Thrombocytopenia in intensive care unit patients: A scoping review.

BACKGROUND: Thrombocytopenia is frequent in intensive care unit (ICU) patients and may be associated with adverse outcomes. We aimed to assess the incidence, risk factors, and outcomes associated with thrombocytopenia in adult ICU patients. METHODS: We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included study reports on adult ICU patients with thrombocytopenia and assessed patient-important outcomes, including mortality and health-related quality-of-life. RESULTS: We included a total of 70 studies comprising a total of 215 098 patients; 57 were cohort studies. The incidence of thrombocytopenia varied from 8 to 56 per 100 admissions (very low quality of evidence). We identified several risk factors including age, sepsis, and higher disease severity (low quality of evidence). Thrombocytopenia was associated with bleeding, use of life support, length of stay in the ICU, and increased mortality (low/very low quality of evidence). Data on platelet transfusion before invasive procedures and transfusion thresholds were limited. No studies assessed the benefits and harms of thromboprophylaxis in ICU patients with thrombocytopenia. CONCLUSIONS: Thrombocytopenia is common and associated with increased morbidity and mortality in adult ICU patients. Several risk factors for thrombocytopenia exists, but the evidence-base on management strategies, including transfusion thresholds and thromboprophylaxis in ICU patients is very limited.

Heterogenous treatment effects of transfusion thresholds by patient age: Post-hoc analysis of the TRISS trial.

BACKGROUND: Use of a lower haemoglobin (Hb) threshold to guide red blood cell (RBC) transfusion is now generally recommended in critically ill patients, but uncertainty remains regarding the optimal Hb threshold for RBC transfusion in patients of different ages. METHODS: We conducted a post-hoc analysis of 998 patients with septic shock and anaemia randomised to RBC transfusion at a Hb threshold of 7 g/dl [4.3 mmol/l] vs 9 g/dl [5.6 mmol/l] in the Transfusion Requirements in Septic Shock (TRISS) trial. We assessed if there were heterogeneous effects between the allocated Hb threshold and patient age categorised and on the continuous scale. The primary outcome was 1-year mortality; the secondary outcome was 90-day mortality. Both outcomes were analysed using logistic regression models and in sensitivity analyses with additional adjusting for site of enrolment, presence of haematological malignancy and the Sequential Organ Failure Assessment (SOFA) score. The secondary analyses were Kaplan-Meier curves with corresponding log-rank tests. RESULTS: We found no heterogeneity between patient age and the allocated Hb thresholds for RBC transfusion for 1-year mortality or 90-day mortality in the primary analyses. The sensitivity analyses suggested heterogeneity between age groups regarding 90-day mortality, however, this was not consistent for 1-year mortality or when assessing age on the continuous scale. CONCLUSION: In this post-hoc study of ICU patients with septic shock, we found no reliable heterogeneous effects of transfusion at a Hb threshold of 7 vs 9 g/dl according to patient age on mortality. However, due to low power, this study should only be considered as hypothesis generating.

Bleeding and thrombosis in intensive care patients with thrombocytopenia-Protocol for a topical systematic review.

BACKGROUND: Thrombocytopenia is a common condition in critically ill patients in the intensive care unit (ICU). It is associated with prolonged stay in the ICU, increased transfusion requirements, risk of bleeding and mortality. The evidence regarding the use of prophylactic platelet transfusion and thrombosis prophylaxis in patients with thrombocytopenia in the ICU is unknown. To direct future research, we aim to assess the current evidence regarding prophylactic platelet transfusion and thrombosis prophylaxis on patient-important benefits and harms in the ICU population. METHODS: We will conduct a topical systematic review of all study designs (ie no study design will per se be excluded from the proposed review) in accordance with the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) statements. We will include studies on adult patients in the ICU where the incidence of thrombocytopenia and the predefined outcome measures, including mortality, quality-of-life, thrombotic events and haemorrhagic events are reported. We will provide descriptive analyses of the included studies/trials, ie no meta-analyses will be conducted, and the quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. CONCLUSION: The outlined topical systematic review will provide important data on the benefits and harms of prophylactic platelet transfusion and thrombosis prophylaxis in ICU patients with thrombocytopenia and provide estimates on the rate of thrombocytopenia in this vulnerable population.

Lower vs higher transfusion threshold in septic shock patients of different ages: A study protocol.

BACKGROUND: Current evidence indicates that it is safe to use a lower haemoglobin (Hb) threshold for red blood cell (RBC) transfusion as compared to a higher Hb-threshold. However, the recent Transfusion Requirements in Cardiac Surgery (TRICS-3) trial reported a significant interaction between patient age and the effect of lower vs higher Hb-thresholds for RBC transfusion. The interaction between patient age and transfusion strategy appears to differ between trials. METHODS: This is the protocol and statistical analysis plan for a post hoc analysis of the Transfusion Requirements in Septic Shock (TRISS) trial. We will assess the effect of a lower vs a higher Hb-threshold for RBC transfusion in patients of different ages with septic shock. The primary and secondary outcomes are 1-year mortality and 90-day mortality respectively. We will assess age divided into six age groups and as a continuous variable and present baseline characteristics and odds ratios derived from both simple and adjusted (for the Sequential Organ Failure Assessment score, haematological malignancy, age and trial site) logistic regression models and P-values for the test-of-interaction. Furthermore, we will compare outcomes according to Hb-threshold in each age group using Kaplan-Meier curves and log-rank tests. DISCUSSION: The outlined study will make a detailed assessment of potential interaction of patient age with transfusion strategy in patients with septic shock. This may inform future trials on the benefits and harms of RBC transfusion.

Use of red blood cells in Danish intensive care units: A population-based register study.

BACKGROUND: Red blood cell (RBC) transfusion is common in the intensive care unit (ICU). Recent trials have shown that a restrictive transfusion strategy is safe in most patients, and recent guidelines recommend such a strategy in most ICU patients. It is unknown if this has translated into a change in clinical practice. METHODS: We conducted a population-based register study of RBC transfusions in ICUs in the Danish Capital Region between 1st of January 2011 and 31st of December 2016 by linking data from the regional blood bank and the Danish Intensive Care Database. We used crude data and run- and control-charts to analyse changes in the number of RBC transfusions. RESULTS: We included 27 835 ICU admissions of which 6936 received 40 889 RBC units. The crude use was 36.2 RBC units per one-hundred patient bed-days in 2011 vs 29.8 in 2016. The run-chart analysis did not confirm a change in the total use of RBC units in all ICUs combined, and we observed no change in the proportion of transfused patients or in the use of RBCs among transfused patients. Sensitivity analyses showed decreased use of RBC units in two general ICUs, and a reduced use of RBC units among medical ICU patients. CONCLUSIONS: In this population-based register study, we did not with certainty observe changes over time in the use of RBC transfusions in all patients in all ICUs in the Danish Capital Region. A reduction in RBC use may have occurred in some general ICUs and in medical ICU patients.

The effect of systemic corticosteroids on the incidence of gastrointestinal bleeding in critically ill adults: a systematic review with meta-analysis.

PURPOSE: To assess the effect of systemic corticosteroids on the incidence of gastrointestinal bleeding in adult critically ill patients. METHODS: We systematically reviewed randomised clinical trials comparing systemic corticosteroids administered for more than 24 h with placebo/no treatment in adult critically ill patients. Trial selection, data abstraction and risk of bias assessments were performed in duplicate. We used trial sequential analysis (TSA) to assess the risk of random errors and the grading of recommendations, assessment, development, and evaluations (GRADE) approach to assess the quality of evidence. The primary outcome was the incidence of clinically important gastrointestinal bleeding within 90 days. The secondary outcome was the incidence of gastrointestinal bleeding of any severity within 90 days. RESULTS: Twenty-five trials (n = 14,615) reported data for the primary outcome and 55 trials (n = 21,792) for the secondary outcome. The pooled incidence of clinically important gastrointestinal bleeding was 2.3% in the corticosteroid group and 1.8% in the control group (RR, 1.26; 95% CI, 1.01-1.57; I2 = 0%, TSA-adjusted CI 0.51-3.14). We observed no difference in the risk of gastrointestinal bleeding of any severity (RR, 1.10; 95% CI, 0.92-1.32; I2 = 0%, TSA-adjusted CI 0.87-1.38). The GRADE quality of evidence was low (risk of bias and imprecision). CONCLUSIONS: We observed an overall low incidence of clinically important gastrointestinal bleeding among adult critically ill patients. Corticosteroids may slightly increase the incidence of clinically important gastrointestinal bleeding, but not bleeding of any severity. Rarity of events, infrequent trial reporting and high risk of bias reduced the quality of evidence.

Blood Product Administration in the Critical Care and Perioperative Settings.

The critical care and perioperative settings are high consumers of blood products, with multiple units and different products often given to an individual patient. The recommendation of this review is always to consider the risks and benefits for a specific blood product for a specific patient in a specific clinical setting. Optimize patient status by treating anemia and preventing the need for red blood cell transfusion. Consider other options for correction of anemia and coagulation disorders and use an imperative non-overtransfusion policy for all blood products.

[Danish public research investments in clinical trials].

Clinical trials are important to ensure that patients and society benefit from healthcare interventions. Among the Danish public research investments in medical sciences the main part of funding is given to preclinical and translational research, and less than ten per cent is given to clinical trials. This imbalance may have negative consequences for patients and society, because public investment in clinical trials is likely to ensure broader availability of tested interventions independent of diseases, patient groups, caregivers and clinical settings.

Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis.

PURPOSE: To assess the effect of low dose corticosteroids on outcomes in adults with septic shock. METHODS: We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay. RESULTS: There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89-1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91-1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90-1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03-2.70, p = 0.04, I2 = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) -1.52 days; 95% CI -1.71 to -1.32, p < 0.0001], duration of mechanical ventilation (MD -1.38 days; 95% CI -1.96 to -0.80, p < 0.0001), and ICU stay (MD -0.75 days; 95% CI -1.34 to -0.17, p = 0.01) were shorter with corticosteroids versus placebo. CONCLUSIONS: In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced. PROSPERO registration no. CRD42017084037.