A tailored multicomponent program to reduce discomfort in critically ill patients: a cluster-randomized controlled trial

Purpose

Critically ill patients are exposed to stressful conditions and experience several discomforts. The primary objective was to assess whether a tailored multicomponent program is effective for reducing self-perceived discomfort.

Methods

In a cluster-randomized two-arm parallel trial, 34 French adult intensive care units (ICUs) without planned interventions to reduce discomfort were randomized, 17 to the arm including a 6-month period of program implementation followed by a 6-month period without the program (experimental group), and 17 to the arm with an inversed sequence (control group). The tailored multicomponent program consisted of assessment of ICU-related self-perceived discomforts, immediate and monthly feedback to healthcare teams, and site-specific tailored interventions. The primary outcome was the overall discomfort score derived from the 16-item IPREA questionnaire (0, minimal, 100, maximal overall discomfort) and the secondary outcomes were the discomfort scores of each IPREA item. IPREA was administered on the day of ICU discharge with a considered timeframe from the ICU admission until ICU discharge.

Results

During a 1-month assessment period, 398 and 360 patients were included in the experimental group and the control group, respectively. The difference (experimental minus control) of the overall discomfort score between groups was ? 7.00 (95% CI ? 9.89 to ? 4.11, p < 0.001). After adjustment (age, gender, ICU duration, mechanical ventilation duration, and type of admission), the program effect was still positive for the overall discomfort score (difference ? 6.35, SE 1.23, p < 0.001) and for 12 out of 16 items.

Conclusions

This tailored multicomponent program decreased self-perceived discomfort in adult critically ill patients. Trial Registration: Clinicaltrials.gov Identifier NCT02442934.

     

Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG)

Although much progress has been made in understanding the pathogenesis of Alzheimer's disease (AD), the current therapeutic approaches are merely symptomatic, intended for the treatment of cognitive symptoms, such as disturbances in memory and perception. Novel promising strategies suggest the use of anti-inflammatory drugs, antioxidants including natural occurring plant flavonoids, iron-complexing molecules, neurotrophic factor delivery, inhibitors of the amyloid-beta protein precursor processing secretases, gamma and beta, that generate amyloid-beta peptides and the interference with lipid and cholesterol metabolism. Human epidemiological and new animal data suggest that tea drinking may decrease the incidence of dementia, AD and Parkinson's disease. In particular, its main catechin polyphenol constituent (-)-epigallocatechin-3-gallate (EGCG) has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders. This review provides a detailed overview on the multimodal activities of green tea polyphenols with emphasis on their iron chelating, neurorescue/neuroregenerative and mitochondrial stabilization action.     

Permissive Hypercapnia with and without Expiratory Washout in Patients with Severe Acute Respiratory Distress Syndrome

Background: Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia.

Methods: Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2 O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia.

Results: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO sub 2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2 O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l [center dot] min sup -1 [center dot] m sup -2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01).     

Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients

IntroductionIn a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.MethodsWe looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10⁻⁵ digit with no replacement).ResultsA total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.ConclusionIn a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.

Trial registration

Clinicaltrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01002482","term_id":"NCT01002482"}}NCT01002482. Registered 26 October 2009.     

Pulmonary embolism with overflow pulmonary edema

We report the case of a patient with a febrile acute respiratory failure associated with alveolar opacities localized in the left upper lobe on chest-X-ray. Diagnosis was related to pulmonary embolism with overflow pulmonary edema. Complete recovery was obtained after mechanical ventilation, anticoagulation and a short course of intra venous dobutamine.     

Expiratory washout versus optimization of mechanical ventilation during permissive hypercapnia in patients with severe acute respiratory distress syndrome.

The aim of this study was to compare three ventilatory techniques for reducing PaCO2 in patients with severe acute respiratory distress syndrome treated with permissive hypercapnia: (1) expiratory washout alone at a flow of 15 L/min, (2) optimized mechanical ventilation defined as an increase in the respiratory frequency to the maximal rate possible without development of intrinsic positive end- expiratory pressure (PEEP) combined with a reduction of the instrumental dead space, and (3) the combination of both methods. Tidal volume was set according to the pressure-volume curve in order to obtain an inspiratory plateau airway pressure equal to the upper inflection point minus 2 cm H2O after setting the PEEP at 2 cm H2O above the lower inflection point and was kept constant throughout the study. The three modalities were compared at the same inspiratory plateau airway pressure through an adjustment of the extrinsic PEEP. During conventional mechanical ventilation using a respiratory frequency of 18 breaths/min, respiratory acidosis (PaCO2 = 84 +/- 24 mm Hg and pH = 7.21 +/- 0.12) was observed. Expiratory washout and optimized mechanical ventilation (respiratory frequency of 30 +/- 4 breaths/min) had similar effects on CO2 elimination (DeltaPaCO2 = -28 +/- 11% versus -27 +/- 12%). A further decrease in PaCO2 was observed when both methods were combined (DeltaPaCO2 = -46 +/- 7%). Extrinsic PEEP had to be reduced by 5.3 +/- 2.1 cm H2O during expiratory washout and by 7.3 +/- 1.3 cm H2O during the combination of the two modes, whereas it remained unchanged during optimized mechanical ventilation alone. In conclusion, increasing respiratory rate and reducing instrumental dead space during conventional mechanical ventilation is as efficient as expiratory washout to reduce PaCO2 in patients with severe ARDS and permissive hypercapnia. When used in combination, both techniques have additive effects and result in PaCO2 levels close to normal values.     

Candida albicans fungemia with pulmonary localization treated with fluconazole. A case report

We report a case of Candida albicans fungemia complicated by a pulmonary localization in a non-immunocompromised patient. Complete recovery was obtained after a long course of high-dose fluconazole in spite of in vitro resistance of the Candida to fluconazole. The usefulness of fluconazole therapy, the best dosage regimen and the in vitro and in vivo correlations are discussed.