Effects of red-cell storage duration on patients undergoing cardiac surgery.

BACKGROUND: Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS: We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS: The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS: The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock.

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms.

Pharmacologic suppression of inflammation by a diphenyldifluoroketone, EF24, in a rat model of fixed-volume hemorrhage improves survival.

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)-mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase-1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2-mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1ß were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies.

Epidural anesthesia needle guidance by forward-view endoscopic optical coherence tomography and deep learning.

Epidural anesthesia requires injection of anesthetic into the epidural space in the spine. Accurate placement of the epidural needle is a major challenge. To address this, we developed a forward-view endoscopic optical coherence tomography (OCT) system for real-time imaging of the tissue in front of the needle tip during the puncture. We tested this OCT system in porcine backbones and developed a set of deep learning models to automatically process the imaging data for needle localization. A series of binary classification models were developed to recognize the five layers of the backbone, including fat, interspinous ligament, ligamentum flavum, epidural space, and spinal cord. The classification models provided an average classification accuracy of 96.65%. During puncture, it is important to maintain a safe distance between the needle tip and the dura mater. Regression models were developed to estimate that distance based on the OCT imaging data. Based on the Inception architecture, our models achieved a mean absolute percentage error of 3.05% ± 0.55%. Overall, our results validated the technical feasibility of using this novel imaging strategy to automatically recognize different tissue structures and measure the distances ahead of the needle tip during the epidural needle placement.

Multicenter Prospective Evaluation of Parenteral Nutrition Preparation Time and Resource Utilization: 3-Chamber Bags Compared With Hospital Pharmacy-Compounded Bags.

BACKGROUND: Parenteral nutrition (PN) is a complex and costly therapy that places significant demands on healthcare resources. Commercially manufactured 3-chamber bags (3CBs) offer potential time and cost advantages compared with hospital pharmacy-compounded bags (HCBs); however, no data are yet available from studies comparing these delivery systems in US hospitals. The primary aim of this study was to evaluate the PN preparation time and resource utilization required for 3CBs compared with HCBs in US hospitals. METHODS: A prospective, multicenter, time and motion study was performed to evaluate the time from transcription to completion of PN preparation and costs for 3CBs compared with HCBs. The cost per bag included labor, PN products, medical consumables, and equipment. RESULTS: One hundred thirty-six PN prescriptions were prepared during the study (66 prescriptions for 3CBs and 70 prescriptions for HCBs). The mean ± standard deviation total time required for transcription, review, validation, and preparation of PN was 5.5 ± 1.3 minutes for 3CBs vs 14.3 ± 6.2 minutes for HCBs (P < .001). The mean total cost per PN bag was $81.60 for 3CBs and $131.17 for HCBs (mean difference, -$49.57). CONCLUSION: Commercial 3CBs reduced staff time by 62% and direct costs by 37% compared with HCBs. The results demonstrate that 3CBs offer potential cost-savings for hospitalized patients who require PN in US hospitals.

Same-patient reproducibility of state entropy: a comparison of simultaneous bilateral measurements during general anesthesia.

BACKGROUND: State Entropy (SE) is an index of anesthetic depth similar to Bispectral Index (BIS). Both indices use a single-channel electroencephalogram, recorded from a unilaterally applied electrode on the forehead, as their input. Intrapatient reproducibility of BIS was questioned in a recent study in which simultaneous measurements from two electrodes applied to the same patient showed conflicting anesthetic depths. Our purpose was to determine whether SE results are similarly reproducible, even though their computation uses a different algorithm than BIS. In this study, we investigated the reproducibility of SE measurements simultaneously obtained from bilaterally applied electrodes in the same patient. METHODS: Entropy electrodes were applied bilaterally on 21 patients under general inhaled anesthesia. Simultaneous SE measurements from both electrodes were recorded every 10 s from each patient. Data were analyzed with Bland-Altman statistics. RESULTS: We obtained 14,379 pairs of SE measurements. Four percent of the individual measurements suggested conflicting anesthetic depth along with a numeric difference more than 10 points. Bias was not clinically significant (-0.3). Ninety-five percent limits of agreement were -11.7 and +11.6. CONCLUSIONS: SE showed a clinically significant degree of disagreement when probes were applied on both sides of the forehead in the same patient. Bland-Altman statistics showed better same-patient reproducibility in SE than did a similar study on BIS. Nevertheless, 4% of the simultaneously measured pairs of SE suggested different anesthetic depths and differed by more than 10 points. Caution is advised when using SE as a clinical index of anesthetic depth.

Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial.

CONTEXT: Ventilator-associated pneumonia (VAP) causes substantial morbidity. A silver-coated endotracheal tube has been designed to reduce VAP incidence by preventing bacterial colonization and biofilm formation. OBJECTIVE: To determine whether a silver-coated endotracheal tube would reduce the incidence of microbiologically confirmed VAP. DESIGN, SETTING, AND PARTICIPANTS: Prospective, randomized, single-blind, controlled study conducted in 54 centers in North America. A total of 9417 adult patients (> or = 18 years) were screened between 2002 and 2006. A total of 2003 patients expected to require mechanical ventilation for 24 hours or longer were randomized. INTERVENTION: Patients were assigned to undergo intubation with 1 of 2 high-volume, low-pressure endotracheal tubes, similar except for a silver coating on the experimental tube. MAIN OUTCOME MEASURES: Primary outcome was VAP incidence based on quantitative bronchoalveolar lavage fluid culture with 10(4) colony-forming units/mL or greater in patients intubated for 24 hours or longer. Other outcomes were VAP incidence in all intubated patients, time to VAP onset, length of intubation and duration of intensive care unit and hospital stay, mortality, and adverse events. RESULTS: Among patients intubated for 24 hours or longer, rates of microbiologically confirmed VAP were 4.8% (37/766 patients; 95% confidence interval [CI], 3.4%-6.6%) in the group receiving the silver-coated tube and 7.5% (56/743; 95% CI, 5.7%-9.7%) (P = .03) in the group receiving the uncoated tube (all intubated patients, 3.8% [37/968; 95% CI, 2.7%-5.2%] and 5.8% [56/964; 95% CI, 4.4%-7.5%] [P = .04]), with a relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; all intubated patients, 34.2% [95% CI, 1.2%-67.9%]). The silver-coated endotracheal tube was associated with delayed occurrence of VAP (P = .005). No statistically significant between-group differences were observed in durations of intubation, intensive care unit stay, and hospital stay; mortality; and frequency and severity of adverse events. CONCLUSION: Patients receiving a silver-coated endotracheal tube had a statistically significant reduction in the incidence of VAP and delayed time to VAP occurrence compared with those receiving a similar, uncoated tube. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00148642.

Organ Donor Management: Part 1. Toward a Consensus to Guide Anesthesia Services During Donation After Brain Death.

Worldwide 715 482 patients have received a lifesaving organ transplant since 1988. During this time, there have been advances in donor management and in the perioperative care of the organ transplant recipient, resulting in marked improvements in long-term survival. Although the number of organs recovered has increased year after year, a greater demand has produced a critical organ shortage. The majority of organs are from deceased donors; however, some are not suitable for transplantation. Some of this loss is due to management of the donor. Improved donor care may increase the number of available organs and help close the existing gap in supply and demand. In order to address this concern, The Organ Donation and Transplantation Alliance, the Association of Organ Procurement Organizations, and the Transplant and Critical Care Committees of the American Society of Anesthesiologists have formulated evidence-based guidelines, which include a call for greater involvement and oversight by anesthesiologists and critical care specialists, as well as uniform reporting of data during organ procurement and recovery.

Practical Application of the Revised Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: A Case Study Approach.

BACKGROUND: Nutrition therapy is an essential component of the care plan for critically ill and injured patients. There is consensus that critically ill patients are at risk for malnutrition, and the associated consequences of increased infectious morbidity, multiorgan dysfunction, prolonged hospitalization, and disproportionate mortality can be minimized with specialized enteral and/or parenteral nutrition therapy. METHODS: In this article, we describe 2 case studies that are intended to introduce the nutrition support clinician to key updates in the recently released Guidelines for Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). RESULTS: The case studies demonstrate a pragmatic approach to nutrition therapy in the intensive care unit (ICU) and are intended to elicit dialogue for timely, appropriate nutrition care at policy meetings, professional conferences, and ICU daily rounds. CONCLUSIONS: While explicitly stated in the formal document, it is worth repeating that the guidelines are directed toward generalized patient populations, but as with any therapeutic intervention in the ICU, nutrition therapy should be tailored to the individual patient. In addition, protocols and procedures should reflect the local institutional culture and meet with approval of critical care clinicians.

Nanovesicular liposome-encapsulated hemoglobin (LEH) prevents multi-organ injuries in a rat model of hemorrhagic shock.

The goals of resuscitation in hemorrhagic shock are to correct oxygen deficit and to maintain perfusion pressure to the vital organs. We created liposome-encapsulated hemoglobin (LEH) as a nanoparticulate oxygen carrier (216±2nm) containing 7.2g/dl hemoglobin, and examined its ability to prevent the systemic manifestations of hemorrhagic shock (45% blood loss) in a rat model. We collected plasma after 6h of shock and LEH resuscitation, and determined the circulating biomarkers of systemic inflammation and functions of liver, gut, heart, and kidney. As is typical of the shock pathology, a significant increase in the plasma levels of cardiac troponin, liver function enzymes, soluble CD163 (macrophage activation), and creatinine, and the liver/gut myeloperoxidase activity was observed in the hemorrhaged rats. The plasma levels of TNF-α, IL-6, IL-1α, CINC-1, and IL-22 also increased after hemorrhagic shock. LEH administration prevented the hemorrhagic shock-induced accumulation of the markers of injury to the critical organs and pro-inflammatory cytokines. LEH also decreased the plasma levels of stress hormone corticosterone in hemorrhaged rats. Although saline also reduced the circulating corticosterone and a few other tissue injury markers, it was not as effective as LEH in restraining the plasma levels of creatinine, alanine transaminase, CD163, TNF-α, IL-6, and IL-1α. These results indicate that resuscitation with nanoparticulate LEH creates a pro-survival phenotype in hemorrhaged rats, and because of its oxygen-carrying capacity, LEH performs significantly better than saline in hemorrhagic shock.

Nutrients with immune-modulating effects: what role should they play in the intensive care unit?

PURPOSE OF REVIEW: This review will summarize recent clinical and experimental data on the use of immune-modulating nutrients in critical illness. It will present the concept of these nutrients as pharmacologic agents or 'nutraceuticals' administered in addition to protein, calorie, vitamin, and trace element sources. RECENT FINDINGS: Studies have defined the physiologic roles of arginine in critical illness, such as its role as a precursor for the production of nitric oxide. Investigations have determined that, in critical illness, glutamine levels decrease and severe glutamine deficiency is associated with increased mortality. Experimental studies have revealed that glutamine attenuates proinflammatory cytokine responses, improves gut barrier and immune cell functions, increases the ability to mount a stress response, and decreases mortality. Clinical trials and meta-analyses of studies testing immune-modulating nutritional formulations have reported numerous benefits but also some conflicting results. Dose and route of administration are key factors that influence the benefit, or lack thereof, of these nutraceuticals. SUMMARY: Cumulative studies of enteral immune-modulating nutritional formulations report benefits in surgical critically ill patients such as burn, trauma, or gastrointestinal surgery populations. Conflicting data in patients with sepsis warrant concern and further evaluation; in particular, controversy seems to stem around the use of arginine. Glutamine is beneficial when given in high doses or via the parenteral route (>0.20-0.30 g/kg per day or >or=30 g/day). Providing both omega-3 and omega-6 polyunsaturated fatty acids is important in immune modulation. The best doses and combinations of immune-modulating components remain unclear.