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Table 2 Summary of findings

From: Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials

Outcomes

№ of participants (studies)

Follow-up

Certainty of the evidence (GRADE)

Relative effect (95% CI)

Anticipated absolute effects

Risk with no infusion (but intermittent as needed NMBA)*

Risk difference with an infusion of neuromuscular blockade

Hospital mortality subgroup (compared to light sedation)

1006 (1 RCT)

Moderatea,b

RR 0.99 (0.86 to 1.15)

428 per 1000

4 fewer per 1000 (60 fewer to 64 more)

Hospital mortality subgroup (compared to deep sedation)

431 (3 RCTs)

Lowb,c

RR 0.72 (0.58 to 0.91)

471 per 1000

132 fewer per 1000 (198 fewer to 42 fewer)

Mortality–28-day mortality (pooled for all trials)

1598 (7 RCTs)d

Lowb,e,f

RR 0.74 (0.56 to 0.98)

369 per 1000

96 fewer per 1000 (162 fewer to 7 fewer)

Mortality–hospital/90-day mortality (pooled for all trials)

1478 (5 RCTs)

Lowb,g

RR 0.78 (0.60 to 1.01)

437 per 1000

96 fewer per 1000 (175 fewer to 4 more)

Mental health at 6 months

267 (1 RCT)

Lowb,h

RR 1.03 (0.69 to 1.55)

254 per 1000

8 more per 1000 (79 fewer to 140 more)

Cognitive function (MOCA scores)

287 (1 RCT)

Lowi,j

The mean cognitive Function (MOCA Scores) was 22.8 points

MD 0.6 points lower (1.71 lower to 0.51 higher)

Quality of life

401 (1 RCT)k

Lowb,l,m

The mean quality of life was 0.73 units

MD 0.07 units lower (0.15 lower to 0.01 higher)

Adverse events

1437 (4 RCTs)

Lowb,n

RR 1.63 (0.98 to 2.72)

31 per 1000

19 more per 1000 (1 fewer to 53 more)

ICU-acquired weakness

885 (4 RCTs)

Moderateb,o

RR 1.16 (0.98 to 1.37)

346 per 1000

55 more per 1000 (7 fewer to 128 more)

Hospital/90-day mortality (subgroup of patients with ARDS and P/F > 100)

542 (4 RCTs)

Lowb,p,q

RR 0.87 (0.71 to 1.06)

444 per 1000

58 fewer per 1000 (129 fewer to 27 more)

Hospital/90-day mortality (subgroup of patients with ARDS and P/F≤100)

895 (4 RCTs)

Lowb,r,s

RR 0.95 (0.82 to 1.11)

427 per 1000

21 fewer per 1000 (77 fewer to 47 more)

Hospital/90-day mortality (sensitivity analysis using ROSE late use of NMBA)

975 (5 RCTs)

Very lowb,h,t

RR 0.78 (0.57 to 1.06)

431 per 1000

95 fewer per 1000 (185 fewer to 26 more)

Barotrauma

1437 (4 RCTs)

Moderateb,u

RR 0.55 (0.35 to 0.85)

73 per 1000

33 fewer per 1000 (47 fewer to 11 fewer)

Ventilator-free days at 28 days

1487 (5 RCTs)

Lowb,v,w

The mean ventilator-free days at 28 days was 14 days

MD 0.72 days more (0.44 fewer to 1.88 more)

PO2/FiO2 post-randomization–PO2/FiO2 at 24 h post-randomization

1267 (4 RCTs)

Lowb,x,y

The median PO2/FiO2 post-randomization -PO2/FiO2 at 24 h post-randomization was 120

MD 7.76 higher (3.74 lower to 19.27 higher)

PO2/FiO2 post-randomization–PO2/FiO2 at 72 h post-randomization

1011 (4 RCTs)

Lowb,x,z

The mean pO2/FiO2 post-randomization -PO2/FiO2 at 72 h post-randomization was 100

MD 15.21 higher (1.9 higher to 28.52 higher)

  1. GRADE Working Group grades of evidence
  2. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
  3. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
  4. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
  5. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
  6. CI confidence interval, RR, risk ratio, MD mean difference
  7. *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
  8. Explanations
  9. aWe downgraded the certainty in the evidence by one level for serious imprecision; the CI included both small benefit and harm
  10. bWe were not able to assess for publication bias using traditional methods because we identified less than 10 studies
  11. cWe downgraded the certainty of evidence by two levels for very serious imprecision, the total number of events was small (174 events)
  12. d7 RCTs reported this outcome, including Gainnier M, et al. Crit Care Med. 2004;32(1):113-9.; Forel JM, et al. Crit Care Med. 2006;34(11):2749-57.; Papazian L, et al. N Engl J Med. 2010;363(12):1107-16.; Lyu G, et al. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014;26(5):325-9.; Guervilly C, et al. Intensive Care Med. 2017;43(3):408-18.; N Engl J Med. 2019;380(21):1997–2008
  13. eWe downgraded the certainty of evidence by two levels for very serious inconsistency, although the I2 was 45%, there is inconsistency between the results of the most recent and large RCT (ROSE Trial) and the rest of the studies, which was not explained by any of the subgroup analyses, difficulty in reconciling and explaining the differences in results have lead us to lower our certainty in the estimates by 2 levels
  14. fThe 7 RCTs reported 547 deaths which is enough for us to consider the pooled estimates precise
  15. gWe downgraded the certainty of evidence by two levels for very serious inconsistency, although the I2 was 55%, there is inconsistency between the results of the most recent and large RCT (ROSE Trial) and the rest of the studies, which was not explained by any of the subgroup analyses, difficulty in reconciling and explaining the differences in results have lead us to lower our certainty in the estimates by 2 levels
  16. hWe downgraded the certainty of evidence by two levels for very serious imprecision; the CI was very wide including both substantial benefit and harm
  17. iWe downgraded the certainty of evidence by one level for serious risk of bias; many patients who were randomized did not complete the assessment
  18. jWe downgraded the certainty of evidence by one level for serious imprecision, the sample size was small
  19. kN Engl J Med. 2019;380(21):1997–2008
  20. lWe downgraded the certainty of evidence by one level for risk of bias; the outcome is subjective and the trial was unblinded
  21. mWe downgraded the certainty of evidence by one level for serious imprecision; the CI included both harm and benefit, and the number of patients who were included the analysis at 3 months is small (< 50% of the original sample size)
  22. nWe downgraded the certainty of evidence by two levels for serious imprecision; the CI included both substantial harm and small/no benefit. In addition, the number of events was small (n = 58 events)
  23. oWe downgraded the certainty of evidence by one level for serious imprecision; the CI included both substantial harm and trivial benefit
  24. pWe downgraded the certainty of evidence by one level for serious indirectness, the ROSE Trial which contributed to 55% of the weight in the analysis for this subgroup, included patients with ARDS and P/F > 120 not 100
  25. qWe downgraded the certainty of evidence by one level for serious imprecision; the CI included both substantial benefit and small harm
  26. rWe downgraded the certainty of evidence by one level for serious inconsistency; although the I2=0% the Forest plot showed that the results of the ROSE Trial are inconsistent with the results of other trials
  27. sWe downgraded the certainty of evidence by one level for serious indirectness, the ROSE Trial which contributed to 81% of the weight in the analysis for this subgroup, included patients with ARDS and P/F < 120 not only < 100
  28. tWe downgraded the certainty of evidence by two levels for very serious inconsistency; the I2 = 65%
  29. uWe downgraded the certainty of evidence by one level for serious imprecision; the number of events was small and the confidence interval although did not include 1, it included substantial variation in benefit
  30. vAlthough I2 = 34%, we did not downgrade for inconsistency
  31. wWe downgraded the certainty in the evidence by two levels for very serious imprecision; the CI included extreme benefit and harm
  32. xWe downgraded the certainty of evidence by one level for serious indirectness, the intervention, and control in the ROSE Trial differed from other trials (early NMBA and targeting light sedation)
  33. yWe downgraded the certainty of the evidence by one level for serious imprecision; the CI included both benefit and harm
  34. zWe downgraded the certainty in the evidence by one level for serious imprecision; the CI included both trivial and moderate benefit