Risk factors for mortality in severe COVID-19: Exploring the interplay of immunomodulatory therapy and coinfection.

Patients with severe clinical manifestations of coronavirus disease 2019 (COVID-19) present particular diagnostic and management challenges to critical care physicians, including identifying and responding to concurrent bacterial and fungal coinfections. This study evaluates risk factors for in-hospital mortality in patients admitted to the intensive care unit with severe COVID-19 during circulation of the B.1.617.2 (Delta) variant, including the impact of immunomodulators and bacterial and/or fungal coinfection. This retrospective cohort study enrolled patients with severe COVID-19. A Cox proportional hazard ratio analysis identified risk factors for in-hospital mortality. Outcomes were also compared between patients receiving and not receiving immunomodulatory therapy alongside standard care. Ninety patients admitted to the intensive care unit were enrolled. On multivariate analysis, the greatest risk factors for in-hospital mortality were invasive mechanical ventilation (hazard ratio (HR) = 15.27; 95% confidence interval (CI) 3.29-71.0; P < 0.001), elevated body mass index (HR = 1.07 per unit; 95% CI 1.02-1.13; P = 0.007) and older age (HR = 1.53 per decade; 95% CI 1.05-2.24; P = 0.028). Bacterial and/or fungal coinfection occurred at equal frequency in patients receiving and not receiving immunomodulatory therapy. However, in patients receiving immunomodulators, coinfection carried a significantly higher mortality risk (63.0%) compared with those without coinfection (15.4%; P = 0.038). Mortality from severe COVID-19 is significantly higher in older patients and those with elevated body mass index and requiring mechanical ventilation. Immunomodulatory therapy necessitates vigilance towards evolving coinfection in the intensive care setting.

Mitral regurgitation in the critically ill: the devil is in the detail.

Mitral regurgitation (MR) is common in the critically unwell and encompasses a heterogenous group of conditions with diverging therapeutic strategies. MR may present acutely with haemodynamic instability or more insidiously with failure to wean from mechanical ventilation. Critical illness is associated with marked physiological stress and haemodynamic changes that dynamically influence the severity and implication of MR. The expanding role of critical care echocardiography uniquely positions the intensivist to apply advanced bedside valvular assessment to recognise haemodynanically significant MR, manipulate and optimise cardiopulmonary physiology and identify patients requiring urgent cardiology and surgical referral. This review will consider common clinical scenarios, therapeutic strategies and the pearls and pitfalls of echocardiographic assessment and quantification in the critically unwell.

Audit of low tidal volume ventilation in patients with hypoxic respiratory failure in a tertiary Australian intensive care unit.

A low tidal volume ventilation (LTVV) strategy improves outcomes in patients with acute respiratory distress syndrome (ARDS). Subsequently, a LTVV strategy has become the standard of care for patients receiving mechanical ventilation. This strategy is poorly adhered to within intensive care units (ICUs). A retrospective analysis was conducted of prescribed tidal volumes in mechanically ventilated patients with hypoxic respiratory failure between April 2013 and March 2017. Data collection included the establishment of a new data-entry box for patient height in March 2016, aimed at assisting the calculation of LTVV. We reviewed 836 ICU admissions, comprising 19,884 hours of ventilation. A total of 92% of admissions lacked patient height recording. When height was recorded, 54% of hours of ventilation were LTVV adherent. Non-LTVV hours for both groups involved higher tidal volumes (38%) rather than lower tidal volumes (8%). Non-LTVV-adherent hours were significantly (P<0.001) more likely to be associated with patient mortality than LTVV-adherent hours were. For all hours of ventilation, mean tidal volume before March 2016 was significantly higher (496 (standard deviation (SD) 101) ml, compared to after March 2016 (451 (SD 107) ml, P<0.001, 95% confidence interval for true difference in means 42 to 48 ml). However, this trend gradually reversed over time. There was a clinician preference for multiples of 50 ml. There was poor adherence to LTVV strategy in patients with hypoxic respiratory failure, which was associated with an increase in patient mortality. An electronic medical record intervention was successful in producing change, but this was not sustainable over time. Clinician ventilation prescribing habits were based on numerical simplicity rather than evidence-based practice.

Changes in Right Ventricle Function After Mitral Valve Repair Surgery.

BACKGROUND: Right ventricular (RV) dysfunction can occur after cardiac surgery and persist for years. We assessed perioperative RV systolic function in patients undergoing mitral valve (MV) repair and further compared minimally invasive robotic-assisted mitral valve repair (MIMVr) vs standard 'open' MV repair (MVr). Speckle tracking (RV free wall strain [RVS]) was used as a sensitive echocardiography method to assess RV function. METHODS: Retrospective analysis, over 3 years, of consecutive patients (n = 158) referred to Mayo Clinic (Rochester, MN, USA). Preoperative, pre-discharge and 1 year transthoracic echocardiograms were reviewed. A prospective pilot study was performed for sample size estimation. Primary outcome was RV free wall strain (RVS). RESULTS: Right ventricular free wall strain declined after MV repair surgery (-22.6 ± 7% vs -15 ± 6%, p < 0.001). There were smaller reductions in RVS in MIMVr vs MVr group (-6.0 ± 9% vs -10.3 ± 8%, p < 0.01), which persisted after adjusting for baseline values (RVS treatment effect 1.5%, p = 0.007). There was greater recovery in MIMVr vs MVr group at 1 year follow-up vs pre-surgery values (-3.4 ± 9% vs -8.1 ± 8% respectively, p < 0.001, RVS treatment effect 1.7%, p = 0.001). Bypass time was higher in the MIMVr group (80min ± 22 vs 40min ± 20, p < 0.0001). The echo findings remained significant correcting for age, pulmonary pressures and change in ejection fraction. CONCLUSIONS: Right ventricular systolic dysfunction is common after MV repair surgery. Deterioration in RV contraction is less pronounced following MIMVr vs MVr and is associated with enhanced RV functional recovery at 1 year, albeit not to preoperative levels. This may potentially be associated with clinical functional improvement but further studies are warranted to investigate this.

Calibrated cardiac output monitoring versus standard care for fluid management in the shocked ICU patient: a pilot randomised controlled trial.

BACKGROUND: Despite the evidence for calibrated cardiac monitored devices to determine fluid responsiveness, there is minimal evidence that the use of cardiac output monitor devices leads to an overall change in IV fluid use. We sought to investigate the feasibility of performing a randomised controlled study using calibrated cardiac output monitoring devices in shocked ICU patients and whether the use of these devices led to a difference in total volume of IV fluid administered. METHODS: We performed a single-centre non-blinded randomised controlled study which included patients who met the clinical criteria for shock on admission to ICU. Patients were divided into two groups (cardiac output monitors or standard) by block randomisation. Patients allocated to the cardiac output monitor all received EV1000 with Volume View sets. Daily intravenous fluid administration and cumulative fluid balance was recorded for 3 days. The primary outcome assessed was the difference in daily intravenous fluid administration and cumulative fluid balance at 72 h between the two groups. We also assessed how often the clinicians used the cardiac monitor to guide fluid therapy and the different reasoning for initiating further intravenous fluids. RESULTS: Eighty patients were randomised and 37 received calibrated cardiac output monitors. We found no adverse outcomes in the use of calibrated cardiac output monitoring devices and that was feasible to perform a randomised controlled trial. There was no significant difference between the standard care group vs the cardiac monitoring group for cumulative fluid balance (2503 ± 3764 ml vs 2458 ± 3560 ml, p = 0.96). There was no significant difference between the groups for daily intravenous fluid administration on days 1, 2 or 3. In the cardiac monitored group, only 43% of the time was the EV1000 output incorporated into the decision to give further intravenous fluids. CONCLUSION: It is feasible to perform a randomised controlled trial using calibrated cardiac output monitoring devices. In addition, there was no trend to suggest that the use of a cardiac monitors leads to lower IV fluid use in the shocked patient. Further trials will require study designs to optimise the use of a cardiac output monitor to determine the utility of these devices in the shocked patient. TRIAL REGISTRATION: ANZCTR, ACTRN12618001373268. Registered 15 August 2018-retrospectively registered.

Paradoxical septal motion: A diagnostic approach and clinical relevance.

Abnormal septal motion (commonly referred to as septal bounce) is a common echocardiographic finding that occurs with several conditions, including the following: mitral stenosis, left bundle branch block, pericardial syndromes and severe pulmonary hypertension. We explore the subtle changes that occur on M-mode imaging of the septum, other associated echocardiographic features, the impact of inspiratory effort on septal motion and relevant clinical findings. Finally, we discuss the impact of abnormal septal motion on cardiac form and function, proposing there is a clinically significant impact on biventricular filling and ejection.

Application of updated guidelines on diastolic dysfunction in patients with severe sepsis and septic shock.

BACKGROUND: Left ventricular diastolic dysfunction is suggested to be associated with higher mortality in severe sepsis and septic shock, yet the methods of diagnosis described in the literature are often inconsistent. The recently published 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) guidelines offer the opportunity to apply a simple pragmatic diagnostic algorithm for the detection of diastolic dysfunction; however, it has not been tested in this cohort. AIMS: We sought to assess the applicability in septic patients of recently published 2016 ASE/EACVI guidelines on diastolic dysfunction compared with the 2009 ASE guidelines. Our hypothesis was that there would be poor agreement in classifying patients. METHODS: Prospective observational study includes patients identified as having severe sepsis and septic shock. Patients underwent transthoracic echocardiography on day 1 and day 3 of their ICU admission. Patients with normal and abnormal (ejection fraction < 52%) systolic function had their diastolic function stratified according to both the 2009 ASE and 2016 ASE/EACVI guidelines. RESULTS: On day 1 echocardiography, of the 62 patients analysed, 37 (60%) had diastolic dysfunction according to the 2016 ASE/EACVI guideline with a further 23% having indeterminate diastolic function, compared to the 2009 ASE guidelines where only 13 (21%) had confirmed diastolic dysfunction with 46 (74%) having indeterminate diastolic dysfunction. On day 3, of the 55 patients studied, 22 patients (40%) were defined as having diastolic dysfunction, with 6 (11%) having indeterminate diastolic dysfunction according to the 2016 ASE/EACVI guidelines, compared to the 2009 guidelines where 11 (20%) were confirmed to have diastolic dysfunction and 41 (75%) had indeterminate diastolic function. Systolic dysfunction was identified in 18 of 62 patients (29%) on day 1 and 18 of 55 (33%) on day 3. These patients were classified as having abnormal diastolic function in 94 and 89% with the 2016 guidelines on day 1 and day 3, respectively, compared with 50 and 28% using the 2009 guidelines. The 2016 guidelines had less patients with indeterminate diastolic function on days 1 and 3 (11 and 6%) compared to the 2009 guidelines (50 and 72%). Normal systolic function was identified in 44 patients on day 1 and 37 on day 3. In this group, abnormal diastolic function was present in 45 and 54% on days 1 and 3 according to the 2016 ASE/EACVI guidelines, compared with 9 and 16% using the 2009 guidelines, respectively. In those with normal systolic function, the 2016 guidelines had less indeterminate patients with 30 and 16% on days 1 and 3, respectively, compared to 84 and 76% in the 2009 guidelines. CONCLUSION: The 2016 ASE/EACVI diastolic function guidelines identify a significantly higher incidence of dysfunction in patients with severe sepsis and septic shock compared to the previous 2009 guidelines. Although the new guidelines seem to be an improvement, issues remain with the application of guidelines using traditional measures of diastolic dysfunction in this cohort.

Basic critical care echocardiography: How many studies equate to competence? A pilot study using high fidelity echocardiography simulation.

BACKGROUND: Assessment of competence in basic critical care echocardiography is complex. Competence relies on not only imaging accuracy but also interpretation and appropriate management decisions. The experience to achieve these skills, real-time, is likely more than required for imaging accuracy alone. We aimed to assess the feasibility of using simulation to assess number of studies required to attain competence in basic critical care echocardiography. METHODS: This is a prospective pilot study recruiting trainees at various degrees of experience in basic critical care echocardiography using experts as reference standard. We used high fidelity simulation to assess speed and accuracy using total time taken, total position difference and total angle difference across the basic acoustic windows. Interpretation and clinical application skills were assessed using a clinical scenario. 'Cut-off' values for number of studies required for competence were estimated. RESULTS: Twenty-seven trainees and eight experts were included. The subcostal view was achieved quickest by trainees (median 23 s, IQR 19-37). Eighty-seven percent of trainees did not achieve accuracy across all views; 81% achieved accuracy with the parasternal long axis and the least accurate was the parasternal short axis (44% of trainees). Fewer studies were required to be considered competent with imaging acquisition compared with competence in correct interpretation and integration (15 vs. 40 vs. 50, respectively). DISCUSSION: The use of echocardiography simulation to determine competence in basic critical care echocardiography is feasible. Competence in image acquisition appears to be achieved with less experience than correct interpretation and correct management decisions. Further studies are required.

Detecting impaired myocardial relaxation in sepsis with a novel tissue Doppler parameter (septal e'/s').

BACKGROUND: Left ventricular diastolic dysfunction is associated with mortality outcomes in severe sepsis and septic shock. There are ongoing issues with diagnosing diastolic dysfunction in this cohort, partly owing to the poor applicability of traditional parameters in the hyperdynamic circulation. In this feasibility study, we sought to assess the utility of a novel parameter (septal e'/s') to identify diastolic dysfunction in patients with severe sepsis and septic shock who had normal systolic function against the 2016 American Society Echocardiography and European Association of Cardiovascular Imaging (ASE/EACI) guidelines on diastolic dysfunction. METHODS: In this prospective observational pilot study, patients identified as having severe sepsis and septic shock underwent transthoracic echocardiography on day 1 and day 3 of their intensive care unit admission. In patients with normal systolic function, septal e'/s' was calculated using the peak modal velocity of the s' compared with the e' from the septal annulus tissue Doppler imaging and compared with their diastolic grade according to the 2016 ASE/EACI guidelines on diastolic dysfunction. RESULTS: On day 1 of admission, 44 of 62 patients with severe sepsis and septic shock had normal systolic function. There was a strong association of those with diastolic dysfunction having a reduced septal e'/s' compared with patients with normal diastolic function (AUC 0.91). A similar relationship was seen with patients who had indeterminate diastolic dysfunction. On day 3, 37 patients had normal systolic function. Again, there was a strong association of those with diastolic dysfunction and a reduced septal e'/s' (AUC 0.95). CONCLUSIONS: A reduction in septal e'/s' may indicate diastolic dysfunction in patients with severe sepsis and septic shock who have normal systolic function. As opposed to limited traditional measures of diastolic dysfunction, it is applicable in those with hyperdynamic systolic function.

Use of Angle-Independent M-Mode Sonography for Assessment of Diaphragm Displacement.

OBJECTIVES: Sonographic assessment of diaphragm displacement has conventionally been conducted with M-mode sonography via an anterior subcostal approach. This method is subject to measurement errors when diaphragm displacement is not in line with the M-mode plane. We aimed to compare measurements obtained by offline angle-independent (anatomic) M-mode sonography with conventional M-mode sonography. METHODS: Fifty healthy adults were imaged with conventional and angle-independent M-mode sonography of the bilateral hemidiaphragms at 60% maximal inspiratory capacity using an inspiratory spirometer. RESULTS: Left hemidiaphragm displacement was successfully imaged by conventional M-mode sonography in only 70% (n = 35), as lung expansion obscured imaging, whereas 92% (n = 46) were assessable by angle-independent M-mode sonography. All right hemidiaphragm displacement could be assessed. Conventional M-mode results were higher than angle-independent M-mode results on the right (mean ± SD, 4.9 ± 1.4 versus 4.6 ± 1.2 cm, respectively; P= .003) and left (5.4 ± 1.3 versus 4.6 ± 1.0 cm; P < .001). Displacement values were different for right versus left hemidiaphragms on conventional M-mode sonography (mean difference, 0.6 ± 0.2 cm; P = .005), with only mild agreement (R2 = 0.35; P < .001). There was no laterality seen in the diaphragm displacement on angle-independent M-mode sonography (mean difference, 0.1 ± 0.1 cm; P = .47), with good agreement (R2 = 0.76; P < .001). CONCLUSIONS: Angle-independent M-mode sonography leads to better visualization and assessment of the left hemidiaphragm. It records lower displacement than conventional M-mode sonography in the bilateral diaphragms, likely because of fewer orientation and translation errors. Future study is indicated to assess the clinical utility of angle-independent M-mode sonography in a population with diaphragm dysfunction.

Diaphragm assessment by two dimensional speckle tracking imaging in normal subjects.

BACKGROUND: Conventionally, ultrasonographic assessment of diaphragm contractility has involved measuring respiratory changes in diaphragm thickness (thickening fraction) using B-mode or caudal displacement with M-mode. Two-dimensional speckle-tracking has been increasingly used to assess muscle deformation ('strain') in echocardiography. We sought to determine in a pilot study if this technology could be utilized to analyze diaphragmatic contraction. METHODS: Fifty healthy adult volunteers with normal exercise capacity underwent ultrasound imaging. A linear array transducer was used for the assessment of diaphragm thickness, thickening fraction (TF), and strain in the right anterior axillary line at approximately the ninth intercostal space. A phased array transducer was applied subcostally for the assessment of diaphragm displacement on the right mid-clavicular line. Diaphragmatic images were recorded from the end of expiration through the end of inspiration at 60 % maximal inspiratory capacity. Diaphragm strain was analyzed off-line by speckle tracking imaging. Blinded inter- and intra-rater variability was tested in 10 cases. RESULTS: Mean right diaphragm thickness at end-expiration (±SD: standard deviation) was 0.24 cm (±0.1), with TF of 45.1 % (±12) at 60 % peak inspiratory effort. Mean right diaphragm caudal displacement was 4.9 cm (±1). Mean right diaphragm strain was -40.3 % (±9). A moderate correlation was seen between longitudinal strain and TF (R(2) 0.44, p < 0.0001). A weak correlation was seen between strain and caudal displacement (R(2) 0.14, p < 0.01), and an even weaker correlation was seen between caudal displacement and TF (R(2) 0.1, p = 0.04). Age, gender, and body mass index were not significantly associated with right diaphragm strain or TF. Although inter- and intra-rater variability was overall good for TF, caudal displacement, and strain (inter-rater R(2); 0.8, 0.9, and 0.7, respectively [p < 0.01], intra-rater R(2); 0.9, 0.7, and 0.9, respectively [p < 0.01]), strain values did have a slightly lower inter-rater repeatability. CONCLUSIONS: Diaphragmatic strain estimated by speckle tracking imaging was associated with conventional ultrasound measures of diaphragmatic function (TF and caudal displacement). Further clinical studies are warranted to investigate its clinical utility.

Bedside lung ultrasound, mobile radiography and physical examination: a comparative analysis of diagnostic tools in the critically ill.

OBJECTIVE: To compare lung ultrasonography (LUS), chest xray (CXR) and physical examination (Ex) for the detection of pathological abnormalities in the lungs of critically ill patients. DESIGN, SETTING AND PARTICIPANTS: A prospective cohort study of 145 patients in the intensive care unit of a tertiary teaching hospital who were undergoing echocardiography for a clinical indication. MAIN OUTCOME MEASURES: Each patient was independently assessed by Ex, CXR and LUS on the same day. Examiners were asked to comment on the presence or absence and severity of pleural effusion, lung consolidation and alveolar interstitial syndrome (AIS). Independent expert examiners performed the LUS and an independent radiologist reported on the CXR. RESULTS: Ex, CXR and LUS were in fair agreement with each other in detecting a pulmonary abnormality (CXR v LUS, κ = 0.31; CXR v Ex, κ = 0.29; LUS v Ex, κ = 0.22). LUS detected more abnormalities than did CXR (16.2%; χ(2) = 64.1; P < 0.001) or Ex (23.5%; χ(2) = 121.9; P < 0.001). CXR detected more pleural effusions than LUS (9.3%; χ(2) = 7.6; κ = 0.39), but LUS detected more pleural effusions than Ex (22.8%; χ(2) = 36.4; κ = 0.18). There was no significant difference in the performance of LUS and CXR in quantifying the size of a pleural effusion (Z = -1.2; P = 0.23). Ex underestimated size compared with CXR or LUS. LUS detected more consolidation than CXR (17%; χ(2) = 115.9; P < 0.001) and Ex (16.2%; χ(2) = 90.3; P < 0.001). We saw no difference in performance between CXR and Ex in detecting lung consolidation (0.9%; χ(2) = 0.51; P < 0.48). LUS detected more cases of AIS than CXR (5.5%; χ(2) = 7.9; P = 0.005) and Ex (13%; χ(2) = 25.8; P < 0.001). CONCLUSIONS: There was only fair-to-moderate agreement between LUS, CXR and Ex in detecting pulmonary abnormalities, including pleural effusion, lung consolidation and AIS. The higher rate of detection from LUS, combined with its ease of use and increasing accessibility, makes for a powerful diagnostic tool in the ICU.

Effect of positive end-expiratory pressure on porcine right ventricle function assessed by speckle tracking echocardiography.

BACKGROUND: Right ventricle (RV) dysfunction and hypotension can be induced by high levels of positive end-expiratory pressure (PEEP). We sought to determine in an animal model if a novel ultrasound analysis technique: speckle tracking echocardiography (STE), could determine deterioration in RV function induced by PEEP and to compare this to a conventional method of RV analysis: fractional area change (FAC). STE is a sensitive, angle-independent method for describing cardiac deformation ('strain') and is particularly useful in analyzing RV function as has been shown in pulmonary hypertension cohorts. METHODS: Ten pigs, 40-90 kg, anaesthetized, fully mechanically ventilated at 6 ml/kg were subject to step-wise escalating levels of PEEP at two-minute intervals (0, 5, 10, 15, 20, 25 and 30 cmH20). Intracardiac echocardiography was used to image the RV as transthoracic and transesophageal echocardiography did not give sufficient image quality or flexibility. Off-line STE analysis was performed using Syngo Velocity Vector Imaging (Seimens Medical Solutions Inc., USA). STE systolic parameters are RV free wall strain (RVfwS) and strain rate (RVfwSR) and the diastolic parameter RV free wall strain rate early relaxation (RVfwSRe). RESULTS: With escalating levels of PEEP there was a clear trend of reduction in STE parameters (RVfwS, RVfwSR, RVfwSRe) and FAC. Significant hypotension (fall in mean arterial blood pressure of 20 mmHg) occurred at approximately PEEP 15 cmH2O. Comparing RVfwS, RVfwSR and RVfwSRe values at different PEEP levels showed a significant difference at PEEP 0 cmH2O vs PEEP 10 cmH2O and above. FAC only showed a significant difference at PEEP 0 cmH2O vs PEEP 20 cmH2O and above. 30% of pigs displayed dyssychronous RV free wall contraction at the highest PEEP level reached. CONCLUSIONS: STE is a sensitive method for determining RV dysfunction induced by PEEP and deteriorated ahead of a conventional assessment method: FAC. RVfwS decreased to greater extent compared to baseline than FAC, earlier in the PEEP escalation process and showed a significant decrease before there was a clinical relevant decrease in mean arterial blood pressure. Studies in ICU patients using transthoracic echocardiography are warranted to further investigate the most sensitive echocardiography method for detecting RV dysfunction induced by mechanical ventilation.

Outcome prediction in sepsis: speckle tracking echocardiography based assessment of myocardial function.

INTRODUCTION: Speckle tracking echocardiography (STE) is a relatively novel and sensitive method for assessing ventricular function and may unmask myocardial dysfunction not appreciated with conventional echocardiography. The association of ventricular dysfunction and prognosis in sepsis is unclear. We sought to evaluate frequency and prognostic value of biventricular function, assessed by STE in patients with severe sepsis or septic shock. METHODS: Over an eighteen-month period, sixty patients were prospectively imaged by transthoracic echocardiography within 24 hours of meeting severe sepsis criteria. Myocardial function assessment included conventional measures and STE. Association with mortality was assessed over 12 months. RESULTS: Mortality was 33% at 30 days (n = 20) and 48% at 6 months (n = 29). 32% of patients had right ventricle (RV) dysfunction based on conventional assessment compared to 72% assessed with STE. 33% of patients had left ventricle (LV) dysfunction based on ejection fraction compared to 69% assessed with STE. RV free wall longitudinal strain was moderately associated with six-month mortality (OR 1.1, 95% confidence interval, CI, 1.02-1.26, p = 0.02, area under the curve, AUC, 0.68). No other conventional echocardiography or STE method was associated with survival. After adjustment (for example, for mechanical ventilation) severe RV free wall longitudinal strain impairment remained associated with six-month mortality. CONCLUSION: STE may unmask systolic dysfunction not seen with conventional echocardiography. RV dysfunction unmasked by STE, especially when severe, was associated with high mortality in patients with severe sepsis or septic shock. LV dysfunction was not associated with survival outcomes.