Traumatic Brain Injury Causes Chronic Cortical Inflammation and Neuronal Dysfunction Mediated by Microglia.

Traumatic brain injury (TBI) can lead to significant neuropsychiatric problems and neurodegenerative pathologies, which develop and persist years after injury. Neuroinflammatory processes evolve over this same period. Therefore, we aimed to determine the contribution of microglia to neuropathology at acute [1 d postinjury (dpi)], subacute (7 dpi), and chronic (30 dpi) time points. Microglia were depleted with PLX5622, a CSF1R antagonist, before midline fluid percussion injury (FPI) in male mice and cortical neuropathology/inflammation was assessed using a neuropathology mRNA panel. Gene expression associated with inflammation and neuropathology were robustly increased acutely after injury (1 dpi) and the majority of this expression was microglia independent. At 7 and 30 dpi, however, microglial depletion reversed TBI-related expression of genes associated with inflammation, interferon signaling, and neuropathology. Myriad suppressed genes at subacute and chronic endpoints were attributed to neurons. To understand the relationship between microglia, neurons, and other glia, single-cell RNA sequencing was completed 7 dpi, a critical time point in the evolution from acute to chronic pathogenesis. Cortical microglia exhibited distinct TBI-associated clustering with increased type-1 interferon and neurodegenerative/damage-related genes. In cortical neurons, genes associated with dopamine signaling, long-term potentiation, calcium signaling, and synaptogenesis were suppressed. Microglial depletion reversed the majority of these neuronal alterations. Furthermore, there was reduced cortical dendritic complexity 7 dpi, reduced neuronal connectively 30 dpi, and cognitive impairment 30 dpi. All of these TBI-associated functional and behavioral impairments were prevented by microglial depletion. Collectively, these studies indicate that microglia promote persistent neuropathology and long-term functional impairments in neuronal homeostasis after TBI.SIGNIFICANCE STATEMENT Millions of traumatic brain injuries (TBIs) occur in the United States alone each year. Survivors face elevated rates of cognitive and psychiatric complications long after the inciting injury. Recent studies of human brain injury link chronic neuroinflammation to adverse neurologic outcomes, suggesting that evolving inflammatory processes may be an opportunity for intervention. Here, we eliminate microglia to compare the effects of diffuse TBI on neurons in the presence and absence of microglia and microglia-mediated inflammation. In the absence of microglia, neurons do not undergo TBI-induced changes in gene transcription or structure. Microglial elimination prevented TBI-induced cognitive changes 30 d postinjury (dpi). Therefore, microglia have a critical role in disrupting neuronal homeostasis after TBI, particularly at subacute and chronic timepoints.

Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation.

Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod-shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse-chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI-induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll-like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI-induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.

Cognitive deficits develop 1month after diffuse brain injury and are exaggerated by microglia-associated reactivity to peripheral immune challenge.

Traumatic brain injury (TBI) elicits immediate neuroinflammatory events that contribute to acute cognitive, motor, and affective disturbance. Despite resolution of these acute complications, significant neuropsychiatric and cognitive issues can develop and progress after TBI. We and others have provided novel evidence that these complications are potentiated by repeated injuries, immune challenges and stressors. A key component to this may be increased sensitization or priming of glia after TBI. Therefore, our objectives were to determine the degree to which cognitive deterioration occurred after diffuse TBI (moderate midline fluid percussion injury) and ascertain if glial reactivity induced by an acute immune challenge potentiated cognitive decline 30 days post injury (dpi). In post-recovery assessments, hippocampal-dependent learning and memory recall were normal 7 dpi, but anterograde learning was impaired by 30 dpi. Examination of mRNA and morphological profiles of glia 30 dpi indicated a low but persistent level of inflammation with elevated expression of GFAP and IL-1ß in astrocytes and MHCII and IL-1ß in microglia. Moreover, an acute immune challenge 30 dpi robustly interrupted memory consolidation specifically in TBI mice. These deficits were associated with exaggerated microglia-mediated inflammation with amplified (IL-1ß, CCL2, TNFα) and prolonged (TNFα) cytokine/chemokine expression, and a marked reactive morphological profile of microglia in the CA3 of the hippocampus. Collectively, these data indicate that microglia remain sensitized 30 dpi after moderate TBI and a secondary inflammatory challenge elicits robust microglial reactivity that augments cognitive decline. STATEMENT OF SIGNIFICANCE: Traumatic brain injury (TBI) is a major risk factor in development of neuropsychiatric problems long after injury, negatively affecting quality of life. Mounting evidence indicates that inflammatory processes worsen with time after a brain injury and are likely mediated by glia. Here, we show that primed microglia and astrocytes developed in mice 1 month following moderate diffuse TBI, coinciding with cognitive deficits that were not initially evident after injury. Additionally, TBI-induced glial priming may adversely affect the ability of glia to appropriately respond to immune challenges, which occur regularly across the lifespan. Indeed, we show that an acute immune challenge augmented microglial reactivity and cognitive deficits. This idea may provide new avenues of clinical assessments and treatments following TBI.

Two Methods of Hemodynamic and Volume Status Assessment in Critically Ill Patients: A Study of Disagreement.

INTRODUCTION: The invasive nature and potential complications associated with pulmonary artery (PA) catheters (PACs) have prompted the pursuit of less invasive monitoring options. Before implementing new hemodynamic monitoring technologies, it is important to determine the interchangeability of these modalities. This study examines monitoring concordance between the PAC and the arterial waveform analysis (AWA) hemodynamic monitoring system. METHODS: Critically ill patients undergoing hemodynamic monitoring with PAC were simultaneously equipped with the FloTrac AWA system (both from Edwards Lifesciences, Irvine, California). Data were concomitantly obtained for hemodynamic variables. Bland-Altman methodology was used to assess CO measurement bias and κ coefficent to show discrepancies in intravascular volume. RESULTS: Significant measurement bias was observed in both CO and intravascular volume status between the 2 techniques (mean bias, -1.055 ± 0.263 liter/min, r = 0.481). There was near-complete lack of agreement regarding the need for intravenous volume administration (κ = 0.019) or the need for vasoactive agent administration (κ = 0.015). CONCLUSIONS: The lack of concordance between PAC and AWA in critically ill surgical patients undergoing active resuscitation raises doubts regarding the interchangeability and relative accuracy of these modalities in clinical use. Lack of awareness of these limitations can lead to errors in clinical decision making when managing critically ill patients.

Comorbidity-polypharmacy score: a novel adjunct in post-emergency department trauma triage.

OBJECTIVE: Post-emergency department triage of older trauma patients continues to be challenging, as morbidity and mortality for any given level of injury severity tend to increase with age. The comorbidity-polypharmacy score (CPS) combines the number of pre-injury medications with the number of comorbidities to estimate the severity of comorbid conditions. This retrospective study examines the relationship between CPS and triage accuracy for older (≥45y) patients admitted for traumatic injury. METHODS: Patients aged 45y and older presenting to level 1 trauma center from 2005 to 2008 were included. Basic data included patient demographics, injury severity score, morbidity and mortality, and functional outcome measures. CPS was calculated by adding total numbers of comorbid conditions and pre-injury medications. Patients were divided into three triage groups: undertriage (UT), appropriate triage (AT), and overtriage (OT). UT criteria included initial admission to the floor or step-down unit followed by an unplanned transfer to intensive care unit (ICU) within 24h of admission. OT was defined as initial ICU admission for <1d without stated need for ICU level of care (i.e., lack of evidence for tracheal intubation or mechanical ventilation, injury-related hemorrhage, or other traditional ICU indications, such as intracranial bleeding). All other patients were presumed to be correctly triaged. The three triage groups were then analyzed looking for contributors to mistriage. RESULTS: Charts for 711 patients were evaluated (mean age, 63.5y; 55.7% male; mean ISS, 9.02). Of those, 11 (1.55%) met criteria for UT and 14 (1.97%) for OT. The remaining 686 patients had no evidence of mistriage. The three groups were similar in terms of injury severity and GCS. The groups were significantly different with respect to CPS, with UT CPSs (14.9±6.80) being nearly three times higher than OT CPSs (5.14±3.48). There were more similarities between AT and OT groups, with the UT group being characterized by greater number of complications and lower functional outcomes at discharge (all, P<0.05). The UT group had significantly higher mortality (27%) than the AT and OT groups (6% and 0%, respectively). CONCLUSIONS: In the era of medication reconciliation, CPS is easy to obtain and calculate in patients who are not critically injured. This study suggests that CPS may be a promising adjunct in identifying older trauma patients who are more likely to be undertriaged. The significance of our findings is especially important when considering that injury severity in the UT group was similar to that in the other groups. Further evaluation of CPS as a triage tool in acute trauma is warranted.

Sonographic evaluation of intravascular volume status in the surgical intensive care unit: a prospective comparison of subclavian vein and inferior vena cava collapsibility index.

BACKGROUND: Traditional methods for intravascular volume status assessment are invasive and are associated significant complications. While focused bedside sonography of the inferior vena cava (IVC) has been shown to be useful in estimating intravascular volume status, it may be technically difficult and limited by patient factors such as obesity, bowel gas, or postoperative surgical dressings. The goal of this investigation is to determine the feasibility of subclavian vein (SCV) collapsibility as an adjunct to IVC collapsibility in intravascular volume status assessment. METHODS: A prospective study was conducted on a convenience sample of surgical intensive care unit patients to evaluate interchangeability of IVC collapsibility index (IVC-CI) and SCV-CI. After demographic and acuity of illness information was collected, all patients underwent serial, paired assessments of IVC-CI and SCV-CI using portable ultrasound device (M-Turbo; Sonosite, Bothell, WA). Vein collapsibility was calculated using the formula [collapsibility (%) = (max diameter - min diameter)/max diameter × 100%]. Paired measurements from each method were compared using correlation coefficient and Bland-Altman measurement bias analysis. RESULTS: Thirty-four patients (mean age 56 y, 38% female) underwent a total of 94 paired SCV-CI and IVC-CI sonographic measurements. Mean acute physiology and chronic health evaluation II score was 12. Paired SCV- and IVC-CI showed acceptable correlation (R(2) = 0.61, P < 0.01) with acceptable overall measurement bias [Bland-Altman mean collapsibility difference (IVC-CI minus SCV-CI) of -3.2%]. In addition, time needed to acquire and measure venous diameters was shorter for the SCV-CI (70 s) when compared to IVC-CI (99 s, P < 0.02). CONCLUSIONS: SCV collapsibility assessment appears to be a reasonable adjunct to IVC-CI in the surgical intensive care unit patient population. The correlation between the two techniques is acceptable and the overall measurement bias is low. In addition, SCV-CI measurements took less time to acquire than IVC-CI measurements, although the clinical relevance of the measured time difference is unclear.

Optimizing Perioperative Fluid Management in Complex Abdominal Wall Reconstruction to Prevent Postoperative Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a serious postoperative complication of abdominal wall reconstruction that can significantly impact outcomes of these patients. This study examines AKI following abdominal wall hernia repair to determine incidence and risk factors and outline potential mitigation strategies. METHODS: Using a single institution IRB-approved prospective database, patients undergoing complex abdominal wall reconstruction from 2013 to 2021 were identified. Patients with AKI were compared to controls and preoperative and intraoperative characteristics were evaluated. Multivariate analysis was utilized to identify factors associated with development of AKI. RESULTS: 297 patients were reviewed, 21.2 % (n = 63 patients) had AKI. Patients with AKI had a greater decrease in postoperative GFR to preoperative GFR (40.5% vs 18.3%, p <0.0001). Factors associated with AKI included ASA score >2 (odds ratio (OR) = 2.10, [1.50; 5.12], p = 0.02), HTN (OR = 2.05, [1.05; 4.0], p = 0.04), higher baseline Cr (OR = 5.98, [2.56; 13.98], p <0.0001), and diabetes (OR = 0.135, [0.0275; 0.666], p = 0.01). Operative time was longer in patients who developed AKI [average 400 min (range: 278-510 min) vs 310 min (range: 260-374 min), p = 0.04] and was an independent predictor of developing AKI (OR = 319.59, [137.25; 744.65], p <0.0001). DISCUSSION: Preoperative identification of patients with medical comorbidities undergoing elective complex abdominal wall reconstruction continues to be imperative to improve outcomes. This study demonstrates that perioperative management for high risk patients requires flexibility, including potential adjustments to enhanced recovery after surgery protocols in order to adequately address the risks for AKI.

Comparison between midline and lateral fluid percussion injury in mice reveals prolonged but divergent cortical neuroinflammation.

Animal models are critical for determining the mechanisms mediating traumatic brain injury-induced (TBI) neuropathology. Fluid percussion injury (FPI) is a widely used model of brain injury typically applied either midline or parasagittally (lateral). Midline FPI induces a diffuse TBI, while lateral FPI induces both focal cortical injury (ipsilateral hemisphere) and diffuse injury (contralateral hemisphere). Nonetheless, discrete differences in neuroinflammation and neuropathology between these two versions of FPI remain unclear. The purpose of this study was to compare acute (4-72 h) and subacute (7 days) neuroinflammatory responses between midline and lateral FPI. Midline FPI resulted in longer righting reflex times than lateral FPI. At acute time points, the inflammatory responses to the two different injuries were similar. For instance, there was evidence of monocytes and cytokine mRNA expression in the brain with both injuries acutely. Midline FPI had the highest proportion of brain monocytes and highest IL-1ß/TNFα mRNA expression 24 h later. NanoString nCounter analysis 7 days post-injury revealed robust and prolonged expression of inflammatory-related genes in the cortex after midline FPI compared to lateral FPI; however, Iba-1 cortical immunoreactivity was increased with lateral FPI. Thus, midline and lateral FPI caused similar cortical neuroinflammatory responses acutely and mRNA expression of inflammatory genes was detectable in the brain 7 days later. The primary divergence was that inflammatory gene expression was greater and more diverse subacutely after midline FPI. These results provide novel insight to variations between midline and lateral FPI, which may recapitulate unique temporal pathogenesis.

Evaluation of Rectal Vancomycin Irrigation for Treatment of Clostridioides difficile Infection in Patients Post-Colectomy for Toxic Colitis.

Background: Clostridioides difficile infection (CDI) accounts for as many as 25% of episodes of antibiotic-associated diarrhea and is the most common cause of healthcare-associated diarrhea. Rectal vancomycin irrigation is a therapy option; however, evidence is limited for its value post-colectomy. The objective of this study was to describe outcomes of patients who underwent total colectomy for fulminant C. difficile colitis and received rectal vancomycin post-operatively. Methods: This was a single-center retrospective chart review of adult patients who underwent total colectomy for fulminant CDI. Efficacy outcomes were all-cause in-hospital death, intensive care unit (ICU) and hospital length of stay, ventilator-free days at day 28 post-procedure, development of proctitis or pseudomembranes, need for re-initiation of CDI therapy, and normalization of infectious signs and symptoms at completion of CDI therapy. The primary safety outcome was the incidence of rectal stump blowout. Results: Of the 50 patients included, 38 (76%) received treatment with rectal vancomycin at the discretion of the surgeon. The Sequential Organ Failure Assessment score on the day of the procedure was higher in the rectal vancomycin group; however, this difference did not reach statistical significance. No difference was observed between the groups in the primary outcome of all-cause death. There was no significant difference between the groups for hospital length of stay, but there was a trend toward longer ICU length of stay for patients who received rectal vancomycin (9.5 days vs. 2.5 days; p = 0.05). No differences in the remaining secondary efficacy outcomes were observed. No episodes of rectal stump blowout were observed in either group. Conclusions: This study aimed to add to the limited data on the use of rectal vancomycin irrigation post-colectomy for toxic C. difficile colitis. Although our results do not support routine use of rectal vancomycin irrigation, they suggest that this therapy is not harmful if providers are considering its use for severe infections refractory to alternative treatment.

µImpact of a nursing-driven sedation protocol with criteria for infusion initiation in the surgical intensive care unit.

PURPOSE: Analgesia and sedation protocols (ASPs) reduce duration of mechanical ventilation (MV) in the medical intensive care unit (ICU), but data in the surgical ICU (SICU) are limited. The objective of this study was to determine the impact of a nursing-driven ASP with criteria for infusion initiation in the SICU. MATERIALS AND METHODS: A single-center, retrospective study compared ventilator-free days at day 28 from start of MV (VFD28) before and after ASP implementation. Secondary endpoints included cumulative opioid and sedative requirements, level of sedation, incidence of delirium, SICU and hospital length of stay. RESULTS: One hundred thirty two patients were included (66 per group). The protocol group had greater VFD28 compared to the control group (21 vs. 14.5 days, p = .04). Lower rates of benzodiazepine (42.4% vs. 84.8%, p < .001) and opioid (24.2 vs. 78.8, p < .001) infusion use occurred in the protocol group, resulting in lower cumulative doses per ventilator-day through day 7. The protocol group had more documented sedation scores within target range. There were no differences in ICU delirium, SICU or hospital length of stay. CONCLUSIONS: A nursing-driven ASP with criteria for infusion initiation in mechanically-ventilated SICU patients may increase ventilator-free time, maintain patients at the target sedation goal, and reduce opioid and benzodiazepine utilization.

Modeling Human Cancer-induced Cachexia.

Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.

Improving the mortality index by capturing patient acuity through interprofessional real-time documentation improvement in a single hospital system.

BACKGROUND: The observed to expected mortality ratio is a standardized way for reporting inpatient mortality and is used as a measure for hospital quality rankings and Centers for Medicare & Medicaid Services value-based payments. The goal of this study is to describe a single institution's mortality index improvement initiative through improved documentation of patient severity. METHODS: Data were prospectively collected October 2016 through May 2017 on patients discharged from the acute care surgery, open heart surgery, neurosurgery, and University Hospital East. Mortalities were reviewed by a multidisciplinary committee for missed coding opportunities. These captured codes were adjusted based on the Vizient risk-adjustment model for mortality and the observed to expected mortality ratio was calculated. RESULTS: Every service reviewed showed improvement in the expected mortality rate. Additional coding opportunities were present in 55.6% of acute care surgery, 24.3% of neurosurgery, 18.3% of open heart surgery, and 35.3% of University Hospital East cases. A total of 70 codes were improved during the 8-month period. The acute care surgery service showed the most improvement, with a 0.45 improvement in the observed to expected mortality ratio, followed by neurosurgery, with 0.43 improvement. CONCLUSION: Institutional observed to expected mortality ratio can be improved by targeting high-acuity services and capturing coding opportunities, leading to improvement in value-based payments and rankings.

Daily review of AHRQ patient safety indicators has important impact on value-based purchasing, reimbursement, and performance scores.

BACKGROUND: The Patient Safety Indicators (PSIs) Composite (PSI 90) of the Agency for Healthcare Research and Quality has been found to have low positive predictive values. Because scores can affect hospital reimbursement and ranking, our institution designed a review process to ensure accurate data and incur minimal penalties under the Hospital Value-Based Purchasing Program. METHODS: A multidisciplinary team was assembled to review PSI 90 within a performance period. The positive predictive value of each PSI was calculated. Weight-adjusted PSI rates were used to recalculate the PSI 90 Performance Period Index Value (PPIV). The adjusted PPIV was used to estimate what the achievement points and financial impact would have been if PSI review had not been implemented. Differences in PPIV, achievement points, and financial impact before and after PSI review were calculated. RESULTS: A total of 1,470 cases were flagged for PSI over a 2-year period. The positive predictive value was 63.3%. Refuting 36.7% of PSIs resulted in a decrease in the PPIV from 0.696 to 0.508, an increase in achievement points from 5 to 10, resulting in a decreased net loss of $111,773. CONCLUSION: Multidisciplinary review processes are practical and effective in identifying false-positive patient safety events. The real-time process affects hospital performance and resultant Medicare reimbursement substantially.

Mortality and readmission of outcomes after discharge from the surgical intensive care unit to long-term, acute-care hospitals.

BACKGROUND: Patients with prolonged hospitalizations in the surgical intensive care unit often have ongoing medical needs that require further care at long-term, acute-care hospitals upon discharge. Setting expectations for patients and families after protracted operative intensive care unit hospitalization is challenging, and there are limited data to guide these conversations. The purpose of this study was to determine patient survival and readmission rates after discharge from the surgical intensive care unit directly to a long-term, acute-care hospital. METHODS: All patients who were admitted to the surgical intensive care unit at an academic, tertiary care medical center from 2009-2014 and discharged directly to long-term, acute-care hospitals were retrospectively reviewed. Patients represented all surgical subspecialties excluding cardiac and vascular surgery patients. Primary outcomes included 30-day readmission, and 1- and 3-year mortality rates following discharge. RESULTS: In total, 296 patients were discharged directly from the surgical intensive care unit to a long-term, acute-care hospital during the study period. There were 190 men (64%) and mean age was 61 ± 16 years. Mean duration of stay in the surgical intensive care unit was 27 ± 17 days. The most frequent complication was prolonged mechanical ventilation (277, 94%) followed by pneumonia (139, 47%), sepsis (78, 26%), and acute renal failure (32, 11%); 93% of patients required tracheostomy and enteral feeding access prior to discharge, and 19 patients (6%) were newly dependent on hemodialysis. The readmission rate was 20%. There were 86 deaths within 1 year from discharge (29%) with an overall 3-year mortality of 32%. In a multiple logistic regression analysis, a history of end-stage renal disease had a greater odds of readmission (odds ratio 6.07, P = .028). Patients with history of cancer had greater odds of 1- and 3-year mortality (odds ratio = 2.99, P = .028 and odds ratio 2.56, P = .053, respectively), and patients with a neurologic diagnosis had greater odds of 3-year mortality (odds ratio 4.69, P = .031). Readmission significantly increased the odds of 1- and 3-year mortality (odds ratio 3.12, P = .020 and odds ratio 2.90, P = .027, respectively). Patients who had both private insurance and Medicare had greater odds of 1- and 3-year mortality (odds ratio 10.39, P = .005 and odds ratio 10.65, P = .004, respectively). CONCLUSION: Patients who are discharged to long-term, acute-care hospitals have prolonged hospitalizations with high complication rates. These patients have high readmission and 1-year mortality rates. Patients and families should be counseled regarding these outcomes related to post-intensive care unit recovery after discharge to a long-term, acute-care hospital to allow for realistic expectations of survival after prolonged intensive care unit hospitalization.

Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator for Postoperative Respiratory Failure (PSI 11) does not identify accurately patients who received unsafe care.

BACKGROUND: The Agency for Healthcare Research and Quality Patient Safety Indicator 11 is used to identify postoperative respiratory failure events and detect areas for quality improvement. This study examines the accuracy of Patient Safety Indicator 11 in identifying clinically valid patient safety events. METHODS: All cases flagged for Patient Safety Indicator 11 from July 2013 to July 2015 by Agency for Healthcare Research and Quality QI Version 4.5 including International Classification of Diseases-9 codes were evaluated. Code-confirmed cases underwent independent review by 2 physicians. Inpatient electronic medical records were used to identify clinical factors for postoperative respiratory failure in each case to determine if postoperative respiratory failure was a result of unsafe care. The clinical true-positive rate and positive predictive value were calculated. RESULTS: A total of 166 postoperative respiratory failure cases were reviewed; 51 were recoded and reversed due to coding or documentation errors; 115 cases met the Agency for Healthcare Research and Quality definition of postoperative respiratory failure. A total of 71 (61.7%) of the 115 cases were false positives and did not reflect unsafe care, while 44 cases were true positives with a positive predictive value of 38.3%. χ(2) analysis did not reveal an association between demographics, clinical characteristics, or operative procedure with true-positive cases. CONCLUSION: Administrative coding data for Agency for Healthcare Research and Quality Patient Safety Indicator 11 do not identify accurately patients who received unsafe care when taking into account unpreventable clinical factors causing postoperative respiratory failure. The use of Agency for Healthcare Research and Quality Patient Safety Indicator 11 as a hospital performance measure should be reconsidered until inclusion and exclusion criteria are revised.

Priming the inflammatory pump of the CNS after traumatic brain injury.

Traumatic brain injury (TBI) can lead to secondary neuropsychiatric problems that develop and persist years after injury. Mounting evidence indicates that neuroinflammatory processes progress after the initial head injury and worsen with time. Microglia contribute to this inflammation by maintaining a primed profile long after the acute effects of the injury have dissipated. This may set the stage for glial dysfunction and hyperactivity to challenges including subsequent head injury, stress, or induction of a peripheral immune response. This review discusses the evidence that microglia become primed following TBI and how this corresponds with vulnerability to a 'second hit' and subsequent neuropsychiatric and neurodegenerative complications.

Impact of late fluid balance on clinical outcomes in the critically ill surgical and trauma population.

PURPOSE: Management of fluid status in critically ill patients poses a significant challenge due to limited literature. This study aimed to determine the impact of late fluid balance management after initial adequate fluid resuscitation on in-hospital mortality for critically ill surgical and trauma patients. MATERIALS AND METHODS: This single-center retrospective cohort study included 197 patients who underwent surgical procedure within 24 hours of surgical intensive care unit admission. Patients with high fluid balance on postoperative day 7 (>5 L) were compared with those with a low fluid balance (≤5 L) with a primary end point of in-hospital mortality. Subgroup analyses were performed based on diuretic administration, diuretic response, and type of surgery. RESULTS: High fluid balance was associated with significantly higher in-hospital mortality (30.2 vs 3%, P<.001) compared with low fluid balance; this relationship remained after multivariable regression analysis. High fluid balance was associated with increased mortality, independent of diuretic administration, diuretic response, and type of surgery. CONCLUSIONS: Consistent with previous literature, high fluid balance on postoperative day 7 was associated with increased in-hospital mortality. Patients who received and responded to diuretic therapy did not demonstrate improved clinical outcomes, which questions their use in the postoperative period.

Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1ß, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1ß and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1-7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications.

Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients.

PURPOSE: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. MATERIALS AND METHODS: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB), beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. RESULTS: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%). Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB) patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. CONCLUSIONS: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB) when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.