Abstract

OBJECTIVES The objective of this study was to critically appraise and synthesise evidence for blood conservation strategies in intensive care. Blood sampling is a critical aspect of intensive care to guide clinical decision-making. Repeated blood sampling can result in blood waste and contamination, leading to iatrogenic anaemia and systemic infection. REVIEW METHOD USED Cochrane systematic review methods were used including meta-analysis, and independent reviewers. DATA SOURCES A systematic search was conducted in Medline, CINAHL, PUBMED and EMBASE databases. The search was limited to randomised controlled trials (RCTs) and cluster RCTs, published in English between 2000 and 2021. REVIEW METHODS Paired authors independently assessed database search results and identified eligible studies. Trials comparing any blood conservation practice or product in intensive care were included. Primary outcomes were blood sample volumes and haemoglobin change. Secondary outcomes included proportion of patients receiving transfusions and infection outcomes. Quality appraisal employed the Cochrane Risk of Bias tool. Meta-analysis using random effects approach and narrative synthesis summarised findings. RESULTS Eight studies (n = 1027 patients), all RCTs were eligible. Six studies included adults, one studied paediatrics and one studied preterm infants. Seven studies evaluated a closed loop blood sampling system, and one studied a conservative phlebotomy protocol. Studies were of low to moderate quality. Meta-analysis was not possible for interventions targeting blood sample volumes or haemoglobin. Decreased blood sample volumes reported in four studies were attributable to a closed loop system or conservative phlebotomy. No study reported a significant change in haemoglobin. Meta-analysis demonstrated that use of a closed system (compared to open system) reduced the proportion of patients receiving transfusion [Risk Ratio (RR) 0.65, 95% CI 0.46-0.92; 287 patients] and reduced intraluminal fluid colonisation [RR 0.25, 95% CI 0.07-0.58; 500 patients]. CONCLUSIONS Limited evidence demonstrates closed loop blood sampling systems reduced transfusion use and fluid colonisation. Simultaneous effectiveness-implementation evaluation of these systems and blood conservation strategies is urgently required. PROSPERO PROTOCOL REGISTRATION REFERENCE CRD42019137227.

Abstract

BACKGROUND Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. METHODS This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. RESULTS Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR-) were 4.24 [3.18-5.65] and 0.39 [0.29-0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR- were 1.39 [1.36-1.42] and 0.87 [0.85-0.89], respectively. CONCLUSIONS Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality.

Abstract

BACKGROUND Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT. METHODS We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure. RESULTS Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5). CONCLUSIONS Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.

Abstract

OBJECTIVE To perform a systematic review and meta-analysis comparing two pre-operative transfusion regimens (conservative versus aggressive) in children with sickle cell disease(SCD) undergoing adenotonsillectomy in terms of post-operative complications, complications related to SCD and transfusion related complications. DATA SOURCES AND REVIEW METHODS A literature review was performed through PubMed, EMBASE, Cochrane, and Ovid databases using the following phrases: (Adenotonsillectomy OR Tonsillectomy) AND (Sickle Cell Disease OR Sickle Cell Trait). Using predetermined inclusion and exclusion criteria, seven articles were selected for systemic review and two control trials were included in meta-analysis. RESULTS Out of a total of 3,146 results, seven articles were selected for review and two controlled trials were included in the meta-analysis. There was no statistically significant difference in the rate of primary and secondary hemorrhage between the aggressive and conservative transfusion regimens (RR = 3.1, CI = 0.84-11.4, p-value = 0.089). The rate of sickle cell disease related complications including vaso-occlusive crisis and acute chest syndrome was also not statistically significant between the two transfusion groups (RR = 1.4, CI = 0.7-2.8, p-value = 0.339). Even though, the transfusion related complications did not reach statistical significance, there was a higher complication rate in the group receiving aggressive blood transfusion. CONCLUSION In SCD children undergoing adenotonsillectomy, an aggressive transfusion regimen that focuses on reducing the Hemoglobin S ratio to below 30% has not been shown to be more effective in reducing post-operative complications when compared to a conservative transfusion regimen. Therefore, it is reasonable to utilize a conservative transfusion regimen, thereby reducing the transfusion-associated risks.

Abstract

OBJECTIVE To evaluate red blood cell use during delivery in patients with placenta accreta spectrum. DATA SOURCES We searched MEDLINE, EMBASE, CINAHL, Cochrane Central, ClinicalTrials.gov, and Scopus for clinical trials and observational studies published between 2000 and 2021 in countries with developed economies. METHODS OF STUDY SELECTION Abstracts (n=4,275) and full-text studies (n=599) were identified and reviewed by two independent reviewers. Data on transfused red blood cells were included from studies reporting means and SDs, medians with interquartile ranges, or individual patient data. The primary outcome was the weighted mean number of units of red blood cells transfused per patient. Between-study heterogeneity was assessed with an I2 statistic. Secondary analyses included red blood cell usage by placenta accreta subtype. TABULATION, INTEGRATION, AND RESULTS Of the 599 full-text studies identified, 20 met criteria for inclusion in the systematic review, comprising 1,091 cases of placenta accreta spectrum. The number of units of red blood cells transfused was inconsistently described across studies, with five studies (25.0%) reporting means, 11 (55.0%) reporting medians, and four (20.0%) reporting individual patient data. The weighted mean number of units transfused was 5.19 (95% CI 4.12-6.26) per patient. Heterogeneity was high across studies (I2=91%). In a sensitivity analysis of five studies reporting mean data, the mean number of units transfused was 6.61 (95% CI 4.73-8.48; n=220 patients). Further quantification of units transfused by placenta accreta subtype was limited due to methodologic inconsistencies between studies and small cohort sizes. CONCLUSION Based on the upper limit of the CI in our main analysis and the high study heterogeneity, we recommend that a minimum of 6 units of red blood cells be available before delivery for patients with placenta accreta spectrum. These findings may inform future guidelines for predelivery blood ordering and transfusion support. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42021240993.

Abstract

BACKGROUND This meta-analysis aimed to explore the impact of red blood cell (RBC) transfusion on mortality during extracorporeal membrane oxygenation (ECMO). Previous studies investigated the prognostic impact of RBC transfusion during ECMO on the risk of mortality, but no meta-analysis has been published before. METHODS The PubMed, Embase, and the Cochrane library were systematically searched for papers published up to 13 December 2021, using the MeSH terms "ECMO", "'Erythrocytes", and "Mortality" to identify meta-analyses. Total or daily RBC transfusion during ECMO and mortality were examined. RESULTS The random-effect model was used. Eight studies (794 patients, including 354 dead) were included. The total volume of RBC was associated with higher mortality standardized weighted difference (SWD = -0.62, 95% CI: -1.06,-0.18, p = .006; I2 = 79.7%, P(heterogeneity) = 0.001). The daily volume of RBC was associated with higher mortality (SWD = -0.77, 95% CI: -1.11,-0.42, p < .001; I2 = 65.7%, P(heterogeneity) = 0.020). The total volume of RBC was associated with mortality for venovenous (VV) (SWD = -0.72, 95% CI: -1.23, -0.20, p = .006) but not venoarterial ECMO (p = .126) or when reported together (p = .089). The daily volume of RBC was associated with mortality for VV (SWD = -0.72, 95% CI: -1.18, -0.26, p = 0.002; I2 = 0.0%, P(heterogeneity) = 0.642) and venoarterial (SWD = -0.95, 95% CI: -1.32, -0.57, p < .001) ECMO, but not when reported together (p = .067). The sensitivity analysis suggested the robustness of the results. CONCLUSION When considering the total and daily volumes of RBC transfusion during ECMO, the patients who survived received smaller total and daily volumes of RBC transfusion. This meta-analysis suggests that RBC transfusion might be associated with a higher risk of mortality during ECMO.

Abstract

BACKGROUND Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017. OBJECTIVES To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination. SEARCH METHODS We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE). MAIN RESULTS We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m(2), 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life. AUTHORS' CONCLUSIONS We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.

Abstract

Persistent air leaks (PALs) are associated with prolonged hospital stays, contamination and sustained infection of the pleural space, and significant morbidity. A fistulous tract between the alveoli and the pleural space is referred to as an alveolar-pleural fistula (APF), whereas a fistulous tract between the bronchiole and the pleural space is referred to as a bronchopleural fistula (BPF). There is no consensus on the treatment, and multiple modalities exist for the management of persistent air leak (PAL). Autologous blood patch (ABP) is a relatively safe and inexpensive method that has been used for many years for the treatment of PALs. We conducted an electronic database search between 08/24/2022 and 08/27/2022 in PubMed, Embase, and Cochrane using keywords. The following keywords were used: "Blood patch" OR "Autologous blood patch" AND "pleurodesis." Our study included all original studies with the prime focus on the etiology of PALs, clinical characteristics, procedural details of ABP, and outcomes of the proposed treatment. The primary outcomes that were the focus of our study were the time to seal the air leak, the time to remove the chest tube after air leak cessation, and the time to discharge from the hospital. To determine the safety of ABP, we also evaluated the procedural outcomes. Our findings suggest a statistically significant decrease in the time to air leak cessation when compared to the control group (mean difference of -3.75 {95% CI: -5.65 to -1.85; P=0.001}) with considerable heterogeneity of I(2)=85% and P=0.001. However, the difference was not statistically significant when a lower dose of ABP (50 mL) was compared to a higher dose (100 mL) (mean difference of 1.48 {95% CI: -0.07 to 3.02; P=0.06}) and considerable heterogeneity of I(2)=80% and P=0.03. There was no statistically significant difference in the time to discharge when compared to the control group (mean difference of -2.12 {95% CI: -4.83 to 0.59; P=0.13}) and considerable heterogeneity (I(2)=95% and P<0.001). When compared to the control group, ABP did not provide any statistically significant difference in the risk ratio for infection (1.18 {95% CI: 0.52 to 2.65; P=0.70} and moderate heterogeneity {I(2)=33% and P=0.20}), pain (1.18 {95% CI: 0.52 to 2.65; P=0.70} and moderate heterogeneity {I(2)=33% and P=0.20}), and fever (0.54 {95% CI: 0.27 to 1.10; P=0.09} and no heterogeneity {I(2)=0% and P=0.50}). Our study concludes that using ABP caused a statistically significant decrease in the time to air leak cessation when compared to the control group. However, the procedure does not provide a statistically significant difference in the time to discharge from the hospital when compared to conservative treatment. Similarly, there was no statistically significant difference in the risk ratio for complications such as infection, pain, and fever when compared to conservative management. More studies need to be conducted to fully understand the efficacy and safety of ABP in the management of PALs.

Abstract

BACKGROUND There is a growing concern with inappropriate, excessive perioperative blood transfusions. Understanding the influence of low preoperative hemoglobin (Hgb) on perioperative blood transfusion (PBT) in head and neck cancer (HNC) surgery with free flap reconstruction may help guide clinical practice to reduce inappropriate treatment among these patients. The objective is to synthesize evidence regarding the association between preoperative Hgb and PBT among major HNC free flap surgeries. METHODS Terms and synonyms for HNC surgical procedures, Hgb and PBT were used to search MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Reviews from inception to February 2020. Reference lists of included full texts and studies reporting the preoperative Hgb, anemia or hematocrit (exposure) and the PBT (outcome) in major HNC surgery with free flap reconstruction were eligible. Studies examining esophageal, thyroid and parathyroid neoplasms were excluded; as were case reports, case series (n < 20), editorials, reviews, perspectives, viewpoints and responses. Two independent, blinded reviewers screened titles, abstracts and full texts in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. A random-effects model was used to pool reported data. The primary outcome was the proportion of patients who had a PBT. Subgroup analysis examined sources of heterogeneity for perioperative predictors of PBT (age, sex, flap type, flap site and preoperative Hgb). We also examined mean preoperative Hgb in the PBT and no PBT groups. RESULTS Patients with low preoperative Hgb were transfused more than those with normal Hgb (47.62%, 95% CI = 41.19-54.06, I(2) = 0.00% and 13.92%, 95% CI = 10.19-17.65, I(2) = 20.69%, respectively). None of the predictor variables explained PBT. The overall pooled mean preoperative Hgb was 12.96 g/dL (95% CI = 11.33-14.59, I(2) = 0.00%) and was 13.58 g/dL (95% CI = 11.95-15.21, I(2) = 0.00%) in the no PBT group and 12.05 g/dL (95% CI = 10.01 to 14.09, I(2) = 0.00%) in the PBT group. CONCLUSIONS The heterogeneity between studies, especially around the trigger for PBT, highlights the need for additional research to guide clinical practice of preoperative Hgb related to PBT to enhance patient outcomes and improve healthcare stewardship.

Abstract

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to review the clinical evidence of efficacy and safety of skin photosensitivity treatments in individuals with EPP or XLP. We systematically searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov. A total of 40 studies with data on 18 treatment modalities were included. Comprehensive treatment safety data were obtained from the European Medicines Agency and the United States Food and Drug Administration. The studies used different outcome measures to evaluate the sensitivity without a generally accepted method to assess treatment effect on skin photosensitivity. Of the included studies, 13 were controlled trials. Gathered, the trials showed moderate positive effect of inorganic sunscreen application and subcutaneous implant of afamelanotide and no effect of organic sunscreen application, or oral treatment with beta-carotene, cysteine, N-acetylcysteine, vitamin C, or warfarin. Studies without control groups suggested treatment effect of foundation cream, dihydroxyacetone/lawsone cream, narrow-band ultraviolet B phototherapy, erythrocyte transfusion, extracorporeal erythrocyte photodynamic therapy, or oral treatment with zinc sulphate, terfenadine, cimetidine, or canthaxanthin, but the real effect is uncertain. Assessment of treatment effect on photosensitivity in patients with EPP or XLP carries a high risk of bias since experienced photosensitivity varies with both weather conditions, exposure pattern, and pigmentation. Controlled trials of promising treatment options are important although challenging in this small patient population.