Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Changes in Oxygen Saturation During Fiberoptic Bronchoscopy: High-Flow Nasal Cannula versus Standard Oxygen Therapy.

BACKGROUND: Hypoxemia is a relatively common complication in stable patients during fiberoptic bronchoscopy (FOB). To prevent this complication, high-flow nasal cannula (HFNC) has been described as an alternative to standard oxygen therapy. However, the advantages of HFNC over standard oxygen therapy in acute care patients receiving supplemental oxygen before FOB performed with an oral approach are unknown. METHODS: We conducted an observational study that involved subjects with a presumptive diagnosis of pneumonia and a clinical indication for a bronchial aspirate sample. The type of oxygen support (standard oxygen therapy vs HFNC) was selected according to availability. The oxygen flow in the HFNC group was 60 L/min. In both groups, the FIO2 was set at 0.40. Hemodynamic, respiratory dynamics, and gas exchange data were collected at baseline, before, during, and 24 h after FOB. RESULTS: Forty subjects were included, 20 in each group (HFNC and standard oxygen therapy). The study was performed on day 5 of hospitalization in the HFNC group and on day 4 in the standard oxygen therapy group (P = .10). No significant between-group differences in baseline characteristics were observed. HFNC vs standard oxygen therapy was associated with a smaller decrease in SpO2 levels during the procedure (94% vs 90%; P = .040, respectively) and with less variation between the last SpO2 measured before FOB and the lowest SpO2 during FOB (Δ SpO2 ): 2% versus 4.5% (P = .01, respectively). CONCLUSIONS: In acute subjects who required oxygen support before FOB, the use of HFNC during FOB with an oral approach was associated with a smaller decrease in SpO2 and lower Δ SpO2 compared with standard oxygen therapy.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Protocolo de inmunosupresión en trasplante hepático: revisión de la literatura / Immunosuppression protocol in liver transplantation: review article

El trasplante de hígado es el último recurso para el tratamiento de hepatopatías. Para evitar el rechazo del injerto se requieren esquemas de inmunosupresión que han ido evolucionando a lo largo de los años. Se realizó una revisión bibliográfica en la base de datos PubMed sobre las terapias inmunosupresoras disponibles para evitar el rechazo del injerto en el trasplante hepático, los esquemas utilizados, efectos adversos, interacciones y sus modificaciones desde la fase de inducción hasta el seguimiento posterior. Se encontró que la inducción habitual es con esteroides o terapia inmunológica clonal. En el mantenimiento, los inhibidores de la calcineurina son los más utilizados, las dosis se deben ajustar según sus niveles séricos y la presencia de efectos adversos como nefrotoxicidad o diabetes. Por otra parte, los inhibidores del mTOR han sido considerados como agentes reductores del riesgo de recidiva de cáncer hepatocelular. Las características del paciente y sus comorbilidades (embarazo, insuficiencia renal, diabetes, sepsis, carcinoma hepatocelular) requieren modificar el tratamiento e individualizarlo

Liver transplantation is the last option for the treatment of liver disease. Immunosuppression schemes are required to avoid graft rejection, which have evolved over the years. A literature review was carried out in PubMed on the immunosuppressive therapies available to avoid graft rejection in liver transplantation, as well as on the schemes used, adverse effects, interactions and their modifications from the induction phase to subsequent follow-up. The usual induction was found to be with steroids or clonal immune therapy. In maintenance, calcineurin inhibitors are the most widely used, and their doses should be adjusted according to their serum levels and the presence of adverse effects such as nephrotoxicity or diabetes. On the other hand, mTOR inhibitors have been considered to reduce the risk of hepatocellular cancer recurrence. The characteristics of the patient and their comorbidities (pregnancy, kidney failure, diabetes, sepsis, hepatocellular carcinoma) require modification and individualization of the treatment.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Patient-ventilator interaction with conventional and automated management of pressure support during difficult weaning from mechanical ventilation.

PURPOSE: Optimizing pressure support ventilation (PSV) can improve patient-ventilator interaction. We conducted a two-center, randomized cross-over study to determine whether automated PSV lowers asynchrony rate during difficult weaning from mechanical ventilation. METHODS: Thirty patients failing the first weaning attempt were randomly ventilated for 2 three-hour consecutive periods with: 1)PSV managed by physicians (convPSV); 2)PSV managed by Smartcare® (autoPSV). These 2 periods were applied in the afternoon and overnight, for a 12-h total study time. Two independent clinicians offline analyzed ventilator waveforms to compute asynchrony index(AI). RESULTS: AI was lower during autoPSV than during convPSV (medians[interquartile ranges] 5.1[2.6-9.5]% vs. 7.3[2.3-13.4]%, p = 0.02), without changes in the proportion of patients with AI>10%(p = 0.31). Pressure support (PS) variability was higher during autoPSV (p < 0.001), but average PS did not vary. In patients with baseline PS > 12 cmH2O (n = 15), PS and tidal volume were lower with autoPSV (12 [10-15]cmH2O vs. 15 [14-18]cmH2O,p = 0.003; 7.2[6.2-8.3]ml/Kg vs. 8.2[7.1-9.1]ml/Kg, p = 0.02) and AI reduction was driven by lower tidal volume (p = 0.03). In patients with baseline PS ≤ 12 cmH2O, AI reduction during autoPSV was mediated by increased PS variability (p = 0.04). CONCLUSION: During difficult weaning, autoPSV improves patient-ventilator interaction by lowering tidal volume and enhancing PS variability. In expert centres, however, the size effect of the intervention appears clinically small, likely because physicians themselves adequately limit PS and tidal volume.

Lung volumes and lung volume recruitment in ARDS: a comparison between supine and prone position.

BACKGROUND: The use of positive end-expiratory pressure (PEEP) and prone position (PP) is common in the management of severe acute respiratory distress syndrome patients (ARDS). We conducted this study to analyze the variation in lung volumes and PEEP-induced lung volume recruitment with the change from supine position (SP) to PP in ARDS patients. METHODS: The investigation was conducted in a multidisciplinary intensive care unit. Patients who met the clinical criteria of the Berlin definition for ARDS were included. The responsible physician set basal PEEP. To avoid hypoxemia, FiO2 was increased to 0.8 1 h before starting the protocol. End-expiratory lung volume (EELV) and functional residual capacity (FRC) were measured using the nitrogen washout/washin technique. After the procedures in SP, the patients were turned to PP and 1 h later the same procedures were made in PP. RESULTS: Twenty-three patients were included in the study, and twenty were analyzed. The change from SP to PP significantly increased FRC (from 965 ± 397 to 1140 ± 490 ml, p = 0.008) and EELV (from 1566 ± 476 to 1832 ± 719 ml, p = 0.008), but PEEP-induced lung volume recruitment did not significantly change (269 ± 186 ml in SP to 324 ± 188 ml in PP, p = 0.263). Dynamic strain at PEEP decreased with the change from SP to PP (0.38 ± 0.14 to 0.33 ± 0.13, p = 0.040). CONCLUSIONS: As compared to supine, prone position increases resting lung volumes and decreases dynamic lung strain.

End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics.

BACKGROUND: End-inspiratory pause (EIP) prolongation decreases dead space-to-tidal volume ratio (Vd/Vt) and PaCO2. We do not know the physiological benefits of this approach to improve respiratory system mechanics in acute respiratory distress syndrome (ARDS) patients when mild hypercapnia is of no concern. METHODS: The investigation was conducted in an intensive care unit of a university hospital, and 13 ARDS patients were included. The study was designed in three phases. First phase, baseline measurements were taken. Second phase, the EIP was prolonged until one of the following was achieved: (1) EIP of 0.7 s; (2) intrinsic positive end-expiratory pressure ≥1 cmH2O; or (3) inspiratory-expiratory ratio 1:1. Third phase, the Vt was decreased (30 mL every 30 min) until PaCO2 equal to baseline was reached. FiO2, PEEP, airflow and respiratory rate were kept constant. RESULTS: EIP was prolonged from 0.12 ± 0.04 to 0.7 s in all patients. This decreased the Vd/Vt and PaCO2 (0.70 ± 0.07 to 0.64 ± 0.08, p < 0.001 and 54 ± 9 to 50 ± 8 mmHg, p = 0.001, respectively). In the third phase, the decrease in Vt (from 6.3 ± 0.8 to 5.6 ± 0.8 mL/Kg PBW, p < 0.001) allowed to decrease plateau pressure and driving pressure (24 ± 3 to 22 ± 3 cmH2O, p < 0.001 and 13.4 ± 3.6 to 10.9 ± 3.1 cmH2O, p < 0.001, respectively) and increased respiratory system compliance from 29 ± 9 to 32 ± 11 mL/cmH2O (p = 0.001). PaO2 did not significantly change. CONCLUSIONS: Prolonging EIP allowed a significant decrease in Vt without changes in PaCO2 in passively ventilated ARDS patients. This produced a significant decrease in plateau pressure and driving pressure and significantly increased respiratory system compliance, which suggests less overdistension and less dynamic strain.

Bedside adjustment of proportional assist ventilation to target a predefined range of respiratory effort.

OBJECTIVES: During proportional assist ventilation with load-adjustable gain factors, peak respiratory muscle pressure can be estimated from the peak airway pressure and the percentage of assistance (gain). Adjusting the gain can, therefore, target a given level of respiratory effort. This study assessed the clinical feasibility of titrating proportional assist ventilation with load-adjustable gain factors with the goal of targeting a predefined range of respiratory effort. DESIGN: Prospective, multicenter, clinical observational study. SETTINGS: Intensive care departments at five university hospitals. PATIENTS: Patients were included after meeting simple criteria for assisted mechanical ventilation. INTERVENTIONS: Patients were ventilated in proportional assist ventilation with load-adjustable gain factors. The peak respiratory muscle pressure, estimated in cm H2O as (peak airway pressure-positive end-expiratory pressure)×[(100-gain)/gain], was calculated from a grid at the bedside. The gain adjustment algorithm was defined to target a peak respiratory muscle pressure between 5 and 10 cm H2O. Additional recommendations were available in case of hypoventilation or hyperventilation. RESULTS: Fifty-three patients were enrolled. Median time spent under proportional assist ventilation with load-adjustable gain factors was 3 days (interquartile range, 1-5). Gain was adjusted 1.0 (0.7-1.8) times per day, according to the peak respiratory muscle pressure target range in 91% of cases and because of hypoventilation or hyperventilation in 9%. Thirty-four patients were ventilated with proportional assist ventilation with load-adjustable gain factors until extubation, which was successful in 32. Eighteen patients required volume assist-controlled reventilation because of clinical worsening and need for continuous sedation. One patient was intolerant to proportional assist ventilation with load-adjustable gain factors. CONCLUSIONS: This first study assessing the clinical feasibility of titrating proportional assist ventilation with load-adjustable gain factors in an attempt to target a predefined range of effort showed that adjusting the level of assistance to maintain a predefined boundary of respiratory muscle pressure is feasible, simple, and often sufficient to ventilate patients until extubation.

Prone positioning in acute respiratory distress syndrome (ARDS): when and how?

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure. It remains one of the most devastating conditions in the intensive care unit. Mechanical ventilation with positive end-expiratory pressure is a cornerstone therapy for ARDS patients. One adjuvant alternative is to place the patient in a prone position. Since it was first described in 1976, prone positioning has been safely employed to improve oxygenation in many patients with ARDS. Prone positioning may also minimize secondary lung injury induced by mechanical ventilation, although this benefit has not been investigated as extensively, despite its potential. In spite of a strong physiological justification, prone positioning is still not widely accepted as an adjunct therapy in ARDS patients and it is only used regularly in only 10% of ICUs. This may be explained in part by the reluctance to change position, risks and unclear effects on relevant outcomes. In this paper, we review all aspects of prone positioning, from the pathophysiology to the clinical studies of patient outcome, and we also discuss the latest controversies surrounding this treatment.