Neuromuscular blocking agents in patients with acute respiratory distress syndrome: a summary of the current evidence from three randomized controlled trials

Medical Intensive Care Unit, ABC Medical School (FMABC), Av, Lauro Gomes, Santo André, 2000, Brazil. .
Annals of Intensive Care (Impact Factor: 3.31). 07/2012; 2(1):33. DOI: 10.1186/2110-5820-2-33
Source: PubMed


Acute respiratory distress syndrome (ARDS) is a potentially fatal disease with high mortality. Our aim was to summarize the current evidence for use of neuromuscular blocking agents (NMBA) in the early phase of ARDS.
Systematic review and meta-analysis of publications between 1966 and 2012. The Medline and CENTRAL databases were searched for studies on NMBA in patients with ARDS. The meta-analysis was limited to: 1) randomized controlled trials; 02) adult human patients with ARDS or acute lung injury; and 03) use of any NMBA in one arm of the study compared with another arm without NMBA. The outcomes assessed were: overall mortality, ventilator-free days, time of mechanical ventilation, adverse events, changes in gas exchange, in ventilator settings, and in respiratory mechanics.
Three randomized controlled trials covering 431 participants were included. Patients treated with NMBA showed less mortality (Risk ratio, 0.71 [95 % CI, 0.55 - 0.90]; number needed to treat, 1 - 7), more ventilator free days at day 28 (p = 0.020), higher PaO2 to FiO2 ratios (p = 0.004), and less barotraumas (p = 0.030). The incidence of critical illness neuromyopathy was similar (p = 0.540).
The use of NMBA in the early phase of ARDS improves outcome.

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Available from: Ary Serpa Neto, Feb 20, 2015
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    • "It is noteworthy that the beneficial effect of cisatracurium on mortality was limited to the patients presenting a PaO2 to FiO2 ratio of less than 120 mmHg. These results were recently confirmed in a meta-analysis [51]. The observed improvements in mortality and gas exchange raise the question of the mechanisms involved. "
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    ABSTRACT: Pharmacological interventions are commonly considered in acute respiratory distress syndrome (ARDS) patients. Inhaled nitric oxide (iNO) and neuromuscular blockers (NMBs) are used in patients with severe hypoxemia. No outcome benefit has been observed with the systematic use of iNO. However, a sometimes important improvement in oxygenation can occur shortly after starting administration. Therefore, its ease of use and its good tolerance justify iNO optionally combined with almitirne as a rescue therapy on a trial basis. Recent data from the literature support the use of a 48-h infusion of NMBs in patients with a PaO2 to FiO2 ratio <120 mmHg. No strong evidence exists on the increase of ICU-acquired paresis after a short course of NMBs. Fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, patients with hemodynamic failure must receive early and adapted fluid resuscitation. Liberal and conservative fluid strategies therefore are complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, albumin treatment does not appear to be justified for limitation of pulmonary edema and respiratory morbidity. Aerosolized beta2-agonists do not improve outcome in patients with ARDS and one study strongly suggests that intravenous salbutamol may worsen outcome in those patients. The early use of high doses of corticosteroids for the prevention of ARDS in septic shock patients or in patients with confirmed ARDS significantly reduced the duration of mechanical ventilation but had no effect or even increased mortality. In patients with persistent ARDS after 7 to 28 days, a randomized trial showed no reduction in mortality with moderate doses of corticosteroids but an increased PaO2 to FiO2 ratio and thoracopulmonary compliance were found, as well as shorter durations of mechanical ventilation and of ICU stay. Conflicting data exist on the interest of low doses of corticosteroids (200 mg/day of hydrocortisone) in ARDS patients. In the context of a persistent ARDS with histological proof of fibroproliferation, a corticosteroid treatment with a progressive decrease of doses can be proposed.
    Annals of Intensive Care 07/2013; 3(1):20. DOI:10.1186/2110-5820-3-20 · 3.31 Impact Factor
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    • "The present systematic review builds on the similar findings of a recent review by Neto et al. [26]. We analyzed important new and previously unpublished data about hospital mortality, an outcome that carries more weight in clinical decision making and clinical-practice guidelines. "
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    ABSTRACT: Introduction Randomized trials investigating neuromuscular blocking agents in adult acute respiratory distress syndrome (ARDS) have been inconclusive about effects on mortality, which is very high in this population. Uncertainty also exists about the associated risk of ICU-acquired weakness. Methods We conducted a systematic review and meta-analysis. We searched the Cochrane (Central) database, MEDLINE, EMBASE, ACP Journal Club, and clinical trial registries for randomized trials investigating survival effects of neuromuscular blocking agents in adults with ARDS. Two independent reviewers abstracted data and assessed methodologic quality. Primary study investigators provided additional unpublished data. Results Three trials (431 patients; 20 centers; all from the same research group in France) met inclusion criteria for this review. All trials assessed 48-hour infusions of cisatracurium besylate. Short-term infusion of cisatracurium besylate was associated with lower hospital mortality (RR, 0.72; 95% CI, 0.58 to 0.91; P = 0.005; I2 = 0). This finding was robust on sensitivity analyses. Neuromuscular blockade was also associated with lower risk of barotrauma (RR, 0.43; 95% CI, 0.20 to 0.90; P = 0.02; I2 = 0), but had no effect on the duration of mechanical ventilation among survivors (MD, 0.25 days; 95% CI, 5.48 to 5.99; P = 0.93; I2 = 49%), or the risk of ICU-acquired weakness (RR, 1.08; 95% CI, 0.83 to 1.41; P = 0.57; I2 = 0). Primary studies lacked protracted measurements of weakness. Conclusions Short-term infusion of cisatracurium besylate reduces hospital mortality and barotrauma and does not appear to increase ICU-acquired weakness for critically ill adults with ARDS.
    Critical care (London, England) 03/2013; 17(2):R43. DOI:10.1186/cc12557 · 4.48 Impact Factor
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    ABSTRACT: Le traitement du syndrome de détresse respiratoire aiguë (SDRA) fait l’objet, depuis longtemps, de nombreux travaux de recherche, sources d’intenses controverses. L’actualité dans ce domaine est riche et très variée. Les effets sur le pronostic du SDRA de traitements couramment utilisés ont pu récemment être précisés. Par exemple, il a été démontré que le décubitus ventral, qui n’avait montré jusqu’ici qu’une amélioration de l’hématose sans effet sur la mortalité, pouvait améliorer la survie des patients les plus sévèrement hypoxémiques. L’utilisation de curares à la phase aiguë du SDRA a également montré un effet bénéfique sur la survie. La place de l’oxygénation par membrane extracorporelle (ECMO) dans la prise en charge du SDRA reste à définir, malgré des données laissant supposer une possible efficacité. Par ailleurs, une voie de recherche s’est ouverte avec l’avènement des thérapies cellulaires. En effet, les cellules souches mésenchymateuses semblent pouvoir à la fois favoriser la réparation de l’épithélium alvéolaire et prévenir des risques infectieux. Leur efficacité dans les modèles animaux de SDRA demande à être confirmée par des études chez l’homme. Enfin, certaines thérapeutiques prometteuses ont montré leurs limites. C’est le cas notamment des agonistes béta-adrénergiques et des acides gras oméga-3 qui ont montré leur inefficacité dans plusieurs grandes études cliniques sur le SDRA.
    Réanimation 01/2012; 22(2). DOI:10.1007/s13546-012-0566-6
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