Target-controlled Infusion Of Propofol Used As A Sedative For Patients Undergoing Mechanical Ventilation In Surgical Intensive Care Unit

Research background and Object:Patients in Surgical Intensive Care Unit mostly experienced multi-traumas orlarge operations combined with high risk factors or hemodynamic disorders andrespiratory disorders simultaneously. After moving into ICU, former diseases,invasive testings and treatments, daily nursing, long-term immobilization can causepain to the patient; continuous noisy, continuous surrounding light, various stimuli,sleep disturbances, worry about his own disease can cause anxiety to the patient;extreme anxiety, pain, phrenitis, side effects of drugs or interaction of drugs, anoxia,low blood pressure, low blood glucose, drug or alcohol withdrawal response cancause mania, which all can result in strong stress response, human-machine resist,removal of devices and canals involuntarily. So sedation and pain controll are routinetreatments for patients in ICU.Propofol is a ramification of alkyl-phenolic. It is highly fat-soluble and can passthe blood-brain-barrier very fast, so it takes effect fast. It can redistribute through thetissue rapidly, the metabolism and excretion are also very fast, so the duration ofaction is very short and the patient can recover quickly after stop injection. According to reports, continuous injection of propofot for 8 hours, the context sensitive half timeis less than 40 minutes, therefore, even prolong the duration of injection, the patientcan also recover quickly. In patients with renal and hepatic impairment,propofolplasma clearance rate no obvious decline. The main effect of propofol to the centralnervous system includes hypnosis, sedation and forgetting, also includesdose-dependent anticonvulsion. In 1993, American Food and Drug Administrationpermited propofol can be used as a sedative for patients undergoing mechanicalventilation in intensive care unit. Propofol can cause dose-dependent reduction ofblood pressure, low heart rate, slight dose-dependent respiration depression, reductionof oxygen consumption.Target-controlled infusion(TCI) is based on pharmacokinetics andpharmacodynamics, it's target is the plasma concentration or effect compartmentconcentration, the speed of infusion is controlled by a computer, so it can modulatethe depth of anesthesia and sedation according to clinical requirements. TCI canmodulate blood concentration or effect compartment concentration according toclinical requirements, if a higher concentration is set as a target, the machine canincrease the speed of infusion automatedly, if the target concentration decreases, themachine can stop infusion to wait the blood concentration to decrease to targetconcentration, and then the machine starts in.fusion at an appropriate speed tomaintain the target concentration, it can give a little drug rapidly and automatedly toresume the target concentration after changing syringe. It can avoid the drugaccumulation when the duration of infusion is prolonged.Currently propofol TCI common pharmacokinetic models Marsh model and themodel Schnider. Two models of propofol pharmacokinetics respectively defined thetwo-compartment model and the three-compartment model. Both models will havedifferent infusion program. Both models can be used 15～100 aged adults, also can be used for patients weighing 30-200Kg. But Marsh model without considering the age,for more than 55-year-old patient, Schnider model more accurate.TCI in anesthesia has been widely studied and applied. TCI in the ICU patientsedation at home and abroad regard some preliminary research. Most of the researchis at TCI of propofol in ICU phase of the feasibility study. TCI this administration forthe way in ICU patients application characteristics and advantages, and currently onlyMing-hui CAO and so on research. However, this experimental each experimentalgroup has fixed dose of propofol. But in actual clinical use must be in accordancewith the actual circumstances of timely adjustment of drug dosage. Moreover thisexperiment the patient which non-mechanical ventilation, and use of epiduralanalgesia. But some in ICU patients required mechanical ventilation, and manypatients can not use epidural analgesia. So, SICU mechanically ventilated patients inthe united intravenous analgesia, TCI of propofol administration this way there willbe what kind of features and advantages?Our study compared TCI of propofol and continuous infusion of propofol bymicro-pump used as a sedative in patients undergoing mechanical ventilation in SICU,both assisted by continuous intravenous pump of sufentanil for pain controll. Inorder to study the effect and characteristics of TCI of propofol as a sedative forpatients undergoing mechanical ventilation in SICU, we evaluated sedativeeffect(Ramsay score of 2-5/total Ramsay score), time to recovery following cessationof the infusion, times of drug adjustment, drug dose,adverse events, changes of lifesign before and after TCI, detection of life sign at different time during TCI.Methods:40 patients older than 18 years in SICU undergoing mechanical ventilation wereselected and divided two groups randomly with 20 cases each. Patients in group Breceived TCI of propofol, patients in group C received continuous intravenous infusion of propofol. Exclude patients with serious head trauma and hepatic and renalfunction damage. Loading dose and (or) continuous infusion of propofol were givenin 2 hours. Exclude patients whose sedation had been established with agent otherthan propofol for more than 24 hours and patients received long-lasting local orregional anesthetic blocks, patients with long-term usage of opioid drug were alsoexcluded.After patients moving into ICU, ventilator was used to asist repiration andinfusion of propofol was performed by Base Primea Orechestra drug infusionworkstation. Sedation score used Ramsay Scale (Ramsay Scale: 1-sober, anxious orrestless or both; 2-sober, cooperative, orientated and tranquil; 3-sober, responding tocommands; 4-sleep, brisk response to stimutus such as percus on glabellum or loudauditory stimulus; 5-sleep, sluggish response to stimulus; 6-sleep, no response tostimulus).Target blood drug concentration of group B was set as 0.5μg/ml, patients ingroup C was given loading dose by intravenous infusion in the range of 0.5 or1.0mg/kg (Anesthesia not regain consciousness without the patient's agitation dose of0.5mg/kg, Other patients a dose of 10mg/kg.).The induction time of both groups was1 minute. Ramsay Scale was recorded every 1 hour.Target blood drug concentrationof group B was set in the range of 0.5-2.0μg/ml to maintain target sedationdepth(Ramsay Scale of 2-5); patients in group C were maintained at the samesedation depth by intravenous infusion at the speed in the range of 0.5-2mg/kg/h. Inboth groups, the sedation depth at night was relatively deeper(Ramsay Scale in therange of 4-5), at morning and before extubation, the sedation depth became lowergradually(Ramsay Scale in the range of 2-3), Before sputum suction and turningover, increase the target concentration by 0.3μg/ml and set back after that, patients ingroup C were given 0.5mg/kg at one time. Patients in both groups were given sulfentanil in the range of 0.05μg/kg/h forpain controll by intravenous infusion.Continuously monitored heart rate, blood pressure, respiration, SpO₂, and alsorecorded MBP, HR, SpO₂ at different time, including before sedation(T1), 1 hourafter sedation(T2), 2 hours after sedation(T3), time of stoping sedation(T4), the timeof recovery(T5), the time before nursing manipulation(including sputum suction andturning over, T6), the time during nursing manipulation(T7), the time after nursingmanipulation(T8).Recorded times of adjustment of dose during sedation, the total dose ofsulfentanil and propofol, total time of sedation, time to recovery after stop sedation,total times of performing Ramsay Scale, times of performing Ramsay Scale in therange of 2-5, calculate sedation efficiency times of performing Ramsay Scale in therange of 2-5/total times of performing Ramsay Scale.Recorded adverse event(hypotension, tachycardia, excessive sedation, lightsedation, respiration depression, re-asleep, nausea, vomit).All data in the form of (?)±S were analyzed by SPSS13.0. Adverse events,times of adjustment of propofol, total sedation time, dose of sulfentanil, dose ofpropofol were analyzed by two dependent samples t test, recovery time and sedationefficiency were analyzed by covariance analysis, MBP, HR, SpO₂ at different timewere analyzed by variance analysis of repeated measures data. Set p＜0.05 as thesignificant level.Results:1. There were no significant differences in age, gender, weight, severity ofdiseases(APACHEâ…¡Scale) of patients between target-controlled infusion group andcontinuous infusion group(P＞0.05).2. There were no significant differences in total sedation time and dose of sufentanil and propofol between two groups(P＞0.05).3. Sedation efficiency in target-controlled infusion group(89.6±10.9) washigher than that in continuous infusion group(77.0±20.8)(P＜0.05).4. Recovery time in target-controlled infusion group was 10.5±7.7 min,recovery time in continuous infusion group was 9.4±4.9, there were no significantdifferences in recovery time between two groups(P＞0.05).5. Times of adjustment of drug in target-controlled infusion group(1.9±1.7) wasless than that in continuous infusion group(3.2±2.0)(P＜0.05).6. Scales of adverse events in target-controlled infusion group(1.0±1.0) waslower than that in continuous infusion group(1.8±1.1)(P＜0.05).7. There were no significant differences in MBP,HR,SpO₂ at T1, T2, T3, T4, T5across groups(P＞0.05). Comparing within group, MBP at T5 showed a tendency toincrease, there were significant differences between T5 and T1, T2, T3,T4 (P＜0.05).HR has the drop tendency in T1 and T4,there were also significant differencesbetween T1 and T2, T3, T4(P＜0.01), HR at T5 showed a tendency to increase,significant defferences were founded between T5 and T2, T3, T4(P＜0.05); nosignificant defferences were founded in SpO₂ at different time(P＞0.05).8. There were no significant differences in MBP,HR,SpO₂ at T6, T7, T8 acrossgroups(P＞0.05). Compared within group, significant differences in MBP, HR, SpO₂were founded at T7 and T6, T8(P＜0.05).Conclusions:1. TCI of propofol can be used to mechanically ventilated patients in ICUsedation therapy.2. Compared with continuous infusion, there are less adverse events intarget-controlled infusion, it can provide highter sedation efficiency, more stablesedation and it is easier to controll sedation depth with less adjustment of dose, aditionally, it is more convenient to manipulate.3. There are no great affetion of both methods to dose of propofol and revoverytime during short-time sedation in 24 h.4. Both target-controlled infusion and continuous infusion can maitain stableblood pressure and SpO₂, reduce HR.