Clinical guideline on reversal of direct oral anticoagulants in patients with life threatening bleeding.

BACKGROUND: Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. DESIGN: A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. RESULTS: So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DISCUSSION: DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. CONCLUSION: In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.

Dosing of tranexamic acid in trauma.

PURPOSE OF REVIEW: Tranexamic acid is routinely used as part of the management of traumatic bleeding. The dose recommendation in trauma was extrapolated from other clinical settings and the results of pragmatic randomized trials rather than pharmaco-kinetic and -dynamic evaluations. The review addresses current evidence on dosing of tranexamic acid in traumatized patients with a focus on efficacy, safety and risk-benefit profile. RECENT FINDINGS: A majority, but not all, of existing randomized clinical trials reports a reduction in mortality and/or blood loss with tranexamic acid administration. Increasing dose above the general recommendation (1 g bolus + 1 g infusion/8 h intravenously) has not been shown to further increase efficacy and could potentially increase side effects. SUMMARY: The benefit of tranexamic acid as adjuvant therapy in the management of bleeding trauma patients on mortality and transfusion requirements is clear and well documented, being most effective if given early and to patients with clinical signs of hemorrhagic shock. Recent reports suggest that in some patients presenting with a shutdown of their fibrinolytic pathway the administration of tranexamic acid could be associated with an increased risk of thromboembolic events and poor outcomes. A more personalized approach based on bedside assessment of fibrinolytic activation and pharmacokinetic-based dose regimen should be developed moving forward.

Arm lean mass determined by dual-energy X-ray absorptiometry is superior to characterize skeletal muscle and predict sarcopenia-related mortality in cirrhosis.

Sarcopenia worsens survival in patients with advanced liver disease including cirrhosis. In this study, we aimed to characterize skeletal muscle status by dual-energy X-ray absorptiometry (DXA) in patients with cirrhosis and examine the association between different skeletal muscle compartments and mortality. We included 231 men and 84 women (Child A, B, and C) with cirrhosis and 315 healthy matched controls (231 men and 84 women). Body composition was assessed with DXA. Appendicular skeletal muscle index (ASMI), arms index (AI), and legs index (LI) were calculated by normalizing lean mass to height squared. Low ASMI was defined as ASMI < 7.0 kg/m2 in men and <5.5 kg/m2 in women. Biochemical and hemodynamic data were recorded for cirrhotic patients and mortality data retrieved from registers. Low ASMI was more prevalent in both men (49%) and women (43%) with cirrhosis compared with healthy men (8%) and women (5%) (P < 0.001). ASMI and LI were lowest in Child B, whereas AI decreased gradually with advancing Child class. ASMI was inversely associated with mortality in men [HR = 0.74 (0.59-0.93), P < 0.01], and this was mainly driven by AI [HR = 0.37 (0.18-0.71), P < 0.01]. AI showed closer association than ASMI or LI to both the severity of liver disease and to mortality, which may be due to increasing prevalence of leg edema with disease progression in this population. Determination of arm lean mass may add information on survival in patients with cirrhosis.NEW & NOTEWORTHY Sarcopenia increases mortality in patients with end-stage liver disease. We show that arm lean mass determined by dual-energy X-ray absorptiometry is a better marker than the traditional appendicular skeletal muscle mass when predicting sarcopenia-related mortality in patients with cirrhosis of different severity. The findings add to the dispute about the optimal method for repeated assessments of skeletal muscle status in patients with cirrhosis and may have implications for clinical decision making.

Efficacy and Safety of Antifibrinolytic Drugs in Pediatric Surgery: A Systematic Review.

Antifibrinolytic drugs are used to reduce blood loss and subsequent transfusions during surgery and following trauma, but the optimal dosing regimen in the pediatric population is still unresolved. The aim of this systematic review was to evaluate efficacy and safety of antifibrinolytic drugs in pediatric surgery and trauma to determine the optimal dosing regimen. A literature search was performed in PubMed, Embase, Cochrane, and Web of Science on May 3, 2020. We included randomized controlled studies investigating the effect of tranexamic acid (TXA), aprotinin, and epsilon-aminocaproic acid, in terms of reducing blood loss, blood transfusions, reoperations, and rebleeds in pediatric patients aged 0 to 18 years undergoing cardiac surgery, noncardiac surgery, or trauma. Fifty randomized controlled trials (RCTs) were included; 28 RCTs investigated cardiac surgery and 22 investigated noncardiac surgery. No RCTs regarding trauma met the inclusion criteria. All antifibrinolytic drugs reduced postoperative blood loss and transfusions when used in pediatric surgery. The dosing regimen varied between studies, but similar effect sizes were found in terms of reduced blood loss regardless of the cumulative dose used. Few studies found adverse events, and no difference in incidence or type of adverse events was seen between the antifibrinolytic and the placebo group. In conclusion, use of antifibrinolytics is efficient and safe in children undergoing surgery. We propose TXA as the drug of choice based on its level of evidence and safety profile; we recommend a dosing regimen composed of a loading dose of 10 to 15 mg/kg prior to surgery followed by 1 to 5 mg/kg/h as continuous infusion throughout surgery.

Effect of tranexamic acid on markers of inflammation in children undergoing craniofacial surgery.

BACKGROUND: Tranexamic acid (TXA) reduces blood loss and transfusion requirements during craniosynostosis surgery in small children. Possible interaction from TXA on the inflammatory system is unknown. OBJECTIVE: To evaluate the effect of TXA on a wide range of inflammatory markers in children receiving TXA in a randomized, blinded, and placebo controlled study design. METHODS: Thirty children undergoing craniosynostosis surgery with significant blood loss received TXA (bolus dose of 10 mg kg-1 followed by 8 hours continuous infusion of 3 mg kg-1  h-1 ) or placebo in a randomized, double-blinded study design. Using a new proximity extension assays employing a panel of inflammatory biomarkers samples was used for analysis of blood samples obtained pre-operatively, 4 and 24 hours after operation. RESULTS: Ninety-two inflammatory parameters were measured. TXA did not affect any of the measured parameters as compared with placebo. Among 34 of the 92 pro- and antiinflammatory parameters investigated changes were observed between pre-operative, 4 or 24 hours, respectively, reflecting immune activation during surgical stress. CONCLUSION: TXA administration in a low-dose regimen including bolus followed by 8 hours infusion during craniosynostosis surgery did not change any of 92 inflammatory markers as compared with placebo.

Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shine-trauma trial.

BACKGROUND: Traumatic injury accounts for 800 000 deaths in the European Union annually. The main causes of deaths in trauma patients are exsanguination and multiple organ failure (MOF). We have studied >1000 trauma patients and identified shock-induced endotheliopathy (SHINE), the pathophysiological mechanism responsible for MOF and high mortality. Pilot studies indicate that low-dose iloprost (1 ng/kg/min) improves endothelial functionality in critically ill patients suggesting this intervention may improve patient outcome in traumatic SHINE. MATERIAL AND METHODS: This is a multicentre, randomized, blinded clinical investigator-initiated phase 2B trial in trauma patients with haemorrhagic shock-induced endotheliopathy. Patients are randomized 1:1 to 72 hours infusion of iloprost 1 ng/kg/min or Placebo (equal volume of saline). A total of 220 trauma patients will be included. The primary endpoint is the number of intensive care unit (ICU)-free days, within 28 days of admission. Secondary endpoints include 28- and 90-day all-cause mortality, hospital length of stay, vasopressor-free days in the intensive care unit (ICU) within 28 days, ventilator-free days in the ICU within 28 days, renal replacement-free days in the ICU within 28 days, number of serious adverse reactions and serious adverse events within the first 4 days of admission. DISCUSSION: This trial will test the safety and efficacy of administration of iloprost vs placebo for 72 hours in trauma patients with haemorrhagic shock-induced endotheliopathy. Trial endpoints focus on the potential effect of iloprost to reduce the need for ICU stay secondary to mitigation of organ failure. TRIAL REGISTRATION: SHINE-TRAUMA trial-EudraCT no. 2019-000936-24-Clinicaltrials.gov: NCT03903939 Ethics Committee no. H-19014482.

Patients' assessment of care for type 2 diabetes: Results of the Patient Assessment of Chronic Illness Care scale in a Danish population.

BACKGROUND: The Patient Assessment of Chronic Illness Care (PACIC) scale is the most appropriate for assessing self-reported experience in chronic care. We aimed to validate the PACIC questionnaire by (1) assess patients' perception of the quality of care for Danish patients with type 2 diabetes, (2) identify which factors are most important to the quality of care designated by the five subscales in PACIC, and (3) the validity of the questionnaire. METHODS: A survey of 7,745 individuals randomly selected from the National Diabetes Registry. Descriptive statistics inter-item and item-rest correlations and factor analysis assessed the PACIC properties. Quality of care was analysed with descriptive statistics; linear and multiple regression assessed the effect of forty-nine covariates on total and subscale scores. RESULTS: In total, 2,696 individuals with type 2 diabetes completed ≥ 50 % of items. The floor effect for individual items was 8.5-74.5 %; the ceiling effect was 4.1-47.8 %. Cronbach's alpha was 0.73-0.86 for the five subscales. The comparative fit index (CFI) and the Tucker-Lewis index (TLI) were 0,87, and 0,84, respectively. Mean PACIC score was 2.44 (± 0.04). Respondents, who receive diabetes care primarily at general practice and outpatient clinics had higher scores compared to those receiving care at a private specialist. Receiving rehabilitation was followed by higher scores in all subscales. Those 70 years or older had lower mean total and subscale scores compared to younger patient groups. A higher number of diabetes visits were associated with higher total scores; a higher number of emergency department visits were associated with lower total scores. The effects of healthcare utilisation on subscale scores varied. CONCLUSIONS: These results provide insight into variations in the quality of provided care and can be used for targeting initiatives towards improving diabetes care. Factors important to the quality of perceived care are having a GP or hospital outpatient clinic as the primary organization. Also having a higher number of visits to the two organizations are perceived as higher quality of care as well as participating in a rehabilitation program. Floor and ceiling effects were comparable to an evaluation of the PACIC questionnaire in a Danish population. Yet, floor effects suggest a need for further evaluation and possible improvement of the PACIC questionnaire in a Danish setting. Total PACIC scores were lower than in other healthcare systems, possible being a result of different contexts and cultures, and of a need for improving diabetes care in Denmark.

Results following prolonged recovery show satisfactory functional and patient-reported outcome after intramedullary nailing of a tibial shaft fracture: a prospective 5-year follow-up cohort study.

INTRODUCTION: Although a large number of previous studies have investigated the outcome in patients following tibial shaft fractures, the literature provides limited information on prospectively reported patients with mid- to long-term follow-up. The present study aimed to investigate prospectively the 5-year development in patient-reported quality of life after intramedullary nailing of a tibial shaft fracture. MATERIAL AND METHODS: The design was a prospective, 5-year follow-up cohort study. Quality of life (QOL) was measured with the questionnaire Eq5d-5L and compared to the 1-year outcome reported by the same patients. Secondary outcome measurements were the Knee Injury and Osteoarthritis Outcome Score (KOOS), recordings of pain, gait and muscle strength. RESULTS: Twenty-nine patients were eligible for participation. Mean patient age at the time of the 5-year follow-up was 46.3 years. The 5-year postoperative mean Eq5d-5L index was 0.864 (95% CI 0.809-0.918). The mean Eq5d-5L VAS was 88.4 (95% CI 83.4-93.5). Compared with the same patients' Eq5d-5L index scores at the 1-year follow-up (0.784), a significant increase was observed (P = 0.014). A comparison to the Danish Eq.5D reference population showed no statistically significant difference. CONCLUSIONS: Patient-reported quality of life among patients treated with intramedullary nailing following a tibial shaft fracture increased significantly between the 1-year and 5-year follow-up. In contrast to the 1-year patient-reported quality of life, results are comparable to those of a reference population at the 5-year follow-up. In a clinical setting, these results highlight that patients may expect a prolonged period to recover. However, of most importance is that patients can expect a satisfactory outcome years after fracture and treatment.

Age and prior exercise in vivo determine the subsequent in vitro molecular profile of myoblasts and nonmyogenic cells derived from human skeletal muscle.

The decline in skeletal muscle regenerative capacity with age is partly attributed to muscle stem cell (satellite cell) dysfunction. Recent evidence has pointed to a strong interaction between myoblasts and fibroblasts, but the influence of age on this interaction is unknown. Additionally, while the native tissue environment is known to determine the properties of myogenic cells in vitro, how the aging process alters this cell memory has not been established at the molecular level. We recruited 12 young and 12 elderly women, who performed a single bout of heavy resistance exercise with the knee extensor muscles of one leg. Five days later, muscle biopsies were collected from both legs, and myogenic cells and nonmyogenic cells were isolated for in vitro experiments with mixed or separated cells and analyzed by immunostaining and RT-PCR. A lower myogenic fusion index was detected in the cells from the old versus young women, in association with differences in gene expression levels of key myogenic regulatory factors and senescence, which were further altered by performing exercise before tissue sampling. Coculture with nonmyogenic cells from the elderly led to a higher myogenic differentiation index compared with nonmyogenic cells from the young. These findings show that the in vitro phenotype and molecular profile of human skeletal muscle myoblasts and fibroblasts is determined by the age and exercise state of the original in vivo environment and help explain how exercise can enhance muscle stem cell function in old age.

Reduced perioperative blood loss in children undergoing craniosynostosis surgery using prolonged tranexamic acid infusion: a randomised trial.

BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusion during paediatric craniosynostosis surgery. Additional reduction of postoperative blood loss may further reduce exposure to allogeneic blood products. We studied the effect of combined intra- and postoperative TXA treatment on postoperative blood loss in children. METHODS: Thirty children admitted for craniosynostosis surgery were randomised to combined intra- and postoperative TXA treatment or placebo. The primary endpoint was postoperative blood loss. Secondary endpoints included total blood loss, transfusion requirements, and clot stability evaluated by tissue plasminogen activator-stimulated clot lysis assay. RESULTS: TXA reduced postoperative blood loss by 18 ml kg-1 (95% confidence interval 8.9) and total blood loss from a mean of 52 ml kg-1 (standard deviation [SD]; 20) ml kg-1 to 28 (14) ml kg-1 (P<0.001). Intraoperative red blood cell (RBC) and fresh frozen plasma (FFP) transfusions were reduced in the treatment group from RBC 14.0 (5.2) ml kg-1 to 8.2 (5.1) ml kg-1 (P=0.01) and from FFP 13.0 (6.3) ml kg-1 to 7.8 (5.9) ml kg-1 (P=0.03). Postoperative RBC transfusion median was 5 (inter-quartile range [IQR] 0-6) ml kg-1 in the placebo group and 0 (0-5.7) ml kg-1 in the TXA group. Resistance to lysis was higher in the treatment group (P<0.001). CONCLUSIONS: Combined intra- and postoperative tranexamic acid treatment reduced postoperative and overall blood loss and transfusion requirements. Improved clot stability represents a possible mechanism for blood loss reduction.

Load magnitude affects patellar tendon mechanical properties but not collagen or collagen cross-linking after long-term strength training in older adults.

BACKGROUND: Regular loading of tendons may counteract the negative effects of aging. However, the influence of strength training loading magnitude on tendon mechanical properties and its relation to matrix collagen content and collagen cross-linking is sparsely described in older adults. The purpose of the present study was to compare the effects of moderate or high load resistance training on tendon matrix and its mechanical properties. METHODS: Seventeen women and 19 men, age 62-70 years, were recruited and randomly allocated to 12 months of heavy load resistance training (HRT), moderate load resistance training (MRT) or control (CON). Pre- and post-intervention testing comprised isometric quadriceps strength test (IsoMVC), ultrasound based testing of in vivo patellar tendon (PT) mechanical properties, MRI-based measurement of PT cross-sectional area (CSA), PT biopsies for assessment of fibril morphology, collagen content, enzymatic cross-links, and tendon fluorescence as a measure of advanced glycation end-products (AGEs). RESULTS: Thirty three participants completed the intervention and were included in the data analysis. IsoMVC increased more after HRT (+ 21%) than MRT (+ 8%) and CON (+ 7%) (p < 0.05). Tendon stiffness (p < 0.05) and Young's modulus (p = 0.05) were also differently affected by training load with a reduction in CON and MRT but not in HRT. PT-CSA increased equally after both MRT and HRT. Collagen content, fibril morphology, enzymatic cross-links, and tendon fluorescence were unaffected by training. CONCLUSION: Despite equal improvements in tendon size after moderate and heavy load resistance training, only heavy. load training seemed to maintain tendon mechanical properties in old age. The effect of load magnitude on tendon biomechanics was unrelated to changes of major load bearing matrix components in the tendon core. The study is a sub-study of the LISA study, which was registered at http://clinicaltrials.gov (NCT02123641) April 25th 2014.

Intra- and Postoperative Blood Loss and Transfusion Requirements in Children Undergoing Craniofacial Surgery.

Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14-33 mL/kg) and postoperatively 27 mL/kg (18-37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10-24 mL/kg) and postoperative 14 mL/kg (9-21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0-6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60-300 minutes).Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.

European guidelines on perioperative venous thromboembolism prophylaxis: Surgery in the elderly.

: The risk for postoperative venous thromboembolism (VTE) is increased in patients aged more than 70 years and in elderly patients presenting with co-morbidities, for example cardiovascular disorders, malignancy or renal insufficiency. Therefore, risk stratification, correction of modifiable risks and sustained perioperative thromboprophylaxis are essential in this patient population. Timing and dosing of pharmacoprophylaxis may be adopted from the non-aged population. Direct oral anti-coagulants are effective and well tolerated in the elderly; statins may not replace pharmacological thromboprophylaxis. Early mobilisation and use of non-pharmacological means of thromboprophylaxis should be exploited. In elderly patients, we suggest identification of co-morbidities increasing the risk for VTE (e.g. congestive heart failure, pulmonary circulation disorder, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy) and correction if present (e.g. anaemia, coagulopathy) (Grade 2C). We suggest against bilateral knee replacement in elderly and frail patients (Grade 2C). We suggest timing and dosing of pharmacological VTE prophylaxis as in the non-aged population (Grade 2C). In elderly patients with renal failure, low-dose unfractionated heparin (UFH) may be used or weight-adjusted dosing of low molecular weight heparin (Grade 2C). In the elderly, we recommend careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation (Grade 1C). We recommend multi-faceted interventions for VTE prophylaxis in elderly and frail patients, including pneumatic compression devices, low molecular weight heparin (and/or direct oral anti-coagulants after knee or hip replacement) (Grade 1C). : This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to:Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73-76.A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Executive summary. Eur J Anaesthesiol 2018; 35:77-83.

European guidelines on perioperative venous thromboembolism prophylaxis: Mechanical prophylaxis.

: Institutional protocols need to address the indications for pharmacological and mechanical thromboprophylaxis. The use of graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) strongly differs between institutions. As a consequence, no strong recommendations can be made based on the contemporary high-level evidence. Although different clinical practices can be supported, such approaches should be part of an institutional strategy to reduce the burden of venous thromboembolism (VTE). We recommend against the use of GCS alone without pharmacological thromboprophylaxis for prevention of VTE in patients at intermediate and high risk. For patients at high risk of VTE with contraindications for pharmacological thromboprophylaxis, we recommend the use of mechanical prophylaxis and suggest the use of IPC over GCS. However, for those patients receiving pharmacological thromboprophylaxis who are without a very high risk of VTE prophylaxis, we recommend against the routine use of mechanical thromboprophylaxis either with GCS or IPC. We suggest combined mechanical and pharmacological prophylaxis in selected patients at very high risk of VTE prophylaxis and suggest IPC rather than GCS in these selected patients.

Decreased QOL and muscle strength are persistent 1 year after intramedullary nailing of a tibial shaft fracture: a prospective 1-year follow-up cohort study.

INTRODUCTION: To evaluate the development in patient-reported quality of life (QOL) and muscle strength in the period from surgery to 12 months postoperatively after intramedullary nailing of a tibial shaft fracture. MATERIALS AND METHODS: The design was a prospective, follow-up cohort study. QOL was measured with the questionnaire Eq5D-5L and compared to norm data from a reference population. Recordings of pain and contralateral muscle strength (isometric maximal voluntary contraction (MVC) for knee flexion and extension were collected at 6 weeks, 3, 6, and 12 months postoperatively. Ipsilateral MVCs were recorded at 6 and 12 months. RESULTS: Forty-nine patients were included. The mean age at the time of fracture was 43.1 years (18-79 years). Twelve months postoperatively, the mean Eq5D-5L index was 0.792 (95 % CI 0.747-0.837). Throughout the 12 months postoperatively, patients reported worse QOL compared to the reference population. Six and 12 months after surgery patients demonstrated decreased muscle strength in the injured leg compared to the non-injured leg for knee extension and flexion (P < 0.001). Twelve months postoperatively, increasing relative difference in muscle strength during knee extension show a fair correlation to worse QOL (R = 0.541, P < 0.001). CONCLUSIONS: Throughout the 12 months postoperatively, patients reported worse QOL compared to the reference population. Muscle strength in the non-injured leg improved over time and was higher after 6 and 12 months compared with the injured leg.

Evaluation of dynamic parameters of thrombus formation measured on whole blood using rotational thromboelastometry in children undergoing cardiac surgery: a descriptive study.

BACKGROUND: Total thrombus formation velocity calculated using amplitude parameters obtained at different times could be used to estimate the amplification and the propagation phases observed during coagulation processes, and therefore might be useful to predict postoperative hemostatic products administration in pediatric patients. METHODS: We retrospectively analyzed data from 49 children <3 months of age who underwent cardiac surgery. Children ≤1 month of age routinely received fresh frozen plasma during bypass while children >1 month of age did not. The EXTEM parameters were used to calculate velocity curves using amplitudes obtained at different times, the area under the curve called total thrombus formation and the maximum rate of thrombus formation. These parameters were compared between children who received fresh frozen plasma and those who did not. Receiver operating characteristics curves were used to define variables that could be used to predict postoperative fresh frozen plasma transfusion. RESULTS: Total thrombus formation and maximum rate of thrombus formation significantly increased in children who received fresh frozen plasma compared to those who did not. Both total thrombus formation and maximum rate of thrombus formation have a better specificity to predict postoperative fresh frozen plasma transfusion compared to clotting time or maximal clot firmness. CONCLUSION: Based on this descriptive study, dynamic ROTEM(®) parameters of total thrombus formation could be used to estimate the amplification and the propagation phases of coagulation in children. These parameters might be used in further well-designed study to predict the need for hemostatic products in children undergoing cardiac surgery with cardiopulmonary bypass.

Prostacyclin in trauma patients with hemorrhagic shock: A randomized clinical trial.

BACKGROUND: A main cause of trauma morbidity and mortality is multiple-organ failure, and endotheliopathy has been implicated. Pilot studies indicate that low-dose prostacyclin improves endothelial functionality in critically ill patients, suggesting that this intervention may improve trauma patient outcome. METHODS: We conducted a multicenter, randomized, blinded, clinical investigator-initiated trial in 229 trauma patients with hemorrhagic shock who were randomized 1:1 to 72 hours infusion of the prostacyclin analog iloprost (1 ng/kg/min) or placebo. The primary outcome was the number of intensive care unit (ICU)-free days alive within 28 days of admission. Secondary outcomes included 28-day all-cause mortality and hospital length of stay. RESULTS: The mean number of ICU-free days alive within 28 days was 15.64 days in the iloprost group versus 13.99 days in the placebo group (adjusted mean difference, -1.63 days [95% confidence interval (CI), -4.64 to 1.38 days]; p = 0.28). The 28-day mortality was 18.8% in the iloprost group versus 19.6% in the placebo group (odds ratio, 1.01 [95% CI, 0.51-2.0]; p = 0.97). The mean hospital length of stay was 19.96 days in the iloprost group versus 27.32 days in the placebo group (adjusted mean difference, 7.84 days [95% CI, 1.66-14.02 days], p = 0.01). CONCLUSION: Iloprost did not result in a statistically significant increase in the number of ICU-free days alive within 28 days of admission, whereas it was safe and a statistically significant reduction in hospital length of stay was observed. Further research on prostacyclin in shocked trauma patients is warranted. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Wound infusion of bupivacaine following radical retropubic prostatectomy: a randomised placebo-controlled clinical study.

CONTEXT: The effectiveness of postoperative analgesia through a wound catheter is subject to considerable debate. OBJECTIVE: To test the hypothesis that local wound infusion with bupivacaine followed by continuous infusion could reduce postoperative need for opioids in patients undergoing retropubic prostatectomy. DESIGN: Single-centre prospective, double-blinded, placebo-controlled trial. SETTING: A major university hospital in Denmark. PATIENTS: Following written informed consent, 60 patients scheduled for prostatectomy were recruited to the study and 50 completed the protocol to reach data analysis. INTERVENTIONS: Thirty millilitre bolus of bupivacaine (2.5 mg ml) or isotonic saline was injected through a subfascially placed wound catheter followed by continuous infusion at 5 ml h during the following 48 h. All patients were prescribed paracetamol, non-steroidal anti-inflammatory drugs, morphine and oxycodone if needed. OUTCOME MEASURES: Primary outcome was the opioid requirement. Secondary outcomes included pain scores at rest and with activity, and nausea and vomiting scores. RESULTS: The total amount of morphine required during the postoperative period was not significantly higher (P=0.49) in the placebo group (12 mg, 25 to 75% percentile 5 to 18) than the bupivacaine group (10 mg, 25 to 75% percentile 0 to 16). Similarly, the total amount of oxycodone required was not significantly different (P=0.99) and was equal among the groups (5 mg, 25 to 75% percentile 5 to 10). At 2 h postoperatively, a significantly (P=0.0488) higher number of patients required additional morphine in the placebo group. No differences between the groups were detected at any time point regarding pain scores or the presence of nausea and vomiting. CONCLUSION: Additional use of a wound catheter in patients undergoing prostatectomy in the present perioperative setting appears superfluous.