Thoracic ultrasound for pleural effusion in the intensive care unit: A narrative review from diagnosis to treatment

Pleural effusion (PLEFF), mostly caused by volume overload, congestive heart failure, and pleuropulmonary infection, is a common condition in critical care patients. Thoracic ultrasound (TUS) helps clinicians not only to visualize pleural effusion, but also to distinguish between the different types. Furthermore, TUS is essential during thoracentesis and chest tube drainage as it increases safety and decreases life-threatening complications. It is crucial not only during needle or tube drainage insertion, but also to monitor the volume of the drained PLEFF. Moreover, TUS can help diagnose co-existing lung diseases, often with a higher specificity and sensitivity than chest radiography and without the need for X-ray exposure. We review data regarding the diagnosis and management of pleural effusion, paying particular attention to the impact of ultrasound. Technical data concerning thoracentesis and chest tube drainage are also provided

Phantom model and scoring system to assess ability in ultrasound-guided chest drain positioning

Background: Chest tube positioning is an invasive procedure associated with potentially serious injuries. In the last few years, we have been running a project directed at developing a practical simulator of a surgical procedure taught on our medical training program. The phantom model reconstructs the pleural anatomy, visible by lung ultrasound, used for the assessed performance of the Seldinger technique. The aim of the present study was to investigate the validity of this simulation technology for assessing residents in anesthesia and intensive care medicine; specifically, their skill in positioning a US-guided chest tube drain was tested using the simulator device. The second aim of the paper was to evaluate the learning curve of our residents over their 5-year study course and validate the phantom scoring system. Methods: This was a prospective, single-blinded observational study. Participants were recruited from residents in anesthesia and intensive care medicine and divided into two groups: \u2018Novice\u2019 and \u2018Expert,\u2019 based on the course year attended (years 1, 2, and 3 vs. years 4 and 5, respectively). We asked them to position a chest tube drain in a phantom model, guided by ultrasound, to drain a simulated pleural effusion. Each subject performed two tests that simulated pleural effusions of 4 and 2\ua0cm, respectively. Every step of the maneuver was constantly monitored and the performance scored by the investigators. We then performed a Spearman correlation analysis to evaluate the effect of experience level on the performance of the two groups of residents. Results: Thirty-one residents were included in this study: 20 in the Novice group and 11 in the Expert group. The mean performance rating score was 0.75\ua0\ub1\ua04.38 for the Novice Group and 5.91\ua0\ub1\ua03.75 for the Expert group (p\ua0=\ua00.0026). The Spearman correlation analysis examining the relationship between year of residency and performance rating score confirmed a positive correlation (r\ua0=\ua00.58, p\ua0=\ua00.0006). Post-test trend analysis revealed a statistically significant linear trend for skill growth across time, i.e., course year (p\ua0=\ua00.0022). Conclusions: Our simulated procedure using a phantom model of lung anatomy can accurately and reliably be used to assess the skill levels of operators in their ability to drain pleural effusion

Quantitative lung ultrasonography: A putative new algorithm for automatic detection and quantification of B-lines

Background: This pilot study was designed to develop a fully automatic and quantitative scoring system of B-lines (QLUSS: quantitative lung ultrasound score) involving the pleural line and to compare it with previously described semi-quantitative scores in the measurement of extravascular lung water as determined by standard thermo-dilution. Methods: This was a prospective observational study of 12 patients admitted in the intensive care unit with acute respiratory distress and each provided with 12 lung ultrasound (LUS) frames. Data collected from each patient consisted in five different scores, four semi-quantitative (nLUSS, cLUSS, qLUSS, %LUSS) and quantitative scores (QLUSS). The association between LUS scores and extravascular lung water (EVLW) was determined by simple linear regression (SLR) and robust linear regression (RLR) methods. A correlation analysis between the LUS scores was performed by using the Spearman rank test. Inter-observer variability was tested by computing intraclass correlation coefficient (ICC) in two-way models for agreement, basing on scores obtained by different raters blinded to patients' conditions and clinical history. Results: In the SLR, QLUSS showed a stronger association with EVLW (R 2 = 0.57) than cLUSS (R 2 = 0.45) and nLUSS (R 2 = 0.000), while a lower association than qLUSS (R 2 = 0.85) and %LUSS (R 2 = 0.72) occurred. By applying RLR, QLUSS showed an association for EVLW (R 2 = 0.86) comparable to qLUSS (R 2 = 0.85) and stronger than %LUSS (R 2 = 0.72). QLUSS was significantly correlated with qLUSS (r = 0.772; p = 0.003) and %LUSS (r = 0.757; p = 0.005), but not with cLUSS (r = 0.561; p = 0.058) and nLUSS (r = 0.105; p = 0.744). Moreover, QLUSS showed the highest ICC (0.998; 95%CI from 0.996 to 0.999) among the LUS scores. Conclusions: This study demonstrates that computer-aided scoring of the pleural line percentage affected by B-lines has the potential to assess EVLW. QLUSS may have a significant impact, once validated with a larger dataset composed by multiple real-time frames. This approach has the potentials to be advantageous in terms of faster data analysis and applicability to large sets of data without increased costs. On the contrary, it is not useful in pleural effusion or consolidations

Could the use of bedside lung ultrasound reduce the number of chest x-rays in the intensive care unit?

Background: Lung ultrasound can be used as an alternative to chest radiography (CXR) for the diagnosis and follow-up of various lung diseases in the intensive care unit (ICU). Our aim was to evaluate the influence that introducing a routine daily use of lung ultrasound in critically ill patients may have on the number of CXRs and as a consequence, on medical costs and radiation exposure. Methods: Data were collected by conducting a retrospective evaluation of the medical records of adult patients who needed thoracic imaging and were admitted to our academic polyvalent ICU. We compared the number of CXRs and relative costs before and after the introduction of lung ultrasound in our ICU. Results: A total of 4134 medical records were collected from January 2010 to December 2014. We divided our population into two groups, before (Group A, 1869 patients) and after (Group B, 2265 patients) the introduction of a routine use of LUS in July 2012. Group A performed a higher number of CXRs compared to Group B (1810 vs 961, P = 0.012), at an average of 0.97 vs 0.42 exams per patient. The estimated reduction of costs between Groups A and B obtained after the introduction of LUS, was 57%. No statistically significant difference between the outcome parameters of the two groups was observed. Conclusions: Lung ultrasound was effective in reducing the number of CXRs and relative medical costs and radiation exposure in ICU, without affecting patient outcome

Comparison of diuretic strategies in diuretic-resistant acute heart failure: A systematic review and network meta-analysis

OBJECTIVE: Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF. MATERIALS AND METHODS: We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases. RESULTS: Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison. CONCLUSIONS: None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF

Jugular vein distensibility predicts fluid responsiveness in septic patients

Introduction: The purpose of the study was to verify the efficacy of using internal jugular vein (IJV) size and distensibility as a reliable index of fluid responsiveness in mechanically ventilated patients with sepsis. Methods: Hemodynamic data of mechanically ventilated patients with sepsis were collected through a radial arterial indwelling catheter connected to continuous hemodynamic monitoring system (Most Care®, Vytech Health, Padova, Italy), including cardiac index (CI) (L/min/M2), heart rate (beats/min), mean arterial pressure (MAP) (mmHg), central venous pressure (CVP) (mmHg) and arterial pulse pressure variation (PPV), coupled with ultrasound evaluation of IJV distensibility (%), defined as a ratio of the difference between IJV maximal antero-posterior diameter during inspiration and minimum expiratory diameter to minimum expiratory diameter x100. Patients were retrospectively divided into two groups; fluid responders (R), if CI increase of more than or equal to 15% after a 7 ml/kg crystalloid infusion, and non-responders (NR) if CI increased more than 15%. We compared differences in measured variables between R and NR groups and calculated receiver-operator-characteristic (ROC) curves of optimal IJV distensibility and PPV sensitivity and specificity to predicting R. We also calculated a combined inferior vena cava distensibility-PPV ROC curve to predict R. Results: We enrolled 50 patients, of these, 30 were R. Responders presented higher IJV distensibility and PPV before fluid challenge than NR (P <0.05). An IJV distensibility more than 18% prior to volume challenge had an 80% sensitivity and 85% specificity to predict R. Pairwise comparison between IJV distensibility and PPV ROC curves revealed similar ROC area under the curve results. Interestingly, combining IJV distensibility more than 9.7% and PPV more than 12% predicted fluid responsiveness with a sensitivity of 100% and specificity of 95%. Conclusion: IJV distensibility is an accurate, easily acquired non-invasive parameter of fluid responsiveness in mechanically ventilated septic patients with performance similar to PPV. The combined use of IJV distensibility with left-sided indexes of fluid responsiveness improves their predictive value

Fluid balance and urine volume are independent predictors of mortality in acute kidney injury.

INTRODUCTION: In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI. METHODS: We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression. RESULTS: Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50\%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95\%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95\%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95\%CI 0.12 to 0.52; <0.001). CONCLUSIONS: In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients

Minor-but-Complex Liver Resection: An Alternative to Major Resections for Colorectal Liver Metastases Involving the Hepato-Caval Confluence

Major hepatectomy (MH) is often considered the only possible approach for colorectal liver metastasis (CRLM) at the hepato-caval confluence (CC), but it is associated with high morbidity and mortality. With the aim to reduce MH, we developed the "minor-but-complex" (MbC) technique, which consists in the resection of less than 3 adjacent liver segments with exposure of the CC and preservation of hepatic outflow until spontaneous maturation of peripheral intrahepatic shunts between main hepatic veins. We have evaluated applicability and outcome of MbC resections for the treatment of CRLM involving the CC. In this retrospective cohort study, all consecutive liver resections (LR) performed for CRLM located in segments 1, 7, 8, or 4a were classified as MINOR - removal of bC - removal of = 3 adjacent segments. The rate of avoided MH was obtained by the difference between the rate of potentially MH (PMH) plus potentially inoperable cases and the rate of the MH performed. Taking into account that postoperative mortality is mainly related to the amount of resected liver, MbC was compared with minor resections for safety, complexity, and outcome. Of the 59 LR analyzed, 29 (49.1%) were deemed PMH and 4 (6.8%) potentially inoperable. Eventually, MH was performed only in 8 (13.5%) with a decrease rate of 42.4%. Minor LR was performed in 23 (39.0%) and MbC LR in 28 (47.5%) patients. Among MbC cases, 32.1% had previous liver treatments, 39.3% required vascular reconstruction (no reconstructed vessel thrombosis occurred before maturation of peripheral intrahepatic shunts between main hepatic veins), and 7.1% had grade IIIb-IV complications, their median hospital stay was 9 days and 90-day mortality was 0%. After a median follow-up of 22.2 months, oncological results were comparable with those of minor resections. MbC hepatectomy lowers the need for MH and allows for the resection of potentially inoperable patients without negative impact on safety and survival

Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial

OBJECTIVES: To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. TRIAL DESIGN: The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. PARTICIPANTS: Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from &gt; 24 hours 3. Invasive mechanical ventilation from &lt; 96 hours 4. PaO2/FiO2 ratio lower than 150 mmHg 5. D-dimer level &gt; 6 times the upper limit of normal reference range 6. C-reactive Protein &gt; 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age &lt; 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count &lt; 100.000/mm3 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit" 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: \u2022 LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. \u2022 LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. \u2022 UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. MAIN OUTCOMES: Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. RANDOMIZATION: A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (&lt;30/ 6530) and Age (&lt;75/ 6575). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. BLINDING (MASKING): Participants to the study will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. TRIAL STATUS: Protocol version 1.1 of April 26th, 2020. Recruitment start (expected): September 1st, 2020 Recruitment finish (expected): June 30th, 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30 , registered on April 15th, 2020 AIFA approval on May 4th, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol