Abstract: Objective To observe the efficacy and safety of low dose morphine in the patients with severe hand foot mouth disease during the mechanical ventilation of. Methods From January 2010 to December 2014,78 patients with severe hand foot and mouth disease were randomly divided into control group(Con) and low dose morphine group(Mor).The ptients in Con group were given midazolam 0.1 mg/kg,and 0.05-0.15 mg/(kg·h) infusion continuously;sufentanil 0.1 μg/kg,and 0.03-0.06 μg/(kg·h) infusion continuously;while the patients in Mor group were given morphine 40 μg/kg,to 10-30 μg/(kg·h) infusion continuously.The primary outcomes included Ramsay scores,inspiratory peak pressure(PIP),oxygenation index(OI),creatine kinase (CK-MB),mechanical ventilation time;andthe secondary outcomes included blood gas,PICU time,hospital costs,etc. Results All patients achieved the perfect calm state.The inspiratory peak pressure decreased gradually to normal duration of the mechanical ventilation,but the PIP in Mor group was significantly lower than that in Con group at T_12h,D₁ point(P=0.04;P=0.03).With the mechanical ventilation time prolonged,the OI of patients turned gradually to normal,and the OI in Mor group was better than that in Con group at T_12h,D₁ point(P=0.01;P=0.04).The creatine kinase decreased gradually with the mechanical ventilation time prolonged too,but the CK-MB in Con group was still significantly higher than that in Mor group at T_12h,D₁ and before the extubation(P=0.05;P=0.05;P=0.03).The mechanical ventilation time in Mor group was less than that in Con group(P=0.02).The duration of PICU in Mor group was less than that in Con group(P=0.02).The charge of Mor group was less too(P<0.01). Conclusion Low dose of morphine and midazolam combined with sufentanil both can achieve satisfactory sedation state to the children with severe hand,foot and mouth disease during mechanical ventilation.The low dose of morphine can improve rapidly the hypoxia and ischemia symptoms,improve heart and lung function,and reduce significantly the mechanical ventilation time,the duration of PICU and hospital costs.