Comparison between inhaled sedation with Sevoflurane vs endovenous sedation with Propofol in the Intensive Care Unit: a randomized prospective trial

INTERVENTION: Trade Name: SEVOFLURANE PIRAMAL ‐ 100% V/V LIQUIDO PER INALAZIONE 1 FLACONE IN VETRO DA 250 ML Product Name: Sevoflurano Product Code: N01AB08 Pharmaceutical Form: Pressurised inhalation, solution INN or Proposed INN: SEVOFLURANO CAS Number: 28523‐86‐6 Current Sponsor code: SEVOFLURANO Other descriptive name: Sevoflurane Concentration unit: % percent Concentration type: range Concentration number: 0‐2 Trade Name: PROPOFOL KABI ‐ 20MG/ML EMULSIONE INIETTABILE O PER INFUSIONE 10 FLACONCINI DA 50 ML Product Name: Propofol Product Code: N01AX10 Pharmaceutical Form: Solution for injection INN or Proposed INN: PROPOFOL CAS Number: 2078‐54‐8 Current Sponsor code: PROPOFOL Other descriptive name: Propofol Concentration unit: mg/kg/h milligram(s)/kilogram/hour Concentration type: range Concentration number: 0‐3 CONDITION: Preoperative‐scheduled sedation in surgical patients admitted in the Intensive Care Unit (ICU) for postoperative monitoring ; MedDRA version: 21.1 Level: LLT Classification code 10049124 Term: Sedation during medical procedure System Organ Class: 100000004865 Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] ‐ Anesthesia and Analgesia [E03] PRIMARY OUTCOME: Main Objective: The primary objective of the study is to demonstrate the reduction of the extubation time in the Sevoflurane sedated group compared to the group of patients sedated with Propofol, starting from similar depth of sedation. Primary end point(s): The extubation time will be evaluated quantitatively: when the ICU physician will consider the patient ready to be weaned from mechanical ventilation (according to routine clinical criteria) sedation with Propofol or Sevoflurane will be suspended. From the "stop" of sedation the time needed to allow a complite consciousness and safetly extubation will be recorded. Secondary Objective: Evaluate the total duration of mechanical ventilation in the ICU between the two study groups.; Evaluate the hemodynamic pattern in patients sedated with Sevoflurane compared to patients sedated with Propofol.; Evaluate the quality of waking in patients sedated with Sevoflurane compared with patients sedated with Propofol.; Assess the quality of sleep during sedation with Sevoflurane compared to Propofol.; Quantify plasma and urine inorganic fluoride concentration during sedation.; Evaluate the outcome of patients in the two study groups.; Evaluate the glicaemic stability in the two study groups. Timepoint(s) of evaluation of this end point: In the two study groups we will compare the time required from the patients to be safetly extubated from the Prpofol or Sevoflurane interruption. This data (expressed in minutes) will be reported as median and interquartile range and formaly recorded at the time of extubation. INCLUSION CRITERIA: • Consent, obtained during the preoperative period, for data treatment , randomization and participation in the study. • Age > 18 years • Pre‐operative indications for post‐operative monitoring in the ICU Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20 SECONDARY OUTCOME: Secondary end point(s): We will evaluate the total duration of mechanical ventilation (calcolated in minutes) between the two study groups, from the admission in the ICU to the removal of the orotracheal tube.; From the admission in the ICU systolic, diastolic and meanl arterial blood pressure will be recorded (in mmHg), as well as the heart rate (bpm) and the need for inotropic / vasopressor support (in mcg/kg/min).; The quality of patients awakening will be evaluated trought the "Richmond Agitation‐Sedation Scale" after the extubation.; The quality of sleep will be evaluated in the two study groups through a sleep profiler: comparing the total sleep time (TST, in minutes) and the percentages of N1, N2 and N3 spleep compared to TST (in percentages) in the first 12 hours of sedation.; The plasmatic and urinary inorganic fluoride concentrations (in ppm) will be measured by PH‐meter with ion‐selective probe.; The outcome of the patients will be expressed in terms of: ICU lenght of stay (day), hospital lenght of stay (day), ICU mortality (percentage), and hospital mortality (percentage).; Glicaemic metabolic control will be expressed as glucose variability (ratio between standard deviation of glicaemia and the means observed during the sedation). Timepoint(s) of evaluation of this end point: This timing will be expressed in minutes, it will be recorde at the time of extubation and will be compared in the final analysis between the two groups. ; All these parameters will be measured hourly during the entire sedation.; This evaluation will be performed 30 minutes after the extubation.; This evaluation will be continuously performed in the first 12 hours of sedation.; These concentrations will be evaluated at the time of extubation and after 24 hours. ; These assesments will be performed at the ICU discharge and at the hospital discharge or at the patient's death.; Glucose variability will be expressed at the end of the study considering all glicaemia values observed at hemogasanalysis required for routine practice in postoperative patients.