Successful rituximab therapy in a lupus patient with diffuse alveolar haemorrhage.

Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Specific therapy is based on a heavy immunosuppressive treatment that usually associates corticosteroid and cyclophosphamide boluses and plasma exchange. Despite this treatment, an early mortality rate of 20-50% is reported in the literature. Immunosuppression-related complications are responsible for further mortality and morbidity. Rituximab, a specific anti-CD20 antigen B-cell antibody, has been used with success for the treatment of several refractory autoimmune disorders, but rarely for SLE-induced DAH. We report here the first case of SLE-induced DAH treated successfully with rituximab without cyclophosphamide administration in a patient intolerant to cyclophosphamide. We review the two other cases of SLE-induced DAH managed with rituximab as a part of the immunosuppressive regimen.

[Severe H1N1 2009 influenza infection in adults: the French experience]. / Formes graves de la grippe H1N1 2009 chez l'adulte: l'expérience française.

The REVA-Flu-SRLF register allowed collection of data from 562 patients infected with H1N1 influenza virus 2009 and hospitalized in the intensive care unit (ICU). The overall mortality of these patients was 20%. The use of invasive ventilation, heart failure, and immunosuppression were associated with mortality. Three hundred forty-one (82%) among the 417 mechanically ventilated patients had an acute respiratory distress syndrome (ARDS). One hundred sixty-nine (30%) had a bacterial co-infection. Corticosteroid therapy was associated with an increased mortality in patients with ARDS. The occupancy rate associated with influenza patients crossed the threshold of 15% in many ICUs.

Physiological effects of adding ECCO2R to invasive mechanical ventilation for COPD exacerbations.

BACKGROUND: Extracorporeal CO2 removal (ECCO2R) could be a valuable additional modality for invasive mechanical ventilation (IMV) in COPD patients suffering from severe acute exacerbation (AE). We aimed to evaluate in such patients the effects of a low-to-middle extracorporeal blood flow device on both gas exchanges and dynamic hyperinflation, as well as on work of breathing (WOB) during the IMV weaning process. STUDY DESIGN AND METHODS: Open prospective interventional study in 12 deeply sedated IMV AE-COPD patients studied before and after ECCO2R initiation. Gas exchange and dynamic hyperinflation were compared after stabilization without and with ECCO2R (Hemolung, Alung, Pittsburgh, USA) combined with a specific adjustment algorithm of the respiratory rate (RR) designed to improve arterial pH. When possible, WOB with and without ECCO2R was measured at the end of the weaning process. Due to study size, results are expressed as median (IQR) and a non-parametric approach was adopted. RESULTS: An improvement in PaCO2, from 68 (63; 76) to 49 (46; 55) mmHg, p = 0.0005, and in pH, from 7.25 (7.23; 7.29) to 7.35 (7.32; 7.40), p = 0.0005, was observed after ECCO2R initiation and adjustment of respiratory rate, while intrinsic PEEP and Functional Residual Capacity remained unchanged, from 9.0 (7.0; 10.0) to 8.0 (5.0; 9.0) cmH2O and from 3604 (2631; 4850) to 3338 (2633; 4848) mL, p = 0.1191 and p = 0.3013, respectively. WOB measurements were possible in 5 patients, indicating near-significant higher values after stopping ECCO2R: 11.7 (7.5; 15.0) versus 22.6 (13.9; 34.7) Joules/min., p = 0.0625 and 1.1 (0.8; 1.4) versus 1.5 (0.9; 2.8) Joules/L, p = 0.0625. Three patients died in-ICU. Other patients were successfully hospital-discharged. CONCLUSIONS: Using a formalized protocol of RR adjustment, ECCO2R permitted to effectively improve pH and diminish PaCO2 at the early phase of IMV in 12 AE-COPD patients, but not to diminish dynamic hyperinflation in the whole group. A trend toward a decrease in WOB was also observed during the weaning process. Trial registration ClinicalTrials.gov: Identifier: NCT02586948.

Persistent swallowing disorders after extubation in mechanically ventilated patients in ICU: a two-center prospective study.

BACKGROUND: Persistent swallowing disorders (SD) are non-pulmonary complications of mechanical ventilation (MV). However, there are few clinical studies on persistent SD in critically ill patients undergoing tracheal intubation for MV. The aim of the present study was to assess the incidence and characteristics of clinical manifestations associated with persistent SD. METHODS: We prospectively evaluated in patients requiring more than 7 days of invasive MV the incidence and characteristics of clinical manifestations related to persistent SD. For this purpose, quality of swallowing was assessed within 24 h after extubation by an experienced physical therapist not directly involved in patient management. Swallowing assessment consisted in a specific standardized test combining a swallowing test and a full clinical evaluation of the cranial nerves involved in swallowing. In patients with SD on the first test, a second test was done within 48 h in order to discriminate between transient and persistent SD. RESULTS: Among the 482 patients mechanically ventilated more than 7 days, 138 were enrolled in this study. The first test performed 24 h after extubation revealed SD in 35 patients (25%). According to the second test performed 48 h later, SD were considered transient in 21 (15%) and persistent in 14 (10%) cases. Patients with persistent SD were older (66 ± 16 vs 58 ± 15 years), had lower bodyweight at admission (76 ± 15 vs 87 ± 23 kg) and received less often neuromuscular blocking agents (36% vs 66%) compared to patients without or with only transient SD. Patients with persistent SD had longer duration of Intensive Care Unit (ICU) stay after first extubation and longer delay to oral feeding than patients without or with only transient SD, respectively, 11 ± 9 vs 7 ± 6 days and 23 ± 33 vs 5 ± 7 days. CONCLUSIONS: Based on a specific standardized clinical test, 25% of patients mechanically ventilated more than 7 days exhibited clinical manifestations of SD. However, SD were considered as persistent after extubation in only 10% of them. Persistent SD were associated with longer duration of ICU stay after extubation and longer time of enteral feeding. TRIAL REGISTRATION: The study is registered with Clinical Trials (NCT01360580).

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure. METHODS: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods. RESULTS: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use. CONCLUSION: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

An autopsy case of acute multiple sclerosis (Marburg's type) during pregnancy.

We report a case of a 9-month pregnant woman who presented acute psychiatric and neurological symptoms with extensive involvement of the white matter on MRI and no oligoclonal bands on CSF examination. Despite high doses of intravenous steroids, plasmapheresis and immunosuppressive drugs, a fatal outcome (coma) was noted 8 months later. Neuropathological examination confirmed the diagnosis of Marburg's type of multiple sclerosis showing sharp-edged lesions of demyelination, giant astrocytes, numerous macrophages and little perivascular inflammation. We discuss the definition and limits of the Marburg entity with reference to acute disseminated encephalomyelitis, impact of pregnancy, unusual MRI features, neuropathology and treatment.

A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study.

INTRODUCTION: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low. AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints). METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles). RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one). CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.

[Free and intracellular bacteria on peripheral blood smears: an uncommon situation related to an adverse prognosis]. / Présence de bactéries libres et intraleucocytaires sur l'étalement sanguin : une situation rare mais de pronostic vital.

Bacterial infections are responsible for several changes in the cell blood count, which are usually non specific, although some morphological changes of polymorphonuclear neutrophils may be indicative of sepsis. The presence of bacteria on peripheral blood smears is a rare but extreme situation, related in most instances to a fatal prognosis. The presence of both free and intracellular bacteria was observed in the peripheral blood smear of a critically ill patient with a pneumococcal septicaemia which led to a fatal outcome within the next following hours. If the finding of bacteria on the blood smear is a sign of severe sepsis, the literature review shows that less than 10% of septic patients demonstrate bacteria on the blood smear, and routine search for the diagnosis of sepsis is not recommended. Samples taken from infected central venous catheters are another situation of bacteraemia which must be known, but prognosis is usually not fatal if prompt medical care is performed. Some preanalytical conditions are also associated with the presence of bacteria on the peripheral blood smear, but unrelated to infection of the relevant patient.

Consumption of cosmetic products by the French population second part: Amount data.

The aim of the study was to assess the amount per use of cosmetic products consumed at home by the adult, child and baby French population. 1078 men and women participated in the study which was performed in four cities of France. This enquiry was performed on 106 cosmetics including general hygiene, skin care, hair care, hair styling, make-up, fragrances, solar, shaving and depilatory, and baby products. Coupled to frequency data previously obtained (Ficheux et al., 2015), these amounts per use data will be used in order to assess the exposure to cosmetics by the French population. These current exposure values could be useful for safety assessors and for safety agencies.

[Invasive pulmonary aspergillosis complicating septic shock]. / Aspergillose pulmonaire invasive compliquant un choc septique.

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is an opportunistic infection with a poor prognosis, occurring primarily in patients who are severely immunocompromised. CASE REPORT: We report a case of IPA that occurred in a 37-year-old woman with no history of previous immunosuppression or significant co-morbidity. She was admitted to our intensive care unit (ICU) with septic shock and multi-organ failure complicating a bacterial pneumonia. After an initial improvement, her condition deteriorated on the 10th day after admission with fever and lesions consistent with IPA seen on high-resolution computed tomography (HRCT). IPA was confirmed by isolating Aspergillus fumigatus from bronchoalveolar lavage and by a positive circulating galactomannan test (sandwich ELISA). First line therapy with voriconazole had to be stopped after 12 days due to hepatic toxicity. The patient was successfully treated with caspofungine for 2 months then itraconazole for 4 months with progressive improvement of HRCT abnormalities. Her galactomannan test became negative at 6 months. CONCLUSION: The diagnosis of IPA must be considered in critically ill patients even in the absence of underlying immunosupression where suggestive HRCT abnormalities occur in the context of septic shock and multiple organ failure.

Global energetic failure in brain-dead patients.

The objective of this prospective, clinical study of consecutive patients was to test the hypothesis of a global energetic failure in brain-dead patients by analyzing indices of peripheral oxygenation during brain-dead resuscitation. Subjects comprised 24 subjects with brain death criteria from a multidisciplinary intensive care unit. The causes of brain death were multiple: severe traumatic head injury, cerebrovascular event, cerebral anoxia, primary brain tumor, and gunshot wound to the head. Interventions used were radial and pulmonary artery catheterization. Hemodynamic and gasometric parameters and blood lactate levels were measured immediately after the diagnosis of brain death (T0) and 4 hr later (T4), while patients were receiving a therapeutic protocol (fluids, vasopressive drugs) adjusted to reach a mean arterial pressure of 75 mmHg. In 18 of our 24 patients, a blood lactate level > or = 2 mmol/L (mean +/- SD: 4 +/- 2 mmol/L) associated with an increased mean lactate to pyruvate ratio (14.4 +/- 3.2) was observed at T0, while oxygen delivery (DO2) was high (533 +/- 208 ml/min/m2) and mean arterial pressure was 76 +/- 21 mmHg. Patients were subdivided into two groups according to changes in DO2 from T0 to T4: group D comprised 14 patients (10 with hyperlactatemia and 4 with normal lactate) in whom DO2 and oxygen consumption (VO2) simultaneously decreased from T0 to T4 without significant change in lactate level; group I comprised 10 patients (8 with hyperlactatemia and 2 with normal lactate) in whom DO2 and VO2 simultaneously increased, while the blood lactate level decreased significantly from 3.5 +/- 2.5 mmol/L at T0 to 2.1 +/- 1.0 mmol/L at T4 (P < 0.05). Our results indicate that the brain-dead state was frequently associated with a global energetic failure probably due to a cellular oxygen deficit, despite blood pressure within the normal range. This energetic failure, because it is associated with high levels of DO2, could result from a defect in peripheral oxygen extraction. Aggressive therapy, achieved by producing a further increase in DO2, may reduce this global tissue oxygen deficit.

An outbreak of pneumococcal pneumonia in two men's shelters.

We report a retrospective study of 39 homeless men hospitalized for acute pneumonia from April 1988 to March 1989. All of them had recently stayed in one of two shelters. A Streptococcus pneumoniae serotype 1, resistant to cotrimoxazole, was isolated in 29 patients (74 percent). Blood cultures were positive in 24 (61 percent). The patients were relatively young; none was over 70 years old. Thirty-five (90 percent) were heavy smokers; 32 (82 percent) were alcoholics. The radiologic pattern was atypical in 14 cases (36 percent). The only fatal case was linked to the adult respiratory distress syndrome. It is likely that the rate of outbreaks of pneumococcal pneumonia is underestimated. The homeless are at high risk for pneumococcal pneumonia. In addition, the closeness existing in shelters favors the occurrence of outbreaks. Consequently, we suggest that shelter residents would benefit from pneumococcal vaccination.

Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome.

To assess the cardiorespiratory effects of pressure-controlled ventilation (PCV) and pressure-controlled inverse ratio ventilation (PC-IRV), we compared pressure-controlled ventilation with an inspiratory-to-expiratory time ratio (I/E) of 1/2 (PCV) and of 2/1 (PC-IRV) to volume-controlled ventilation (VCV) with an I/E of 1/2 in 10 patients suffering from the adult respiratory distress syndrome. In all modes, the inspiratory oxygen fraction, tidal volume, respiratory rate, and total positive end-expiratory pressure (PEEPt = applied PEEP + intrinsic PEEP) were kept constant. Each ventilatory mode was applied for 1 h in a randomized order. No significant differences in PaO2 were observed among the three modes. The PaCO2 was lower (p < 0.05) in PC-IRV (39 +/- 4 mm Hg) than in PCV (43 +/- 5 mm Hg) and in VCV (45 +/- 5 mm Hg). The peak airway pressure was significantly lower in PC-IRV than in PCV (p < 0.05) and in PCV than in VCV (p < 0.05), but plateau pressure was not different in the 3 modes. The mean airway pressure (mPaw) was significantly higher (p < 0.05) in PC-IRV (21.4 +/- 0.7 cm H2O) than in PCV (17.1 +/- 0.7 cm H2O) and VCV (16.4 +/- 0.5 cm H2O). As a consequence of this increased mPaw, PC-IRV induced a decrease in cardiac index (CI) (3.3 +/- 0.2 vs 3.7 +/- 0.2 L/min/m2 in VCV; p < 0.05) and hence in oxygen delivery (DO2) (424 +/- 28 vs 469 +/- 38 ml/min/m2 in VCV; p < 0.05). Our results suggest that neither PCV nor PC-IRV bring any benefit over VCV in terms of arterial oxygenation. Moreover, the increase in mPaw induced by PC-IRV may be deleterious to the CI and DO2.

[Atypical mycobacterial infections]. / Mycobactérioses atypiques.

Infrequent and forgotten before the advent of the acquired immune deficiency syndrome (AIDS), non-tuberculous mycobacterial infections are now often encountered, predominately in patients positive for the human immune deficiency virus (HIV). In non-AIDS patients, Mycobacterium kansasii, M. avium and M. xenopi are the most common causal agents of pulmonary mycobacterial infections. Nodes and skin diseases are less frequent. M. kansasii infections are treated for 12 months with a standard combination of rifampin, isoniazid and ethambutol. The treatment for M. xenopi and M. avium infections have not yet been standardized. The AIDS epidemia has modified the epidemiology of these disease and there has been a 10-fold increase in incidence. Disseminated M. avium infections occur in 15% of patients at end-stage AIDS. This new epidemia has triggered research leading to the discovery of new diagnostic procedure including blood culture media for mycobacteria, polymerase chain reaction (PCR) and new active drugs. New active macrolides such as clarithromycine and azithromycine are active against M. avium and new rifampicin-related drugs such as rifabutine and new quinolones are under investigation.

[Management of serious pulmonary embolism]. / Gestion de l'embolie pulmonaire grave.

In-hospital mortality is high when pulmonary embolism is complicated by hemodynamic instability and/or pulmonary hypertension. Death occurs frequently within the first hours after admission. This implies specific diagnostic and therapeutic management. Spiral CT seems to be an excellent diagnostic procedure in this setting. However, pulmonary angiography and perfusion lung scan can also be employed. Cardiac echography can help in the diagnosis and therapeutic decision making. Supportive therapy mainly includes correction of hypovolemia if present, a limited volume loading in other cases, and the use of dobutamine. Norepinephrine is the drug of choice when hypotension is present. Thrombolytic agents are indicated in case of hemodynamic instability. Modalities of administration and contra indications are currently well established. Surgical embolectomy should be performed in cases of uncontrolled shock, when thrombolysis is contra-indicated or uneffective.

Effect of different seated positions on lung volume and oxygenation in acute respiratory distress syndrome.

RATIONALE: Lung volume available for ventilation is markedly decreased during acute respiratory distress syndrome. Body positioning may contribute to increase lung volume and partial verticalization is simple to perform. This study evaluated whether verticalization had parallel effects on oxygenation and end expiratory lung volume (EELV). METHODS: Prospective multicenter study in 40 mechanically ventilated patients with ALI/ARDS in five university hospital MICUs. We evaluated four 45-min successive trunk position epochs (supine slightly elevated at 15°; semi recumbent with trunk elevated at 45°; seated with trunk elevated at 60° and legs down at 45°; back to supine). Arterial blood gases, EELV measured using the nitrogen washin/washout, and static compliance were measured. Responders were defined by a PaO2/FiO2 increase >20 % between supine and seated position. Results are median [25th-75th percentiles]. RESULTS: With median PEEP = 10 cmH2O, verticalization increased lung volume but only responders (13 patients, 32 %) had a significant increase in EELV/PBW (predicted body weight) compared to baseline. This increase persisted at least partially when patients were positioned back to supine. Responders had a lower EELV/PBW supine [14 mL/kg (13-15) vs. 18 mL/kg (15-27) (p = 0.005)] and a lower compliance [30 mL/cmH2O (22-38) vs. 42 (30-46) (p = 0.01)] than non-responders. Strain decreased with verticalization for responders. EELV/PBW increase and PaO2/FiO2 increase were not correlated. DISCUSSION: Verticalization is easily achieved and improves oxygenation in approximately 32 % of the patients together with an increase in EELV. Nonetheless, effect of verticalization on EELV/PBW is not predictable by PaO2/FiO2 increase, its monitoring may be helpful for strain optimization.

Potentially harmful effects of inspiratory synchronization during pressure preset ventilation.

PURPOSE: Pressure preset ventilation (PPV) modes with set inspiratory time can be classified according to their ability to synchronize pressure delivery with patient's inspiratory efforts (i-synchronization). Non-i-synchronized (like airway pressure release ventilation, APRV), partially i-synchronized (like biphasic airway pressure), and fully i-synchronized modes (like assist-pressure control) can be distinguished. Under identical ventilatory settings across PPV modes, the degree of i-synchronization may affect tidal volume (VT), transpulmonary pressure (PTP), and their variability. We performed bench and clinical studies. METHODS: In the bench study, all the PPV modes of five ventilators were tested with an active lung simulator. Spontaneous efforts of -10 cmH2O at rates of 20 and 30 breaths/min were simulated. Ventilator settings were high pressure 30 cmH2O, positive end-expiratory pressure (PEEP) 15 cmH2O, frequency 15 breaths/min, and inspiratory to expiratory ratios (I:E) 1:3 and 3:1. In the clinical studies, data from eight intubated patients suffering from acute respiratory distress syndrome (ARDS) and ventilated with APRV were compared to the bench tests. In four additional ARDS patients, each of the PPV modes was compared. RESULTS: As the degree of i-synchronization among the different PPV modes increased, mean VT and PTP swings markedly increased while breathing variability decreased. This was consistent with clinical comparison in four ARDS patients. Observational results in eight ARDS patients show low VT and a high variability with APRV. CONCLUSION: Despite identical ventilator settings, the different PPV modes lead to substantial differences in VT, PTP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high VT is undesirable.