Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub-study of the PLOT-ICU cohort.

INTRODUCTION: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. METHODS: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. CONCLUSIONS: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.

Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study.

BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 109/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 1011 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 1011 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 109/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.

Platelet transfusions and thrombocytopenia in intensive care units: Protocol for an international inception cohort study (PLOT-ICU).

INTRODUCTION: Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. METHODS: We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 × 109 /L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. CONCLUSION: The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.

Prevalence of acute liver dysfunction and impact on outcome in critically ill patients with hematological malignancies: a single-center retrospective cohort study.

Patients with hematological malignancies (HM) often require ICU admission, and acute respiratory or renal failure are then independent risk factors for mortality. Data are scarce on acute liver dysfunction (ALD), despite HM patients cumulating risk factors. The objective of this retrospective cohort study was to assess the prevalence of ALD in critically ill HM patients and its impact on outcome. Data of all patients with HM admitted to the medical ICU between 2008 and 2018 were extracted from electronic medical records. ALD was defined by ALT > 165 U/L, AST > 230 U/L, or total bilirubin > 4 mg/dL. Univariate and multivariate logistic regressions were used to analyze hospital mortality. Charts of survivors with ALD were reviewed to assess impact of ALD on subsequent anti-cancer treatment. We included 971 patients (60% male), age 64 (54-72) years, of whom 196 (20%) developed ALD. ALD patients were younger, more frequently had liver cirrhosis or acute leukemia, and had increased severity of illness and vital organ support needs. ALD was associated with hospital mortality in univariate (OR 4.14, 95% CI 2.95-5.80, p < 0.001) and multivariate analysis (OR 1.86, 95% CI 1.07-3.24, p = 0.03). Hospital mortality was 46% in ALD patients; among 106 survivors, a third of patients requiring therapy received it as previously planned, and half of the patients were alive at 1 year. In summary, in a large population of critically ill patients with hematological malignancies, 20% developed ALD, which was an independent risk factor for hospital mortality and occasionally altered further anti-cancer treatment.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

Autopsy findings in patients with acute myeloid leukemia and non-Hodgkin lymphoma in the modern era: a focus on lung pathology and acute respiratory failure.

We aimed to report autopsy findings in patients with acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL) in the modern era, and also to focus on lung pathology in the subgroup of patients with acute respiratory failure (ARF) of unknown etiology, which is associated with especially high mortality rates. Charts and autopsy reports of 107 patients (59 AML and 48 NHL) autopsied between 2003 and 2018 were reviewed. More than 50% of patients had missed major diagnoses found at autopsy with 95% of lungs displaying abnormal findings. Malignant infiltration in at least one organ was observed in about 70% of patients with either no complete remission or relapse at the time of death (n = 92) versus 20% in patients without signs of active malignancy (n = 15) (p = 0.001). In patients with ARF of unknown etiology (n = 59), the proportion of malignant lung infiltration was 27% and equilibrated with bacterial pneumonias (29%), fungal pneumonias represented 8%, and isolated alveolar damage or pulmonary edema were the only findings in 32% of patients. Overall, 85% of patients with ARF of unknown etiology had either relapsed or not achieved remission at time of death and 80% of patients with malignant lung infiltration had ARF of unknown etiology. Ninety percent of malignant infiltration and fungal infections were observed in patients with no complete remission or relapse. Autopsy remains valuable in AML and NHL patients; besides infections, malignant infiltration is a significant contributor to ARF of unknown etiology and is rarely diagnosed ante mortem.

Influenza and associated co-infections in critically ill immunosuppressed patients.

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Bacterial Pneumonias in Immunocompromised Patients.

With the overall improvement in survival of cancer patients and the widespread use of novel immunotherapy drugs for malignant as well as nonmalignant diseases, the prevalence of immunosuppression is rising in the population. Immunocompromised patients are particularly exposed to pulmonary infections which remain a leading cause for acute hypoxic respiratory failure and intensive care unit admission. Although fungal or opportunistic infections are always a concern, bacterial pneumonia remains the most common cause of pulmonary infection, is associated with a significant mortality, and has some specificity in this population. Adequate and timely prevention, diagnosis, and management of bacterial pneumonias require knowledge about the complex interplay between host factors (type and severity of immunosuppression) and bacterial pathogenesis, to improve the outcome. We provide an overview of bacterial pneumonias in immunocompromised patients including their epidemiology, risk factors with respect to the pattern of immunosuppression, microbiological characteristics, diagnostic approach, management, and prevention.

Characteristics of pulmonary complications in non-Hodgkin's lymphoma patients treated with rituximab-containing chemotherapy and impact on survival.

Patients with non-Hodgkin's lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555-1338) days after chemotherapy. They had a higher prevalence of congestive heart failure and lung or pleural involvement at diagnosis as compared to patients who did not develop complications. Overall, 58 episodes of pulmonary complications were observed after median (interquartile) times from the first and last rituximab doses of 205 (75-580) days and 27 (14-163) days respectively. Infectious etiologies accounted for 75% of the respiratory complications, followed by heart failure exacerbation, lymphomatous involvement, and ARDS. Two Pneumocystis jirovecii pneumonias were observed, and no complication was ascribed to rituximab toxicity. Respiratory complications required ICU admission in 19 cases (33%) and invasive mechanical ventilation in 14 cases (24%). Using a time-dependent Cox regression analysis, we observed that the occurrence of respiratory complications was associated with a 170% increase in death hazard (hazard ratio 2.65, 95% CI 1.60-4.40, p = 0.001). In conclusion, respiratory complications in NHL patients receiving chemotherapy are relatively frequent, severe, and mostly infectious and are associated with increased mortality.

Effect of leukapheresis on blood coagulation in patients with hyperleukocytic acute myeloid leukemia.

INTRODUCTION: Leukapheresis has been proposed to reduce white blood cell (WBC) count in hyperleukocytic acute myeloid leukemia (AML). However, no survival benefit has been proven and leukapheresis can potentially affect coagulation and worsen bleeding and disseminated intravascular coagulation (DIC). We analyzed the effect of leukapheresis on coagulation tests in a cohort of hyperleukocytic AML patients. METHODS: Retrospective chart review of hyperleukocytic AML patients who underwent leukapheresis between 2003 and 2014. Blood coagulation tests (platelets, PT, INR, aPTT, fibrinogen, D-Dimers and fibrin degradation products (FDP)) were collected before and after each procedure and DIC score was computed. Transfusions of platelets and coagulation factors were collected. RESULTS: Ninety patients and 129 leukapheresis sessions were screened. After exclusion of the sessions associated with transfusions, we observed in 44 patients a significant decrease in platelets (from 75.69±89.48 to 44.59±47.71.109/L, p=0.001) and fibrinogen (from 4.05±1.29 to 3.35±1.37g/L, p<0.0005) along with an increase in PT (from 14.62±2.73 to 15.62±3.63s, p=0.001), aPTT (from 33.70±6.32 to 39.24±13.53s, p=0.009) and INR (from 1.33±0.2 to 1.45±0.34, p=0.002) after the first procedure. Bleeding complications, all intracerebral hemorrhages, were documented in 3 patients within 24h of leukapheresis. After combining 73 repeat procedures, we observed similar significant results except for the aPTT prolongation. The platelets and PT components of the DIC score, but not the fibrinogen component, were significantly increased after leukapheresis. CONCLUSIONS: In hyperleukocytic AML patients, leukapheresis is associated with clinically significant decreases in platelets and fibrinogen and prolonged clotting times.

Etiologies and Outcome of Patients with Solid Tumors Admitted to ICU with Acute Respiratory Failure: A Secondary Analysis of the EFRAIM Study.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3-9). The types of solid tumor were mostly lung cancer (n = 111, 21%), breast cancer (n = 52, 9.8%), and digestive cancer (n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection (n = 220, 41.6%), extrapulmonary sepsis (n = 62, 11.7%), or related to cancer or treatment toxicity (n = 83, 15.7%), or fungal infection (n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% (n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09-2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51-4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16-0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

Characteristics and outcomes of patients with acute myeloid leukemia admitted to intensive care unit with acute respiratory failure: a post-hoc analysis of a prospective multicenter study.

BACKGROUND: Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed. METHODS: This is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with ARF admitted to ICU. We evaluated hospital mortality and associated risk factors in patients with AML and ARF; secondly, we aimed to define specific subgroups within our study population through a cluster analysis. RESULTS: Overall, 201 of 1611 immunocompromised patients with ARF had AML and were included in the analysis. Hospital mortality was 46.8%. Variables independently associated with mortality were ECOG performance status ≥ 2 (OR = 2.79, p = 0.04), cough (OR = 2.94, p = 0.034), use of vasopressors (OR = 2.79, p = 0.044), leukemia-specific pulmonary involvement [namely leukostasis, pulmonary infiltration by blasts or acute lysis pneumopathy (OR = 4.76, p = 0.011)] and liver SOFA score (OR = 1.85, p = 0.014). Focal alveolar chest X-ray pattern was associated with survival (OR = 0.13, p = 0.001). We identified 3 clusters, that we named on the basis of the most frequently clinical, biological and radiological features found in each cluster: a "leukemic cluster", with high-risk AML patients with isolated, milder ARF; a "pulmonary cluster", consisting of symptomatic, highly oxygen-requiring, severe ARF with diffuse radiological findings in heavily immunocompromised patients; a clinical "inflammatory cluster", including patients with multi-organ failures in addition to ARF. When included in the multivariate analysis, cluster 2 and 3 were independently associated with hospital mortality. CONCLUSIONS: Among AML patients with ARF, factors associated with a worse outcome are related to patient's background (performance status, leukemic pulmonary involvement), symptoms, radiological findings, the need for vasopressors and the liver SOFA score. We identified three specific ARF syndromes in AML patients, which showed a prognostic significance and could guide clinicians to optimize management strategies.

Research priorities for therapeutic plasma exchange in critically ill patients.

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes associated with critical illness, TPE in the intensive care unit (ICU) setting has not been studied extensively. A group of eighteen experts around the globe from different clinical backgrounds used a modified Delphi method to phrase key research questions related to "TPE in the critically ill patient". These questions focused on: (1) the pathophysiological role of the removal and replacement process, (2) optimal timing of treatment, (3) dosing and treatment regimes, (4) risk-benefit assumptions and (5) novel indications in need of exploration. For all five topics, the current understanding as well as gaps in knowledge and future directions were assessed. The content should stimulate future research in the field and novel clinical applications.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Oxygen deficit and H2S in hemorrhagic shock in rats.

INTRODUCTION: Hemorrhagic shock induced O2 deficit triggers inflammation and multiple organ failure (MOF). Endogenous H2S has been proposed to be involved in MOF since plasma H2S concentration appears to increase in various types of shocks and to predict mortality. We tested the hypothesis that H2S increases during hemorrhagic shock associated with O2 deficit, and that enhancing H2S oxidation by hydroxocobalamin could reduce inflammation, O2 deficit or mortality. METHODS: We used a urethane anesthetized rat model, where 25 ml/kg of blood was withdrawn over 30 minutes. O2 deficit, lactic acid, tumor necrosis factor (TNF)-alpha and H2S plasma concentrations (Siegel method) were measured before and after the bleeding protocol in control animals and animals that received 140 mg/kg of hydroxocobalamin. The ability to oxidize exogenous H2S of the plasma and supernatants of the kidney and heart homogenates was determined in vitro. RESULTS: We found that withdrawing 25 ml/kg of blood led to an average oxygen deficit of 122 ± 23 ml/kg. This O2 deficit was correlated with an increase in the blood lactic acid concentration and mortality. However, the low level of absorbance of the plasma at 670 nm (A670), after adding N, N-Dimethyl-p-phenylenediamine, that is, the method used for H2S determination in previous studies, did not reflect the presence of H2S, but was a marker of plasma turbidity. There was no difference in plasmatic A670 before and after the bleeding protocol, despite the large oxygen deficit. The plasma sampled at the end of bleeding maintained a very large ability to oxidize exogenous H2S (high µM), as did the homogenates of hearts and kidneys harvested just after death. Hydroxocobalamin concentrations increased in the blood in the µM range in the vitamin B12 group, and enhanced the ability of plasma and kidneys to oxidize H2S. Yet, the survival rate, O2 deficit, H2S plasma concentration, blood lactic acid and TNF-alpha levels were not different from the control group. CONCLUSIONS: In the presence of a large O2 deficit, H2S did not increase in the blood in a rat model of untreated hemorrhagic shock. Hydroxocobalamin, while effective against H2S in vitro, did not affect the hemodynamic profile or outcome in our model.

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study.

PURPOSE: To study prevalence of targeted therapy (TT)-related adverse events requiring ICU admission in solid tumor patients. METHODS: Retrospective multicenter study from the Nine-i research group. Adult patients who received TT for solid tumor within 3 months prior to ICU admission were included. Patients admitted for TT-related adverse event were compared to those admitted for other reasons. RESULTS: In total, 140 patients, median age of 63 (52-69) years were included. Primary cancer site was mostly digestive (n=27, 19%), kidney (n=27, 19%), breast (n=24, 17%), and lung (n=20, 14%). Targeted therapy was anti-VEGF/VEGFR for 27% (n=38) patients, anti-EGFR for 22% (n=31) patients, anti-HER2 for 14% (n=20) patients and anti-BRAF for 9% (n=5) patients. ICU admission was related to TT adverse events for 30 (21%) patients. The most frequent complications were interstitial pneumonia (n=7), cardiac failure (n=5), anaphylaxis (n=4) and bleeding (n=4). At ICU admission, no significant difference was found between patients admitted for a TT-related adverse event and the other patients. One-month survival rate was higher in patients admitted for TT adverse event (OR=5.733 [2.031-16.182] P<0.001). CONCLUSIONS: Adverse events related to targeted therapy accounted for 20% of ICU admission in our population and carried a 16% one-month mortality. Outcome was associated with admission for TT related to adverse event, breast cancer and good performance status.

Plasma exchange in the intensive care unit: a narrative review.

In this narrative review, we discuss the relevant issues of therapeutic plasma exchange (TPE) in critically ill patients. For many conditions, the optimal indication, device type, frequency, duration, type of replacement fluid and criteria for stopping TPE are uncertain. TPE is a potentially lifesaving but also invasive procedure with risk of adverse events and complications and requires close monitoring by experienced teams. In the intensive care unit (ICU), the indications for TPE can be divided into (1) absolute, well-established, and evidence-based, for which TPE is recognized as first-line therapy, (2) relative, for which TPE is a recognized second-line treatment (alone or combined) and (3) rescue therapy, where TPE is used with a limited or theoretical evidence base. New indications are emerging and ongoing knowledge gaps, notably regarding the use of TPE during critical illness, support the establishment of a TPE registry dedicated to intensive care medicine.