Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

The effect of passive leg raising test on intracranial pressure and cerebral autoregulation in brain injured patients: a physiological observational study.

BACKGROUND: The use of the passive leg raising (PLR) is limited in acute brain injury (ABI) patients with increased intracranial pressure (ICP) since the postural change of the head may impact on ICP and cerebral autoregulation. However, the PLR use may prevent a positive daily fluid balance, which had been recently associated to worse neurological outcomes. We therefore studied early and delayed effects of PLR on the cerebral autoregulation of patients recovering from ABI. MATERIALS AND METHODS: This is a Prospective, observational, single-center study conducted in critically ill patients admitted with stable ABI and receiving invasive ICP monitoring, multimodal neuromonitoring and continuous hemodynamic monitoring. The fluid challenge consisted of 500 mL of crystalloid over 10 min; fluid responsiveness was defined as cardiac index increase ≥ 10%. Comparisons between different variables at baseline and after PLR were made by paired Wilcoxon signed-rank test. The correlation coefficients between hemodynamic and neuromonitoring variables were assessed using Spearman's rank test. RESULTS: We studied 23 patients [12 patients (52.2%) were fluid responders]. The PLR significantly increased ICP [from 13.7 (8.3-16.4) to 15.4 (12.0-19.2) mmHg; p < 0.001], cerebral perfusion pressure (CPP) [from 51.1 (47.4-55.6) to 56.4 (49.6-61.5) mmHg; p < 0.001] and the pressure reactivity index (PRx) [from 0.12 (0.01-0.24) to 0.43 (0.34-0.46) mmHg; p < 0.001]. Regarding Near Infrared Spectroscopy (NIRS)-derived parameters, PLR significantly increased the arterial component of regional cerebral oxygen saturation (O2Hbi) [from 1.8 (0.8-3.7) to 4.3 (2.5-5.6) µM cm; p < 0.001], the deoxygenated hemoglobin (HHbi) [from 1.6 (0.2-2.9) to 2.7 (1.4-4.0) µM cm; p = 0.007] and total hemoglobin (cHbi) [from 3.6 (1.9-5.3) to 7.8 (5.2-10.3): p < 0.001]. In all the patients who had altered autoregulation after PLR, these changes persisted ten minutes afterwards. After the PLR, we observed a significant correlation between MAP and CPP and PRx. CONCLUSIONS: In ABI patient with stable ICP, PLR test increased ICP, but mostly within safety values and thresholds. Despite this, cerebral autoregulation was importantly impaired, and this persisted up to 10 min after the end of the maneuvre. Our results discourage the use of PLR test in ABI even when ICP is stable.

Inferior vena cava distensibility during pressure support ventilation: a prospective study evaluating interchangeability of subcostal and trans­hepatic views, with both M­mode and automatic border tracing.

The Inferior Vena Cava (IVC) is commonly utilized to evaluate fluid status in the Intensive Care Unit (ICU),with more recent emphasis on the study of venous congestion. It is predominantly measured via subcostal approach (SC) or trans-hepatic (TH) views, and automated border tracking (ABT) software has been introduced to facilitate its assessment. Prospective observational study on patients ventilated in pressure support ventilation (PSV) with 2 × 2 factorial design. Primary outcome was to evaluate interchangeability of measurements of the IVC and the distensibility index (DI) obtained using both M-mode and ABT, across both SC and TH. Statistical analyses comprised Bland-Altman assessments for mean bias, limits of agreement (LoA), and the Spearman correlation coefficients. IVC visualization was 100% successful via SC, while TH view was unattainable in 17.4% of cases. As compared to the M-mode, the IVC-DI obtained through ABT approach showed divergences in both SC (mean bias 5.9%, LoA -18.4% to 30.2%, ICC = 0.52) and TH window (mean bias 6.2%, LoA -8.0% to 20.4%, ICC = 0.67). When comparing the IVC-DI measures obtained in the two anatomical sites, accuracy improved with a mean bias of 1.9% (M-mode) and 1.1% (ABT), but LoA remained wide (M-mode: -13.7% to 17.5%; AI: -19.6% to 21.9%). Correlation was generally suboptimal (r = 0.43 to 0.60). In PSV ventilated patients, we found that IVC-DI calculated with M-mode is not interchangeable with ABT measurements. Moreover, the IVC-DI gathered from SC or TH view produces not comparable results, mainly in terms of precision.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

Transpulmonary thermodilution.

PURPOSE OF REVIEW: The purpose of this article is to systematically review and critically assess the existing data regarding the use of transpulmonary thermodilution (TPTD), by providing a detailed description of technical aspects of TPTD techniques, appraising the use of TPTD-derived parameters in specific clinical settings, and exploring the limits of this technique. RECENT FINDINGS: The aim of hemodynamic monitoring is to optimize cardiac output ( CO ) and therefore improve oxygen delivery to the tissues. Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. TPTD is a reliable, multiparametric, advanced cardiopulmonary monitoring technique providing not only hemodynamic parameters related to cardiac function, but also to the redistribution of the extravascular water in the thorax. The hemodynamic monitors available in the market usually couple the intermittent measurement of the CO by TPTD with the arterial pulse contour analysis, offering automatic calibration of continuous CO and an accurate assessment of cardiac preload and fluid responsiveness. SUMMARY: The TPTD is an invasive but well tolerated, multiparametric, advanced cardiopulmonary monitoring technique, allowing a comprehensive assessment of cardiopulmonary condition. Beyond the CO estimation, TPTD provides several indices that help answering questions that clinicians ask themselves during hemodynamic management. TPTD-guided algorithm obtained by pulse contour analysis may be useful to optimize fluid resuscitation by titrating fluid therapy according to functional hemodynamic monitoring and to define safety criteria to avoid fluid overload by following the changes in the extravascular lung water (EVLW) and pulmonary vascular permeability index (PVPI).

Can carotid artery Doppler variations induced by the end-expiratory occlusion maneuver predict fluid responsiveness in septic shock patients?

BACKGROUND: An increase in cardiac index (CI) during an end-expiratory occlusion test (EEOt) predicts fluid responsiveness in ventilated patients. However, if CI monitoring is unavailable or the echocardiographic window is difficult, using the carotid Doppler (CD) could be a feasible alternative to track CI changes. This study investigates whether changes in CD peak velocity (CDPV) and corrected flow time (cFT) during an EEOt were correlated with CI changes and if CDPV and cFT changes predicted fluid responsiveness in patients with septic shock. METHODS: Prospective, single-center study in adults with hemodynamic instability. The CDPV and cFT on carotid artery Doppler and hemodynamic variables from the pulse contour analysis EV1000™ were recorded at baseline, during a 20-s EEOt, and after fluid challenge (500 mL). We defined responders as those who increased CI ≥ 15% after a fluid challenge. RESULTS: We performed 44 measurements in 18 mechanically ventilated patients with septic shock and without arrhythmias. The fluid responsiveness rate was 43.2%. The changes in CDPV were significantly correlated with changes in CI during EEOt (r = 0.51 [0.26-0.71]). A significant, albeit lower correlation, was found for cFT (r = 0.35 [0.1-0.58]). An increase in CI ≥ 5.35% during EEOt predicted fluid responsiveness with 78.9% sensitivity and 91.7% specificity, with an area under the ROC curve (AUROC) of 0.85. An increase in CDPV ≥ 10.5% during an EEOt predicted fluid responsiveness with 96.2% specificity and 53.0% sensitivity with an AUROC of 0.74. Sixty-one percent of CDPV measurements (from - 13.5 to 9.5 cm/s) fell within the gray zone. The cFT changes during EEOt did not accurately predict fluid responsiveness. CONCLUSIONS: In septic shock patients without arrhythmias, an increase in CDPV greater than 10.5% during a 20-s EEOt predicted fluid responsiveness with > 95% specificity. Carotid Doppler combined with EEOt may help optimize preload when invasive hemodynamic monitoring is unavailable. However, the 61% gray zone is a major limitation (retrospectively registered on Clinicaltrials.gov NCT04470856 on July 14, 2020).

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression.

BACKGROUND: Pulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia. METHODS: Systematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables. RESULTS: We selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46-63). The pooled AUC for the PPV was 0.77 (0.73-0.80), with a mean threshold of 10.8 (10.6-11.0). The pooled AUC for the SVV was 0.76 (0.72-0.80), with a mean threshold of 12.1 (11.6-12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40-62) and 57% (46-83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position. CONCLUSION: The overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability. TRIAL REGISTRATION: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120.

Agreement between Capillary Refill Time measured at Finger and Earlobe sites in different positions: a pilot prospective study on healthy volunteers.

BACKGROUND: Capillary Refill Time (CRT) is a marker of peripheral perfusion usually performed at fingertip; however, its evaluation at other sites/position may be advantageous. Moreover, arm position during CRT assessment has not been fully standardized. METHODS: We performed a pilot prospective observational study in 82 healthy volunteers. CRT was assessed: a) in standard position with participants in semi-recumbent position; b) at 30° forearm elevation, c and d) at earlobe site in semi-recumbent and supine position. Bland-Altman analysis was performed to calculate bias and limits of agreement (LoA). Correlation was investigated with Pearson test. RESULTS: Standard finger CRT values (1.04 s [0.80;1.39]) were similar to the earlobe semi-recumbent ones (1.10 s [0.90;1.26]; p = 0.52), with Bias 0.02 ± 0.18 s (LoA -0.33;0.37); correlation was weak but significant (r = 0.28 [0.7;0.47]; p = 0.01). Conversely, standard finger CRT was significantly longer than earlobe supine CRT (0.88 s [0.75;1.06]; p < 0.001) with Bias 0.22 ± 0.4 s (LoA -0.56;1.0), and no correlation (r = 0,12 [-0,09;0,33]; p = 0.27]. As compared with standard finger CRT, measurement with 30° forearm elevation was significantly longer (1.17 s [0.93;1.41] p = 0.03), with Bias -0.07 ± 0.3 s (LoA -0.61;0.47) and with a significant correlation of moderate degree (r = 0.67 [0.53;0.77]; p < 0.001). CONCLUSIONS: In healthy volunteers, the elevation of the forearm significantly prolongs CRT values. CRT measured at the earlobe in semi-recumbent position may represent a valid surrogate when access to the finger is not feasible, whilst earlobe CRT measured in supine position yields different results. Research is needed in critically ill patients to evaluate accuracy and precision at different sites/positions.

Cardiac dysfunction in patients affected by subarachnoid haemorrhage affects in-hospital mortality: A systematic review and metanalysis.

BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition with associated brain damage. Moreover, SAH is associated with a massive release of catecholamines, which may promote cardiac injury and dysfunction, possibly leading to haemodynamic instability, which in turn may influence a patient's outcome. OBJECTIVES: To study the prevalence of cardiac dysfunction (as assessed by echocardiography) in patients with SAH and its effect on clinical outcomes. DESIGN: Systematic review of observational studies. DATA SOURCES: We performed a systematic search over the last 20 years on MEDLINE and EMBASE databases. ELIGIBILITY CRITERIA: Studies reporting echocardiography findings in adult patients with SAH admitted to intensive care. Primary outcomes were in-hospital mortality and poor neurological outcome according to the presence or absence of cardiac dysfunction. RESULTS: We included a total of 23 studies (4 retrospective) enrolling 3511 patients. The cumulative frequency of cardiac dysfunction was 21% (725 patients), reported as regional wall motion abnormality in the vast majority of studies (63%). Due to the heterogeneity of clinical outcome data reporting, a quantitative analysis was carried out only for in-hospital mortality. Cardiac dysfunction was associated with a higher in-hospital mortality [odds ratio 2.69 (1.64 to 4.41); P  < 0.001; I2 = 63%]. The GRADE of evidence assessment resulted in very low certainty of evidence. CONCLUSION: About one in five patients with SAH develops cardiac dysfunction, which seems to be associated with higher in-hospital mortality. The consistency of cardiac and neurological data reporting is lacking, reducing the comparability of the studies in this field.

Pressure response to fluid challenge administration in hypotensive surgical patients: a post-hoc pharmacodynamic analysis of five datasets.

In this study we evaluated the effect of fluid challenge (FC) administration in elective surgical patients with low or normal blood pressure. Secondarily, we appraised the pharmacodynamic effect of FC in normotensive and hypotensive patients. We assessed five merged datasets of patients with a baseline mean arterial pressure (MAP) above or below 65 mmHg and assessed the changes of systolic, diastolic, mean and dicrotic arterial pressures, dynamic indexes of fluid responsiveness and arterial elastance over a 10-min infusion. The hemodynamic effect was assessed by considering the net area under the curve (AUC), the maximal percentage difference from baseline (dmax), the time when the maximal value was observed (tmax) and change from baseline at 5-min (d5) after FC end. A stroke volume index increase > 10% with respect to the baseline value after FC administration indicated fluid response. Two hundred-seventeen patients were analysed [102 (47.0%) fluid responders]. On average, FC restored a MAP [Formula: see text] 65 mmHg after 5 min. The AUCs and the dmax of pressure variables and arterial elastance of hypotensive patients were all significantly greater than normotensive patients. Pressure variables and arterial elastance changes in the hypotensive group were all significantly higher at d5 as compared to the normotensive group. In hypotensive patients, FC restores a MAP [Formula: see text] 65 mmHg after 5 min from infusion start. The hemodynamic profile of FC in hypotensive and normotensive patients is different; both the magnitude of pressure augmentation and duration is greater in the hypotensive group.

Challenges in the hemodynamic management of acute nontraumatic neurological injuries.

PURPOSE OF REVIEW: To appraise the evidence from the literature and suggest an integrated hemodynamic approach of early and delayed phases of acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). RECENT FINDINGS: In AIS, the research aims to evaluate the optimal pressure control before, during and after the revascularization, to optimize the perfusion in the ischemic areas, minimizing the risk of hemorrhage or secondary damage to already infarcted areas. In the early phase of SAH, systemic pressure should be controlled to balance the risk of stroke, hypertension-related rebleeding, and maintenance of cerebral perfusion pressure. The late phase aims to minimize the risk of cerebral vasospasm by adapting systemic pressure and volemia to cerebral and systemic physiological hemodynamic targets. In the mild-to-moderate ICH, achieving SAP of less than 140 mmHg and greater than 110 mmHg may be considered as a beneficial target. Caution should be considered in lowering intensively SAP in severe ICH. SUMMARY: In nontraumatic brain injuries, the hemodynamic management is strictly related to fluctuating physiology of these diseases, needing a strict control of pressure and flow variable to ensure both cerebral and systemic homeostasis.

COVID-19: dealing with ventilator shortage.

PURPOSE OF REVIEW: To describe different strategies adopted during coronavirus disease 2019 pandemic to cope with the shortage of mechanical ventilators. RECENT FINDINGS: Short-term interventions aimed to increase ventilator supply and decrease demand. They included: redistributing and centralizing patients, repurposing operating rooms into intensive care units (ICUs) and boosting ventilator production and using stocks and back-ups; support by the critical care outreach team to optimize treatment of patients in the ward and permit early discharge from the ICU, ethical allocation of mechanical ventilators to patients who could benefit more from intensive treatment and short term ICU trials for selected patients with uncertain prognosis, respectively. Long-term strategies included education and training of non-ICU physicians and nurses to the care of critically-ill patients and measures to decrease viral spread among the population and the progression from mild to severe disease. SUMMARY: The experience and evidence gained during the current pandemic is of paramount importance for physicians and law-makers to plan in advance an appropriate response to any future similar crisis. Intensive care unit, hospital, national and international policies can all be improved to build systems capable of treating an unexpectedly large number of patients, while keeping a high standard of safety.

Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades.

INTRODUCTION: Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000-2010 and 2011-2021. METHODS: We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold. RESULTS: We included 124 studies, 32 (25.8%) published in 2000-2010 and 92 (74.2%) in 2011-2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011-2021 compared to the 2000-2010 period. CONCLUSIONS: In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000-2010 decade, in 2011-2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.

Effects of positive end-expiratory pressure on lung ultrasound patterns and their correlation with intracranial pressure in mechanically ventilated brain injured patients.

BACKGROUND: The effects of positive end-expiratory pressure (PEEP) on lung ultrasound (LUS) patterns, and their relationship with intracranial pressure (ICP) in brain injured patients have not been completely clarified. The primary aim of this study was to assess the effect of two levels of PEEP (5 and 15 cmH2O) on global (LUStot) and regional (anterior, lateral, and posterior areas) LUS scores and their correlation with changes of invasive ICP. Secondary aims included: the evaluation of the effect of PEEP on respiratory mechanics, arterial partial pressure of carbon dioxide (PaCO2) and hemodynamics; the correlation between changes in ICP and LUS as well as respiratory parameters; the identification of factors at baseline as potential predictors of ICP response to higher PEEP. METHODS: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP. Total and regional LUS scores, ICP, respiratory mechanics, and arterial blood gases values were analyzed at PEEP 5 and 15 cmH2O. RESULTS: Thirty patients were included; 19 of them (63.3%) were male, with median age of 65 years [interquartile range (IQR) = 66.7-76.0]. PEEP from 5 to 15 cmH2O reduced LUS score in the posterior regions (LUSp, median value from 7 [5-8] to 4.5 [3.7-6], p = 0.002). Changes in ICP were significantly correlated with changes in LUStot (rho = 0.631, p = 0.0002), LUSp (rho = 0.663, p < 0.0001), respiratory system compliance (rho = - 0.599, p < 0.0001), mean arterial pressure (rho = - 0.833, p < 0.0001) and PaCO2 (rho = 0.819, p < 0.0001). Baseline LUStot score predicted the increase of ICP with PEEP. CONCLUSIONS: LUS-together with the evaluation of respiratory and clinical variables-can assist the clinicians in the bedside assessment and prediction of the effect of PEEP on ICP in patients with acute brain injury.

Effects of Varying Levels of Inspiratory Assistance with Pressure Support Ventilation and Neurally Adjusted Ventilatory Assist on Driving Pressure in Patients Recovering from Hypoxemic Respiratory Failure.

BACKGROUND: Driving pressure can be readily measured during assisted modes of ventilation such as pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). The present prospective randomized crossover study aimed to assess the changes in driving pressure in response to variations in the level of assistance delivered by PSV vs NAVA. METHODS: 16 intubated adult patients, recovering from hypoxemic acute respiratory failure (ARF) and undergoing assisted ventilation, were randomly subjected to six 30-min-lasting trials. At baseline, PSV (PSV100) was set with the same regulation present at patient enrollment. The corresponding level of NAVA (NAVA100) was set to match the same inspiratory peak of airway pressure obtained in PSV100. Therefore, the level of assistance was reduced and increased by 50% in both ventilatory modes (PSV50, NAVA50; PSV150, NAVA150). At the end of each trial, driving pressure obtained in response to four short (2-3 s) end-expiratory and end-inspiratory occlusions was analyzed. RESULTS: Driving pressure at PSV50 (6.6 [6.1-7.8] cmH2O) was lower than that recorded at PSV100 (7.9 [7.2-9.1] cmH2O, P = 0.005) and PSV150 (9.9 [9.1-13.2] cmH2O, P < 0.0001). In NAVA, driving pressure at NAVA50 was reduced compared to NAVA150 (7.7 [5.1-8.1] cmH2O vs 8.3 [6.4-11.4] cmH2O, P = 0.013), whereas there were no changes between baseline and NAVA150 (8.5 [6.3-9.8] cmH2O vs 8.3 [6.4-11.4] cmH2O, P = 0.331, respectively). Driving pressure at PSV150 was higher than that observed in NAVA150 (P = 0.011). CONCLUSIONS: NAVA delivers better lung-protective ventilation compared to PSV in hypoxemic ARF patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: The present trial was prospectively registered at www.clinicatrials.gov (NCT03719365) on 24 October 2018.

Pharmacodynamic analysis of a fluid challenge with 4 ml kg-1 over 10 or 20 min: a multicenter cross-over randomized clinical trial.

PURPOSE: A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg-1. METHODS: Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg-1 of crystalloids in 10 (FC10) or 20 (FC20) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (dmax), time when the dmax was observed (tmax), change from baseline at 1-min (d1) and 5-min (d5) after FC end. RESULTS: After FC10 and FC20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The dmax and the tmax were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end. CONCLUSIONS: The infusion time of FC administration affects fluid responsiveness, being higher for FC10 as compared to FC20. The effect on flow variables of either FCs fades 5 min after the end of infusion.

The impact of COVID-19 pandemic on radiology residents in Northern Italy.

OBJECTIVES: To assess changes in working patterns and education experienced by radiology residents in Northwest Italy during the COVID-19 pandemic. METHODS: An online questionnaire was sent to residents of 9 postgraduate schools in Lombardy and Piedmont, investigating demographics, changes in radiological workload, involvement in COVID-19-related activities, research, distance learning, COVID-19 contacts and infection, changes in training profile, and impact on psychological wellbeing. Descriptive and χ2 statistics were used. RESULTS: Among 373 residents invited, 300 (80%) participated. Between March and April 2020, 44% (133/300) of respondents dedicated their full time to radiology; 41% (124/300) engaged in COVID-19-related activities, 73% (90/124) of whom working in COVID-19 wards; 40% (121/300) dedicated > 25% of time to distance learning; and 66% (199/300) were more involved in research activities than before the pandemic. Over half of residents (57%, 171/300) had contacts with COVID-19-positive subjects, 5% (14/300) were infected, and 8% (23/300) lost a loved one due to COVID-19. Only 1% (3/300) of residents stated that, given the implications of this pandemic scenario, they would not have chosen radiology as their specialty, whereas 7% (22/300) would change their subspecialty. The most common concerns were spreading the infection to their loved ones (30%, 91/300), and becoming sick (7%, 21/300). Positive changes were also noted, such as being more willing to cooperate with other colleagues (36%, 109/300). CONCLUSIONS: The COVID-19 pandemic changed radiology residents' training programmes, with distance learning, engaging in COVID-19-related activities, and a greater involvement in research becoming part of their everyday practice. KEY POINTS: • Of 300 participants, 44% were fully dedicated to radiological activity and 41% devoted time to COVID-19-related activities, 73% of whom to COVID-19 wards. • Distance learning was substantial for 40% of residents, and 66% were involved in research activities more than before the COVID-19 pandemic. • Over half of residents were exposed to COVID-19 contacts and less than one in twenty was infected.

Perioperative liberal versus restrictive fluid strategies and postoperative outcomes: a systematic review and metanalysis on randomised-controlled trials in major abdominal elective surgery.

BACKGROUND: Postoperative complications impact on early and long-term patients' outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality. METHODS: Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded. RESULTS: After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (- 0.02; 0.04); p value = 0.62; I2 (95% CI) = 38.6% (0-66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02-0.09); p value = 0.001]. We found no difference in either early (p value = 0.33) or late (p value = 0.22) postoperative mortality between restrictive and liberal subgroups CONCLUSIONS: In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive. TRIAL REGISTRATION: CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218059 .

Association between perioperative fluid administration and postoperative outcomes: a 20-year systematic review and a meta-analysis of randomized goal-directed trials in major visceral/noncardiac surgery.

BACKGROUND: Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients' hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid). RESULTS: The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = - 0.10 (- 0.14, - 0.07); Chi2 = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications. CONCLUSIONS: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality. TRIAL REGISTRATION: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866.

Mini fluid chAllenge aNd End-expiratory occlusion test to assess flUid responsiVEness in the opeRating room (MANEUVER study): A multicentre cohort study.

BACKGROUND: The fluid challenge response in surgical patients can be predicted by functional haemodynamic tests. Two tests, the mini-fluid challenge (mini-FC) and end-expiratory occlusion test (EEOT), have been assessed in a few small single-centre studies with conflicting results. In general, functional haemodynamic tests have not performed reliably in predicting fluid responsiveness in patients undergoing laparotomy. OBJECTIVE: This trial is designed to address and compare the reliability of the EEOT and the mini-FC in predicting fluid responsiveness during laparotomy. DESIGN: Prospective, multicentre study. SETTING: Three university hospitals in Italy. PATIENTS: A total of 103 adults patients scheduled for elective laparotomy with invasive arterial monitoring. INTERVENTIONS: The study protocol evaluated the changes in the stroke volume index (SVI) 20 s (EEOT20) and 30 s (EEOT30) after an expiratory hold and after a mini-FC of 100 ml over 1 min. Fluid responsiveness required an increase in SVI at least 10% following 4 ml kg-1 of Ringer's solution fluid challenge infused over 10 min. MAIN OUTCOME MEASUREMENTS: Haemodynamic data, including SVI, were obtained from pulse contour analysis. The area under the receiver operating characteristic curves of the tests were compared with assess fluid responsiveness. RESULTS: Fluid challenge administration induced an increase in SVI at least 10% in 51.5% of patients. The rate of fluid responsiveness was comparable among the three participant centres (P = 0.10). The area under the receiver operating characteristic curves (95% CI) of the changes in SVI after mini-FC was 0.95 (0.88 to 0.98), sensitivity 98.0% (89.5 to 99.6) and specificity 86.8% (75.1 to 93.4) for a cut-off value of 4% of increase in SVI. This was higher than the SVI changes after EEOT20, 0.67 (0.57 to 0.76) and after EEOT30, 0.73 (0.63 to 0.81). CONCLUSION: In patients undergoing laparotomy the mini-FC reliably predicted fluid responsiveness with high-sensitivity and specificity. The EEOT showed poor discriminative value and cannot be recommended for assessment of fluid responsiveness in this surgical setting. TRIAL REGISTRATION: NCT03808753.