Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

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.

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality. Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P = 0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P = 0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P = 0.02]. Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.

Corrective effect of diaphragm pacing on the decrease in cardiac output induced by positive pressure mechanical ventilation in anesthetized sheep.

Positive pressure ventilation (PPV) is a fundamental life support measure, but it decreases cardiac output (CO). Diaphragmatic contractions produce negative intrathoracic and positive abdominal pressures, promoting splanchnic venous return. We hypothesized that: 1) diaphragm pacing alone could produce adequate ventilation without decreasing CO; 2) diaphragm pacing on top of PPV could improve CO. Of 11 anesthetized and mechanically ventilated ewes (39.6±5.9kg), 3 were discarded from analysis because of hemodynamic instability during the experiment, and 8 retained for analysis. Phrenic stimulation electrodes were inserted in the diaphragm (implanted phrenic nerve stimulation, iPS). CO was measured by the thermodilution technique (pulmonary artery catheter). CO during end-expiratory apnea served as reference. Median CO was 9.77 [6.25-11.25] lmin-1 during end-expiratory apnea, 8.25 [5.06-9.25] lmin-1 during "PPV" (-15%) (p<0.05), 9.19 [5.60-10.19] lmin-1 during "PPV-iPS" (NS vs apnea) and 9.37 [6.12-10.48] lmin-1 during "iPS" (NS vs. apnea). iPS-driven ventilation was comparable to its PPV counterpart (median 92% [74-97], NS). Diaphragm pacing alone can produce adequate ventilation without reducing CO. Superimposed onto PPV, diaphragm pacing can reduce the PPV-induced decrease in CO.

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.

Sickle cell disease in the ICU.

PURPOSE OF REVIEW: The review focuses on severe acute vaso-occlusive manifestations of sickle cell disease leading adult patients to the ICU. RECENT FINDINGS: Careful 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. SUMMARY: Acute 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.

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.

Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction.

INTRODUCTION: The objective was to compare the impact of three assistance levels of different modes of mechanical ventilation; neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), and pressure support ventilation (PSV) on major features of patient-ventilator interaction. METHODS: PSV, NAVA, and PAV were set to obtain a tidal volume (VT) of 6 to 8 ml/kg (PSV100, NAVA100, and PAV100) in 16 intubated patients. Assistance was further decreased by 50% (PSV50, NAVA50, and PAV50) and then increased by 50% (PSV150, NAVA150, and PAV150) with all modes. The three modes were randomly applied. Airway flow and pressure, electrical activity of the diaphragm (EAdi), and blood gases were measured. VT, peak EAdi, coefficient of variation of VT and EAdi, and the prevalence of the main patient-ventilator asynchronies were calculated. RESULTS: PAV and NAVA prevented the increase of VT with high levels of assistance (median 7.4 (interquartile range (IQR) 5.7 to 10.1) ml/kg and 7.4 (IQR, 5.9 to 10.5) ml/kg with PAV150 and NAVA150 versus 10.9 (IQR, 8.9 to 12.0) ml/kg with PSV150, P <0.05). EAdi was higher with PAV than with PSV at level100 and level150. The coefficient of variation of VT was higher with NAVA and PAV (19 (IQR, 14 to 31)% and 21 (IQR 16 to 29)% with NAVA100 and PAV100 versus 13 (IQR 11 to 18)% with PSV100, P <0.05). The prevalence of ineffective triggering was lower with PAV and NAVA than with PSV (P <0.05), but the prevalence of double triggering was higher with NAVA than with PAV and PSV (P <0.05). CONCLUSIONS: PAV and NAVA both prevent overdistention, improve neuromechanical coupling, restore the variability of the breathing pattern, and decrease patient-ventilator asynchrony in fairly similar ways compared with PSV. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT02056093 . Registered 18 December 2013.

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.

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.

Cardiac arrest and succinylcholine-induced hyperkalemia in a patient with a triton tumor.

We report a case of succinylcholine-induced hyperkalemia in a patient with a mediastinal triton tumor, which is characterized by a rhabdomyosarcomatous differentiation. Caution should be taken with succinylcholine use in patients presenting with a rhabdomyosarcomatous tumor or with a tumor of unknown cell type when histopathological diagnosis is not available.