A prospective study on the correlation between thromboelastometry and standard laboratory tests - influence of type of surgery and perioperative sampling times.

This prospective study aimed at investigating the influence of surgery type and perioperative sampling times on the correlations between rotational thromboelastometry (ROTEM) parameters and standard laboratory coagulation tests assessing comparable coagulation phases. Patients undergoing glioblastoma multiforme resection (GBR group, n = 60) or laparoscopic colon cancer resection (CCR group, n = 40) were prospectively included. Blood samples for ROTEM and laboratory assessments were consecutively drawn within 24-hours prior to surgery (baseline), and at 2, 24 and 48-hours after surgery. Correlations between perioperative ExTEM clotting-time (CT-exTEM) and prothrombin time (PT), and between FibTEM maximum clot firmness (MCF-fibTEM) with and plasma fibrinogen (pFB) concentration (Clauss method), were evaluated using the Spearman's rho test. The efficiency of recommended cut-offs of CT-exTEM (>75 s) and MCF-fibTEM (<10 mm) for predicting a prolonged PT (>15 s) or a low pFB (<2 g/L), respectively, was assessed using Receiver-Operator Characteristic curves. Correlations between CT-exTEM and PT were weak in GBR (rho = 0.25 [0.12-0.38], p < .01), and very weak in CCR (rho = 0.06 [-0.12-0.27]). Those between MCF-fibTEM and pFB, were strong in both GBR (rho = 0.69 [0.61-0.76], p < .01) and CCR (rho = 0.70 [0.60-0.78], p < .01). These correlations remained largely unchanged over the studied perioperative period in both groups. Recommended CT-exTEM and MCF-fibTEM cut-offs had poor sensitivity for predicting a prolonged PT (17% [8-31]) or a low pFB (46% [32-62]), without group-related differences. Neither the type of surgery nor the perioperative sampling times had a significant influence on the correlations between ROTEM parameters and standard laboratory tests. ClinicalTrials.gov ID: NCT02652897.

Relationship of thromboelastography and conventional clotting test values with severe bleeding in critically ill patients with coagulopathy: A prospective study.

INTRODUCTION: This study aimed to ascertain the associations of thromboelastography (TEG® ) and standard laboratory test (SLTs) values with the presence of bleeding in critically ill patients with known coagulopathy. METHODS: Three groups of coagulopathic patients with (a) hepatic failure, (b) postoperative period after prolonged cardiac surgery, and (c) complex abdominal surgery with sepsis were prospectively included in this study. On intensive care unit (ICU) admission, patients were stratified into two groups according to whether they had major bleeding (MB) (evident overt bleeding, important bleeding apparent on imaging studies, and/or need for moderate-massive blood transfusion and hemodynamic instability). Blood samples were drawn for the SLTs (international normalized ratio [INR], activated partial thromboplastin time [aPTT], platelet count, and fibrinogen level [Clauss]) and TEG whole blood coagulation assays. Receiver operating characteristic (ROC) curves were generated to determine the efficiency of TEG and SLTs for detecting bleeding. The correlations between SLTs and TEG parameters with similar coagulation profiles were evaluated by Spearman rank-order analysis. RESULTS: Eighty-three patients were included, and bleeding was confirmed in 45 (54%). The fibrinogen level demonstrated the best accuracy for detecting bleeding with an area under the curve and 95% confidence intervals [AUC (95% CI)] of 0.74 (0.63-0.85) with the best cutoff value of ≤ 2 g/L. Regarding TEG-MA, the AUC (CI) obtained with the optimal cutoff value of ≤ 51 mm was 0.68 (0.56-0.80). CONCLUSIONS: Both conventional clotting tests and TEG values were poorly associated with bleeding in this critically ill cohort of patients with coagulopathy.

Reliability of the portable coagulometer qLabs to accurately measure the activated thromboplastin time and international normalized ratio: a prospective study in critically ill patients.

: The current prospective study was aimed at investigating whether a portable coagulometer (qLabs) can be used to reliably monitor activated thromboplastin time (aPTT) and international normalized ratio (INR) in critically ill patients, as compared with standard central laboratory measurement. Both precision and accuracy of INR and aPTT measured by qLabs were assessed in this observational study by finger prick group (N = 30 patients) and blood droplet group from central venous catheter drawn (N = 60). For accuracy, clinical agreement percentage was ±0.3 for INR and ±10 s for aPTT. Precision of INR measurement in qLabs showed excellent intraclass correlation coefficient (ICC > 90%). Precision of aPTT measurement in qLabs was less acceptable for both finger prick [ICC: 0.70; Bland-Altman plot: 2.2 s (-19.8, 24.2)] and blood droplet [ICC: 0.50; Bland-Altman plot: 0.4 s (-70.9, 71.8)] groups. Accuracy of qLabs was acceptable for INR assessment (clinical agreement 90 and 81%, for finger prick and blood droplet groups, respectively), but not for aPTT (clinical agreement 55 and 68%, respectively). Accuracy of finger prick and blood droplet measurements in qLabs was better for INR and aPTT values near-to-normal (1.2 and 37 s, respectively). INR values from qLabs were consistent with the 'gold standard'. qLabs measurement is only reliable for aPTT values near-to-normal.

Red Blood Cell Transfusion Guided by Near Infrared Spectroscopy in Neurocritically Ill Patients with Moderate or Severe Anemia: A Randomized, Controlled Trial.

In neurocritically ill patients (NCPs), the use of hemoglobin level as the sole indicator for red blood cell transfusion (RBCT) can result in under- or over-transfusion. This randomized controlled trial was conducted to ascertain whether a transcranial oxygen saturation (rSO2) threshold, as measured by near-infrared spectroscopy, reduces RBCT requirements in anemic NCPs (closed traumatic brain injury, subarachnoid, or intracerebral hemorrhage), compared with a hemoglobin threshold alone. Patients with hemoglobin 70-100 g/L received RBCTs to attain an rSO2 > 60% (rSO2 arm) or to maintain hemoglobin between 85 and 100 g/L (hemoglobin arm). A total of 102 NCPs (51 in each group) were included in the intention-to-treat analysis, and 97 were included in the per-protocol analysis (51 and 46, respectively). Compared with those from the hemoglobin arm, patients in rSO2 arm received fewer RBC units (1.0 ± 0.1 vs. 1.5 ± 1.4 units/patient; p < 0.05) and showed lower hemoglobin levels while in protocol. There were no differences between the study arms regarding the percentage of transfused patents (59% vs. 71%; relative risk 0.83 [95% CI 0.62-1.11]), stay on neurocritical care unit (21 vs. 20 days), unfavorable Glasgow Outcome Scale scores on hospital discharge (57% vs. 71%), in-hospital mortality (6% vs. 10%), or 1 year mortality (24% vs. 24%). Among NCPs with hemoglobin concentrations of 70-85 g/L, withholding transfusion until rSO2 is <60% may result in reduced RBCs requirements compared with routinely transfusing to attain a hemoglobin level >85 g/L. Further studies are required to confirm this finding and its possible impact on clinically significant outcomes.

Effects of Red Blood Cell Transfusion on Long-Term Disability of Patients with Traumatic Brain Injury.

BACKGROUND: This 3-year prospective study examined the association between red blood cell transfusion (RBCT) and 1-year neurocognitive and disability levels in 309 patients with traumatic brain injury (TBI) admitted to the neurological intensive care unit (NICU). METHODS: Using a telephone interview-based survey, functional outcomes were assessed by the Glasgow Outcome Scale (GOS), Rancho Los Amigos Levels of Cognitive Functioning Scale (RLCFS), and Disability Rating Scale (DRS) and dichotomized as favorable and unfavorable (dependent variable). The adjusted influence of RBCT on unfavorable results was assessed by conventional logistic regression, controlling for illness severity and propensity score (introduced as a continuous variable and by propensity score-matched patients). RESULTS: Overall, 164 (53 %) patients received ≥1 unit of RBCT during their NICU stay. One year postinjury, transfused patients exhibited significantly higher unfavorable GOS (46.0 vs. 22.0 %), RLCFS (37.4 vs. 15.4 %), and DRS (39.6 vs. 18.7 %) scores than nontransfused patients. Although transfused patients were more severely ill upon admission, their adjusted odds ratios (95 % confidence intervals) for unfavorable GOS, RLCFS, and DRS scores were 2.5 (1.2-5.1), 3.0 (1.4-6.3), and 2.3 (1.1-4.8), respectively. These odds ratios remained largely unmodified when the calculated propensity score was incorporated as an independent continuous variable into the multivariate analysis. Furthermore, in 76 pairs of propensity score-matched patients, the rate of an unfavorable RLCFS score at the 1-year (but not 6-month) follow-up was significantly higher in transfused than nontransfused patients [3.0 (1.1-8.2)]. CONCLUSION: Our results strongly suggest an independent association between RBCT and unfavorable long-term functional outcomes of patients with TBI.

Administration of fibrinogen concentrate for refractory bleeding in massively transfused, non-trauma patients with coagulopathy: a retrospective study with comparator group.

BACKGROUND: This retrospective, single centre study was conducted to investigate the efficacy of fibrinogen concentrate (FBNc) in decreasing blood requirements and reaching optimal fibrinogen level, in non-trauma, massively transfused, bleeding patients with coagulopathy. METHODS: Over a 3-years period, all patients for whom a massive transfusion protocol was activated and had received ≥ 4 units of allogeneic blood components within a ≤ 4 h period, were included. Patients were classified according to whether they received FBNc or achieved an optimal fibrinogen level of ≥ 2 g/L within 24 h after FBNc administration. RESULTS: Seventy-one patients received 2 [2,4] g of FBNc (FBNc group) and 72 did not (comparator group). FBNc was administered after transfusing 5 [5,9] blood component units, 3 [2,6] hours after massive transfusion protocol activation. Linear regression analysis showed that SOFA (AOR 0.75 [95% CI:0.08-1.43]) and admission fibrinogen level (AOR -2.7 [95% CI:-4.68 - -0.78]), but not FBNc administration, were independently associated with total transfused units. There was a significant inverse relation between both admission and target fibrinogen levels, and total transfused components. Logistic regression showed a direct relationship between admission fibrinogen level and achieving a target level ≥ 2 g/L (AOR 3.29 [95% CI;1.95-5.56]). No thromboembolic events associated with FBNc were observed. CONCLUSIONS: In massively transfused, non-trauma patients with coagulopathy and refractory bleeding, late administration of low FBNc dosage was not associated with decreased blood transfusion or increased post-infusion fibrinogen level. Given that both fibrinogen upon admission and target fibrinogen levels were associated with decreased blood transfusion, earlier administration and higher doses of FBNc could be needed.

Efficacy of the prothrombin complex concentrate prothromplex in patients requiring urgent reversal of vitamin K antagonists or presenting with uncontrolled bleeding: a retrospective, single center study.

The objective of the present study was to investigate the efficacy of a four-factor prothrombin complex concentrate (Prothromplex, PTX) in shortening prolonged international normalized ratio or controlling life-threatening bleeding. The study was a retrospective single-centre study that included 142 patients treated with PTX and allocated in three groups: patients on vitamin K antagonists (VKA) (acenocumarol) and undergoing invasive procedure or presenting with severe bleeding (n = 76), patients treated with VKA presenting with intracranial haemorrhage (n = 22), and patients not on VKA and presenting with uncontrolled bleeding (n = 44). The primary outcome variable was international normalized ratio (INR) return to the norm after PTX infusion. Secondary outcome variables included bleeding control and reduction of transfusion rate. Overall, patients received a median of 1200 IU (≈15 IU/kg) of PTX, and INR decreased from 4 ±â€Š3 to 1.7 ±â€Š1.2 (P < 0.01) in all groups, although it remained at least 1.4 in 38% of patients (29.3% among patients receiving 25 IU/kg vs. 42.6% among those receiving 15 IU/kg; P < 0.05). Patients with initial INR at least 4 benefited the most from treatment. After PTX administration, there was a significant reduction in both transfused blood components units (P < 0.01) and estimated blood loss volume (from 1500 ±â€Š1500 to 200 ±â€Š100 ml; P < 0.01), and only one episode of deep venous thrombosis was observed. Administration of fixed doses of PTX shortened prolonged international normalized ratio and improved life-threatening bleeding in patients with or without VKA therapy. Higher dose attained a more adequate post-infusion INR.

Red blood cell transfusion in non-bleeding critically ill patients with moderate anemia: is there a benefit?

PURPOSE: This study was undertaken to investigate the efficacy of red blood cell transfusion (RBCT) at reversing the deleterious effects of moderate anemia in critically ill, non-bleeding patients. METHODS: This was a retrospective, pair-matched (ratio 1:1) cohort study. Non-bleeding critically ill patients with moderate anemia (nadir hemoglobin level between 70 and 95 g/l), admitted to the ICU over a 27-month period, were included. Anemic patients were included upon meeting five matching criteria of having the same nadir hemoglobin (±5 g/l), APACHE II score (±5), SOFA score (±2), admission diagnostic group, and age (±5 years). Outcome events occurring over the whole ICU stay and after RBCT were collected. After hospital discharge, all patients had a 2-year follow-up period. RESULTS: Two hundred fourteen non-transfused anemic patients (NTAPs) were successfully matched with 214 transfused anemic patients (TAPs). In addition to the matching criteria, at baseline, both groups were homogenous with respect to multiple comorbidities. Compared with TAPs, NTAPs showed significantly lower rates of hospital mortality (21 vs.13 %, respectively; p < 0.05) and ICU re-admission (7.4 vs. 1.9 %, respectively; p < 0.05). Additionally, NTAPs had significantly lower rates of nosocomial infection (12.9 vs. 6.7 %, respectively; p < 0.05) and acute kidney injury (24.8 vs. 16.7 %, respectively; p < 0.05). Similar results were obtained in subgroup analysis where only more anemic patients (68 matched pairs) or patients with cardiovascular comorbidities (63 matched pairs) were considered. CONCLUSIONS: RBCT does not improve the clinical outcome in non-bleeding critically ill patients with moderate anemia.

Impact of national transfusion indicators on appropriate blood usage in critically ill patients.

BACKGROUND: The objective was to investigate the impact of three national blood transfusion indicators (NBTIs) specifically designed for critical care regarding the appropriate blood transfusion indications. STUDY DESIGN AND METHODS: This was a prospective, single-center study, carried out at a university hospital. A total of 1808 patients admitted to the intensive care unit (ICU) in 1 year were included. RESULTS: The study consisted of four 90-day periods (P). P1 was a control period with no intervention. P2 followed the inclusion of NBTIs into the ICU database, aimed at reinforcing NBTI knowledge. After presenting and discussing the results of P1 and P2, the early (P3) and late (P4) impacts of NBTI knowledge were evaluated. All patients who were transfused with at least 1 unit of any blood component (33.3%) were included. Thirteen percent of red blood cell transfusions (RBCTs) were given outside of NBTI protocols (13% deviation of NBTIs for RBCTs) without a significant change throughout the duration of the study. Most RBCTs (95%) were prescribed for a hemoglobin threshold of less than 90 g/L. There was a steady and significant improvement in the adherence to NBTI guidelines for platelet concentrate transfusions (PCTs) from 36% (P1) to 52% (P4; p < 0.01). In contrast, the lack of adherence to NBTI guidelines for fresh-frozen plasma transfusions (FFPTs) remained high (74%) and stable throughout the study period. The most frequent reason for inappropriate use of FFPTs or PCTs was absence of severe bleeding. CONCLUSION: The introduction of NBTI guidelines demonstrated a variable impact on the appropriateness of blood component transfusions in critically ill patients.

Gender influences cerebral oxygenation after red blood cell transfusion in patients with severe traumatic brain injury.

BACKGROUND: Important differences with respect to gender exist in the prognosis and mortality of traumatic brain injury (TBI) patients. The objective of this study was to assess the role of gender as an independent factor in cerebral oxygenation variations following red blood cell transfusion (RBCT). METHODS: This retrospective analysis of a prospective study was conducted on patients with severe TBI. Hemoglobin levels were measured at baseline and 6 h after transfusion. Brain tissue oxygen pressure (PbrO(2)), cerebral perfusion pressure (CPP), intracranial pressure (ICP), and mean arterial pressure (MAP) were measured at baseline, at the end of RBCT and at 1, 2, 3, 4, 5, and 6 h after transfusion. After the patients were stratified into two groups according to gender, the effect of RBCT on PbrO(2) (cerebral oxygenation) was analyzed using a multivariate analysis of variance with repeated measures (MANOVA). The MANOVA was repeated after adjusting for all covariables with baseline differences between groups. RESULTS: At baseline, we found differences in age (P = 0.01), weight (P = 0.03), MAP (P = 0.01), ISS (P = 0.05), and CCP (P = 0.01) between the groups. After adjusting for these co-variables, we observed that gender and age were related to the increase in PbrO(2) (P = 0.05 and P = 0.04, respectively). CONCLUSIONS: Our results suggest that the effect of RBCT on cerebral oxygenation, as measured by PbrO(2), is greater in women than in men.

Invasive and noninvasive assessment of cerebral oxygenation in patients with severe traumatic brain injury.

PURPOSE: The aim of this study is to investigate the relationship between invasive brain tissue oxygen pressure (PbrO(2)) and noninvasive regional transcranial oxygen saturation (rSO(2)) in 22 stable patients with severe traumatic brain injury (TBI) during a 16 h period. METHODS: This was a prospective, observational study carried out in the Neurocritical Care Unit of a level 1 trauma center in a teaching hospital. A total of 41,809 paired records for neuromonitoring variables were analyzed and compared. RESULTS: A direct and independent correlation between rSO(2) and PbrO(2) was confirmed through adjusted [beta coefficient and (95% confidence interval, CI) = 0.36 (0.35-0.37)] and logistic [PbrO(2) >or=15 mmHg, as a dependent variable; adjusted odds ratio (AOR) and (95% CI) = 1.11 (1.10-1.12)] regression analyses. A receiver-operating characteristic (ROC) curve demonstrated that rSO(2) had low accuracy for detecting moderate (PbrO(2)

Impact of age of transfused blood on cerebral oxygenation in male patients with severe traumatic brain injury.

OBJECTIVE: Prolonged erythrocyte storage time might reduce the efficacy of transfusion. In this study, the effects of transfusion of erythrocytes with four different storage periods (<10 days, n = 18; 10-14 days, n = 15; 15-19 days, n = 17; and >19 days, n = 16 patients) on brain tissue oxygen tension (PtiO2) in stable male patients with severe traumatic brain injury were investigated during a 24-hr follow-up period. DESIGN: Prospective, observational study. SETTING: Neurotrauma critical care unit of a university hospital. PATIENTS: Sixty-six male, nonbleeding, hemodynamically stable anemic patients (hemoglobin <95 g/L) with Glasgow Coma Scale score <9. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PtiO2, cerebral perfusion pressure, mean arterial pressure, intracranial pressure, peripheral oxygen saturation, CO2 pressure at the end of expiration, and intracerebral temperature were recorded in all patients at baseline, immediately after the completion of transfusion, and 1, 2, 3, 4, 5, 6, 12, and 24 hrs posttransfusion. All four groups were homogeneous with respect to multiple baseline variables, except for storage time of transfused erythrocytes (p < .0001). There was a significant short-lasting (3-4 hrs) increase in PtiO2 values after transfusion of erythrocytes stored for <10 days, 10-14 days, or 15-19 days, compared with those at baseline. In contrast, no significant changes in PtiO2 were observed after transfusion of erythrocytes stored >19 days. CONCLUSIONS: Transfusion of erythrocytes increased cerebral oxygenation in patients with severe traumatic brain injury, except in those transfused with erythrocytes stored >19 days.

Transfusion of erythrocyte concentrates produces a variable increment on cerebral oxygenation in patients with severe traumatic brain injury: a preliminary study.

OBJECTIVE: To investigate the long-term influence of erythrocyte transfusion on cerebral oxygenation in patients with severe traumatic brain injury. DESIGN: Prospective and observational study. SETTING: Neurotrauma intensive care unit of trauma center level I. PATIENTS: Sixty consecutive, hemodynamically stable patients with severe traumatic brain injury, pretransfusion hemoglobin<100g/l, non-bleeding and monitored through intracranial pressure and brain tissue partial pressure of oxygen (PtiO(2)) catheters were included. INTERVENTIONS: Transfusion of 1-2 units of red blood cells. MEASUREMENTS AND RESULTS: Ten sets of variables (pretransfusion, end of transfusion, and 1, 2, 3, 4, 5, 6, 12 and 24h after transfusion) were recorded, including: PtiO(2), cerebral perfusion pressure (CPP), end-tidal CO(2), peripheral saturation of oxygen, temperature, hemoglobin, lactate and PaO(2)/FiO(2) ratio. Transfusion was associated with an increase in PtiO(2) during a 6-h period, with a peak at 3h (26.2%; p=0.0001) in 78.3% of the patients. No relationship was observed between PtiO(2), CPP and hemoglobin increments. The relative increment in PtiO(2) at hour 3 was only correlated with baseline PtiO(2) (r(2) 0.166; p=0.001). All of the patients with basal PtiO(2)<15mmHg showed an increment in PtiO(2) versus 74.5% of patients with basal PtiO(2)>or=15mmHg (p<0.01, hour 3). CONCLUSIONS: Erythrocyte transfusion is associated with a variable and prolonged increment of cerebral tissue oxygenation in anemic patients with severe traumatic brain injury. Low baseline PtiO(2) levels (<15mmHg) could define those patients who benefit the most from erythrocyte transfusion.