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LetterCorrespondence

Neuromuscular Blocking Agents for ARDS: Firm Evidence for ICU Mortality but Not for Long-Term Mortality

Maria Vargas and Giuseppe Servillo
Respiratory Care May 2021, 66 (5) 887-888; DOI: https://doi.org/10.4187/respcare.08926
Maria Vargas
Department of Neurosciences Reproductive and Odontostomatological Sciences University of Naples “Federico II” Naples, Italy
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  • For correspondence: [email protected]
Giuseppe Servillo
Department of Neurosciences Reproductive and Odontostomatological Sciences University of Naples “Federico II” Naples, Italy
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To the Editor:

Optimal ventilation and weaning strategies in patients with ARDS should be carefully assessed.1,2 We read with interest the systematic review by Torbic et al,3 which sought to evaluate mortality when using neuromuscular blocking agents (NMBAs) in early, moderate-to severe ARDS compared to usual care or placebo. The authors included 6 randomized controlled trials (RCTs), but only 2 of the 6 RCTs had a low risk of bias.3 We applaud the effort of the authors, but we have some concerns.

First, the fragility index, which is an intuitive measure of the robustness of RCTs, was introduced in critical care medicine and has been utilized in different systematic reviews.4–6 The fragility index is achieved by using a two-by-two contingency table and P value calculated with the Fisher exact test.4 When we calculated the fragility index of RCTs included in the systematic review by Torbic et al,3 we found that all of the included studies had a fragility index of zero (P > .05). According to this, the RCTs evaluating mortality when using NMBAs in early and moderate-to severe ARDS are very fragile and the evidence from these studies is very weak.

Second, the authors reported that the use of NMBAs reduced the risk for ICU and 21–28-d mortality but not 90-d mortality. According to these results, we further performed a trial sequential analysis to evaluate whether this meta-analysis had sufficient statistical power to detect or reject the intervention effects.7 For ICU mortality, the 95% CI adjusted with the trial sequential analysis ranged from 0.41 to 0.8 and indicated that 431 of 433 subjects were enough to reach the required information size. According to this, firm evidence existed in favor of the use of the NMBAs to reduce ICU mortality. For 21–28-d mortality, the trial sequential analysis was not conclusive because the inclusion of 1,485 subjects was far short of the required sample size of 18,618 subjects to ensure conclusive evidence. By evaluating the robustness of RCTs and trial sequential analysis, our analysis supports the reported effects of NMBAs to reduce ICU mortality but not the 21–28-d and 90-d mortality. We believe we would need 18,470 subjects with moderate-to-severe ARDS to be treated with NMBAs to achieve firm evidence on long-term mortality.

Footnotes

  • Correspondence: Maria Vargas MD, Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Via Pansini 80100, Naples, Italy. E-mail: vargas.maria82{at}gmail.com
  • The authors have disclosed no conflicts of interest.

  • Copyright © 2021 by Daedalus Enterprises

References

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    1. Pelosi P,
    2. Vargas M
    . Mechanical ventilation and intraabdominal hypertension: ‘beyond good and evil’. Crit Care 2012;16(6):187.
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    1. Manganelli F,
    2. Vargas M,
    3. Iovino A,
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    . Brainstem involvement and respiratory failure in COVID-19. Neurol Sci 2020;41(7):1663–1665.
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  3. 3.↵
    1. Torbic H,
    2. Krishnan S,
    3. Harnegie MP,
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    . Neuromuscular blocking agents for ARDS: a systematic review and meta-analysis. Respir Care 2021;66(1):120–128.
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  4. 4.↵
    1. Vargas M,
    2. Servillo G
    . The end of corticosteroid in sepsis: fragile results from fragile trials. Crit Care Med 2018;46(12):e1228
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    1. Vargas M,
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    . Liberal versus conservative oxygen therapy in critically ill patients: using the fragility index to determine robust results. Crit Care 2019;23(1):132
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    1. Vargas M,
    2. Buonanno P,
    3. Iacovazzo C,
    4. Servillo G
    . Epinephrine for out of hospital cardiac arrest: a systematic review and meta-analysis of randomized controlled trials [published correction appears in Resuscitation. 2019 Dec;145:R1]. Resuscitation 2019;136:54–56.
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    . Trial sequential analysis in systematic reviews with meta-analysis. BMC Med Res Methodol 2017;17(1):39.
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Respiratory Care: 66 (5)
Respiratory Care
Vol. 66, Issue 5
1 May 2021
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Neuromuscular Blocking Agents for ARDS: Firm Evidence for ICU Mortality but Not for Long-Term Mortality
Maria Vargas, Giuseppe Servillo
Respiratory Care May 2021, 66 (5) 887-888; DOI: 10.4187/respcare.08926

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Neuromuscular Blocking Agents for ARDS: Firm Evidence for ICU Mortality but Not for Long-Term Mortality
Maria Vargas, Giuseppe Servillo
Respiratory Care May 2021, 66 (5) 887-888; DOI: 10.4187/respcare.08926
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