Propofol or midazolam for short-term alterations in sedation [Sedative-analgesic medication in intensive care patients needing ventilator treatment]. 2% propofol for sedation in the intensive care unit Cost of ICU sedation: comparison of empirical and controlled sedation methods. Use of 2 % propofol to produce diurnal sedation in critically ill patients Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU. Sedation of critically ill patients during mechanical ventilation. A comparison of propofol and midazolam. Propofol or midazolam for sedation and early extubation following cardiac surgery Patterns of prescribing and administering drugs for agitation and pain in patients in a surgical intensive care unit Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial. COMPARISON OF PROPOFOL AND MIDAZOLAM FOR SEDATION IN CRITICALLY ILL PATIENTS [Propofol for sedation during postoperative mechanical ventilation. A comparative study with Lytic Mixture]. Propofol versus midazolam for intensive care unit sedation after coronary artery bypass grafting Comparison of propofol and midazolam for sedation in intensive care unit patients. Continuous intravenous infusions of lorazepam versus midazolam for sedation during mechanical ventilatory support: A prospective, randomized study Comparison of the sedative and amnesic effects of midazolam and propofol. An economic evaluation of propofol/fentanyl compared with midazolam/fentanyl on recovery in the ICU following cardiac surgery Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis. Synergistic sedation with propofol and midazolam in intensive care patients after coronary artery bypass grafting. Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost. Propofol for long‐term sedation in the intensive care unit * A comparison with papaveretum and midazolam A cost analysis of alfentanil+propofol vs morphine+midazolam for the sedation of critically ill patients. Propofol sedation after open heart surgery A clinical and pharmacokinetic study Economic Analysis of Health Care Technology: A Report on Principles Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Cardiovascular Responses during Sedation after Coronary Revascularization: Incidence of Myocardial Ischemia and Hemodynamic Episodes with Propofol Versus Midazolam Propofol and alfentanil infusions for sedation in intensive therapy. Propofol Versus Midazolam: Safety and Efficacy for Sedating the Severe Trauma Patient [The use of ketamine and midazolam for analgesia and sedation in ventilated patients subject to obligatory treatment with catecholamines]. Light Versus Heavy Sedation After Cardiac Surgery: Myocardial Ischemia and the Stress Response Midazolam sedation following open heart surgery. Isoflurane compared with midazolam for sedation in the intensive care unit. [Propofol versus midazolam. Long-term sedation in the intensive care unit]. Urine and Plasma Catecholamine and Cortisol Concentrations after Myocardial Revascularization: Modulation by Continuous Sedation
It is often necessary to adjust a patient ’s sedation level while they are in the intensive care unit . The purpose of this study was to compare propofol with midazolam for controlling short-term alterations in sedation .  Twenty-three patients undergoing an interactive procedure , physiotherapy , during mechanical ventilation of the lungs were studied . The patients were r and omly assigned to receive infusions of propofol or midazolam for sedation . Sedation was assessed using the method of Ramsay , where 3 is drowsy responding only to comm and s ; and 5 is asleep with a slow response to light glabellar tap . Prior to physiotherapy sedation was deepened from 3 to 5 by increasing the sedative infusion rate , and level 5 was maintained during physiotherapy by adjusting the infusion rate whenever necessary . After physiotherapy , the sedative dose was reduced until level 3 was again achieved . During physiotherapy , sedation level 5 was achieved for 53.9 % of the time with propofol but for only 25.7 % with midazolam ( P < 0.01 ) . After physiotherapy , those patients se date d with propofol  re-awakened to level 3 faster ( 8.3 ± 2.3 min , mean ±SE ) than those receiving midazolam ( 92.8 ± 35.0 min , P < 0.05 ) . After physiotherapy , a further 1.8 ± 0.5 dose adjustments were required to the  midazolam  infusion while only 0.4 ± 0.2 adjustments were required to the propofol infusion ( P < 0.05 ) . During physiotherapy 3.0 ± 0.5 dose adjustments to the propofol dose were required compared with 3.6 ± 0.5 adjustments to the midazolam dose ( NS ) . It is concluded that , during a st and ardized stimulus , physiotherapy , propofol infusion allowed a desired sedation score to be maintained for more of the time than did infusion of midazolam . Subsequently , when the infusion rates were reduced , less time was taken to re-awaken to baseline levels after physiotherapy , with fewer adjustments to the infusion rate , in those patients receiving propofol than midazolam . RésuméAux soins intensifs , il faut fréquemment modifier le niveau de sédation ; cette étude compare le propofol au midazolam pour contrôler ces changements de courte durée . Vingt-trois patients sous ventilateur mécanique soumis à des manoeuvres de physiothérapie interactive sont inclus dans l’étude . Ils reçoivent au hasard en sédation une perfusion de profopol ou de midazolam . La sédation est évaluée selon l’échelle de Ramsey ; on accorde 3 pour la somnolence avec réponse aux ordres et 5 au sommeil avec réponse lente à la légère percussion de la glabelle . Avant la physiothérapie , la sédation est approfondie du niveau 3 au niveau 5 en augmentant la perfusion au besoin . Après la physiothérapie , on réduit la perfusion jusqu’au retour au niveau 3 . Pendant la physiothérapie , le niveau 5 est atteint pendant 53,9 % de la durée du traitement avec le propofol contre seulement 25,7 % avec le midazolam ( P < 0,01 ) . Après la physiothérapie , les patients sous propofol reviennent au niveau 3 plus rapidement ( 8,3 ± 2,3 min , moyenne ± SD ) que ceux qui reçoivent du midazolam ( 92,8 ± 35,0 min , P < 0,05 ) . Après la physiothérapie , le dosage de midazolam nécessite 1,8 ± 0.5 ajustements comparativement à 0,4 ± 0,2 pour le propofol ( P < 0,05 ) . Pendant la physiothérapie , la posologie du propofol doit être ajustée 3,0 ± 0,5 fois comparativement à 3,6 ± 0,5 pour celle du midazolam ( NS ) . En conclusion , pendant une stimulation st and ardisée , la perfusion de propofol permet de maintenir le niveau de sédation désiré plus souvent que la perfusion de midazolam . Par la suite , lorsqu’on diminue la perfusion , le temps requis pour le retour à la ligne de base nécessite moins d’ajustements pour le propofol que pour le midazolam UNLABELLED It was the aim of this study to compare two regimens for sedation and analgesia during ventilator treatment in intensive care patients . Special regard was given to endocrine stress response , neuro-monitoring , hemodynamic parameters and clinical practicability . METHODS A total number of 16 patients of an operative ICU were r and omly allocated to the following groups : ( 1 ) Fentanyl-group , approximately 0.2 mg/h fentanyl , 2.5 mg/h midazolam and 2 mg/h pancuronium in intermittent doses , ( 2 ) ketamine-group , about 50 mg/h ketamine and 2.5 mg/h midazolam by syringe pump , in addition 2 mg/h pancuronium . During a period of 2 days and in intervalls of 6 h , plasma levels of epinephrine and norepinephrine ( by HPLC/ECD ) , ADH , ACTH and cortisol ( by RIA ) , ketamine ( by GC ) and stress-metabolites ( glucose , lactate , free glycerol ) were determined . Hemodynamic parameters were investigated in intervalls of 12 h , EEG ( Compressed Spectral Array , CSA ) in intervalls of 24 h. In addition , routine laboratory data , vigilance and adaptation to the respirator were observed . RESULTS Plasma levels of adrenaline , noradrenaline , dopamine , ADH , ACTH , cortisol and stress-metabolites were comparable in both groups . Levels of ADH , ACTH , cortisol and free glycerol did not leave the normal range . In three patients , in which epinephrine- or norepinephrine-infusions were necessary to improve cardiocirculatory stability , this treatment could be finished after beginning of the ketamine application . In both groups , CSA showed a dominant delta- und theta-activity according to the clinical aspects of sufficient sedation and analgesia . Hemodynamic parameters were comparable in both groups . ( ABSTRACT TRUNCATED AT 250 WORDS A 2 % solution of propofol has been compared with the 1 % formulation for sedation in patients whose lungs were being mechanically ventilated in an intensive care unit following coronary artery bypass surgery . There were no significant differences in the amount of  propofol  used in the two groups , the rate of  propofol infusion or the number of changes made to the infusion rate to maintain the desired level of sedation . Recovery times and times to tracheal extubation were similar . The mean heart rates of those receiving 2 % propofol were significantly higher throughout the period of the study for no apparent reason . Propofol 2 % was found to be safe , easy to administer and a practical alternative to the 1 % solution for sedating cardiac surgical patients A r and omised crossover study was undertaken to compare the quality and cost of controlled versus empirical sedation with midazolam in critically ill patients . Patients ( n = 40 ) entering the ICU were enrolled provided they satisfied the strict entry criteria . During 90 hours of midazolam sedation , patients received r and omly allocated 10-hour periods of controlled or empirical sedation . With empirical sedation , the mean dose of midazolam  and the cost of sedation were almost double those with controlled sedation . The quality of sedation was superior with the controlled method . In a separate study on 352 patients , a cost-benefit analysis of controlled sedation with midazolam or propofol infusion or bolus injections of morphine plus diazepam showed that the quality of sedation achieved with propofol was superior to the other two regimens and that , with morphine plus diazepam , the quality of sedation was unacceptably poor . Although the direct purchase price of propofol was higher than that of other agents , the total cost of sedation with propofol was lower than that for midazolam for short-term intensive care ( less than 24 hours ) and comparable to midazolam for longer-term use . However , indirect benefits of sedation with propofol include a much shorter ICU stay with the attendant reduced nursing costs and greater throughout the patients , and this more than compensates for the higher purchase price of the agent Objective : The assessment of propofol to produce diurnal sedation in critically ill patients Design : Prospect i ve clinical study Setting : Intensive Care Unit , University Hospital Patients and participants : Thirty consecutive patients admitted to the Intensive Care Unit older than 18 years who were expected to be se date d for more than 50 h Interventions : The patients were r and omised into two groups . All received sedation with a constant background infusion of morphine and a variable infusion rate of propofol , which was altered hourly to maintain the intended sedation score . The first group received constant light sedation ( CLS ) over 50 h aim ing for a Ramsay score of 2–3 . The second group received CLS between 0600 h and 2200 h and additional night sedation ( ANS ) with propofol between 2200 h and 0600 h , aim ing for a sedation score of 4–5 . Measurements and results : Patients were studied for 50 h from 1800 h on the first day of admission . Recordings of heart rate , blood pressure , sedation scores and propofol and morphine infusion rates were made hourly . An APACHE II score was recorded for each patient . Sedation scores were analysed by blind visual assessment and cosinor analysis , which is used in chronobiology to examine the correlation of data with a cosine curve . Patients in the ANS group had significantly better rhythmicity of sedation levels using cosinor analysis ( r = 26 % v 8 % ) p < 0.01 . There was no difference between the CLS and ANS groups with respect to age , sex or APACHE II scores . Nine out of 15 patients in the ANS group achieved diurnal sedation . Three patients in the CLS group showed diurnal rhythmicity of sedation , which can be attributed to natural sleep , and had a median APACHE II score of 12 . Five patients in the CLS group and three in the ANS group showed a deep constant sedation pattern . They had high APACHE II scores ( median 21.5 ) and an obtunded conscious level on admission due to severe sepsis . Conclusion : Propofol can safely provide diurnal sedation in the critically ill when titrated against the Ramsay score . Sedation levels can not be manipulated in some severely ill patients Sedation was studied in 30 patients requiring overnight ventilation in the intensive therapy unit ( ITU ) . Patients received an infusion of either alfentanil or pethidine , supplemented with midazolam . The infusion rates were adjusted to provide optimal sedation as judged by a nurse , and measurements were made of quality of sedation , recovery and serum cortisol concentration . In addition , blood concentrations of alfentanil were measured to permit pharmacokinetic and pharmacodynamic analysis . Satisfactory sedation was achieved in both groups . The required infusion rate for alfentanil was between 0.4 and 0.5 micrograms kg-1 min-1 . Recovery was good in both groups , apart from one patient in the alfentanil group , in whom recovery was greatly prolonged and alfentanil pharmacokinetics were abnormal . A difference was found in the metabolic response to surgery between the two groups , the response in the alfentanil group being significantly less marked Propofol ( P ) and midazolam ( M ) are frequently given by continuous infusion for sedation in critically ill , mechanically ventilated patients . We compared these drugs with regard to : ( 1 ) time-to-awaken ; ( 2 ) reproducibility of bedside assessment s of level of sedation ; ( 3 ) time-to-sedation ; and ( 4 ) change in oxygen consumption ( V O2 ) from awake to se date d state . Seventy-three patients were prospect ively r and omized to receive either P ( n=37 ) or M ( n=36 ) . Wake-up times after stopping the drug were assessed by blinded and unblinded observers , by asking patients to perform simple tasks . Times to se date were assessed by consensus agreement among nurses and investigators . Demographics and APACHE II scores were not different between P and M. The P group had a significantly narrower range of wake-up times with a higher likelihood of waking in less than 60 min . Blinded versus unblinded observations had excellent correlation . Average time to se date and decrease in V O2 were not different . We conclude that in this patient population : ( 1 ) both P and M achieved optimal sedation in a large fraction of patients when administered by specified dosing protocol s ; ( 2 ) P had a faster , more reliable , wake-up time ; ( 3 ) assessment s of time-to-awaken were objective and reproducible ; ( 4 ) time to sedation was not significantly different ; ( 5 ) V O2 decreased similarly with both Purpose The purpose of this r and omized , double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery . Methods ASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45 % were eligible . All patients received a st and ardized sufentanil/isoflurane anaesthesa . Dunng cardiopulmonary bypass 100 μg · kg−1 · mm−1 propofol was substituted for isoflurane . Upon amval in the Intensive Care Unit ( ICU ) . patients were r and omized to either 10 μg · kg · min−1 propofol ( n = 21 ) or 0.25 μg · kg · mm−1 midazolam ( n = 20 ) . Infusion rates were adjusted to maintain sedation within a predetermined range ( Ramsay 2–4 ) . The infuson was terminated after four hours . Patients were weaned from mechanical ventilation and their tracheas extubated when haemodynamic stability , haemostasis , normothermia and mental orientation were confirmed . Haemodynamic measurements , artenal blood gas tensions and pulmonary function tests were recorded at specified times . Results There were no differences between the two groups for the time spent at each level of sedation , number of infusion rate adjustments , amount of analgesic and vasoactive drugs , times to awakening and extubation . The costs of propofol were higher than those of midazolam . There were no differences in haemodynamic values , artenal blood gas tensions and pulmonary function . Conclusion We conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher . RésuméButLe but de cette étude r and omisée , à double insu était d’évaluer l’efficacité du midazolam et du propofol pour sédation postopératoire en vue d’une extubation précoce postchirurgie cardiaqueMéthodologieTout patient ASA II-III admis pour une première chirurgie cardiaque élective ayant une fraction d’éjection > 45 % était éligible . Tous les patients ont reçu une anesthésie st and ard à base de sufentanil/isoflurane . Durant la circulation extracorporelle , le propofol ( 100μg · kg−1 · min−1 ) a été substitué à l’isoflurane . Dès l’arnvée aux soins intensifs , les patients furent r and omisés soit au propofol ( n = 21)à 10 μg · kg−1 · mm−1 sort au midazolam ( n = 20 ) 0.25 μg · kg−1 · mm−1 . Les débits de perfusion étaient ajustés pour maintenir un niveau de sédation prédéterminée ( Ramsay 2–4 ) . La perfusion était cessée après quatre heures . Les patients étaient sevrés de la ventilation mécanique et extubés  lorsque la stabilité hémodynamique , l’hémostase , la normothermie et l’orientation mentale étaient confirmées . Des bilans hémodynamiques , gaz arténels et fonction pulmonaire furent enregistrés à des intervalles spécifiques . RésultatsIl n’y avait pas de différence entre les groupes pour le temps occupé aux différents niveaux de sédation , d’ajustement de perfusion , le temps d’éveil et d’extubation . Le coût du propofol était plus élevé que celui du midazolam . La dem and e d’analgésique et l’utilisation d’agents vasoactifs étaient similaires . Aucune différence de fonction pulmonaire , gaz arténels et hémodynamique n’a été décelée . Conclusion Nous concluons que le midazolam et le propofol sont sécuritaires et efficaces comme agents de sédation permettant une extubation précoce pour ce groupe de patients cardiaques sélectionnés mais le coût du propofol est plus élevé Objectives To describe the variety of medications prescribed along with the doses administered and routes of administration , and to delineate the clarity of orders written and the accuracy of transcription of drugs used for sedation , anxiety , pain , and neuromuscular blockade in a surgical intensive care unit ( ICU ) . Design A prospect i ve , observational study of drug-related information collected from forms used by physicians and nurses . Setting Three adult surgical ICUs at an academic medical center . Patients were admitted to a surgical service and co-managed by the surgical ICU team and primary surgical service . Patients Consecutive patients admitted to all of these units from September 1992 to January 1993 . Interventions None . Measurements and Main Results Information on prescribing and administering sedatives , analgesics , and neuromuscular blocking drugs was obtained from data collected on 221 patients . A total of 202 ( 91 % ) patients received , on average , 1.9 ± 1.4 study drugs ( range 0 to 9 ) in a wide variety of combinations . There were 2,103 total doses administered from 448 drug orders . Ninety percent of study drug orders were written for administration on an “ as-needed ” basis ; in 42 % of these orders , the indication for use was not specified . On average , only 27 % of the maximal allowable daily dose was administered ; this number ranged from 15 % for hydromorphone to 77 % for chlordiazepoxide . Morphine sulfate , the most commonly prescribed drug , was ordered primarily for intravenous administration in 84 % of patients . Morphine sulfate was prescribed using 19 different doses ( written as a range of doses ) and 13 different dosing intervals . Transcription discrepancies were observed in 17 % of orders . In 2.7 % of doses , the actual dose that was administered could not be determined . Conclusions A wide variety of sedatives and analgesics are frequently used in surgical ICU patients . These agents are often ordered on an “ as-needed ” basis using a range of doses , sometimes without adequate directions about the indication for their use . Daily doses received are significantly less than their maximum allowable daily doses . Orders for these medications are sometimes transcribed and charted incorrectly . In contrast , neuromuscular blocking agents are not commonly prescribed . Future studies are needed to improve order writing of these agents , and to determine the criteria used by physicians and nurses in the selection and administration of these agents , the outcomes of therapy , and the most cost-effective regimen . ( Crit Care Med 1994 ; 22:974–980 OBJECTIVES To compare the effectiveness , characteristics , duration of action , hemodynamic and biochemical effects , and side effects of propofol and midazolam used for continuous intravenous sedation of ventilated critically ill patients . DESIGN Multicenter , prospect i ve , r and omized , nonblinded study . SETTING Nine Spanish general intensive care units ( ICUs ) . PATIENTS Ninety-eight patients admitted to the ICU who were mechanically ventilated and required sedation for a minimum of 48 hrs . INTERVENTIONS Propofol or midazolam was used for induction and maintenance of continuous intravenous sedation for a maximum of 5 days . The effectiveness of those two regimens was assessed according to their effects on ventilatory management and the presence of agitation . MEASUREMENTS AND MAIN RESULTS In 93 % of the patients studied , there was a medical cause necessitating mechanical ventilation . The mean ( + /-SD ) duration of sedation was 81 + /- 25 hrs and 88 + /- 27 hrs for the propofol and midazolam groups , respectively . The induction dose was 2.24 + /- 0.43 mg/kg over 318 + /- 363 secs for propofol , and 0.22 + /-0.07 mg/kg over 33 + /-29 secs for midazolam . The maintenance dose was 2.8 + /-1.1 mg/kg/hr for propofol and 0.14 + /- 0.10 mg/kg/hr for midazolam . There was no difference regarding the opiate and muscle relaxant requirements between the two groups . Sedation with propofol was more effective in achieving patient-ventilator synchrony than that with midazolam after the first hour of treatment ( p < .01 ) . Patients se date d with propofol awoke more rapidly and with less variability that those patients se date d with midazolam ( 23 + /- 16 mins vs. 137 + /- 185 mins , respectively , p < .05 ) , particularly in those patients requiring deep sedation ( 27 + /- 16 mins vs. 237 + /- 222 mins , respectively , p < .01 ) . No hemodynamic or biochemical changes were detected in any of the treatment groups . During induction , five patients in the propofol group and two patients in the midazolam group had hypotension . CONCLUSIONS In this population of critically ill patients , propofol is an effective and safe alternative for sedation , with some advantages , such as short duration of action and high effectiveness over the conventional regimen with benzodiazepines and opiates 101 critically ill patients admitted to five intensive-care units were allocated r and omly to receive a continuous intravenous infusion of either propofol or midazolam for sedation for up to 24 h. In addition , morphine was given to provide analgesia . The mean duration of infusion was 20.2 h ( range 3.0 - 24.5 ) in the propofol group and 21.3 h ( 4.0 - 47.0 ) in the midazolam group and infusion rates were 1.77 mg/kg/h ( range 0.40 - 5.00 ) and 0.10 mg/kg/h ( 0.01 - 0.26 ) , respectively . The infusion rates were adjusted as necessary , and the desired level of sedation was achieved easily in most patients in both groups . There were slight falls in arterial pressure , but there were no significant differences between the groups . Heart rate was lower in patients who received propofol . Some small changes occurred in biochemical and haematological variables in both groups , but they were not clinical ly significant . There was no indication that either drug substantially impaired adrenal steroidogenesis . When the infusion was discontinued , there was less variability in recovery of consciousness in patients who had received propofol . In a subgroup of patients , weaning from mechanical ventilation was achieved significantly faster after discontinuation of propofol than of midazolam . Propofol proved to be a satisfactory agent for sedation of these critically ill patients and compared favourably with midazolam Propofol infusion was found to provide excellent sedation and rapid recovery in intensive care . The present study compared Propofol with lytic solution ( lytic solution = mixture of 100 mg Pethidine , 50 mg Promethazine and 0.6 mg Dihydroergotamine ) during 6 hours of postoperative artificial ventilation . 60 patients after major abdominal surgical procedures were studied with ethical committee approval and informed consent . Patients were r and omly allocated to receive either Propofol or lytic solution . We aim ed at a sedation level of stage 5 according to the Ramsey score . The mean drug dosages were 3.9 mg/kg/h of Propofol and 4.2 ml/h of lytic solution .  Hemodynamic values , blood gases as well as various biochemical measures did not show any difference between the groups . At the end of the sedation period triglyceride concentrations were significantly higher in patients receiving Propofol ( 166 + 79 mg/dl ) compared to the control group ( 97 + 60 mg/dl ) . Significant and relevant differences were found for the times of recovery after discontinuation of the sedative . These times were very short in the Propofol group . Furthermore , in view of a longer recovery time after lytic solution in this group the respiratory rate was significantly slower up to the end of the observation period . We conclude that a major advantage of Propofol in the present study was the rapid recovery after 6 hour sedation . Patients gain vigilance rapidly and sufficient spontaneous respiration within minutes . Not at least thanks to these facts patient 's safety can be improved in the recovery period Objective To compare the safety and effectiveness of propofol ( 2,6-diisopropylphenol ) to midazolam for sedation of mechanically ventilated patients after coronary artery bypass grafting . Design Open , r and omized , prospect i ve trial . Setting Cardiothoracic intensive care unit ( ICU ) , Clevel and Clinic Foundation . Patients Eighty-four patients with normal or moderately impaired left ventricular function who underwent elective coronary artery bypass graft surgery under high-dose opioid anesthesia . Interventions Patients were r and omly selected to receive either propofol ( mean loading dose 0.24 mg/kg ; mean maintenance dose 0.76 mg/kg/hr ) or midazolam ( mean loading dose 0.012 mg/kg ; mean maintenance dose 0.018 mg/kg/hr ) . Infusion rates were titrated to keep patients comfortable , drowsy , and responsive to verbal stimulation . Study duration , 8 to 12 hrs ; infusions were started in the ICU when patients were awake and hemodynamically stable . Measurements and Main Results During therapy , both groups had lower mean arterial pressures and heart rates compared with baseline measurements ; however , the propofol group had significantly lower heart rates than the midazolam group during the first 2 hrs of infusion . The propofol group also had significantly lower blood pressure measurements 5 and 10 mins after the initial dose , although there was no difference during infusion . Baseline cardiac output was measured before starting the infusion , and measurements were repeated during continuous infusion at 4 , 8 , and 12 hrs . Cardiac output values were similar . Propofol maintenance infusions ranged from 3 to 30 μg/kg/min and midazolam infusions ranged from 0.1 to 0.7 μg/kg/min . At these infusion rates . both groups had adequate sedation , based on nurse and patient evaluations ; however , the propofol group used significantly lower total doses of sodium nitroprusside and supplemental opioids . Conclusions Both propofol and midazolam provided safe and effective sedation of coronary artery bypass graft patients recovering from high-dose opioid anesthesia . The reduced need for both antihypertensive medication and opioids seen in the propofol group may be advantageous . However , the hypotension seen after the initial bolus dose of propofol may be a concern . No difference between the two drugs could be demonstrated in time to extubation or ICU discharge , although it is probable that time to extubation was governed more by residual operative opioids than the study agents . ( Crit Care Med 1994 ; 22:1415–1423 OBJECTIVES To evaluate the comparative safety and effectiveness of intravenous infusion of propofol or midazolam when used for 12 to 24 hrs of sedation and to evaluate the quality of sedation during stimulation . DESIGN An open , comparative , prospect i ve , r and omized study . SETTING Surgical intensive care unit ( ICU ) in a university hospital . PATIENTS Postoperative , intubated , general surgical , and orthopedic patients requiring mechanical ventilation ( n = 60 ) . INTERVENTIONS None . MEASUREMENTS Assessment s were made at baseline ( 0 time ) , 5 , 10 , 15 , 30 , 45 , and 60 mins ; at 2 , 4 , 6 , 8 , 10 , 12 , 14 , 16 , 18 , 20 , 22 , and 24 hrs ; and at the end of sedation . The assessment s included systolic , mean , and diastolic blood pressures , heart rate , two-lead electrocardiogram , pulse oximetry oxygen saturation , FIO2 , end-tidal CO2 , respiratory rate , ventilator rate , tidal volume , and sedation scale . Vital signs and the sedation scale were obtained at 30 , 60 , and 90 mins and at 2 , 4 , 12 , and 24 hrs after the end of sedation . At approximately 8 hrs and 24 hrs ( or at the end of sedation ) , the patient 's CO2 production was calculated over a 5-min interval . Every 4 hrs , the nurse would summarize and rate patient response during stimulation as well as the overall rating of the sedation and patient ability to tolerate the ICU setting . MAIN RESULTS There were no significant differences in pulse oximetry , arterial blood gas values , or respiratory measurements during sedation with propofol or midazolam . The mean heart rate was slower in the propofol group throughout the sedation and postsedation periods . The rating of sedation and tolerance of the ICU environment were significantly better for the propofol-treated group . Postsedation , the propofol group woke up faster on discontinuation of the sedative . CONCLUSIONS Propofol was as safe and as efficacious as midazolam for continuous intravenous sedation . The quality of sedation was better in the propofol group To evaluate the efficacy of continuous infusions of lorazepam vs. midazolam for sedation in the intensive care unit ( ICU ) . Design : Prospect i ve , r and omized study . Setting : Large , urban university hospital . Patients : Twenty adult medical ICU patients receiving mechanical ventilatory support . Interventions : Patients were r and omized to receive either lorazepam or midazolam .  The infusion rate was adjusted at the bedside by the ICU nurse according to a st and ardized study protocol to achieve and maintain sedation at Ramsay 's sedation level 2 or 3 . Measurements and Main Results : Ten patients were r and omized to receive lorazepam and ten to receive midazolam .  The groups were similar in demographics , Acute Physiology and Chronic Health Evaluation ( APACHE ) II scores , ICU admission diagnosis , underlying disease processes , and supplemental analgesic administration . The mean time to achieve initial adequate sedation was 124 mins for lorazepam and 105 mins for midazolam . The mean infusion rate at the point of initial sedation was 0.06 mg/kg/hr for lorazepam and 0.15 mg/kg/hr for midazolam . The maximum and mean infusion rates for the entire study period were 0.1 and 0.06 mg/kg/hr , respectively , for lorazepam and 0.29 and 0.24 mg/kg/hr , respectively , for midazolam . The number of infusion rate adjustments per day was 1.9 mg/kg/hr for lorazepam and 3.6 mg/kg/hr for midazolam . Of the surviving patients , the mean time to return to baseline mental status after discontinuation of the benzodiazepine infusion was 261 mins for lorazepam and 1815 mins for midazolam . The mean volume of fluid per day required to deliver the maximum dose of benzodiazepine was 1.2 L for lorazepam ( maximum 2.4 L ) and 1.3 L for midazolam ( maximum 3.6 L ) . Conclusions : While there was a tendency to a longer time required for return to baseline mental status in patients receiving midazolam , this was not statistically signficant . Findings of interest concerning both midazolam and lorazepam were : a ) time to achieve sedation in medical ICU patients is often prolonged ; b ) actual dose requirements necessary to maintain sedation in this patient population are larger than the current literature describes ; c ) time to awaken after discontinuation of the infusion was occasionally delayed for > 24 hrs ; d ) large volumes of fluid were required to deliver these doses of drug via this route of administration . ( Crit Care Med 1994 ; 22:1241–1247 We have compared the sedative and amnesic effects of midazolam and propofol in 35 volunteers . Sedation was measured by simple reaction time immediately before and after a bolus injection and 1 h after the commencement of a subsequent continuous infusion . Memory was measured three times using two memory tests : perceptual facilitation provided an implicit memory measure and recognition provided an explicit memory measure . Propofol and midazolam had similar sedative effects both immediately after bolus doses and after 1-h continuous infusions of the drugs . In contrast , midazolam had a more profound amnesic effect than propofol on the recognition memory test . The drugs had little effect on performance with the implicit memory test . Performance on the memory tests was unrelated to sedation A comparison was made of the drug costs and nursing dependency of patients undergoing elective cardiac surgery and routine postoperative recovery for two anaesthetic techniques using either propofol with low dose fentanyl or midazolam with high dose fentanyl . Estimates of re source use were based on a r and omised clinical trial undertaken at the Northern General Hospital , Sheffield . Times from entry to the intensive care unit until extubation and discharge were recorded for 70 patients and were transformed to nursing shifts . Nursing dependency was calculated on the basis of one nurse per ventilated patient and 0.5 nurse from the start of the shift after extubation . Nursing costs were allocated on the basis of the patient 's status at the beginning of each shift in line with the hospital 's staffing policy . All drugs used from the morning of the operation until discharge were recorded . Costs of nursing and drugs were calculated . The total cost of patients in the propofol group was 13.3 % less than midazolam patients ( p = 0.043 , for geometric means Cl 0.4 % to 27.8 % ) . The clinical study was not design ed for economic endpoints ; however , it demonstrated achievable savings in propofol‐treated patients The purpose of this study was to evaluate and compare the clinical effects , safety , and economic cost of propofol and midazolam in the sedation of patients undergoing mechanical ventilation in the ICU . Eighty-eight critically ill patients were studied and r and omly allocated to receive short-term ( less than 24 h ) , medium-term ( 24 h to 7 days ) , and prolonged ( more than 7 days ) continuous sedation with propofol ( n = 46 ) or midazolam ( n = 42 ) . Mean doses required were 2.36 mg/kg/h for propofol and 0.17 mg/kg/h for midazolam . Patients in the group receiving propofol showed a percentage of hours of sedation at the desired level ( grade 2 , 3 , 4 , or 5 on the Ramsay scale ) of 93 percent , compared with 82 percent ( p < 0.05 ) in the group receiving midazolam . Both agents were considered safe with respect to the induction of adverse reactions during their use in prolonged sedation . Recovery after interrupting sedation was significantly faster in patients treated with propofol than in those se date d with midazolam ( p < 0.05 ) . Recovery of total consciousness was predictable according to sedation time in propofol-treated subgroups ( r = 0.98 , 0.88 , and 0.92 , respectively ) , while this correlation was not observed in the midazolam-treated group . In the subgroup with sedation of less than 24 h , propofol provided a cost savings of approximately 2,000 pesetas ( pts ) per patient , due to shorter stays in the ICU . We conclude that propofol is a sedative agent with the same safety , higher clinical effectiveness , and a better cost-benefit ratio than midazolam in the continuous sedation of critically ill patients OBJECTIVES To evaluate and compare the clinical efficacy , impact on hemodynamics , safety profiles , and cost of combined administration of propofol and midazolam ( synergistic sedation ) vs. midazolam and propofol administered as sole agents , for sedation of mechanically ventilated patients after coronary artery bypass grafting . DESIGN Prospect i ve , controlled , r and omized , double-blind clinical trial . SETTING Intensive care unit of SCIAS-Hospital de Barcelona . PATIENTS Seventy-five mechanically ventilated patients who underwent coronary artery bypass graft surgery under low-dose opioid anesthesia .  INTERVENTIONS According to the double-blind method , patients were r and omly assigned to receive propofol ( n = 25 ) , midazolam ( n = 25 ) , or propofol combined with midazolam ( n = 25 ) . Infusion rates were adjusted to stay between 8 and 11 points on Glasgow Coma Score modified by Cook and Palma . MEASUREMENTS AND MAIN RESULTS Mean + /- SD duration of sedation was 14.4 + /- 1.5 hrs , 14.1 + /- 1.1 hrs , and 14.7 + /- 1.9 hrs for the propofol , midazolam , and synergistic groups , respectively . The induction dose was 0.55 + /- 0.05 mg/kg for propofol as sole agent , 0.05 + /- 0.01 mg/kg for midazolam as sole agent , and 0.22 + /- 0.03 mg/kg for propofol administered in combination with 0.02 + /- 0.00 mg/kg of midazolam ( p = .001 ) . The maintenance dose was 1.20 + /- 0.03 mg/kg/hr for propofol as sole agent , 0.08 + /- 0.01 mg/kg/hr for midazolam as sole agent , and 0.50 + /- 0.09 mg/kg/hr for propofol administered in combination with 0.03 + /- 0.01 mg/kg/hr of midazolam ( p < .001 ) . All sedative regimens achieved similar efficacy in percentage of hours of adequate sedation ( 93 % for propofol , 88 % for midazolam , and 90 % for the synergistic group , respectively ) . After induction , both propofol and midazolam groups had significant decreases in systolic blood pressure , diastolic blood pressure , left atrial pressure , and heart rate . Patients in the synergistic group had significant bradycardia throughout the study , without impairment in other hemodynamic parameters . Patients se date d with propofol or synergistic regimen awoke sooner and could be extubated before those patients se date d with midazolam ( 0.9 + /- 0.3 hrs and 1.2 + /- 0.6 hrs vs. 2.3 + /- 0.8 hrs , respectively , p = .01 ) . Synergistic sedation produced cost savings of 28 % with respect to midazolam and 68 % with respect to propofol . CONCLUSIONS In the study conditions , the new synergistic treatment with propofol and midazolam administered together is an effective and safe alternative for sedation , with some advantages over the conventional regimen with propofol or midazolam administered as sole agents , such as absence of hemodynamic impairment , > 68 % reduction in maintenance dose , and lower pharmaceutical cost OBJECTIVES To evaluate and compare the clinical efficacy , impact on hemodynamic and oxygen transport variables , safety profiles , and cost efficiency of sedation and anxiolysis with lorazepam vs. continuous infusion of midazolam in critically ill , intensive care unit patients . DESIGN Multicenter , prospect i ve , r and omized , open-label study . SETTING Teaching hospitals . PATIENTS Ninety-five critically ill , mechanically ventilated patients with fiberoptic pulmonary artery catheters in place were r and omly assigned to receive short-term ( 8 hrs ) sedation with either intermittent intravenous injection lorazepam ( group A , n = 50 ) or continuous intravenous infusion midazolam ( group B , n = 45 ) titrated to clinical response . MEASUREMENTS AND MAIN RESULTS The severity of illness , demographic characteristics , levels of anxiety and agitation , hemodynamic parameters , oxygen transport variables , quality of sedation , nursing acceptance , and laboratory chemistries reflecting drug safety were recorded . There were no significant differences with regard to demographic data , hemodynamic and oxygen transport variables , or levels of anxiety/agitation between the two groups at baseline , 5 mins , 30 mins , and 4 and 8 hrs after administration of sedation . There were no significant differences in the quality of sedation or anxiolysis . Midazolam-treated patients used significantly larger amounts of drug for similar levels of sedation and anxiolysis ( 14.4 + /- 1.2 mg/8 hrs vs. 1.6 + /- 0.1 mg/8 hrs , p = .001 ) . Both drugs were safely administered and patient and nurse satisfaction was similar . CONCLUSIONS Sedation and anxiolysis with lorazepam and midazolam in critically ill patients is safe and clinical ly effective . Hemodynamic and oxygen transport variables are similarly affected by both drugs . The dose of midazolam required for sedation is much larger than the dose of lorazepam required for sedation , and midazolam is therefore less cost-efficient Thirty‐seven patients with a wide range of illnesses were studied during mechanical ventilation of the lungs in an intensive care unit . Fifteen were se date d with a continuous propofol infusion , with analgesia provided by bolus doses of papaveretum . Twelve received a continuous infusion of papaveretum , supplemented by bolus doses of midazolam . The level of sedation was assessed every four hours and measurements were made of haemodynamic and respiratory variables . Levels of sedation were generally satisfactory in both groups . Six patients who received propofol required the use of muscle relaxants , because of their strong respiratory drives , to achieve synchronisation with the ventilator . There was no significant difference in respiratory or haemodynamic variables between the groups , but several patients required inotropic support because of their disease . There was no evidence of inhibition of adrenal steroidogenesis in the propofol group . Propofol can be a useful sedative agent in the intensive care unit , but sedative regimens should be tailored to individual patient requirements Morphine + midazolam and alfentanil + propofol are regimens offering well tolerated and effective sedation for critically ill patients . However , morphine + midazolam is associated with accumulation in these patients , result ing in prolonged recovery characteristics . Alfentanil+propofol , although more expensive , has a shorter elimination half-life , is not associated with accumulation problems and results in a rapid recovery . This study compared sedation quality , patient recovery characteristics and the cost of alfentanil + propofol and morphine + midazolam for sedating critically ill patients in the intensive care setting . 26 patients were r and omly allocated to receive sedation with alfentanil + propofol ( n = 17 ) or morphine + midazolam ( n = 9 ) . Outcome measures were the times until extubation , intensive care unit ( ICU ) transfer and final hospital discharge . Cost analysis assessed both drug-related costs , including drug acquisition and administration , and non-drug-related costs , including bed occupancy . Age , gender , diagnosis , Acute Physiological and Chronic Health Evaluation ( APACHE ) II scores and sedation quality did not differ significantly between groups . The times to extubation and until patients were fit for transfer from ICU were significantly shorter for patients se date d with alfentanil + propofol than for those se date d with morphine + midazolam . The total costs ( at the time of the study Pounds 1 was equivalent to $ US1.59 ) for ICU hospital stay per patient for alfentanil + propofol and morphine + midazolam were 3063 Pounds and 9511 Pounds , respectively , because the shorter recovery characteristics of alfentanil + propofol led to a reduction in ICU stay . Corresponding costss for total hospital stay were 6063 Pounds and 13735 Pounds , respectively . In conclusion , alfentanil + propofol has a better pharmacoeconomic profile than morphine + midazolam for sedating critically ill patients in the ICU setting One hundred adult patients who required mechanical ventilation after open heart surgery for coronary revascularisation were studied . All received a st and ard premedication and a high dose opioid anaesthetic . On arrival in the intensive care unit they were allocated r and omly to receive either propofol or midazolam to maintain sedation within a predetermined range . Patients who received propofol underwent extubation of the trachea , using st and ard criteria , after a mean time ( log‐transformed ) of 7.6 minutes after sedation for approximately 17 hours . The corresponding time was 125 minutes in those given midazolam . There were significantly higher morphine requirements during sedation , and higher arterial carbon dioxide tensions 30 minutes after extubation of the trachea , in patients who received midazolam . Pharmacokinetic analysis in 20 patients showed that the elimination half‐life of propofol was prolonged ( 470 minutes ) and clearance was reduced ( 1.14 litres/minute ) compared with subjects who had not undergone cardiopulmonary bypass . The rapid clinical recovery was reflected in a rapid redistribution half‐life ( 13.4 minutes ) , but this was also longer than the redistribution time of 2–4 minutes in other patients Preamble Although economic outcomes research is an evolving field in health services research , there are correct and incorrect ways to conduct and report on economic outcomes studies . Research practice s that help to minimize real or perceived bias will increase the quality and usefulness of such studies for those who sponsor , publish , and use them . Because of public concerns about the potential for bias in the design , analysis , and reporting of economic analyses of health care technology , we formed a task force to develop principles to enhance the credibility of these studies . The Task Force on Principles for Economic Analysis of Health Care Technology included participants from academia , the pharmaceutical industry , the public sector , and private research organizations . As health care re sources become increasingly constrained , the information used to make re source allocation decisions must be as reliable , valid , and free of bias as possible . Getting it right at the level at which economic results are produced will help to protect consumers and will advance the health of the public . Bias stems from two broad categories : lack of appropriate independence for research ers and lack of consensus about methods . We focused heavily on the first of these categories for two major reasons . First , few have yet considered the unique issues of research er independence in economic outcomes research [ 1 , 2 ] . Second , other investigators have begun to consider and define proper methods for economic outcomes work ( an area of considerable controversy ) [ 3 - 5 ] . We also looked closely at the requirements for the reporting of economic analyses , which are intended to ensure method ologic transparency and accountability . The Need for Voluntary Guidelines Widespread use of economic analysis as part of the development of pharmaceutical , biotechnologic , and medical devices is relatively new . To date , many economic analyses of health care have focused on pharmaceutical agents , and many such studies have been funded by pharmaceutical companies . Results of these economic outcomes studies are used by medical technology firms to support the pricing and marketing of new interventions and to influence national health care systems and third-party payers in their development of coverage and payment decisions . Managed care organizations , hospitals , and government-subsidized health care programs rely on economic analysis of medical technology to help make formulary purchasing and utilization decisions . Physicians may use the results of these analyses to help guide treatment and prescription decisions . Health care economic outcomes projects are sponsored and conducted by pharmaceutical , biotechnologic , and medical device companies ; government agencies ; nonprofit foundations ; academic investigators ; and private research and consulting firms . The st and ards and methods used to evaluate the safety and efficacy of pharmaceutical products in r and omized , controlled trials have evolved over 50 years of collaboration among research ers in private , public , and academic setting s. Compared with those established to ensure the safety and efficacy of clinical trials , the principles and methods for the conduct of economic studies of health care technology are far less developed . Problems of conduct , reporting , and bias exist in all types of research [ 6 - 14 ] . In response , codes of conduct , such as those developed by the American Federation for Clinical Research and the Institute of Medicine , have been developed for many scientific disciplines [ 15 - 24 ] . These are good models on which to base principles of conduct for economic outcomes analysis . Although many published principles apply to economic studies , others should be modified and new ones should be developed to guide the conduct and reporting of economic outcomes analyses . Economic outcomes research requires unique guidelines for the following reasons : 1 ) As a field , it continues to evolve and is often misunderstood by end users ; 2 ) peer review of it requires special expertise that often exceeds the capabilities of review ers and scientific journals ; 3 ) it often uses secondary data and requires that many assumptions be made [ for example , attribution of a dollar cost to a unit of re source use ] ; 4 ) it offers unique method ologic choices , such as which types of costs to include ( direct , indirect , intangible , induced ) , which perspective to apply ( that of society , payer , provider , patient ) , which design to adopt ( cost- identification , costbenefit , cost-effectiveness , costutility ) , from where to obtain costs [ indemnity data base , managed care or capitated data base , hospital cost systems , Medicare , Medicaid ] , and whether to collect re source consumption data prospect ively or retrospectively through various modeling techniques ; and 5 ) economic studies play an increasingly important role in health care decision making because of increasing financial constraints throughout the health care industry . The financial and medical implication s of decision making done on the basis of these studies , coupled with the lack of widely accepted guidelines about the conduct and reporting of economic analyses , undermine the credibility of this research . A major issue is that the primary source of funding for this research is often the primary financial beneficiary of positive study results . Unfortunately , even valid studies done under the best of circumstances may be suspect [ 25 - 29 ] . This has led at least one major journal to conclude that these analyses should be viewed much like editorials or review articles are viewed in terms of potential for conflicts of interest [ 30 ] . We developed the guidelines reported here after extensive consultation with experts from the public , private , and academic sectors . We recommend that research ers and sponsors adhere to these guidelines , and we suggest they state publicly within their manuscripts that they have done so . End users , including journal editors and readers , consumers , and social decision makers , may then feel more secure in accepting the results of the research , while recognizing that intensive critique of the research will always be necessary . Operations of the Task Force The Task Force on Principles for Economic Analysis of Health Care Technology was initiated and organized by faculty from the Leonard Davis Institute ( LDI ) Center for Health Policy of the University of Pennsylvania . However , because not all LDI faculty were involved , this paper does not represent an official LDI position statement . The Task Force was funded by a coalition of pharmaceutical companies ( Appendix A ) . Funding was also requested ( but not obtained ) from various government and private foundations . All funding was provided in the form of unrestricted research grants or gifts to the University of Pennsylvania . Guidelines derive their credibility in part from the composition of the panel that creates them and the process by which they are developed . C and i date s for participation in the Task Force from the private sector and the academic research community were identified by the frequency with which they were cited in the health economics literature , which was obtained using a MEDLINE search of literature related to economic analyses of medical technology published between 1983 and 1992 . Approximately 15 members attended each meeting . Minutes were distributed after each meeting and approved by all members present . Members from the sponsoring pharmaceutical companies and the academic organizers rotated so that they numbered three and one , respectively , at the table for each formal Task Force meeting . Several professional and governmental organizations , including the Institute of Medicine , the Agency for Health Care Policy and Research , the Food and Drug Administration ( FDA ) , the Health Care Financing Administration , the Centers for Disease Control and Prevention , and a managed care organization , were asked to suggest persons who might participate . In addition , other organizations with a stake in economic analyses were each asked to suggest a person who , because of his or her professional background , had extensive knowledge of or experience with economic analyses . An academic pharmacist , an academic research er , a private research er , an ethicist and patient advocate , and an attorney specializing in medical ethics rounded out the Task Force ( Appendix B ) . Two members withdrew from participation . A small audience consisting of industry sponsors , academic organizers , staff , and a few other interested parties were invited to each meeting and allowed to comment . Four formal meetings of the Task Force were held in Philadelphia during 1993 and 1994 , and the most substantial work was done by various subcommittees between these meetings . The three main subcommittees were titled Ethical Conduct , Responsibility and Control ( the findings of these two subcommittees were later merged into one report ) , and Reporting Requirements for Economic Evaluations ( Appendix C ) . The Task Force was assisted by a professional facilitator . Although Task Force members sought consensus wherever possible on the key issues , consensus was not forced and recommendations were issued only when substantial agreement existed among the members . Task Force members were not asked to formally represent any organization . Formal endorsement of the final document was not sought . Copies of this report will be distributed to all organizations that were asked to suggest a participant and to other parties who responded to announcements placed in The New Engl and Journal of Medicine , Scrip , and the Pink Sheet . The Task Force findings will also be reported at academic conferences , medical profession meetings , and appropriate trade conventions . Findings and Recommendations Valid approaches to economic analyses can be defined ; acceptable methods can be differentiated from unacceptable ones . Bias in economic research stems from two major sources : lack of appropriate independence for OBJECTIVE To compare the effectiveness of sedation , the time required for weaning , and the costs of prolonged sedation of critically ill mechanically ventilated patients with midazolam and propofol .  DESIGN Open-label , r and omized , prospect i ve , phase IV clinical trial . SETTING Medical and surgical intensive care unit ( ICU ) in a community hospital . PATIENTS All ICU admissions ( medical , surgical and trauma ) requiring mechanical ventilation for > 24 hrs . A total of 108 patients were included in the study . INTERVENTIONS Patients were r and omized to receive midazolam or propofol .  The dose range allowed for each drug was 0.1 to 0.5 mg/kg/hr for midazolam and 1 to 6 mg/kg/hr for propofol . The lowest dose that achieved an adequate patient-ventilator synchrony was infused . All patients received 0.5 mg/kg/24 hrs of morphine chloride . MEASUREMENTS AND MAIN RESULTS The level of sedation was quantified by the Ramsay scale every 2 hrs until weaning from mechanical ventilation was started . If sedation could not be achieved by infusing the highest dose of midazolam or propofol , the case was recorded as a therapeutic failure . In the propofol group , serum triglycerides were determined every 72 hrs . Concentrations of > 500 mg/dL were also recorded as a therapeutic failure . When the patient was ready for weaning according to defined criteria , sedation was interrupted abruptly and the time from interruption of sedation to the first T-bridge trial and to extubation was measured . Cost analysis was performed based on the cost of intensive care in our unit ( $ 54/hr ) . In the midazolam group ( n = 54 ) , 15 ( 27.8 % ) patients died ; 11 ( 20.4 % ) patients had therapeutic failure ; and 28 ( 51.8 % ) patients were subjected to a T-bridge trial . In the propofol group ( n = 54 ) , these proportions were 11 ( 20.4 % ) , 18 ( 33.4 % [ including seven due to inadequate sedation , and 11 due to hypertriglyceridemia ] ) , and 25 ( 46.2 % ) , respectively . None of these values was significantly different between the two groups . Duration of sedation was 141.7 + /- 89.4 ( SD ) hrs and 139.7 + /- 84.7 hrs ( p = NS ) , and cost ( US dollars ) attributed to sedation was $ 378 + /- 342 and $ 1,047 + /- 794 ( p = .0001 ) for the midazolam and propofol groups , respectively . In the midazolam group , time from discontinuation of the drug infusion to extubation was 97.9 + /- 54.6 hrs ( 48.9 + /- 47.2 hrs to the first disconnection , and 49.0 + /- 23.7 hrs to extubation ) . In the propofol group , time from discontinuation of the drug infusion to extubation was 34.8 + /- 29.4 hrs ( 4.0 + /- 3.9 hrs to the first disconnection , and 30.8 + /- 29.2 hrs to extubation ) . The difference between the two groups in the weaning time was 63.1 + /- 12.5 ( SEM ) hrs ( p < .0001 ) . Cost per patient in the midazolam group ( including ICU therapy and sedation with midazolam ) was $ 10,828 + /- 5,734 . Cost per patient in the propofol group was $ 9,466 + /- 5,820 , $ 1,362 less than in the midazolam group . CONCLUSIONS In our population of critically ill patients se date d with midazolam or propofol over prolonged periods , midazolam and propofol were equally effective as sedative agents . However , despite remarkable differences in the cost of sedation with these two agents , the economic profile is more favorable for propofol than for midazolam due to a shorter weaning time associated with propofol administration Background Propofol sedation offers advantages for titration and rapid emergence in the critically ill patient , but concern for adverse hemodynamic effects potentially limits its use in these patients . The current study compares the cardiovascular effects of sedation with propofol versus midazolam during the first 12 h after coronary revascularization . Methods Three hundred fifty‐one patients undergoing coronary revascularization were anesthetized using a st and ardized sufentanil/midazolam regimen , and assigned r and omly to 12 h of sedation with either propofol or midazolam while tracheally intubated . The incidence and characteristics of hemodynamic episodes , defined as heart rate less than 60 or greater than 100 beats/min or systolic blood pressure greater than 140 or less than 90 mmHg , were determined using data electronically recorded at 1‐min intervals . The presence of myocardial ischemia was determined using continuous three‐channel Holter electrocardiography ( ECG ) and of myocardial infa rct ions ( MI ) using 12‐lead ECG ( Q wave MI , Minnesota Code ) or creatine kinase isoenzymes ( CK‐MB ) analysis ( non‐Q wave MI , peak CK‐MB > 70 ng/ml , or CK‐MB > 70 IU/l ) . Results Ninety‐three percent of patients in both treatment groups had at least one hemodynamic episode during the period of postoperative sedation . Propofol sedation result ed in a 17 % lower incidence of tachycardia ( 58 % vs. 70 % , propofol vs. midazolam ; P = 0.04 ) , a 28 % lower incidence of hypertension ( 39 % vs. 54 % ; P = 0.02 ) , and a greater incidence of hypotension ( 68 % vs. 51 % ; P = 0.01 ) . Despite these hemodynamic effects , the incidence of myocardial ischemia did not differ between treatment groups ( 12 % propofol vs. 13 % midazolam ; P = 0.66 ) , nor did its severity , as measured by ischemic minutes per hour monitored ( 8.7+/‐5.8 vs. 6.2+/‐4.6 min/h , propofol vs. midazolam ; P = 0.19 ) or ischemic area under the curve ( 6.8+/‐4.0 vs. 5.3+/‐4.2 ; P = 0.37 ) . The incidence of cardiac death ( one per group ) , Q wave MI ( propofol , n = 7 ; midazolam , n = 3 ; P = 0.27 ) , or non Q wave MI ( propofol , n = 16 ; midazolam , n = 18 ; P = 0.81 ) did not differ between treatment groups . Conclusions Hemodynamic episodes occur frequently in the first 12 h after coronary revascularization . Compared with a st and ard sedation regimen ( midazolam ) , propofol sedation appears to modulate postoperative hemodynamic responses by reducing the incidence and severity of tachycardia and hypertension and increasing the incidence of hypotension . Both sedation regimens appear similarly safe with respect to myocardial ischemia . These findings indicate that propofol infusion provides effective sedation without deleterious hemodynamic effects in patients recovering from cardiac surgery Forty-four patients , with admission APACHE II scores between 5 and 24 , undergoing mechanical ventilation in the intensive therapy unit , received a sedative regimen consisting of continuous infusions of propofol and alfentanil .  Patients were r and omly allocated to one of three groups to receive either alfentanil 0.25 microgram kg-1 min-1 ( 10 patients ) , 0.50 microgram kg-1 min-1 ( 15 patients ) or 0.75 microgram kg-1 min-1 ( 18 patients ) for analgesia . An infusion of propofol 20 - 200 mg h-1 ran concurrently to maintain a satisfactory level of sedation .  Patients received the infusions for between 4 and 260 h and 38 patients spent more than 90 % of this time at satisfactory sedation levels . After stopping the infusions all patients had short times to wakening ( mean 3 - 18 min ) and to establish spontaneous respiration ( mean 8 - 28 min ) , suggesting no significant cumulation . Some depression of blood pressure was seen on starting the infusions , which was in general easily treated with fluids or small increases in inotropic agents . One patient , however , was withdrawn from the trial because of haemodynamic instability . This combination of drugs can be recommended for sedation of general intensive-therapy patients , provided the cost is not felt to be prohibitive Previous studies have compared sedation profiles with midazolam ( Mz ) and propofol ( Pf ) , particularly in heterogeneous population s of patients .Decreases in blood pressure and heart rate have been reported after the administration of propofol . These side effects are potentially deleterious in severe trauma patients , particularly in patients with head trauma . To assess the safety and efficacy of Mz and Pf , alone or in combination , in the prolonged sedation of severe trauma patients , we design ed a prospect i ve , controlled , r and omized , study . One hundred consecutively admitted trauma patients requiring mechanical ventilation and sedation for more than 48 h were studied . Patients were se date d according to three different protocol s based on the continuous IV administration of Mz alone , Pf alone , and Mz in combination with Pf . All patients received morphine chloride .  Safety and efficacy were assessed during the sedation and wake-up periods according to clinical and laboratory variables . Cerebral hemodynamics were also studied in patients with head trauma . Patients were se date d for 6.3 + /- 4.0 days ( mean + /- SD ) . All three sedation regimens were equally efficacious in achieving the desired sedation goal . The incidence of adverse events during the sedation period was also similar . In head trauma patients with intracranial pressure ( ICP ) monitoring , we did not find differences in ICP , cerebral perfusion pressure , or jugular venous oxygen saturation among the three groups . The serum triglyceride concentration was significantly higher in the Pf group . Wake-up time was significantly shorter in the Pf group . We conclude that both Mz and Pf are safe and efficacious in the sedation of severe trauma patients . The use of Pf in these patients is associated with a high incidence of hypertriglyceridemia and a shorter wake-up time . Implication s : In a prospect i ve , controlled , r and omized study , we confirmed the safety and efficacy of midazolam and propofol , alone or in combination , in the prolonged sedation of a homogeneous group of severe trauma patients , particularly in patients with head trauma . The propofol group had shorter wake-up times and higher triglyceride levels . ( Anesth Analg 1998;86:1219 - 24 This study was undertaken to compare two regimens for analgesic sedation in intensive care patients with exogenous catecholamine therapy , giving special regard to catecholamine dem and and hemodynamic parameters . A total of 20 ventilated patients in a surgical intensive care unit were investigated in a prospect ively r and omized design . Exogenous catecholamine therapy with epinephrine and /or norepinephrine was started at systolic pressure ( SAP ) less than 85 mmHg or mean arterial pressure ( MAP ) less than 65 mmHg to maintain cardiovascular function . For analgesic sedation , patients received bolus injections of about 0.2 mg/h fentanyl and 2.5 mg/h midazolam ( fentanyl group , n = 10 ) or an infusion of about 50 mg/h ketamine and 2.5 mg/h midazolam by syringe pump ( ketamine group , n = 10 ) . Before the investigation , all patients received fentanyl and midazolam . The study period was 48 h. During the course of the study , mean catecholamine dosage increased significantly in the fentanyl group from 12.1 to 16.3 micrograms/min ( + 33 % , P = 0.003 ) . In the ketamine group , mean catecholamine dosage decreased from 43.9 to 38 micrograms/min ( -13 % , P = 0.19 ) . No significant differences in group levels or time course were observed with regard to MAP , heart rate , cardiac index , pulmonary capillary wedge pressure , and shunt volume . Levels of pulmonary artery pressure ( PAP ) were comparable in both groups ( ketamine group 29 mmHg , fentanyl group 26 mmHg ) . In time course , PAP increased by about 5 mmHg in the ketamine group but not in the fentanyl group ( P = 0.009 ) . The average central venous pressure ( CVP ) was 12 mmHg in both groups . At the end of the investigation , CVP decreased in the fentanyl group and increased in the ketamine group ( P = 0.0001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The influence of light versus heavy sedation after coronary artery bypass graft ( CABG ) surgery on the development of postoperative myocardial ischemia has not been described . After uncomplicated CABG surgery , 50 patients were r and omly assigned to receive LOW ( n = 24 ; target Ramsay Sedation Score [ RSS ] = 2 ) or HIGH ( n = 26 ; target RSS = 4 ) sedation with propofol . Analgesia was provided to maintain a visual analog scale ( VAS ) pain score < 7 . Myocardial ischemia was identified perioperatively using continuous 3-lead Holter monitoring . By measuring creatine kinase ( CK ) MB levels preoperatively , at entry to the intensive care unit ( ICU ) , and every 12 h for 48 h ; and by obtaining serial 12-lead electrocardiograms ( ECG ) ( preoperatively ; 2 , 4 , 12 , 24 , and 48 h after ICU admission , 8:00 AM the morning after surgery ; and 5 min pre- and postextubation ) , myocardial infa rct ion was identified . Endocrine stress response was assessed by measuring serum cortisol levels preoperatively , on admission to the ICU , and 24 h postoperatively . In a subset of patients ( LOW n = 10 , HIGH n = 11 ) , plasma and urinary catecholamine levels were also measured . There were no between-group differences in demographics , operative course , hemodynamic variables , or cortisol levels while in the ICU . The VAS pain score and target RSS were achieved and sustained , and they differed between groups . There were three myocardial infa rct ions in each group by CKMB criteria alone . No ECG-identifiable myocardial infa rct ion occurred . The ST segment versus time curve ( LOW 187 + /- 295 versus HIGH 1071 + /- 2137 mm/min ) differed between groups . Urinary and plasma catecholamine levels were similar between groups over the observation period . We conclude that the use of a reduced sedation regimen in combination with adequate analgesia did not result in an increased endocrine stress response or risk of myocardial ischemia . Implication s : This r and omized study of patients after coronary artery bypass surgery examined whether light ( versus heavy ) sedation with propofol in the intensive care unit was associated with an increased degree of myocardial ischemia . Using techniques to detect myocardial ischemia , including Holter monitoring , electrocardiogram , and myocardial enzyme measurements , no differences were found . We conclude that light sedation does not increase the endocrine stress response or the risk of myocardial infa rct ion . ( Anesth Analg 1997;85:971 - 8 Midazolam given as hourly intermittent injections was compared with the same dose given by infusion for postoperative sedation in patients after cardiopulmonary bypass . A stable concentration was rapidly attained with the infusion whereas 6 - 8 h was required to attain stable plasma ( trough ) concentrations in the intermittent injection group . Plasma concentrations decreased rapidly to low values within 6 h of discontinuation of therapy . High plasma concentrations and a long ( 16 h ) half-life were noted in one patient who may be a slow metabolizer of the drug OBJECTIVE --To compare isoflurane with midazolam for sedation of ventilated patients . DESIGN --R and omised control study . Setting --Intensive care unit in university teaching hospital . PATIENTS --Sixty patients aged 18 - 76 who required mechanical ventilation . INTERVENTIONS --Sedation with either 0.1 - 0.6 % isoflurane in an air-oxygen mixture ( 30 patients ) or a continuous intravenous infusion of midazolam 0.01 - 0.20 mg/kg/h ( 30 patients ) . Sedation was assessed initially and hourly thereafter on a six point scale . Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required . The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours ( whichever was earlier ) . END POINT -- Achievement of a predetermined level of sedation for as much of the time as possible . MAIN RESULTS --Isoflurane produced satisfactory sedation for a greater proportion of time ( 86 % ) than midazolam ( 64 % ) , and patients se date d with isoflurane recovered more rapidly from sedation . CONCLUSION --Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit Sedative-analgesic treatment of patients on long-term artificial ventilation aims at protection from stress related to their disease or therapy . By stabilising both the patient 's vital functions and psychological state this treatment may contribute to therapeutic success . The choice of drugs depends primarily on the nature and course of the underlying disease . Midazolam and propofol are available as hypnotics for short-term sedation during the post-operative period . The purpose of this study was to evaluate the effects of both agents on cardiovascular function , cortisol production , lipometabolism , and the recovery period following 24-h sedation . METHODS . Twenty female patients ( mean body weight : 72 kg , mean age : 60 years ) were r and omly assigned to receive either midazolam or propofol over 24 h following major abdominal surgery . Balanced anaesthesia ( halothane/O2/N2O/fentanyl ) was administered for the surgical procedure . Assisted ventilation was used in all patients during the post-operative sedation period . Sedation depth was maintained at III-IV on the Ramsey scale . On arrival in the intensive care unit ( ICU ) , an initial i.v . bolus of midazolam 0.1 mg/kg or propofol 1 mg/kg was followed by a continuous infusion ( midazolam : 0.1 mg/kg.h ; propofol : 2 mg/kg.h ) . Supplementary boluses of one-half the initial dose were given if required . Post-operative analgesia was achieved with 3 mg intravenous piritramide at 2-h intervals . A 7F Swan-Ganz catheter was inserted in the pulmonary artery and haemodynamic and biochemical parameters were monitored at 4-h intervals over 24 h starting 2 h after arrival in the ICU . Catecholamines were measured by high-pressure lipid chromatography ( HPLC ) , cortisol by radioimmunoassay , midazolam by HPLC and ultraviolet detection , and propofol by HPLC and fluorescence detection . Data were calculated as means . The statistical analysis was performed according to the Mann-Whitney test , and significance was accepted for P less than 0.05 . RESULTS . On administration of the propofol bolus at the onset of sedation , a decrease in blood pressure was particularly observed in patients with masked hypovolaemia , however , this decrease was easily controlled by volume administration . Independent of the type of sedation , the haemodynamic parameters remained unchanged throughout the observation period . At all times of measurement the mean heart rate was lower in the propofol group ( 90/min ) when compared with the midazolam group ( 100/min ) , however , this difference did not reach significance . There were also no significant differences in cardiac index at all times of measurement , although it increased in both groups within the first 12 h by 0.6 l/min.min2 . In both groups this increase was associated with a reduction in peripheral resistance and an increase in rectal temperature . To achieve the desired sedation depth , midazolam was administered at a mean dosage of 0.11 mg/kg.h and propofol at 1.9 mg/kg.h . Catecholamine levels decreased in both groups within the first 8 h : after 8 h of sedation the plasma levels of noradrenaline and adrenaline were 525 and 65 pg/ml , respectively , in the midazolam group and 327 and 51 pg/ml in the propofol group . ( ABSTRACT TRUNCATED AT 400 WORDS Background : Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12‐h postoperative sedation using propofol . Methods : One hundred twenty‐one patients having primary elective cardiopulmonary bypass graft ( CABG ) surgery were enrolled in a double‐blind , r and omized trial and anesthetized using a st and ardized sufentanil‐midazolam regimen . When arriving at the intensive care unit ( ICU ) , patients were r and omly assigned to either group SC ( st and ard care ) , in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable ; or group CP ( continuous propofol ) , in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply se date d. Serial perioperative measurements of plasma and urine cortisol , epinephrine , norepinephrine , and dopamine were obtained ; heart rate and blood pressure were recorded continuously , and medication use , including requirements for opioids and vasoactive drugs , was recorded . Repeated‐ measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time . Results : In the control state‐before the initiation of postoperative sedation in the ICU‐no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations . During the ICU study period , for the first 6–8 h , significant differences were found between study groups SC and CP in plasma cortisol ( SC = 28 + /‐ 15 mg/dl ; CP = 19 + /‐ 12 mg/dl ; estimated mean difference [ EMD ] = 9 mg/dl ; P = 0.0004 ) , plasma epinephrine ( SC = 132 + /‐ 120 micro gram/ml ; CP = 77 + /‐ 122 micro gram/ml ; EMD = 69 micro gram/ml ; P = 0.009 ) , urine cortisol ( SC = 216 + /‐ 313 micro gram/ml ; CP = 93 + /‐ 129 micro gram/ml ; EMD = 127 micro gram/ml ; P = 0.007 ) , urine dopamine ( SC = 85 + /‐ 48 micro gram ; CP = 52 + /‐ 43 micro gram ; EMD = 32 micro gram ; P = 0.002 ) , urine epinephrine ( SC = 7 + /‐ 8 micro gram ; CP = 4 + /‐ 5 micro gram ; EMD = 3 micro gram ; P = 0.009 ) , and urine norepinephrine ( SC = 24 + /‐ 14 mg ; CP = 13 + /‐ 9 mg ; EMD = 11 mg ; P = 0.0004 ) . Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12‐h propofol infusion period and then rapidly returned toward control ( SC group ) values after propofol was discontinued . Postoperative opioid use was reduced in the CP group ( SC = 97 % ; CP = 49 % ; P = 0.001 ) , as was the incidence of ( SC = 79 % ; CP = 60 % ; P = 0.04 ) and hypertension ( SC = 58 % ; CP = 33 % ; P = 0.01 ) , but the incidence of hypotension was increased ( SC = 49 % ; CP = 81 % ; P = 0.001 ) . Conclusions : Cardiopulmonary bypass graft surgery is associated with substantial increases in plasma and urine catecholamine and cortisol concentrations , which persist for 12 or more h. This hormonal response may be mitigated by a technique of intensive continuous 12‐h postoperative sedation with propofol , which is associated with a decrease in tachycardia and hypertension and an increase in hypotension
CONTEXT Sedation has become an integral part of critical care practice in minimizing patient discomfort ; however , sedatives have adverse effects and the potential to prolong mechanical ventilation , which may increase health care costs .
OBJECTIVE To determine which form of sedation is associated with optimal sedation , the shortest time to extubation , and length of intensive care unit ( ICU ) stay .