Evaluation of continuous aspiration of subglottic secretion in an in vivo study* Lorenzo Berra, MD; Lorenzo De Marchi, MD; Mauro Panigada, MD; Zu-Xi Yu, PhD; Andrea Baccarelli, MD; Theodor Kolobow, MD V entilator-associated pneumonia (VAP) carries a high morbidity and mortality rate in patients intubated and mechanically ventilated. Preventive strategies to reduce bacterial colonization of the aerodigestive tract and aspiration of contaminated secre- tions are believed to reduce the incidence of VAP (1– 4). Over the past 10 yrs, four randomized clinical trials evaluated the role of aspi- ration of subglottic secretions: The im- pact on pneumonia was mixed, and mor- tality rate did not change (5– 8). Surprisingly, no previous laboratory ani- mal studies had been conducted before those clinical trials assessing safety and efficacy of this new clinical device (Hi-Lo Evac, Mallinckrodt, St. Louis, MO). Nev- ertheless, continuous aspiration of sub- glottic secretions (CASS) is now listed in many guidelines for the prevention of VAP (4, 9, 10), without apparently chang- ing the clinical practice of many intensive care units (11, 12). Semirecumbency is another nonphar- macologic strategy to prevent VAP, broadly used in intensive care units. Dra- kulovic et al. (13) showed that semire- cumbent body position (45°) reduces the frequency and risk of nosocomial pneu- monia (14). However, recent clinical tri- als did not confirm those results (15, 16). Recently, we have shown that the hor- izontal orientation of the endotracheal tube (ETT), and of the trachea, prevented accumulation of secretions above the ETT cuff, prevented leakage of oropha- ryngeal contents around the ETT cuff, and promoted the outward drainage of bacteria-laden mucus from within the ETT (17, 18). In the same animal model, with sheep mechanically ventilated for 72 hrs, we explored safety and efficacy of CASS in preventing bacterial coloniza- tion of the lower respiratory tract with the ETT both horizontal and elevated 30° above horizontal, as in patients lying su- pine or semirecumbent. MATERIALS AND METHODS End Points The primary end point of this laboratory investigation was whether the use of CASS *See also p. 2160. From the Section on Pulmonary and Cardiac Assist Devices (LB, LDM, MP, TK), Pulmonary and Critical Care Medicine Branch, and the Pathology Core (Z-XY), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and the Genetic Epidemiology Branch (AB), Division of Cancer Epide- miology and Genetics, National Cancer Institute, Na- tional Institutes of Health, Department of Health and Human Services, Bethesda, MD. Supported, in part, by the National Heart, Lung and Blood Institute, Division of Intramural Research, Na- tional Institutes of Health, Department of Health and Human Services, Bethesda, MD. Address requests for reprints to: Theodor Kolobow, MD, National Institutes of Health, NHLBI, PCCMB, 9000 Rockville Pike, Bldg 10, Rm 5D-07, Bethesda, MD. E-mail: kolobowt@nhlbi.nih.gov Copyright © 2004 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/01.CCM.0000142575.86468.9B Objective: Continuous aspiration of subglottic secretions (CASS) is believed to lower the incidence of ventilator-associated pneumonia. Animal studies to establish safety and efficacy of CASS have not been conducted. Design: Prospective randomized animal study. Setting: Animal-research facility at the U.S. National Institutes of Health. Subjects: Twenty-two sheep. Interventions: Sheep were randomized into three groups. In group C (control), eight sheep were kept prone, intubated with a standard endotracheal tube (ETT), and mechanically ventilated for 72 hrs with head and ETT elevated at an angle of 30°. In group CASS-HU (CASS, head up), seven sheep were managed as group C and intubated with a Hi-Lo Evac, Mallinckrodt ETT (CASS suction kept at <20 mm Hg). In group CASS-HD (CASS, head down), seven sheep were kept prone with CASS, and the ETT and trachea were horizontal to promote spontaneous drainage of mucus from the ETT. Measurements and results: The lower respiratory tract in the CASS-HU group was heavily colonized in all seven sheep (median 4.6  10 9 , range, 1.5  10 8 to 7.9  10 9 colony-forming units/g), with a reduction of lung bacterial colonization compared with the C group (p  .05). In group CASS-HD, the lower respiratory tract was not colonized in six of seven sheep. One sheep showed low levels of bacterial growth (median, 0; range, 0 –2.2  10 5 ). At autopsy, in all 14 sheep with CASS, we found tracheal mucosal injury of different degrees of severity at the level of the suction port of the ETT. Conclusions: In group CASS-HU, regardless of finding a mar- ginal decrease of the bacterial colonization of the lower airways, there was pervasive trachea-bronchial-lung bacterial coloniza- tion. Second, there was minimal, or absent, bacterial colonization when the orientation of the CASS ETT was at, or just below, horizontal. Third, there was widespread injury to tracheal muco- sa/submucosa from the use of CASS. Note that results of studies conducted in an animal model are always difficult to extrapolate to the clinical practice due to anatom- ical and functional differences. (Crit Care Med 2004; 32:2071–2078) KEY WORDS: mechanical ventilation; aspiration; ventilator-asso- ciated pneumonia; endotracheal tube; continuous aspiration of subglottic secretions 2071 Crit Care Med 2004 Vol. 32, No. 10