No mode of ventilation is burdened with more emotional baggage than airway pressure release ventilation (APRV). The mere suggestion of its use is met with either the delight of recognizing an old friend whom you are meeting for the first time, or the type of disgust typically reserved for the likes of snake oil salesmen. This divide, is rarely crossed, and typically only breached to hurl physiologic insults before ducking behind one’s own tightly held ventilatory beliefs.
The origins of this conflict are likely due to the inconsistencies in the clinical trials examining APRVs utility for mechanically ventilated patients. Supporters would argue this variation in signal is primarily due to the large assortment of inverse ratio strategies employed under the guise of APRV (1). In order to truly judge the merit of this nontraditional approach, only trials that utilize a patient specific release phase should be considered. This form of APRV tailors the exhalation time (referred to as T-low in the APRV community) to the patient’s individual respiratory mechanics and maintains recruitment by limiting the time allowed to exhale. But until recently no prospective randomized trials utilizing this preferred technique existed in the medical literature.
Published in Intensive Care Medicine in November of 2017, Zhou et al enrolled patients presenting to a single center with hypoxic respiratory failure (2), requiring mechanical ventilatory support, who fulfilled the diagnostic criteria of ARDS according to the Berlin definition, had a PaO2/FiO2 of ?250, and were mechanically ventilated for less than 48 hours. Patients randomized to receive a traditional ARDSNet lung protective strategy, which consisted of a targeted tidal volume of 6 mL/ kg predicted body weight (PBW), PEEP levels determined by a PEEP-FiO2 table and respiratory rates titrated to limit hypercapnia and respiratory acidosis. Patients randomized to the APRV arm were placed on a high airway pressure (P-high) according to the plateau pressure that was obtained on their previous traditional volume control setting. The low airway pressure (P-low) was set to 5 cm H2O and the T-low was titrated to the patients’ intrinsic compliance in order to allow for a 50% decrease in peak expiratory flow rates.
From May 2015 through to October 2016, a total of 138 patients with ARDS were enrolled in this intention-to-treat analysis: 71 patients in the APRV group and 67 patients in the LTV group. It was a fairly sick cohort of patients with APACHE II scores of of 22.0 ± 7.9 and 20.2 in the APRV and LTV groups respectively. Likewise, the number of patients with PaO2/FiO2 less than 150 was 66.2 and 61.2%, respectively.
Overall the patients randomized to receive an APRV strategy did remarkably better than their low-tidal volume counterparts, boasting significantly fewer ventilator days (8 [5–14] vs 15 [7–22] p=0.001), higher rate of successful extubation (66.2% vs 38.8% p=0.001), and fewer tracheostomies (12.7% vs 29.9% p= 0.013). They also required less additional supportive measures including paralysis, recruitment maneuvers, and prone positioning. And while not statistically significant, the point estimate of both ICU mortality and hospital mortality trended strongly in favor of the APRV group (ICU mortality 19.7% vs 34.3% p= 0.053, hospital mortality 23.9% vs 37.3% p=0.088).
These results are intrinsically limited by the trial’s design. The single center nature and small sample size make it susceptible to random error, potentially artificially inflating APRV’s beneficial properties. Additionally, this trial was performed by a group of APRV enthusiasts which may limit the trial’s external validity. Despite these limitations the trail allows us to address some of the more egregious myths often cited in vain against the use of APRV.
There is an increased rate of hypercapnia, due to a decrease in the overall minute ventilation associated with the use of APRV.
Never mind the more important question of whether hypercapnia is harmful in ARDS, there are numerous models demonstrating that the increase in mean airway pressure promotes alveolar recruitment, improving ventilatory efficiency and increasing CO2 removal, despite a decrease in the total minute ventilation (3,4) Zhou et al found similar results. At 3 days the patients in the APRV group had an almost identical PCO2 to the patients in the low-tidal volume group (40.8 ± 7.3 42.3 ± 8.6 respectively). In fact, if you look at the respective minute ventilation in each arm (6.86 ± 2.06 vs 8.22 ± 2.30), it was significantly less in the patients randomized to the APRV group, suggesting that the high mean airway pressure deployed by this ventilatory strategy decreased V/Q mismatch and optimized CO2 exchange.
The high airway pressures lead to a greater degree of hemodynamic instability when compared to a low-tidal volume strategy.
While on first glance this statement seems intuitive, observational data would seem to suggest it is untrue. There have been a number of observational studies examining patients with ARDS ventilated using APRV, in whom pulmonary artery catheters were placed. The patients were switched from traditional ventilation to APRV, and the authors observed that all hemodynamic indices improved following the initiation of APRV (5.6). Zhou et al observed similar results. The authors observed no difference in the mean arterial pressure, or pressor requirements despite the APRV arm having significantly higher mean airway pressures.
APRV can lead to excessive overdistention and barotrauma.
The elevated mean airway pressures associated with APRV have been accused of causing overdistention, leading to an increased rate of barotrauma. While on first glance this seems physiologically plausible, this claim is supported by almost no evidence. In fact, most of the preclinical data demonstrates decreased strain on the individual lung units due to APRV’s superior recruitment capabilities (7,8, 9). At least in its limited capacity the Zhou et al trial confirmed these findings. There was no statistical difference in the rate of pneumothoraces between the two groups and the point estimate noticeably favored the APRV arm (4.2% vs 10.4% p-value of 0.199).
APRV is uncomfortable, requiring larger doses of sedation and potentially prolonging time to extubation.
This empirically does not seem to be true. In an observational cohort performed by Fan et al, published in the Journal of Intensive Care Medicine in 2008 (10), the authors found that patients on APRV required less sedation and had higher RASS scores than their traditionally ventilated counterparts. The trial by Zhou et al supports these assertions. Patients randomized to the APRV group received less fentanyl, midazolam, and propofol, and achieved higher RASS scores over the course of the first 7-days following enrollment.
The debate on the therapeutic efficacy of APRV is often described in broad dichotomies. Detractors of APRV are viewed as empiric in nature, emboldened by the scientific fact that low-tidal volume ventilation saves lives. While APRV supporters are seen as zealots who base their practice on flawed physiological reasoning, ignoring scientific truths.
While a low-tidal volume strategy for the management of ARDS has some scientific merit, it is by no means an undeniable truth. Its success suggests superiority to a previous age of more deleterious ventilatory practices, but the results of the ARMA trial are not indicative of therapeutic perfection. Despite its methodological flaws the Zhou et al trial infers that this non-traditional approach to mechanical ventilation may offer some advantages compared our current status quo. At the very least APRV should be thought of as more than just a last ditch effort for refractory hypoxic respiratory failure on the path to extracorporeal support.
- Jain SV, Kollisch-singule M, Sadowitz B, et al. The 30-year evolution of airway pressure release ventilation (APRV). Intensive Care Med Exp. 2016;4(1):11.
- Zhou Y, Jin X, Lv Y, et al. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017;43(11):1648-1659.
- A. Mercat, J. Diehl, F. Michard, et al.Extending inspiratory time in acute respiratory distress syndrome Crit Care Med, 29 (1) (2001), pp. 40-44
- Knelson, W. Howatt, G. DeMuthEffect of respiratory pattern on alveolar gas exchange J Appl Physiol, 29 (3) (1970), pp. 328-331
- S. Fuleihan, R. Wilson, H. PontoppidanEffect of mechanical ventilation with end?inspiratory pause on blood?gas exchange Anesth Analg, 55 (1) (1976), pp. 122-130
- Taha A, Shafie A, Mostafa M, Hon H, Marktanner R. Airway pressure release ventilation restores hemodynamic stability in patients with cardiogenic shock: initial experience in cardiac intensive care. Critical Care. 2014;18(Suppl 1):P282. doi:10.1186/cc13472.
- Kaplan LJ, Bailey H, Formosa V. Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome. Critical Care. 2001;5(4):221-226.
- Kollisch-Singule M, Emr B, Smith B, Roy S, Jain S, Satalin J, Snyder K, Andrews P, Habashi N, Bates J, Marx W, Nieman G, Gatto LA (2014) Mechanical breath profile of airway pressure release ventilation: the effect on alveolar recruitment and microstrain in acute lung injury. JAMA Surg 149:1138–1145
- Kollisch-Singule M, Emr B, Smith B, Ruiz C, Roy S, Meng Q, Jain S, Satalin J, Snyder K, Ghosh A, Marx W, Andrews P, Habashi N, Nieman G, Gatto LA (2014) Airway pressure release ventilation reduces conducting airway micro-strain in lung injury. J Am Coll Surg 219:9
- Kollisch-Singule M, Jain S, Andrews P, Smith BJ, Hamlington-Smith KL, Roy S, DiStefano D, Nuss E, Satalin J, Meng Q, Marx W, Bates JH, Gatto LA, Nieman GF, Habashi NM (2016) Effect of airway pressure release ventilation on dynamic alveolar heterogeneity. JAMA Surg 151(1):64–72
- Fan E, Khatri P, Mendez-tellez PA, Shanholtz C, Needham DM. Review of a large clinical series: sedation and analgesia usage with airway pressure release and assist-control ventilation for acute lung injury. J Intensive Care Med. 2008;23(6):376-83
Other Great FOAM Resources:
–PulmCrit- APRV: Resurrection of the open-lung strategy?