A Breath-Based In Vitro Diagnostics for Lower Respiratory Tract Infection.

Lower Respiratory Tract Infections (LRTIs) represent the leading cause of death due to infectious diseases. Current diagnostic modalities primarily depend on clinical symptoms and lack specificity, especially in light of common colonization without overt infection. To address this, we developed a noninvasive diagnostic approach that employs BreathBiomics™, an advanced human breath sampling system, to detect protease activities induced by bacterial infection in the lower respiratory tract. Specifically, we engineered a high-sensitivity and high-specificity molecular sensor for human neutrophil elastase (HNE). The sensor undergoes cleavage in the presence of HNE, an event that is subsequently detected via Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). Application of this methodology to clinical samples, breath specimens collected from intubated patients with LRTIs, demonstrated the detection of the cleaved sensor by MALDI-TOF MS. Our findings indicate that this novel approach offers a noninvasive and specific diagnostic strategy for people with LRTIs.

Human exhaled air diagnostic markers for respiratory tract infections in subjects receiving mechanical ventilation.

Diagnosing respiratory tract infections (RTIs) in critical care settings is essential for appropriate antibiotic treatment and lowering mortality. The current diagnostic method, which primarily relies on clinical symptoms, lacks sensitivity and specificity, resulting in incorrect or delayed diagnoses, putting patients at a heightened risk. In this study we developed a noninvasive diagnosis method based on collecting non-volatile compounds in human exhaled air. We hypothesized that non-volatile compound profiles could be effectively used for bacterial RTI diagnosis. Exhaled air samples were collected from subjects receiving mechanical ventilation diagnosed with or without bacterial RTI in intensive care units at the Johns Hopkins Hospital. Truncated proteoforms, a class of non-volatile compounds, were characterized by top-down proteomics, and significant features associated with RTI were identified using feature selection algorithms. The results showed that three truncated proteoforms, collagen type VI alpha three chain protein, matrix metalloproteinase-9, and putative homeodomain transcription factor II were independently associated with RTI with thep-values of 2.0 × 10-5, 1.1 × 10-4, and 1.7 × 10-3, respectively, using multiple logistic regression. Furthermore, a score system named 'TrunScore' was constructed by combining the three truncated proteoforms, and the diagnostic accuracy was significantly improved compared to that of individual truncated proteoforms, with an area under the receiver operator characteristic curve of 96.9%. This study supports the ability of this noninvasive breath analysis method to provide an accurate diagnosis for RTIs in subjects receiving mechanical ventilation. The results of this study open the doors to be able to potentially diagnose a broad range of diseases using this non-volatile breath analysis technique.

Correction to: Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials.

In the article entitled "Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials" Can J Anesth 2018; 65: 529-42, we wish to clarify the following items.

Outcomes of Tracheostomy With Concomitant and Delayed Percutaneous Endoscopic Gastrostomy in the Neuroscience Critical Care Unit.

BACKGROUND: In patients with severe neurologic conditions, percutaneous endoscopic gastrostomy (PEG) is typically performed either alone or with a tracheostomy. The characteristics and outcomes of patients receiving PEG concomitantly with a tracheostomy (CTPEG) and those receiving delayed PEG (DPEG) after a tracheostomy were compared. METHODS: Retrospective cohort study in a 24-bed neuroscience critical care unit (NCCU) at a tertiary care hospital. Consecutive patients admitted to the NCCU from April 2007 to July 2013 who underwent percutaneous tracheostomy and gastrostomy by the percutaneous tracheostomy team were included and grouped according to the timing of PEG placement: CTPEG versus DPEG. RESULTS: Of the 290 patients, 234 (81%) received CTPEG. Demographic and clinical characteristics were similar among the 2 groups except for a lower median (interquartile range [IQR]) body mass index (BMI; 27 [22.67-31.60] versus 30.8 [24.55-40.06], P = .017) and lower rate of acute respiratory distress syndrome (3.85% vs 10.71%, P = .048) in the CTPEG cohort. Furthermore, 59% of CTPEG cohort were neurology patients while 63% of DPEG were neurosurgery patients, P = .004. Primary outcomes showed shorter mean NCCU length of stay (LOS; 25 [12] vs 33 [17] days, P < .001) and median hospital LOS (32 [25-43] vs 37 [31-56] days, P = .002) for the CTPEG cohort. Secondary outcomes showed higher predischarge prealbumin levels (15.6 [7.75] vs 11.58 [5.41], P = .021) and lower median overall hospital cost (US$123 860.20 [US$99 024-US$168 713.40] vs US$159 633.50 [US$121 312-US$240 213.10], P = .0003) in the CTPEG group. Anatomic contraindications were the most common reason for DPEG (30%). CONCLUSIONS: Among institutions with a tracheostomy team, the practice of tracheostomy with concomitant PEG placement may be considered as feasible as delayed PEG in carefully selected neurocritically ill patients with possible advantages of overall shorter NCCU and hospital LOS, higher predischarge prealbumin, and lower hospital costs. These findings may aid in decisions regarding the timing of PEG placement in the NCCU. Further prospective studies are warranted.

Glasgow Coma Scale Score Fluctuations are Inversely Associated With a NIRS-based Index of Cerebral Autoregulation in Acutely Comatose Patients.

BACKGROUND: The Glasgow Coma Scale (GCS) is an essential coma scale in critical care for determining the neurological status of patients and for estimating their long-term prognosis. Similarly, cerebral autoregulation (CA) monitoring has shown to be an accurate technique for predicting clinical outcomes. However, little is known about the relationship between CA measurements and GCS scores among neurological critically ill patients. This study aimed to explore the association between noninvasive CA multimodal monitoring measurements and GCS scores. METHODS: Acutely comatose patients with a variety of neurological injuries admitted to a neurocritical care unit were monitored using near-infrared spectroscopy-based multimodal monitoring for up to 72 hours. Regional cerebral oxygen saturation (rScO2), cerebral oximetry index (COx), GCS, and GCS motor data were measured hourly. COx was calculated as a Pearson correlation coefficient between low-frequency changes in rScO2 and mean arterial pressure. Mixed random effects models with random intercept was used to determine the relationship between hourly near-infrared spectroscopy-based measurements and GCS or GCS motor scores. RESULTS: A total of 871 observations (h) were analyzed from 57 patients with a variety of neurological conditions. Mean age was 58.7±14.2 years and the male to female ratio was 1:1.3. After adjusting for hemoglobin and partial pressure of carbon dioxide in arterial blood, COx was inversely associated with GCS (ß=-1.12, 95% confidence interval [CI], -1.94 to -0.31, P=0.007) and GCS motor score (ß=-1.06, 95% CI, -2.10 to -0.04, P=0.04). In contrast rScO2 was not associated with GCS (ß=-0.002, 95% CI, -0.01 to 0.01, P=0.76) or GCS motor score (ß=-0.001, 95% CI, -0.01 to 0.01, P=0.84). CONCLUSIONS: This study showed that fluctuations in GCS scores are inversely associated with fluctuations in COx; as COx increases (impaired autoregulation), more severe neurological impairment is observed. However, the difference in COx between high and low GCS is small and warrants further studies investigating this association. CA multimodal monitoring with COx may have the potential to be used as a surrogate of neurological status when the neurological examination is not reliable (ie, sedation and paralytic drug administration).

Antiepileptic drugs in critically ill patients.

BACKGROUND: The incidence of seizures in intensive care units ranges from 3.3% to 34%. It is therefore often necessary to initiate or continue anticonvulsant drugs in this setting. When a new anticonvulsant is initiated, drug factors, such as onset of action and side effects, and patient factors, such as age, renal, and hepatic function, should be taken into account. It is important to note that the altered physiology of critically ill patients as well as pharmacological and nonpharmacological interventions such as renal replacement therapy, extracorporeal membrane oxygenation, and target temperature management may lead to therapeutic failure or toxicity. This may be even more challenging with the availability of newer antiepileptics where the evidence for their use in critically ill patients is limited. MAIN BODY: This article reviews the pharmacokinetics and pharmacodynamics of antiepileptics as well as application of these principles when dosing antiepileptics and monitoring serum levels in critically ill patients. The selection of the most appropriate anticonvulsant to treat seizure and status epileptics as well as the prophylactic use of these agents in this setting are also discussed. Drug-drug interactions and the effect of nonpharmacological interventions such as renal replacement therapy, plasma exchange, and extracorporeal membrane oxygenation on anticonvulsant removal are also included. CONCLUSION: Optimal management of antiepileptic drugs in the intensive care unit is challenging given altered physiology, polypharmacy, and nonpharmacological interventions, and requires a multidisciplinary approach where appropriate and timely assessment, diagnosis, treatment, and monitoring plans are in place.

Intraoperative cerebral oximetry-based management for optimizing perioperative outcomes: a meta-analysis of randomized controlled trials.

PURPOSE: Although evidence from observational studies in a variety of clinical settings supports the utility of cerebral oximetry as a predictor of outcomes, prospective clinical trials thus far have reported conflicting results. This systematic review and meta-analysis was designed to evaluate the influence of management associated with intraoperative cerebral oximetry on postoperative outcomes. The primary outcome was postoperative cognitive dysfunction (POCD), with secondary outcomes that included postoperative delirium, length of intensive care unit (ICU) stay, and hospital length of stay (LOS). SOURCE: After searching the PubMed, EMBASE, Cochrane Library, Scopus, and Google Scholar databases, all randomized controlled trials (RCTs) assessing the impact of intraoperative cerebral oximetry-guided management on clinical outcomes following surgery were identified. PRINCIPAL FINDINGS: Fifteen RCTs comprising 2,057 patients (1,018 in the intervention group and 1,039 in control group) were included. Intraoperative management guided by the use of cerebral oximetry was associated with a reduction in the incidence of POCD (risk ratio [RR] 0.54; 95% confidence interval [CI], 0.33 to 0.90; P = 0.02; I2 = 85%) and a significantly shorter length of ICU stay (standardized mean difference [SMD], -0.21 hr; 95% CI, -0.37 to -0.05; P = 0.009; I2 = 48%). In addition, overall hospital LOS (SMD, -0.06 days; 95% CI, -0.18 to 0.06; P = 0.29; I2 = 0%) and incidence of postoperative delirium (RR, 0.69; 95% CI, 0.36 to 1.32; P = 0.27; I2 = 0%) were not impacted by the use of intraoperative cerebral oximetry. CONCLUSIONS: Intraoperative cerebral oximetry appears to be associated with a reduction in POCD, although this result should be interpreted with caution given the significant heterogeneity in the studies examined. Further large (ideally multicentre) RCTs are needed to clarify whether POCD can be favourably impacted by the use of cerebral oximetry-guided management.

Determining the Upper and Lower Limits of Cerebral Autoregulation With Cerebral Oximetry Autoregulation Curves: A Case Series.

OBJECTIVE: Critical care guidelines recommend a single target value for mean arterial blood pressure in critically ill patients. However, growing evidence regarding cerebral autoregulation challenges this concept and supports individualizing mean arterial blood pressure targets to prevent brain and kidney hypo- or hyperperfusion. Regional cerebral oxygen saturation derived from near-infrared spectroscopy is an acceptable surrogate for cerebral blood flow and has been validated to measure cerebral autoregulation. This study suggests a novel mechanism to construct autoregulation curves based on near-infrared spectroscopy-measured cerebral oximetry. DESIGN: Case-series study. SETTING: Neurocritical care unit in a tertiary medical center. PATIENTS: Patients with acute neurologic injury and Glasgow coma scale score less than or equal to 8. MEASUREMENTS AND MAIN RESULTS: Autoregulation curves were plotted using the fractional-polynomial model in Stata after multimodal continuous monitoring of regional cerebral oxygen saturation and mean arterial blood pressure. Individualized autoregulation curves of seven patients exhibited varying upper and lower limits of autoregulation and provided useful clinical information on the autoregulation trend (curves moving to the right or left during the acute coma period). The median lower and upper limits of autoregulation were 86.5 mm Hg (interquartile range, 74-93.5) and 93.5 mm Hg (interquartile range, 83-99), respectively. CONCLUSIONS: This case-series study showed feasibility of delineating real trends of the cerebral autoregulation plateau and direct visualization of the cerebral autoregulation curve after at least 24 hours of recording without manipulation of mean arterial blood pressure by external stimuli. The integration of multimodal monitoring at the bedside with cerebral oximetry provides a noninvasive method to delineate daily individual cerebral autoregulation curves.

Epidemiology of septic meningitis associated with neuraxial anesthesia: a historical review and meta-analysis.

INTRODUCTION: Neuraxial anesthesia in the form of spinal and epidural are two of the most frequent forms of regional anesthesia. We aimed to describe and compare the relevant epidemiological, clinical and microbiological characteristics of all reported cases of septic meningitis associated with the use of spinal and epidural anesthetics. EVIDENCE ACQUISITION: We performed a systematic review of septic meningitis associated with neuraxial anesthesia. We included all relevant case-reports and observational studies in which authors described septic meningitis in association with spinal, epidural or combined neuraxial anesthesia using local anesthetics. EVIDENCE SYNTHESIS: A total of 234 cases of septic meningitis were reported following review of 71 case-report articles and 22 epidemiological studies. In total, there have been 199, 25 and 10 reported cases of septic meningitis associated to spinal, epidural and combined neuraxial anesthesia, respectively. The lack of use of surgical masks was the most common risk factor (41, 16.7%). Streptococcus salivarius was the most common bacteria (17.0%) related to spinal anesthesia and Staphylococcus aureus (26.7%) was the most common one related to epidural. The time to symptom onset was significantly reduced in spinal (median time, 24 hours IQR [8-72] vs. 96 hours IQR [84-240]; P=0.003) compared to epidural anesthesia. The overall mortality rate is 15.3% and 13.3% for reported cases related to spinal and epidural anesthesia, respectively. CONCLUSIONS: While the true incidence remains speculative, this review suggests that given increasing indications for spinals and epidurals, septic meningitis remains an important associated with neuraxial anesthesia.

Cerebral Autoregulation-oriented Therapy at the Bedside: A Comprehensive Review.

This comprehensive review summarizes the evidence regarding use of cerebral autoregulation-directed therapy at the bedside and provides an evaluation of its impact on optimizing cerebral perfusion and associated functional outcomes. Multiple studies in adults and several in children have shown the feasibility of individualizing mean arterial blood pressure and cerebral perfusion pressure goals by using cerebral autoregulation monitoring to calculate optimal levels. Nine of these studies examined the association between cerebral perfusion pressure or mean arterial blood pressure being above or below their optimal levels and functional outcomes. Six of these nine studies (66%) showed that patients for whom median cerebral perfusion pressure or mean arterial blood pressure differed significantly from the optimum, defined by cerebral autoregulation monitoring, were more likely to have an unfavorable outcome. The evidence indicates that monitoring of continuous cerebral autoregulation at the bedside is feasible and has the potential to be used to direct blood pressure management in acutely ill patients.

A Comparison of Regional Versus General Anesthesia for Lumbar Spine Surgery: A Meta-Analysis of Randomized Studies.

BACKGROUND: General anesthesia (GA) is commonly used for lumbar spine surgery. The advantages of regional anesthesia (RA) for lumbar spine surgery, as compared with GA, remain unclear. The aim of this meta-analysis was to determine the impact of the type of anesthesia on intraoperative events, incidence of postoperative complications, and recovery time of patients undergoing lumbar spine surgery. METHODS: Major databases (PubMed, EMBASE, Cochrane library, ISI Web of Science, and Google Scholar) were systematically searched for randomized clinical trials comparing regional versus GA for lumbar spine surgery. Study-level characteristics, intraoperative events, and postoperative complications were extracted from the articles. Meta-analysis was performed using random-effect models. RESULTS: Fifteen randomized clinical trials comprising 961 patients were included in this meta-analysis. The use of RA for lumbar spine surgery was significantly associated with lower incidence of postoperative nausea and vomiting at 24 hours (risk ratio [RR]=0.42; 95% confidence interval [CI]=0.23-0.77, P=0.005), as well as lower length of stay (standardized mean difference [SMD]=-0.73; 95% CI=-1.17 to -0.29, P=0.001) and intraoperative blood loss (SMD=-1.24; 95% CI=-2.27 to -0.21, P=0.02). There was no statistically significant association with lower pain score (SMD=-0.47; 95% CI=-2.13 to 1.19, P=0.58), lower incidence of urinary retention (RR=1.16; 95% CI=0.73-1.86, P=0.53) or analgesic requirement (RR=0.87; 95% CI=0.64-1.18, P=0.37). CONCLUSIONS: In summary, RA has several advantageous characteristics, including lower incidence of postoperative nausea and vomiting, length of stay, and blood loss. Further well-designed studies with more sample size are needed to clarify the associations with possible neurological complications.

Predicting the need for nonstandard tracheostomy tubes in critically ill patients.

PURPOSE: Few guidelines exist regarding the selection of a particular type or size of tracheostomy tube. Although nonstandard tubes can be placed over the percutaneous kit dilator, clinicians often place standard tracheostomy tubes and change to nonstandard tubes only after problems arise. This practice risks early tracheostomy tube change, possible bleeding, or loss of the airway. We sought to identify predictors of nonstandard tracheostomy tubes. MATERIALS AND METHODS: In this matched case-control study at an urban, academic, tertiary care medical center, we reviewed 1220 records of patients who received a tracheostomy. Seventy-seven patients received nonstandard tracheostomy tubes (cases), and 154 received standard tracheostomy tubes (controls). RESULTS: Sex, endotracheal tube size, severity of illness, and computed tomography scan measurement of the distance from the trachea to the skin at the level of the superior aspect of the anterior clavicle were significant predictors of nonstandard tracheostomy tubes. Specifically, trachea-to-skin distance >4.4 cm and endotracheal tube sizes ≥8.0 were associated with nonstandard tracheostomy. CONCLUSIONS: The findings suggest that clinicians should consider using nonstandard tracheostomy tubes as the first choice if the patient is male with an endotracheal tube size ≥8.0 and has a trachea-to-skin distance >4.4 cm on the computed tomography scan.

Infectious Disease Risk Associated with Contaminated Propofol Anesthesia, 1989-2014(1).

Administration of propofol, the most frequently used intravenous anesthetic worldwide, has been associated with several iatrogenic infections despite its relative safety. Little is known regarding the global epidemiology of propofol-related outbreaks and the effectiveness of existing preventive strategies. In this overview of the evidence of propofol as a source of infection and appraisal of preventive strategies, we identified 58 studies through a literature search in PubMed, Embase, and Lilacs for propofol-related infections during 1989-2014. Twenty propofol-related outbreaks have been reported, affecting 144 patients and resulting in 10 deaths. Related factors included reuse of syringes for multiple patients and prolonged exposure to the environment when vials were left open. The addition of antimicrobial drugs to the emulsion has been instituted in some countries, but outbreaks have still occurred. There remains a lack of comprehensive information on the effectiveness of measures to prevent future outbreaks.

Abnormal movements in critical care patients with brain injury: a diagnostic approach.

Abnormal movements are frequently encountered in patients with brain injury hospitalized in intensive care units (ICUs), yet characterization of these movements and their underlying pathophysiology is difficult due to the comatose or uncooperative state of the patient. In addition, the available diagnostic approaches are largely derived from outpatients with neurodegenerative or developmental disorders frequently encountered in the outpatient setting, thereby limiting the applicability to inpatients with acute brain injuries. Thus, we reviewed the available literature regarding abnormal movements encountered in acutely ill patients with brain injuries. We classified the brain injury into the following categories: anoxic, vascular, infectious, inflammatory, traumatic, toxic-metabolic, tumor-related and seizures. Then, we identified the abnormal movements seen in each category as well as their epidemiologic, semiologic and clinicopathologic correlates. We propose a practical paradigm that can be applied at the bedside for diagnosing abnormal movements in the ICU. This model seeks to classify observed abnormal movements in light of various patient-specific factors. It begins with classifying the patient's level of consciousness. Then, it integrates the frequency and type of each movement with the availability of ancillary diagnostic tests and the specific etiology of brain injury.

A Sudden Change of Heart: A Case of Rapidly Reversed Stress Cardiomyopathy in a Critically Ill Patient.

We report the case of a 79-year-old woman who presented to our hospital for elective removal of an infratentorial meningioma and suffered a periprocedural cardiac arrest. Shortly after uncomplicated induction of anesthesia prior to the surgery, the patient became hypotensive and bradycardic, culminating ultimately in a cardiac arrest with pulseless electrical activity. Return of spontaneous circulation occurred within 90 seconds of arrest, but the patient remained dependent on maximal doses of epinephrine and dopamine for hemodynamic support. Echocardiography performed on the day of cardiac arrest revealed a newly depressed left ventricular ejection fraction (LVEF) of 15-20% with an apical ballooning pattern. Left heart catheterization showed no obstructive coronary lesions to explain her depressed ejection fraction. A diagnosis of stress cardiomyopathy (SCM) was made given the echocardiographic findings and absence of concomitant coronary disease. Within the next 24 hours, the patient was liberated from inotropic support, and at 6-month follow-up, her LVEF returned to 55% and she had no heart failure symptoms.

Difficult airway response team: a novel quality improvement program for managing hospital-wide airway emergencies.

BACKGROUND: Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. METHODS: We developed a quality improvement program-the Difficult Airway Response Team (DART)-to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had 3 core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a Web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. RESULTS: Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index >40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous or current tracheostomy. Twenty-three patients (6%) required emergent surgical airways. Sixty-two patients (17%) were stabilized and transported to the operating room for definitive airway management. There were no airway management-related deaths, sentinel events, or malpractice claims in adult patients managed by DART. Five in situ simulations conducted in the first program year improved DART's teamwork, communication, and response times and increased the functionality of the difficult airway carts. Over the 5-year period, we conducted 18 airway courses, through which >200 providers were trained. CONCLUSIONS: DART is a comprehensive program for improving difficult airway management. Future studies will examine the comparative effectiveness of the DART program and evaluate how DART has impacted patient outcomes, operational efficiency, and costs of care.

Restrictive and liberal red cell transfusion strategies in adult patients: reconciling clinical data with best practice.

Red blood cell (RBC) transfusion guidelines correctly promote a general restrictive transfusion approach for anemic hospitalized patients. Such recommendations have been derived from evaluation of specific patient populations, and it is important to recognize that engaging a strict guideline approach has the potential to incur harm if the clinician fails to provide a comprehensive review of the patient's physiological status in determining the benefit and risks of transfusion. We reviewed the data in support of a restrictive or a more liberal RBC transfusion practice, and examined the quality of the datasets and manner of their interpretation to provide better context by which a physician can make a sound decision regarding RBC transfusion therapy. Reviewed studies included PubMed-cited (1974 to 2013) prospective randomized clinical trials, prospective subset analyses of randomized studies, nonrandomized controlled trials, observational case series, consecutive and nonconsecutive case series, and review articles. Prospective randomized clinical trials were acknowledged and emphasized as the best-quality evidence. The results of the analysis support that restrictive RBC transfusion practices appear safe in the hospitalized populations studied, although patients with acute coronary syndromes, traumatic brain injury and patients at risk for brain or spinal cord ischemia were not well represented in the reviewed studies. The lack of quality data regarding the purported adverse effects of RBC transfusion at best suggests that restrictive strategies are no worse than liberal strategies under the studied protocol conditions, and RBC transfusion therapy in the majority of instances represents a marker for greater severity of illness. The conclusion is that in the majority of clinical settings a restrictive RBC transfusion strategy is cost-effective, reduces the risk of adverse events specific to transfusion, and introduces no harm. In anemic patients with ongoing hemorrhage, with risk of significant bleeding, or with concurrent ischemic brain, spinal cord, or myocardium, the optimal hemoglobin transfusion trigger remains unknown. Broad-based adherence to guideline approaches of therapy must respect the individual patient condition as interpreted by comprehensive clinical review.