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.
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).
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.
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.
analgesia; analgesia based sedation; critical care; fentanyl; propofol; remifentanil; renal function; sedation
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.
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.
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.
Remifentanil discontinuation is independently associated with ICU-acquired infection.
Optimal sedation and analgesia are of key importance in intensive care. The aim of this study was to assess the quality of sedoanalgesia and outcome parameters in regimens containing midazolam and either fentanyl or remifentanil.
A prospective, randomized, open-label, controlled trial was carried out in the ICU unit of a large teaching hospital in Istanbul over a 9-month period. Thirty-four patients were randomly allocated to receive either a remifentanil-midazolam regimen (R group, n = 17) or a fentanyl-midazolam regimen (F group, n = 17).
A strong correlation between Riker Sedation-Agitation Scale (SAS) and Ramsey Scale (RS) measurements was observed. Comparatively, remifentanil provided significantly more potent and rapid analgesia based on Behavioral-Physiological Scale (BPS) measurements and a statistically nonsignificantly shorter time to discharge. On the other hand, remifentanil also caused a significantly sharper fall in heart rate within the first six hours of treatment.
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.
Opioid based; paediatric; remifentanil
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.
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.
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).
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.
Providing effective analgesia and adequate sedation is a generally accepted goal of intensive care medicine. Due to its rapid, organ independent and predictable metabolism the short acting opioid remifentanil might be particularly useful for analgesia-based sedation in the intensive care unit (ICU). This hypothesis was tested by two studies in this issue of Critical Care. The study by Breen et al. shows that remifentanil does not exert prolonged clinical effects when continuously infused in renal failure patients, although the weak acting metabolite remifentanil acid accumulates. The study by Muellejans et al. reports a multicenter trial comparing a remifentanil versus a fentanyl based regimen in ICU patients. With both substances a target analgesia and sedation level was reached, and no major differences were found when frequent assessments of the sedation level and according readjustments of doses were performed. These results are in accordance with other studies suggesting that the adherence to a clear analgesia-based sedation protocol might be more important then the choice of medications itself.
analgesia; sedation; remifentanil; organ failure
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.
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.
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.
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.
Ketamine; Pain scale; Remifentanil; Sedation
This study aimed to compare continuous intravenous infusion combinations of propofol-remifentanil and propofol-ketamine for deep sedation for surgical extraction of all 4 third molars. In a prospective, randomized, double-blinded controlled study, participants received 1 of 2 sedative combinations for deep sedation for the surgery. Both groups initially received midazolam 0.03 mg/kg for baseline sedation. The control group then received a combination of propofol-remifentanil in a ratio of 10 mg propofol to 5 μg of remifentanil per milliliter, and the experimental group received a combination of propofol-ketamine in a ratio of 10 mg of propofol to 2.5 mg of ketamine per milliliter; both were given at an initial propofol infusion rate of 100 μg/kg/min. Each group received an induction loading bolus of 500 μg/kg of the assigned propofol combination along with the appropriate continuous infusion combination . Measured outcomes included emergence and recovery times, various sedation parameters, hemodynamic and respiratory stability, patient and surgeon satisfaction, postoperative course, and associated drug costs. Thirty-seven participants were enrolled in the study. Both groups demonstrated similar sedation parameters and hemodynamic and respiratory stability; however, the ketamine group had prolonged emergence (13.6 ± 6.6 versus 7.1 ± 3.7 minutes, P = .0009) and recovery (42.9 ± 18.7 versus 24.7 ± 7.6 minutes, P = .0004) times. The prolonged recovery profile of continuously infused propofol-ketamine may limit its effectiveness as an alternative to propofol-remifentanil for deep sedation for third molar extraction and perhaps other short oral surgical procedures, especially in the ambulatory dental setting.
Propofol; Ketamine; Remifentanil; Deep sedation; TIVA
Somatosensory evoked potentials (SSEP) are being used for the investigation and monitoring of the integrity of neural pathways during surgical procedures. Intraoperative neurophysiologic monitoring is affected by the type of anesthetic agents. Remifentanil is supposed to produce minimal or no changes in SSEP amplitude and latency. This study aims to investigate whether high doses of remifentanil influence the SSEP during spinal surgery under total intravenous anesthesia.
Ten patients underwent spinal surgery. Anesthesia was induced with propofol (2 mg/Kg), fentanyl (2 mcg/Kg) and a single dose of cis-atracurium (0.15 mg/Kg), followed by infusion of 0.8 mcg/kg/min of remifentanil and propofol (30-50 mcg/kg/min). The depth of anesthesia was monitored by Bispectral Index (BIS) and an adequate level (40-50) of anesthesia was maintained. Somatosensory evoked potentials (SSEPs) were recorded intraoperatively from the tibial nerve (P37) 15 min before initiation of remifentanil infusion. Data were analysed over that period.
Remifentanil induced prolongation of the tibial SSEP latency which however was not significant (p > 0.05). The suppression of the amplitude was significant (p < 0.001), varying from 20-80% with this decrease being time related.
Remifentanil in high doses induces significant changes in SSEP components that should be taken under consideration during intraoperative neuromonitoring.
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.
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.
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.
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.
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.
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.
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.
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.
Hyperalgesia; Pregabalin; Remifentanil; Tolerance
This prospective study evaluated the effects of continuous sedation using midazolam, with or without remifentanil, on postoperative nausea and vomiting (PONV) in patients undergoing myringoplasty.
Materials and Methods
Sixty patients undergoing myringoplasty were sedated with midazolam in the presence of remifentanil (group MR), or after saline injection instead of remifentanil (group M).
Three patients (10%) in group M complained of nausea; two vomited. Four patients (13%) in group MR complained of nausea and vomited within 24 h after surgery. Rescue drugs were given to the six patients who vomited. No significant difference was detected between the two groups regarding the incidence or severity of nausea, incidence of vomiting, or need for rescue drugs.
Midazolam-based continuous sedation can reduce PONV after myringoplasty. Compared with midazolam alone, midazolam with remifentanil produced no difference in the incidence or severity of nausea, incidence of vomiting, or need for rescue drugs.
Midazolam; myringoplasty; PONV; remifentanil
Hospitals are increasingly forced to consider the economics of technology use. We estimated the incremental cost-consequences of remifentanil-based analgo-sedation (RS) vs. conventional analgesia and sedation (CS) in patients requiring mechanical ventilation (MV) in the intensive care unit (ICU), using a modelling approach.
A Markov model was developed to describe patient flow in the ICU. The hourly probabilities to move from one state to another were derived from UltiSAFE, a Dutch clinical study involving ICU patients with an expected MV-time of two to three days requiring analgesia and sedation. Study medication was either: CS (morphine or fentanyl combined with propofol, midazolam or lorazepam) or: RS (remifentanil, combined with propofol when required). Study drug costs were derived from the trial, whereas all other ICU costs were estimated separately in a Dutch micro-costing study. All costs were measured from the hospital perspective (price level of 2006). Patients were followed in the model for 28 days. We also studied the sub-population where weaning had started within 72 hours.
The average total 28-day costs were €15,626 with RS versus €17,100 with CS, meaning a difference in costs of €1474 (95% CI -2163, 5110). The average length-of-stay (LOS) in the ICU was 7.6 days in the RS group versus 8.5 days in the CS group (difference 1.0, 95% CI -0.7, 2.6), while the average MV time was 5.0 days for RS versus 6.0 days for CS. Similar differences were found in the subgroup analysis.
Compared to CS, RS significantly decreases the overall costs in the ICU.
Dexmedetomidine is an α2-receptor agonist administered by continuous infusion in the intensive care unit (ICU) for sedation of critically ill patients who are undergoing mechanical ventilation following intubation. Relative to ICU patients receiving midazolam (a γ-aminobutyric acid agonist) for sedation, those receiving dexmedetomidine spent less time on ventilation, had fewer episodes of delirium, and had a lower incidence of tachycardia and hypertension.
To assess the economic impact, in a Canadian context, of dexmedetomidine, relative to midazolam, for sedation in the ICU.
This economic evaluation was based on a cost–consequences analysis, from the perspective of the Canadian health care system. The selected time horizon was an ICU stay (maximum 30 days). Clinical data were obtained from a previously published prospective, randomized, double-blind trial comparing dexmedetomidine and midazolam. This evaluation considered the costs of the medications, mechanical ventilation, and delirium episodes, as well as costs associated with adverse events requiring an intervention. All costs were adjusted to 2010 and are reported in Canadian dollars.
The average cost of the medication was higher for dexmedetomidine than midazolam ($1929.57 versus $180.10 per patient), but the average costs associated with mechanical ventilation and management of delirium were lower with dexmedetomidine than with midazolam ($2939 versus $4448 for ventilation; $2127 versus $3012 for delirium). The overall cost per patient was lower with dexmedetomidine than with midazolam ($7022 versus $7680). Deterministic sensitivity analysis confirmed the robustness of the difference.
The use of dexmedetomidine was, in most contexts, a more favourable strategy than the use of midazolam, in terms of clinical consequences and economic impact. Dexmedetomidine was less expensive than midazolam and was associated with lower occurrence of delirium and shorter duration of mechanical ventilation.
dexmedetomidine; sedation; intensive care unit; economic evaluation; dexmédétomidine; sédation; unité de soins intensifs; évaluation économique
An important concern of intra-operative infusion of remifentanil is the possible development of acute opioid tolerance, which manifests as an increased postoperative analgesia requirement. We have examined the effect of the timing of intra operative morphine administration on the need for morphine consumption for pain control during the first 24 hours after operation.
Sixty adult patients scheduled for elective open unilateral nephrolithotomy surgery were recruited for this prospective randomized double-blind study. Anesthesia was induced with 0.03 mg/kg midazolam, 1 µg/kg remifentanil, and 1.5-2 mg/kg propofol. Anesthesia was maintained with 100 µg/kg/min propofol, and 0.25 µg/kg/min remifentanil. Both groups received 0.1 mg/kg morphine intravenously at 2 different times; in the first group (group E) immediately after intubation and in the second group (group L) 20-30 min before the anticipated end of operation.
There was no difference in pain scores at awakening, the amount of morphine given to the 2 groups for pain control, or the time to discharge from PACU between the 2 groups. The pain scores at admission to ward and at every 4 hours thereafter, until 24 hours, were not significantly different between the 2 groups. The cumulative amount of the first 24 hours morphine consumption in the ward in E group was 28.2 ± 20.1 mg and 26.5 ± 15 mg in L group, respectively (P = 0.71).
Early intra-operative administration of morphine compared to that of morphine in the end of surgery did not affect postoperative morphine consumption and pain scores during the first 24 hours after surgery for open nephrolithotomy. Newer pharmacologic interventions for prevention of acute tolerance of opioids seems rational (Clinical trial registration No. ACTRN: 12609000570280).
Morphine; Postoperative pain; Propofol; Remifentanil
Our case series prospectively evaluate the concept of Patient/Family-Controlled Sedation with midazolam, as an alternative to sedation by continuous infusion in terminal cancer patients.
Our method was applied in 8 pts. Midazolam was administered in a Patient Control Analgesia mode. The infusion pump was activated "as-needed" by the pt or a caretaker. Sedation was rated as: 1) awake 2) arousable to voice 3) arousable to light pain or 4) unarousable. Family satisfaction was rated as: 1) good, 2) fair, 3) poor, or 4) unacceptable. Mean midazolam consumption was 12 – 40 mg/24 hours. We did not observe respiratory depression. Death occurred 1–6 days after sedation started. Family satisfaction was mainly good and median sedation was in the range 2 – 3.
Patient/Family-Controlled Sedation with midazolam was effective in providing comfort, by allowing titration of sedation to each patient's needs.
This prospective study evaluated the use of continuous sedation using propofol and remifentanil when carpal tunnel release (CTR) was performed under local anesthesia.
We sedated 60 patients undergoing CTR using local anesthesia with remifentanil at loading and continuous doses of 0.5 µg kg-1 and 0.05 µg kg-1min-1, respectively, and propofol, using a target controlled infusion (TCI) pump set to a target of 2 µg mL-1 (group A), or with the same drug doses except that the continuous remifentanil dose was 0.07 µg kg-1min-1 (group B) or 0.1 µg kg-1min-1 (group C).
In group B, the levels of pain when local anesthetics were administered (p = 0.001), intraoperative pain (p < 0.001) and anxiety (p = 0.001) were significantly lower than those of group A. Furthermore, the incidence of adverse events, including desaturation (p < 0.001) and vomiting (p = 0.043), was significantly lower in group B than in group C.
Continuous sedation using an appropriate dose of remifentanil and propofol can be used as safe, efficacious ambulatory anesthesia in cases of CTR under local anesthesia, performed using only 2 mL of local anesthetic, with a high degree of patient satisfaction.
Carpal tunnel syndrome; Propofol; Remifentanil
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.
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.
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.
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.
analgesia based sedation; critical care; offset times; pharmacodynamics; remifentanil; renal function; safety
In this randomized, double-blind study, we investigated the analgesic efficacy and side effects of continuous constant-dose infusions of remifentanil after total abdominal hysterectomy and compared it to fentanyl.
Materials and Methods
Fifty-six adult female patients scheduled for elective total abdominal hysterectomy were enrolled in this study. Patients were randomly assigned to two groups according to fentanyl (group F, n = 28) or remifentanil (group R, n = 28) for postoperative analgesia. Patients in group F were given fentanyl intravenously with an infusion rate of fentanyl 0.5 µg/kg/hr; group R was given remifentanil with an infusion rate of remifentanil 0.05 µg/kg/min for 2 days. Pain intensity at rest, occurrence of postoperative nausea and vomiting (PONV), dizziness, pruritus, and respiratory depression were assessed 1 hr after arrival at the post-anesthesia care unit, at 6; 12; 24; and 48 hr postoperation and 6 hr post-infusion of the study drug. Pain was evaluated by using visual analogue scale (VAS; 0 - 10). The time that patients first requested analgesics was recorded as well as additional analgesics and antiemetics.
There were no significant differences in VAS, time to first postoperative analgesics, and additional analgesics between the 2 groups. The incidences and severities of PONV and opioid related side effects were not different between the groups; however, there were 3 episodes (10.7%) of serious respiratory depression in group R.
Continuous infusion technique of remifentanil did not reveal any benefits compared to fentanyl. Furthermore, it is not safe for postoperative analgesia in the general ward.
Postoperative nausea and vomiting; postoperative pain control; remifentanil; respiratory depression
Sedation is widely used in intensive care unit (ICU) patients to limit the risk of pulmonary barotrauma and to decrease oxygen needs. However, adverse effects of cc5128sedation have not been fully evaluated; in particular, effects of benzodiazepine and opiates on microcirculation have not been extensively studied. The aim of this study was to evaluate the microcirculatory effects of a sedation protocol commonly prescribed in the ICU.
Ten non-septic patients under controlled ventilation requiring sedation for therapeutic purposes were enrolled in a prospective observational study conducted in an ICU of a university hospital. Sedation was conducted in two successive steps: first, each patient received midazolam (0.1 mg/kg per hour after a bolus of 0.05 mg/kg, then adapted to reach a Ramsay score of between 3 and 5). Second, after one hour, sufentanil was added (0.1 μg/kg per hour after a bolus of 0.1 μg/kg). Arterial pressure, heart rate, cardiac output determined by transthoracic impedance, transcutaneous oxygen (tcPO2) and carbon dioxide (tcPCO2) pressures, and microcirculatory blood flow determined by laser Doppler flowmetry at rest and during a reactive hyperaemia challenge were measured before sedation (NS period), one hour after midazolam infusion (H period), and one hour after midazolam-sufentanil infusion (HS period).
Arterial pressure decreased in both sedation periods, but heart rate, cardiac output, tcPO2, and tcPCO2 remained unchanged. In both sedation periods, microcirculatory changes occurred with an increase in cutaneous blood flow at rest (H period: 207 ± 25 perfusion units [PU] and HS period: 205 ± 25 PU versus NS period: 150 ± 22 PU, p < 0.05), decreased response to ischaemia (variation of blood flow to peak: H period: 97 ± 16 PU and HS period: 73 ± 9 PU versus NS period: 141 ± 14 PU, p < 0.05), and attenuation of vasomotion.
Sedation with midazolam or a combination of midazolam and sufentanil induces a deterioration of vasomotion and microvascular response to ischaemia, raising the question of whether this effect may further alter tissue perfusion when already compromised, as in septic patients.
The purpose of this study was to prospectively characterize the safety and effectiveness of moderate sedation/analgesia for performing radiologic non-vascular abdominal intervention.
Materials and Methods
During a 3-month period, a total of 63 adult patients with a mean age of 64 years (range: 27-82) underwent moderate sedation for 72 radiologic non-vascular interventional procedures. A combination of fentanyl citrate and midazolam hydrochloride, based on the patient's body weight, was intravenously administered until the patient was drowsy and tranquil. The adverse events associated with this moderate sedation were assessed. The visual analog scale format was used to measure the subjective feelings of the patient's pre-procedural anxiety and intraprocedural pain.
The mean total dose per kilogram of body weight of fentanyl used in PTBD was 1.148 µg, it was 1.157 µg for PTGBD, 1 µg for AD, 1 µg for PCN, 1.641 µg for TDC, 1 µg for DJS, 2 µg for BS, 1 µg for GS and 2 µg for RFA. The mean total dose per kilogram of body weight of midazolam was 0.035 mg in PTBD, PTGBD, AD, PCN, DJS, GS and RFA, 0.039 mg in TDC, and 0.043 mg in BS. A temporary reduction of systolic blood pressure to less than 80 mmHg was observed during 5 procedures (6.9%), whereas a temporary elevation of systolic blood pressure above 150 mmHg was observed during 10 procedures (13.8%). A reduction of arterial oxygen saturation to less than 90% was observed during 14 procedures (19.4%). None of the patients required pharmacologic reversal agents or cardiopulmonary resuscitation. The mean anxiety score recorded before all procedures was 5.2 (distressing). The mean pain score during the procedure, which was recorded after all procedures, was 2.9 (mild).
Moderate sedation allows performance of safe and effective radiologic non-vascular intervention, and it is also easy for an interventional radiologist to use. The patients should be continuously monitored to check their vital signs and arterial oxygen saturation during the procedures.
Anesthesia; Abdomen, interventional procedures
The aim of this study was to define the optimal target concentration of remifentanil which effectively achieves conscious sedation without significant vital sign changes and side effects during spinal anesthesia.
Sixty patients underwent spinal anesthesia with 0.5% hyperbaric bupivacaine (8-16 mg), and were infused with a target controlled infusion (TCI) of remifentanil at 1.0 ng/ml (group R10, n = 15), 2.0 ng/ml (group R20, n = 15), 3.0 ng/ml (group R30, n = 15), and 3.5 ng/ml (group R35, n = 15). Observer's assessment of alertness/sedation (OAA/S) scale, the bispectral index (BIS), anxiety levels and infusion rate of remifentanil were monitored during the operation.
OAA/S scale was significantly lower in groups R30 (3.96) and R35 (3.34) than groups R10 (4.31) and R20 (4.26). Incidence of intraoperative respiratory depression events, post operative nausea and vomiting were significantly higher in group R35 than the other groups. There were no significant differences in BIS, anxiety level and incidences of recall of the operative procedure among the groups.
We conclude that the TCI of remifentanil at 3.0 ng/ml produces an effective sedation and anti-anxiety effects without significant side effects during spinal anesthesia.
Conscious sedation; Remifentanil; Spinal anesthesia; Target controlled Infusion
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.
remifentanil; ketamine; paracetamol; postoperative pain; hyperalgesia.
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.
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.
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.
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.
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.
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.
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.
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.
Infusion Pumps; Remifentanil; Propofol; Desflurane; Consciousness Monitors