Perioperative medicine training resources: U4M3: Patient blood management

Keywords: intraoperative cell salvage; patient blood management; transfusion.

Abstract
Background: Patients with chronic kidney disease (CKD) often present with iron depletion and iron deficiency anaemia (IDA) because of frequent blood (and iron) loss. Therapy consists of repletion of iron stores and intravenous (i.v.) iron has become the standard care in this setting. However, older i.v. iron preparations have their limitations. This study primarily investigated the safety, and also the efficacy, of ferric carboxymaltose (FCM), a next-generation i.v. iron formulation, given as a bolus-push injection in patients with CKD undergoing maintenance haemodialysis (HD).

Methods: Patients (aged 18-65 years) with IDA undergoing HD received 100-200 mg of iron as FCM via an i.v. bolus-push injection into the HD venous line, two to three times weekly for or=1.0 g/dl increase in haemoglobin (Hb) from baseline at any time during the study. Enrolled patients (safety population) receiving >or=1 dose of study medication were included in the efficacy analyses [intent-to-treat (ITT) population].

Results: Of 163 patients enrolled, 150 (92%) completed the study. The mean +/- SD total cumulative dose of iron as FCM administered was 2133.3 +/- 57.7 mg. In total, 193 AEs were reported in 89 out of 163 (54.6%) patients. Almost three-quarters of patients (73.6%) received erythropoiesis-stimulating agents (ESAs), but the dose remained stable during the study. Serious AEs occurred in 12 out of 163 (7.4%) patients and two patients died; none of these was considered by the investigator to be related to the study medication. Only five out of 163 (3.1%) patients discontinued study medication due to an AE. Overall, 100 out of 162 (61.7%; ITT population) patients were treatment responders, and mean Hb levels increased from 9.1 +/- 1.30 g/dl at baseline to 10.3 +/- 1.63 g/dl at follow-up.

Conclusions: FCM is well-tolerated and effective in the correction of Hb levels and iron stores in patients with IDA undergoing HD. As changes in anaemia treatment other than i.v. FCM (e.g. increased ESA doses) were not permitted during the study, the clinically relevant increase in Hb in the majority of patients can be solely attributed to efficient iron utilization. The incidence of AEs was as expected for this population.

Abstract
Background: Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.

Methods: This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.

Findings: 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).

Interpretation: Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.

Funding: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

Keywords: anemia; bleeding; blood conservation; blood transfusion; cardiac surgery; patient blood management.

Abstract
Each year in the United States, millions of units of fresh frozen plasma and platelets are transfused. A substantial proportion of these units are given to nonbleeding patients to "decrease the risk" of bleeding at the time of invasive procedures. The decision to transfuse is frequently triggered by an elevated prothrombin time (PT; international normalized ratio ) or activated partial thromboplastin time test result or by a depressed platelet count. This review summarizes published studies on the extent to which mild to moderate abnormalities of common laboratory tests of hemostasis reflect an increased risk of bleeding at the time of invasive bedside procedures, including central line placement, liver biopsy, paracentesis, thoracentesis, gastrointestinal endoscopy and biopsy, renal biopsy, bronchoscopy and transbronchial lung biopsy, and lumbar punctures. The poor predictive value of the PT (INR) is understandable in the context of the design and performance of this assay. Whether mild to moderate abnormalities of commonly used laboratory tests have any clinically relevant predictive value as appropriate triggers for prophylactic transfusions before invasive procedures should be investigated in formal randomized clinical trials.

Abstract
Background: Postpartum haemorrhage (PPH) is often complicated by impaired coagulation. We aimed to determine whether the level of ionised calcium (Ca2+), an essential coagulation co-factor, at diagnosis of PPH is associated with bleeding severity.

Methods: This was a retrospective cohort study of women diagnosed with PPH during vaginal delivery between January 2009 and April 2020. Ca2+ levels at PPH diagnosis were compared between women who progressed to severe PPH (primary outcome) and those with less severe bleeding. Severe PPH was defined by transfusion of ≥2 blood units, arterial embolisation or emergency surgery, admission to ICU, or death. Associations between other variables (e.g. fibrinogen concentration) and bleeding severity were also assessed.

Results: For 436 patients included in the analysis, hypocalcaemia was more common among patients with severe PPH (51.5% vs 10.6%, P<0.001). In a multivariable logistic regression model, Ca2+ and fibrinogen were the only parameters independently associated with PPH severity with odds ratios of 1.14 for each 10 mg dl-1 decrease in fibrinogen (95% confidence interval [CI], 1.05-1.24; P=0.002) and 1.97 for each 0.1 mmol L-1 decrease in Ca2+ (95% CI, 1.25-3.1; P=0.003). The performance of Ca2+ or fibrinogen was not significantly different (area under the curve [AUC]=0.79 [95% CI, 0.75-0.83] vs AUC=0.86 [95% CI, 0.82-0.9]; P=0.09). The addition of Ca2+ to fibrinogen improved the model, leading to AUC of 0.9 (95% CI, 0.86-0.93), P=0.03.

Conclusions: Ca2+ level at the time of diagnosis of PPH was associated with risk of severe bleeding. Ca2+ monitoring may facilitate identification and treatment of high-risk patients.

Abstract
Patient blood management is now high on national and international health-system agendas. Serious supply challenges as a result of changing population dynamics, escalating cost of blood, ongoing safety challenges and questions about transfusion efficacy and outcomes are necessitating change in transfusion practice. Numerous initiatives are underway to bring about change, including the institution of comprehensive patient blood management programmes. In 2008, the Western Australia Department of Health initiated a 5-year project to implement a comprehensive health-system-wide Patient Blood Management Program with the aim of improving patient outcomes while reducing costs. Clinically, the Program was structured on the three pillars of patient blood management, namely (1) optimising the patient's own red cell mass, (2) minimising blood loss and (3) harnessing and optimising the patient-specific anaemia reserve. It employs multiple strategies to bring about a cultural change from a blood-product focus to a patient focus. This Program was undertaken in a State that already had one of the lowest red blood cell issuance rates per 1000 population in the developed world (30.47 red blood cell units per 1000 population). The Program identified reasons and drivers for practice change. From financial years 2008-09 to 2011-12, issuance has progressively decreased in Western Australia to 27.54 units per 1000. During the same years, despite increasing activity, total issuance of red blood cells to the entire State decreased from 70,103 units to 65,742. Nationally and internationally, other initiatives are underway to bring about change and implement patient blood management. The World Health Assembly in May 2010 adopted resolution WHA63.12 endorsing patient blood management and its three-pillar application. The United States Advisory Committee on Blood Safety and Availability met in 2011 to consider the implications of this resolution and its implementation.

Abstract
Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.

Abstract
Anemia, iron deficiency and other hematinic deficiencies are a major cause of perioperative transfusion needs and are associated with increased morbidity and mortality. Anemia can be caused either by decreased production of hemoglobin or red blood cells or by increased consumption and blood loss. Decreased production can involve anything from erythropoietin or vitamin B12 insufficiency to absolute or functional lack of iron. Thus, to achieve the goal of patient blood management, anemia must be addressed by addressing its causes. The traditional parameters to diagnose anemia, despite offering elaborate options, are not ideally suited to giving a simple overview of the causes of anemia, e.g., iron status for erythropoiesis, especially during the acute phase of inflammation, acute blood loss or iron deficiency. Reticulocyte hemoglobin can thus help to uncover the cause of the anemia and to identify the main factors inhibiting erythropoiesis. Regardless of the cause of anemia, reticulocyte hemoglobin can also quickly track the success of therapy and, together with the regular full blood count it is measured alongside, help in clearing the patient for surgery.

Abstract
Objective: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.

Design: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.

Data sources: Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.

Trial selection: Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.

Data extraction: Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.

Results: 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference -1.43, 95% confidence interval -2.01 to -0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.

Conclusions: Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.

Abstract
The use of cell salvage is recommended when it can be expected to reduce the likelihood of allogeneic (donor) red cell transfusion and/or severe postoperative anaemia. We support and encourage a continued increase in the appropriate use of peri-operative cell salvage and we recommend that it should be available for immediate use 24 h a day in any hospital undertaking surgery where blood loss is a recognised potential complication (other than minor/day case procedures).

Abstract
Background: Evidence suggests that patients with normal hemoglobin (Hgb) levels on hospital admission who subsequently develop hospital-acquired anemia (HAA) may be at risk for adverse outcomes. Our objectives were to (1) determine the prevalence of HAA and (2) examine whether HAA is associated with increased mortality, length of stay (LOS), and total hospital charges.

Methods: The population consisted of 417,301 adult hospitalizations from January 1, 2009 to August 31, 2011, in an academic medical center and 9 community hospitals. Patients with anemia on admission, and hospitals in the health system without available laboratory data were excluded; 188,447 hospitalizations were included in the analysis. Demographics, comorbidities, and outcomes were retrieved from administrative data; Hgb values were taken from the electronic medical record. Regression modeling was used to examine the association between demographics, comorbidity, hospitalization type, and HAA variables (mild: Hgb >11 and <12 g/dL for women, and >11 and <13 g/dL for men; moderate: Hgb 9.1 to ≤ 11.0 g/dL; severe: Hgb ≤ 9.0 g/dL) on mortality, LOS, and hospital charges.

Results: Among 188,447 hospitalizations, 139,807 patients (74%) developed HAA: mild, 40,828 (29%); moderate, 57,184 (41%); and severe, 41,795 (30%). Risk-adjusted odds ratios and 95% confidence intervals for in-hospital mortality with HAA were: mild, 1.0 (0.88-1.17; P = 0.8); moderate, 1.51 (1.33-1.71, P < 0.001); and severe, 3.28 (2.90-3.72, P < 0.001). Risk-adjusted relative mean LOS and hospital charges relative to no HAA were higher with HAA: LOS: mild, 1.08 (1.08-1.10, P < 0.001); moderate, 1.28 (1.26-1.29, P < 0.001); severe, 1.88 (1.86-1.89, P < 0.001). Hospital charges: mild, 1.06 (1.06-1.07, P < 0.001); moderate, 1.18 (1.17-1.19, P < 0.001); severe, 1.80 (1.79-1.82, P < 0.001).

Conclusions: HAA is common and associated with increased mortality and resource utilization. Factors related to its development necessitate further study.

Abstract
The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient's tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

Abstract
Background: Evidence on the role of intravenous iron (IVI) supplementation after colorectal cancer (CRC) surgery is rather scant. This study was aimed at assessing the benefit of post-operative IVI administration after elective CRC surgery at our institution.

Materials and methods: This was a single-centre, retrospective observational study including all patients who underwent CRC surgery during 2014. Anaemia was defined as a haemoglobin (Hb) <13 g/dL, regardless of gender. Anaemic patients received 200 mg IVI up to three times a week to cover iron deficiency (IVI group). Those who did not receive IVI were placed on standard care (NIVI group). The primary outcome was the proportion of anaemic patients on post-operative day (POD)1 and POD30. Secondary outcomes included Hb changes from POD1 to POD30, transfusion requirements and complication rates.

Results: Of the 159 patients studied, 139 (87%) presented with anaemia: 47 (34%) of these received post-operative IVI and 92 (66%) did not. Patients in the IVI group had lower POD1 Hb levels compared to those in the NIVI group (p=0.001). On POD30, only 103 had their Hb measured (34 IVI, 69 NIVI). Anaemia was more prevalent and more severe among the patients in the IVI group (p=0.027), despite their greater increment in Hb (2.0±1.5 g/dL vs 1.1±1.2 g/dL; p=0.001). Eleven patients needed post-operative transfusions (7 IVI, 4 NIVI; p=0.044). There were no differences in post-operative complication rates between the groups. No IVI-related adverse events were recorded DISCUSSION: Compared with standard care, post-operative IVI administration to anaemic patients improved the recovery of Hb levels at POD30, without increasing post-operative complications.

Abstract
Importance: Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH).

Objective: To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion.

Design, setting, and participants: Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016.

Main outcomes and measures: Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively.

Results: A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = -0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders.

Conclusions and relevance: Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials.

Abstract
Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Abstract
Background: Whether a restrictive threshold for hemoglobin level in red-cell transfusions, as compared with a liberal threshold, reduces postoperative morbidity and health care costs after cardiac surgery is uncertain.

Methods: We conducted a multicenter, parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal transfusion threshold (hemoglobin level <9 g per deciliter). The primary outcome was a serious infection (sepsis or wound infection) or an ischemic event (permanent stroke [confirmation on brain imaging and deficit in motor, sensory, or coordination functions], myocardial infarction, infarction of the gut, or acute kidney injury) within 3 months after randomization. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months after surgery.

Results: A total of 2007 patients underwent randomization; 4 participants withdrew, leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group. Transfusion rates after randomization were 53.4% and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91 to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup. There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P=0.045). Serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups.

Conclusions: A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN70923932.).

Abstract
Background: Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects.

Methods: In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery.

Results: Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fisher's exact test).

Conclusions: Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639 .).

Abstract
Background: There is accumulating evidence that restricting blood transfusions improves outcomes, with newer trials showing greater benefit from more restrictive strategies. We systematically evaluated the impact of various transfusion triggers on clinical outcomes.

Methods: The MEDLINE database was searched from 1966 to April 2013 to find randomized trials evaluating a restrictive hemoglobin transfusion trigger of <7 g/dL, compared with a more liberal trigger. Two investigators independently extracted data from the trials. Outcomes evaluated included mortality, acute coronary syndrome, pulmonary edema, infections, rebleeding, number of patients transfused, and units of blood transfused per patient. Extracted data also included information on study setting, design, participant characteristics, and risk for bias of the included trials. A secondary analysis evaluated trials using less restrictive transfusion triggers, and a systematic review of observational studies evaluated more restrictive triggers.

Results: In the primary analysis, pooled results from 3 trials with 2364 participants showed that a restrictive hemoglobin transfusion trigger of <7 g/dL resulted in reduced in-hospital mortality (risk ratio [RR], 0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65-0.98), rebleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44; CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial infections (RR, 0.86; CI, 0.73-1.00), compared with a more liberal strategy. The number needed to treat with a restrictive strategy to prevent 1 death was 33. Pooled data from randomized trials with less restrictive transfusion strategies showed no significant effect on outcomes.

Conclusions: In patients with critical illness or bleed, restricting blood transfusions by using a hemoglobin trigger of <7 g/dL significantly reduces cardiac events, rebleeding, bacterial infections, and total mortality. A less restrictive transfusion strategy was not effective.

Abstract
The use of alternatives to allogeneic blood continues to rest on the principles that blood transfusions have inherent risks, associated costs, and affect the blood inventory available for health-care delivery. Increasing evidence exists of a fall in the use of blood because of associated costs and adverse outcomes, and suggests that the challenge for the use of alternatives to blood components will similarly be driven by costs and patient outcomes. Additionally, the risk-benefit profiles of alternatives to blood transfusion such as autologous blood procurement, erythropoiesis-stimulating agents, and haemostatic agents are under investigation. Nevertheless, the inherent risks of blood, along with the continued rise in blood costs are likely to favour the continued development and use of alternatives to blood transfusion. We summarise the current roles of alternatives to blood in the management of medical and surgical anaemias.

Abstract
Introduction
Intraoperative surgical site bleeding is usually common in different types of surgeries. Even though there are different prevention techniques for intraoperative bleeding disorder, now adays deliberate hypotension is highly recommended as management options. Uncontrolled intraoperative bleeding may contribute to disability and even death. It can be the initial sign, and lead to incapacitating symptoms in patients undergoing moderate to major surgery.
Method
Electronic search strategies used the following databases: Cochrane library, Pub Med, Medline and various internet search routines, for English publications. Key search terms included in our review are: Deliberate/controlled/induced/permissive hypotension, Intraoperative blood loss, Bleeding control, Intraoperative monitoring, Complication and anesthetic management. Availability of each referenced literature database was assessed until March 15–2019. References classified by evidence levels were selected by one individual and checked by another investigator.
Discussion
Deliberate hypotension is listed as one of the blood conservation techniques to be considered with MAP between 50 and 65 mmHg and SBP between 80 and 90 mmHg with little to no reports of complication. A reduction of the patient's blood pressure improved the surgical field operating conditions. Resuscitation should be started after bleeding sites arrested. The most significant factor in deciding when to transfuse is based on one's attitude towards transfusion and the related ‘trigger’ criterion for transfusion.
Conclusion
Hypotensive anesthesia protocol allowed perfect hemostasis control significantly with shorter operative time compared with other intraoperative controlling mechanisms for prevention of surgical site bleeding. The range of mean arterial pressure and blood pressure has to be closely monitored and any decrement from the expected range should be managed with vasoactive drugs.

Abstract
Background: Prognostic significance of serum calcium level in patients with intracerebral hemorrhage is not well studied. The aim of the study was to identify if a relationship between admission serum calcium level and prognosis exists in patients with intracerebral hemorrhage.

Methods: A total of 1262 confirmed intracerebral hemorrhage patients were included. Demographic data, medical history, medicine history, laboratory data, imaging data, clinical score, and progress note were collected from their medical records. All images of head computed tomography were reanalyzed. Ninety-day prognosis was recorded, and poor outcome was defined as death or major disability caused by intracerebral hemorrhage.

Results: During the 90-day follow-up period, 504 patients died and 226 patients suffered from major disability. Death and major disability were combined as poor prognosis. The remaining 532 patients showed good prognosis. Admission serum calcium level was lower in the patients with poor prognosis than in the patients with good prognosis (2.41 ± 0.23 mmol/l, 2.55 ± 0.26 mmol/l, P < 0.001). Admission INR and hematoma volume were higher in the patients with poor prognosis than in the patients with good prognosis (INR: 1.74 ± 0.29, 1.70 ± 0.29, P = 0.029; hematoma volume: 11.6 ± 4.4 ml, 10.7 ± 4.1 ml, P < 0.001). There was no difference in admission APTT level between the two prognosis groups (28.4 ± 5.6 s, 27.8 ± 5.4 s, P = 0.056). A multivariate COX regression analysis reported that admission serum calcium level ≤ 2.41 mmol/l was associated with the increased risk of poor prognosis (death or major disability) in the patients (HR 1.45, 95% CI 1.32-1.60). In addition, there was a significant linear association of serum calcium level with coagulation function markers and hematoma volume on admission (APTT: r = - 0.091, P = 0.001; INR: r = - 0.063, P = 0.025; hematoma volume: r = -0.108, P < 0.001).

Conclusions: Admission serum calcium level might be a prognostic marker for intracerebral hemorrhage. Potential mechanism involved calcium-induced coagulation function abnormality.

Abstract
Background: Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.

Methods: In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.

Findings: Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65-1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52-0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88-1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.

Interpretation: Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.

Funding: London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.