Inclusion Criteria:  need mechanical ventilation for more than 48 hours more than 18 years old without hospital-acquired infection before admission to ICU volunteer to participate in this study  Exclusion Criteria:  allergic or contraindicated to the drug severe cardiac insufficiency, conduction block and bradycardia recent use of analgesic, sedative and antidepressant drugs psychiatric or neurological diseases or neurosurgery-related diseases history of steroid cortisol and immunosuppressants severe liver dysfunction or renal dysfunction pregnancy refuse to enrollment