Variations of pulse pressure and central venous pressure may predict fluid responsiveness in mechanically ventilated patients during lung recruitment manoeuvre: an ancillary study.

BACKGROUND: Maintaining a constant driving pressure during a prolonged sigh breath lung recruitment manoeuvre (LRM) from 20 to 45 cmH20 peak inspiratory pressure in mechanically ventilated patients has been shown to be a functional test to predict fluid responsiveness (FR) when using a linear regression model of hemodynamic parameters, such as central venous pressure (CVP) and pulse pressure (PP). However, two important limitations have been raised, the use of high ventilation pressures and a regression slope calculation that is difficult to apply at bedside. This ancillary study aimed to reanalyse absolute variations of CVP (ΔCVP) and PP (ΔPP) values at lower stages of the LRM, (40, 35, and 30 cm H20 of peak inspiratory pressure) for their ability to predict fluid responsiveness. METHODS: Retrospective analysis of a prospective study data set in 18 mechanically ventilated patients, in an intensive care unit. CVP, systemic arterial pressure parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL crystalloid volume expansion. Patients were considered as fluid responders if SV increased more than 10%. Receiver-operating curves (ROC) analysis with the corresponding grey zone approach were performed. RESULTS: Areas under the ROC to predict fluid responsiveness for ΔCVP and ΔPP were not different between the successive stepwise increase of inspiratory pressures [0.88 and 0.89 for ΔCVP at 45 and 30 cm H20 (P = 0.89), respectively, and 0.92 and 0.95 for ΔPP at 45 and 30 cm H20, respectively (P = 0.51)]. Using a maximum of 30 cmH2O inspiratory pressure during the LRM, ΔCVP and ΔPP had a threshold value to predict fluid responsiveness of 2 mmHg and 4 mmHg, with sensitivities of 89% and 89% and specificities of 67% and 89%, respectively. Combining ΔPP and ΔCVP decreased the proportion of the patients in the grey zone from 28 to 11% and showed a sensitivity of 88% and a specificity of 83%. CONCLUSIONS: A stepwise PEEP elevation recruitment manoeuvre of up to 30 cm H20 may predict fluid responsiveness as well as 45 cm H20. The combination of ΔPP and ΔCVP optimizes the categorization of responder and non-responder patients.

Slope analysis for the prediction of fluid responsiveness by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients.

OBJECTIVE: Assessment of fluid responsiveness is problematic in intensive care unit patients. Lung recruitment maneuvers (LRM) can be used as a functional test to predict fluid responsiveness. We propose a new test to predict fluid responsiveness in mechanically ventilated patients by analyzing the variations in central venous pressure (CVP) and systemic arterial parameters during a prolonged sigh breath LRM without the use of a cardiac output measuring device. DESIGN: Prospective observational cohort study. SETTING: Intensive Care Unit, Saint-Etienne University Central Hospital. PATIENTS: Patients under mechanical ventilation, equipped with invasive arterial blood pressure, CVP, pulse contour analysis (PICCO™), requiring volume expansion, with no right ventricular dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CVP, systemic arterial parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL fluid expansion to asses fluid responsiveness. 25 patients were screened and 18 patients analyzed. 9 patients were responders to volume expansion and 9 were not. Evaluation of hemodynamic parameters suggested the use of a linear regression model. Slopes for systolic arterial pressure, pulse pressure (PP), CVP and SV were all significantly different between responders and non-responders during the pressure increase phase of LRM (STEP-UP) (p = 0.022, p = 0.014, p = 0.006 and p = 0.038, respectively). PP and CVP slopes during STEP-UP were strongly predictive of fluid responsiveness with an AUC of 0.926 (95% CI, 0.78 to 1.00), sensitivity = 100%, specificity = 89% and an AUC = 0.901 (95% CI, 0.76 to 1.00), sensibility = 78%, specificity = 100%, respectively. Combining sensitivity of PP and specificity of CVP, prediction of fluid responsiveness can be achieved with 100% sensitivity and 100% specificity (AUC = 0.96; 95% CI, 0.90 to 1.00). One patient showed inconclusive values using the grey zone approach (5.5%). CONCLUSIONS: In patients under mechanical ventilation with no right heart dysfunction, the association of PP and CVP slope analysis during a prolonged sigh breath LRM seems to offer a very promising method for prediction of fluid responsiveness without the use and associated cost of a cardiac output measurement device. TRIAL REGISTRATION: NCT04304521 , IRBN902018/CHUSTE. Registered 11 March 2020, Fluid responsiveness predicted by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients (STEP-PEEP).

View of U.S. spine surgeons regarding cost reduction measures.

BACKGROUND: This is a cross-sectional study. Our objective is to survey spine surgeons' views of responsibility to reduce healthcare costs, enthusiasm for cost reduction strategies, and agreement regarding roles in cost containment. The rising cost of healthcare has spurred debate about reducing expenditures. Previous studies have found that attitudes of anesthesiologists are predominantly in alignment with those of American physicians, but less is known about the views of spine surgeons. METHODS: After obtaining institutional approval, an electronic survey was disseminated to active members of AO Spine North America (AOSNA) via email. Respondents were asked eight questions about their age, gender, years in practice, practice facility, political views and opinions regarding management of healthcare costs. RESULTS: From 91 respondents, most were under the age of 60 years (87%), male (96%), and in practice for less than 30 years (91%), practiced at university hospitals (47%) and held politically conservative views (47%). Most responsibility was allocated to hospital and health systems, health insurance companies, pharmaceutical companies, and device manufacturers. Respondents were most enthusiastic about rooting out fraud and abuse and aware of their role in managing the cost of healthcare. Spine surgeons who were in practice for longer were more enthusiastic about reducing cost by reducing overall physician reimbursement via bundled payments, Medicare payment reduction, ending fee-for-service, penalizing surgeons for patient readmissions, and lowering compensation to individual spine surgeons. CONCLUSIONS: Spine surgeons allocated responsibility to reduce healthcare costs to healthcare systems, were most enthusiastic about eliminating wasteful spending, and were in agreement regarding their responsibility to control the costs of healthcare. Compared to US physicians of various specialties and anesthesiologists, spine surgeons assigned less responsibility to trials lawyers and expressed markedly less enthusiasm for limiting access to expensive treatments.

Two-Year Follow-up Survey: Views of US Anesthesiologists About Health Care Costs and Future Practice Roles.

Anesthesiologists' perspectives on US health care finance reform are increasingly germane to recent policy reforms. The aim of this follow-up survey was to examine how anesthesiologists' views of health care costs and future practice roles have changed since 2014. Six thousand randomly chosen active members of the American Society of Anesthesiologists were again surveyed and were also asked several new questions regarding specialties and perioperative management. Results showed an increase in self-reported understanding of the perioperative surgical home. Government, insurance companies, and pharmaceutical companies saw an increase in perceived "major responsibility" for cost reduction. Respondents vastly preferred that patient care under the perioperative surgical home be multidisciplinary.

Respiratory variation in aortic blood flow peak velocity to predict fluid responsiveness in mechanically ventilated children: a systematic review and meta-analysis.

BACKGROUND: Dynamic indices of preload have been shown to better predict fluid responsiveness than static variables in mechanically ventilated adults. In children, dynamic predictors of fluid responsiveness have not yet been extensively studied. AIM: To evaluate the diagnostic accuracy of respiratory variation in aortic blood flow peak velocity (ΔVPeak) for the prediction of fluid responsiveness in mechanically ventilated children. METHOD: PubMed, Embase, and the Cochrane Database of Systematic Reviews were screened for studies relevant to the use of ΔVPeak to predict fluid responsiveness in children receiving mechanical ventilation. Clinical trials published as full-text articles in indexed journals without language restriction were included. We calculated the pooled values of sensitivity, specificity, diagnostic odds ratio (DOR), and positive and negative likelihood ratio using a random-effects model. RESULTS: In total, six studies (163 participants) met the inclusion criteria. Data are reported as point estimate with 95% confidence interval. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR of ΔVPeak to predict fluid responsiveness for the overall population were 92.0% (84.1-96.7), 85.5% (75.6-92.5), 4.89 (2.92-8.18), 0.13 (0.07-0.25), and 50.44 (17.70-143.74), respectively. The area under the summary receiver operating characteristic curve was 0.94. Cutoff values for ΔVPeak to predict fluid responsiveness varied across studies, ranging from 7% to 20%. CONCLUSION: Our results confirm that the ΔVPeak is an accurate predictor of fluid responsiveness in children under mechanical ventilation. However, the question of the optimal cutoff value of ΔVPeak to predict fluid responsiveness remains uncertain, as there are important variations between original publications, and needs to be resolved in further studies. The potential impact of intraoperative cardiac output optimization using goal-directed fluid therapy based on ΔVPeak on the perioperative outcome in the pediatric population should be subsequently evaluated.

Health Care Costs and the Perioperative Surgical Home: A Survey Study.

BACKGROUND: The perceptions of anesthesiologists of US health care finance reform are germane to informing the future of our specialty. For this reason, we sought to assess anesthesiologists' views of their own importance in cost-reduction strategies. In addition, respondents were asked a series of questions related to the Perioperative Surgical Home. METHODS: A cross-sectional survey was sent through email to 6000 randomly chosen active members of the American Society of Anesthesiologists. Respondents were asked to indicate what level of responsibility they perceive stakeholders to have in reducing the cost of health care and perioperative care delivery. Respondents were then asked to describe their relative enthusiasm for cost-reduction strategies. To validate the primary outcome, we took advantage of the American Society of Anesthesiologists' recent focus on the Perioperative Surgical Home to ask a series of related questions as comparators. RESULTS: Thirty-eight percent (95% confidence interval, 35-42) of respondents indicated that physicians bear "major responsibility" for cost reduction, 58% (55-61) indicated that physicians bear "some responsibility," and 4%, only a small fraction (0.7-7.5) indicated that physicians bear "no responsibility." Respondents also indicated that other entities listed bear "major responsibility" for cost reduction including hospitals (57% [54-61]) and insurance companies (54% [51-57]). Comparator data from questions not designed to directly measure the primary outcome are reported, including questions about the Perioperative Surgical Home. CONCLUSIONS: US anesthesiologists surveyed perceive other stakeholders, such as hospitals and insurance companies, as having a major responsibility in cost reduction. Furthermore, they are not enthusiastic about substantial financial reform such as cuts to Medicare payments.

Total joint Perioperative Surgical Home: an observational financial review.

BACKGROUND: The numbers of people requiring total arthroplasty is expected to increase substantially over the next two decades. However, increasing costs and new payment models in the USA have created a sustainability gap. Ad hoc interventions have reported marginal cost reduction, but it has become clear that sustainability lies only in complete restructuring of care delivery. The Perioperative Surgical Home (PSH) model, a patient-centered and physician-led multidisciplinary system of coordinated care, was implemented at UC Irvine Health in 2012 for patients undergoing primary elective total knee arthroplasty (TKA) or total hip arthroplasty (THA). This observational study examines the costs associated with this initiative. METHODS: The direct cost of materials and services (excluding professional fees and implants) for a random index sample following the Total Joint-PSH pathway was used to calculate per diem cost. Cost of orthopedic implants was calculated based on audit-verified direct cost data. Operating room and post-anesthesia care unit time-based costs were calculated for each case and analyzed for variation. Benchmark cost data were obtained from literature search. Data are presented as mean ± SD (coefficient of variation) where possible. RESULTS: Total per diem cost was $10,042 ± 1,305 (13%) for TKA and $9,952 ± 1,294 (13%) for THA. Literature-reported benchmark per diem cost was $17,588 for TKA and $16,267 for THA. Implant cost was $7,482 ± 4,050 (54%) for TKA and $9869 ± 1,549 (16%) for THA. Total hospital cost was $17,894 ± 4,270 (24%) for TKA and $20,281 ± 2,057 (10%) for THA. In-room to incision time cost was $1,263 ± 100 (8%) for TKA and $1,341 ± 145 (11%) for THA. Surgery time cost was $1,558 ± 290 (19%) for TKA and $1,930 ± 374 (19%) for THA. Post-anesthesia care unit time cost was $507 ± 187 (36%) for TKA and $557 ± 302 (54%) for THA. CONCLUSIONS: Direct hospital costs were driven substantially below USA benchmark levels using the Total Joint-PSH pathway. The incremental benefit of each step in the coordinated care pathway is manifested as a lower average length of stay. We identified excessive variation in the cost of implants and post-anesthesia care.

Postoperative global amnesia reversed with flumazenil.

Global postoperative amnesia (profound anterograde and retrograde amnesia) is rare and usually attributed to transient global amnesia-a poorly understood condition with no broadly accepted mechanism. We report an incident of probable transient global amnesia in a patient after endoscopic retrograde cholangiopancreatogram under general anesthesia, which was successfully treated with flumazenil. On the basis of the results of flumazenil administration in this and a previous case report, we would recommend a trial dose of 0.2 mg for cases of global postoperative amnesia, repeated if the first dose seems effective.

Roles of CCR2 and CXCR3 in the T cell-mediated response occurring during lupus flares.

OBJECTIVE: Infiltrating lymphocytes have been demonstrated to play an important role in the tissue injury that occurs in systemic lupus erythematosus (SLE). Inflammatory chemokines control lymphocyte traffic through their interaction with T cell chemokine receptors. In this study we assessed the expression of chemokine receptors on T cell subsets of patients with active or inactive SLE. METHODS: Forty-four SLE patients (40 women and 4 men) were included in the study. The patients were divided according to their SLE Disease Activity Index (SLEDAI), which resulted in a group of patients with inactive SLE (n = 27) and a group with active SLE (n = 17). The control group was composed of 22 healthy blood donors. A disease control group consisted of 18 patients infected with human immunodeficiency virus. Expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3, CXCR4, and CX3CR1 was assessed on whole blood samples by immunofluorescence analysis. RESULTS: On T lymphocytes, significant differences between the SLE patients and controls were observed only in the expression of CCR2 and CXCR3. On monocytes, no significant differences in CCR2 expression were observed between the healthy controls and the SLE patients. The proportion of CD8+,CCR2+ T cells was significantly lower in the SLE patients compared with the controls (mean +/- SD 2.3 +/- 1.3% and 3.5 +/- 3.2% in the active and inactive SLE groups, respectively, versus 21 +/- 24% in controls; P < 0.0001 for both). The CD4+,CCR2+ subset was represented similarly among the controls and patients with inactive SLE (16.7 +/- 5.8% and 12.8 +/- 8.1%, respectively) but was depleted in patients with active SLE (7.1 +/- 4.4%; P < 0.0001 versus controls). The active SLE group expressed significantly lower circulating levels of CD4+,CCR2+ T cells than did the inactive disease group (P = 0.007). A negative correlation was found between the proportion of CD4+,CCR2+ T cells and the SLEDAI (r = -0.43, P = 0.005, by Spearman's correlation). Proportions of CD8+,CXCR3+ T cells were similar between the SLE groups and the control group (58 +/- 22.6% in active SLE, 47.1 +/- 20% in inactive SLE, and 59.4 +/- 17.3% in controls). The proportion of CXCR3-expressing CD4+ T cells was decreased in the active disease group (23.5 +/- 3.2% versus 39.9 +/- 12.5% in controls; P = 0.008) but not in the inactive disease group (34.8 +/- 9.5%). A trend toward a significant negative correlation was observed between the decreased proportion of CD4+,CXCR3+ T cells and the SLEDAI (P = 0.08). Following in vitro activation of purified CD4 T cells, only CCR2 was internalized, whereas expression of CXCR3 was retained in activated CD4 cells. CONCLUSION: The numbers of circulating CD4+,CXCR3+ and CD4+,CCR2+ T cells are selectively decreased during SLE flares. A decrease in the number of circulating CD4+ T cells expressing CCR2 and/or CXCR3 could serve as a biomarker of the SLE flare.

Characterization of vitreous B-cell infiltrates in patients with primary ocular lymphoma, using CDR3 size polymorphism analysis of antibody transcripts.

PURPOSE: Histopathology usually cannot be performed and cytology is unfortunately frequently insufficient to confirm a suspicion of primary intraocular lymphoma (PIOL). The purpose of this study was to evaluate the Immunoscope technique for the identification of ocular B-cell monoclonal infiltrates in patients with malignant or immune conditions. METHODS: Polymorphism analysis of the size of the third complementarity-determining region (CDR3) of heavy chain antibody transcripts was used to differentiate between a polyclonal infiltrate and a monoclonal infiltrate within a clinical vitreous sample of two groups of patients. PIOL was confirmed in all patients of the first group (n = 6). Five patients with autoimmune uveitis or immune-recovery uveitis associated with AIDS were included in the control group. The level of IL-10 in the vitreous was determined in all patients. RESULTS: In five cases of severe PIOL, CDR3 polymorphism analysis confirmed the presence of a dominant B-cell clone within the eye. In one case of confirmed PIOL presenting with mild vitritis, CDR3 polymorphism analysis was consistent with the existence of a polyclonal profile in the ocular sample studied. Conversely, it was shown that the detection of an intraocular monoclonal B-cell population does not necessarily imply ocular lymphoma. A clonal expansion was detected in a control patient who exhibited merely a nonmalignant response associated with immune-recovery uveitis. CONCLUSIONS: This PCR-based technique can make an important contribution to the characterization of intraocular B cells, but it alone cannot confirm or exclude the existence of a malignant lymphocyte proliferation. In the evaluation of a patient with intraocular inflammation in whom PIOL is suspected, CDR3 polymorphism analysis is recommended to confirm clonality. In general, the information about lymphocyte diversity provided by this technology opens up new possibilities for the analysis of ocular infiltrates.

Binding of small molecules to an adaptive protein-protein interface.

Understanding binding properties at protein-protein interfaces has been limited to structural and mutational analyses of natural binding partners or small peptides identified by phage display. Here, we present a high-resolution analysis of a nonpeptidyl small molecule, previously discovered by medicinal chemistry [Tilley, J. W., et al. (1997) J. Am. Chem. Soc. 119, 7589-7590], which binds to the cytokine IL-2. The small molecule binds to the same site that binds the IL-2 alpha receptor and buries into a groove not seen in the free structure of IL-2. Comparison of the bound and several free structures shows this site to be composed of two subsites: one is rigid, and the other is highly adaptive. Thermodynamic data suggest the energy barriers between these conformations are low. The subsites were dissected by using a site-directed screening method called tethering, in which small fragments were captured by disulfide interchange with cysteines introduced into IL-2 around these subsites. X-ray structures with the tethered fragments show that the subsite-binding interactions are similar to those observed with the original small molecule. Moreover, the adaptive subsite tethered many more compounds than did the rigid one. Thus, the adaptive nature of a protein-protein interface provides sites for small molecules to bind and underscores the challenge of applying structure-based design strategies that cannot accurately predict a dynamic protein surface.