Therapy Ventilation with lower tidal volumes as compared to conventional tidal volumes
This review may be edited
Summary
Posted By:	Elizabeth Sweetman
E-Mail:	easweetm@nsccahs.health.nsw.gov.au
Posted Date:	13/01/10
Title:	Ventilation with lower tidal volumes as compared to conventional tidal volumes
Authors:	Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ.
Reference:	Crit Care. 2010 Jan 7;14(1):R1
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	INTRODUCTION: Recent cohort studies have identified use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional versus lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at onset of mechanical ventilation. METHODS: Randomized controlled non-blinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary endpoint was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary endpoint was development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality. RESULTS: One hundred fifty patients (74 conventional vs. 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly stronger in the lower tidal volume group (from 51 [20 - 182] ng/ml to 11 [5 - 20] ng/ml vs. 50 [21 - 122] ng/ml to 21 [20 - 77] ng/ml; P = 0.01). The trial was stopped prematurely for safety reasons because development of lung injury was higher in the conventional tidal volume group as compared to the lower tidal volume group (13.5% vs. 2.6%, P = 0.01). Univariate analysis showed statistical relations between baseline lung injury score, randomization group, level of positive end-expiratory pressure (PEEP), number of transfused blood products, presence of a risk factor for ALI and baseline IL-6 lavage fluid levels and development of lung injury. Multivariate analysis revealed randomization group and level of PEEP as independent predictors of the development of lung injury. CONCLUSIONS: Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production as measured in plasma. Our data suggest mechanical ventilation with conventional tidal volumes contributes to development of lung injury in patients without ALI at onset of mechanical ventilation. Trial registration: ISRCTN82533884.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Yes. Authors state that randomisation was performed using sealed opaque envelopes in blocks of 50 patients.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	152 patients were randomised in this trial according to the quorum flow diagram (76 conventional group vs 76 lower tidal volume group). Two patients were not included in the analysis. These patients were lost to follow up from the control group due to; 1 patient being transferred to another hospital and 1 patient being excluded following randomisation due to having ARDS.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes patients were analysed in the groups with which they were randomised.
3. Were patients, health workers, and study personnel blind to treatment?
	The two independent physicians who were responsible for diagnosing Acute Lung Injury (ALI) were blinded to randomization group and all clinical parameters.
4. Were the groups similar at the start of the trial?
	The demographics of both patient groups are reported in Table 1. There was a higher number of current smokers in the lower tidal volume group vs the conventional tidal volume group (76% vs 61%, p = 0.04). This imbalance would not explain the findings of improved outcome in the lower tidal volume group.
5. Aside from the experimental intervention, were the groups treated equally?
	Unsure. A table documenting treatments/interventions (aside from the study intervention) was not provided. Authors did not comment on whether both study groups were treated the same or different.
What are the Results?
1. How large was the treatment effect?
	Primary Outcome: Cytokine (TNF-a, IL-1B & IL-6) levels in bronchoalveolar lavage fluid and plasma during MV No difference in TNF-a, IL-B & IL-6 in bronchoalveolar lavage fluid levels between groups (*Values available from figure 4) A greater decrease of plasma IL-6 after 4 days in the lower tidal volume group than the conventional tidal volume group (51 [20-182]ng/ml to 11[5-20]ng/ml vs 50 [21-122] ng/ml to 21[9-99]ng/ml, P = 0.01). Secondary Outcomes: Development of Lung Injury: Higher number of patients in the conventional tidal volume group developed 'lung injury' than in the lower tidal volume group 10/74 (13.5%) vs 2/76 (2.6%), P = 0.01. Number of Ventilator free days at 28 days: no difference between groups 24.0 [20.7-26.8] days in the conventional tidal volume group vs 24.0 [2.15-25.5] in the lower tidal volume group. 28 Day mortality: no difference between groups 31% mortality in the conventional tidal volume group vs 32% mortality in the lower tidal volume group (P = 0.94).
2. How precise was the estimate of the treatment effect?
	Confidence intervals not reported for primary outcomes.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	Yes, these critically ill patients are similar to those in our ICUs. We are familiar with and can use the ARDSnet low tidal volume ventilation protocol and could follow the slightly modified version presented in this paper.
2. Were all clinically important outcomes considered?
	All reasonable major outcomes, except for workload (costs) are reported. The authors report 28 day mortality. Longer term (60 or 90 day) mortality may be desirable.
3. Are the likely treatment benefits worth the potential harms and costs?
	The authors report that formal stopping rules were not set before the trial was begun. Even after the realization that interim 'safety' analyses would be undertaken, the authors did not set stopping rules. The positive findings reported in a secondary outcome in this paper should be viewed with skepticism. Fortunately, most patients in ANZ are NOT ventilated like the conventional arm patients were. It is unlikely that we can use this trial to change practice away from our currently preferred use of pressure modes of ventilation. These novel findings should be confirmed in a larger trial.
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