Emmanuel Besnier

The Use of Ferritin to Identify Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis.

Objectives:Thrombocytopenia is a common, multifactorial, finding in ICU. Hemophagocytosis is one of the main explanatory mechanisms, possibly integrated into hemophagocytic lymphohistiocytosis syndrome, of infectious origin in the majority of cases in ICU. The hemophagocytic lymphohistiocytosis is probably underdiagnosed in the ICU, although it is associated with dramatic outcomes. The main objectives of this work were to identify the frequency of secondary hemophagocytic lymphohistiocytosis, and the main prognostic factors for mortality. Design/Setting:We conducted a retrospective observational study in all adult patients admitted with suspected or diagnosed hemophagocytic lymphohistiocytosis, between January 1, 2000, and August 22, 2012. Patients:A total of 106 patients (42%) had significant hemophagocytosis on bone marrow examination, performed for exploration of thrombocytopenia, bicytopenia, or pancytopenia. Measurements and Main Results:The median age was 56 (45–68) and the median Simplified Acute Physiology Score 2 was 55 (38–68). The main reason for ICU admission was hemodynamic instability (58%), predominantly related to sepsis (45% cases). The main precipitating factor found was a bacterial infection in 81 of 106 patients (76%), including 32 (30%) with Escherichia coli infection. Forty six of 106 patients (43%) died in the ICU. They were significantly older, had higher Simplified Acute Physiology Score 2, plasma lactate deshydrogenase bilirubin, and serum ferritin. The fibrinogen and the percentage of megakaryocytes were significantly lower in nonsurvivors when compared with survivors. In multivariate analysis, only serum ferritin significantly predicted death related to hemophagocytosis. A serum ferritin greater than 2,000 &mgr;g/L predicted death with a sensitivity of 71% and a specificity of 76%. A decreased percentage of megakaryocytes also predicted patient death in the ICU. Conclusions:Hemophagocytosis is common in thrombocytopenic patients with sepsis, frequently included in a postinfectious hemophagocytic lymphohistiocytosis setting. Our study reveals that ferritin could be a reliable prognostic marker in these patients, and hold particular interest in discussing a specific treatment for hemophagocytic lymphohistiocytosis.

Fulminant giant-cell myocarditis on mechanical circulatory support: Management and outcomes of a French multicentre cohort

AIMS Giant-cell myocarditis (GCM) is a rare and often fatal form of myocarditis. Only a few reports have focused on fulminant forms. We describe the clinical characteristics, management and outcomes of GCM patients rescued by mechanical circulatory support (MCS). METHODS AND RESULTS The clinical features, diagnoses, treatments and outcomes of MCS-treated patients in refractory cardiogenic shock secondary to fulminant GCM admitted to eight French intensive care units (2002-2016) were analysed. We also conducted a systematic review of this topic. Thirteen patients (median age 44 [range 21-76]years, Simplified Acute Physiology Score II 55 [40-79]) in severe cardiogenic shock (median [range] left ventricular ejection fraction 15% [15-35%] and blood lactate 4 mmol/L) were placed on MCS 4 [0-28]days after hospital admission. Severe arrhythmic disturbances were frequent (77%), with six (46%) patients experiencing an electrical storm prior to MCS. Venoarterial extracorporeal membrane oxygenation was the first MCS option for 11 (85%) patients. GCM was diagnosed in five (38%) patients before transplant or death and treated with immunosuppressants; infections were the main complication (80%). Four patients died on MCS and no patient presented long-term survival free from heart transplant (nine patients, 69%). All transplanted patients were alive 1year later and no GCM recurrence was reported after median follow-up of 42 [12-145]months. CONCLUSION Outcomes of fulminant GCMs may differ from those of milder forms. In this context, heart transplant might likely be the only long-term survival option.

Ketamine and Etomidate Down-regulate the Hypothalamic–Pituitary–Adrenal Axis in an Endotoxemic Mouse Model

BACKGROUND We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis. METHODS Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3β-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11β-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD). RESULTS At 12 h, lipopolysaccharide induced an overexpression of corticotropin-releasing hormone (32 ± 5 vs. 18 ± 6, P < 0.01), proopiomelanocortin (21 ± 3 vs. 8 ± 0.9, P < 0.0001), P450 side-chain cleavage (32 ± 4 vs. 23 ± 10, P < 0.05), 21-hydroxylase (17 ± 5 vs. 12 ± 2, P < 0.05), and 11β-hydroxylase (11 ± 4 vs. 6 ± 0.5, P = 0.001), and an elevation of corticosterone (642 ± 165 vs. 98.3 ± 63 ng/ml, P < 0.0001). Etomidate and ketamine reduced P450 side-chain cleavage (19 ± 7 and 19 ± 3 vs. 32 ± 4, P < 0.01), 21-hydroxylase (8 ± 0.8 and 8 ± 1 vs. 17 ± 5, P < 0.001), 11β-hydroxylase (4 ± 0.5 and 7 ± 1 vs. 11 ± 4, P < 0.001 and P < 0.05), and corticosterone (413 ± 189 and 260 ± 161 vs. 642 ± 165 ng/ml, P < 0.05 and P < 0.01). Ketamine also inhibited adrenocorticotropin hormone production (2.5 ± 3.6 vs. 36 ± 15 pg/ml, P < 0.05). At 48 h, all four adrenal enzymes were down-regulated by lipopolysaccharide administration with corticosterone levels similar to the control group. Ketamine and etomidate did not modify corticosterone plasma levels. CONCLUSIONS Our endotoxemic model induces an initial activation of the hypothalamic-pituitary-adrenal axis, followed by a secondary inhibition of adrenal steroidogenesis processes. Ketamine and etomidate inhibit the enzyme expression and activity of the adrenal gland at the early stage.

Delaying intubation with high-flow nasal cannula therapy: a dilemma between the technique and clinical management!

Dear Editor, We read with interest the article by Kang et al. [1] suggesting that highflow nasal cannula (HFNC) could potentially have a harmful effect on outcome and survival by delaying the intubation time in unselected patients with acute hypoxemic respiratory failure (AHRF). HFNC is an emerging oxygenation technique with numerous physiological advantages [2]. Consequently, HFNC has been shown to be more tolerated and associated with better oxygenation than standard oxygen therapy, allowing one to rapidly relieve the AHRF symptoms [3]. First of all, the clinical benefit of HFNC on adult AHRF patient outcome has now been demonstrated in a large French prospective randomized controlled trial, the ‘‘FLORALI’’ study, which is currently under consideration for publication [4]. In fact, the Kang et al. [1] retrospective study emphasizes more the risks of HFNC management than those of the technique per se. We understand that the routine HFNC strategy used (greater than 9 l/min of conventional oxygen needed) was also applied to patients in general wards. Despite the management by a skilled medical emergency team, this clinical practice could be highly hazardous in terms of surveillance and prompt intubation. In this way, it would be interesting to know the late intubation rate performed in ICU and general ward, respectively. Also, no data is provided regarding the level of HFNC gas flow used in the two groups. Indeed, gas flow is essential to consider as many physiological mechanisms of HFNC are highly related to the level used. In practice, it should be recommended to start HFNC with high gas flow (at least 50 l/min) in order to rapidly reverse AHRF symptoms [3]. Although HFNC was not applied in patients with hypercapnia, this may be questionable as more than 30 % of ARF etiologies occurred in acute-onchronic respiratory failure patients and more patients with hypercapnic ARF were intubated and died in the late intubation group. Although some physiological mechanisms of HFNC may suggest its potential benefit in hypercapnic ARF, no clinical study has been yet conducted in this selected population and noninvasive ventilation (NIV) remains, currently, the ventilatory strategy recommended in these patients. The median duration of HFNC before intubation was also very different between the early (10 h) and late (126 h) intubation groups. Clearly, maintaining AHRF patients on HFNC for more than 5 days does not appear reasonable and such a delay has never been previously reported, even in do-notintubated ARF patients [5]. Paradoxically, numerous patients (31 %) have been tracheostomized in the early intubation group and considering tracheostomy as a weaning success may be debatable. The overall ICU mortality was very high in the study (46 %) and higher in the late (67 %) than the early (39 %) intubation group. This could be due to the high proportion of immunocompromised patients (more than 50 %), but also to the severity of the underlying organ failure, 9 % exhibiting a septic shock. In our view, HFNC should be reserved for patients without hemodynamic instability. Finally, the 14and 28-day mortality was not different, suggesting that hospital mortality was similar between both groups. This result should greatly limit the study interpretation and conclusion. Nevertheless, the study by Kang et al. [1] has the merit of pointing out the potential risk of HFNC to unnecessary delay the intubation time, as it has been and may be still debated with NIV. Therefore, clinicians should be aware of this risk and, like NIV, HFNC success should consider the population selection, experience and close monitoring with HFNC in a safe environment. Moreover simple and very early clinical signs of HFNC failure have been described and should be very useful for routine practice [3].

High-Flow Nasal Cannula Therapy: Principles and Potential Use in Obese Patients

Oxygen therapy is probably one of the most frequent treatments administrated in hospital setting. Its main goal is to correct or prevent the occurrence of hypoxemia, potentially provider of cellular or tissue hypoxia. A large panel of devices is currently available to administer conventional oxygen therapy (COT) using various interfaces and/or flows. However, some cases can catch out its use, and some major disadvantages can limit the expected benefits. Since few years, a new technique of oxygen therapy has been developed as an alternative to COT, the high-flow nasal cannula (HFNC) oxygen therapy. The HFNC consists of an air/oxygen blender connected via an active heated humidifier to specific nasal cannula and allows adjustment of the inspired fraction of oxygen (FIO2: 21–100%) independently from the gas mixture flow rate (up to 70 L/min in adults).

Background noise lowers the performance of anaesthesiology residents’ clinical reasoning when measured by script concordance: A randomised crossover volunteer study

BACKGROUND Noise, which is omnipresent in operating rooms and ICUs, may have a negative impact not only patients but also on the concentration of and communication between clinical staff. OBJECTIVE The present study attempted to evaluate the impact of noise on the performance of anaesthesiology residents’ clinical reasoning. Changes in clinical reasoning were measured by script concordance tests (SCTs). DESIGN This was a randomised and crossover study. SETTING Single centre at Rouen University Hospital in April 2014. POPULATION All year 1 to 4 residents enrolled in the anaesthesiology training programme were included. INTERVENTION Performance was assessed using a 56-item SCT. Two resident groups were formed, and each was exposed to both quiet and noisy atmospheres during SCT assessment. Group A did the first part of the assessment (28 SCT) in a quiet atmosphere and the second part (28 SCT) in a noisy atmosphere. Group B did the same in reverse order. MAIN OUTCOME MEASURES The primary outcome of this study was residents’ performance as measured by SCT, with and without noise (mean of 100 points 95% confidence interval). RESULTS Forty-two residents were included. Residents’ performance, measured by SCT, was weaker in a noisy environment than in a quiet environment [59.0 (56.0 to 62.0) vs 62.8 (60.8 to 64.9), P = 0.04]. This difference lessened as medical training advanced, as this difference in performance in noisy vs quiet environments was not observed in year 3 and 4 residents [62.9 (59.2 to 66.5) vs 64.0 (61.9 to 66.1), P = 0.60], whereas it was higher for year 1 and 2 residents [54.8 (50.6 to 59.1) vs 61.5 (57.9 to 65.1), P = 0.02]. CONCLUSION Our study suggests that noise affects clinical reasoning of anaesthesiology residents especially junior residents when measured by SCT. This observation supports the hypothesis that noise should be prevented in operating rooms especially when junior residents are providing care.