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.
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.
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.
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
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.
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
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.
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).
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.
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.
analgesia-based sedation; fentanyl; intensive care; morphine; remifentanil
Diagnostic and therapeutic endoscopy can successfully be performed by applying moderate (conscious) sedation. Moderate sedation, using midazolam and an opioid, is the standard method of sedation, although propofol is increasingly being used in many countries because the satisfaction of endoscopists with propofol sedation is greater compared with their satisfaction with conventional sedation. Moreover, the use of propofol is currently preferred for the endoscopic sedation of patients with advanced liver disease due to its short biologic half-life and, consequently, its low risk of inducing hepatic encephalopathy. In the future, propofol could become the preferred sedation agent, especially for routine colonoscopy. Midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam. Among opioids, pethidine and fentanyl are the most popular. A number of other substances have been tested in several clinical trials with promising results. Among them, newer opioids, such as remifentanil, enable a faster recovery. The controversy regarding the administration of sedation by an endoscopist or an experienced nurse, as well as the optimal staffing of endoscopy units, continues to be a matter of discussion. Safe sedation in special clinical circumstances, such as in the cases of obese, pregnant, and elderly individuals, as well as patients with chronic lung, renal or liver disease, requires modification of the dose of the drugs used for sedation. In the great majority of patients, sedation under the supervision of a properly trained endoscopist remains the standard practice worldwide. In this review, an overview of the current knowledge concerning sedation during digestive endoscopy will be provided based on the data in the current literature.
Gastrointestinal endoscopy; Endoscopy; Sedation; Analgesia; Digestive system
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
OBJECTIVE--To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN--Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS--Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS--Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT--Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS--Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION--Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.
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
Even with an adequate pain assessment, critically ill patients under sedation experience pain during procedures in the intensive care unit (ICU). We evaluated the effects of adjunctive administration of Remifentanil, a short-acting drug, in deeply sedated patient on variation of Bispectral Index (BIS) during a fiberoptic bronchoscopy.
A prospective, randomized, blinded, placebo-controlled study was conducted in 18-bed ICU. Patients needing a tracheal fibroscopy under deep sedation (midazolam (0.1 mg/kg per hour) fentanyl (4 μg/kg per hour)) and neuromuscular blocking (atracurium 0.5 mg/kg) were included in the study. A continuous monitoring of BIS, arterial pressure, and heart rate were realized before, during, and after the fiberoptic exam. An adjunctive continuous placebo or Remifentanil infusion was started just before the fiberoptic exam with a target effect-site concentration of 4 ng/ml using a Base Primea pump.
Mean arterial pressure and heart rates were comparable between the placebo and Remifentanil groups at all times of the procedure. We did not observe differences in the variation of BIS values between the two groups during procedure. We described no change in BIS values relative to the placebo group in this population.
In deeply sedated and paralyzed patients, receiving analgesic support based on a scale score an additional administration of short-acting analgesic drug, such as Remifentanil, seems not to be necessary for acute pain control.
Pain; Intensive care; Bispectral index; Remifentanil
Sedation and analgesia are provided by using different agents and techniques in different countries. The goal is to achieve early spontaneous breathing and to obtain an awake and cooperative pain-free patient. It was the aim of this study to conduct a survey of the agents and techniques used for analgesia and sedation in intensive care units in Germany.
A survey was sent by mail to 261 hospitals in Germany. The anesthesiologists running the intensive care unit were asked to fill in the structured questionnaire about their use of sedation and analgesia.
A total of 220 (84%) questionnaires were completed and returned. The RAMSAY sedation scale was used in 8% of the hospitals. A written policy was available in 21% of hospitals. For short-term sedation in most hospitals, propofol was used in combination with sufentanil or fentanyl. For long-term sedation, midazolam/fentanyl was preferred. Clonidine was a common part of up to two-thirds of the regimens. Epidural analgesia was used in up to 68%. Neuromuscular blocking agents were no longer used.
In contrast to the US 'Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult', our survey showed that in Germany different agents, and frequently neuroaxial techniques, were used.
Endoscopic retrograde cholangiopancreatography ERCP is a painful and long procedure requiring transient deep analgesia and conscious sedation. An ideal anaesthetic that guarantees a rapid and smooth induction, good quality of maintenance, lack of adverse effects and rapid recovery is still lacking.
This study aimed to compare safety and efficacy of a continuous infusion of low dose remifentanil plus ketamine combined with propofol in comparison to the standard regimen dose of remifentanil plus propofol continuous infusion during ERCP.
322 ASAI-III patients, 18–85 years old and scheduled for planned ERCP were randomized. Exclusion criteria were a predictable difficult airway, drug allergy, and ASA IV–V patients.
We evaluated Propofol 1 mg/kg/h plus Remifentanil 0.25 μg/kg/min (GR) vs. Propofol 1 mg/kg/h plus Ketamine 5 μg/kg/min and Remifentanil 0.1 μg/kg/min (GK).
Main outcome measures were respiratory depression, nausea/vomiting, quality of intraoperative conditions, and discharge time. P≤0.05 was statistically significant (95% CI).
Respiratory depression was observed in 25 patients in the GR group compared to 9 patients in the GK group (p=0.0035). ERCP was interrupted in 9 cases of GR vs. no cases in GK; patients ventilated without any complication. Mean discharge time was 20±5 min in GK and 35±6 min in GR (p=0.0078) and transfer to the ward delayed because of nausea and vomiting in 30 patients in GR vs. 5 patients in GK (p=0.0024). Quality of intraoperative conditions was rated highly satisfactory in 92% of GK vs. 67% of GR (p=0.028).
The drug combination used in GK confers clinical advantages because it avoids deep sedation, maintains adequate analgesia with conscious sedation, and achieves lower incidence of postprocedural nausea and vomiting with shorter discharge times.
conscious sedation for ERCP; ketamine; sedation outside the operating room
For logistical reasons sedation studies are often carried out in elective surgical patients and the results extrapolated to the general intensive care unit (ICU) population. We question the validity of this approach. We compared the two sedation regimens used in our general ICU in a trial structured to mimic clinical practice as closely as possible.
Forty patients were randomised to intermittent diazepam or continuous midazolam and sedation monitored with hourly sedation scores; 31 patients completed the study. Scores indicating undersedation were more common with diazepam (P <0.01); overall adequate sedation midazolam 64.7%, diazepam 35.7% (P =0.21). No patient exhibited inappropriately prolonged sedation. Cost was: midazolam AUS$1.98/h; diazepam AUS$0.06/h.
Both regimens produced rapid onset of acceptable sedation but undersedation appeared more common with the cheaper diazepam regimen. At least 140 patients should be studied to provide evidence applicable to the general ICU population. Used alone, a sedation score may be an inappropriate outcome measure for a sedation trial.
critical care; midazolam; diazepam; sedatives; nonbarbiturate; therapeutic use; comparative study
There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.
It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl.
A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared.
260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups.
This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case.
Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
Balanced propofol sedation; Alfentanil; Fentanyl; Deep sedation; Diagnostic endoscopy; Cost benefit
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
We studied intra-individual and inter-individual variability of two online sedation monitors, BIS® and Entropy®, in volunteers under sedation.
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.
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.
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.
clinicaltrials.gov Nr. NCT00641563.
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
The purpose of this study was to evaluate sedation practice in UK intensive care units (ICUs), particularly the implementation of daily sedation holding, written sedation guidelines, sedation scoring tools and choice of agents.
A national postal survey was conducted in all UK ICUs.
A total of 192 responses out of 302 addressed units were received (63.5%). Of the responding ICUs, 88% used a sedation scoring tool, most frequently the Ramsey Sedation Scale score (66.4%). The majority of units have a written sedation guideline (80%), and 78% state that daily sedation holding is practiced. A wide variety of sedating agents is used, with the choice of agent largely determined by the duration of action rather than cost. The most frequently used agents were propofol and alfentanil for short-term sedation; propofol, midazolam and morphine for longer sedation; and propofol for weaning purposes.
Most UK ICUs use a sedation guideline and sedation scoring tool. The concept of sedation holding has been implemented in the majority of units, and most ICUs have a written sedation guideline.
Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments.
The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.
Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.
Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.
The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared.
This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day.
Trial registration number
Dutch Trial Register NTR2551, http://www.trialregister.nl
Analgesia; Labour; Remifentanil; Patient controlled analgesia; Epidural
ERCP practically requires moderate to deep sedation controlled by a combination of benzodiazepine and opiod. Propofol as a sole agent may cause oversedation. A combination (cocktail) of infused propofol, meperidine, and midazolam can reduce the dosage of propofol and we hypothesized that it might decrease the risk of oversedation. We prospectively compare the efficacy, recovery time, patient satisfactory, and side effects between cocktail and conventional sedations in patients undergoing ERCP.
ERCP patients were randomized into 2 groups; the cocktail group (n = 103) and the controls (n = 102). For induction, a combination of 25 mg of meperidine and 2.5 mg of midazolam were administered in both groups. In the cocktail group, a bolus dose of propofol 1 mg/kg was administered and continuously infused. In the controls, 25 mg of meperidine or 2.5 mg/kg of midazolam were titrated to maintain the level of sedation.
In the cocktail group, the average administration rate of propofol was 6.2 mg/kg/hr. In the control group; average weight base dosage of meperidine and midazolam were 1.03 mg/kg and 0.12 mg/kg, respectively. Recovery times and patients’ satisfaction scores in the cocktail and control groups were 9.67 minutes and 12.89 minutes (P = 0.045), 93.1and 87.6 (P <0.001), respectively. Desaturation rates in the cocktail and conventional groups were 58.3% and 31.4% (P <0.001), respectively. All desaturations were corrected with temporary oxygen supplementation without the need for scope removal.
Cocktail sedation containing propofol provides faster recovery time and better patients’ satisfaction for patients undergoing ERCP. However, mild degree of desaturation may still develop.
Cocktail sedation containing propofol; Meperidine; Midazolam; ERCP
The aim of the study was to assess the effect of three different types of anaesthesia on perioperative bleeding control and to analyse the mean arterial blood pressure and heart rate in patients undergoing endoscopic paranasal sinus surgery. Ninety patients (30 women and 60 men, aged 18–85 years) scheduled to undergo functional endoscopic sinus surgery in the years 2008–2010 were identified as candidates for inclusion in the study. Patients were randomly assigned to one of three groups (30 patients each) according to the type of general anaesthesia to be administered. Groups I and II both received inhalation anaesthesia (sevoflurane for sedation) and intravenous anaesthesia (fentanyl in group I, remifentanil in group II). Anaesthesia was delivered solely via intravenous route (TIVA) in group III, with propofol used for sedation and remifentanil for analgesia. Blood pressure and heart rate were monitored during surgery and post-surgically for 4 h. Mean anaesthesia duration in groups I, II and III was 108.7 ± 20.8, 112.6 ± 22.2 and 103.7 ± 17.5 min and the surgery duration was 71.3 ± 16.7, 78.8 ± 24.2 and 66.5 ± 15.5 min, respectively. Mean blood loss during surgery was 365.0 ± 176.2, 340.0 ± 150.5 and 225.0 ± 91.7 ml, with a mean blood loss rate of 5.1 ± 2.4, 4.5 ± 2.2 and 3.4 ± 1.1 ml/min in groups I, II and III, respectively. Technologically advanced control of the drug dose with the TIVA technique allows for better control of perioperative bleeding.
Type of anaesthesia; Perioperative bleeding; Functional endoscopic sinus surgery (FESS)
Analgesia and sedation are usually required for the comfort of the patient and surgeon during tympanoplasty surgery done under local anesthesia. In this study, satisfaction scores and effectiveness of sedation and analgesia with dexmedetomidine were compared with a combination of midazolam-fentanyl.
Materials and Methods:
Ninety patients undergoing tympanoplasty under local anesthesia randomly received either IV dexmedetomidine 1 μg kg-1 over 10 min followed by 0.2 μg kg-1h-1 infusion (Group D) or IV midazolam 0.06 mg kg-1 plus IV fentanyl 1 μg kg-1 over 10 min (Group MF) followed by normal saline infusion at 0.2 ml kg-1h-1. Sedation was titrated to Ramsay sedation score (RSS) of three. Vital parameters, rescue analgesics (fentanyl 1 μg kg-1) and sedatives (midazolam 0.01 mg kg-1), patient and surgeon satisfaction scores were recorded.
Patient and surgeon satisfaction score was better in Group D than Group MF (median interquartile range (IQR) 9 (8-10) vs. 8 (6.5-9.5) and 9 (8.5-9.5) vs. 8 (6.75-9.25), P = 0.0001 for both). Intraoperative heart rate and mean arterial pressure in Group D were lower than the baseline values and the corresponding values in Group MF (P < 0.05). Percentage of patients requiring rescue fentanyl was higher in Group MF than Group D (40% vs. 11.1%, P = 0.01). One patient in Group D while four in Group MF (8.8%) required rescue sedation with midazolam (P > 0.17). Seven patients in Group D had dry mouth vs. none in Group MF (P = 0.006). One patient in Group D had bradycardia with hypotension which was effectively treated.
Dexmedetomidine is comparable to midazolam-fentanyl for sedation and analgesia in tympanoplasty with better surgeon and patient satisfaction. Hemodynamics need to be closely monitored.
Dexmedetomidine; sedation; midazolam fentanyl sedation; monitored anesthesia care; satisfaction scores; surgery; otological
The economic implications of sedative choice in the management of patients receiving mechanical ventilation are unclear because of differences in costs and clinical outcomes associated with specific sedatives. Therefore, we aimed to determine the cost-effectiveness of the most commonly used sedatives prescribed for mechanically ventilated critically ill patients.
Design, Setting, and Patients
Adopting the perspective of a hospital, we developed a probabilistic decision model to determine if continuous propofol or intermittent lorazepam was associated with greater value when combined with daily awakenings. We also evaluated the comparative value of continuous midazolam in secondary analyses. We assumed that patients were managed in a medical intensive care unit and expected to require ventilation for at least 48 hours. Model inputs were derived from primary analysis of randomized controlled trial data, medical literature, Medicare reimbursement rates, pharmacy databases, and institutional data.
We measured cost-effectiveness as costs per mechanical ventilator-free day within the first 28 days after intubation. Our base-case probabilistic analysis demonstrated that propofol dominated lorazepam in 91% of simulations and, on average, was both $6,378 less costly per patient and associated with over three additional mechanical ventilator-free days. The model did not reveal clinically meaningful differences between propofol and midazolam on costs or measures of effectiveness.
Propofol has superior value compared to lorazepam when used for sedation among the critically ill who require mechanical ventilation when used in the setting of daily sedative interruption.
cost-effectiveness; cost-benefit analysis (MeSH); critical illness (MeSH); respiration; artificial (MeSH)