Hemostatic Profiles of Patients Who Underwent Transcatheter Versus Surgical Aortic Valve Replacement Versus Percutaneous Coronary Intervention.

Guidelines for transcatheter aortic valve replacement (TAVR) antithrombotic prophylaxis are extrapolated predominantly from percutaneous coronary intervention (PCI) data. Here, we examined temporal coagulation changes occurring in the early perioperative period to determine the pathobiologic validity of this supposition. This was a prospective observational study of consecutive patients who underwent transfemoral TAVR (n = 27), PCI (n = 12), or surgical aortic valve replacement (SAVR) requiring cardiopulmonary bypass and cross-clamping (n = 12). Blood samples were taken at 4 time points: T1 (baseline), after general anesthesia or sedation; T2, after heparin administration; T3, at the end of the procedure; and T4, 6 hours after the procedure. The samples were assessed concurrently using standard laboratory coagulation tests and viscoelastic tests of whole blood clotting, including the latest generation thromboelastometry (ROTEM sigma) and thromboelastometry (TEG 6s). Patients in the TAVR cohort were older and a had lower baseline hemoglobin level than patients in the PCI and SAVR cohorts. The baseline platelet function was similar between the TAVR and PCI cohorts and impaired in the SAVR cohort Figure S1. The baseline hemostatic measures were comparable among cohorts. Regarding the per-patient change from baseline, the TAVR cohort showed an overall more prothrombotic state than the other cohorts, with the most marked differences from the SAVR cohort after intraoperative heparin administration and from the PCI cohorts 6 hours after the procedure. In addition, the ROTEM and TEG parameters were well correlated but not interchangeable. In conclusion, patients who underwent TAVR have a more prothrombotic hemostatic profile than PCI and SAVR patients. These findings question the current guidelines that extrapolate antithrombotic regimens from PCI to TAVR settings.

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study.

The temporal trends in haematological parameters and their associations with blood product transfusion requirements in patients supported with extracorporeal membrane oxygenation (ECMO) are poorly understood. We performed a retrospective data analysis to better understand the behaviour of haematological and coagulation parameters and their associations with transfusion requirements during ECMO. METHODS: Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. RESULTS: Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5-13) days and 13 (8-23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. CONCLUSION: ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.

Nursing experiences in antimicrobial optimisation in the intensive care unit: A convergent analysis of a national survey.

BACKGROUND: Recent evidence highlights the need for an interdisciplinary approach to antimicrobial stewardship (AMS). Nursing involvement in optimising antimicrobials in the intensive care unit (ICU) remains understudied. OBJECTIVE: The objective of this study was to explore nurses' perceptions and experiences of antimicrobial optimisation or stewardship in ICUs in Australia. METHODS: An anonymous web-based survey was deployed nationally in early 2021 through two ICU nursing networks. Associations between survey responses were analysed descriptively and by using nonparametric tests (with statistical significance established at p ≤ 0.05). Free-text survey responses underwent qualitative thematic analysis. Interpretation and reporting of quantitative and qualitative data were integrated. RESULTS: A total of 226 ICU nurses completed the survey. The majority (197/226; 87%) responded that lack of education limits engagement in AMS. Only 13% (30/226) reported the presence of AMS education and training for nurses in their ICUs. Only about half (108/226; 48%) of the nurses were confident to question prescribers when they considered that the antimicrobial prescribed was unnecessary, with nurses in senior roles more likely to do so than nurses providing bedside care (p < 0.05). Gaps in education (including unfamiliarity with AMS roles), noninclusive antimicrobial discussions, moral distress, and potential workload burden were seen as potential barriers/challenges to engagement. CONCLUSION: The multifactorial barriers identified that inhibit nurses from performing AMS tasks could be addressed by strengthening interprofessional education at all levels and by applying practical AMS interventions that are inclusive for nursing participation. A purposeful culture change that fosters psychological safety and collaborative practice is paramount to supporting nurses in these roles.

The impact of reduction in intensity of mechanical ventilation upon venovenous ECMO initiation on radiographically assessed lung edema scores: A retrospective observational study.

Background: Patients with severe acute respiratory distress syndrome (ARDS) typically receive ultra-protective ventilation after extracorporeal membrane oxygenation (ECMO) is initiated. While the benefit of ECMO appears to derive from supporting "lung rest", reductions in the intensity of mechanical ventilation, principally tidal volume limitation, may manifest radiologically. This study evaluated the relative changes in radiographic assessment of lung edema (RALE) score upon venovenous ECMO initiation in patients with severe ARDS. Methods: Digital chest x-rays (CXR) performed at baseline immediately before initiation of ECMO, and at intervals post (median 1.1, 2.1, and 9.6 days) were reviewed in 39 Adult ARDS patients. One hundred fifty-six digital images were scored by two independent, blinded radiologists according to the RALE (Radiographic Assessment of Lung Edema) scoring criteria. Ventilatory data, ECMO parameters and fluid balance were recorded at corresponding time points. Multivariable analysis was performed analyzing the change in RALE score over time relative to baseline. Results: The RALE score demonstrated excellent inter-rater agreement in this novel application in an ECMO cohort. Mean RALE scores increased from 28 (22-37) at baseline to 35 (26-42) (p < 0.001) on D1 of ECMO; increasing RALE was associated with higher baseline APACHE III scores [ß value +0.19 (0.08, 0.30) p = 0.001], and greater reductions in tidal volume [ß value -2.08 (-3.07, -1.10) p < 0.001] after ECMO initiation. Duration of mechanical ventilation, and ECMO support did not differ between survivors and non-survivors. Conclusions: The magnitude of reductions in delivered tidal volumes correlated with increasing RALE scores (radiographic worsening) in ARDS patients receiving ECMO. Implications for patient centered outcomes remain unclear. There is a need to define appropriate ventilator settings on venovenous ECMO, counterbalancing the risks vs. benefits of optimal "lung rest" against potential atelectrauma.

Outcomes of Prolonged ICU Stay for Patients Undergoing Cardiac Surgery in Australia and New Zealand.

OBJECTIVE: To determine the effect of intensive care unit (ICU) length of stay (LOS) on hospital mortality and non-home discharge for patients undergoing cardiac surgery over a 16-year period in Australia and New Zealand. DESIGN: A retrospective, multicenter cohort study covering the period January 1, 2004 to December 31, 2019. SETTING: One hundred one hospitals in Australia and New Zealand that submitted data to the Australia New Zealand Intensive Care Society Adult Patient Database. PARTICIPANTS: Adult patients (aged >18) who underwent coronary artery bypass grafting, valve surgery, or combined valve + coronary artery surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed 252,948 cardiac surgical patients from 101 hospitals, with a median age of 68.3 years (IQR 60-75.5), of whom 74.2% (187,632 of 252,948) were male patients. A U-shaped relationship was observed between ICU LOS and hospital mortality, with significantly elevated mortality at short (<20 hours) and long (>5 days) ICU LOS, which persisted after adjustment for illness severity and across clinically important subgroups (odds ratio for mortality with ICU LOS >5 days = 3.21, 95% CI 2.88-3.58, p < 0.001). CONCLUSIONS: Prolonged duration of ICU LOS after cardiac surgery is associated with increased hospital mortality in a U-shaped relationship. An ICU LOS >5 days should be considered a meaningful definition for prolonged ICU stay after cardiac surgery.

The association between erector spinae plane block timing and reduced rib fracture related respiratory complications: A cohort study.

STUDY OBJECTIVE: Is erector spinae plane (ESP) catheter insertion within 24 h of hospital admission for rib fractures associated with a lower incidence of respiratory complications compared to those having an ESP within 48 h or after 48 h of admission. DESIGN: Retrospective cohort study. SETTING: Hospital. PATIENTS: 199 patients admitted for rib fractures, who received an ESP catheter. INTERVENTIONS: Timing of ESP performance was assessed by dividing the study cohort into three subgroups: prompt block within 24 h, early block within 48 h and late block after 48 h of admission. MEASUREMENTS: The primary outcome of interest was the development of respiratory complications. This included pneumonia, pulmonary embolism and respiratory failure. Secondary outcomes included intensive care unit (ICU) length of stay and hospital length of stay. MAIN RESULTS: A prompt ESP within 24 h was performed in 14.5% (n = 29) of patients, 47% (n = 95) received an early block within 48 h and 37% (n = 75) of patients received a late block after 48 h from admission. There was a significantly higher rate of respiratory complications (p = 0.005) with late block. A late block was associated with a significantly longer ICU length of stay (7.82 ± 5.2 days) compared to patients who received an early block (5.84 ± 2.8 days; p = 0.044). There was no significant association with hospital length of stay (p = 0.06). There were no differences between the prompt (within 24 h) and early (within 48 h) block groups for any outcome. CONCLUSIONS: The performance of an ESP block after 48 h of admission was associated with an increased incidence of respiratory complications and ICU length of stay. There appears to be no added benefit associated with the provision of a prompt ESP within 24 h.

A Comparison of the Commonly Used Surrogate Markers for Citrate Accumulation and Toxicity during Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

INTRODUCTION: Continuous renal replacement therapy using regional citrate anticoagulation is commonly used as a modality of organ support in the critically ill population. Currently, citrate accumulation or toxicity is assessed using surrogate markers, notably the uncorrected total-to-ionized calcium ration. The accuracy and utility of this method have been questioned. OBJECTIVES/AIMS: The aim of this study was to compare the surrogate markers used for assessing citrate accumulation or toxicity using the measurement of plasma citrate as the gold standard. METHODS: Blood was sampled from 20 patients before, during, and after episodes of filtration with citrate concentration measured using spectrophotometry. Demographic and other clinical and biochemical data were also collected. According to protocol, a 15 mmol/L solution of trisodium citrate was used as the prefilter anticoagulant. Results were analyzed using STATA (v16.0) and presented as mean (SD), median (IQR), or simple proportion. Univariate linear regression using citrate concentration as the dependent variable was performed with all surrogate markers. RESULTS: Twenty patients (17 males) were enrolled in the study with a mean (SD) age of 62.7 (9.9) years. The uncorrected calcium ratio had the best fit to the citrate data with an R2 value of 0.39. The albumin-corrected calcium ratio, pH, anion gap (AG), albumin-corrected AG, standard base excess, and strong ion gap all had R2 values less than 0.05. CONCLUSION(S): In the absence of direct measurement of citrate concentration, uncorrected total-to-ionized calcium ratio is superior to other surrogate markers, though not ideal, in assessing citrate accumulation or toxicity.

Impact of fasting on the gastric volume of critically ill patients before extubation: a prospective observational study using gastric ultrasound.

Background: A period of fasting before tracheal extubation of ventilated patients in the ICU is common practice, aiming to reduce gastric volume and aspiration risk. As the volume of gastric content is unknown at the time of extubation, the efficacy of this practice is uncertain. Methods: A prospective, observational study using gastric ultrasound was undertaken. Images were obtained at four time points: (i) at baseline, with gastric feeds running; (ii) after suctioning of gastric contents through a gastric tube; (iii) after a 4 h period with no gastric feed running; and (iv) after both a 4 h fasting period and gastric tube suctioning. The primary outcome was the proportion of patients classed as low risk of aspiration with each intervention, using qualitative and quantitative gastric ultrasound. Results: Fifty-four patients in the ICU were enrolled. Forty-four (81%) subjects had images that were suitable for analysis. Suctioning of stomach content through a gastric tube and fasting were equivalent with 39/44 (88.6%) and 5/44 (11.4%) subjects classified as low risk and at risk of aspiration, respectively. A period of fasting followed by suction resulted in 41/44 (93.2%) patients being at low risk. Conclusions: Suctioning of stomach contents through the gastric tube and a 4 h fasting period appear equivalent at reducing gastric volume below a safe threshold. A small percentage did not reach the threshold despite all interventions.

Development and validation of a tool to appraise guidelines on SARS-CoV-2 infection control strategies in healthcare workers.

BACKGROUND: Clinical guidelines on infection control strategies in healthcare workers (HCWs) play an important role in protecting them during the severe acute respiratory syndrome coronavirus 2 pandemic. Poorly constructed guidelines that are incomprehensive and/or ambiguous may compromise HCWs' safety. OBJECTIVE: The objective of this study was to develop and validate a tool to appraise guidelines on infection control strategies in HCWs based on the guidelines published early in the coronavirus disease 2019 pandemic. DESIGN, SETTING, AND OUTCOMES: A three-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was performed. The tool was validated by appraising 40 international, specialty-specific, and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income. RESULTS: Overall consensus (≥75%) was reached at the end of three rounds for all six domains included in the tool. The Delphi panel recommended an ideal infection control guideline should encompass six domains: general characteristics (domain 1), engineering recommendations (domain 2), personal protective equipment (PPE) use (domain 3), and administrative aspects (domain 4-6) of infection control. The appraisal tool performed well across the six domains, and the inter-rater agreement was excellent for the 40 guidelines. All included guidelines performed relatively better in domains 1-3 than in domains 4-6, and this was more evident in guidelines originating from lower income countries. CONCLUSION: The guideline appraisal tool was robust and easy to use. Engineering recommendations aspects of infection control, administrative measures that promote optimal PPE use, and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high-quality HCW infection control guidelines during the severe acute respiratory syndrome coronavirus 2 pandemic and may also provide a framework for future guideline development.

Nasogastric tube placement under sonographic observation: A comparison study of ultrasound and chest radiography in mechanically ventilated patients.

BACKGROUND: Nasogastric tube insertion in the intensive care setting is common. Placement verification is required to avoid complications of bronchotracheal misplacement that range from aspiration of infused contents to death from associated causes. The gold standard of practice is chest radiography. Ultrasound is a growing modality and is readily available in most intensive care units. OBJECTIVE: The objective of this study was to examine the diagnostic accuracy of ultrasound imaging of nasogastric tube placements by nonradiologists compared with chest radiography in mechanically ventilated patients. METHODS: This is a dual-centre prospective, single-blind study. Correct placement was captured with a hyperechoic ultrasound image of a nasogastric tube in the oesophagus and epigastrium, which was compared with chest radiography. Patient enrolment included general adult intensive care unit admissions who were mechanically ventilated and required a nasogastric tube for either the treatment or monitoring of their illness. RESULTS: A total of 25 patients were enrolled (15 men, 10 women), and their mean age was 68.1 ± 13.8 years. Outcome measures were the percentage of correctly identified nasogastric tubes in the oesophagus and epigastrium. The sensitivity of oesophagus ultrasound was 88%, and the positive predictive value was 100%. The subxiphoid sensitivity was 64%, and the positive predictive value was 100%. Comparison sensitivity and specificity of oesophagus versus subxiphoid ultrasound was 64% and 33%, respectively. There was a positive predictive value of 88% and a negative predictive value of 11%. The results showed a variance in detection sensitivity in the ultrasound scans of the oesophagus (0.88) and subxiphoid (0.64) (N = 25, p = 0.012). CONCLUSION: Nasogastric tube placement verification via ultrasound in critically ill mechanically ventilated patients conducted by nonradiologists with minimal training is associated with diagnostic accuracy. These results add to the limited evidence in the current literature; however, they should be considered with awareness that placement in the stomach in this study was detected in 64% of cases, alongside the missed captured evidence of the sonographer's ability to identify misplacement.

The Association of Oxygenation, Carbon Dioxide Removal, and Mechanical Ventilation Practices on Survival During Venoarterial Extracorporeal Membrane Oxygenation.

Introduction: Oxygenation and carbon dioxide removal during venoarterial extracorporeal membrane oxygenation (VA ECMO) depend on a complex interplay of ECMO blood and gas flows, native lung and cardiac function as well as the mechanical ventilation strategy applied. Objective: To determine the association of oxygenation, carbon dioxide removal, and mechanical ventilation practices with in-hospital mortality in patients who received VA ECMO. Methods: Single center, retrospective cohort study. All consecutive patients who received VA ECMO in a tertiary ECMO referral center over a 5-year period were included. Data on demographics, ECMO and ventilator support details, and blood gas parameters for the duration of ECMO were collected. A multivariable logistic time-series regression model with in-hospital mortality as the primary outcome variable was used to analyse the data with significant factors at the univariate level entered into the multivariable regression model. Results: Overall, 52 patients underwent VA ECMO: 26/52 (50%) survived to hospital discharge. The median PaO2 for the duration of ECMO support was 146 mmHg [IQR 131-188] and PaCO2 was 37.2 mmHg [IQR 35.3, 39.9]. Patients who survived to hospital discharge had a significantly lower median PaO2 (117 [98, 140] vs. 154 [105, 212] mmHg, P = 0.04) and higher median PaCO2 (38.3 [36.1, 41.1] vs. 36.3 [34.5, 37.8] mmHg, p = 0.03). Survivors also had significantly lower median VA ECMO blood flow rate (EBFR, 3.6 [3.3, 4.2] vs. 4.3 [3.8, 5.2] L/min, p = < 0.001) and greater measured minute ventilation (7.04 [5.63, 8.35] vs. 5.32 [4.43, 6.83] L/min, p = 0.01). EBFR, PaO2, PaCO2, and minute ventilation, however, were not independently associated with death in a multivariable analysis. Conclusion: This exploratory analysis in a small group of VA ECMO supported patients demonstrated that hyperoxemia was common during VA ECMO but was not independently associated with increased mortality. Survivors also received lower EBFR and had greater minute ventilation, but this was also not independently associated with survival. These findings highlight that interactions between EBFR, PaO2, and native lung ventilation may be more relevant than their individual association with survival. Further research is indicated to determine the optimal ECMO and ventilator settings on outcomes in VA ECMO.

Non-home discharge after cardiac surgery in Australia and New Zealand: a cross-sectional study.

OBJECTIVE: To determine the proportion of patients surviving their cardiac surgery who experienced non-home discharge (NHD) over a 16-year period in Australia and New Zealand (ANZ). DESIGN: Retrospective, multicentre, cross-sectional study over the time period 01 January 2004 to 31 December 2019. SETTING: Adult patients who underwent cardiac surgery from the Australia New Zealand Intensive Care Society Adult Patient Database (APD). PARTICIPANTS: Adult patients (age 18 and above) who underwent index coronary artery bypass grafting, cardiac valve surgery or combined valve/coronary surgery. EXPOSURE: The primary exposure variable was the calendar year during the which the index surgery was performed. OUTCOME: The primary outcome was NHD after the index surgery. NHD included discharge to locations such as nursing home, chronic care facility, rehabilitation and palliative care. RESULTS: We analysed 252 924 index cardiac surgical admissions from 101 discrete sites with a median age of 68 years (IQR 60-76), of which 74.2% (187 662 out of 252 920) were males. Of these, 4302 (1.7%) patients died in hospital and 213 011 (84.2%) were discharged home, 18 010 (7.1%) were transferred to another hospital and 17 601 (7%) experienced NHD. In Australia, 14 457 (6.4%) of patients progressed to NHD, compared with 3144 (11.7%) in New Zealand. The rate of NHD increased significantly over time (adjusted OR per year=1.06, 95% CI, 1.06 to 1.07, p<0.001). Increasing age, female sex, non-elective surgery, surgery type and Acute Physiology and Chronic Health Evaluation III Score were all associated with significant increase in NHD. CONCLUSIONS: There was significant increase in NHD after cardiac surgery over time in ANZ. This has significant clinical relevance for informed consent discussions between healthcare providers and patients, and for healthcare services planning.

Barriers-enablers-ownership approach: a mixed methods analysis of a social intervention to improve surgical antibiotic prescribing in hospitals.

OBJECTIVES: To assess an intervention for surgical antibiotic prophylaxis (SAP) improvement within surgical teams focused on addressing barriers and fostering enablers and ownership of guideline compliance. DESIGN: The Queensland Surgical Antibiotic Prophylaxis (QSAP) study was a multicentre, mixed methods study designed to address barriers and enablers to SAP compliance and facilitate engagement in self-directed audit/feedback and assess the efficacy of the intervention in improving compliance with SAP guidelines. The implementation was assessed using a 24-month interrupted time series design coupled with a qualitative evaluation. SETTING: The study was undertaken at three hospitals (one regional, two metropolitan) in Australia. PARTICIPANTS: SAP-prescribing decisions for 1757 patients undergoing general surgical procedures from three health services were included. Six bimonthly time points, pre-implementation and post implementation of the intervention, were measured. Qualitative interviews were performed with 29 clinical team members. SAP improvements varied across site and time periods. INTERVENTION: QSAP embedded ownership of quality improvement in SAP within surgical teams and used known social influences to address barriers to and enablers of optimal SAP prescribing. RESULTS: The site that reported senior surgeon engagement showed steady and consistent improvement in prescribing over 24 months (prestudy and poststudy). Multiple factors, including resource issues, influenced engagement and sites/time points where these were present had no improvement in guideline compliance. CONCLUSIONS: The barriers-enablers-ownership model shows promise in its ability to facilitate prescribing improvements and could be expanded into other areas of antimicrobial stewardship. Senior ownership was a predictor of success (or failure) of the intervention across sites and time periods. The key role of senior leaders in change leadership indicates the critical need to engage other specialties in the stewardship agenda. The influence of contextual factors in limiting engagement clearly identifies issues of resource distributions/inequalities within health systems as limiting antimicrobial optimisation potential.

Evaluation of latest viscoelastic coagulation assays in the transcatheter aortic valve implantation setting.

BACKGROUND: Point of care viscoelastic measures with thromboelastography (TEG; Haemonetics Corporation, Switzerland) and thromboelastometry (ROTEM, Tem Innovations GmbH, Germany) now supersede laboratory assays in the perioperative assessment and management of coagulation. To the best of our knowledge, this sophisticated coagulation assessment has not been performed to characterise thrombotic changes in the transcatheter aortic valve implantation (TAVI) setting, nor have the two latest iteration cartridge-based systems been directly compared in the elective perioperative period. METHODS: Patients undergoing TAVI were prospectively recruited. Samples (n=44) were obtained at four timepoints (postinduction of anaesthesia, postheparin (100 IU/kg), postprotamine (1 mg/100 IU heparin) and 6 hours postoperatively). Each sample was concurrently assessed with standard laboratory tests (prothrombin time/international normalised ratio, activated partial thromboplastin time, thrombin clotting time, platelet count and direct fibrinogen, ROTEMSigma and TEG6s). RESULTS: Clot strength showed a statistically significant increase postheparin/TAVI deployment. When considering the subgroup of samples taken following the administration heparin, the heparinase channel of the TEG6s did not yield clotting strength results in 55% of samples and clotting time exceeded the upper limit of normal in 70% of samples. It was retrospectively recognised that the arachidonic acid channel of the TEG6s Platelet Mapping Cartridge had been decommissioned prohibiting assessment of aspirin effect. CONCLUSIONS: This study demonstrated a small intraprocedural prothrombotic change of uncertain clinical importance during the transcatheter aortic valve procedure. Further comparison with percutaneous coronary intervention and aortic valve replacement cohorts are needed to assess the merits of current antithrombotic guidelines, which are extrapolated from the PCI setting. The heparin effect was more consistently quantified by ROTEM.

Measurement of the Concentration of Citrate in Human Biofluids in Patients Undergoing Continuous Renal Replacement Therapy Using Regional Citrate Anticoagulation: Application of a Two-Step Enzymatic Assay.

BACKGROUND: Continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) is now commonly used to treat acute kidney injury in critically ill patients. The concentration of citrate is not routinely measured, with citrate accumulation and/or toxicity primarily assessed using surrogate measures. OBJECTIVES: The aim of this study was to measure the concentration of citrate in plasma and ultrafiltrate in patients receiving CRRT with RCA using a modified commercial enzymatic assay. METHODS: After meeting inclusion criteria, blood was sampled from 20 patients before, during, and after episodes of filtration. Using spectrophotometry, samples were tested for citrate concentration. Demographic and other clinical and biochemical data were also collected. Throughout, a 15 mmol/L solution of trisodium citrate was used as the prefilter anticoagulant. Results were analysed using STATA (v15.0) and presented as mean (SD), median (IQR), or simple proportion. Comparisons were made using either the Student t test or the Wilcoxon rank-sum test. Correlation was assessed using Pearson's r. RESULTS: Twenty patients (17 males) were enrolled in the study. Mean (SD) age was 63.7 years (9.9). Median (IQR) ICU length of stay was 281 h (199, 422) with 85% undergoing intermittent positive pressure ventilation. Median APACHE 3 score was 95 (87, 117) with an overall 30% mortality rate. Median filtration time was 85 h (46, 149). No difference was found between pre- and post-filtration plasma citrate concentrations (79 µmol/L [50] vs. 71 µmol/L [42], p = 0.65). Mean citrate concentration during filtration was 508 µmol/L (221) with a maximum of 1,070 µmol/L. This was significantly higher than the pre/post levels (p < 0.001). CONCLUSIONS: Plasma concentrations of citrate rose significantly during episodes of CRRT using RCA returning back to normal after cessation of treatment.

Skeletal muscle microvascular perfusion responses to cuff occlusion and submaximal exercise assessed by contrast-enhanced ultrasound: The effect of age.

Impairments in skeletal muscle microvascular function are frequently reported in patients with various cardiometabolic conditions for which older age is a risk factor. Whether aging per se predisposes the skeletal muscle to microvascular dysfunction is unclear. We used contrast-enhanced ultrasound (CEU) to compare skeletal muscle microvascular perfusion responses to cuff occlusion and leg exercise between healthy young (n = 12, 26 ± 3 years) and older (n = 12, 68 ± 7 years) adults. Test-retest reliability of CEU perfusion parameters was also assessed. Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: (a) 5-min of thigh-cuff occlusion, and (b) 5-min of submaximal intermittent isometric plantar-flexion exercise (400 N) using CEU. Whole-leg blood flow was measured using strain-gauge plethysmography. Repeated measures were obtained with a 15-min interval, and averaged responses were used for comparisons between age groups. There were no differences in post-occlusion whole-leg blood flow and muscle microvascular perfusion between young and older participants (p > .05). Similarly, total whole-leg blood flow during exercise and post-exercise peak muscle microvascular perfusion did not differ between groups (p > .05). The overall level of agreement between the test-retest measures of calf muscle perfusion was excellent for measurements taken at rest (intraclass correlation coefficient [ICC] 0.85), and in response to cuff occlusion (ICC 0.89) and exercise (ICC 0.95). Our findings suggest that healthy aging does not affect muscle perfusion responses to cuff-occlusion and submaximal leg exercise. CEU muscle perfusion parameters measured in response to these provocation tests are highly reproducible in both young and older adults.

An Experimental Series Investigating the Effects of Hyperinsulinemic Euglycemia on Myocardial Blood Flow Reserve in Healthy Individuals and on Myocardial Perfusion Defect Size following ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Incomplete restoration of myocardial blood flow (MBF) is reported in up to 30% of ST-segment elevation myocardial infarction (STEMI) despite prompt mechanical revascularization. Experimental hyperinsulinemic euglycemia (HE) increases MBF reserve (MBFR). If fully exploited, this effect may also improve MBF to ischemic myocardium. Using insulin-dextrose infusions to induce HE, we conducted four experiments to determine (1) how insulin infusion duration, dose, and presence of insulin resistance affect MBFR response; and (2) the effect of an insulin-dextrose infusion given immediately following revascularization of STEMI on myocardial perfusion. METHODS: The MBFR was determined using myocardial contrast echocardiography. Experiment 1 (insulin duration): 12 participants received an insulin-dextrose or saline infusion for 120 minutes. MBFR was measured at four time intervals during infusion. Experiment 2 (insulin dose): 22 participants received one of three insulin doses (0.5, 1.5, 3.0 mU/kg/minute) for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 3 (insulin resistance): five metabolic syndrome and six type 2 diabetes (T2DM) participants received 1.5 mU/kg/minute of insulin-dextrose for 60 minutes. Baseline and 60-minute MBFRs were determined. Experiment 4 (STEMI): following revascularization for STEMI, 20 patients were randomized to receive either 1.5 mU/kg/minute insulin-dextrose infusion for 120 minutes or standard care. Myocardial contrast echocardiography was performed at four time intervals to quantify percentage contrast defect length. RESULTS: Experiment 1: MBFR increased with time through to 120 minutes in the insulin-dextrose group and did not change in controls. Experiment 2: compared with baseline, MBFR increased in the 1.5 (2.42 ± 0.39 to 3.25 ± 0.77, P = .002), did not change in the 0.5, and decreased in the 3.0 (2.64 ± 0.25 to 2.16 ± 0.33, P = .02) mU/kg/minute groups. Experiment 3: compared with baseline, MBFR increase was only borderline significant in metabolic syndrome and T2DM participants (1.98 ± 0.33 to 2.59 ± 0.45, P = .04, and 1.67 ± 0.35 to 2.14 ± 0.21, P = .05). Experiment 4: baseline percentage contrast defect length was similar in both groups but with insulin decreased with time and was significantly lower than in controls at 60 minutes (2.8 ± 5.7 vs 13.7 ± 10.6, P = .02). CONCLUSIONS: Presence of T2DM, insulin infusion duration, and dose are important determinants of the MBFR response to HE. When given immediately following revascularization for STEMI, insulin-dextrose reduces perfusion defect size at one hour. Hyperinsulinemic euglycemia may improve MBF following ischemia, but further studies are needed to clarify this.

Acute stroke patients not meeting their nutrition requirements: Investigating nutrition within the enriched environment.

BACKGROUND & AIMS: Malnutrition is common after stroke. We investigated the impact of environmental enrichment strategies on dietary intake and rates of malnutrition in an acute stroke unit. METHODS: We performed a before-after study. In standard care, meals were delivered to participants' rooms whilst in the enriched environment, communal meals with assistance were offered and nutritional intake reminders were placed at the patient bedside. Nutrition supplementation was provided to both groups if indicated. Breakfast and lunch meals were directly observed while remaining intake was calculated using food charts. Nutrition requirements were calculated for energy (ratio method), protein (1 g/kg) and proportion of requirements met. Malnutrition was assessed using the Subjective Global Assessment and body weight. ANCOVA adjusting for stroke severity was used to determine between group differences. Stepwise multivariable logistic regression was performed to assess predictors of nutritional outcomes, adjusting for intervention group, demographic, clinical and baseline nutritional factors. RESULTS: Neither standard care (n = 30, age 76.0yrs ± SD12.8) nor enriched environment (n = 30, age 76.7yrs ± SD12.1, p = 0.84) met daily requirements for energy (70.7% ± SD16.8 vs. 70.7% ± SD17.3, p = 0.94) or protein intake (73.2% ± SD18.6 vs. 69.8% ± SD17.3, p = 0.70). Mean body weight dropped: standard care 0.92 kg ± SD2.47 vs. enriched 0.64 kg ± SD3.12 (p = 0.53) and malnutrition increased: standard care 3.3%-26.6% vs. enriched 6.6%-13.3% (p = 0.07). Predictors of malnutrition on discharge in logistic regression models were: length of stay (p < 0.01) and protein (p < 0.01) or energy intake (p = 0.02). CONCLUSIONS: Acute stroke patients were not meeting nutritional requirements and losing body weight. The enriched environment showed no effect on nutritional intake. Malnutrition was associated with lower energy and protein intakes and increased length of stay.

Risk Factors for Mortality in Patients Undergoing Cardiothoracic Surgery for Infective Endocarditis.

BACKGROUND: This study aimed to identify risk factors associated with mortality of patients who undergo cardiac surgery for infective endocarditis. METHODS: A retrospective review was performed of patients with infective endocarditis who underwent cardiac surgery at a quaternary Australian hospital between 2004 and 2014. Patient data were collected and prospectively analyzed. RESULTS: In all, 465 patients underwent surgery during the study period, with 30 deaths (6.45%). Factors independently associated with in-hospital mortality were increasing age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01 to 1.07; P = .009), active bacterial endocarditis at time of operation (OR 4.91; 95% CI, 1.01 to 23.8; P = .048), preoperative invasive positive pressure ventilation (OR 3.65; 95% CI, 1.18 to 11.27; P = .025), increasing cardiopulmonary bypass time (OR 1.01; 95% CI, 1.006 to 1.014; P < .001), and increasing European System for Cardiac Operative Risk Evaluation score (OR 21.73; 95% CI, 2.12 to 223.11; P < .01). CONCLUSIONS: The in-hospital mortality of patients with infective endocarditis remains significant, with potential risk factors including increasing age, active bacterial endocarditis, preoperative invasive positive pressure ventilation, increasing cardiopulmonary bypass time, and high European System for Cardiac Operative Risk Evaluation score.

Nosocomial infection prevalence in patients undergoing extracorporeal membrane oxygenation (ECMO): protocol for a point prevalence study across Australia and New Zealand.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) provides cardiac and/or respiratory support when other therapies fail. Nosocomial infection is reported in up to 64% of patients receiving ECMO and increases morbidity and mortality. These patients are at high risk of infection due, in part, to the multiple invasive devices required in their management, the largest being the cannulae through which ECMO is delivered. Prevalence of nosocomial infection in ECMO patients, including ECMO cannula-related infection, is not well described across Australia and New Zealand. METHODS AND ANALYSIS: This is a prospective, observational point prevalence study of 12 months duration conducted at 11 ECMO centres across Australia and New Zealand. Data will be collected for every patient receiving ECMO during 12 predetermined data collection weeks. The primary outcome is the prevalence of laboratory-confirmed bloodstream infection, and suspected or probable nosocomial infections; and the secondary outcomes include describing ECMO cannula dressing and securement practices, and adherence to local dressing and securement guidelines. Data collection will be finalised by March 2019. ETHICS AND DISSEMINATION: Relevant ethical and governance approvals have been received. Study results will describe the prevalence of suspected and confirmed nosocomial infection in adult, paediatric and neonatal patients receiving ECMO across Australia and New Zealand. It is expected that the results will be hypothesis generating and lead to interventional trials aimed at reducing the high infection rates seen in this cohort. Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ANZCTRN12618001109291; Pre-results.