A Secondary Retrospective Analysis of the Predictive Value of Neutrophil-Reactive Intensity (NEUT-RI) in Septic and Non-Septic Patients in Intensive Care.

BACKGROUND: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil-reactive intensity (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. MATERIALS: This study is a secondary, retrospective, observational analysis. Clinical data upon ICU admission were collected. We enrolled septic patients and a control group of critically ill patients without sepsis criteria. The patients were divided into subgroups based on renal function for biomarker evaluation with 28-day outcomes reported for septic and non-septic patients. RESULTS: A total of 200 patients were included in this study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65-59.05] vs. 48.00 [46.00-49.90] FI, p < 0.001, respectively). NEUT-RI and procalcitonin (PCT) distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42-12.09] vs. 32.59 [8.83-100.00], <0.001 and NEUT-RI 51.50 [47.80-56.30] vs. 56.20 [52.30-61.92], p = 0.005). NEUT-RI, PCT, and CRP values were significantly different in patients with "renal failure". NEUT-RI and PCT at admission in the ICU in the septic group were higher in patients who died (58.80 [53.85-73.10] vs. 53.05 [48.90-57.22], p = 0.005 and 39.56 [17.39-83.72] vs. 3.22 [0.59-32.32], p = 0.002, respectively). Both NEUT-RI and PCT showed a high negative predictive value and low positive predictive value. CONCLUSIONS: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis and could have a possible role in anticipating the outcome. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission.

Foot drop in critically ill patients: a narrative review of an elusive complication with intricate implications for recovery and rehabilitation.

Foot drop is a condition characterized by the inability to lift the foot upwards towards the shin bone. This condition may affect a proportion of critically ill patients, impacting on their recovery after the acute phase of the illness. The occurrence of foot drop in critical care patients may result from various underlying causes, including neurological injuries, muscular dysfunction, nerve compression, or vascular compromise. Understanding the etiology and assessing the severity of foot drop in these patients is essential for implementing appropriate management strategies and ensuring better patient outcomes. In this comprehensive review, we explore the complexities of foot drop in critically ill patients. We search for the potential risk factors that contribute to its development during critical illness, the impact it has on patients' functional abilities, and the various diagnostic techniques adopted to evaluate its severity. Additionally, we discuss current treatment approaches, rehabilitation strategies, and preventive measures to mitigate the adverse effects of foot drop in the critical care setting. Furthermore, we explore the roles of critical care physical therapists, neurologists, and other healthcare professionals in the comprehensive care of patients with foot drop syndrome and in such highlighting the importance of a multidisciplinary approach.

The Potential Role of Neutrophil-Reactive Intensity (NEUT-RI) in the Diagnosis of Sepsis in Critically Ill Patients: A Retrospective Cohort Study.

The diagnosis of sepsis is often difficult and belated, substantially increasing mortality in affected patients. Its early identification allows for us to choose the most appropriate therapies in the shortest time, improving patients' outcomes and eventually their survival. Since neutrophil activation is an indicator of an early innate immune response, the aim of the study was to evaluate the role of Neutrophil-Reactive Intensity (NEUT-RI), which is an indicator of their metabolic activity, in the diagnosis of sepsis. Data from 96 patients consecutively admitted to the Intensive Care Unit (ICU) were retrospectively analyzed (46 patients with and 50 without sepsis). Patients with sepsis were further divided between sepsis and septic shock according to the severity of the illness. Patients were subsequently classified according to renal function. For the diagnosis of sepsis, NEUT-RI showed an AUC of >0.80 and a better negative predictive value than Procalcitonin (PCT) and C-reactive protein (CRP) (87.4% vs. 83.9% and 86.6%, p = 0.038). Unlike PCT and CRP, NEUT-RI did not show a significant difference within the "septic" group between patients with normal renal function and those with renal failure (p = 0.739). Similar results were observed among the "non-septic" group (p = 0.182). The increase in NEUT-RI values could be useful in the early ruling-out of sepsis, and it does not appear to be influenced by renal failure. However, NEUT-RI has not proved to be efficient in discriminating the severity of sepsis at the time of admission. Larger, prospective studies are needed to confirm these results.

Hysteresis and Lung Recruitment in Acute Respiratory Distress Syndrome Patients: A CT Scan Study.

OBJECTIVES: Hysteresis of the respiratory system pressure-volume curve is related to alveolar surface forces, lung stress relaxation, and tidal reexpansion/collapse. Hysteresis has been suggested as a means of assessing lung recruitment. The objective of this study was to determine the relationship between hysteresis, mechanical characteristics of the respiratory system, and lung recruitment assessed by a CT scan in mechanically ventilated acute respiratory distress syndrome patients. DESIGN: Prospective observational study. SETTING: General ICU of a university hospital. PATIENTS: Twenty-five consecutive sedated and paralyzed patients with acute respiratory distress syndrome (age 64 ± 15 yr, body mass index 26 ± 6 kg/m, PaO2/FIO2 147 ± 42, and positive end-expiratory pressure 9.3 ± 1.4 cm H2O) were enrolled. INTERVENTIONS: A low-flow inflation and deflation pressure-volume curve (5-45 cm H2O) and a sustained inflation recruitment maneuver (45 cm H2O for 30 s) were performed. A lung CT scan was performed during breath-holding pressure at 5 cm H2O and during the recruitment maneuver at 45 cm H2O. MEASUREMENTS AND MAIN RESULTS: Lung recruitment was computed as the difference in noninflated tissue and in gas volume measured at 5 and at 45 cm H2O. Hysteresis was calculated as the ratio of the area enclosed by the pressure-volume curve and expressed as the hysteresis ratio. Hysteresis was correlated with respiratory system compliance computed at 5 cm H2O and the lung gas volume entering the lung during inflation of the pressure-volume curve (R = 0.749, p < 0.001 and R = 0.851, p < 0.001). The hysteresis ratio was related to both lung tissue and gas recruitment (R = 0.266, p = 0.008, R = 0.357, p = 0.002, respectively). Receiver operating characteristic analysis showed that the optimal cutoff value to predict lung tissue recruitment for the hysteresis ratio was 28% (area under the receiver operating characteristic curve, 0.80; 95% CI, 0.62-0.98), with sensitivity and specificity of 0.75 and 0.77, respectively. CONCLUSIONS: Hysteresis of the respiratory system computed by low-flow pressure-volume curve is related to the anatomical lung characteristics and has an acceptable accuracy to predict lung recruitment.

Bedside calculation of mechanical power during volume- and pressure-controlled mechanical ventilation.

BACKGROUND: Mechanical power (MP) is the energy delivered to the respiratory system over time during mechanical ventilation. Our aim was to compare the currently available methods to calculate MP during volume- and pressure-controlled ventilation, comparing different equations with the geometric reference method, to understand whether the easier to use surrogate formulas were suitable for the everyday clinical practice. This would warrant a more widespread use of mechanical power to promote lung protection. METHODS: Forty respiratory failure patients, sedated and paralyzed for clinical reasons, were ventilated in volume-controlled ventilation, at two inspiratory flows (30 and 60 L/min), and pressure-controlled ventilation with a similar tidal volume. Mechanical power was computed both with the geometric method, as the area between the inspiratory limb of the airway pressure and the volume, and with two algebraic methods, a comprehensive and a surrogate formula. RESULTS: The bias between the MP computed by the geometric method and by the comprehensive algebraic method during volume-controlled ventilation was respectively 0.053 (0.77, - 0.81) J/min and - 0.4 (0.70, - 1.50) J/min at low and high flows (r2 = 0.96 and 0.97, p < 0.01). The MP measured and computed by the two methods were highly correlated (r2 = 0.95 and 0.94, p < 0.01) with a bias of - 0.0074 (0.91, - 0.93) and - 1.0 (0.45, - 2.52) J/min at high-low flows. During pressure-controlled ventilation, the bias between the MP measured and the one calculated with the comprehensive and simplified methods was correlated (r2 = 0.81, 0.94, p < 0.01) with mean differences of - 0.001 (2.05, - 2.05) and - 0.81 (2.11, - 0.48) J/min. CONCLUSIONS: Both for volume-controlled and pressure-controlled ventilation, the surrogate formulas approximate the reference method well enough to warrant their use in the everyday clinical practice. Given that these formulas require nothing more than the variables already displayed by the intensive care ventilator, a more widespread use of mechanical power should be encouraged to promote lung protection against ventilator-induced lung injury.

Body Position Alters Mechanical Power and Respiratory Mechanics During Thoracic Surgery.

BACKGROUND: During thoracic surgery, patients are usually positioned in lateral decubitus and only the dependent lung ventilated. The ventilated lung is thus exposed to the weight of the contralateral hemithorax and restriction of the dependent chest wall. We hypothesized that mechanical power would increase during one-lung ventilation in the lateral position. METHODS: We performed a prospective, observational, single-center study from December 2016 to May 2017. Thirty consecutive patients undergoing general anesthesia with mechanical ventilation (mean age, 68 ± 11 years; body mass index, 25 ± 5 kg·m) for thoracic surgery were enrolled. Total and partitioned mechanical power, lung and chest wall elastance, and esophageal pressure were compared in supine and lateral position with double- and one-lung ventilation and with closed and open chest both before and after surgery. Mixed factorial ANOVA for repeated measurements was performed, with both step and the period before or after surgery as 2 within-subject factors, and left or right body position during surgery as a fixed, between-subject factor. Appropriate interaction terms were included. RESULTS: The mechanical power was higher in lateral one-lung ventilation compared to both supine and lateral position double-lung ventilation (11.1 ± 3.0 vs 8.2 ± 2.7 vs 8.7 ± 2.6; mean difference, 2.9 J·minute [95% CI, 1.4-4.4 J·minute] and 2.4 J·minute [95% CI, 0.9-3.9 J·minute]; P < .001 and P = .002, respectively). Lung elastance was higher during lateral position one-lung ventilation compared to both lateral and supine double-lung ventilation (24.3 ± 8.7 vs 9.5 ± 3.8 vs 10.0 ± 3.8; mean difference, 14.7 cm H2O·L [95% CI, 11.2-18.2 cm H2O·L] and 14.2 cm H2O·L [95% CI, 10.8-17.7 cm H2O·L], respectively) and was higher compared to predicted values (20.1 ± 7.5 cm H2O·L). Chest wall elastance increased in lateral position double-lung ventilation compared to supine (11.1 ± 3.8 vs 6.6 ± 3.4; mean difference, 4.5 cm H2O·L [95% CI, 2.6-6.3 cm H2O·L]) and was lower in lateral position one-lung ventilation with open chest than with a closed chest (3.5 ± 1.9 vs 7.1 ± 2.8; mean difference, 3.6 cm H2O·L [95% CI, 2.4-4.8 cm H2O·L]). The end-expiratory esophageal pressure decreased moving from supine position to lateral position one-lung ventilation while increased with the opening of the chest wall. CONCLUSIONS: Mechanical power and lung elastance are increased in the lateral position with one-lung ventilation. Esophageal pressure monitoring may be used to follow these changes.

Dynamic hyperinflation and intrinsic positive end-expiratory pressure in ARDS patients.

BACKGROUND: In ARDS patients, changes in respiratory mechanical properties and ventilatory settings can cause incomplete lung deflation at end-expiration. Both can promote dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP). The aim of this study was to investigate, in a large population of ARDS patients, the presence of intrinsic PEEP, possible associated factors (patients' characteristics and ventilator settings), and the effects of two different external PEEP levels on the intrinsic PEEP. METHODS: We made a secondary analysis of published data. Patients were ventilated with a tidal volume of 6-8 mL/kg of predicted body weight, sedated, and paralyzed. After a recruitment maneuver, a PEEP trial was run at 5 and 15 cmH2O, and partitioned mechanics measurements were collected after 20 min of stabilization. Lung computed tomography scans were taken at 5 and 45 cmH2O. Patients were classified into two groups according to whether or not they had intrinsic PEEP at the end of an expiratory pause. RESULTS: We enrolled 217 sedated, paralyzed patients: 87 (40%) had intrinsic PEEP with a median of 1.1 [1.0-2.3] cmH2O at 5 cmH2O of PEEP. The intrinsic PEEP significantly decreased with higher PEEP (1.1 [1.0-2.3] vs 0.6 [0.0-1.0] cmH2O; p < 0.001). The applied tidal volume was significantly lower (480 [430-540] vs 520 [445-600] mL at 5 cmH2O of PEEP; 480 [430-540] vs 510 [430-590] mL at 15 cmH2O) in patients with intrinsic PEEP, while the respiratory rate was significantly higher (18 [15-20] vs 15 [13-19] bpm at 5 cmH2O of PEEP; 18 [15-20] vs 15 [13-19] bpm at 15 cmH2O). At both PEEP levels, the total airway resistance and compliance of the respiratory system were not different in patients with and without intrinsic PEEP. The total lung gas volume and lung recruitability were also not different between patients with and without intrinsic PEEP (respectively 961 [701-1535] vs 973 [659-1433] mL and 15 [0-32] % vs 22 [0-36] %). CONCLUSIONS: In sedated, paralyzed ARDS patients without a known obstructive disease, the amount of intrinsic PEEP during lung-protective ventilation is negligible and does not influence respiratory mechanical properties.

Inflammation and primary graft dysfunction after lung transplantation: CT-PET findings.

BACKGROUND: The leading cause of early mortality after lung transplantation is Primary graft dysfunction (PGD). We assessed the lung inflammation, inflation status and inhomogeneities after lung transplantation. Our purpose was to investigate the possible differences between patients who did or did not develop PGD. METHODS: We designed a prospective observational study enrolling patients who underwent a CT-PET study within 1 week after lung transplantation. Twenty-four patients (10 after double- and 14 after single-lung) were enrolled. Respiratory and hemodynamic data were collected before, during and after lung transplantation. Each patient underwent computed tomography-positron emission tomography (CT-PET) scan early after surgery. Broncho-alveolar lavage (BAL) fluid collection was performed to analyze inflammatory mediators. RESULTS: The grafts showed a [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake rate of 26[18-33]*10-4 mLblood/mLtissue/min (reference values 11[7-15]*10-4). Three double- and six single-lung recipients developed PGD. The grafts of patients who developed PGD had similar [18F]FDG uptake than grafts of patients who did not (28[18-26]*10-4 versus 26[22-31]*10-4, P=0.79). Not-inflated tissue fraction was significantly higher (28[20-38]% versus 14[7-21]%, P=0.01) while well-inflated fraction was significantly lower (29[25-41]% versus 53[39-65]%, P<0.01). Inhomogeneity extent was higher in patients who developed PGD (23[18-26]% versus 14[10-20]%, P=0.01)The lung weight was 650[591-820]g versus 597[480-650]g (P=0.09)). BAL fluid analysis for inflammatory mediators did not detect a difference between the study groups. CONCLUSIONS: Compared to healthy lungs, all the grafts showed increased [18F]FDG uptake rate, but there were no differences between patients who developed PGD and patients who did not. Of note, the PGD patients showed a worse inflation status of lungs and a higher inhomogeneity extent.

What's Next After ARDS: Long-Term Outcomes.

ARDS is a life-threatening organ failure due to several pulmonary and extrapulmonary injuries with an incidence between 5 and 60 cases/100,000 persons/y. Patients with ARDS have non-cardiogenic pulmonary edema and dyspnea often requiring invasive mechanical ventilation and intensive care admission. Although the short-term mortality rate has significantly decreased in the last decade, mainly due to the widespread application of lung-protective ventilation and better general support, long-term outcomes are still unsatisfactory. Besides simply evaluating the outcome at hospital discharge, several recent studies have assessed the health-related quality of life, neuropsychological disability, radiological findings, and pulmonary dysfunction up to 5 y. This paper reviews the literature regarding the long-term outcomes in patients with ARDS.

Mechanical Power and Development of Ventilator-induced Lung Injury.

BACKGROUND: The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. METHODS: Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H2O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. RESULTS: In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight (r = 0.41, P = 0.001) and lung elastance (r = 0.33, P < 0.01) and decrease in PaO2/FIO2 (r = 0.40, P < 0.001) at the end of the study. CONCLUSION: In piglets, VILI develops if a mechanical power threshold is exceeded.

Lung inhomogeneities, inflation and [18F]2-fluoro-2-deoxy-D-glucose uptake rate in acute respiratory distress syndrome.

The aim of the study was to determine the size and location of homogeneous inflamed/noninflamed and inhomogeneous inflamed/noninflamed lung compartments and their association with acute respiratory distress syndrome (ARDS) severity.In total, 20 ARDS patients underwent 5 and 45 cmH2O computed tomography (CT) scans to measure lung recruitability. [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) uptake and lung inhomogeneities were quantified with a positron emission tomography-CT scan at 10 cmH2O. We defined four compartments with normal/abnormal [(18)F]FDG uptake and lung homogeneity.The homogeneous compartment with normal [(18)F]FDG uptake was primarily composed of well-inflated tissue (80±16%), double-sized in nondependent lung (32±27% versus 16±17%, p<0.0001) and decreased in size from mild, moderate to severe ARDS (33±14%, 26±20% and 5±9% of the total lung volume, respectively, p=0.05). The homogeneous compartment with high [(18)F]FDG uptake was similarly distributed between the dependent and nondependent lung. The inhomogeneous compartment with normal [(18)F]FDG uptake represented 4% of the lung volume. The inhomogeneous compartment with high [(18)F]FDG uptake was preferentially located in the dependent lung (21±10% versus 12±10%, p<0.0001), mostly at the open/closed interfaces and related to recruitability (r(2)=0.53, p<0.001).The homogeneous lung compartment with normal inflation and [(18)F]FDG uptake decreases with ARDS severity, while the inhomogeneous poorly/not inflated compartment increases. Most of the lung inhomogeneities are inflamed. A minor fraction of healthy tissue remains in severe ARDS.

Lung inhomogeneities and time course of ventilator-induced mechanical injuries.

BACKGROUND: During mechanical ventilation, stress and strain may be locally multiplied in an inhomogeneous lung. The authors investigated whether, in healthy lungs, during high pressure/volume ventilation, injury begins at the interface of naturally inhomogeneous structures as visceral pleura, bronchi, vessels, and alveoli. The authors wished also to characterize the nature of the lesions (collapse vs. consolidation). METHODS: Twelve piglets were ventilated with strain greater than 2.5 (tidal volume/end-expiratory lung volume) until whole lung edema developed. At least every 3 h, the authors acquired end-expiratory/end-inspiratory computed tomography scans to identify the site and the number of new lesions. Lung inhomogeneities and recruitability were quantified. RESULTS: The first new densities developed after 8.4 ± 6.3 h (mean ± SD), and their number increased exponentially up to 15 ± 12 h. Afterward, they merged into full lung edema. A median of 61% (interquartile range, 57 to 76) of the lesions appeared in subpleural regions, 19% (interquartile range, 11 to 23) were peribronchial, and 19% (interquartile range, 6 to 25) were parenchymal (P < 0.0001). All the new densities were fully recruitable. Lung elastance and gas exchange deteriorated significantly after 18 ± 11 h, whereas lung edema developed after 20 ± 11 h. CONCLUSIONS: Most of the computed tomography scan new densities developed in nonhomogeneous lung regions. The damage in this model was primarily located in the interstitial space, causing alveolar collapse and consequent high recruitability.

Body temperature affects cerebral hemodynamics in acutely brain injured patients: an observational transcranial color-coded duplex sonography study.

INTRODUCTION: Temperature changes are common in patients in a neurosurgical intensive care unit (NICU): fever is frequent among severe cases and hypothermia is used after cardiac arrest and is currently being tested in clinical trials to lower intracranial pressure (ICP). This study investigated cerebral hemodynamics when body temperature varies in acute brain injured patients. METHODS: We enrolled 26 patients, 14 with acute brain injury who developed fever and were given antipyretic therapy (defervescence group) and 12 who underwent an intracranial neurosurgical procedure and developed hypothermia in the operating room; once admitted to the NICU, still under anesthesia, they were re-warmed before waking (re-warming group). We measured cerebral blood flow velocity (CBF-V) and pulsatility index (PI) at the middle cerebral artery using transcranial color-coded duplex sonography (TCCDS). RESULTS: In the defervescence group mean CBF-V decreased from 75 ± 26 (95% CI 65 to 85) to 70 ± 22 cm/s (95% CI 61 to 79) (P = 0.04); the PI also fell, from 1.36 ± 0.33 (95% CI 1.23 to 1.50) to 1.16 ± 0.26 (95% CI 1.05 to 1.26) (P = 0.0005). In the subset of patients with ICP monitoring, ICP dropped from 16 ± 8 to 12 ± 6 mmHg (P = 0.003). In the re-warming group mean CBF-V increased from 36 ± 10 (95% CI 31 to 41) to 39 ± 13 (95% CI 33 to 45) cm/s (P = 0.04); the PI rose from 0.98 ± 0.14 (95% CI 0.91 to 1.04) to 1.09 ± 0.22 (95% CI 0.98 to 1.19) (P = 0.02). CONCLUSIONS: Body temperature affects cerebral hemodynamics as evaluated by TCCDS; when temperature rises, CBF-V increases in parallel, and viceversa when temperature decreases. When cerebral compliance is reduced and compensation mechanisms are exhausted, even modest temperature changes can greatly affect ICP.