Multiplex Polymerase Chain Reaction Assay to Detect Nasopharyngeal Viruses in Immunocompromised Patients With Acute Respiratory Failure.

BACKGROUND: In immunocompromised patients with acute respiratory failure (ARF), the clinical significance of respiratory virus detection in the nasopharynx remains uncertain. RESEARCH QUESTION: Is viral detection in nasopharyngeal swabs associated with causes and outcomes of ARF in immunocompromised patients? STUDY DESIGN AND METHODS: This preplanned post hoc analysis of a randomized controlled trial enrolled immunocompromised patients admitted to 32 ICUs for ARF between May 2016 and December 2017. Nasopharyngeal swabs sampled at inclusion were assessed for 23 respiratory pathogens using multiplex polymerase chain reaction (PCR) assay. Causes of ARF were established by managing physicians and were reviewed by three expert investigators masked to the multiplex PCR assay results. Associations between virus detection in nasopharyngeal swabs, causes of ARF, and composite outcome of day 28 mortality, invasive mechanical ventilation (IMV), or both were assessed. RESULTS: Among the 510 sampled patients, the multiplex PCR assay results were positive in 103 patients (20.2%), and a virus was detected in 102 samples: rhinoviruses or enteroviruses in 35.5%, coronaviruses in 10.9%, and flu-like viruses (influenza virus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus) in 52.7%. The cause of ARF varied significantly according to the results of the multiplex PCR assay, especially the proportion of viral pneumonia: 50.0% with flu-like viruses, 14.0% with other viruses, and 3.6% when no virus was detected (P < .001). No difference was found in the composite outcome of day 28 mortality, IMV, or both according to positive assay findings (54.9% vs 54.7%; P = .965). In a pre-established subgroup analysis, flu-like virus detection was associated with a higher rate of day 28 mortality, IMV, or both among recipients of allogeneic hematopoietic stem cell transplantation compared with those without detected virus. INTERPRETATION: In immunocompromised patients with ARF, the results of nasopharyngeal multiplex PCR assays are not associated with IMV or mortality. A final diagnosis of viral pneumonia is retained in one-third of patients with positive assay results and in one-half of the patients with a flu-like virus.

Clinical spectrum and prognostic impact of cancer in critically ill patients with HIV: a multicentre cohort study.

BACKGROUND: Both AIDS-defining and non-AIDS-defining cancers (ADC/NADC) predispose people living with HIV (PLHIV) to critical illnesses. The objective of this multicentre study was to investigate the prognostic impact of ADC and NADC in PLHIV admitted to the intensive care unit (ICU). METHODS: All PLHIV admitted over the 2015-2020 period in 12 university-affiliated ICUs in France were included in the study cohort. The effect of ADC and NADC on in-hospital mortality (primary study endpoint) was measured through logistic regression with augmented backward elimination of potential independent variables. The association between ADC/NADC and treatment limitation decision (TLD) during the ICU stay (secondary study endpoint) was analysed. One-year mortality in patients discharged alive from the index hospital admission (exploratory study endpoint) was compared between those with ADC, NADC or no cancer. RESULTS: Amongst the 939 included PLHIV (median age, 52 [43-59] years; combination antiretroviral therapy, 74.4%), 97 (10.3%) and 106 (11.3%) presented with an active NADC (mostly lung and intestinal neoplasms) and an active ADC (predominantly AIDS-defining non-Hodgkin lymphoma), respectively. Inaugural admissions were common. Bacterial sepsis and non-infectious neoplasm-related complications accounted for most of admissions in these subgroups. Hospital mortality was 12.4% in patients without cancer, 30.2% in ADC patients and 45.4% in NADC patients (P < 0.0001). NADC (adjusted odds ratio [aOR], 7.00; 95% confidence interval [CI], 4.07-12.05) and ADC (aOR, 3.11; 95% CI 1.76-5.51) were independently associated with in-hospital death after adjustment on severity and frailty markers. The prevalence of TLD was 8.0% in patients without cancer, 17.9% in ADC patients and 33.0% in NADC patients (P < 0.0001)-organ failures and non-neoplastic comorbidities were less often considered in patients with cancer. One-year mortality in survivors of the index hospital admission was 7.8% in patients without cancer, 17.0% in ADC patients and 33.3% in NADC patients (P < 0.0001). CONCLUSIONS: NADC and ADC are equally prevalent, stand as a leading argument for TLD, and strongly predict in-hospital death in the current population of PLHIV requiring ICU admission.

Immune checkpoint inhibitor-associated capillary leak syndrome: A systematic review and a worldwide pharmacovigilance study.

BACKGROUND: Although a few case reports have shown that immune checkpoint inhibitors (ICIs) are potential inducers of capillary leak syndrome (CLS), an incidental finding cannot be ruled out. The aim of this study was to describe the clinical characteristics of ICI-induced CLS through a systematic review and to assess a potential safety signal. METHODS: Medline/PubMed, Embase, and Reactions Weekly were screened, and a global disproportionality study was performed using the World Health Organization pharmacovigilance database through January 15, 2023. A signal of disproportionate reporting was defined as a Bayesian information component (IC) with a 95% credibility interval (CrI) lower boundary that exceeds 0. RESULTS: A total of 47 cases of ICI-associated CLS were included, 14 from the systematic review (of 61 screened articles) and 33 from VigiBase (of 34,058,481 reports of adverse drug reactions). The median time to CLS onset from the start of ICI was 12 weeks (interquartile range 8-49, n = 24). A total of 57% (8/14) of patients experienced an immune-related adverse event (irAE) before CLS. A fatal outcome was reported in 23% (7/31) of patients. A significant overreporting of CLS was found with ICIs compared with all other drugs (IC 2.4, 95% CrI from 1.8 to 2.8). CONCLUSION: This study showed a significant signal of disproportionality reporting for ICI-induced CLS, characterized by a long time to onset, and compared with the idiopathic form of the disease with a less abrupt onset and a less consistent hemoconcentration pattern.

Effect of a Musical Intervention During the Implantation of a Central Venous Catheter or a Dialysis Catheter in the Intensive Care Unit: A Prospective Randomized Pilot Study.

BACKGROUND: Listening to music may reduce anxiety during medical procedures. However, the magnitude of any effect may differ with respect to patient and procedure. We evaluated the effect of a musical intervention on patient anxiety during a central venous catheter or dialysis catheter implantation in an intensive care unit. METHODS: A prospective single-center controlled open-label 2-arm randomized trial was conducted in a medical intensive care unit (ICU) from February 2018 to February 2019. Patients undergoing central venous catheterization were randomized to listening to music or not during the procedure. Patients randomized to music listened to the Music Care application via headphones. The primary outcome was the change in anxiety assessed on a 100-mm Visual Analogue Scale between the beginning and end of the catheterization procedure. Secondary outcomes included postprocedural pain. RESULTS: We included 37 patients in the musical intervention group and 35 in the standard care group. The primary reasons for intensive care unit admission were the need for a central catheter for chemotherapy for hematologic malignancy and sepsis and/or septic shock in both groups. Postprocedural anxiety and pain assessments were missing in 1 (2.7%) and 4 (11.4%) patients in the intervention and standard care groups. We found no between-group difference in change in anxiety score: median -1 (interquartile range, -3 to 0) vs 0 (-3 to 0) in the musical intervention and standard care groups (median difference, -1 [-2 to 0]) (P = .24). Postprocedural pain score did not differ between the groups: median 0 (0-2) and 0 (0-3.75) in the musical intervention and standard care groups (median difference, -0 [0-0]) (P = .40). To account for missing outcome assessments, sensitivity analyses were performed using 2 extreme scenarios, one favoring the standard care group (scenario 1) and the other favoring the intervention group (scenario 2). In either scenario, change in anxiety score did not differ between the intervention and standard care groups: -1 (-3 to 0) vs 0 (-4 to 0) (P = .88) in scenario 1 and -1 (-3 to 0) vs 0 (-2.75 to 1) (P = .07) in scenario 2. CONCLUSIONS: In this first randomized pilot study of musical intervention for central venous catheterization in awake patients in the intensive care unit, the musical intervention did not reduce patients' anxiety as compared with usual care.

Management of HIV-infected patients in the intensive care unit.

The widespread use of combination antiretroviral therapies (cART) has converted the prognosis of HIV infection from a rapidly progressive and ultimately fatal disease to a chronic condition with limited impact on life expectancy. Yet, HIV-infected patients remain at high risk for critical illness due to the occurrence of severe opportunistic infections in those with advanced immunosuppression (i.e., inaugural admissions or limited access to cART), a pronounced susceptibility to bacterial sepsis and tuberculosis at every stage of HIV infection, and a rising prevalence of underlying comorbidities such as chronic obstructive pulmonary diseases, atherosclerosis or non-AIDS-defining neoplasms in cART-treated patients aging with controlled viral replication. Several patterns of intensive care have markedly evolved in this patient population over the late cART era, including a steady decline in AIDS-related admissions, an opposite trend in admissions for exacerbated comorbidities, the emergence of additional drivers of immunosuppression (e.g., anti-neoplastic chemotherapy or solid organ transplantation), the management of cART in the acute phase of critical illness, and a dramatic progress in short-term survival that mainly results from general advances in intensive care practices. Besides, there is a lack of data regarding other features of ICU and post-ICU care in these patients, especially on the impact of sociological factors on clinical presentation and prognosis, the optimal timing of cART introduction in AIDS-related admissions, determinants of end-of-life decisions, long-term survival, and functional outcomes. In this narrative review, we sought to depict the current evidence regarding the management of HIV-infected patients admitted to the intensive care unit.

Critically Ill Patients With HIV: 40 Years Later.

The development of combination antiretroviral therapies (cARTs) in the mid-1990s has dramatically modified the clinical presentation of critically ill, HIV-infected patients. Most cART-treated patients aging with controlled HIV replication are currently admitted to the ICU for non-AIDS-related events, mostly bacterial pneumonia and exacerbation of comorbidities, variably affected by chronic HIV infection (COPD, cardiovascular diseases, or solid neoplasms). Today, Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis, TB, and other severe opportunistic infections only occur in patients with unknown viral status, limited access to cART, viral resistance, or compliance issues. Acute respiratory failure, neurological disorders, and sepsis remain the main conditions that lead HIV-infected patients to the ICU, although admissions for liver diseases or acute kidney injury are increasing. Case fatality dropped substantially over the past decades, reaching figures of HIV-uninfected critically ill patients with similar demographic characteristics, comorbidities, and level of organ dysfunctions. Several other facets of critical care management have evolved in this population, including diagnostic procedures, cART management at the acute phase of critical illness, and ethical considerations. The goal of this narrative review was to depict the current evidence and emerging challenges for the management of critically ill, HIV-infected patients, almost 40 years following the onset of the AIDS epidemic.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.

Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure.

BACKGROUND: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. METHODS: Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. RESULTS: The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30-1.72]; RCT: p value 0.004, median OR 1.51 [1.36-1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. CONCLUSION: Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.

High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial.

BACKGROUND: Acute respiratory failure (ARF) is the leading reason for intensive care unit (ICU) admission in immunocompromised patients. High-flow nasal oxygen (HFNO) therapy is an alternative to standard oxygen. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates via nasal cannula devices, with FiO2 values of nearly 100%. Benefits include alleviation of dyspnea and discomfort, decreased respiratory distress and decreased mortality in unselected patients with acute hypoxemic respiratory failure. However, in preliminary reports, HFNO benefits are controversial in immunocompromised patients in whom it has never been properly evaluated. METHODS/DESIGN: This is a multicenter, open-label, randomized controlled superiority trial in 30 intensive care units, part of the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (GRRR-OH). Inclusion criteria will be: (1) adults, (2) known immunosuppression, (3) ARF, (4) oxygen therapy ≥ 6 L/min, (5) written informed consent from patient or proxy. Exclusion criteria will be: (1) imminent death (moribund patient), (2) no informed consent, (3) hypercapnia (PaCO2 ≥ 50 mmHg), (4) isolated cardiogenic pulmonary edema, (5) pregnancy or breastfeeding, (6) anatomical factors precluding insertion of a nasal cannula, (7) no coverage by the French statutory healthcare insurance system, and (8) post-surgical setting from day 1 to day 6 (patients with ARF occurring after day 6 of surgery can be included). The primary outcome measure is day-28 mortality. Secondary outcomes are intubation rate, comfort, dyspnea, respiratory rate, oxygenation, ICU length of stay, and ICU-acquired infections. Based on an expected 30% mortality rate in the standard oxygen group, and 20% in the HFNO group, error rate set at 5%, and a statistical power at 90%, 389 patients are required in each treatment group (778 patients overall). Recruitment period is estimated at 30 months, with 28 days of additional follow-up for the last included patient. DISCUSSION: The HIGH study will be the largest multicenter, randomized controlled trial seeking to demonstrate that survival benefits from HFNO reported in unselected patients also apply to a large immunocompromised population. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02739451 . Registered on 15 April 2016.

Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study.

BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). RESULTS: A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO2 (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2 < 100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38). CONCLUSION: HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.

Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear. OBJECTIVE: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015. INTERVENTIONS: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). MAIN OUTCOMES AND MEASURES: The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay. RESULTS: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. CONCLUSIONS AND RELEVANCE: Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01915719.

Temporal trends in critical events complicating HIV infection: 1999-2010 multicentre cohort study in France.

PURPOSE: Multicentre data are limited to appraise the management and prognosis of critically ill human immunodeficiency virus (HIV)-infected patients. We sought to describe temporal trends in demographic and clinical characteristics, indications for intensive care and outcome in this patient population. METHODS: We conducted a cohort study of unselected HIV-infected patients admitted between 1999 and 2010 to 34 French ICUs contributing to the CUB-Réa prospective database. RESULTS: We included 6,373 consecutive patients. Over the 12-year period, increases occurred in median age (39 years in 1999-2001; 47 years in 2008-2010, p < 0.0001) and prevalence of comorbidities (notably malignancies, from 6.7 to 16.4%, p < 0.0001). Admissions for respiratory failure (39.8% overall), shock (8.1%) and coma (22.7%) decreased (p < 0.0001), while those for sepsis (19.3%) remained stable. The main final diagnoses were bacterial sepsis (24.6%) and non-bacterial acquired immune deficiency syndrome (AIDS)-defining diseases (steady decline from 26.0 to 17.5%, p < 0.0001). Patients increasingly received mechanical ventilation (from 42.9 to 54.0%) and renal replacement therapy (from 9.6 to 16.8%) (p < 0.0001), whereas vasopressor use remained stable (27.4%). ICU readmissions increased after 2004 (p < 0.0001). ICU and hospital mortality (17.6 and 26.9%, respectively) dropped markedly in the most severely ill patients requiring multiple life-sustaining therapies. Malignancies and chronic liver disease were heavily associated with hospital mortality by multivariate analysis, while the most common AIDS-defining complications (Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis and tuberculosis) had no independent impact. CONCLUSIONS: Progressive ageing, increasing prevalence of comorbidities (mainly malignancies), a steady decline in AIDS-related illnesses and improved benefits from life-sustaining therapies were the main temporal trends in HIV-infected patients requiring ICU admission.

[Multi-drug resistant Pseudomonas aeruginosa: towards a therapeutic dead end?]. / Multirésistance chez Pseudomonas aeruginosa: vers l'impasse thérapeutique?].

Pseudomonas aeruginosa is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis or those hospitalized in intensive care units. In this context, the current increase in incidence of multi-drug resistant (MDR) isolates of P. aeruginosa (MDRPA) raises serious concerns. MDR in P. aeruginosa is defined as the resistance to 3 or 4 of the following antibiotic classes: penicillins/cephalosporins/monobactams, carbapenems, aminoglycosides, and fluoroquinolones. These strains constantly cumulate several resistance mechanisms as a consequence of multiple genetic events, i.e., chromosomal mutations or horizontal transfers of resistance genes. Involved mechanisms may include active efflux, impermeability resulting from porins loss, plasmid-encoded b-lactamases/carbapenemases or aminoglycosides-modifying enzymes, and enzymatic or mutation-associated changes in antibiotics targets. Antibiotic selection pressure represents the leading risk factor for MDRPA acquisition. Colistin (polymyxin E) remains active on virtually all MDRPA isolates, and increasingly appears as the last available option to treat infections caused by these strains. However, the emergence of colistin resistance has been reported in P. aeruginosa, which may announce the spread of pan-resistant strains in a close future.