November 30, 2020

An article review from the ESICM Journal Review Club

New rapid practice guideline providing continuous up-to-date clinical recommendations for the use of NMBA in patients with ARDS

This paper is an Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) – a document producing reliable clinical practice recommendations on topical questions related to critical illness diagnosis and/or management. The guideline was produced by a panel consisting of 20 international experts and two patient representatives.

The ICM-RPG aimed to formulate evidence-based guidance for the use of neuromuscular blocking agents (NMBA) in adult patients with Acute Respiratory Distress Syndrome (ARDS).

The clinical practice guidelines were published by several professional Societies, although they did not strongly recommend the use of NMBA infusion in patients with moderate to severe ARDS.

These recommendations are based on the results of three randomised controlled trials (RCT) enrolling 431 patients.

The recommendations of these clinical practical guidelines were, however, questioned in the ROSE trial, published in the New England Journal of Medicine in 2019.   In this large RCT, no benefit was shown for either an infusion of cisatracurium, or intermittent boluses. This potentially changing clinical practice trial was the reason to conduct an ICM-RPG.

The question to be answered by the panel was if NMBA infusion is recommended in preference to on-demand boluses in mechanically-ventilated adults with ARDS.

The panel performed a systematic review and meta-analysis using the Population, Intervention, Comparator and Outcomes (PICO) format to answer the question. The outcomes were listed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The panel composed seven crucial outcomes.

A total of 7 RCT were used, enrolling 1,598 patients. The overall certainty of the evidence for each outcome was regarded as low.

The panel concluded with one recommendation and two suggestions, all with low certainty of evidence:

  1. It advised against the routine use of NMBA infusion before optimising mechanical ventilation and assessing ARDS severity
  2. It suggested not using NMBA infusion if lighter sedation is tolerated. If NMBA is required to facilitate lung-protective ventilation, intermittent boluses with judiciously deep sedation is suggested.
  3. In patients requiring continuous deep sedation and NMBA to facilitate lung-protective ventilation and prone positioning, it suggested using NMBA infusion for up to 48 hours.

It is mentioned that cisatracurium was the only agent studied in the large RCTs and is, therefore, the preferred agent to use. Also, the anti-inflammatory effects of cisatracurium may have a potential benefit on top of neuromuscular blockade.

No recommendations were made about which strategy to be used to assess the adequacy of paralysis and the panel advises a strategy that clinicians are most comfortable with.

In a separate table, recommendations are made for how to implement this ICM-RPG in a low-resource setting.

When new trials arise, the IMC-RPG will be updated accordingly.

STUDY STRENGTHS & LIMITATIONS
  • a clear and focused clinical question was formulated by the panel, and a structured approach was used to answer the question.
  • a precise algorithm is presented on the use of NMBA.
  • as mentioned in the paper, cisatracurium was the only agent studied in large RCTs, and the impact of using other NMBA infusions is uncertain.
  • the ICM-RPG was peer- and editorial-reviewed through ICM.
  • cost-effectiveness was also considered for low-resource settings, and suggestions were made in a separate table.
TAKE HOME MESSAGE

ICM-RPG is a new concept translating evidence in clinical practice in a fast manner, making it a reliable resource. In this ICM-RPG, the routine use of NMBA infusion is not recommended for all adults with ARDS.  It suggested avoiding NMBA infusion for patients who are lightly sedated. Nevertheless, for patients who require deep sedation to enable lung-protective ventilation or prone positioning and require NMBA, an infusion for 48 hours is an option.

This article review was prepared and submitted by Dr Anna Hall, ZorgSaam Hospital, Terneuzen, the Netherlands, on behalf of the ESICM Journal Review Club.


REFERENCES

Alhazzani et al. Neuromuscular blockade in patients with ARDS: a rapid practice guideline. Intensive Care Med. 2020 Nov;46(11):1977-1986

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