IV infusion in seven, and having no overall preference in four. Patient experience had a strong effect on preferences, with treatment-experienced patients preferring their current administration route in most studies. Patients preferring SC administration tended also to prefer treatment at home, mainly due to the convenience and comfort of home treatment and the avoidance of having to attend hospital. By contrast, patients preferring IV infusion tended to cite the lower treatment frequency and a dislike of self-injecting, and preferred hospital treatment, mainly due to the presence of healthcare professionals and resulting feelings of safety. CONCLUSION In general patients with chronic immune system disorders tend to be more likely to choose SC administration than IV infusion, but preferences may vary according among individuals. These findings may assist discussions around appropriate treatment choices for each patient.
The effectiveness of infliximab for Kawasaki disease in children: systematic review and meta-analysis
Translational pediatrics. 2021;10(5):1294-1306
BACKGROUND Kawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms (CAAs) and threatens children's health and lives. The therapeutic effects of single intravenous immunoglobulin gamma (IVIG) vs. infliximab (IFX) (with or without IVIG) in young children with KD remain unclear. Thus, we made a meta-analysis and systematic review, including all of the studies which have evaluated the effectiveness and safety of IFX and IVIG KD patients. METHODS The databases of the Cochrane Library, PubMed and Embase websites were searched for articles appearing from inception until December 31, 2020. Clinical studies that compared IFX either as initial therapy plus IVIG or rescue therapy after IVIG (IFX group) failure compared with IVIG treatment alone (IVIG group) in treating KD patients were included. RESULTS The meta-analysis included nine studies characterizing 712 patients. The treatment response was significantly higher in the adjunctive IFX therapy group than in the IVIG therapy group [odds ratio (OR) 2.64; 95% CI: 1.52-4.59; P=0.0005]. Subgroup analysis, the effect of IFX therapy on treatment response is more effectiveness in the group of the high-risk KD patients than IVIG therapy (OR 6.07; 95% CI: 2.30-16.04; P=0.0003; random-effects model). Further analysis showed no difference in the improvement of CAAs in short-term follow-up between the two groups. However, adding IFX either as initial therapy or as additional therapy all showed an advantageous effect regarding the ∆Z score of the left anterior descending (LAD) (MD =0.29; 95% CI: 0.27-0.31; P<0.00001) and right coronary artery (RCA) (MD =0.24; 95% CI: 0.22-0.26; P<0.00001). Further, IFX exhibited significant effect on the treatment response compared with IVIG therapy in the Asian group (OR, 2.84; 95% CI: 1.51-5.36; P=0.001; random-effects model), and the beneficial effects of IFX were given without increasing the risk of AEs. CONCLUSIONS This meta-analysis emphasizes the importance of IFX on the treatment response in the high-risk KD patients. IFX may play a role in the Asian KD patients and prevention of progressive CAA, and does not increase the risk of AEs in KD patients.
Invasive Group A Streptococcal Infections: Benefit of Clindamycin, Intravenous Immunoglobulins and Secondary Prophylaxis
Frontiers in pediatrics. 2021;9:697938
Introduction: Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. The added value of both clindamycin and immunoglobulins in such treatment is still controversial, as is the need for antibiotic secondary prophylaxis. It is unlikely that conclusive randomized clinical studies will ever definitively end these controversies. Materials and Methods: A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature to determine the benefit of adding clindamycin and immunoglobulins to β-lactams in the management of iGAS, as well as the need for secondary prophylaxis measures in close contacts. Results: This review includes two meta-analyses, two randomized controlled trials, four prospective studies, five retrospective studies, and microbiological studies. To reduce mortality and morbidity, it appears useful to add clindamycin to β-lactams in severe clinical presentations, including necrotizing fasciitis or streptococcal toxic shock syndrome, and immunoglobulins for the latter two presentations. The high risk of secondary infection in household contacts justifies the need of taking preventive measures. Conclusions: Both clinical studies and available experimental evidence suggest that adding clindamycin and immunoglobulins as adjunctive therapies in the management of invasive group A streptococcal infections may reduce mortality. Household contacts should be warned about the increased risk of secondary infection, and chemoprophylaxis may be considered in certain situations.
Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding: A Systematic Review and Meta-Analysis
Critical care medicine. 2021
OBJECTIVES To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies. DATA SOURCES Embase, Pubmed, Web of Science, and the Cochrane Library. STUDY SELECTION Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage. DATA EXTRACTION Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event. DATA SYNTHESIS A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents. CONCLUSIONS Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.
Comparison of Published Guidelines for the Diagnosis and the Management of Vaccine-Induced Immune Thrombotic Thrombocytopenia
Critical care explorations. 2021;3(9):e0519
The development of thrombocytopenia and thrombosis after the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines has been recently described. This new condition has been called vaccine-induced immune thrombotic thrombocytopenia. The objective of this review is to summarize the clinical characteristics and therapeutic options of vaccine-induced immune thrombotic thrombocytopenia based on available published case series. Furthermore, we provide a comparison of the diagnostic pathway and treatment recommendations provided by six major medical societies. DATA SOURCES We searched MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases. STUDY SELECTION We included case series and case reports on patients who developed vaccine-induced immune thrombotic thrombocytopenia. We also included guidelines for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia from major medical societies. DATA EXTRACTION We examined baseline risk factors, symptoms, physical signs, laboratory and imaging findings, and treatment in patients with vaccine-induced immune thrombotic thrombocytopenia reported in the case series. We also analyzed the diagnostic and treatment recommendations provided by major societal guidelines on the management of vaccine-induced immune thrombotic thrombocytopenia. DATA SYNTHESIS Patients who developed vaccine-induced immune thrombotic thrombocytopenia were more likely to be young women (age 20-50) who were given the AstraZeneca or Johnson & Johnson/Janssen 4-28 days prior to presentation. Patients showed signs, symptoms, and imaging findings consistent with cerebral venous sinus thrombosis and splanchnic thrombosis. Laboratory findings showed thrombocytopenia, low fibrinogen, and elevate d-dimer levels, while positive platelet factor 4 antibodies were always positive. Major societal guidelines recommend avoidance of heparin and platelets. Treatment with nonheparin anticoagulants and IV immunoglobulin is also recommended. CONCLUSIONS Vaccine-induced immune thrombotic thrombocytopenia is a rare but highly morbid complication related to the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines. Clinicians should be prepared for the early identification of patients with suspicious symptoms and prompt treatment should be initiated to avoid catastrophic deterioration. Major societal guidelines provide useful recommendations for the diagnosis and management of patients with vaccine-induced immune thrombotic thrombocytopenia.
Mesh fixation with fibrin glue versus tacker in laparoscopic totally extraperitoneal inguinal hernia repair
ANZ journal of surgery. 2021
BACKGROUND The advent of mesh was a breakthrough in the field of hernia surgery. Mechanical methods of mesh fixation are hypothesized to cause more tissue trauma than nonmechanical methods. The present study was conducted to study the outcomes of mesh fixation using fibrin glue, a nonmechanical method versus tackers in totally extraperitoneal repair (TEP) of unilateral inguinal hernia. METHODS A randomized controlled single blinded study was conducted in India from June 2017 to March 2019. Patients diagnosed with unilateral uncomplicated inguinal hernia with a hernial sac of size not more than 5 cm were invited to participate in the study. Sample size was 60 patients randomized into groups just before mesh fixation. In group A mesh was fixed using tackers while in group B mesh was fixed using fibrin glue. Patients were followed-up prospectively for 3 months. RESULTS There was no statistical difference between the two groups with respect to operating time. Average hospital stay and pain scores at all follow-ups were better for fibrin glue group. There was no difference in the incidence of postoperative urinary retention, seroma formation and hematoma formation between the two groups. Patients of fibrin glue group had early restart of daily activities at 15 days follow-up when compared to tacker group. CONCLUSION Fibrin glue fixation technique should be advocated over tackers for mesh fixation in TEP considering the better outcomes and cost-effectiveness of the technique.
Albumin replacement therapy in immunocompromised patients with sepsis - Secondary analysis of the ALBIOS trial
Journal of critical care. 2021;63:83-91
BACKGROUND The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear. METHODS We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay. RESULTS Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69-1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709-1.352) as compared to crystalloid. CONCLUSION Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis.
Randomized Trial of Different initial IVIG Regimens in Kawasaki Disease
Pediatrics international : official journal of the Japan Pediatric Society. 2021
BACKGROUND We aimed to assess the efficacy of different initial intravenous immunoglobulin (IVIG) regimens in Kawasaki disease (KD) patients to find more cost-effective therapy options. METHODS A multicentre, open-label, blind-endpoint randomized controlled trial was conducted from January 2014 to December 2015. KD Patients within 10 days of illness were randomly assigned to receive different IVIG regimens (Group A, 2 g/kg once; Group B, 1 g/kg for 2 consecutive days; Group C, 1 g/kg once) and aspirin 30mg/kg/d. Primary outcomes included hours to defervescence and development of coronary artery lesions (CAL) during the study period. Major secondary outcomes included total fever days, total dose of IVIG, changes of laboratory data, length of stay, and hospitalization expenses. (ClinicalTrials.gov: NCT02439996). RESULTS A total of 404 patients underwent randomization. No difference was found in the outcomes of defervescence among three groups at 6, 12, 24, and 36 hours after completion of initial IVIG infusion. There were no differences in the incidence of CAL during the study period (at week 2, month 1, month 3, and month 6 of illness), changes of laboratory data, total fever days and length of stay. Group C patients had the lowest total dose of IVIG (mean: 1.2 vs 2.2 vs 2.1 g/kg; P<0.001) and hospitalization expenses (mean: 8443.8 vs 10798.4 vs 11011.4 RMB; P<0.001) than other two groups. CONCLUSIONS A single dose of 1g/kg IVIG is a low-cost treatment with the same efficacy as 2 g/kg IVIG and can be an option for the initial therapy of KD patients.
A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis
The New England journal of medicine. 2021;384(9):808-817
BACKGROUND Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown. METHODS We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. RESULTS A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group. CONCLUSIONS In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).
Hospitalized patients with cirrhosis enrolled in the ATTIRE trial (n= 777).
Targeted 20% human albumin solution (n= 380).
Standard care (n= 397).
The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. The percentage of patients with a primary end point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference. More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group.