Douglas M. Watson

A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time

IntroductionFresh frozen plasma (FFP) is widely used, but few studies have described patterns of plasma use in critical care. We carried out a multicentre study of coagulopathy in intensive care units (ICUs) and here describe overall FFP utilisation in adult critical care, the indications for transfusions, factors indicating the doses used and the effects of FFP use on coagulation.MethodsWe conducted a prospective, multicentre, observational study of all patients sequentially admitted to 29 adult UK general ICUs over 8 weeks. Daily data throughout ICU admission were collected concerning coagulation, relevant clinical outcomes (including bleeding), coagulopathy (defined as international normalised ratio (INR) >1.5, or equivalent prothrombin time (PT)), FFP and cryoprecipitate use and indications for transfusion.ResultsOf 1,923 admissions, 12.7% received FFP in the ICU during 404 FFP treatment episodes (1,212 FFP units). Overall, 0.63 FFP units/ICU admission were transfused (0.11 units/ICU day). Reasons for FFP transfusion were bleeding (48%), preprocedural prophylaxis (15%) and prophylaxis without planned procedure (36%). Overall, the median FFP dose was 10.8 ml kg-1, but doses varied widely (first to third quartile, 7.2 to 14.4 ml kg-1). Thirty-one percent of FFP treatments were to patients without PT prolongation, and 41% were to patients without recorded bleeding and only mildly deranged INR (<2.5). Higher volumes of FFP were administered when the indication was bleeding (median doses: bleeding 11.1 ml kg-1, preprocedural prophylaxis 9.8 ml kg-1, prophylaxis without procedure 8.9 ml kg-1; P = 0.009 across groups) and when the pretransfusion INR was higher (ranging from median dose 8.9 ml kg-1 at INR ≤1.5 to 15.7 ml kg-1 at INR >3; P < 0.001 across ranges). Regression analyses suggested bleeding was the strongest predictor of higher FFP dose. Pretransfusion INR was more frequently normal when the transfusion indication was bleeding. Overall, posttransfusion corrections of INR were consistently small unless the pretransfusion INR was >2.5, but administration during bleeding was associated with greater INR corrections.ConclusionsThere is wide variation in FFP use by ICU clinicians, and a high proportion of current FFP transfusions are of unproven clinical benefit. Better evidence from clinical trials could significantly alter patterns of use and modify current treatment costs.

Restrictive versus liberal transfusion strategies for older mechanically ventilated critically ill patients: a randomized pilot trial.

Objectives:To compare hemoglobin concentration (Hb), RBC use, and patient outcomes when restrictive or liberal blood transfusion strategies are used to treat anemic (Hb ⩽ 90 g/L) critically ill patients of age ≥ 55 years requiring ≥ 4 days of mechanical ventilation in ICU. Design:Parallel-group randomized multicenter pilot trial. Setting:Six ICUs in the United Kingdom participated between August 2009 and December 2010. Patients:One hundred patients (51 restrictive and 49 liberal groups). Interventions:Patients were randomized to a restrictive (Hb trigger, 70 g/L; target, 71–90 g/L) or liberal (90 g/L; target, 91–110 g/L) transfusion strategy for 14 days or the remainder of ICU stay, whichever was longest. Measurements and Main Results:Baseline comorbidity rates and illness severity were high, notably for ischemic heart disease (32%). The Hb difference among groups was 13.8 g/L (95% CI, 11.5–16.0 g/L); p < 0.0001); mean Hb during intervention was 81.9 (SD, 5.1) versus 95.7 (6.3) g/L; 21.6% fewer patients in the restrictive group were transfused postrandomization (p < 0.001) and received a median 1 (95% CI, 1–2; p = 0.002) fewer RBC units. Protocol compliance was high. No major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications were observed during intensive care and hospital follow-up. Mortality at 180 days postrandomization trended toward higher rates in the liberal group (55%) than in the restrictive group (37%); relative risk was 0.68 (95% CI, 0.44–1.05; p = 0.073). This trend remained in a survival model adjusted for age, gender, ischemic heart disease, Acute Physiology and Chronic Health Evaluation II score, and total non-neurologic Sequential Organ Failure Assessment score at baseline (hazard ratio, 0.54 [95% CI, 0.28–1.03]; p = 0.061). Conclusions:A large trial of transfusion strategies in older mechanically ventilated patients is feasible. This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice.

Prevalence, management, and outcomes of critically ill patients with prothrombin time prolongation in United Kingdom intensive care units.

Objective:Coagulopathy occurs frequently in critically ill patients, but its epidemiology, current treatment, and relation to patient outcome are poorly understood. We described the prevalence, risk factors, and treatment of prolongation of the prothrombin time in critically ill patients using the international normalized ratio to standardize data and explored its association with intensive care unit survival. Design:Prospective multiple center observational cohort study. Setting:Twenty-nine adult intensive care units in the United Kingdom. Patients:All sequentially admitted patients over an 8-wk period. Interventions:None. Measurements and Main Results:Prospective daily data were collected concerning prevalence, predefined risk factors, and treatment of coagulopathy throughout intensive care unit admission. Of 1923 intensive care unit admissions, 30% developed abnormal international normalized ratio values (defined as an international normalized ratio >1.5). Most international normalized ratio abnormalities were minor and short-lived (73% of worst international normalized ratio values 1.6–2.5). Male sex, chronic liver disease, sepsis, warfarin therapy, increments in Acute Physiology and Chronic Health Evaluation II score, severity of renal and hepatic dysfunction, and red cell transfusions were all independent risk factors for international normalized ratio abnormalities (all p < .001). In all regression models, there was a strong independent association between abnormal international normalized ratio values and greater intensive care unit mortality (p < .0001), particularly when international normalized ratio increased after intensive care unit admission. Among patients with abnormal international normalized ratios, 33% received fresh-frozen plasma transfusions during their intensive care unit stay, but the pretransfusion international normalized ratio value varied widely. Fifty-one percent of fresh-frozen plasma treatments were to nonbleeding patients and 40% to nonbleeding patients whose international normalized ratio was normal or only modestly deranged (≤2.5). The dose of fresh-frozen plasma administered was highly variable (median dose 10.8 mL/kg−1 (first, third quartile 7.2, 14.4; range, 2.4–41.1 mL/kg−1). Conclusions:Prothrombin time prolongation is prevalent in critically ill patients and is independently associated with greater intensive care unit mortality. Wide variation in fresh-frozen plasma treatment exists suggesting clinical uncertainty regarding best practice, particularly as a prophylactic treatment.

Thrombocytopenia and platelet transfusion in UK critical care: a multicenter observational study.

BACKGROUND: Platelet (PLT) transfusions are widely used, but few studies have described patterns of use in critical care.

Multicentre cohort study of red blood cell use for revision hip arthroplasty and factors associated with greater risk of allogeneic blood transfusion

BACKGROUND Revision hip arthroplasty (RHA) is associated with high rates of allogeneic blood transfusion (ABT). We aimed to determine factors associated with ABT in patients undergoing RHA in Scottish hospitals, with particular focus on perioperative cell salvage (PCS). METHODS A prospective observational cohort study of RHA procedures performed in 11 hospitals over 7 months was performed. We recorded predefined patient, surgery-related, and blood conservation factors that may influence perioperative ABT, together with postoperative haemoglobin (Hb) data and ABTs to day 7. We explored factors with strongest independent association with ABT during the perioperative period using multiple regression analysis. RESULTS Two hundred and ten cases were studied, of whom 58% received ABTs (mean 1.8 units), most of which (52%) occurred on the day of surgery. Eighty-eight (42%) patients received PCS, of whom 68 had red cells re-infused [mean re-infusion volume 312 ml (1st, 3rd quartile: 260, 363 ml)]. In unadjusted comparisons, patients receiving PCS had lower intraoperative (9% vs 40%) and total (55% vs 63%) exposure to ABTs. The mean (95% confidence interval) theatre blood loss was 1013 (899-1128) ml and was higher for combined femoral/acetabular revision and femoral revision than other categories. The mean postoperative Hb transfusion trigger was 80 g litre(-1). In multivariable models, preoperative Hb [odds ratio (OR) 0.35; P<0.001], patient weight (OR 0.96; P=0.004), operating theatre blood loss (OR 1.002; P<0.001), and re-infusion of PCS blood (OR 0.31; P=0.02) were independent predictors of ABT exposure. CONCLUSIONS PCS is an effective blood conservation strategy for RHA, especially for patients with preoperative anaemia, low body weight, or both.

Factors associated with prophylactic plasma transfusion before vascular catheterization in non-bleeding critically ill adults with prolonged prothrombin time: a case–control study

BACKGROUND Fresh-frozen plasma (FFP) is widely used in critically ill patients, despite a weak evidence base. Factors that influence the decision to transfuse FFP before intravascular catheter insertion are poorly described. METHODS We undertook a case-controlled study based on a prospective cohort study of 1923 admissions to 29 intensive care units in the UK. Non-bleeding patients with an international normalized ratio (INR) ≥1.5 who underwent intravascular catheterization, but no other invasive procedure, were identified. We compared patient characteristics, illness-related factors, and biochemical and haematological variables between patients who did or did not receive pre-procedural FFP. RESULTS One hundred and eighty-six patients fulfilled the criteria; 26 received FFP during the 24 h before line insertion (cases) and 160 did not (controls). Factors associated with greater use of prophylactic FFP by clinicians were pre-existing chronic liver disease (P=0.01), higher serum bilirubin before procedure (P=0.01), lower platelet count (P=0.01), higher activated partial thromboplastin time (P=0.001), lower fibrinogen (P=0.01), and concurrent red cell transfusion despite the absence of bleeding (P=0.001). There was no difference in pre-procedural INR [median (1st, 3rd quartile) cases: 1.95 (1.85, 2.6); controls 1.8 (1.6, 2.3); P=0.19]. The mean FFP dose was 11.1 ml kg(-1) (sd 5.7 ml kg(-1)); 53.8% of cases were transfused <10 ml kg(-1). CONCLUSIONS Chronic liver disease and more abnormal coagulation tests were associated with greater probability of pre-procedural FFP administration before vascular catheterization, whereas the severity of prothrombin time prolongation alone was not. FFP was more likely to be administered when red cells were also transfused, even in the absence of bleeding.

Interventions to reduce wrong blood in tube errors in transfusion: A systematic review

This systematic review addresses the issue of wrong blood in tube (WBIT). The objective was to identify interventions that have been implemented and the effectiveness of these interventions to reduce WBIT incidence in red blood cell transfusion. Eligible articles were identified through a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, Cinahl, BNID, and the Transfusion Evidence Library to April 2013. Initial search criteria were wide including primary intervention or observational studies, case reports, expert opinion, and guidelines. There was no restriction by study type, language, or status. Publications before 1995, reviews or reports of a secondary nature, studies of sampling errors outwith transfusion, and articles involving animals were excluded. The primary outcome was a reduction in errors. Study characteristics, outcomes measured, and methodological quality were extracted by 2 authors independently. The principal method of analysis was descriptive. A total of 12,703 references were initially identified. Preliminary secondary screening by 2 reviewers reduced articles for detailed screening to 128 articles. Eleven articles were eventually identified as eligible, resulting in 9 independent studies being included in the review. The overall finding was that all the identified interventions reduced WBIT incidence. Five studies measured the effect of a single intervention, for example, changes to blood sample labeling, weekly feedback, handwritten transfusion requests, and an electronic transfusion system. Four studies reported multiple interventions including education, second check of ID at sampling, and confirmatory sampling. It was not clear which intervention was the most effective. Sustainability of the effectiveness of interventions was also unclear. Targeted interventions, either single or multiple, can lead to a reduction in WBIT; but the sustainability of effectiveness is uncertain. Data on the pre- and postimplementation of interventions need to be collected in future trials to demonstrate effectiveness, and comparative studies are needed of different interventions.

Thrombocytopenia and platelet transfusion in UK critical care: a multicenter observational study: PLT TRANSFUSIONS IN CRITICAL CARE

BACKGROUND: Platelet (PLT) transfusions are widely used, but few studies have described patterns of use in critical care.

Thrombocytopenia and platelet transfusion in UK critical care

BACKGROUND: Platelet (PLT) transfusions are widely used, but few studies have described patterns of use in critical care.