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Veno-arterial extracorporeal life support (V-A ECLS) has become a cornerstone in the management of critical cardiogenic shock, but it can also precipitate organ injury, e.g., acute kidney injury (AKI). Available studies highlight the effect of non-cardiac organ injury on patient outcomes. Only very little is known about the impact of non-cardiac organ recovery on patient survival. AKI occurs frequently during cardiogenic shock and carries a poor prognosis. We have developed descriptive models to hypothesize on the role of AKI severity versus that of recovery of renal function for patient survival.Retrospective, observational study including 175 patients who were successfully decannulated from V-A ECLS. We assessed AKI severity using the "Kidney Disease: Improving Global Outcomes" (KDIGO) criteria. We defined recovered or preserved renal function (RPRF) prior to decannulation from V-A ECLS as 0 (AKI with no improvement) or 1 (no AKI or AKI with improvement). We classified patient outcomes as alive or dead at hospital discharge.78% (n = 138) of all patients survived hospital discharge of which 38% (n = 67) never developed AKI. After adjusting for shock severity and non-renal organ injury, RPRF emerged as an independent predictor of survival in both the overall cohort [OR (95% CI) - 4.11 (1.72-9.79)] and the AKI-only sub-cohort [OR (95% CI) - 5.18 (1.8-14.92)]. Neither maximum KDIGO stage nor KDIGO stage at the end of V-A ECLS was independently associated with survival.Our model identifies RPRF, but not AKI severity, as an independent predictor of hospital survival in patients undergoing V-A ECLS for cardiogenic shock. We hypothesize that recovered or preserved non-cardiac organ function during V-A ECLS is crucial for patient survival.

Surgical site infections (SSIs) are an undesired perioperative outcome. Recent studies have shown increases in hospital acquired infections during the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study was to evaluate postoperative SSIs in the COVID-19-era compared to a historical cohort at a large, multicenter, academic institution.A retrospective review of all patients who underwent National Health and Safety Network (NHSN) inpatient surgical procedures between January 1, 2018 and December 31, 2020. Patients from the COVID-19-era (March-December 2020) were compared and matched 1:1 with historical controls (2018/2019) utilizing the standardized infection ratio (SIR) to detect difference.During the study period, 29,904 patients underwent NHSN procedures at our institution. When patients from the matched cohort (2018/2019) were compared to the COVID-19-era cohort (2020), a decreased risk of SSI was observed following colorectal surgery (RR = 0.94, 95% CI [0.65, 1.37], P = .76), hysterectomy (RR = 0.88, 95% CI [0.39, 1.99], P = .75), and knee prothesis surgery (RR = 0.95, 95% CI [0.52, 1.74], P = .88), though not statistically significant. An increased risk of SSI was observed following hip prosthesis surgery (RR 1.09, 95% CI [0.68, 1.75], P = .72), though not statistically significant.The risk of SSI in patients who underwent NHSN inpatient surgical procedures in 2020 with perioperative COVID-19 precautions was not significantly different when compared to matched controls at our large, multicenter, academic institution.

The 23rd Acute Disease Quality Initiative (ADQI-23) consensus conference proposed a framework to integrate biomarkers into the staging of acute kidney injury (AKI). It is unknown whether tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulinlike growth factor binding protein 7 (IGFBP7) could be used for staging.To test whether higher levels of urinary [TIMP-2] × [IGFBP7] are associated with lower survival among patients with the same functional stage of AKI.This cohort study was performed using data from the Protocolized Care for Early Septic Shock (ProCESS) trial, which enrolled critically ill patients with septic shock who presented at academic and community emergency departments and intensive care units in the US from March 2008 to May 2013. Patients with end-stage kidney disease, a reference serum creatinine level of 4 mg/dL or greater (to convert to μmol/L, multiply by 76.25), or missing data on serum creatinine levels or urinary levels of [TIMP-2] × [IGFBP7] were excluded. Data were analyzed from October 2020 to October 2021.The presence of AKI, assessed using Kidney Disease: Improving Global Outcomes criteria within 24 hours after enrollment and the highest AKI stage as well as urinary [TIMP-2] × [IGFBP7] level at 6 hours after enrollment. A previously reported high-specificity cutoff level for [TIMP-2] × [IGFBP7] of 2.0 (ng/mL)2/1000 was used to categorize patients (including those without functional criteria of AKI) according to the new staging system proposed by the ADQI-23 as biomarker negative (urinary [TIMP-2] × [IGFBP7] level ≤2.0 [ng/mL]2/1000) or biomarker positive ([TIMP-2] × [IGFBP7]2.0 [ng/mL]2/1000).Survival (assessed using Kaplan-Meier plots and the log-rank test) and mortality (assessed using relative risk [RR] 30 days after enrollment).The analysis included 999 patients with a median age of 61 years (IQR, 50-73 years); 554 (55.5%) were male. Biomarker-positive patients had lower survival and higher mortality at 30 days in the groups with AKI stage 1 (RR, 2.20; 95% CI, 1.02-4.72), stage 2 (RR, 1.53; 95% CI, 1.04-2.27), and stage 3 (RR, 1.61; 95% CI, 1.00-2.60). The associations were specific to patients with AKI. No difference in 30-day survival was found between biomarker-positive and biomarker-negative patients in the absence of functional criteria for AKI (RR, 1.16; 95% CI, 0.45-3.01).The findings suggest that assessment of the cell-cycle arrest biomarkers TIMP-2 and IGFBP7 may augment AKI staging for patients with functional criteria for AKI.

Rationale: Urinary TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor–binding protein 7) can predict acute kidney injury (AKI) in patients with sepsis.Objectiv...

Extracorporeal membrane oxygenation (ECMO), a form of extracorporeal life support (ECLS), represents a life-saving intervention in patients with cardiac and/or respiratory failure not responding to medical therapy. Blood is drained from a central vein (V), pumped through a membrane oxygenator for oxygenation and CO2 removal, and ultimately returned into a central vein or artery (A). Veno-arterial (V-A) ECMO is primarily used for patients in cardiogenic shock and provides both hemodynamic and respiratory support. V-A ECMO can limit or prevent secondary end-organ damage and allow time for myocardial recovery while a decision is made for the best definitive treatment. Conventional peripheral V-A ECMO, that is, return via femoral artery, carries the risks of differential oxygenation with upper body hypoxemia and extremity ischemia. Veno-venous (V-V) ECMO can rescue patients with the most severe respiratory failure but does not provide hemodynamic support. V-V ECMO allows for lung rest in patients who otherwise would receive potentially injurious ventilator support. Both V-A and V-V ECMO are invaluable, life-saving tools in patients who are failing maximum medical therapy.

Introduction About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD. Methods Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2∗IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD. Results Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. Conclusions AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed., Graphical abstract

Interfacility transport of a critically ill patient with acute respiratory distress syndrome (ARDS) may be necessary for a higher level of care or initiation of extracorporeal membrane oxygenation (ECMO). During the COVID-19 pandemic, ECMO has been used for patients with severe ARDS with successful results. Transporting a patient after ECMO cannulation by the receiving facility brings forth logistic challenges, including availability of adequate personal protective equipment for the transport team and hospital capacity management issues. We report our designated ECMO transport team's experience of 5 patients with COVID-19-associated severe ARDS after cannulation at the referring facility. Focusing on transport-associated logistics, creation of checklists, and collaboration with emergency medical services partners is necessary for safe and good outcomes for patients while maintaining team safety.

Objective To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. Methods We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. Results A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19–directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. Conclusion Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Introduction: During the COVID-19 pandemic, hospitals across the globe have been challenged with following the chain of survival with Get With The Guidelines (GWTG) metrics of time to epinephrine, CPR and early defibrillation while ensuring resuscitation teams are protected with recommended PPE. Healthcare organizations are seeking innovative processes to implement PPE during resuscitation events (codes) while maintaining a timely response. Hypothesis: Utilization of for PPE for Airborne Precautions for all resuscitation events can be achieved without compromising patient outcomes or GWTG metrics. Methods: In collaboration with Infection Prevention and Control (IPAC), the Resuscitation Subcommittee at an academic medical center developed a modified airborne PPE workflow for both inpatient and outpatient resuscitation events. For staff safety, all patients are considered as COVID-19 positive during a code response. Identifying timely donning and doffing techniques of PPE as paramount for maintaining GWTG metrics, a Safety Officer was implemented as an additional member of the code team. The role of the Safety Officer is to assist with the PPE process and to monitor code team compliance. Other measures implemented included attaching PPE supply bags to all code carts for easy access, adding viral filters on the bag valve masks, conducting educational mock code events, and providing online resources for staff. To measure process outcomes, pre COVID-19 pandemic GWTG metrics, mortality, and survival to discharge rates were compared with COVID-19 metrics utilizing the modified airborne PPE workflow. Conclusions: Despite additional use of PPE, the hospital has maintained patient outcomes and adhered to the GWTG resuscitation measures of time to epinephrine, CPR and defibrillation while ensuring the utmost safety of the code team during the COVID-19 pandemic. Table 1: GWTG-Award Measures *Preliminary Results

Objectives Effective communication among health care providers is critically important for patient safety. Handoff of patient care from the operating room (OR) to the intensive care unit (ICU) is particularly prone to errors. The process is more complicated in an academic environment in which junior clinicians are being trained. Standardization of, and training in, transitions of care can be a crucial means to improve patient safety. Study design Pre- and postintervention surveys of health care providers. Methods Based on a workflow analysis and qualitative needs assessments, we developed a 3-step protocol to standardize the handoff of care from the OR to the ICU for adult patients after cardiac surgery and to provide an effective learning environment. The process starts during surgery, continues when the patient leaves the OR, and concludes with the actual face-to-face transfer of care between providers, at the bedside, in the ICU. We conducted pre- and postimplementation surveys among physician trainees and nursing staff regarding their perception of the handoff process. Results We surveyed 42 clinicians before and 33 after implementation of the handoff process. Prior to implementation, most clinicians expressed a need to improve the current process; this perceived need was significantly greater in health care professionals with 4 or fewer years of experience. Post implementation, clinicians saw a significant improvement in information provided, efficiency, relevance to patient care, and psychological safety, a concept in which participants feel accepted and respected in a group setting without fear of negative consequences or judgement. Conclusions Our workflow-oriented, standardized process for handoff of care from the OR to the ICU can improve perceived communication and psychological safety, especially for junior clinicians.

Objectives To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. Design The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. Setting The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. Interventions We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. Measurements and main results In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. Conclusions Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

Interactions between lung and kidney can significantly affect the course of acute diseases, a phenomenon that was first observed in the 1950s by describing pulmonary dysfunction in uremic patients. From animal experiments there is ample evidence for remote lung injury following acute kidney injury (AKI), with an increased risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS). Coincident ARDS and AKI are associated with higher rates of intubation and mechanical ventilation, significantly prolonged weaning from mechanical ventilation and increased mortality. On the other hand, acute lung diseases and mechanical ventilation can promote the development of AKI and are associated with increased mortality when AKI is also present. These bidirectional interactions may include hemodynamic adverse effects during mechanical ventilation or volume overload as well as the release or decreased clearance and metabolism of proinflammatory mediators (e.g., interleukin-6 and tumor necrosis factor-α), which may induce and aggravate distant organ injury. The aim of this work is to examine the interactions between lung and the kidney in critically ill patients, as well as discuss potential preventive approaches.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical circulatory support for patients with advanced cardiogenic shock, facilitating myocardial recovery and limiting multi-organ failure. In patients with severely limited left ventricular ejection, peripheral VA-ECMO can further increase left ventricular and left atrial pressures (LAP). Failure to decompress the left heart under these circumstances can result in pulmonary edema and upper body hypoxemia, that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in these situations. However, the effects of atrial septostomy on upper body oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult VA-ECMO patients between January 2011 and June 2016 who also underwent atrial septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), Pa O2 /Fi O2 ratios (blood samples from right radial artery), intrathoracic volume status, and resolution of pulmonary edema before and up to 48 h after septostomy. There were no procedure-related complications. Thirty-day survival was 44%. LAP/PCWP decreased by approximately 40% immediately following septostomy and remained so for at least 24 h. Pa O2 /Fi O2 ratios significantly increased from 0.49 (0.38-2.12) before to 5.35 (3.01-7.69) immediately after septostomy and continued so for 24 h, 6.6 (4.49-10.93). Radiographic measurements also indicated a significant improvement in thoracic intravascular volume status after atrial septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and intrathoracic vascular volume status in patients developing severe refractory pulmonary edema while undergoing peripheral VA-ECMO. Atrial septostomy therefore appears safe and suitable to reduce the risk of upper body ischemia under these circumstances.

Cytokines play a critical role in coordinating and amplifying a host immune response to infection. The normal pattern of localized and systemic release of proinflammatory and anti-inflammatory cytokines varies on the basis of the disease process. A dysregulated cytokine response can lead to a hyper-inflammatory condition called a cytokine storm. This is believed to contribute to the pathophysiology of sepsis and septic shock, a condition carrying high morbidity and mortality in critically ill patients. Extracorporeal cytokine hemoadsorption is an emerging technology utilized in the treatment of dysregulated inflammatory states such as sepsis, although there is a paucity of clinical evidence supporting its outcomes benefits. We assess the peer-reviewed literature relating to cytokine hemoadsorption in the context of sepsis and suggest areas of future research incorporating this novel technology.

BACKGROUND:. Chimeric antigen receptor T-cell therapies (CAR-T) are transforming the treatment of B-cell leukemias and lymphomas. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome represent common, potentially life-threatening toxicities from chimeric antigen receptor T-cell therapy treatment. CASE SUMMARY:. We present a 53-year-old patient with primary refractory high-grade B-cell lymphoma who developed severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy but exhibited complete recovery after extracorporeal blood purification with CytoSorb (CytoSorbents, Monmouth Junction, NJ). Six days after chimeric antigen receptor T-cell therapy infusion, the patient developed cytokine release syndrome grade 3, prompting administration of dexamethasone and tocilizumab, a monoclonal antibody against the interleukin-6 receptor. His C-reactive protein levels started to decrease with tocilizumab and dexamethasone treatments. However, his ferritin levels continued to rise, and his interleukin-6 levels were above the upper detection threshold. Thirty-six hours later, the patient showed improved cytokine release syndrome but developed severe immune effector cell-associated neurotoxicity syndrome with predominant encephalopathy (grade 3) despite treatment with dexamethasone/methylprednisolone, tocilizumab, and anakinra. We therefore sought a rescue strategy to remove inflammatory mediators. Following emergency use authorization, we initiated extracorporeal blood purification with CytoSorb (CytoSorbents). Four-day extracorporeal blood purification resulted in complete resolution of immune effector cell-associated neurotoxicity syndrome and greater than 95% reduction in interleukin-6 levels without side effects. The patient was discharged home 10 days later with no signs of neurotoxicity or other secondary end-organ dysfunction. CONCLUSIONS:. Our case represents the first reported, successful application of extracorporeal blood purification with CytoSorb (CytoSorbents) to treat severe, refractory neurotoxicity following chimeric antigen receptor T-cell therapy.

Objective To assess the prevalence of acute kidney injury in patients with subarachnoid hemorrhage patients. Design Retrospective analysis of all subarachnoid hemorrhage admissions. Settings Neurocritical care unit. Patients All patients with a diagnosis of subarachnoid hemorrhage between 2009 and 2014. Interventions None. Measurements and main results Of 1,267 patients included in this cohort, 16.7% developed acute kidney injury, as defined by Kidney Disease Improving Global Outcome criteria (changes in creatinine only). Compared to patients without acute kidney injury, patients with acute kidney injury had a higher prevalence of diabetes mellitus (21.2% vs 9.8%; p Conclusions Critically ill patients with subarachnoid hemorrhage show a strong association between hyperchloremia and acute kidney injury as well as acute kidney injury and mortality.

Background Mounting evidence suggests that sepsis-induced morbidity and mortality are due to both immune activation and immunosuppression. Resistin is an inflammatory cytokine and uremic toxin. Septic hyperresistinemia (plasma resistin >20 ng/ml) has been associated with greater disease severity and worse outcomes, and it is further exacerbated by concomitant acute kidney injury (AKI). Septic hyperresistinemia disturbs actin polymerization in neutrophils leading to impaired neutrophil migration, a crucial first-line mechanism in host defense to bacterial infection. Our experimental objective was to study the effects of hyperresistinemia on other F-actin-dependent neutrophil defense mechanisms, in particular intracellular bacterial clearance and generation of reactive oxygen species (ROS). We also sought to examine the effects of hemoadsorption on hyperresistinemia and neutrophil dysfunction. Methods Thirteen patients with septic shock and six control patients were analyzed for serum resistin levels and their effects on neutrophil migration. In vitro, following incubation with resistin-spiked serum samples, Pseudomonas aeruginosa clearance and ROS generation in neutrophils were measured. Phosphorylation of 3-phosphoinositide-dependent protein kinase-1 (PDPK1) was assessed using flow cytometry. In vitro hemoadsorption with both Amberchrome™ columns (AC) and CytoSorb® cartridges (CC) were used to test correction of hyperresistinemia. We further tested AC for their effect on cell migration and ROS generation and CC for their effect on bacterial clearance. Results Patients with septic shock had higher serum resistin levels than control ICU patients and showed a strong, negative correlation between hyperresistinemia and neutrophil transwell migration (ρ= − 0.915, p

Peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO) has gained increasing value in the management of patients with critical cardiogenic shock (cCS), allowing time for myocardial recovery. Failure of myocardial recovery has life-altering consequences: transition to durable mechanical circulatory support (dMCS), urgent heart transplantation, or withdrawal of support. Clinical factors controlling myocardial recovery under these circumstances remain largely unknown. Using a retrospective cohort, we developed a model for early prediction of transition to dMCS in patients undergoing pVA-ECMO for cCS. To promote myocardial recovery, our clinical management centered around left ventricular pressure unloading, that is, targeting pulmonary capillary wedge pressures (PCWP) ≤18 mm Hg. We collected demographic data, laboratory findings, inotrope use, and two-dimensional transthoracic echocardiography measurements, all limited to the first 72h of pVA-ECMO (D1-3). Out of 70 patients who were alive after pVA-ECMO, 27 patients underwent implantation of dMCS. There was no significant difference in survival to hospital discharge between patients with or without transition to dMCS. Ejection fractionD1-3 (per 10% increase, OR 0.37 [0.17-0.79]) and amount of inotropic supportD1-3 (OR 4.77 [1.6-14.18]) but neither myocardial wall tension nor PCWP emerged as significant predictors of transition to dMCS. Optimism-corrected c-index (0.90 [0.89-0.90]) revealed an excellent discriminative ability of our model. In summary, our model for early prediction of transition to dMCS in patients with cCS undergoing pVA-ECMO identifies indicators of inotropic state as relevant factors. Absence of markers for myocardial oxygen consumption or left ventricular pressure loading allows us to hypothesize sufficient cardiac unloading in our cohort with PCWP-targeted management.

Background Sepsis-induced immunosuppression is a key factor contributing to the morbidity and mortality of critically ill patients, and polymorphonuclear neutrophil dysfunction is believed to be a hallmark of this immunosuppression. Circulating myeloid cells produce the cytokine resistin (RETN), which has been associated with poor outcomes in sepsis/septic shock and can directly inhibit neutrophil function. We previously demonstrated that resistin caused a dose-dependent impairment in neutrophil migration, reactive oxygen species production, and bacterial clearance in neutrophil cell lines. However, the relative antimicrobial responses of other innate immune cells to Gram-positive and Gram-negative infections in the presence of elevated levels of resistin have not been evaluated. We hypothesized that resistin directly contributes to sepsis-induced immunosuppression by selectively targeting the neutrophil component of the innate cellular immune system. Thus, the goal of the present study was to compare the effect of resistin on bacterial killing using monocultures or co-cultures of monocyte and neutrophil cell lines, as well as to extend our findings to primary immune cells. Results Our results indicate that human resistin impairs the ability of neutrophils to kill the Gram-negative bacterium Pseudomonas aeruginosa and the Gram-positive bacterium Staphylococcus aureus. In contrast, with the exception of macrophages incubated with P. aeruginosa, resistin did not affect the ability of macrophages or monocytes to kill either Gram-positive or Gram-negative organisms. Furthermore, co-incubation of neutrophils with increasing proportions of monocytes did not enhance bacterial killing. Resistin blocked bactericidal activity through partial reduction of F-actin polymerization and suppression of the oxidative burst in neutrophils. Conclusions Our studies indicate that resistin selectively impairs neutrophil bacterial killing. These findings further support the notion that resistin can mimic cell type-dependent immunosuppressive effects. This is consistent with its putative role in the pathogenesis of bacterial sepsis.

Acute kidney injury (AKI) now is recognized as a systemic disease. It occurs frequently in critically ill patients and has profound effects on morbidity and mortality. Recent research efforts have shown a bidirectional interplay between AKI and the immune system. Both innate and adaptive immune responses mediate renal injury as well as recovery from AKI. Dendritic cells, monocytes/macrophages, neutrophils, T lymphocytes, and B lymphocytes all play specific roles in the development of AKI. M2 macrophages and regulatory T cells also are pivotal in controlling inflammation, tissue remodeling, and repair after AKI. Conversely, existing evidence also suggests that increased production and decreased clearance of cytokines as well as dysfunction of immune cells, in particular neutrophils, can contribute to immune dysfunction and impaired bacterial clearance during AKI. Clinical data indicate that AKI is a risk factor for infections after various forms of critical illness, including cardiac surgery, malignancies, or severe trauma. Available evidence does not suggest that standard renal replacement therapies improve outcome from AKI beyond control of fluid balance and azotemia. Thus, novel approaches likely will be necessary to prevent or treat AKI-induced dysregulation of the inflammatory response.

Rather than simply being a co-morbidity, acute kidney injury (AKI) in critically ill patients has emerged as a systemic disease process with potentially fatal outcomes. AKI has both short-term and long-term effects. Short-term complications include acidosis, hyperkalemia, and fluid overload. They are usually amendable to conventional modes of renal replacement therapy (RRT). Unfortunately, these well-known, easily corrected short-term effects do not provide plausible explanation as to why AKI has such deleterious effects on morbidity and mortality. Morbidity and mortality from AKI remain high despite continuing attempts to advance mode, dose and delivery of RRT. Extensive experimental work as well as small clinical studies have revealed new, principal insight into the remote effects of AKI, in particular the interactions between AKI and innate immunity. Two crucial consequences of AKI regarding innate immunity have been recognized so far: • AKI reduces systemic cytokine clearance while increasing renal cytokine production, leading to an overall prolonged increase of pro-inflammatory cytokine levels during acute systemic inflammatory processes. • AKI attenuates recruitment of neutrophils to the site of inflammation. Impaired signaling and F-actin formation represent intracellular correlates of AKI-induced neutrophil dysfunction. Whereas elevated levels of pro-inflammatory cytokines are sufficient to explain some remote organ injuries seen in patients with AKI, e.g. acute lung injury, AKI-induced neutrophil dysfunction presents a plausible mechanism for increased infection rates seen in patients with AKI. Resistin, an inflammatory cytokine and uremic toxin, is sufficient to reproduce the effects of AKI-induced neutrophil dysfunction but does not appear to be cleared by conventional RRT.

The liver and kidney are key organs of metabolic homeostasis in the body and display complex interactions. Liver diseases often have direct and immediate effects on renal physiology and function. Conversely, acute kidney injury (AKI) is a common problem in patients with both acute and chronic liver diseases. AKI in patients with acute liver failure is usually multifactorial and involves insults similar to those seen in the general AKI population. Liver cirrhosis affects and is directly affected by aberrations in systemic and renal hemodynamics, inflammatory response, renal handling of sodium and free water excretion, and additional nonvasomotor mechanisms. Subsequent problems, for example, worsening ascites, hyponatremia, and AKI, often complicate management of patients with chronic progressive liver disease and add to their morbidity and mortality. Thus, AKI must be carefully defined and diagnosed in patients with liver disease. The kidney also plays a pivotal role in balancing acid–base disturbances resulting from advanced liver disease, making AKI in the setting of end-stage liver disease very difficult to manage clinically. While renal dysfunction in these patients often resolves following orthotopic liver transplant, dialysis may be required as a bridge to transplantation to mitigate the metabolic disarray found in these critically ill patients.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl− concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl− concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia. Discussion In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl− content on serum Cl− concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl− concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia. Trial registration Clinicaltrials.gov, NCT03204955. Registered on 28 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3007-7) contains supplementary material, which is available to authorized users.

PREVENTING unplanned or unintentional perioperative hypothermia has been a quality measure of The Joint Commission and the Centers for Medicare and Medicaid Services since 2009, when the Surgical Care Improvement Project (SCIP) went into effect.1 Research shows that hypothermia can lead to a host of

To assess the reversibility of acute kidney injury-induced neutrophil dysfunction and to identify involved mechanisms.Controlled laboratory experiment and prospective observational clinical study.University laboratory and hospital.C57BL/6 wild-type mice.Patients with septic shock with or without acute kidney injury.Murine acute kidney injury was induced by intraperitoneal injections of folic acid (nephrotoxic acute kidney injury) or by IM injections of glycerol (rhabdomyolysis-induced acute kidney injury). After 24 hours, we incubated isolated neutrophils for 3 hours in normal mouse serum or minimum essential medium buffer. We further studied the effects of plasma samples from 13 patients with septic shock (with or without severe acute kidney injury) on neutrophilic-differentiated NB4 cells.Experimental acute kidney injury significantly inhibited neutrophil migration and intracellular actin polymerization. Plasma levels of resistin, a proinflammatory cytokine and uremic toxin, were significantly elevated during both forms of acute kidney injury. Incubation in serum or minimum essential medium buffer restored normal neutrophil function. Resistin by itself was able to induce acute kidney injury-like neutrophil dysfunction in vitro. Plasma resistin was significantly higher in patients with septic shock with acute kidney injury compared with patients with septic shock alone. Compared with plasma from patients with septic shock, plasma from patients with septic shock and acute kidney injury inhibited neutrophilic-differentiated NB4 cell migration. Even after 4 days of renal replacement therapy, plasma from patients with septic shock plus acute kidney injury still showed elevated resistin levels and inhibited neutrophilic-differentiated NB4 cell migration. Resistin inhibited neutrophilic-differentiated NB4 cell migration and intracellular actin polymerization at concentrations seen during acute kidney injury, but not at normal physiologic concentrations.Acute kidney injury-induced neutrophil dysfunction is reversible in vitro. However, standard renal replacement therapy does not correct this defect in patients with septic shock and acute kidney injury. Resistin is greatly elevated during acute kidney injury, even with ongoing renal replacement therapy, and is sufficient to cause acute kidney injury-like neutrophil dysfunction by itself.

Purpose Peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO) has gained increasing value in the management of advanced cardiogenic shock. Unloading the left ventricle (LV) while reducing myocardial oxygen consumption (MVO2) are crucial for myocardial recovery during pVA-ECMO. To study the effects of a pulmonary capillary wedge pressure (PCWP)-directed protocol in patients on pVA-ECMO (goal: PCWP Methods Following IRB approval, we identified 99 patients with advanced cardiogenic shock undergoing pVA-ECMO and at least one formal transthoracic echocardiography study (TTE) during pVA-ECMO. We analyzed demographic data, routine laboratory data, hemodynamic parameters, and TTE results. We used PCWP measurements and calculations of LV systolic wall tension (LVSWT) to assess LV unloading and MVO2 during pVA-ECMO, respectively. Statistical analyses included Mann-Whitney-U test and logistic regression modeling. Data are given as median (interquartile range). Results Survival to hospital discharge was 60.6%. 27.3% of all patients required transition to dMCS to be weaned off pVA-ECMO. 10.1% of all patients developed refractory LV distention with pulmonary edema despite maximum medical treatment and required either atrial septostomy or additional mechanical support. Minimum PCWP readings during pVA-ECMO were 12.8 mmHg (11.0-14.4) in patients without and 10.0 mmHg (8.0-17.0) in patients with need for dMCS (p=0.236). Minimum LVSWT during pVA-ECMO were 2.7 × 105 dynes/cm (2.0-3.5) in patients without and 3.5 × 105 dynes/cm (3.1-4.0) in patients with need for dMCS (p=0.002). Adjusting for age and race in a logistic regression model revealed that only post-cardiotomy pVA-ECMO and LVSWT, but not minimum PCWP were independently associated with need for dMCS after pVA-ECMO. Conclusion We show that strict medical management can lead to LV unloading, i.e. minimum PCWP

Interactions between the liver and the kidneys are complex and convoluted. Many primary disorders of liver disease have direct and immediate effects on renal physiology and function. Kidney injury and dysfunction are frequent problems in patients with acute liver failure. However, the etiology of acute kidney injury in patients with acute liver failure is usually multifactorial and involves insults similar to those seen in the general acute kidney injury population.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical circulatory support for patients with advanced cardiogenic shock, facilitating myocardial recovery and limiting multi-organ failure. In patients with severely limited left ventricular ejection, peripheral VA-ECMO can further increase left ventricular and left atrial pressures (LAP). Failure to decompress the left heart under these circumstances can result in pulmonary edema and upper body hypoxemia, that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in these situations. However, the effects of atrial septostomy on upper body oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult VA-ECMO patients between January 2011 and June 2016 who also underwent atrial septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), P

Acute kidney injury (AKI) is a systemic disease occurring commonly in patients who are critically ill. Etiologies of AKI can be septic or aseptic (nephrotoxic, or ischemia–reperfusion injury). Recent evidence reveals that innate and adaptive immune responses are involved in mediating damage to renal tubular cells and in recovery from AKI. Dendritic cells, monocytes/macrophages, neutrophils, T lymphocytes, and B lymphocytes all contribute to kidney injury. Conversely, M2 macrophages and regulatory T cells are essential in suppressing inflammation, tissue remodeling and repair following kidney injury. AKI itself confers an increased risk for developing infection owing to increased production and decreased clearance of cytokines, in addition to dysfunction of immune cells themselves. Neutrophils are the predominant cell type rendered dysfunctional by AKI. In this review, we describe the bi-directional interplay between the immune system and AKI and summarize recent developments in this field of research.

Background Future supply with allogeneic blood transfusions faces several crucial challenges that warrant thorough (re-)evaluation of existing alternatives. Meta-analyses have indicated a significant potential for autologous blood conservation (ABC) measures to reduce the need for allogeneic blood transfusions. The quality of currently available studies, however, prohibits definite conclusions. Under these circumstances, mathematical modeling offers unique opportunities to compare various ABC measures and to test the impact of different variables on efficacy and effectiveness. Study Design and Methods We performed an extensive search for clinical ABC studies, focusing on acute normovolemic hemodilution (ANH), intraoperative blood salvage (IBS), or preoperative autologous deposit (PAD). Only ABC studies providing a minimum set of clinical variables were included. Using a clinically validated mathematical model, we then calculated maximal allowable blood loss (efficacy) and increase in red blood cell (RBC) mass (effectiveness) to rank the three techniques. Results We identified 21 clinical ABC studies, including 3926 patients, as suitable for our model. Our model shows that IBS with high recovery rates is the most efficacious and effective ABC measure. PAD will reveal nearly similar efficacy and effectiveness, only if sufficient time for RBC regeneration has passed and if 4 PAD units or more are available. Our model further demonstrates that ANH as well as IBS with low recovery rates are the least efficacious and effective alternatives. Conclusions IBS appears to be the most efficacious and effective ABC measure. PAD can only reduce the need for allogeneic blood transfusions under certain circumstances. ANH does not appear to play an important role in ABC.

Septic shock is a common cause of acute kidney injury (AKI), and fluid resuscitation is a major part of therapy.To determine if structured resuscitation designed to alter fluid, blood, and vasopressor use affects the development or severity of AKI or outcomes.Ancillary study to the ProCESS (Protocolized Care for Early Septic Shock) trial of alternative resuscitation strategies (two protocols vs. usual care) for septic shock.We studied 1,243 patients and classified AKI using serum creatinine and urine output. We determined recovery status at hospital discharge, examined rates of renal replacement therapy and fluid overload, and measured biomarkers of kidney damage. Among patients without evidence of AKI at enrollment, 37.6% of protocolized care and 38.1% of usual care patients developed kidney injury (P = 0.90). AKI duration (P = 0.59) and rates of renal replacement therapy did not differ between study arms (6.9% for protocolized care and 4.3% for usual care; P = 0.08). Fluid overload occurred in 8.3% of protocolized care and 6.3% of usual care patients (P = 0.26). Among patients with severe AKI, complete and partial recovery was 50.7 and 13.2% for protocolized patients and 49.1 and 13.4% for usual care patients (P = 0.93). Sixty-day hospital mortality was 6.2% for patients without AKI, 16.8% for those with stage 1, and 27.7% for stages 2 to 3.In patients with septic shock, AKI is common and associated with adverse outcomes, but it is not influenced by protocolized resuscitation compared with usual care.