Abstract

Severely injured trauma patients are often coagulopathic and early hemostatic resuscitation is essential. Previous studies have revealed linear relationships between thrombelastography (TEG(®)) five- and ten-min amplitudes (A5 and A10), and maximum amplitude (MA), using TEG(®) 5000 technology. We aimed to investigate the performance of A5 and A10 in predicting low MA in severely injured trauma patients and identify optimal cut-off values for hemostatic intervention based on early amplitudes, using the cartridge-based TEG(®) 6s technology. Adult trauma patients with hemorrhagic shock were included in the iTACTIC randomized controlled trial at six European Level I trauma centers between 2016 and 2018. After admission, patients were randomized to hemostatic therapy guided by conventional coagulation tests (CCT) or viscoelastic hemostatic assays (VHA). Patients with available admission-TEG(®) 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG(®) and RapidTEG(®), and <17 mm for TEG(®) functional fibrinogen (FF). One hundred eighty-seven patients were included. Median time to MA was 20 (Kaolin TEG(®)), 21 (RapidTEG(®)) and 12 (TEG(®) FF) min. For Kaolin TEG(®), the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG(®) optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG(®) FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity). In summary, we found that TEG(®) 6s early amplitudes were sensitive and specific predictors of MA in severely injured trauma patients. Intervening on early amplitudes can save valuable time in hemostatic resuscitation.

Abstract

Rapid wound closure is important after arthroplasty procedures to prevent postoperative complications. Platelets are rich in growth factors and leukocytes contribute to innate immunity. We hypothesized that topical leukocyte platelet-rich plasma (L-PRP) derived from the blood of patients would be beneficial to wound healing. In this randomized controlled trial, patients subjected to elective total hip arthroplasty (THA) were assigned by concealed allocation either L-PRP application onto the sutured fascia or no application (control) after the THA intervention. In addition, all patients received 1.5 g protein/kg, 5 g L-arginine, 500 mg vitamin C and 44 mg zinc daily over the 4-week postoperative period to obtain optimal nutrition. The primary endpoint was complete healing of the skin incision. The secondary endpoints were blood transfusions, length of hospital stay, pain and wound infections. Sixteen patients in the L-PRP group and 17 patients in the control group completed the trial. L-PRP treatment accelerated complete wound healing after 3 weeks (seven in the L-PRP group vs. zero in the control group, p = 0.003) and after 4 weeks (12 in the L-PRP group vs. six in the control group, p = 0.037). No postoperative superficial wound infections occurred within 4 weeks, and there were no significant differences in the other secondary outcomes. L-PRP generated in 10 sex-matched healthy volunteers revealed increased concentrations of platelets (5.8-fold) and leukocytes (2.3-fold) compared with those in whole blood. Furthermore, the concentration of keratinocyte mitogen epidermal growth factor in L-PRP (380 ± 130 pg/ml, mean ± SD) was higher (p < 0.001) than that in serum (130 ± 26 pg/ml). In conclusion, a single intraoperative local application of L-PRP promoted wound healing after THA, possibly mediated by EGF receptor agonists.

Abstract

PURPOSE Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Abstract

OBJECTIVES To evaluate whether the donation of 900 mL of blood reduces the central blood volume (CBV) assessed by thoracic electrical impedance (TI) and plasma pro-atrial natriuretic peptide (proANP). BACKGROUND Donation of 450 mL of blood carries a 1% risk of a vasovagal reaction. Withdrawal of 900 mL of blood decreases cardiac output; however, the effect on CBV remains unknown. METHODS/MATERIALS A randomised, single-blinded, placebo-controlled, crossover design was used, where 21 healthy semi-recumbent men donated 2 × 450 mL blood or were sham-phlebotomised. Changes in CBV were estimated by proANP and TI at 1.5 (TI(1.5) ) and 100 (TI(100) ) kHz, reflecting extracellular volume and (regional) total body water, respectively, and the index value (IDX; 1/T(1.5) -1/TI(100) ) was used to estimate changes in intracellular (red cell) volume. Systolic, diastolic and mean arterial blood pressure; heart rate; stroke volume; cardiac output; and systemic vascular resistance were monitored. After completion of the study, 1000 mL of isotonic saline was infused. RESULTS Changes (mean% ± SD) in TI(1.5) , TI(100) and IDX were similar after 450 mL (-0.2 ± 1.6%, 0.0 ± 1.1%, -0.4 ± 10.1%) and 900 mL (0.1 ± 1.6%, 0.2 ± 1.5% and -2.0 ± 15.8%) of blood donation compared to after a sham donation of 450 mL (-0.9 ± 1.2%, -0.5 ± 1.5% and -0.1 ± 6.1%) and 900 mL (-1.2 ± 1.5%, -0.6 ± 1.3% and 0.5 ± 9.9%). In addition, changes in plasma proANP were similar after 450 and 900 mL of blood donation (-0.8 ± 6.7% and -7.6 ± 7.9%) as after sham donations (1.3 ± 7.3% and -4.5 ± 5.6%). Monitoring haemodynamic variables revealed that stroke volume decreased after the donation of 900 mL of blood (-12 ± 12 mL) compared to sham donations. CONCLUSION During a 900-mL blood loss in semi-recumbent men, CBV measured by TI and plasma proANP is not affected.

Abstract

Major burn surgery is often associated with excessive bleeding and massive transfusion, and the development of a coagulopathy during major burn surgery is associated with increased morbidity and mortality. The aim of this study was to review the literature on intraoperative haemostatic resuscitation of burn patients during necrectomy to reveal strategies applied for haemostatic monitoring and resuscitation. We searched PubMed, EMBASE, and CENTRAL for studies published in the period 2006-2017 concerning bleeding issues related to burn surgery i.e. coagulopathy, transfusion requirements and clinical outcomes. In a broad search, a total of 1375 papers were identified. 124 of these fulfilled the inclusion criteria, and six of these were included for review. The literature confirmed that transfusion requirements increases with burn injury severity and that haemostatic monitoring by TEG((R)) (thrombelastography) or ROTEM((R)) (rotational thromboelastometry) significantly decreased intraoperative transfusions and was useful in predicting and goal-directing haemostatic therapy during excision surgery. Resuscitation of bleeding during major burn surgery in many instances was neither standardized nor haemostatic. We suggest that resuscitation should aim for normal haemostasis during the bleeding phase through close haemostatic monitoring and resuscitation. Randomised controlled trials are highly warranted to confirm the benefit of this concept.

Abstract

PURPOSE Patients in the intensive care unit (ICU) are often transfused with red blood cells (RBC). During storage, the RBCs and storage medium undergo changes, which may have clinical consequences. Several trials now have assessed these consequences, and we reviewed the present evidence on the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients. METHODS We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials including adult ICU patients transfused with fresher versus older or standard issue blood. RESULTS We included seven trials with a total of 18,283 randomised ICU patients; two trials of 7504 patients were judged to have low risk of bias. We observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97-1.11; 7349 patients; TSA-adjusted CI 0.93-1.15), adverse events (1.26, 0.76-2.09; 7332 patients; TSA-adjusted CI 0.16-9.87) or post-transfusion infections (1.07, 0.96-1.20; 7332 patients; TSA-adjusted CI 0.90-1.27). The results were unchanged by including trials with high risk of bias. TSA confirmed the results and the required information size was reached for mortality for a relative risk change of 20%. CONCLUSIONS We may be able to reject a clinically meaningful effect of RBC storage time on mortality in transfused adult ICU patients as our trial sequential analyses reject a 10% relative risk change in death when comparing fresher versus older blood for transfusion.

Abstract

BACKGROUND Management of the critically bleeding patient can be encountered in many medical and surgical settings. Common for these patients is a high risk of dying from exsanguination secondary to developing coagulopathy. The purpose of this meta-analysis was to systematically review and assess randomised controlled trials (RCTs) performed on patients in acute need for blood transfusions due to bleeding to evaluate the effect of viscoelastic haemostatic assay (VHA) guidance on bleeding, transfusion requirements and mortality. METHODS PubMed and EMBASE were searched for RCTs that 1) randomised patients into receiving transfusions based on either a VHA-guided (thromboelastography [TEG] or rotational thromboelastometry [ROTEM]) algorithm (intervention group) or at the clinician's discretion and/or based on conventional coagulation tests (control group) and 2) adequately reported on the outcomes bleeding and/or transfusions and/or mortality. Data on bleeding, transfusions and mortality were extracted from each trial and included in a meta-analysis. RESULTS Fifteen RCTs (n = 1238 patients) were included. Nine trials referred to cardiothoracic patients, one to liver transplantation, one to surgical excision of burn wounds and one to trauma. One trial was conducted with cirrhotic patients, one with patients undergoing scoliosis surgery while one trial randomised treatment in post-partum females presenting with bleeding. The amount of transfused red blood cells (RBCs), fresh frozen plasma (FFP) and bleeding volume was found to be significantly reduced in the VHA-guided groups, whereas no significant difference was found for platelet transfusion requirements or mortality.

Abstract

OBJECTIVES The primary objective of this feasibility study was to identify quality of life (QoL) scores and symptom scales as tools for measuring patient-reported outcomes (PRO) associated with haemoglobin level in chemotherapy-treated cancer patients. Secondary objectives included comparing QoL and symptoms between randomisation arms. BACKGROUND Anaemia in cancer patients undergoing chemotherapy is associated with decreased QoL. One treatment option is red blood cell transfusion (RBCT). However, the optimal haemoglobin trigger for transfusion is unknown. METHODS Patients were randomised to a haemoglobin trigger for RBCT of either < 9.7 g dL-1 (arm A) or < lower normal level, female: 11.5 g dL-1 , male: 13.1 g dL-1 (arm B). Four PROs were used: Functional Assessment of Cancer Therapy-General (FACT-G) and the FACT-Anaemia (FACT-An), a Numeric Rating Scale on symptoms of anaemia and self-reported Performance Status (PS). The association between haemoglobin and PRO variables was assessed using a linear mixed model with random effects. RESULTS A total of 133 patients were enrolled, of which 86 patients received RBCT (28 in arm A, 58 in arm B). Baseline questionnaires were filled out in 79.7% of cases. Haemoglobin levels were significantly correlated with FACT-An, FACT-An Total Outcome Index (TOI), Functional Well-Being, fatigue and PS. Improvement on several PRO variables was observed in both arms after RBCT, with clinically minimal important differences observed in FACT-G, Physical Well-Being, FACT-An, FACT-An TOI, fatigue and dyspnoea. CONCLUSIONS QoL scores of physical and functional domains as well as self-reported anaemia-related symptoms correlated well with haemoglobin level in chemotherapy-treated cancer patients.

Abstract

BACKGROUND Capillary leakage, secondary to endothelial breakdown, is common in patients undergoing major surgical procedures with extensive tissue injury and this is associated with increased morbidity and mortality. Prostacyclin has been ascribed cytoprotective properties together with its vasodilatory and antiplatelet effects. The present pilot study investigated the safety and endothelial protective effects of low-dose prostacyclin infusion. PATIENTS AND METHODS A randomized placebo-controlled pilot study evaluating the effect of prostacyclin (iloprost) infusion (1.0 ng/kg/min) versus placebo (saline infusion) intraoperatively and 6 h postoperatively in patients undergoing a pancreaticoduodenoctemy was carried out. Hemodynamics were evaluated by Nexfin, hemostasis was evaluated by thrombelastography, and transfusion requirements were registered. Endothelial damage was evaluated by circulating sE-selectin, soluble thrombomodulin, and nucleosomes. RESULTS Comparable baseline demography and surgical time were found. Hemodynamics were comparable between groups. The placebo group received more red blood cells, median 115 ml [interquartile range (IQR): 0-296 ml] versus 0 ml (IQR: 0-0 ml), P=0.027, at the postoperative ward and after 6 h. Thrombelastography maximum clot firmness decreased intraoperatively only in the placebo group (P=0.034)). Soluble thrombomodulin increased more in the placebo group postoperatively [1.63 ng/ml (IQR: 0.65-2.55 ng/ml) versus 0.40 ng/ml (IQR: 0.21-0.63 ng/ml), P=0.027] and 6 h postoperatively [1.83 (1.1-2.36) versus 0.67 (0.42-0.91), P=0.027]. Nucleosomes increased intraoperatively and postoperatively only in the placebo group; thus, the overall level of nucleosomes was higher in the placebo group (P=0.019). CONCLUSION Intraoperative and postoperative low-dose prostacyclin infusion is safe and associated with reduced endothelial cell damage in patients undergoing a pancreaticoduodenoctemy compared with those receiving placebo.

Abstract

PURPOSE We assessed the predefined long-term outcomes in patients randomised in the Transfusion Requirements in Septic Shock (TRISS) trial. METHODS In 32 Scandinavian ICUs, we randomised 1005 patients with septic shock and haemoglobin of 9 g/dl or less to receive single units of leuko-reduced red cells when haemoglobin level was 7 g/dl or less (lower threshold) or 9 g/dl or less (higher threshold) during ICU stay. We assessed mortality rates 1 year after randomisation and again in all patients at time of longest follow-up in the intention-to-treat population (n = 998) and health-related quality of life (HRQoL) 1 year after randomisation in the Danish patients only (n = 777). RESULTS Mortality rates in the lower- versus higher-threshold group at 1 year were 53.5 % (268/501 patients) versus 54.6 % (271/496) [relative risk 0.97; 95 % confidence interval (CI) 0.85-1.09; P = 0.62]; at longest follow-up (median 21 months), they were 56.7 % (284/501) versus 61.0 % (302/495) (hazard ratio 0.88; 95 % CI 0.75-1.03; P = 0.12). We obtained HRQoL data at 1 year in 629 of the 777 (81 %) Danish patients, and mean differences between the lower- and higher-threshold group in scores of physical HRQoL were 0.4 (95 % CI -2.4 to 3.1; P = 0.79) and in mental HRQoL 0.5 (95 % CI -3.1 to 4.0; P = 0.79). CONCLUSIONS Long-term mortality rates and HRQoL did not differ in patients with septic shock and anaemia who were transfused at a haemoglobin threshold of 7 g/dl versus a threshold of 9 g/dl. We may reject a more than 3 % increased hazard of death in the lower- versus higher-threshold group at the time of longest follow-up.