Jérôme Cecchini

Outcomes of Adult Patients With Sickle Cell Disease Admitted to the Icu: A Case Series*

Objective:Sickle cell disease is associated with a decreased life expectancy, half of the deaths occurring in the ICU. We aimed to describe the characteristics of sickle cell disease patients admitted to ICU and to identify early predictors of a complicated outcome, defined as the need for vital support or death. Design:Retrospective observational cohort study of sickle cell disease patients over a 6-year period. Setting:ICU of a French teaching hospital and sickle cell disease referral center. Patients:Hundred thirty-eight ICU admissions in 119 sickle cell disease patients. Interventions:None. Measurements and Main Results:ICU admission was mainly indicated for sickle cell disease–related events, especially acute chest syndrome. Mechanical ventilation, vasoactive drugs, and renal replacement therapy were administered to 25 (18%), 10 (7%), and 10 (7%) episodes, respectively. The complicated outcome group (n = 28; 20%) was characterized by a more aggressive acute disease within the 48 hours preceding ICU admission, with a higher respiratory rate, a more frequent acute kidney injury, and a more sustained drop of hemoglobin (all p < 0.01). All nine deaths (7%) were sickle cell disease related. None of the sickle cell disease baseline characteristics predicted accurately a complicated outcome. In multivariate analysis, hemoglobin less than or equal to 7.8 g/dL (odds ratio, 3.6; 95% CI, 1.1–11.9), respiratory rate more than or equal to 32 cycles/min (odds ratio, 5.6; 95% CI, 1.8–17.2), and acute kidney injury on ICU admission (odds ratio, 11.5; 95% CI, 2.5–52.6) were independently associated with a complicated outcome. Conclusions:Sickle cell disease patients are at high risk of complications when admitted to the ICU. A sustained drop of hemoglobin, acute respiratory distress, and kidney injury at admission are strong predictors of a complicated outcome.

Increased diaphragmatic contribution to inspiratory effort during neurally adjusted ventilatory assistance versus pressure support: an electromyographic study.

Background:Neurally adjusted ventilatory assist (NAVA), regulated exclusively by the electromyographic activity (EA) of the diaphragm (EAdi), could affect the distribution of neural drive to the various inspiratory muscles. The objective of this study was to compare EAdi, EA of the scalene (EAscal), and EA of the alae nasi (EAan), according to the ventilatory mode and assist level in 12 mechanically ventilated patients. Methods:Seven assist levels of pressure support ventilation (PSV) and NAVA were sequentially applied. EAdi, EAscal, and EAan were quantified and expressed as a percentage of their maximum values. The relative contributions of extradiaphragmatic muscles to inspiratory efforts were assessed by calculating EAscal/EAdi and EAan/EAdi ratios. Three assist levels for each of the two ventilatory modes that resulted in EAdi values of 80 to 100%, 60 to 80%, and 40 to 60% were assigned to three groups (N1, N2, and N3). Results are expressed as median and interquartile range. Results:EA of inspiratory muscles decreased during PSV and NAVA (P < 0.0001). Although EAdi remained constant within groups (P = 0.9), EAscal was reduced during NAVA compared with PSV in N1 and N3 (65% [62 to 64] and 27% [18 to 34] in NAVA vs. 90% [81 to 100] and 49% [40 to 55] in PSV, P = 0.007). Altogether, EAscal/EAdi and EAan/EAdi ratios were lower in NAVA than PSV (0.7 [0.6 to 0.7] and 0.7 [0.6 to 0.8] in NAVA vs. 0.9 [0.8 to 1.1] and 0.9 [0.7 to 1.1] in PSV, P < 0.05). Conclusions:NAVA and PSV both reduced extradiaphragmatic inspiratory muscle activity, in proportion to the level of assistance. Compared with PSV, NAVA resulted in a predominant contribution of the diaphragm to inspiratory effort.

Pulmonary Vascular Dysfunction and Cor Pulmonale During Acute Respiratory Distress Syndrome in Sicklers.

Background: Acute chest syndrome (ACS) is the most common cause of death among sickle cell disease (SCD) adult patients. Pulmonary vascular dysfunction (PVD) and acute cor pulmonale (ACP) are common during acute respiratory distress syndrome (ARDS) and their prevalence may be even more important during ARDS related to ACS (ACS-ARDS). The objective of this study was to evaluate the prevalence and prognosis of PVD and ACP during ACS-ARDS. Patients and Methods: This was a retrospective analysis over a 10-year period of patients with moderate-to-severe ARDS. PVD and ACP were assessed by echocardiography. ARDS episodes were assigned to ACS-ARDS or nonACS-ARDS group according to whether the clinical insult was ACS or not, respectively. To evaluate independent factors associated with ACP, significant univariable risk factors were examined using logistic regression and propensity score analyses. Results: A total of 362 patients were analyzed, including 24 ACS-ARDS. PVD and ACP were identified, respectively, in 24 (100%) and 20 (83%) ACS-ARDS patients, as compared with 204 (60%) and 68 (20%) nonACS-ARDS patients (P < 0.0001). The mortality did not differ between ACS-ARDS and nonACS-ARDS patients. Both the crude (odds ratio [OR], 19.9; 95% confidence interval [CI], 6.6–60; P < 0.0001), multivariable adjustment (OR, 27.4; 95% CI, 8.2–91.5; P < 0.001), and propensity-matched (OR, 11.7; 95% CI, 1.2–110.8; P = 0.03) analyses found a significant association between ACS-ARDS and ACP. Conclusions: All SCD patients presenting with moderate-to-severe ARDS as a consequence of ACS experienced PVD and more than 80% of them exhibited ACP. These results suggest a predominant role for PVD in the pathogenesis of severe forms of ACS.

Fatal toxic epidermal necrolysis in a patient on teriflunomide treatment for relapsing multiple sclerosis.

We report a case of toxic epidermal necrolysis in a 46-year-old woman on teriflunomide treatment. Such a severe adverse cutaneous drug reaction with this new therapy for relapsing forms of multiple sclerosis should be early recognized in order to ensure the rapid withdrawal of the drug.

Sickle cell disease in the ICU.

Purpose of reviewThe review focuses on severe acute vaso-occlusive manifestations of sickle cell disease leading adult patients to the ICU. Recent findingsCareful consideration should be paid to look for pulmonary vascular dysfunction and acute kidney injury, because of their prognostic role during acute vaso-occlusive manifestations. Alloimmunization and delayed haemolytic transfusion reactions are emerging complications that should be thought to be diagnosed, as they may imply a conservative management. The life-threatening complication raises the question about the indications of blood transfusion therapy for acute sickle cell disease complications, no randomized controlled trials being available to assess the role of blood transfusion in the acute setting. SummaryAcute vaso-occlusive episodes are characterized by an unpredictable course that needs for vigilance for everyone, and justifies ICU or intermediate care unit admission to allow close monitoring, and supportive treatment in a timely fashion.

Life-threatening endobronchial myiasis

Dear Editor, A 47-year-old homeless man was admitted to our intensive care unit (ICU) for septic shock as a complication of an infected diabetic foot ulcer. His previous medical history included a type 2 diabetes mellitus treated with metformine and gliclazide. The patient was found comatose and covered with flies in a shelter on the shore of a river. The prehospital emergency care personnel performed bag-valve mask ventilation with 100% oxygen and rapid sequence induction (intravenous etomidate 20 mg and succinylcholine 100 mg), which enabled successful tracheal intubation by a physician upon the first attempt. The patient was then mechanically ventilated and transferred to our ICU. Upon admission, the patient had a Glasgow coma scale score of 3, blood pressure of 82/45 mmHg, body temperature of 33.7 C, heart rate at 75/min, and arterial oxygen saturation of 90% with an inspired oxygen fraction (FiO2) of 1. A large necrotic wound on the right foot, in which numerous live larvae were found, was noted. Laboratory tests showed lactic acidosis (pH 6.96, blood lactates [15 mmol/L) and acute renal failure (blood urea 42 mmol/L, creatinine 465 lmol/L); the hemoglobin level was 8.3 g/dL and the white blood cell count was 16,300/mm. No abnormalites were found on the chest X-ray. Arterial blood gases obtained after hemodynamic stabilization was achieved (i.e., 1 h after ICU admission) showed normal oxygenation (PaO2/FiO2 ratio 523 mmHg at FiO2 1). Toxicological screening tests were negative. The conclusion was drawn that the comatose state was due to a profound hemodynamic impairment with severe lactic acidosis. Antibiotic therapy and surgical debridement of the wound were performed. Optic microscopy examination identified the collected larvae as Lucilia sericata. Both blood cultures and wound swabs grew methicillin-sensitive Staphylococcus aureus. On the second day, larvae were seen leaking from both of his nostrils, and nasal cavity infestation was confirmed by endoscopy (Fig. 1). A cranial computed tomography (CT) scan revealed there was neither brain nor sinus involvement. Management consisted of mechanical removal of the larvae and a single dose of ivermectine. On the third day of mechanical ventilation, a ventilator-generated pressure alarm revealed a sudden increase in peak airway pressures that partially impeded tidal volume delivery to the patient. Tracheal suctioning was performed immediately and allowed for the extraction of numerous larvae obstructing the endotracheal tube. Flexible bronchoscopy showed the presence of approximately 30 larvae in the left bronchial tree that were then extracted (Fig. 1). Five larvae were removed during another bronchoscopy the following day. Protective measures, including insecticide spray and patient isolation, were implemented to avoid nosocomial transmission. The patient was kept mechanically ventilated in the FiO2 0.3 state because of protracted coma. He finally recovered and was successfully extubated on day 8 and discharged from the ICU on day 11. Myiasis is a parasitic infestation of live human or vertebrate animal tissues or cavities caused by dipterous larvae (maggots). L. sericata, known as the green bottle blowfly, is a facultative ectoparasite. In humans, L. sericata has been involved in nasal [1], wound [2], gastric, tracheostomy [3], and nosocomial [4, 5] infestations. In this case, predisposing factors for myiasis included a necrotizing wound and a protracted coma with lack of the cough reflex. Whether upper airway manipulations (i.e., bag-valve mask ventilation and laryngoscopy) during endotracheal intubation might have favored the

Profound underdosing of β-lactams in patients with sickle-cell disease

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A clinical risk score for pulmonary artery thrombosis during acute chest syndrome in adult patients with sickle cell disease.

Pulmonary artery thrombosis (PAT) is involved in lung vascular dysfunction during acute chest syndrome (ACS) complicating sickle cell disease (SCD). No clinical score is available to identify patients eligible for multi‐detector computed tomography (MDCT) angiography during ACS. This retrospective study aimed to develop a risk score for PAT during ACS (PAT‐ACS risk score). Patients with SCD were investigated by MDCT during ACS. A logistic regression was performed to determine independent risks factors for PAT and to build the PAT‐ACS risk score. A total of 43 episodes (11·9%) of PAT were diagnosed in 361 episodes of ACS. Multivariate analysis identified four risk factors, which were included in the PAT‐ACS risk score: a baseline haemoglobin >82 g/l, the lack of a triggering factor for ACS, a platelet count >440 × 109/l and a PaCO2 <38 mmHg at ACS diagnosis. The area under the receiver operating characteristic curve for the PAT‐ACS risk score was 0·74 (95% confidence interval [CI] 0·69–0·79) and differed from that of the revised Geneva score (0·63 (95% CI 0·58–0·69); P = 0·04). The negative predictive value of a PAT‐ACS risk score ≥2 was 94%. In conclusion, we propose a simple clinical risk score to identify SCD patients at high risk of PAT during ACS.

Telomere attrition in sickle cell anemia

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