a valve , within the circuit . the purpose of peep is to the trachea of the patient suffering from ards is intubated . the lungs are ventilated in a conventional manner ( controlled mechanical ventilation : cmv ). following tracheal intubation , the sedation is changed over to an alpha - 2 agonist . then , following return of spontaneous ventilation , cmv is switched over to pressure support ( ps ) ventilation . it consists in continuous administration , without any bolus administration or any rapid infusion , of alpha - 2 agonist ( initial dosage : dexmedetomidine 0 . 5 - 1 μg · kg - 1 · h - 1 or clonidine 1 μg · kg - 1 · h - 1 ) 1 . 1 to our knowledge , there are no publications showing some equivalence between the 2 drugs . given the ceiling effect observed with dexmedetomidine 1 . 5 μg · kg - 1 · h - 1 ( 11 ) and the upper dosage for clonidine 2 μg · kg - 1 · h - 1 recommended by the french society of critical care medicine ( 12 ), a 1 ( dexmedetomidine ) to 2 ( clonidine ) equivalence will be taken for granted in this description . finally the initial dosage recommended here is tailored to the very patient , according to his neurological response , and to his renal or hepatic pathology . if , after 3 - 6 h , sedation is inappropriate ( ramsay ( 13 ) scale & lt ; 2 or patient trying to pull out arterial or central venous catheters or tracheal tube or movement of the patient trying to head out of bed or combative patient ) sedation is to be increased to 3 & lt ; ramsay & lt ; 4 : dexmedetomidine and clonidine are to be increased to 1 . 5 - 2 μg · kg - 1 · h - 1 or 2 - 4 μg · kg - 1 · h - 1 respectively . if sedation is still inappropriate , a second sedative agent s ′ is to be administered which is different from alpha - 2 agonist but should not depress ventilatory drive e . g . hydroxyzine 100 - 200 mg at night time ( e . g . 9 pm ) or loxapine 100 mg through the nasogastric tube 4 times per day . this dose should be adjusted to 25 mg * 4 as early as possible to achieve 3 & lt ; ramsay & gt ; 4 ). other sedative agents to be considered are neuroleptics ( e . g . haloperidol ) ( 14 ), ketamine , hydroxyzine , gamma hydroxy butyric acid or other drugs as long as they do not depress ventilatory drive . investigators ( 15 ) recommend to perform a computerized scanner ( ct scan ) of the thorax and a pressure - volume ( pv ) curve ( 16 ) before heading into treatment of severe diffuse ards . the pv curve allows determination of pflex on the incremental or decremental limb of the curve . if pflex cannot be determined , peep has to be set to 15 - 16 cm h2o , according to experienced investigators ( 17 , 18 ). given these recommendations , high peep is set to 10 - 24 cm h20 . given spontaneous ventilation , ps ventilation is set to 5 - 10 cm h2o or to a transpulmonary pressure ( pairway ( at opening ) or pplat - pesophageal measured by an esophageal balloon )& lt ; 25 cm h2o . an esophageal balloon is to be inserted to determine a transpulmonary pressure & lt ; 25 cm h20 . if an esophageal balloon cannot be inserted , absence of sternal notch retraction , thoraco - abdominal dyscoordination and use of accessory muscles should be assessed e . g . by palpation of the sternocleido mastoid muscle . then ps is set to a level ( usually (− 10 cm h2o ) so as to suppress sternal notch retraction , thoraco - abdominal dyscoordination and use of accessory muscles ( e . g sterno cleido mastoid muscle ). as the definition of severe ards is a p / f & lt ; 200 , steps b and c ( oxygenation and reduced respiratory work ) are to be maintained up to an increase in p / f & gt ; 200 . if chest xray , markers of inflammation ( temperature , crp , pct , etc .) are improving together with p / f & gt ; 200 , the trachea of the patient is extubated . this process lasts typically 2 - 5 days using the settings above detailed ( peep = 10 - 24 cm h20 , ps = 5 - 10 cm h20 ). first inspired oxygen is to be reduced to f102 = 0 . 4 as hypoxia and p / f improved . then , when f102 is reduced to 0 . 4 , peep is reduced every 12 or 24 h from 10 - 24 cm h2o stepwise by 5 cm h2o to peep = 5 - 10 cm h20 , as long as p / f keeps increasing toward 200 . other methods of respiratory assistance may be considered : airway pressure release ventilation , bipap , “ noisy ” ps , intermittent assist control ventilation with very low mandatory rate , neurally adjusted artificial ventilation ( nava ), high frequency ventilation , etc . the core of the process is to combine a sedation without any respiratory depressant effect with a high peep and a ventilatory mode as close as possible to spontaneous ventilation to minimize respiratory work and respiratory asynchrony . given a pplat & lt ; 26 - 32 cm h20 , paco2 is to be maintained so as to avoid right ventricular failure ( 19 ). usually , paco2 and ph are to be & lt ; 60 mm hg and & gt ; 7 . 2 respectively . to avoid excessive respiratory work , 2 issues are to be considered : to avoid re - expansion of alveoli upon each inspiration , the closing volume should be maintained above functional residual capacity residual upon end - expiration . to avoid excessive respiratory work , respiratory rate ( rr ) should be maintained as low as possible , especially when oxygen demands are high ( 7 ) ( e . g . sepsis , etc ). while tolerating a rr = 35 - 40 breaths per min ( bpmin ) is possible for a short period of time ( 1 - 3 h ) e . g . to allow for compensation of acidosis , a rr & lt ; 20 bpmin is mandatory for an extended period of time ( 2 - 5 days ) to observe improvement in p / f . therefore , sedation should be adequate ( 3 & lt ; ramsay & lt ; 4 : see above ). in addition , mild hypothermia ( 34 - 36 ° c .) allows one to lower rr & lt ; 20 bpmin : surface cooling , hypothermia evoked by the extra renal therapy , if appropriate for the considered patient . a key objective is to bring enough blood to the alveoli , reopened by a high peep . echocardiography should performed at least daily to observe right and left ventricular function . increasing levels of peep ( 0 - 30 cm h20 ) ( 8 ) are to be used while the rv function is observed qualitatively ( dilatation of rv , septal bulging : inverse positioning of the intra ventricular septum due to high pressure in the right ventricle ) and quantitatively ( tapse : tricuspid annular plane systolic excursion ). when the best compromise between high peep and rv function has been achieved , passive leg rising is to be performed to assess the possibility to increase blood volume and lower the requirements in vasopressors / inotropes . between echocardiographic assessments , oxygen saturation in the superior vena cava is to be assessed every 6 - 12 h and maintained & gt ; 70 - 75 %, as an index of adequacy of cardiac output ( 20 ). step g ) non - invasive ventilation to deal with acute lung injury ( 200 & lt ; p / f & lt ; 300 ). following extubation , sedation with an alpha - 2 agonist should be maintained to observe a quiet cooperative patient ( 2 & lt ; ramsay & lt ; 3 ) able to withstand niv for an extended period of time : usually : 23 h out of 24 h for the first day , then 18 out of 24 h , then 12 out of 24 h , then 6 out of 24 h . mrs x , 63 years old , 1 . 55 m , 145 kg , bmi = 61 , diabetes type 1 , oliguric for ≧ 36 h , associated to mild pulmonary infection , had been bed - ridden with little food intake at home for 3 - 4 days . she was admitted to the ccu on day 2 ( d2 ) for acute renal failure , acute volume overload . upon rapid sequence induction - sellick manoeuver , the patient aspirated . an 8 . 5 mm tracheal tube was inserted . cmv and sedation ( midazolam - sufentanil - cisatracurium ) were begun . a fiberoptic bronchoaspiration was performed . on the morning of d3 , p / f was 56 ( fio2 = 1 , peep = 10 , vt = 5 - 6 ml · kg - 1 , f = 20 , drager evita4 ). chest x - ray showed major bilateral infiltrates , predominating on the right side (“ white ” right lung ). on the morning of d3 , clonidine was begun ( 1 μg · kg · h - 1 , no bolus ). after resuming sv , ps ( 8 - 12 mm hg , trigger set to the minimum , 100 % automatic tube compensation , vt = 3 . 5 - 5 . 5 ml · kg - 1 actual body weight ) maintained 40 ≦ paco2 ≦ 50 mm hg , ph & gt ; 7 . 2 , 15 & lt ; respiratory rate ( rr )& lt ; 25 bpmin , without substernal retraction , use of accessory muscles , nor dyscoordination of thoraco - abdominal muscles . peep was set to 15 cm h2o on d3 , 20 cm h2o on d4 - 5 - 6 , 15 cm h2o on d6 - 7 . peak pressure upon ps remained ≦ 32 mm hg . as pplat could not be red upon ps on the ventilator and as pl was not measured , pplat was equated to peak pressure for simplicity . fio2 was lowered progressively from 1 to 0 . 4 on d4 - 5 - 6 . on d8 , given a p / f = 262 and cleared chest x - ray , peep was reset to 15 . superior vena cava o 2 saturation remained & gt ; 70 % at all intervals with dobutamine ( d3 to d6 ) 2 then 1 μg · kg - 1 · min - 1 . repeated echocardiography showed no right ventricular ( rv ) dilatation , nor septal bulging . cvvhdf combined to forced diuresis ( mean arterial pressure & gt ; 100 mm hg with noradrenaline [ na ] 0 . 45 μg · kg - 1 · min - 1 lowered to 0 . 01 μg · kg - 1 · min - 1 and high dose furosemide + edecrine ) lowered weight ( d3 : 150 kg ; d7 : 143 kg ). under clonidine 1 μg · kg - 1 · h - 1 , the ramsay score progressively lowered ( ramsay 5 - 6 to 2 - 3 ): mrs x communicated with her family on d5 . sedation was increased with clonidine 2 μg · kg - 1 · h - 1 , combined to loxapine 25 - 100 mg , to ramsay ≧ 3 . on d9 , under clonidine 1 μg · kg - 1 · h - 1 , the patient was extubated to non - invasive ventilation ( niv : cpap = 10 + ps = 10 ) and physiotherapy on d8 - 9 - 10 - 11 and discharged to the floor on d12 . this observation show the positive role of alpha - 2 agonists in the treatment of severe diffuse ards ( p / f = 56 ), together with a fine tuning of the ventilator with respect to the considered patient : oxygenation failure per se ( high peep ), as opposed to an absence of respiratory pump failure ( spontaneous ventilation - pressure support ventilation ). evidently , treatment of acute renal failure , volume overload and sepsis were contributive to the outcome . 1 . jardin f . acute leftward septal shift by lung recruitment maneuver . intensive care med . 2005 ; 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a method for treatment of severe diffuse acute respiratory distress syndrome in an intubated - ventilated patient which includes sedating said patient with at least one alpha - 2 agonist , maintaining spontaneous ventilation and applying pressure support ventilation of at least 5 - 10 cmh 2 o combined to a high positive end expiratory pressure of 10 - 24 cmh 2 o . a pharmaceutical composition containing at least one alpha - 2 agonist suitable for treatment of ards in combination with , if appropriate , at least one sedative agent which does not depress ventilatory drive is also disclosed .