Pain Control for Sickle Cell Crisis, a Novel Approach? A Retrospective Study.

Background and Objectives: Pain management poses a significant challenge for patients experiencing vaso-occlusive crisis (VOC) in sickle cell disease (SCD). While opioid therapy is highly effective, its efficacy can be impeded by undesirable side effects. Local regional anesthesia (LRA), involving the deposition of a perineural anesthetic, provides a nociceptive blockade, local vasodilation and reduces the inflammatory response. However, the effectiveness of this therapeutic approach for VOC in SCD patients has been rarely reported up to now. The objective of this study was to assess the effectiveness of a single-shot local regional anesthesia (LRA) in reducing pain and consequently enhancing the management of severe vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD) unresponsive to conventional analgesic therapy. Materials and Methods: We first collected consecutive episodes of VOC in critical care (ICU and emergency room) for six months in 2022 in a French University hospital with a large population of sickle cell patients in the West Indies population. We also performed a systematic review of the use of LRA in SCD. The primary outcome was defined using a numeric pain score (NPS) and/or percentage of change in opioid use. Results: We enrolled nine SCD adults (28 years old, 4 females) for ten episodes of VOC in whom LRA was used for pain management. Opioid reduction within the first 24 h post block was -75% (50 to 96%). Similarly, the NPS decreased from 9/10 pre-block to 0-1/10 post-block. Five studies, including one case series with three patients and four case reports, employed peripheral nerve blocks for regional anesthesia. In general, local regional anesthesia (LRA) exhibited a reduction in pain and symptoms, along with a decrease in opioid consumption post-procedure. Conclusions: LRA improves pain scores, reduces opioid consumption in SCD patients with refractory pain, and may mitigate opioid-related side effects while facilitating the transition to oral analgesics. Furthermore, LRA is a safe and effective procedure.

Impact of a restrictive antibiotic policy on the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an endemic region: a before-and-after, propensity-matched cohort study in a Caribbean intensive care unit.

BACKGROUND: High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection). METHODS: We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality. RESULTS: The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p < 0.01), treatment duration was shorter (5 vs. 6 days; p < 0.01), and administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs. 33.5%; p < 0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs. 19%; p < 0.01) during the RSP. The median time of being ESBL-E-free was 22 days (95% CI 16-NA) in the RSP and 18 days (95% CI 16-21) in the CSP. After propensity score weighting and adjusted analysis, the median time of being ESBL-E-free was independently associated with the RSP (hazard ratio, 0.746 [95% CI 0.575-0.968]; p = 0.02, and hazard ratio 0.751 [95% CI 0.578-0.977]; p = 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%; p < 0.01). CONCLUSIONS: Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.

Spontaneous community-acquired bacterial meningitis in adults admitted to the intensive care units in the Caribbean French West Indies: Unusual prevalence of Klebsiella pneumonia.

An unusual prevalence of Klebsiella pneumoniae (24%) was observed in 25 adults admitted to the intensive care units of two University Hospitals in the French West Indies, for spontaneous community-acquired bacterial meningitis. All tested isolates had several prominent features of hypervirulent isolates, including rmpa and iuc genes, K1 or K2 capsular serotypes.

Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity.

BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutrophil apoptosis and the resolution of inflammation. Given the numerous pathophysiologic roles of neutrophils in the acute respiratory distress syndrome (ARDS), we postulated that neutrophil GILZ expression might be induced during ARDS, to modulate the inflammatory process and participate in lung repair. METHODS: This single-center, prospective, observational cohort study took place in the surgical intensive care unit of Bichat Hospital (Paris, France) and involved 17 ARDS patients meeting the Berlin criteria at inclusion, and 14 ventilated controls without ARDS. Serial blood samples were obtained every 2 days until extubation or death (from 1 to 9 samples per patient). GILZ protein and gene expression was quantified in blood neutrophils, along with markers of inflammation (CRP, extracellular DNA) or its resolution (Annexin A1). RESULTS: Neutrophil GILZ expression was detected at the transcriptional and/or translational level in 9/17 ARDS patients (in particular 7/10 severe ARDS) and in 2/14 ventilated controls. The highest mRNA levels were observed in the most severely ill patients (p < 0.028). GILZ was expressed in about ¾ of the corticosteroid-treated patients and its expression could also occur independently of corticosteroids, suggesting that inflammatory signals may also induce neutrophil GILZ expression in vivo. CONCLUSIONS: In this pilot study, we show for the first time that blood neutrophils from patients with ARDS can express GILZ, in keeping with an anti-inflammatory and regulatory endogenous role of GILZ in humans. Contrary to some markers of inflammation or its resolution, the levels of gilz gene expression were related to ARDS severity.

Does IV Iron Induce Plasma Oxidative Stress in Critically Ill Patients? A Comparison With Healthy Volunteers.

OBJECTIVE: To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers. DESIGN: Multicenter, interventional study. SETTING: Two ICUs and one clinical research center. SUBJECTS: Anemic critically ill patients treated with IV iron and healthy volunteers. INTERVENTIONS: IV infusion of 100 mg of iron sucrose. MEASUREMENTS AND MAIN RESULTS: Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7-9.2]) (men, 25 [66%]; aged 68 yr [48-77]; Simplified Acute Physiology Score II, 48.5 [39-59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29-50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation-8α-isoprostanes, protein oxidation-advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5-12.9] vs 4.6 pmol/L [3.5-5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes. CONCLUSIONS: In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients.

Alveolar fluid in acute respiratory distress syndrome promotes fibroblast migration: role of platelet-derived growth factor pathway*.

OBJECTIVES: Fibroblast migration is an initiating step in fibroproliferation; its involvement during acute lung injury and acute respiratory distress syndrome remains poorly understood. The aims of this study were: 1) to determine whether bronchoalveolar lavage fluids from patients with acute lung injury/acute respiratory distress syndrome modulate lung fibroblast migration; 2) to assess lung fibroblast migration's clinical relevance; and 3) to evaluate the role of the platelet-derived growth factor pathway in this effect. DESIGN: Prospective cohort study. SETTING: Three intensive care units of a large tertiary referral center. PATIENTS: Ninety-three ventilated patients requiring bronchoalveolar lavage fluids were enrolled (48 with acute respiratory distress syndrome, 33 with acute lung injury, and 12 ventilated patients without acute lung injury/acute respiratory distress syndrome). INTERVENTIONS: After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28 days and clinical outcomes were recorded. Migration assays were performed by using a Transwell model; bronchoalveolar lavage fluids platelet-derived growth factor and soluble platelet-derived growth factor receptor-α were characterized by Western blot and measured by ELISA. MEASUREMENTS AND MAIN RESULTS: Most of the bronchoalveolar lavage fluids inhibited basal fibroblast migration. Bronchoalveolar lavage fluids chemotactic index increased with severity of lung injury (28% in patients without acute lung injury/acute respiratory distress syndrome and with acute lung injury vs. 91% in acute respiratory distress syndrome patients; p = .016). In acute lung injury/acute respiratory distress syndrome patients, inhibition of basal fibroblast migration by bronchoalveolar lavage fluids below 52% was independently associated with a lower 28-day mortality (odds ratio [95% confidence interval] 0.313 [0.10-0.98], p = .046). Platelet-derived growth factor-related peptides and soluble platelet-derived growth factor-Rα were detected in all bronchoalveolar lavage fluids from acute lung injury/acute respiratory distress syndrome patients. The effect of bronchoalveolar lavage fluids stimulating migration was inhibited by a specific platelet-derived growth factor receptor inhibitor (AG1296). Bronchoalveolar lavage fluids inhibiting migration reversed the effect of rh-platelet-derived growth factor-BB and reduced by 40% the binding of 125I-platelet-derived growth factor-BB to fibroblast cell surface in favor of a role for platelet-derived growth factor-sRα. CONCLUSIONS: : Together, our results suggest that during acute lung injury, fibroblast migration is modulated by bronchoalveolar lavage fluids through a platelet-derived growth factor/platelet-derived growth factor-sRα balance. Migration is associated with clinical severity and patient 28-day mortality.

Heparin-induced thrombocytopenia after cardiac surgery: an observational study of 1,722 patients.

OBJECTIVES: To assess the characteristics and prognosis of patients in whom heparin-induced thrombocytopenia (HIT) was confirmed (HIT+) among suspected HIT patients after having cardiac surgery and to assess the accuracy of two HIT scoring systems. DESIGN: An observational prospective study. SETTING: A cardiac surgery unit of a tertiary center from November 2005 to September 2007. PARTICIPANTS: Of the 1,722 patients who underwent cardiac surgery, 63 were suspected of HIT based on a platelet count <100 × 10(9)/L, a decrease in platelet count of >30%, or the occurrence of a thrombotic event. INTERVENTION: The HIT criteria were as follows: (1) the absence of another cause of thrombocytopenia, (2) positive antiplatelet factor 4 (PF4) antibodies (>0.5 optical density [OD]/mn) on enzyme-linked immunoabsorbent assay, and (3) recovery in platelet count after the discontinuation of heparin and substitution by danaparoid sodium. MEASUREMENTS AND MAIN RESULTS: HIT was confirmed in 24 patients (1.4% [0.8%-1.9%]); 23 belonged to the 984 treated by intravenous unfractionated heparin (IVUH) (2.3% IQ [1.4%-3.3%]) and 1 to the 738 treated by low-molecularweight heparin (0.14% [0.13%-0.4%]) (OD = 17.6; 95% confidence interval, 2.4-131; p < 0.0001). In the HIT+ patients compared with the unconfirmed HIT patients, thrombocytopenia occurred 7 (range, 6-9) days after surgery versus 3 (range, 3-5) days (p < 0.0001), and kinetics of platelet count showed a biphasic pattern. Six HIT+ patients (25% [7.7-42.3]) presented with an arterial thromboembolic event. Diagnosis performances of HIT scoring systems were low. CONCLUSIONS: Confirmed HIT occurred predominantly in patients treated with IVUH. The timing of thrombocytopenia and the variation pattern of the postoperative platelet count are key factors in diagnosing HIT. The overall incidence of intracardiac thrombotic events was noted to be high.

Alveolar fibrocyte percentage is an independent predictor of poor outcome in patients with acute lung injury.

OBJECTIVE: Fibrocytes are mesenchymal progenitors involved in normal and pathologic repair. The aims of this study were: 1) to quantify fibrocytes in bronchoalveolar lavage fluid from patients with or without acute lung injury and acute respiratory distress syndrome; and 2) to evaluate the prognostic value of bronchoalveolar lavage fibrocyte percentage in patients with acute lung injury and acute respiratory distress syndrome. DESIGN: Prospective cohort study. SETTING: Three intensive care units of a large tertiary referral center. PATIENTS: One hundred twenty-two ventilated patients requiring bronchoalveolar lavage were enrolled (62 acute respiratory distress syndrome, 30 acute lung injury, 30-ventilated patients without acute lung injury and acute respiratory distress syndrome). INTERVENTIONS: After bronchoalveolar lavage collection during standard care, the patients were followed up for 28 days and clinical outcome was recorded. Fibrocytes (CD45+/collagen 1+) were quantified in bronchoalveolar lavage by flow cytometry. Comparison of bronchoalveolar lavage fibrocyte percentage from patients with or without acute lung injury and acute respiratory distress syndrome was performed using a Wilcoxon test. A multivariate analysis using a Cox model was performed to study the independent predictors of survival. MEASUREMENTS AND MAIN RESULTS: Fibrocytes were detected in 90 of 92 (98%) bronchoalveolar lavages from patients with acute lung injury and acute respiratory distress syndrome. The median percentage of bronchoalveolar lavage fibrocytes was significantly higher in patients with acute lung injury and acute respiratory distress syndrome (5.0%) in comparison with ventilated control subjects (0.9%, p < .0001). After adjustment for age, comorbidity of malignancy, and severity of illness, a bronchoalveolar lavage fibrocyte percentage >6% was independently associated with a higher 28-day mortality in patients with acute lung injury and acute respiratory distress syndrome (hazard ratio [95% confidence interval] 6.15 [2.78-13.64], p ≤ .0001). Addition of bronchoalveolar lavage fibrocyte percentage in a clinical model predicting mortality in patients with acute lung injury and acute respiratory distress syndrome improved global fit and discriminatory capacity (c-statistic, 0.78-0.85; p = .007). CONCLUSIONS: Fibrocytes are detectable in bronchoalveolar lavage during acute lung injury and acute respiratory distress syndrome. A bronchoalveolar lavage fibrocyte percentage >6% provides an additive prognostic value to clinical predictors and may be useful to identify patients with acute lung injury and acute respiratory distress syndrome at highest risk of an adverse outcome.

Preoperative iron deficiency increases transfusion requirements and fatigue in cardiac surgery patients: a prospective observational study.

BACKGROUND: Iron deficiency is the commonest cause of anaemia. It is apparent preoperatively in cardiac surgery patients and may influence transfusion requirements. In addition, iron deficiency per se is associated with fatigue. OBJECTIVE: To determine the prevalence of preoperative iron deficiency and its association with perioperative anaemia, blood transfusions and fatigue in cardiac surgery patients. SETTING: Academic hospital in Paris, France. PATIENTS: One hundred consecutive patients without known iron disorder and scheduled for cardiac surgery were prospectively included in this observational study. INTERVENTION: No intervention was performed. MEASUREMENTS: A biological iron profile (transferrin saturation, ferritin, soluble transferrin receptor and C-reactive protein) was assessed on the day of surgery. Diagnosis of iron deficiency was defined using a previously published algorithm. Patient fatigue was assessed before surgery and 1 week afterwards (day 7) using the Multidimensional Fatigue Inventory (MFI-20) score that quotes five distinctive dimensions of fatigue. RESULTS: Thirty-seven out of 100 patients were diagnosed with iron deficiency. These patients were younger [median (first-third quartile) 63 (43-70) vs. 70 (59-77) years (P = 0.004)], and more often female (51 vs. 21%, P = 0.003), than no iron deficiency patients. Preoperative iron deficiency was associated with lower preoperative haemoglobin levels (P = 0.006) and higher perioperative transfusion rates during the first week (62 vs. 35%, P = 0.019). Patients with iron deficiency but without anaemia (n = 25) received more packed red blood cells units than those without iron deficiency or anaemia (n = 50) [2 (0-2) vs. 0 (0-0) units, P < 0.05). Preoperative iron deficiency was associated with higher score of physical fatigue on day 7 (P = 0.01). CONCLUSION: Preoperative iron deficiency is frequent among cardiac surgery patients and is associated with anaemia, higher transfusion requirements and postoperative fatigue.

Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study.

INTRODUCTION: Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting. METHODS: We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive. RESULTS: During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion. CONCLUSION: Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.