Back-calculating baseline creatinine overestimates prevalence of acute kidney injury with poor sensitivity.

AIM: Acute kidney injury (AKI) is diagnosed by a 50% increase in creatinine. For patients without a baseline creatinine measurement, guidelines suggest estimating baseline creatinine by back-calculation. The aim of this study was to evaluate different glomerular filtration rate (GFR) equations and different GFR assumptions for back-calculating baseline creatinine as well as the effect on the diagnosis of AKI. METHODS: The Modification of Diet in Renal Disease, the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Mayo quadratic (MQ) equation were evaluated to estimate baseline creatinine, each under the assumption of either a fixed GFR of 75 mL min-1  1.73 m-2 or an age-adjusted GFR. Estimated baseline creatinine, diagnoses and severity stages of AKI based on estimated baseline creatinine were compared to measured baseline creatinine and corresponding diagnoses and severity stages of AKI. RESULTS: The data of 34 690 surgical patients were analysed. Estimating baseline creatinine overestimated baseline creatinine. Diagnosing AKI based on estimated baseline creatinine had only substantial agreement with AKI diagnoses based on measured baseline creatinine [Cohen's κ ranging from 0.66 (95% CI 0.65-0.68) to 0.77 (95% CI 0.76-0.79)] and overestimated AKI prevalence with fair sensitivity [ranging from 74.3% (95% CI 72.3-76.2) to 90.1% (95% CI 88.6-92.1)]. Staging AKI severity based on estimated baseline creatinine had moderate agreement with AKI severity based on measured baseline creatinine [Cohen's κ ranging from 0.43 (95% CI 0.42-0.44) to 0.53 (95% CI 0.51-0.55)]. CONCLUSION: Diagnosing AKI and staging AKI severity on the basis of estimated baseline creatinine in surgical patients is not feasible. Patients at risk for post-operative AKI should have a pre-operative creatinine measurement to adequately assess post-operative AKI.

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis.

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-) mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+)) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.

Emergent transesophageal echocardiography in hemodynamically unstable obstetric patients.

BACKGROUND: The obstetric population has an increasing incidence of comorbid conditions. These, coupled with the possibility of acute embolic events involving air, amniotic fluid, and thrombus, increase the likelihood of hemodynamic instability. Although the utility of transesophageal echocardiography to guide management in cardiac and high-risk, non-cardiac surgical populations has been well established, the emergent use in critically-ill parturients has not been comprehensively evaluated. METHODS: Using our departmental transesophageal echocardiography database of 28 293 examinations, parturients were identified who underwent emergent transesophageal echocardiography for evaluation of hemodynamic instability, including cardiac arrest, between January 1999 and March 2014. Transesophageal echocardiography findings and their impact on patient management were analyzed. RESULTS: Ten peripartum patients were evaluated. Six patients became unstable during dilation and evacuation procedures; one after a forceps delivery; one during and one after cesarean delivery; and one during a postpartum laparotomy. Six patients proceeded to cardiac arrest; however, all women survived their initial operation and resuscitation. Transesophageal echocardiography was instrumental in determining the etiology and guiding resuscitation in all 10 patients including emergent cardiac surgical intervention with cardiopulmonary bypass (n=2). Seven patients survived to hospital discharge, but three died after experiencing neurologic complications. CONCLUSIONS: Severe hemodynamic instability and cardiac arrest can occur in previously healthy parturients in pregnancy. Our data suggest that emergent transesophageal echocardiography is a valuable tool in determining the etiology and directing therapy of refractory hypotension or cardiac arrest in obstetric patients.

Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis.

Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by trinitrobenzene sulfonic acid were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi, and clinical, immunological, and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared with vehicle controls. Treated groups were pyrexic but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1α-deficient mice, strongly implicating epithelial HIF-1α as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies that the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis.

Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition thought to reflect a failure of the enteral immune system to adequately regulate itself. Inflammatory stress drives upregulation of heat-shock proteins (HSPs), including the pro-inflammatory chaperone, HSP90. This protein sequesters the transcription factor, heat-shock factor 1 (HSF1) in the cytoplasm preventing transcription of a number of anti-inflammatory proteins. We hypothesized that inhibition of HSP90 would exert an anti-inflammatory effect and thereby attenuate intestinal inflammation in murine models of IBD. Inhibition of HSP90 with 17-allylaminogeldanamycin (17-AAG) reduced inflammation in acute dextran sodium sulfate and chronic CD45RB(High) colitis models coinciding with increased interleukin (IL)-10 production in the colon. Regulatory T cells (Tregs) from mice treated with 17-AAG demonstrated significantly greater suppressive capacity in vitro abolished in HSF1-/- or IL-10-/- cells. Finally, Tregs treated with 17-AAG exhibited increased nuclear localization of HSF1 with resultant upregulation of HSF1 response genes, including HSP70, HSP90 and IL-10.

Detrimental role of the airway mucin Muc5ac during ventilator-induced lung injury.

Acute lung injury (ALI) is associated with high morbidity and mortality in critically ill patients. At present, the functional contribution of airway mucins to ALI is unknown. We hypothesized that excessive mucus production could be detrimental during lung injury. Initial transcriptional profiling of airway mucins revealed a selective and robust induction of MUC5AC upon cyclic mechanical stretch exposure of pulmonary epithelia (Calu-3). Additional studies confirmed time- and stretch-dose-dependent induction of MUC5AC transcript or protein during cyclic mechanical stretch exposure in vitro or during ventilator-induced lung injury in vivo. Patients suffering from ALI showed a 58-fold increase in MUC5AC protein in their bronchoalveolar lavage. Studies of the MUC5AC promoter implicated nuclear factor κB in Muc5ac induction during ALI. Moreover, mice with gene-targeted deletion of Muc5ac⁻/⁻ experience attenuated lung inflammation and pulmonary edema during injurious ventilation. We observed that neutrophil trafficking into the lungs of Muc5ac⁻/⁻ mice was selectively attenuated. This implicates that endogenous Muc5ac production enhances pulmonary neutrophil trafficking during lung injury. Together, these studies reveal a detrimental role for endogenous Muc5ac production during ALI and suggest pharmacological strategies to dampen mucin production in the treatment of lung injury.

Laparoscopic splenectomy in a pregnant patient with immune thrombocytopenic purpura.

We describe the perioperative management of a pregnant woman at 19 weeks' gestation with idiopathic thrombocytopenic purpura requiring laparoscopic splenectomy. The preoperative platelet count ranged between 1 and 5 x 10(9)/L and did not respond to conventional medical therapy. To reduce the risk of intracerebral hemorrhage, platelets were transfused before induction of anesthesia to maintain platelet count closer to 20 x 10(9)/L. The blood pressure was monitored continuously via an arterial line and remifentanil was infused to prevent a hypertensive response to induction/intubation, carbon dioxide insufflation, and surgery. After the splenic artery was clamped, additional platelet units were transfused to assure surgical hemostasis.

Remifentanil or sufentanil for coronary surgery: comparison of postoperative respiratory impairment.

BACKGROUND AND OBJECTIVE: High-dose opioid anaesthesia contributes to decreasing metabolic and hormonal stress responses in patients undergoing cardiac surgery. However, the increase in context-sensitive half-life of opioids given as a high-dose regimen can affect postoperative respiratory recovery. In contrast, remifentanil can be given in high doses without prolonging context-sensitive half-life due to its rapid metabolism. Therefore, we performed a prospective, randomized trial to compare anaesthesia consisting of propofol/remifentanil or propofol/sufentanil with regard to postoperative respiratory function and outcome. METHODS: Patients undergoing coronary artery bypass grafting were randomized to a propofol/remifentanil (0.5-1.0 microg kg(-1) min(-1)) or propofol/sufentanil (30-40 ng kg(-1) min(-1)) based anaesthetic. Carbon dioxide response, forced expiratory volume in one second, vital capacity, and functional residual capacity were measured 1 day prior to the operation, 1 h before extubation, 1, 24 and 72 h after extubation. In addition, the incidence of atelectasis, pulmonary infiltrates, intensive care unit and postoperative length of stay were compared. Patients and physicians were blinded to the treatment group. RESULTS: Twenty-five patients in each treatment group completed the study. There was no difference between patients of the treatment groups regarding demographics, risk- or pain scores. In all patients, carbon dioxide response, forced expiratory volume in one second, vital capacity and functional residual capacity were decreased postoperatively compared to baseline. Patients randomized to remifentanil had less depression of carbon dioxide response, less atelectasis and shorter postoperative length of stay (12 d vs. 10 d) than after sufentanil (P < 0.05). CONCLUSIONS: Intraoperative use of high-dose remifentanil for coronary artery bypass grafting may be associated with improved recovery of pulmonary function and shorter postoperative hospital length of stay than sufentanil.

[Perioperative echocardiography: basic principles]. / Perioperative Echokardiographie: Technische Grundlagen für den Kliniker.

Over the past decades, echocardiography has undergone a continuous evolution in technology that has promoted its clinical application and acceptance throughout perioperative medicine. These technological advances include improvements in transducer development that permit superior imaging quality and a wider selection of probes for epicardial, epiaortic, and surface echocardiography which can also be used in conjunction with multiplane transesophageal echocardiography. Moreover, the addition of Doppler technology and digital acquisition has secured the role of echocardiography as a valuable and relatively noninvasive diagnostic tool for the assessment of cardiovascular disease and hemodynamic monitoring throughout the perioperative period. Therefore, it has become increasingly important for perioperative physicians to understand the basic principles and underlying fundamental concepts pertaining to the technology and physics of echocardiography, as well as its inherent limitations. The current review outlines the modes and applications of different echocardiographic techniques used in perioperative echocardiography including M-mode, two-dimensional echocardiography, and Doppler assessment of blood flow. In addition, the limitations of these techniques and typical artifacts associated with the perioperative use of echocardiography are described.

[Preoperative evaluation and perioperative management of patients with increased cardiovascular risk]. / Präoperative Evaluation und perioperatives Vorgehen bei kardialen Risikopatienten.

Due to the increasing age in western countries, combined with high rates of major surgical interventions in high-risk patients, perioperative reduction of cardiovascular complications becomes increasingly more important for perioperative physicians. After identifying patients with increased perioperative risk, specific interventions need to be considered to reduce their risk for cardiovascular complications, either by perioperative medical therapy or specific treatment options (e.g. coronary intervention). Several trials have demonstrated an effect of perioperative beta-blocker-therapy in reducing cardiovascular complications among high-risk patients. Additionally, several monitoring techniques are effective in detecting cardiovascular complications. Nevertheless, it remains unclear whether they are associated with a measurable improvement of outcome. Based on the ACC/AHA-guidelines, the present review describes a stepwise approach to surgical patients to identify perioperative risks, based on specific patient related risk factors, the kind of surgery and on the specific setting (emergency versus elective surgery). In addition, strategies to reduce perioperative cardiovascular complications are discussed.

[Epicardial echocardiography intraoperative diagnostic utility to assess valve function]. / Epikardiale EchokardiographieIntraoperative Beurteilung der Klappenfunktion.

Epicardial echocardiography has been available since the early 1970s as an intraoperative diagnostic modality to assess ventricular and valvular function. With this technique, an ultrasonic transducer is placed directly on the epicardial surface of the heart, following sternotomy and pericardiotomy. Under the guidance of the cardiac anesthesiologist, the surgeon places the transducer so that the desired views of cardiac structures and great vessels can be obtained. The anesthesiologist performs the acquisition, analysis and interpretation of the echocardiographic images. Despite the feasibility of epicardial echocardiography, transesophageal echocardiography (TEE) has emerged over the last two decades as the main form of intraoperative echocardiography. Although TEE allows continuous monitoring of cardiac and valvular function without interruption of the surgical procedure, placement of a TEE probe may be difficult or contraindicated in some patients. In such cases, epicardial echocardiography may be the optimal ultrasonographic imaging modality to assess ventricular and valvular function during cardiac surgery. We describe the use of epicardial echocardiography for intraoperative assessment of valvular function in two patients where TEE was either contraindicated or probe placement could not be performed safely. The first patient underwent surgical repair of the mitral valve for severe mitral regurgitation. After weaning the patient from cardiopulmonary bypass (CPB), epicardial echocardiography was used to confirm successful reconstruction of the valve and to exclude residual mitral regurgitation. The second patient was scheduled for coronary artery bypass grafting (CABG). Prior to the initiation of CPB, the presence of moderate aortic stenosis was confirmed using Doppler echocardiography via an epicardial approach.

[Perioperative implications of heart transplant]. / Perioperative Aspekte der Herztransplantation.

Over the past 30 years, heart transplantation has evolved into a definitive therapy for patients with end-stage cardiomyopathy. However, perioperative management of patients undergoing heart transplantation remains a challenge for anesthesiologists. The presence of biventricular failure, arrhythmias and associated multisystem organ dysfunction may contribute to significant intraoperative hemodynamic instability prior to the initiation of cardiopulmonary bypass (CPB). Even after an uneventful transplantation, weaning from CPB may be difficult. Acute right ventricular failure can develop in the recipient secondary to pre-existing pulmonary hypertension. Treatment options frequently focus on therapeutic interventions directed towards decreasing pulmonary vascular resistance and improving right ventricular contractility. Intraoperative use of transesophageal echocardiography (TEE) enables the anesthesiologist to diagnose acute right ventricular failure early on and guide therapy. Concurrent pathology including kinking of the pulmonary artery anastomosis or valvular insufficiency in the transplanted heart can also be recognized and addressed. The number of patients undergoing cardiac transplantation is continually increasing. In addition, the use of more effective immunosuppressive agents has curtailed transplant rejection and permitted longer survival. Consequently, heart transplant recipients are more frequently presenting for non-cardiac surgical procedures. Thus, an understanding of physiological and pharmacological implications associated with heart transplantation is crucial for managing these patients in the perioperative period.

[Transesophageal echocardiography: perioperative evaluation of valvular function]. / Transösophageale Echokardiographie. Perioperative Beurteilung der Herzklappen.

Since its introduction into the operating room, transesophageal echocardiography (TEE) has proven to be an invaluable diagnostic tool for perioperative patient management. TEE allows direct visualization of structural and functional cardiac abnormalities. Therefore, it has become the most important imaging technique to evaluate valular function. Pressure gradients across a stenotic valve can be calculated by measuring the blood flow velocity within the valve. Additionally, the area of the valve can be estimated by using the continuity equation. The severity of regurgitant blood flow across an incompetent valve can be assessed using color flow, continuous or pulsed-wave Doppler. Surgical patients experience significant changes in blood pressure, intrathoracic pressures and volume status in the perioperative period. Therefore, the interaction between these parameters and valvular function is the focus of recent clinical studies and might in future contribute to the perioperative as well as anesthesiological management of patients with valvular dysfunction.

Effect of tracheal intubation or laryngeal mask airway insertion on intraocular pressure using balanced anesthesia with sevoflurane and remifentanil.

STUDY OBJECTIVES: To study the effect of tracheal intubation or laryngeal mask airway (LMA) insertion on intraocular pressure (IOP) in strabismus patients undergoing balanced anesthesia with sevoflurane and remifentanil. DESIGN: Open, prospective, randomized study. SETTING: Tertiary care academic medical institution. PATIENTS: 40 adult ASA physical status I and II patients scheduled for elective strabismus surgery. INTERVENTION: Patients were randomized to receive either tracheal intubation or LMA insertion following mask induction with sevoflurane in combination with IV remifentanil. MEASUREMENTS: Intraocular pressure, mean arterial pressure (MAP), and heart rate (HR) were measured before induction, immediately following induction, and after airway insertion. MAIN RESULTS: Intraocular pressure after tracheal intubation or LMA insertion did not differ significantly from preoperative baseline values. Mean arterial pressure and HR did not significantly differ between groups at any time point. CONCLUSIONS: Remifentanil and sevoflurane are not associated with an increase in IOP response during tracheal intubation or LMA insertion above baseline in healthy patients undergoing ophthalmic surgery.