Remifentanil versus fentanyl for short-term analgesia-based sedation in mechanically ventilated postoperative children

BACKGROUND: Analgesia-based sedation techniques are becoming more established in the intensive care unit (ICU) setting. The aim of this study was to compare remifentanil and fentanyl infusions for postoperative analgesia in pediatric ICU patients. METHODS: After receiving ethical committee approval, a prospective randomized, double-blind study was performed. Twenty-two postoperative orthopedic surgery patients received either remifentanil 0.1 microg.kg(-1).min(-1) or fentanyl 0.025 microg.kg(-1).min(-1) infusions diluted to the same volume. Analgesic infusion was titrated to predefined levels of analgesia [behavioral pain scale (BPS) score of 3]. Propofol was added if sedation was unsatisfactory after BPS score 3 had been achieved. RESULTS: There were no differences in groups regarding demographics, tracheal extubation times, and pain scores of the patients. After cessation of the opioid infusion, the sedation scores and the heart rates were always higher in the remifentanil group compared with the fentanyl group. The incidences of nausea, vomiting, apnea, desaturation, reintubation within 24 h and constipation were also similar between the two groups. CONCLUSIONS: We conclude that a remifentanil infusion provides clinically comparable analgesia with a fentanyl infusion in mechanically ventilated postoperative pediatric patients. These two drugs are suitable for short-term analgesia-based sedation in pediatric postoperative ICU patients.     

Current Practices in Sedation and Analgesia for Mechanically Ventilated Critically Ill Patients: A Prospective Multicenter Patient-based Study

Background: The authors conducted a patient-based survey of practices to fully describe the assessment and the management of pain and sedation of a large cohort of mechanically ventilated patients during their first week of intensive care unit (ICU) stay.

Methods: A total of 1,381 adult patients were included in a prospective, observational study in 44 ICUs in France. Pain and sedation assessment, analgesic and sedative use, and analgesic management during procedural pain were collected on days 2, 4, and 6 of the ICU stay.

Results: The observed rates of assessment on day 2 for sedation (43%) and analgesia (42%) were significantly smaller than that of use of sedatives (72%) and opioids (90%), also noted on days 4 and 6. The use of protocols/guidelines for sedation/analgesia in the ICU reduced the proportion of patients who were treated, although not evaluated. A large proportion of assessed patients were in a deep state of sedation (40-50%). Minor changes in the dosages of the main prescribed agents for sedation (midazolam, propofol) and analgesia (sufentanil, fentanyl, morphine, remifentanil) were found across 6 days of the patient's ICU stay. Procedural pain was specifically managed for less than 25% of patients; during those procedures, the proportion of patients with pain significantly increased from the baseline pain evaluation.     

Current practices in sedation and analgesia for mechanically ventilated critically ill patients: a prospective multicenter patient-based study

BACKGROUND: The authors conducted a patient-based survey of practices to fully describe the assessment and the management of pain and sedation of a large cohort of mechanically ventilated patients during their first week of intensive care unit (ICU) stay. METHODS: A total of 1,381 adult patients were included in a prospective, observational study in 44 ICUs in France. Pain and sedation assessment, analgesic and sedative use, and analgesic management during procedural pain were collected on days 2, 4, and 6 of the ICU stay. RESULTS: The observed rates of assessment on day 2 for sedation (43%) and analgesia (42%) were significantly smaller than that of use of sedatives (72%) and opioids (90%), also noted on days 4 and 6. The use of protocols/guidelines for sedation/analgesia in the ICU reduced the proportion of patients who were treated, although not evaluated. A large proportion of assessed patients were in a deep state of sedation (40-50%). Minor changes in the dosages of the main prescribed agents for sedation (midazolam, propofol) and analgesia (sufentanil, fentanyl, morphine, remifentanil) were found across 6 days of the patient's ICU stay. Procedural pain was specifically managed for less than 25% of patients; during those procedures, the proportion of patients with pain significantly increased from the baseline pain evaluation. CONCLUSIONS: Excessively deep states of sedation and a lack of analgesia during painful procedures must be prevented. To facilitate systematic pain and sedation assessment and to adjust daily drug dosages accordingly, it seems crucial to promote educational programs and elaboration of protocols/guidelines in the ICU.     

Combined spinal-epidural labor analgesia

Combined spinal-epidural (CSE) labor analgesia is a new neuraxial labor analgesic technique. An intrathecal injection of an opioid alone, or in combination with a local anesthetic, initiates analgesia. An epidural catheter can then be used to maintain pain relief for the duration of labor. The CSE technique combines the advantages of spinal analgesia (low drug doses, rapid onset, immediate sacral block) and epidural analgesia (titratable, able to maintain analgesia indefinitely, ability to convert to epidural anesthesia). Side effects are acceptable with attention to patient selection and technique. The initiation of CSE analgesia with either fentanyl (25 μg) or sufentanil (5.0–7.5 μg) is appropriate for early labor, or in patients for whom an acute decrease in preload is not desirable. Although an equipotent dose of sufentanil has a longer duration of analgesia than fentanyl, both drugs provide excellent analgesia and prolonged duration is of minimal clinical significance when the intrathecal dose is followed by maintenance epidural analgesia. The addition of a local anesthetic to the opioid is required to provide satisfactory analgesia once fetal descent begins. The addition of local anesthetic (usually bupivacaine 1.25–2.5 mg) allows the dose of opioid to be decreased. Markedly lower opioid doses (fentanyl 5 μg or sufentanil 1.0–2.5 μg) can then provide effective analgesia with fewer systemic side effects. Several additives have been shown to prolong the duration of analgesia of opioids and opioids plus bupivacaine, but the short increase in duration of analgesia may not be worth the increased difficulty of combining multiple drugs.     

Remifentanil patient-controlled analgesia following cardiac surgery

Background:  Remifentanil is increasingly used as a component of cardiac anaesthesia. Following cardiac surgery remifentanil is often substituted for alternative opioids on the intensive care unit. We were interested to evaluate postoperative continuation of remifentanil in the form of remifentanil patient control analgesia (RPCA) for those patients who received intraoperative remifentanil. The objectives of this study were to assess the safety, efficacy and feasibility of the RPCA.
Methods:  Ten patients who received an intravenous infusion of remifentanil perioperatively for coronary artery bypass graft surgery (CABG) had their remifentanil infusion converted to RPCA following extubation on the intensive care unit. Remifentanil patient control analgesia delivered an initial background infusion consistent with the infusion rate at extubation and with a bolus facility of 50 µg administered over 5 min followed by a 5-min lockout. Data collection included sedation and pain scores, respiratory rate, arterial blood gases, number of successful/unsuccessful attempts and the background infusion rate for each subject over a period of 12 h following extubation.
Results:  The data from nine male and one female patient were analyzed by using SPSS11 for Windows. During the study period the patients achieved adequate pain control and made more RPCA attempts at lower background infusion rates. No episodes of apnoea, SpO₂ less than 95% or a rise in PaCO₂ greater than 6.5 kPa were observed.
Conclusion:  Remifentanil patient control analgesia with a background infusion was effective and safe for postoperative pain relief in this group of spontaneously breathing ICU patients following cardiac surgery.     

Pain management

Analgesia and hypnosis are two separate entities and should result in distinct assessment and management for patients admitted to an intensive care unit (ICU). Those patients are exposed to moderate-severe pain and they are likely to remember pain as one bothersome experience. Any cause of patient discomfort is sought with the priority given to pain and adequate analgesia. Assessing pain must rely upon the use of clinical scoring systems, although these instruments are still underused in ICU. Satisfactory levels of analgesia by continuous infusion of opioids during times without stimulation do not guarantee against pain reactions during procedures (endotracheal suctioning, mobilization, wound care and dressing change, removal of chest tube). The concept of multimodal analgesia should be extended to the ICU since it may reduce the opioids requirements. In order to facilitate systematic pain and sedation assessment and to adjust daily drug dosages accordingly, it appears crucial to promote educational programs and elaboration of protocols/guidelines in ICU. Protocols/guidelines may help caregivers to rationally use sedatives and opioids and possibly reduce mechanical ventilation and ICU length of stay.     

Remifentanil in the ICU: a new approach to patient care

In recent years, it has become increasingly common practice to sedate patients continuously during their stay in intensive care units (ICUs). The aim has been to keep them calm and comfortable, avoid anxiety and agitation and facilitate processes such as ventilatory support, tracheostomy and extubation. In large part this trend has been due to the availability of the new sedative/hypnotic agents propofol and midazolam, which can provide effective long-term sedation.The focus on sedation (which might more properly be termed hypnosis, since its aim is to make the patient sleepy) has been at the expense of a more precise attention to analgesia. Today we usually titrate the sedative to effect, and consider pain relief as adjunctive therapy. The consequence of this approach is that often our patients are over-sedated. This not only brings the danger of increased morbidity and mortality, it also increases costs, through the need for a greater number of expensive tests such as CAT scans of the brain, prolonged mechanical ventilation and longer stays in both the ICU and hospital. Furthermore, many patients in the ICU continue to feel pain and complain of insufficient analgesia.In future, we should concentrate on pain relief first and add sedation and anxiolysis as and when necessary. Analgesia will in itself relieve much anxiety and many patients will not require sedatives at all.The adoption of a ‘pain relief first’ policy has in the past, however, been hampered by the lack of suitable opioids, due to their unpredictability and their slow onset and offset times. The introduction of a new opioid, remifentanil, should overcome these difficulties. Remifentanil is a new and novel opioid. Unlike many other opioids, which are non-specific, it is selective for the μ receptors that mediate pain. It has uniquely predictable effects, including a rapid onset time (around 1min) and a rapid offset (recovery) time (<10min). This mode of action allows the depth of analgesia to be quickly titratable to the patient's needs. It also means a reduced use in sedative/hypnotic drugs such as propofol and midazolam.The consequences should be an improvement in patient care (not least in better communications between patients, relatives and carers), a reduction in costs and a more efficient use of resources. Improvements in morbidity and mortality might also be expected. Further detailed studies need to be carried out to confirm that routine analgesia with remifentanil improves patient comfort, reduces mortality and mortality and cuts costs.     

A comparison of fentanyl, sufentanil, and remifentanil for fast-track cardiac anesthesia

Cardiac surgery is estimated to cost $27 billion annually in the United States. In an attempt to decrease the costs of cardiac surgery, fast-track programs have become popular. The purpose of this study was to compare the effects of three different opioid techniques for cardiac surgery on postoperative pain, time to extubation, time to intensive care unit discharge, time to hospital discharge, and cost. Ninety adult patients undergoing cardiac surgery were randomized to a fentanyl-based, sufentanil-based, or remifentanil-based anesthetic. Postoperative pain was measured at 30 min after extubation and at 6:30 AM on the first postoperative day. Pain scores at both times were similar in all three groups (P > 0.05). Median ventilator times of 167, 285, and 234 min (P > 0.05), intensive care unit stays of 18.8, 19.8, and 21.5 h (P > 0.05), and hospital stays of 5, 5, and 5 days (P > 0.05) for the Fentanyl, Sufentanil, and Remifentanil groups did not differ. Three patients needed to be tracheally reintubated: two in the Sufentanil group and one in the Fentanyl group. Median anesthetic costs were largest in the Remifentanil group ($140.54 [$113.54-$179.29]) and smallest in the Fentanyl group ($43.33 [$39.36-$56.48]) (P < or = 0.01), but hospital costs were similar in the three groups: $7841 (Fentanyl), $5943 (Sufentanil), and $6286 (Remifentanil) (P > 0.05). We conclude that the more expensive but shorter-acting opioids, sufentanil and remifentanil, produced equally rapid extubation, similar stays, and similar costs to fentanyl, indicating that any of these opioids can be recommended for fast-track cardiac surgery. IMPLICATIONS: To conserve resources for cardiac surgery, fentanyl-, sufentanil-, and remifentanil-based anesthetics were compared for duration of mechanical ventilation, intensive care unit length of stay, hospital length of stay, and cost. The shorter-acting anesthetics, sufentanil and remifentanil, produced equally rapid extubation, similar stays, and similar costs to fentanyl; thus, any of these opioids can be recommended for fast-track cardiac surgery.     

Postoperative analgesia after remifentanil

Providing analgesia is the most important, yet the most difficult aspect of remifentanil anaesthesia, as its effect wears off quickly after infusion is terminated. Longer-acting opioids such as morphine and fentanyl must be given well before patients wake up. Bolus administration of fentanyl approximately 20 minutes before the end of surgery may provide adequate analgesia at emergence and tracheal extubation. However, fentanyl concentration decreases quite rapidly and patients may need repeated dosing until analgesia is attained. Continuous intraoperative low-dose infusion of fentanyl may lead to better analgesia than bolus dosing, because its context-sensitive half-time increases as the infusion lasts longer. Regional anaesthetic technique, such as epidural analgesia and peripheral nerve block can also be used in patients without coagulation abnormalities. Issue of acute tolerance after intraoperative use of remifentanil still awaits further study before final conclusion is reached. Some data suggest that we should not use an unnecessary and high dose of opioid without clear indication. Theoretically, remifentanil infusion can be used in ICU and surgical wards to manage postoperative pain in ventilated as well as spontaneously breathing patients. However, in some susceptible patients, even a very low-rate infusion can still cause significant respiratory depression more than 30 minutes after starting infusion. Pulse oximetry is not sensitive enough to detect early ventilatory depression when patients breathe oxygen-enriched air. Without continuous observation by trained anaesthetists, infusion of remifentanil should not be used casually particularly in non-ventilated patients.     

Sedation in the critically ill patient

Critically ill patients who require intensive care need effective analgesia and sedation to control potentially unpleasant symptoms, such as pain and anxiety. Analgesics and sedatives are also used to allow patients to tolerate nursing procedures and tracheal intubation as well as to aid mechanical ventilation. Metabolism of traditional opioids is dependent on organ function, which is abnormal among critically ill patients. The use of a score system to ensure sufficient but not excessive sedation should be mandatory. Sufentanil and remifentanil are more predictable opioids that are suitable for either sedation or analgesia in critically ill patients to achieve an adequate Ramsay score from 2 to 4.     

The effect of fentanyl and remifentanil, with or without ketoprofen, on pain after thyroid surgery: a randomized-controlled trial

BACKGROUND AND OBJECTIVES: This study was designed to quantify the additional postoperative analgesic efficacy of a single dose of ketoprofen in patients undergoing thyroid surgery using two different intraoperative analgesic regimens. METHODS: One hundred and twenty patients were randomly assigned to one of four groups: intraoperative fentanyl or remifentanil with or without ketoprofen (n = 30 for each group). Intravenous ketoprofen (1.5 mg kg-1) or saline was administered 45 min before the end of surgery. Pain scores, opioid demand and length of stay in the postanaesthesia care unit were assessed in a blinded manner. RESULTS: Patients receiving intraoperative fentanyl with saline had significantly lower visual analogue scale pain scores in the postanaesthesia care unit compared with those receiving intraoperative remifentanil with saline (55 +/- 10 mm vs. 80 +/- 18 mm, P < 0.05) and they stayed shorter in the postanaesthesia care unit (86 +/- 24 min vs. 126 +/- 37 min). In conjunction with intraoperative fentanyl, ketoprofen significantly decreased postoperative pain scores (40 +/- 10 mm, P < 0.05 compared with fentanyl alone) and opioid demand (4 of 30 patients vs. 14 of 30 patients compared with fentanyl alone, P < 0.05). Patients receiving intraoperative remifentanil had no additional analgesic benefit with ketoprofen. CONCLUSION: After thyroid surgery, patients receiving intraoperative fentanyl had lower pain scores and needed less rescue analgesia compared with patients receiving intraoperative remifentanil. The adjunction of ketoprofen further improved analgesia in patients who received intraoperative fentanyl only.     

Remifentanil vs fentanyl/morphine for pain and stress control during pediatric cardiac surgery

BACKGROUND: Remifentanil is a short acting, potent synthetic opioid that does not accumulate after infusion or repeated bolus doses. It may be rapidly titrated to the requirements of individual patients. Titrated infusion of remifentanil may be able to provide potent analgesia required for pediatric cardiac surgery and obtund the stress response in theater whilst not having the persistent respiratory depression and sedation seen with longer acting opioids. METHODS: Twenty patients were randomized to receive a titrated infusion of remifentanil (0-1 microg x kg(-1) x min(-1)) or a standard dose of fentanyl (30 microg x kg(-1)) prebypass plus morphine (1 mg x kg(-1)) on rewarming. Blood samples for glucose and cortisol were taken at regular intervals from induction through bypass and into the first 24 h of postoperative intensive care. In addition to biochemical indicators of the stress response we recorded baseline hemodynamic parameters and any acute physiological events. RESULTS: Ten patients received morphine, seven received remifentanil. There were no statistically significant differences between the two treatment groups in cortisol measurements, mean arterial pressure or heart rate recordings. In the last time period the remifentanil group had a larger rise in blood glucose concentration (baseline 3.9, rise 3 mmol x l(-1)) than the fentanyl/morphine group (baseline 4.2 rise 1.9 mmol x l(-1)), CI -4.3 to -0.2. CONCLUSIONS: The only significant difference was in glucose in the postbypass time periods. Although statistically significant, this difference is insufficient evidence of increased stress in the remifentanil group. The results show that in the patients studied there was no clinically important difference between the two techniques.     

Immediate postoperative pain management in patients undergoing major abdominal surgery after remifentanil-based anesthesia: sufentanil vs tramadol

AIM: The transition from intraoperative analgesia to postoperative analgesia must be planned carefully after remifentanil-based anesthesia, due to the short duration of action of remifentanil. The aim of this study is to compare the efficacy and safety of 2 transition strategies using sufentanil or tramadol for early postoperative pain relief in patients who had major abdominal surgery under general anesthesia with remifentanil/sevoflurane. METHODS: Sixty patients participated in this double-blind, prospective study and were randomly assigned to either sufentanil (S) group or tramadol (T) group. Twenty minutes before the end of surgery the patients received either a bolus of 0.15 microg kg(-1) sufentanil (group S) or tramadol 100 mg (group T). Mean arterial pressure (MAP), heart rate (HR) and rate pressure product (RPP=systolic arterial pressure (SAP)xHR), analgesia by a verbal rating score (VRS) and sedation by a sedation score (SS) were evaluated at emergence from anesthesia. RESULTS: A statistically significant difference in HR between the 2 groups was recorded at extubation (78+/-13 in group S vs 86+/-24 in group T). A significant decrease of RPP values at extubation and 5 minutes later were found in group S in comparison with group T. VRS values were significantly lower in sufentanil group at 5 and 10 minutes after awakening. CONCLUSIONS: Sufentanil provided more effective transition analgesia in comparison with tramadol. The effects of remifentanil dissipated rapidly and analgesia with major opioids was required. A bolus dose of sufentanil 0.15 microg kg(-1) was efficacious in controlling the hemodynamic parameters at awakening from anesthesia. The lower HR values and, consequently the lower RPP values are of utmost importance especially in the aged cardiovascular risk patient.     

Recovery after remifentanil and sufentanil for analgesia and sedation of mechanically ventilated patients after trauma or major surgery

We investigated the analgesic effect and the neurological recoverytime after administration of remifentanil in mechanically ventilatedpatients in an intensive care unit. Twenty patients, after traumaor major surgery with no intracranial pathology, were randomizedto receive either remifentanil/propofol (n=10) or sufentanil/propofol(n=10). A sedation score and a simplified pain score were usedto assess adequate sedation and analgesia. Medication was temporarilystopped after 24 h. Immediately before and 10 and 30 min after,the degree of sedation and pain score were evaluated. Adequateanalgesia and sedation was achieved with remifentanil 10.6 µgkg^–1 h^–1 and propofol 2.1 mg kg^–1 h^–1,or sufentanil 0.5 µg kg^–1 h^–1 and propofol1.3 mg kg^–1 h^–1. The difference in propofol dosebetween groups was significant. Ten minutes after terminatingthe medication, the degree of sedation decreased significantlyafter remifentanil and all patients could follow simple commands.During the following 20 min, all patients with remifentanilemerged from sedation and complained of considerable pain. Bycontrast, in the sufentanil group, only six (7) responded tocommands after 10 (30) min and their pain score remained essentiallyunchanged during the 30-min observation period. We concludethat, in contrast to sufentanil, remifentanil facilitates rapidemergence from analgesia and sedation, allowing a clinical neurologicalexamination within 10–30 min in mechanically ventilatedpatients with no intracranial pathology. Br J Anaesth 2001; 86: 763–8     

Methohexital zur Analgosedierung bei beatmeten Intensivpatienten

Background

Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) as a potentially reversible disturbance of consciousness and a change of cognition caused by a medical condition, drug intoxication, or medication side effect. Delirium affects up to 80?% of intensive care unit (ICU) patients and is associated with increased morbidity and mortality. One risk factor for development of delirium in ventilated intensive care unit patients is sedation. The German S3 guidelines on “Analgesie, Sedierung und Delirmanagement in der Intensivmedizin” (analgesia, sedation and delirium management in intensive care medicine) of the DGAI (German Society for Anesthesiology and Intensive Care Medicine) and the DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine) recommend midazolam and propofol for sedation, although both drugs are associated with a high incidence of delirium.

Aim

Within the framework of this study the question arose whether the barbiturate methohexital could be associated with a lower incidence of delirium in comparison to midazolam or propofol in analgosedated and ventilated ICU patients.

Material and methods

This was a prospective nonrandomized observational cohort study in a mixed medical surgical intensive care unit. Patients ventilated within 72 h after admittance were consecutively allocated to either propofol/remifentanil versus methohexital/remifentanil (expected ventilation duration ≤?7 days) or midazolam/fentanyl versus methohexital/fentanyl (expected ventilation duration >?7 days) by the attending senior consultant anesthetist at the time of admission and/or intubation. Primary endpoint was delirium at any time during the ICU stay. Delirium was checked every 8 h by ICU nurses using the intensive care delirium screening checklist (ICDSC), with delirium defined as ICDSC ≥?4 points. Before evaluation of the ICDSC the Richmond agitation sedation scale (RASS) score and the visual analogue scale for pain (VAS target ≤?4) were measured. To assure reliable evaluation of the ICDSC, the RASS score of the patient at the time of evaluation had to be ≥???2. Assuming an incidence of delirium in the midazolam group of 70?% and in the methohexital group of 35?%, 16 patients were needed each in the midazolam/fentanyl and the methohexital/fentanyl cohorts (p?=?0.05, β =?0.1). Assuming an incidence of delirium in the propofol group of 50?% and in the methohexital group again of 35?%, 94 patients were needed in the propofol/remifentanil and methohexital/remifentanil groups, respectively (p?=?0.05, β =?0.1).

Results

A total of 222 patients were evaluated, 34 in the methohexital vs. midazolam group and 188 in the methohexital vs. propofol group. Out of 16 patients sedated with midazolam, 15 developed delirium (94?%) in contrast to only 5 out of 18 patients sedated with methohexital (28?%). Thus compared to midazolam the sedation with methohexital reduced the incidence of delirium by 66?% (p?<?0.001) corresponding to a number needed to treat (NNT) of 1.5. Out of 94 patients in the propofol/remifentanil group, 64 developed delirium (68?%) in contrast to only 23 out of 94 in the methohexital/remifentanil group (24?%). Thus compared to propofol the sedation with methohexital reduced the incidence of delirium by 44?% (p?<?0.001), corresponding to an NNT of 2.5.

Conclusion

Sedation with methohexital compared to midazolam or propofol reduced the incidence of delirium by more than 50?% in ventilated ICU patients.     

Effect of remifentanil on intracranial pressure and cerebral blood flow velocity in patients with head trauma

BACKGROUND: Remifentanil, an ultra-short-acting opioid, is used as an on-top analgesic in head trauma patients during transient painful procedures, e.g. endotracheal suctioning, physiotherapy, on the intensive care unit. However, previous studies have shown that opioids may increase intracranial pressure and decrease cerebral blood flow. METHODS: The present study investigates the effect of remifentanil on mean arterial blood pressure, intracranial pressure measured with intraparenchymal or epidural probes, and on cerebral blood flow velocity assessed by transcranial Doppler flowmetry in 20 head trauma patients sedated with propofol and sufentanil. Ventilation was adjusted for a target PaCO2 of 4.7-5.1 kPa. After baseline measurements a bolus of remifentanil (0.5 microg x kg(-1) i.v.) was administrated followed by a continuous infusion of remifentanil (0.25 microg x kg(-1) x min(-1) i.v.) for 20 min. RESULTS: There was no change in mean arterial blood pressure, intracranial pressure, and cerebral blood flow velocity in response to remifentanil infusion over time. Statistical analysis was performed using the Wilcoxon Signed Rank test. CONCLUSIONS: These data suggest that remifentanil can be used for on-top analgesia in head trauma patients without adverse effects on cerebrovascular haemodynamics, cerebral perfusion pressure or intracranial pressure.     

Remifentanil

Remifentanil is a potent mu-opioid receptor agonist and has some unique pharmacokinetic characteristics compared to other anilidopiperidine opioids (e.g. fentanyl, alfentanil, and sufentanil). As remifentanil is metabolised rapidly by nonspecific esterases that are widespread throughout the plasma and tissuses, its duration of action is very short. It is cleared very rapidly, and its clearance is not affected by renal and hepatic function. The context-sensitive half-time of remifentanil remains consistently short, even after administration for a long time. Consequently, emergence is quick even after anesthesia of long duration. As other piperidine opioids, remifentnil has some adverse effects such as respiratory depression, muscle rigidity, bradycardia, and nausea as well as vomiting. Because of the rapid dissipation of analgesic effect following remifentanil discontinuation, postoperative analgesia should be provided before or soon after anesthesia using longer-acting opioid analgesics, non-opioid analgesics, or local as well as regional anesthesia.     

Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia

The bispectral index (BIS) and a sedation score were used todetermine and compare the effect of propofol in the presenceof fentanyl, alfentanil, remifentanil and sufentanil. Seventy-fivenon-premedicated patients were assigned randomly into five groups(15 in each) to receive fentanyl, alfentanil, remifentanil,sufentanil or placebo. Opioids were administered using a target-controlledinfusion device, to obtain the following predicted effect-siteconcentrations: fentanyl, 1.5 ng ml^–1; alfentanil, 100ng ml^–1; remifentanil, 6 ng ml^–1; and sufentanil,0.2 ng ml^–1. After this, a target-controlled infusionof propofol (Diprifusor) was started to increase concentrationgradually, to achieve predicted effect-site concentrations of1, 2, and 4 µg ml^–1. At baseline and at each successivetarget effect-site concentration of propofol, the BIS, sedationscore and haemodynamic variables were recorded. At the momentof loss of consciousness (LOC), the BIS and the effect-siteconcentration of propofol were noted. The relationship betweenpropofol effect-site concentration and BIS was preserved withor without opioids. In the presence of an opioid, LOC occurredat a lower effect-site concentration of propofol and at a higherBIS₅₀ (i.e. the BIS value associated with 50% probability ofLOC), compared with placebo. Although clinically the hypnoticeffect of propofol is enhanced by analgesic concentrations ofµ-agonist opioids, the BIS does not show this increasedhypnotic effect. Br J Anaesth 2001; 86: 523–7     

Supplemental remifentanil during coronary artery bypass grafting is followed by a transient postoperative cardiac depression

BACKGROUND: The pharmacokinetic properties of the short-acting micro opioid receptor-agonist remifentanil makes it possible to give cardiac surgical patients a deep intraoperative anesthesia without experiencing postoperative respiratory depression and a prolonged stay in the intensive care unit (ICU). However, previous investigations have shown that patients who received remifentanil required additional analgesia during the early postoperative period as compared to patients who received fentanyl. The aim of the present study therefore was to investigate the effects of supplementing remifentanil to a standard fentanyl-based anesthesia in coronary artery bypass grafting (CABG). METHODS: The study was prospective, randomized, double-blind, and placebo-controlled. Twenty male patients aged 55-70 years were included. All patients received a standard fentanyl and isoflurane-based anesthesia. In addition, the patients were randomized to receive either remifentanil 0.5 micro g kg(-1) min(-1) or placebo during surgery. Hemodynamic recordings and measurements of blood glucose and plasma adrenaline and noradrenaline were performed intra- and postoperatively. RESULTS: Remifentanil reduced the hemodynamic and metabolic response to surgical stress compared to the standard fentanyl-based anesthetic regimen. However, the patients in the remifentanil group had a lower cardiac output (CO), left ventricular stroke work index (LVSWI), and mixed venous oxygen saturation (SvO(2)), and a higher central venous pressure (CVP) than the patients in the placebo group during the early postoperative phase, indicating a postoperative cardiac depression in the remifentanil group. CONCLUSION: In CABG, remifentanil reduces the hemodynamic and metabolic responses during surgery but seems to give a cardiac depression in the early postoperative phase.