I would like to bring to the attention of readers of Anesthesiology some inaccuracies in the Editorial View “Noisy Mechanical Ventilation: Listen to the Melody” by Drs. Shimabukuro and Gropper.1This article provided an overview of the research published in the journal by Spieth et al.,  2“Effects of different levels of pressure support variability in experimental lung injury.” As stated by the editorialists, “Using variability in breathing patterns is not a completely new concept. It was probably first elucidated by Suki et al.  3in Nature  in 1998.” In fact such an approach, subsequently called biologically variable ventilation, was first elucidated in 1996 in work done in my laboratory by Lefevre et al .4Careful reading of the article in Nature  indicates that stochastic resonance was advanced as an explanation for the improvement in compliance and oxygenation with a noisy end-inspiratory pressure based on analysis of data from our publication. We have since extended these observations to more generally indicate where noisy ventilation will be efficacious and where it may be detrimental.5This analysis is based on Jensen’s inequality–a mathematical proof stating that a variable input will enhance an output when a smoothly continuous curvilinear function is convex.6In contrast, if the function describing a relationship is concave, the addition of noise can diminish output and potentially be detrimental. Noisy ventilation is especially advantageous with tidal volume protocols according to the Acute Respiratory Distress Syndrome Network trial because the volume-pressure curve is convex curvilinear in the range of low tidal volumes.7The lone negative animal study examining noisy ventilation in an acute respiratory distress syndrome model may be a consequence of large tidal volumes administered over the concave region of the sigmoidal volume-pressure curve—the portion of the static compliance curve where it may be deleterious to provide positive pressure ventilation based on modeling using Jensen’s inequality.8 

The editorial further raises the question of the use of noisy ventilation in normal lungs. My laboratory has examined the use of noisy ventilation in the experimental setting of baseline anesthesia without lung injury9and during ventilation of the dependent lung during one-lung anesthesia (an article published in Anesthesiology).10Colleagues published, again in Anesthesiology, the first clinical trial examining the application of variable ventilation during abdominal aneurysmectomy.11In each of these studies better gas exchange and respiratory mechanics were seen with noisy ventilation, as compared with conventional monotonous control mode ventilation, similar to the findings by Spieth et al. 

I do concur with the editorialists that “The importance of variability, whether referring to the respiratory system or DNA, in biologic systems should not be underestimated.” Based on the nonlinear amplification of output in convex curvilinear systems as outlined above, we have shown that noisy perfusion can improve cerebral oxygenation,12diminish renal injury,13and enhance delivery of cardioplegia14during cardiopulmonary bypass. These improvements are likely a consequence of better flow with noisy perfusion pressure over the convex curvilinear flow-pressure curve manifest by the microvasculature. An overview of some of these issues is discussed in a short review.15 

I also concur that “the time is here to translate these studies to the bedside.” The article by Spieth et al.  reinforces prior work by this European group, the group in Boston, and the group in Canada, all demonstrating the advantage of adding noise to life support systems.

University of Manitoba, Winnipeg, Manitoba, Canada. amutch@cc.umanitoba.ca

Shimabukuro DW, Gropper MA: Noisy mechanical ventilation: Listen to the melody. Anesthesiology 2009; 110:214–5
Spieth PM, Carvalho AR, Güldner A, Pelosi P, Kirichuk O, Koch T, de Abreu MG: Effects of different levels of pressure support variability in experimental lung injury. Anesthesiology 2009; 110:342–50
Suki B, Alencar AM, Sujeer MK, Lutchen KR, Collins JJ, Andrade JS Jr, Ingenito EP, Zapperi S, Stanley HE: Life-support system benefits from noise. Nature 1998; 393:127–8
Lefevre GR, Kowalski SE, Girling LG, Thiessen DB, Mutch WA: Improved arterial oxygenation after oleic acid lung injury in the pig using a computer-controlled mechanical ventilator. Am J Respir Crit Care Med 1996; 154:1567–72
Brewster JF, Graham MR, Mutch WA: Convexity, Jensen’s inequality and benefits of noisy mechanical ventilation. J R Soc Interface 2005; 2:393–6
Jensen JL: Sur les fonctions convexes et les inégualités entre les valeurs moyennes. Acta Math 1906; 30:175–93
The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301–8
The Acute Respiratory Distress Syndrome Network
Nam AJ, Brower RG, Fessler HE, Simon BA: Biologic variability in mechanical ventilation rate and tidal volume does not improve oxygenation or lung mechanics in canine oleic acid lung injury. Am J Respir Crit Care Med 2000; 161:1797–804
Mutch WA, Eschun GM, Kowalski SE, Graham MR, Girling LG, Lefevre GR: Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia. Br J Anaesth 2000; 84:197–203
McMullen MC, Girling LG, Graham MR, Mutch WA: Biologically variable ventilation improves oxygenation and respiratory mechanics during one-lung ventilation. Anesthesiology 2006; 105:91–7
Boker A, Haberman CJ, Girling L, Guzman RP, Louridas G, Tanner JR, Cheang M, Maycher BW, Bell DD, Doak GJ: Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy. Anesthesiology 2004; 100:608–16
Mutch WA, Lefevre GR, Thiessen DB, Girling LG, Warrian RK: Computer-controlled cardiopulmonary bypass increases jugular venous oxygen saturation during rewarming. Ann Thorac Surg 1998; 65:59–65
Singal RK, Docking LM, Girling LG Graham MR, Nickerson PW, McManus BM, Magil AB, Walker EK, Warrian RK, Cheang MS, Mutch WA: Biologically variable bypass reduces enzymuria after deep hypothermic circulatory arrest. Ann Thorac Surg 2006; 82:1480–8
Graham MR, Warrian RK, Girling LG, Doiron L, Lefevre GR, Cheang M, Mutch WA: Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass. J Thorac Cardiovasc Surg 2002; 123:63–71
Mutch WA, Lefevre GR: Health, ‘small-worlds,’ fractals and complex networks: an emerging field. Med Sci Monit 2003; 9:MT19–23