We hypothesized that combined salbutamol and external positive end-expiratory pressure (PEEPe) may present additive benefits in chronic obstructive pulmonary disease (COPD) exacerbation. In 10 anesthetized, mechanically ventilated, and bronchodilator-responsive COPD patients exhibiting moderate intrinsic PEEP (PEEPi), we assessed respiratory system (rs) mechanics, hemodynamics, and gas exchange at (a) baseline (zero PEEPe [ZEEPe]), (b) 30 min after 5 mg of nebulized salbutamol administration (ZEEPe-S), (c) 30 min after setting PEEPe at baseline PEEPi level (PEEPe), and (d) 30 min after 5 mg of nebulized salbutamol administration with PEEPe maintained unchanged (PEEPe-S). Return of determined variable values to baseline values was confirmed before PEEPe application. Relative to ZEEPe, (a) at ZEEP-S, PEEPi (4.8 +/- 0.7 versus 7.0 +/- 1.1 cm H(2)O), functional residual capacity change (115.6 +/- 23.1 versus 202.1 +/- 46.0 mL), minimal rs (airway) resistance (9.3 +/- 1.4 versus 11.8 +/- 2.2 cm H(2)O.L(-1).s(-1)), and additional rs resistance (5.2 +/- 1.4 versus 7.2 +/- 1.3 cm H(2)O.L(-1).s(-1)) were reduced (P < 0.01), and hemodynamics were improved; (b) at PEEPe, PEEPi (3.7 +/- 1.3 cm H(2)O) was reduced (P < 0.01), and gas exchange was improved; and (c) at PEEPe-S, PEEPi (2.0 +/- 1.2 cm H(2)O) was minimized, and rs mechanics (static rs elastance included), hemodynamics, and gas exchange were improved. Conclusively, in carefully preselected COPD patients, bronchodilation/PEEPe exhibits additive benefits.