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1.  Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomised trial [ISRCTN47583497] 
Critical Care  2005;9(3):R200-R210.
Introduction
This randomised, open-label, multicentre study compared the safety and efficacy of an analgesia-based sedation regime using remifentanil with a conventional hypnotic-based sedation regime in critically ill patients requiring prolonged mechanical ventilation for up to 10 days.
Methods
One hundred and five randomised patients received either a remifentanil-based sedation regime (initial dose 6 to 9 μg kg-1 h-1 (0.1 to 0.15 μg kg-1 min-1) titrated to response before the addition of midazolam for further sedation (n = 57), or a midazolam-based sedation regime with fentanyl or morphine added for analgesia (n = 48). Patients were sedated to an optimal Sedation–Agitation Scale (SAS) score of 3 or 4 and a pain intensity (PI) score of 1 or 2.
Results
The remifentanil-based sedation regime significantly reduced the duration of mechanical ventilation by more than 2 days (53.5 hours, P = 0.033), and significantly reduced the time from the start of the weaning process to extubation by more than 1 day (26.6 hours, P < 0.001). There was a trend towards shortening the stay in the intensive care unit (ICU) by 1 day. The median time of optimal SAS and PI was the same in both groups. There was a significant difference in the median time to offset of pharmacodynamic effects when discontinuing study medication in patients not extubated at 10 days (remifentanil 0.250 hour, comparator 1.167 hours; P < 0.001). Of the patients treated with remifentanil, 26% did not receive any midazolam during the study. In those patients that did receive midazolam, the use of remifentanil considerably reduced the total dose of midazolam required. Between days 3 and 10 the weighted mean infusion rate of remifentanil remained constant with no evidence of accumulation or of a development of tolerance to remifentanil. There was no difference between the groups in SAS or PI score in the 24 hours after stopping the study medication. Remifentanil was well tolerated.
Conclusion
Analgesia-based sedation with remifentanil was well tolerated; it reduces the duration of mechanical ventilation and improves the weaning process compared with standard hypnotic-based sedation regimes in ICU patients requiring long-term ventilation for up to 10 days.
doi:10.1186/cc3495
PMCID: PMC1175879  PMID: 15987391
2.  Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713] 
Critical Care  2003;8(1):R1-R11.
Introduction
This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety of remifentanil and fentanyl for intensive care unit (ICU) sedation and analgesia.
Methods
Intubated cardiac, general postsurgical or medical patients (aged ≥ 18 years), who were mechanically ventilated for 12–72 hours, received remifentanil (9 μg/kg per hour; n = 77) or fentanyl (1.5 μg/kg per hour; n = 75). Initial opioid titration was supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal sedation (i.e. a Sedation–Agitation Scale score of 4).
Results
The mean percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for fentanyl (not significant). Patients with a Sedation–Agitation Scale score of 4 exhibited significantly less between-patient variability in optimal sedation on remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of patients who received fentanyl 40% required propofol, as compared with 35% of those who received remifentanil (median total doses 683 mg and 378 mg, respectively; P = 0.065). Recovery was rapid (median time to extubation: 1.1 hours for remifentanil and 1.3 hours for fentanyl; not significant). Remifentanil patients who experienced pain did so for significantly longer during extubation (6.5% of the time versus 1.4%; P = 0.013), postextubation (10.2% versus 3.6%; P = 0.001) and post-treatment (13.5% versus 5.1%; P = 0.001), but they exhibited similar haemodynamic stability with no significant differences in adverse event incidence.
Conclusion
Analgesia based sedation with remifentanil titrated to response provided effective sedation and rapid extubation without the need for propofol in most patients. Fentanyl was similar, probably because the dosing algorithm demanded frequent monitoring and adjustment, thereby preventing over-sedation. Rapid offset of analgesia with remifentanil resulted in a greater incidence of pain, highlighting the need for proactive pain management when transitioning to longer acting analgesics, which is difficult within a double-blind study but would be quite possible under normal circumstances.
doi:10.1186/cc2398
PMCID: PMC420059  PMID: 14975049
analgesia; analgesia based sedation; critical care; fentanyl; propofol; remifentanil; renal function; sedation
3.  Comparison of sedation effectiveness of remifentanil-dexmedetomidine and remifentanil-midazolam combinations and their effects on postoperative cognitive functions in cystoscopies: A randomized clinical trial 
Background:
The aim of the study is to compare the effects of remifentanil/dexmedetomidine and remifentanil/midazolam combinations in monitored anesthesia care (MAC) during cystoscopies.
Materials and Methods:
Forty patients who received remifentanil infusion of 0.05 μg kg-1 min-1 for cytoscopy procedure were randomized into two groups: Either dexmedetomidine 1 mg kg-1 (Group D) or midazolam 0.2 mg kg-1 h-1 (Group M) was administered intravenously for the first 10 min. Subsequently, anesthesia was maintained by using the bispectral index as a continuous infusion of dexmedetomidine (0.2-0.7 μg kg-1 h-1) or midazolam (0.05-0.15 μg kg-1 h-1). Heart rate, mean arterial pressure, mini-mental state examination findings, levels of sedation andanalgesia, and the patient's and surgeon's satisfaction were recorded.
Results:
Successful sedation and analgesia were achieved in all the patients. We were able to reach the target sedation level faster in Group D (P<0.0001). In Group D, the cognitive functions were less affected than in Group M (P<0.0001). Patient's and surgeon's satisfaction were significantly higher in Group D.
Conclusion:
The targeted sedation levels were achieved in a shorter period with dexmedetomidine-remifentanil compared to midazolam-remifentanil. The dexmedetomidine-remifentanil combination was observed to affect the cognitive functions less than midazolam-remifentanil did with shorter recovery times. Besides, patient's and surgeon's satisfaction rates were superior with dexmedetomidine-remifentanil. It was concluded that dexmedetomidine-remifentanil may be a combination of choice for monitored anesthesia care applications in outpatient surgical procedures of short duration.
PMCID: PMC3724369  PMID: 23914211
Dexmedetomidine; midazolam; remifentanil; monitored anesthesia care; mini mental state examination; cystoscopy
4.  Sedation in the intensive care unit with remifentanil/propofol versus midazolam/fentanyl: a randomised, open-label, pharmacoeconomic trial 
Critical Care  2006;10(3):R91.
Introduction
Remifentanil is an opioid with a unique pharmacokinetic profile. Its organ-independent elimination and short context-sensitive half time of 3 to 4 minutes lead to a highly predictable offset of action. We tested the hypothesis that with an analgesia-based sedation regimen with remifentanil and propofol, patients after cardiac surgery reach predefined criteria for discharge from the intensive care unit (ICU) sooner, resulting in shorter duration of time spent in the ICU, compared to a conventional regimen consisting of midazolam and fentanyl. In addition, the two regimens were compared regarding their costs.
Methods
In this prospective, open-label, randomised, single-centre study, a total of 80 patients (18 to 75 years old), who had undergone cardiac surgery, were postoperatively assigned to one of two treatment regimens for sedation in the ICU for 12 to 72 hours. Patients in the remifentanil/propofol group received remifentanil (6- max. 60 μg kg-1 h-1; dose exceeds recommended labelling). Propofol (0.5 to 4.0 mg kg-1 h-1) was supplemented only in the case of insufficient sedation at maximal remifentanil dose. Patients in the midazolam/fentanyl group received midazolam (0.02 to 0.2 mg kg-1 h-1) and fentanyl (1.0 to 7.0 μg kg-1 h-1). For treatment of pain after extubation, both groups received morphine and/or non-opioid analgesics.
Results
The time intervals (mean values ± standard deviation) from arrival at the ICU until extubation (20.7 ± 5.2 hours versus 24.2 h ± 7.0 hours) and from arrival until eligible discharge from the ICU (46.1 ± 22.0 hours versus 62.4 ± 27.2 hours) were significantly (p < 0.05) shorter in the remifentanil/propofol group. Overall costs of the ICU stay per patient were equal (approximately €1,700 on average).
Conclusion
Compared with midazolam/fentanyl, a remifentanil-based regimen for analgesia and sedation supplemented with propofol significantly reduced the time on mechanical ventilation and allowed earlier discharge from the ICU, at equal overall costs.
doi:10.1186/cc4939
PMCID: PMC1550941  PMID: 16780597
5.  Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care 
Critical Care  2000;4(5):302-308.
The respiratory effects of dexmedetomidine were retrospectively examined in 33 postsurgical patients involved in a randomised, placebo-controlled trial after extubation in the intensive care unit (ICU). Morphine requirements were reduced by over 50% in patients receiving dexmedetomidine. There were no differences in respiratory rates, oxygen saturations, arterial pH and arterial partial carbon dioxide tension (PaCO2) between the groups. Interestingly the arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratios were statistically significantly higher in the dexmedetomidine group. Dexmedetomidine provides important postsurgical analgesia and appears to have no clinically important adverse effects on respiration in the surgical patient who requires intensive care.
Introduction:
The α2-agonist dexmedetomidine is a new class of sedative drug that is being investigated for use in ICU settings. It is an effective agent for the management of sedation and analgesia after cardiac, general, orthopaedic, head and neck, oncological and vascular surgery in the ICU [1]. Cardiovascular stability was demonstrated, with significant reductions in rate-pressure product during sedation and over the extubation period.
Dexmedetomidine possesses several properties that may additionally benefit those critically ill patients who require sedation. In spontaneously breathing volunteers, intravenous dexmedetomidine caused marked sedation with only mild reductions in resting ventilation at higher doses [2]. Dexmedetomidine reduces the haemodynamic response to intubation and extubation [3,4,5] and attenuates the stress response to surgery [6], as a result of the α2-mediated reduction in sympathetic tone. Therefore, it should be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved.
The present study is a retrospective analysis of the respiratory response to dexmedetomidine in 33 postsurgical patients (who were involved in a randomized, double-blind, placebo-controlled trial [1]) after extubation in the ICU.
Methods:
Patients who participated in the present study were admitted after surgery to our general or cardiothoracic ICUs, and were expected to receive at least 6 h of postsurgical sedation and artificial ventilation.
On arrival in the ICU after surgery, patients were randomized to receive either dexmedetomidine or placebo (normal saline) with rescue sedation and analgesia being provided, only if clinically needed, with midazolam and morphine boluses, respectively. Sedation was titrated to maintain a Ramsay Sedation Score [7] of 3 or greater while the patients were intubated, and infusions of study drug were continued for a maximum of 6 h after extubation to achieve a Ramsay Sedation Score of 2 or greater.
The patients were intubated and ventilated with oxygen-enriched air to attain acceptable arterial blood gases, and extubation occurred when clinically indicated. All patients received supplemental oxygen after extubation, which was delivered by a fixed performance device. Assessment of pain was by direct communication with the patient.
Results are expressed as mean ± standard deviation unless otherwise stated. Patient characteristics, operative details and morphine usage were analyzed using the Mann-Whitney U-test. Statistical differences for respiratory measurements between the two groups were determined using analysis of variance for repeated measures, with the Bonferroni test for post hoc comparisons.
Results:
Of the 40 patients who participated in the study, seven patients could not be included in the analysis of respiratory function because they did not receive a study drug infusion after extubation. Consequently, data from 33 patients are used in the analysis of respiratory function; 16 received dexmedetomidine and 17 placebo. Inadequate arterial blood gas analysis was available in five patients (two from the dexmedetomidine group, and three from the placebo group). There were no significant differences in patient characteristics and operative details between the groups.
Requirements for morphine were reduced by more than 50% in patients receiving dexmedetomidine when compared with placebo after extubation (0.003 ± 0.004 vs 0.008 ± 0.006 mg/kg per h; P= 0.040).
There were no statistically significant differences between placebo and dexmedetomidine for oxygen saturations measured by pulse oximetry (P= 0.26), respiratory rate (P= 0.16; Fig. 1), arterial pH (P= 0.77) and PaCO2 (P= 0.75; Fig. 2) for the 6 h after extubation.
The dexmedetomidine group showed significantly higher PaO2: FIO2 ratios throughout the 6-h intubation (P= 0.036) and extubation (P= 0.037) periods (Fig. 3). There were no adverse respiratory events seen in either the dexmedetomidine or placebo group.
Respiratory rate for the 6-h periods before and after extubation. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
PaCO2 (PCO2) for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
PaO2 : FIO2 ratio for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.
Discussion:
Lack of respiratory depression in patients sedated with α2-adrenoceptor agonists was first reported by Maxwell [8] in a study investigating the respiratory effects of clonidine. However, more recent data suggests that clonidine may cause mild respiratory depression in humans [9], and α2-adrenoceptor agonists are well known to produce profound intraoperative hypoxaemia in sheep [10,11]. The effects of dexmedetomidine on other ventilation parameters also appear to be species specific [12].
Belleville et al [2] investigated the ventilatory effects of a 2-min intravenous infusion of dexmedetomidine on human volunteers. According to those investigators, minute ventilation and arterial PaCO2 were mildly decreased and increased, respectively. There was a rightward shift and depression of the hypercapnic response with infusions of 1.0 and 2.0 μg/kg.
Previous studies that investigated the respiratory effects of dexmedetomidine have only been performed in healthy human volunteers, who have received either single intramuscular injections or short (= 10 min) intravenous infusions of dexmedetomidine. It is therefore reassuring that no deleterious clinical effects on respiration and gas exchange were seen in the patients we studied, who were receiving long-term infusions. However, there are important limitations to the present results. No dose/response curve for dexmedetomidine can be formulated from the data, and further investigation is probably ethically difficult to achieve in the spontaneously ventilating intensive care patient. We also have no data on the ventilatory responses to hypercapnia and hypoxia, which would also be difficult to examine practically and ethically. The placebo group received more than twice as much morphine as patients receiving dexmedetomidine infusions after extubation, but there were no differences in respiratory rate or PaCO2 between the groups. We can not therefore determine from this study whether dexmedetomidine has any benefits over morphine from a respiratory perspective.
There were no differences in oxygen saturations between the groups because the administered oxygen concentration was adjusted to maintain satisfactory gas exchange. Interestingly, however, there were statistically significant higher PaO2 : FIO2 ratios in the dexmedetomidine group. This ratio allows for the variation in administered oxygen to patients during the study period, and gives some clinical indication of alveolar gas exchange. However, this variable was not a primary outcome variable for the present study, and may represent a type 1 error, although post hoc analysis reveals that the data have 80% power to detect a significant difference (α value 0.05). Further studies are obviously required.
Sedation continued over the extubation period, has been shown to reduce haemodynamic disturbances and myocardial ischaemia [13]. We have previously shown [1] that dexmedetomidine provides cardiovascular stability, with a reduction in rate-pressure product over the extubation period. A sedative agent that has analgesic properties, minimal effects on respiration and offers ischaemia protection would have enormous potential in the ICU. Dexmedetomidine may fulfill all of these roles, but at present we can only conclude that dexmedetomidine has no deleterious clinical effects on respiration when used in doses that are sufficient to provide adequate sedation and effective analgesia in the surgical population requiring intensive care.
PMCID: PMC29047  PMID: 11056756
α2-Adrenoceptor agonist; analgesia; dexmedetomidine; intensive care; postoperative; respiratory; sedation
6.  Remifentanil infusion as a modality for opioid-based anaesthesia in paediatric practice 
Indian Journal of Anaesthesia  2010;54(4):318-323.
This study was designed to compare the intra-operative and post-operative analgesic requirements and side effects of using fentanyl infusion versus remifentanil infusion during short-duration surgical procedures in children. The study comprised of 40 children randomly allocated into two equal groups: fentanyl (F-group) or remifentanil (R-group). Both were administered a continuous intravenous (i.v.) infusion. Anaesthetic recovery was assessed using the Brussels sedation scale every 5 min from the time of entry till discharge from recovery room. Post-operative analgesia was assessed throughout the first three post-operative (PO) hours using observational pain–discomfort scale (OPS) and adverse events were recorded. Haemodynamic variables showed a non-significant difference between both the groups. Patients who received remifentanil showed significantly shorter time to spontaneous respiration, eye opening, extubation and verbalization compared to those who received fentanyl. Discharge time was significantly shorter in R-group, and 18 patients fulfilled criteria for recovery-room discharge at ≤25 min with a significant difference in favour of remifentanil. Fentanyl provided significantly better PO analgesia than remifentanil and children in F-group showed a significantly lower mean cumulative OPS record than those in R-group; however, the number of patients requiring rescue analgesia did not show a significant difference between both the groups. Two cases in F-group and one in R-group had bradycardia, one case in R-group had mild hypotension and PO vomiting had occurred in three patients in the F-group and two patients in the R-group. In conclusion, remifentanil is appropriate for opioid-based anaesthesia for paediatric patients as it provides haemodynamic stability and rapid recovery with minimal post-operative side effects.
doi:10.4103/0019-5049.68375
PMCID: PMC2943701  PMID: 20882174
Opioid based; paediatric; remifentanil
7.  Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308] 
Critical Care  2004;8(4):R268-R280.
Introduction
This randomised, open-label, observational, multicentre, parallel group study assessed the safety and efficacy of analgesia-based sedation using remifentanil in the neuro-intensive care unit.
Methods
Patients aged 18–80 years admitted to the intensive care unit within the previous 24 hours, with acute brain injury or after neurosurgery, intubated, expected to require mechanical ventilation for 1–5 days and requiring daily downward titration of sedation for assessment of neurological function were studied. Patients received one of two treatment regimens. Regimen one consisted of analgesia-based sedation, in which remifentanil (initial rate 9 μg kg-1 h-1) was titrated before the addition of a hypnotic agent (propofol [0.5 mg kg-1 h-1] during days 1–3, midazolam [0.03 mg kg-1 h-1] during days 4 and 5) (n = 84). Regimen two consisted of hypnotic-based sedation: hypnotic agent (propofol days 1–3; midazolam days 4 and 5) and fentanyl (n = 37) or morphine (n = 40) according to routine clinical practice. For each regimen, agents were titrated to achieve optimal sedation (Sedation–Agitation Scale score 1–3) and analgesia (Pain Intensity score 1–2).
Results
Overall, between-patient variability around the time of neurological assessment was statistically significantly smaller when using remifentanil (remifentanil 0.44 versus fentanyl 0.86 [P = 0.024] versus morphine 0.98 [P = 0.006]. Overall, mean neurological assessment times were significantly shorter when using remifentanil (remifentanil 0.41 hour versus fentanyl 0.71 hour [P = 0.001] versus morphine 0.82 hour [P < 0.001]). Patients receiving the remifentanil-based regimen were extubated significantly faster than those treated with morphine (1.0 hour versus 1.93 hour, P = 0.001) but there was no difference between remifentanil and fentanyl. Remifentanil was effective, well tolerated and provided comparable haemodynamic stability to that of the hypnotic-based regimen. Over three times as many users rated analgesia-based sedation with remifentanil as very good or excellent in facilitating assessment of neurological function compared with the hypnotic-based regimen.
Conclusions
Analgesia-based sedation with remifentanil permitted significantly faster and more predictable awakening for neurological assessment. Analgesia-based sedation with remifentanil was very effective, well tolerated and had a similar adverse event and haemodynamic profile to those of hypnotic-based regimens when used in critically ill neuro-intensive care unit patients for up to 5 days.
doi:10.1186/cc2896
PMCID: PMC522854  PMID: 15312228
analgesia-based sedation; fentanyl; intensive care; morphine; remifentanil
8.  Combined use of remifentanil and propofol to limit patient movement during retinal detachment surgery under local anesthesia 
Saudi Journal of Anaesthesia  2010;4(3):147-151.
Background:
One of the drawbacks of performing ophthalmic surgery under local anesthesia is patient movement, which might affect optimal surgical outcome.
Purpose:
The study aims to evaluate the efficacy of the combined use of propofol and remifentanil as a sedative technique in comparison with the use of propofol alone to limit patient discomfort and movement during local anesthesia for vitreo-retinal surgery lasting for more than two hours.
Materials and Methods:
A total of 140 patients scheduled for vitreo-retinal surgery under local anesthesia, with an expected surgical time of more than two hours, were included in the study. Patients were divided randomly into two equal groups: group I where patients were given propofol and remifentanil by continuous infusion and group II where patients were given propofol alone by continuous infusion.
Results:
The two groups were comparable with regard to age, weight, gender, ASA physical status and duration of surgery. There was a significant decrease in heart rate and mean arterial blood pressure (MABP) in each group 10 minutes after the start of sedation compared with pre-sedation data and continued all through the procedure. There was an insignificant difference between the two groups with regard to changes in heart rate and MABP all through surgical procedure. There was no significant difference between the two groups with regard to the incidence of complications except for an increased incidence of breakthrough pain and discomfort which necessitated the use of fentanyl as a rescue treatment in the propofol group P<0.001. There were no instances of movements with a major effect on the surgical field, which could have affected surgical outcome, in the two groups. The number of patients who did not move was significantly higher, 56 (80%), in group I compared with 38 (54.29%) in group II with P<0.001. The ophthalmologist satisfaction scale was significantly higher in group I (4.5±0.63) compared with group II (3.7±1.04) with P=0.0016.
Conclusion:
The combined use of propofol and remifentanil as a continuous infusion before performance of the block and during lengthy vitreo-retinal surgery was associated with a lower incidence of patient discomfort, breakthrough pain, and patient movement along with high degree of surgeons’ satisfaction and hemodynamic stability.
doi:10.4103/1658-354X.71570
PMCID: PMC2980659  PMID: 21189850
Eye surgery; propofol; regional anesthesia; remifentanil; sedation
9.  Remifentanil-induced pronociceptive effect and its prevention with pregabalin 
Korean Journal of Anesthesiology  2011;60(3):198-204.
Background
Experimental and clinical studies have suggested that remifentanil probably causes acute tolerance or postinfusion hyperalgesia. This study was designed to confirm whether remifentanil given during propofol anesthesia induced postoperative pain sensitization, and we wanted to investigate whether pregabalin could prevent this pronociceptive effect.
Methods
Sixty patients who were scheduled for total abdominal hysterectomy were randomly allocated to receive (1) a placebo as premedication and an intraoperative saline infusion (control group), (2) a placebo as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (remifentanil group), or (3) pregabalin 150 mg as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (pregabalin-remifentanil group). Postoperative pain was controlled by titration of fentanyl in the postanesthetic care unit (PACU), followed by patient-controlled analgesia (PCA) with fentanyl. The patients were evaluated using the visual analogue scale (VAS) for pain scores at rest and after cough, consumption of fentanyl, sedation score and any side effects that were noted over the 48 h postoperative period.
Results
The fentanyl titration dose given in the PACU was significantly larger in the remifentanil group as compared with those of the other two groups. At rest, the VAS pain score in the remifentanil group at 2 h after arrival in the PACU was significantly higher than those in the other two groups.
Conclusions
The results of this study show that remifentanil added to propofol anesthesia causes pain sensitization in the immediate postoperative period. Pretreatment with pregabalin prevents this pronociceptive effect and so this may be useful for the management of acute postoperative pain when remifentanil and propofol are used as anesthetics.
doi:10.4097/kjae.2011.60.3.198
PMCID: PMC3071484  PMID: 21490822
Hyperalgesia; Pregabalin; Remifentanil; Tolerance
10.  Effect of ketamine pretreatment for anaesthesia in patients undergoing percutaneous transluminal balloon angioplasty with continuous remifentanil infusion 
Korean Journal of Anesthesiology  2011;61(4):308-314.
Background
An appropriate level of sedation and pharmacological assist are essential during percutaneous transluminal balloon angioplasty (PTA). Ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability with an opioid sparing effect suggesting that it would be ideal in combination with remifentanil and midazolam in spontaneously breathing patients. We evaluated the effect of a small dose of ketamine added to midazolam and remifentanil on analgesia/sedation for PTA procedures.
Methods
Sixty-four patients receiving PTA were enrolled. The Control group received midazolam 1.0 mg i.v. and continuous infusion of remifentanil 0.05 µg/kg/min. The Ketamine group received, in addition, an intravenous bolus of 0.5 mg/kg ketamine. Patients' haemodynamic data were monitored before remifentanil infusion, 5 min after remifentanil infusion, at 1, 3, 5, 30 min after incision, and at admission to the recovery room. Verbal numerical rating scales (VNRS) and sedation [OAA/S (Observer's Assessment of Alertness/Sedation)] scores were also recorded.
Results
The VNRS values at 1, 3, and 5 min after incision and OAA/S scores at 5 min after remifentanil infusion, and 1, 3, and 5 min after incision were lower in the Ketamine group than in the Control group. In the Control group, the VNRS value at 1 min after incision significantly increased and OAA/S values at 3, 5, and 30 min after incision significantly decreased compared to baseline values, while there were no significant changes in the ketamine group.
Conclusions
A small dose of ketamine as an adjunct sedative to the combination of midazolam and remifentanil produced a better quality of sedation and analgesia than without ketamine and provided stable respiration without cardiopulmonary deterioration.
doi:10.4097/kjae.2011.61.4.308
PMCID: PMC3219777  PMID: 22110884
Ketamine; Pain scale; Remifentanil; Sedation
11.  Bispectral Index Monitoring during Anesthesiologist-Directed Propofol and Remifentanil Sedation for Endoscopic Submucosal Dissection: A Prospective Randomized Controlled Trial 
Yonsei Medical Journal  2014;55(5):1421-1429.
Purpose
Endoscopic submucosal dissection (ESD) is a technically difficult and lengthy procedure requiring optimal depth of sedation. The bispectral index (BIS) monitor is a non-invasive tool that objectively evaluates the depth of sedation. The purpose of this prospective randomized controlled trial was to evaluate whether BIS guided sedation with propofol and remifentanil could reduce the number of patients requiring rescue propofol, and thus reduce the incidence of sedation- and/or procedure-related complications.
Materials and Methods
A total of 180 patients who underwent the ESD procedure for gastric adenoma or early gastric cancer were randomized to two groups. The control group (n=90) was monitored by the Modified Observer's Assessment of Alertness and Sedation scale and the BIS group (n=90) was monitored using BIS. The total doses of propofol and remifentanil, the need for rescue propofol, and the rates of complications were recorded.
Results
The number of patients who needed rescue propofol during the procedure was significantly higher in the control group than the BIS group (47.8% vs. 30.0%, p=0.014). There were no significant differences in the incidence of sedation- and/or procedure-related complications.
Conclusion
BIS-guided propofol infusion combined with remifentanil reduced the number of patients requiring rescue propofol in ESD procedures. However, this finding did not lead to clinical benefits and thus BIS monitoring is of limited use during anesthesiologist-directed sedation.
doi:10.3349/ymj.2014.55.5.1421
PMCID: PMC4108833  PMID: 25048506
Bispectral index; endoscopic submucosal dissection; propofol; remifentanil
12.  Effect of an analgo-sedation protocol for neurointensive patients: a two-phase interventional non-randomized pilot study 
Critical Care  2010;14(2):R71.
Introduction
Sedation protocols are needed for neurointensive patients. The aim of this pilot study was to describe sedation practice at a neurointensive care unit and to assess the feasibility and efficacy of a new sedation protocol. The primary outcomes were a shift from sedation-based to analgesia-based sedation and improved pain management. The secondary outcomes were a reduction in unplanned extubations and duration of sedation.
Methods
This was a two-phase (before-after), prospective controlled study at a university-affiliated, 14-bed neurointensive care unit in Denmark. The sample included patients requiring mechanical ventilation for at least 48 hours treated with continuous sedative and analgesic infusions or both. During the observation phase the participants (n = 106) were sedated as usual (non-protocolized), and during the intervention phase the participants (n = 109) were managed according to a new sedation protocol.
Results
Our study showed a shift toward analgo-sedation, suggesting feasibility of the protocol. We found a significant reduction in the use of propofol (P < .001) and midazolam (P = .001) and an increase in fentanyl (P < .001) and remifentanil (P = .003). Patients selected for daily sedation interruption woke up faster, and estimates of pain free patients increased from 56.8% to 82.7% (P < .001), suggesting efficacy of the protocol. The duration of sedation and unplanned extubations were unchanged.
Conclusions
Our pilot study showed feasibility and partial efficacy of our protocol. Some neurointensive patients might not benefit from protocolized practice. We recommend an interdisciplinary effort to target patients requiring less sedation, as issues of oversedation and inadequate pain management still need more attention.
Trial registration
ISRCTN80999859.
doi:10.1186/cc8978
PMCID: PMC2887194  PMID: 20403186
13.  Remifentanil discontinuation and subsequent intensive care unit-acquired infection: a cohort study 
Critical Care  2009;13(2):R60.
Introduction
Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on intensive care unit (ICU)-acquired infection.
Methods
This was a prospective observational cohort study performed in a 30-bed medical and surgical university ICU, during a one-year period. All patients hospitalised in the ICU for more than 48 hours were eligible. Sedation was based on a written protocol including remifentanil with or without midazolam. Ramsay score was used to evaluate consciousness. The bedside nurse adjusted sedative infusion to obtain the target Ramsay score. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired infection.
Results
Five hundred and eighty-seven consecutive patients were included in the study. A microbiologically confirmed ICU-acquired infection was diagnosed in 233 (39%) patients. Incidence rate of ICU-acquired infection was 38 per 1000 ICU-days. Ventilator-associated pneumonia was the most frequently diagnosed ICU-acquired infection (23% of study patients). Pseudomonas aeruginosa was the most frequently isolated microorganism (30%). Multivariate analysis identified remifentanil discontinuation (odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.28 to 4.99, P = 0.007), simplified acute physiology score II at ICU admission (1.01 per point, 95% CI = 1 to 1.03, P = 0.011), mechanical ventilation (4.49, 95% CI = 1.52 to 13.2, P = 0.006), tracheostomy (2.25, 95% CI = 1.13 to 4.48, P = 0.021), central venous catheter (2.9, 95% CI = 1.08 to 7.74, P = 0.033) and length of hospital stay (1.05 per day, 95% CI = 1.03 to 1.08, P < 0.001) as independent risk factors for ICU-acquired infection.
Conclusions
Remifentanil discontinuation is independently associated with ICU-acquired infection.
doi:10.1186/cc7788
PMCID: PMC2689508  PMID: 19383164
14.  Effect of Gabapentin on morphine demand and pain after laparoscopic sterilization using Filshie clips. A double blind randomized clinical trial 
BMC Anesthesiology  2006;6:12.
Background
A considerable number of patients require opioids during recovery after laparoscopic sterilization. This implies nausea, dizziness and sedation and increases the number of unplanned admissions. Gabapentin has shown excellent postoperative analgesic effect in a number of recent studies with few side effects. This study was designed to test whether gabapentin given preoperatively can reduce the number of patients needing morphine in the recovery period.
Methods
80 females scheduled for laparoscopic sterilization using Filshie clips were randomized to two treatment groups (Gaba group and control group).
All patients received lornoxicam 8 mg p.o. 30 min. before the procedure. Patients in the Gaba group received gabapentin 1200 mg p.o. and patients in the control group received placebo capsules prior to the procedure. All patients were anesthetized according to a protocol, using remifentanil and propofol.
Postoperative analgesia was obtained with patient controlled infusion of morphine. Pain, nausea, dizziness and sedation were scored at 2 and 4 hours after end of anesthesia. The expenditure of morphine was the primary measure for the effect of analgesia and the number of patients demanding morphine was the primary endpoint.
Results
Three patients were excluded because of procedural errors and one because of conversion to open surgery. 38 patients completed the study in each group.
32 (84%) patients in the gabapentin group and 37 (97%) patients in the control group did require morphine in the recovery period. (p = 0,049).
There was no significant difference between mean morphine consumption, pain scores and frequency of adverse effects (nausea, dizziness, sedation and vomiting)
Conclusion
The postoperative analgesic effect of gabapentin given preoperatively was confirmed in this study. For this procedure, with pain predominantly in the immediate recovery period, and of less intensity than after major surgical procedures, the effect demonstrated is much less pronounced than in similar studies of major surgery. General use of gabapentin as analgesic for laparoscopic sterilization is not supported by this study.
Trial Registration
Current Controlled Trials ISCRTN39209275
doi:10.1186/1471-2253-6-12
PMCID: PMC1637100  PMID: 17083725
15.  Effect of Gabapentin on Morphine Consumption and Pain after Surgical Debridement of Burn Wounds: A Double-Blind Randomized Clinical Trial Study 
Archives of Trauma Research  2012;1(1):38-43.
Background:
Burn pain is recognized as being maximal during therapeutic procedures, and wound debridement can be more painful than the burn injury itself. Uncontrolled acute burn pain increases the stress response and the incidence of chronic pain and associated depression. Although opiates are excellent analgesics, they do not effectively prevent central sensitization to pain. The anticonvulsant gabapentin has been proven effective for treating neuropathic pain in large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models with central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain.
Objectives:
The aim of this study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in burn patients undergoing resection of burn wounds.
Patients and Methods:
In a randomized, double-blind, placebo-controlled study, 50 burn patients received a single oral dose of gabapentin (1200mg) or placebo 2h before surgery. Anesthesia was induced with propofol and fentanyl and maintained by infusingpropofol, remifentanil, and 50% N2O in O2. All patients received patient-controlled analgesia with morphine at doses of 2.5 mg bolus and a lock-out time of 10 min for 24h before the operation. Pain was assessed on a visual analog scale (VAS) at rest and during movement at 1,4,8,12,16,20, and 24 h before the operation. Heart rate, oxygen saturation, mean arterial blood pressure, respiratory rate, sedation score, and morphine consumption were studied.
Results:
All the enrolled patients were able to complete the study; therefore, data from 50 patients wereanalyzed. The VAS scores at rest andduring movement at 1,4,8,12,16,20, and 24 h after the operation were significantly lower in the gabapentin group than in the placebo group (P < 0.05). Morphine consumption was significantly lessr in the gabapentin group than in the placebo group (P < 0.05). Sedation scores were similar in the 2 groups at all measured times. There were no differences in adverse effects between the groups.
Conclusions:
A single oral dose of 1200mg gabapentin resulted in a substantial reduction in postoperative morphine consumption and pain scores after surgical debridement in burn patients.
doi:10.5812/atr.5304
PMCID: PMC3955940  PMID: 24719841
Surgery; Postoperative Pain; Gabapentin; Morphine
16.  Optimal effect-site concentration of remifentanil when combined with dexmedetomidine in patients undergoing cystoscopy 
Background
Cystoscopic procedure is a very common practice in the field of urology due to its ability to survey the bladder for a variety of indications. However, patients who undergo cystoscopy feel intense pain and discomfort. This study investigated the half maximal effective concentration (EC50) of remifentanil in preventing cystoscope insertion pain under sedation using dexmedetomidine.
Methods
The study was prospectively conducted on 18 male patients, aged 18 to 65. Remifentail infusion was initiated together with dexmedetomidine, and started at a dose of 2.4 ng/ml on the first patient. The effect-site concentration (Ce) of remifentanil for each subsequent patient was determined by the previous patient's response using Dixon's up-and-down method with an interval of 0.3 ng/ml. Patients received a loading dose of 1.0 µg/kg dexmedetomidine over 10 minutes, followed by a maintenance dose of 0.6 µg/kg/hr. After the patient's OAA/S score (Observer's Assessment of Alertness/Sedation scale) reached 3-4, and the Ce of remifentanil reached target concentration, the urologist was allowed to insert the cystoscope and the pain responses were observed.
Results
The effect-site concentration of remifentanil required to prevent cystoscope insertion pain in 50% of patients under sedation using dexmedetomidine was 1.30 ± 0.12 ng/ml by Dixon's up-and-down method. The logistic regression curve of the probability of response showed that the EC50 and EC95 values (95% confidence limits) of remifentanil were 1.33 ng/ml (1.12-1.52 ng/ml) and 1.58 ng/ml (1.44-2.48 ng/ml), respectively.
Conclusions
Cystoscopic procedure can be carried out successfully without any pain or adverse effects by optimal remifentanil effect-site concentration (EC50, 1.33 ng/ml; EC95, 1.58 ng/ ml) combined with sedation using dexmedetomidine.
doi:10.4097/kjae.2014.66.1.39
PMCID: PMC3927000  PMID: 24567812
Cystoscopy; Dexmedetomidine; Monitored anesthesia care; Remifentanil
17.  Comparison of intraoperative blood loss during spinal surgery using either remifentanil or fentanyl as an adjuvant to general anesthesia 
BMC Anesthesiology  2013;13:46.
Background
Remifentanil enhances intraoperative hemodynamic stability, suggesting that it may decrease intraoperative blood loss when included as an adjuvant to general anesthesia. This retrospective study compared intraoperative blood loss during spinal surgery in patients administered either remifentanil or fentanyl as an opioid adjuvant.
Methods
We reviewed clinical and surgical data from 64 consecutive laminoplasty or laminectomy patients treated at National Hospital Organization Zentsuji Hospital between April 2010 and March 2011. Patients received either remifentanil (n = 35) or fentanyl (n = 29) as an opioid analgesic during general anesthesia. In addition to intraoperative blood loss, indices of hemodynamic stability, including heart rate as well as systolic, mean, and diastolic blood pressure (BP), were compared over the entire perioperative period between remifentanil and fentanyl groups.
Results
The remifentanil group exhibited significantly lower intraoperative arterial BP than the fentanyl group. Intraoperative blood loss was also significantly lower in the remifentanil group (125 ± 67 mL vs. 165 ± 82 mL, P = 0.035).
Conclusions
Intraoperative blood loss during spinal surgery was decreased in patients who received remifentanil as an opioid adjuvant, possibly because of lower intraoperative BP. A larger-scale prospective randomized controlled trial is warranted to confirm our results and to test whether remifentanil can decrease intraoperative blood loss during other surgical procedures.
doi:10.1186/1471-2253-13-46
PMCID: PMC3880217  PMID: 24304964
Intraoperative blood loss; Remifentanil; Hemodynamics; Fentanyl; Spinal surgery; General anesthesia
18.  Comparison of the effects of remifentanil andalfentanil on cardiovascular response to nasotracheal intubation: A prospective, randomized, double-blind study 
Background:
Nasotracheal intubation is often necessary in patients undergoingelective or emergency maxillofacial surgery. Previous studies have suggested that the increase in blood pressure after nasotracheal intubation is significantly greater than the increase after orotracheal intubation. Many drugs, including narcotic analgesics, are effective in modifying cardiovascular responses to orotracheal intubation.
Objective:
The effects of remifentanil and alfentanil on the cardiovascularresponses to nasotracheal intubation were compared in healthy patients scheduled to undergo surgery.
Methods:
This prospective, randomized, double-blind study was conductedat the Department of Anesthesiology and Reanimation, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. Patients aged 16 to 65 years scheduled to undergo elective maxillofacial surgery and who were American Society of Anesthesiologists status I or 11 were randomly assigned to receive remifentanil 1 μg/kg in 10 mL saline over 30 seconds followed by an infusion of 0.5 μg/kg · min, or alfentanil 10 μg/kg in 10 mL saline over 30 seconds followed by an infusion of saline. Anesthesia was then induced with propofol, cisatracurium, and 1% isoflurane with 66% nitrous oxide in oxygen. Heart rate (HR) and systolic and diastolic arterial pressures (SAP and DAP, respectively) were measured noninvasively at 2 minutes before general anesthesia induction (baseline); 2 minutes after induction; and 1, 3, and 5 minutes after nasotracheal intubation. Patients were monitored for cardiac changes using electrocardiography.
Results:
Forty consecutive patients were enrolled in the study. Twenty patients (11 males, 9 females; mean [SD] age, 27.7 [12.6] years) received remifentanil, and 20 patients (12 males, 8 females; mean [SD] age, 31.5 [17.2] years) received alfentanil. Two minutes after anesthesia induction, mean (SD) arterial pressures decreased significantly from baseline in the remifentanil group (changes, 22 [8]/11 [6] mm Hg) and the alfentanil group (changes, 10 [9]/12 [8] mm Hg) (both, P < 0.05). Changes in SAP and DAP followed a similar pattern in both groups, but SAP was significantly lower in the remifentanil group compared with that in the alfentanil group throughout the study period (all, P < 0.05). After 1 minute of intubation, DAP was significantly lower in the remifentanil group compared with that in the alfentanil group (66 [9] mm Hg vs. 73 [20] mm Hg; P < 0.05). Compared with baseline, HR was decreased significantly in both groups throughout the study (all, P < 0.05). Except SAP in the alfentanil group, SAP, DAP, and HR were increased 1 minute after intubation compared with preintubation values. However, SAP, DAP, and HR remained significantly lower compared with baseline values throughout the study period in both groups (all, P < 0.05) except DAP at 1 minute after incubation in the alfentanil group. Five patients in the remifentanil group and 2 patients in the alfentanil group required treatment of hypotension. None of the patients in either group required treatment of bradycardia.
Conclusions:
In this study in healthy surgical patients aged 16 to 65 years, remifentanil 1 μg/kg given over 30 seconds, followed by a remifentanil infusion of 0.5 μg/kg · min, was similarly effective compared with alfentanil 10 μg/kg in attenuating the pressor response to nasotracheal intubation, but the incidence of hypotension in patients administered remifentanil was high.
doi:10.1016/j.curtheres.2005.08.006
PMCID: PMC3964577  PMID: 24672137
remifentanil; alfentanil; cardiovascular responses; nasotracheal intubation
19.  A Comparison of Ketamine and Paracetamol for Preventing Remifentanil Induced Hyperalgesia in Patients Undergoing Total Abdominal Hysterectomy 
Background: The aim of this prospective, randomized, placebo-controlled study was to compare the effects of ketamine and paracetamol on preventing remifentanil induced hyperalgesia.
Methods: Ninety patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups to receive (I) either saline infusion; (II) 0.5 mg/kg ketamine iv bolus or (III) 1000 mg iv paracetamol infusion before induction of anesthesia. Until the skin closure, anesthesia was maintained with 0.4 µg/kg/min remifentanil infusion in all groups, additionally Group II received 5 µg/kg/min ketamine infusion. Pressure pain thresholds were measured the day before surgery during the preoperative visit for baseline measurements and repeated postoperatively at 24 and 48 hours (hrs). Pressure pain thresholds were established by digital algometer on three different peri- incisional regions for calculating mean pressure pain threshold values. The visual analogue scale (VAS), sedation scores, total morphine consumption and side effects were assessed postoperatively.
Results: Demographic characteristics, duration of surgery and anesthesia were similar in the three groups. Pain thresholds at the incision region were significantly lower at 24 and 48 hrs postoperatively in Group I than the other Groups (p< 0.05). In Group І, pain thresholds were lower compared with preoperative baseline values. Thresholds in Group ІІ and Group ІІІ were higher compared with preoperative baseline values (p< 0.05) The VAS scores at all evaluation times were significantly higher in Group І when compared to Group ІІ and at 2, 4, 6 ,12 hrs were higher in Group I than Group ІІІ (p< 0.05). The morphine consumption was higher in Group ІІІ at 24 and 48 hrs postoperatively (p< 0.05).
Conclusion: It was shown that ketamine and paracetamol were both effective in preventing remifentanil induced hyperalgesia.
doi:10.7150/ijms.4222
PMCID: PMC3384914  PMID: 22745573
remifentanil; ketamine; paracetamol; postoperative pain; hyperalgesia.
20.  Intravenous Remifentanil versus Epidural Ropivacaine with Sufentanil for Labour Analgesia: A Retrospective Study 
PLoS ONE  2014;9(11):e112283.
Remifentanil with appropriate pharmacological properties seems to be an ideal alternative to epidural analgesia during labour. A retrospective cohort study was undertaken to assess the efficacy and safety of remifentanil intravenous patient-controlled analgesia (IVPCA) compared with epidural analgesia. Medical records of 370 primiparas who received remifentanil IVPCA or epidural analgesia were reviewed. Pain and sedation scores, overall satisfaction, the extent of pain control, maternal side effects and neonatal outcome as primary observational indicators were collected. There was a significant decline of pain scores in both groups. Pain reduction was greater in the epidural group throughout the whole study period (0∼180 min) (P<0.0001), and pain scores in the remifentanil group showed an increasing trend one hour later. The remifentanil group had a lower SpO2 (P<0.0001) and a higher sedation score (P<0.0001) within 30 min after treatment. The epidural group had a higher overall satisfaction score (3.8±0.4 vs. 3.7±0.6, P = 0.007) and pain relief score (2.9±0.3 vs. 2.8±0.4, P<0.0001) compared with the remifentanil group. There was no significant difference on side effects between the two groups, except that a higher rate of dizziness (1% vs. 21.8%, P<0.0001) was observed during remifentanil analgesia. And logistic regression analysis demonstrated that nausea, vomiting were associated with oxytocin usage and instrumental delivery, and dizziness was associated to the type and duration of analgesia. Neonatal outcomes such as Apgar scores and umbilical-cord blood gas analysis were within the normal range, but umbilical pH and base excess of neonatus in the remifentanil group were significantly lower. Remifentanil IVPCA provides poorer efficacy on labor analgesia than epidural analgesia, with more sedation on parturients and a trend of newborn acidosis. Despite these adverse effects, remifentanil IVPCA can still be an alternative option for labor analgesia under the condition of one-to-one bedside care, continuous monitoring, oxygen supply and preparation for neonatal resuscitation.
doi:10.1371/journal.pone.0112283
PMCID: PMC4227805  PMID: 25386749
21.  Target-controlled infusion of remifentanil with propofol or desflurane under bispectral index guidance: quality of anesthesia and recovery profile 
BACKGROUND:
Our objective was to examine the clinical properties of two anesthetic regimens, propofol target-controlled infusion (TCI), or desflurane using remifentanil TCI under bispectral index (BIS) guidance during ear, nose, and throat (ENT) procedures.
METHODS:
Forty consenting patients who scheduled for ENT procedures were prospectively studied and were included in one of the two groups: TCI group or desflurane (DES) group. General anesthesia was induced with 3 ng mL-1 and 4 μg mL-1 effect site concentrations (Ce) of remifentanil and propofol, respectively, with TCI system. After intubation, while propofol infusion was continued in the TCI group, it was ceased in the DES group and desflurane with an initial delivered fraction of 6% was administered. The Ce of propofol infusion and inspired fraction of desflurane was adjusted in order to keep BIS as 50 ± 10.
RESULTS:
General mean values of mean arterial pressure (MAP) and heart rate (HR) for the TCI group was significantly higher than DES group (89.3 mmHg and 72.4 bpm vs. 77.1 mmHg and 69.5 bpm). Early emergence from anesthesia did not significantly differ between the groups. The rate of patients’ Aldrete score (ARS) to reach 10 was found to be 100% at the 15th min in both groups.
CONCLUSIONS:
Bispectral index guided combinations of remifentanil TCI either with propofol TCI or desflurane anesthetic regimens are both suitable for patients undergoing ENT surgery. The lower blood pressure in the remifentanil TCI with desflurane anesthetic regimens may be a significant advantage.
PMCID: PMC3214372  PMID: 22091283
Infusion Pumps; Remifentanil; Propofol; Desflurane; Consciousness Monitors
22.  Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment 
Critical Care  2003;8(1):R21-R30.
Introduction
This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care.
Methods
A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6–9 μg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain.
Results
There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use.
Conclusion
Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.
doi:10.1186/cc2399
PMCID: PMC420060  PMID: 14975051
analgesia based sedation; critical care; offset times; pharmacodynamics; remifentanil; renal function; safety
23.  Etomidate-Remifentanil is more Suitable for Monitored Anesthesia Care during Gastroscopy in Older Patients than Propofol-Remifentanil 
Background
This prospective and randomized study was designed to compare safety, potential complications, and patient and examiner satisfaction of 2 anesthetic combinations – etomidate-remifentanil and propofol-remifentanil – in elderly patients undergoing diagnostic gastroscopy.
Material/Methods
A group of 720 patients, aged 60–80 years, scheduled for diagnostic gastroscopy under sedation were prospectively randomized. After 0.4–0.6 μg kg−1 of remifentanil was infused, etomidate or propofol was administered. Patients in the etomidate group received doses of etomidate at 0.1–0.15 mg kg−1 followed by 4–6 mg. Patients in the propofol group received doses of propofol at 1–2 mg kg−1 followed by 20–40 mg. Physiological indexes were evaluated for the 715 of 720 patients that completed the treatment. The onset time, duration time, and discharge time were recorded. Physicians, anesthetists, and patients were surveyed to assess their satisfaction.
Results
Systolic pressure and diastolic pressure decreased significantly after the procedure in the propofol group (P<0.001). The average heart rate was significantly lower in the propofol group (P<0.05). No periods of desaturation (SpO2 <95%) were observed in either group. The onset time was earlier in the etomidate group (P=0.00). All adverse events, with the exception of myoclonus, were greater in the propofol group, and physician and patient satisfaction in both groups was similar.
Conclusions
Etomidate-remifentanil administration for sedation and analgesia during gastroscopy resulted in more stable hemodynamic responses and less adverse events in older patients.
doi:10.12659/MSM.891183
PMCID: PMC4288392  PMID: 25553506
Etomidate; Gastroscopy; Propofol
24.  The EC50 of remifentanil to minimize the cardiovascular changes during head holder pinning in neurosurgery 
Korean Journal of Anesthesiology  2012;63(4):327-333.
Background
During neuroanesthesia, head holder pinning commonly results in sympathetic stimulation manifested by hemodynamic changes, such as increased heart rate and arterial blood pressure. Remifentanil has been used successfully to control acute autonomic responses during neurosurgical procedures. The objective of this study was to determine effect-site concentration of remifentanil for suppressing the hemodynamic response to head holder pinning with the probability of 50% (EC50).
Methods
Forty-one ASA physical status I or II patients, between the ages of 20-70, who were scheduled for neurosurgery were recruited into this study. After arrival in the operating room, standard monitoring was applied throughout the study, which included a bispectral index monitor. Both propofol and remifentanil were administered by Target-control infusion device. The Dixon "up-and-down" sequential allocation method was used to determine the EC50 of remifentanil.
Results
The EC50 of remifentanil was 2.19 ± 0.76 ng/ml by the turning point estimate (TPE). In probit analysis, EC50 was 2.42 ng/ml (95% CI : -0.62-4.66) and EC95 was 5.70 ng/ml (95% CI : 4.02-67.53). The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65). The EC95 estimator comes from isotonic regression is 4.28 ng/ml (95% CI : 3.85-4.41).
Conclusions
This study showed that EC50 of remifentanil was 2.19 ± 0.76 ng/ml by TPE. EC50 was 2.42 ng/ml (95% CI -0.62-4.66) in probit analysis, as back up analysis. The EC50 estimator comes from isotonic regression is 2.90 ng/ml (95% CI : 1.78-3.65).
doi:10.4097/kjae.2012.63.4.327
PMCID: PMC3483491  PMID: 23115685
Hemodynamics; Neurosurgery; Propofol; Remifentanil
25.  Intra- and inter-individual variation of BIS-index® and Entropy® during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study 
Critical Care  2009;13(1):R20.
Introduction
We studied intra-individual and inter-individual variability of two online sedation monitors, BIS® and Entropy®, in volunteers under sedation.
Methods
Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS® and Entropy® (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered.
Results
Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy® values showed greater variability than BIS® values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation.
Conclusions
The large intra-individual and inter-individual variability of BIS® and Entropy® values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability.
Trial registration
clinicaltrials.gov Nr. NCT00641563.
doi:10.1186/cc7723
PMCID: PMC2688138  PMID: 19228415

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