Effects of different doses of alfentanil on cardiovascular response to rapid sequence intubation in elderly patients: a parallel-controlled randomized trial.

BACKGROUND: Rapid sequence intubation (RSI) have been shown to be effective in preventing reflux aspiration in patients with a full stomach during anaesthesia induction and endotracheal intubation. However, there is currently no standardized operation protocol or anaesthesia induction drug standard for RSI. Furthermore, there is a lack of evidence regarding the use of RSI in patients older than 65. In this study, we aimed to investigate the cardiovascular effects of different doses of alfentanil combined with propofol and etomidate during RSI in elderly patients aged 65-80 years. METHODS: A total of 96 patients aged 65-80 years who underwent general anaesthesia with tracheal intubation were selected for this study. The patients were randomly assigned to one of four groups using a random number table. Group A patients received an induction dose of 10 µg/kg alfentanil, group B patients received 15 µg/kg alfentanil, group C patients received 20 µg/kg alfentanil, and group D patients received 25 µg/kg alfentanil. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and ejection fraction (EF) were measured at three time points: 5 min before anaesthesia induction (T0), 1 min after endotracheal intubation (T1), and 5 min after endotracheal intubation (T2). Concurrently, 4 ml of arterial blood was collected from patients at three time points, and the concentrations of norepinephrine (NE) and cortisol (Cor) in plasma were detected. Occurrences of hypertension, hypotension, bradycardia and tachycardia during anesthesia induction to 5 min after tracheal intubation were noted. RESULTS: Compared with T0, the HR, MAP, NE and Cor concentrations in group A and group B were increased at the T1 and T2 time points, CI and EF values were decreased (P < 0.05). HR and MAP in groups C and D were increased at the T1 time point, while they were decreased at the T2 time point in group D (P < 0.05). The changes in CI and EF values, concentrations of NE and Cor, were not significant at T1 and T2 time points in group C (P > 0.05). Additionally, they were not significant in group D at the T1 time point (P > 0.05), but decreased at the T2 time point (P < 0.05). Compared with group A, the HR, MAP, NE and Cor concentrations in groups C and D were decreased at T1 and T2 time points (P < 0.05). The CI and EF values of groups C and D were increased at T1 time point but decreased at T2 time point in group D (P < 0.05). The incidence of hypertension and tachycardia in group A was significantly higher than that in group C and group D (P < 0.05), and the incidence of hypotension and bradycardia in group D was significantly higher than that in group A and group B (P < 0.05). CONCLUSION: Alfentanil 20 µg/kg for RSI in elderly patients, can effectively inhibit the violent cardiovascular reaction caused by intubation, and avoid the inhibition of cardiovascular system caused by large dose, hemodynamics more stable. TRIAL REGISTRATION: ChiCTR2200062034 ( www.chictr.org.cn ).

Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil.

PURPOSE: Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep sedation is ambiguous. Deep sedation offers patient comfort as well as greater safety concerns. Unintended deep sedation can occur if drug interactions are overlooked. We present a pharmacodynamic model for moderate sedation using midazolam, alfentanil and propofol. The model is suitable for training and devising rationales for appropriate dosing. METHODS: The study consists of two parts: modeling and validation. In modeling, patients scheduled for esophagogastroduodenoscopy (EGD) or colonoscopy sedation are enrolled. The modified observer's assessment of alertness/sedation (MOAA/S) score < 4 is defined as loss of response to represent moderate sedation. Two patient groups receiving bronchoscopy or endoscopic retrograde cholangiopancreatography (ERCP) are used for validation. Model performance is assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC). Simulations are performed to demonstrate how the model is used to rationally determine drug regimen for moderate sedation. RESULTS: Interaction between propofol and alfentanil is stronger than the other pairwise combinations. Additional synergy is observed with three drugs. ROC AUC is 0.83 for the modeling group, and 0.96 and 0.93 for ERCP and bronchoscopy groups respectively. Model simulation suggests that 1 mg midazolam, 250 µg alfentanil and propofol maximally benefits from drug interactions and suitable for moderate sedation. CONCLUSION: We demonstrate the accurate prediction of a three-drug response surface model for moderate sedation and simulation suggests a rational dosing strategy for moderate sedation with midazolam, alfentanil and propofol.

Evaluation of two different radiotherapy anaesthetic protocols for dogs: a randomized clinical crossover trial.

OBJECTIVES: To describe alfentanil-propofol admixture for induction of anaesthesia for canine radiotherapy and compare it to alfentanil-atropine followed by propofol induction in terms of heart rate (HR), mean arterial pressure (MAP), recovery duration and quality. STUDY DESIGN: Prospective, masked, randomized clinical crossover trial. ANIMALS: A group of 40 client-owned dogs anaesthetized from October 2017 to June 2018. METHODS: Dogs were randomly assigned to be administered one of two protocols. For both protocols, IV preanaesthetic medication was given 30 seconds before rapid IV administration of a set volume of induction agent, with further induction agent administered as needed to permit intubation. For protocol ADMIX, the preanaesthetic medication was 0.04 mL kg-1 0.9% sodium chloride and the induction agent was 0.2 mL kg-1 propofol-alfentanil admixture. For protocol ATRO, the preanaesthetic medication was 10 µg kg-1 alfentanil with 12 µg kg-1 atropine (0.04 mL kg-1 total volume) and the induction agent was 0.2 mL kg-1 propofol. Anaesthesia was maintained with sevoflurane. Cardiorespiratory variables, agitation, hypotension, or inadequate depth of anaesthesia requiring supplemental boluses of propofol or increased vaporizer settings were recorded. Time to extubation, sternal recumbency and walking was noted. Videos were recorded for recovery quality scoring. Owner questionnaires gave feedback about recoveries at home. The other protocol was administered for the next radiotherapy session. RESULTS: The only significantly different variable between protocols was mean HR during anaesthesia, which was lower in ADMIX (p < 0.001). Hypotension was recorded in seven (17.5%) dogs in ATRO and three (7.5%) in ADMIX, with an association (p < 0.005) between ATRO and hypotension. Owners reported animals recovered 'normal' behaviour and appetite by the next morning. CONCLUSIONS AND CLINICAL RELEVANCE: Both protocols were acceptable for dogs undergoing radiotherapy, with minimal differences in anaesthetic quality, recovery duration and quality. Although MAP did not differ overall, the incidence of hypotension was higher in ATRO.

Synergistic antinociceptive effects of alfentanil and propofol in the formalin test.

The present study was conducted to determine the combined analgesic effect of alfentanil and propofol in the formalin test. Diluted formalin was injected into the dorsal surface of the right hind paw in rats. Nociceptive behavior was determined by counting the number of flinches of the injected paw for 1 h after injection; a reduction in formalin­induced flinching was interpreted as an antinociceptive effect. Isobolographic analysis was used to determine the type of antinociceptive interaction (additivity, antagonism or synergism). Extracellular signal­regulated kinase (ERK) and c­fos protein levels were also detected by western blot analysis to determine the potential mechanisms of the synergistic effect. Alfentanil, propofol or an alfentanil­propofol combination had an antinociceptive effect in the formalin test. The median effective dose (ED50), value of the individual drug was also obtained. The derived theoretical ED50 for the antinociceptive effect (4.36 mg/kg) was different from the observed experimental ED50 value (2.51 mg/kg). The interaction between alfentanil and propofol that produced the antinociceptive effect was synergistic according to isobolographic analysis. Furthermore, the combination of alfentanil and propofol treatments may produce synergistically antinociceptive effects by inhibiting the phosphorylation of ERK1/2 and decreasing the expression of c­fos in the spinal cord. These results demonstrated that combined treatment, with alfentanil and propofol, produced synergistic antinociceptive effects in the formalin test and may have therapeutic potential for the treatment of acute pain.

Synergistic analgesic effect of propofol-alfentanil combination through detecting the inhibition of cAMP signal pathway.

OBJECTIVE: The study aims to investigate the possible mechanism of the synergistic analgesic effect of propofol-alfentanil combination. METHODS: The synergistic analgesic effects of propofol-alfentanil combination in Sprague-Dawley (SD) rats were analysed through the von Frey test. Then, we examined the activity of phospholipase C (PLC) and the intracellular levels of Ca(2+) and adenosine 3', 5'cyclic monophosphate (cAMP) in primary neuronal cells of fetal SD rats. We detected the intracellular Ca(2+) concentration by fluorescence and flow cytometry. The PLC activity of the primary neuronal cells was assayed using the EnzChek(®) Direct Phospholipase C Assay Kit. The cAMP content of the cells was assayed using the cAMP Direct Immunoassay Kit (Fluorometric). KEY FINDINGS: Both propofol and alfentanil treatments depressed cAMP levels and PLC activity, but propofol-alfentanil combination decreased these parameters to a greater extent than alfentanil treatment alone. Propofol and alfentanil both inhibited Ca(2+) channel, but propofol-alfentanil combination suppressed this channel to a greater extent than alfentanil treatment alone. Fluorescent image analysis revealed that both propofol and alfentanil reduced the intracellular levels of Ca(2+) , and propofol-alfentanil combination showed weaker signals than alfentanil alone. Propofol-alfentanil combination significantly reduced intracellular Ca(2+) level, cAMP level and PLC activity. CONCLUSION: Propofol and alfentanil exert synergistic analgesic effects through the adenylyl cyclase pathway.

Previously published midazolam-alfentanil response surface model cannot predict patient response well in gastrointestinal endoscopy sedation.

BACKGROUND: A response surface model is a mathematical model used to predict multiple-drug pharmacodynamic interactions. With the use of a previously published volunteer model, we tested the accuracy of the midazolam-alfentanil response surface model during gastrointestinal endoscopy. METHODS: We enrolled 35 adult patients scheduled for combined endoscopic procedures. Patients were sedated with intravenous midazolam and alfentanil, and monitored with real-time auditory evoked potential. Sedation Observer's Assessment of Alertness/Sedation (OAA/S) scores were recorded by an independent observer every 2 minutes. Patients with OAA/S scores of ≥ 4 were designated as "awake". Pharmacokinetic profiles were calculated using the TIVA trainer. The published response surface model was modified to make estimations more reasonable. Patient response (OAA/S score ≥ 4 or <4) was then estimated using the modified version of the model. RESULTS: The average procedural times were 3.3 ± 2 minutes and 6.5 ± 2.3 minutes for esophagogastroduodenoscopy and colonoscopy, respectively. The model poorly predicted patient response during gastrointestinal endoscopic procedure sedation. Accuracy in predicting an OAA/S score of <4 was 6% for the original model and 0% for the modified model. The estimated probability of loss of response ranged from 0.04% to 2.94% at the time of arousal (OAA/S score ≥ 4) and from 0.24% to 15.55% when the patient was asleep (OAA/S score < 4). CONCLUSION: The model showed significant synergy between midazolam and alfentanil; however, it was inadequate in predicting the response of patients undergoing sedated gastrointestinal endoscopic procedures. Future model parameter adjustments are required.

µ-Opioid agonists for preventing emergence agitation under sevoflurane anesthesia in children: a meta-analysis of randomized controlled trials.

BACKGROUND: Emergence agitation (EA) is an adverse effect after sevoflurane anesthesia in pediatric patients. The effectiveness of prophylactic µ-opioid agonists fentanyl, remifentanil, sufentanil, and alfentanil in preventing EA is debatable. METHODS: A literature search was conducted to identify clinical trials that observed the effect of µ-opioid agonists fentanyl, remifentanil, sufentanil, and alfentanil on preventing EA in pediatric patients under sevoflurane anesthesia. The statistical software RevMan 5.3 was used for meta-analysis. Data from each study were combined using the relative ratio (RR), weighted mean differences, and their associated 95% confidence intervals. I(2) was used to evaluate heterogeneity. Subgroup analysis was conducted to investigate the possible influences of patient age, adenotonsillectomy, premedication, N2 O, propofol, and regional block/local anesthetics on preventing EA with prophylactic administration of µ-opioid agonists. Publication bias was checked using funnel plots and Begg's test. RESULTS: This meta-analysis showed the inclusion of 19 randomized controlled trials with 1528 patients (857 patients received µ-opioid agonists therapy and 671 patients had placebo). The pooled data indicated that prophylactic µ-opioid agonists fentanyl, remifentanil, sufentanil, and alfentanil significantly decreased the incidence of EA [RR = 0.49 (0.38, 0.64), I(2) = 42%, P = 0.04; RR = 0.57 (0.33, 0.99), I(2) = 37%, P = 0.19; RR = 0.18 (0.08, 0.39), I(2) = 0%, P = 0.98; and RR = 0.56 (0.40, 0.78), I(2) = 6%, P = 0.34, respectively]. All subgroup analyses strengthened the proof for lower incidence of EA under sevoflurane anesthesia after fentanyl administration. A possibility of publication bias was detected in the fentanyl group. CONCLUSIONS: This meta-analysis suggested that prophylactic µ-opioid agonists fentanyl, remifentanil, sufentanil, and alfentanil could significantly decrease the incidence of EA under sevoflurane anesthesia in children compared to placebo. Considering the limitations of the included studies, more clinical studies are required.

Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimal and noninvasive probes for hepatic and first-pass CYP3A induction.

Systemic and oral clearances of alfentanil (ALF) are in vivo probes for hepatic and first-pass cytochrome P450 (CYP) 3A. Both ALF single-point plasma concentrations and miosis are surrogates for area under the concentration-time curve (AUC) and clearance and are minimal and noninvasive CYP3A probes. This investigation determined ALF sensitivity for detecting graded CYP3A induction and compared it with that of midazolam (MDZ). Twelve volunteers (sequential crossover) received 0, 5, 10, 25, or 75 mg oral rifampin for 5 days. MDZ and ALF were given intravenously and orally on sequential days. Dark-adapted pupil diameter was measured with blood sampling. Graded rifampin decreased plasma MDZ AUCs to 83, 76, 62, and 59% (intravenous (i.v.)) and 78, 66, 39, and 24% (oral) of control. Hepatic and first-pass CYP3A induction were detected comparably by plasma MDZ and ALF AUCs. Single ALF concentrations detected all CYP3A induction, whereas MDZ was less sensitive. ALF miosis detected induction of first-pass but not hepatic CYP3A.

Conscious sedation reduces patient discomfort and improves satisfaction in flexible bronchoscopy.

BACKGROUND: Conscious sedation for patients undergoing flexible bronchoscopy (FB) is suggested to alleviate discomfort and improve satisfaction despite controversy regarding its benefits. In Taiwan, the general FB practice involves local anesthesia only. This study aimed to assess the benefits and risks of conscious sedation in diagnostic FB. METHODS: This prospective case control study enrolled 44 non-sedated and 44 sedated patients who underwent diagnostic FB. All received the standard upper airway preparation, while sedated patients received clinically judged increments of midazolam and alfentanil for conscious sedation. Patient discomforts and the operator's opinions during FB were assessed using the verbal analogue score (VAS, 0-10 scale). Willingness to return was assessed as five scales to monitor patient satisfaction. Safety profiles throughout the procedures were also assessed. RESULTS: Compared to non-sedated patients, sedated ones expressed less discomfort, with lower VAS scores regarding scope insertion (3.5 [0-10] vs. 0 [0-5], p < 0.001), cough (5 [0-10] vs. 0 [0-5], p < 0.001), dyspnea (3 [0-10] vs. 0 [0-8], p < 0.001), pain (3 [0-10] vs. 0 [0-5], p < 0.001), and global tolerance of the procedures (5 [1-10] vs. 0 [0-9], p < 0.001). More sedated patients expressed willingness to return (70.5% vs. 36.4%, p = 0.001). The bronchoscopist also rated lower VAS scores on cough and dyspnea in sedated patients. Sedated patients had less hypertension but more hypoxemic episodes during the procedure, which were all transient and not life-threatening. CONCLUSIONS: Conscious sedation with clinically judged midazolam and alfentanil reduces discomforts, improves satisfaction, and carries slight, but manageable, hypoxemia risks in patients undergoing FB.

The optimal bolus dose of alfentanil for tracheal intubation during sevoflurane induction without neuromuscular blockade in day-case anaesthesia.

BACKGROUND: The purpose of this study was to determine the optimal bolus dose of alfentanil required to provide successful intubating conditions following inhalation induction of anaesthesia using 5% sevoflurane and 60% nitrous oxide without neuromuscular blockade in adult day-case anaesthesia. METHODS: Twenty-four adults, aged 18-60 years, undergoing general anaesthesia for short ambulatory surgery were enroled into the study. After vital capacity induction, with sevoflurane 5% and 60% nitrous oxide in oxygen, pre-determined dose of alfentanil was injected over 30 s. The dose of alfentanil was determined by modified Dixon's up-and-down method (2 microg/kg as a step size). Ninety seconds after the end of bolus administration of alfentanil, the trachea was intubated. Systolic blood pressure, heart rate and SpO2 were recorded at anaesthetic induction, before, 1 min and 3 min after intubation. RESULTS: The bolus dose of alfentanil for successful tracheal intubation was 10.7+/-2.1 microg/kg in 50% of patients during inhalation induction. From probit analysis, 50% effective dose (ED(50)) and ED(95) values (95% confidence limits) of alfentanil were 10.7 microg/kg (8.0-12.9 microg/kg) and 14.9 microg/kg (12.9-31.1 microg/kg), respectively. CONCLUSIONS: Using the modified Dixon's up-and-down method, the bolus dose of alfentanil for successful tracheal intubation was 10.7+/-2.1 microg/kg in 50% of adult patients during inhalation induction using 5% sevoflurane and 60% nitrous oxide in oxygen without neuromuscular blocking agent in day-case anaesthesia.

[New opioids for general anaesthesia and in- and out-hospital analgesia]. / Zastosowanie nowych opioidów podczas znieczulenia ogólnego oraz analgezji wewnatrz- i pozaszpitalnej.

Over the last 30 years, three new opioids of the piperidine family have been introduced to anaesthesia clinical practice: sufentanil, alfentanil and remifentanil. Alfentanil is a derivative of fentanyl, with quicker onset than that of fentanyl and with shorter duration and more intense vagomimetic properties than those of fentanyl and sufentanil. It may cause less intense respiratory depression than equianalgesic doses of fentanyl. Clinical trials indicate that alfentanil can be used effectively as an analgesic, as an analgesic supplement to anaesthesia, and as the major component of a general anaesthetic. Its short duration of effect makes it attractive as an analgesic supplement for short ambulatory surgical procedures. Sufentanil is a more potent and more lipophilic analgesic than fentanyl. It would appear to maintain haemodynamic stability during surgery better than other opioids. Epidural sufentanil produces a rapid onset and good quality of analgesia. In addition, low doses administered intravenously via a PCA pump seem to have a potential role for analgesia during labour. Remifentanil is an opioid analgesic that is rapidly metabolized by non-specific blood and tissue esterases. According to its unique pharmacokinetic profile, remifentanil-based anaesthesia combines high-dosage opioid analgesia intraoperatively with a rapid and predictable postoperative awakening, even after long procedures. Its vagomimetic properties are especially pronounced in small children, the elderly and hypovolaemic patients, and in these groups atropine should be always given before remifentanil administration. Remifentanil also minimises the adrenergic response to endotracheal intubation. Three mju agonist-antagonists have been used for pain treatment: nalbuphine, butorphanol and buprenorphine. They can be used in ambulatory settings. Nalbuphine can be used parenterally. It reverses morphine-induced respiratory depression while maintaining adequate analgesic effect. Buprenorphine can be given sublingually, percutanenously, epidurally and parenterally. It is a potent analgesic, recommended for strong postoperative pain. Butorphanol is a potent analgesic that increases heart rate, arterial and pulmonary blood pressures and cardiac output. It should be given carefully in patients with coronary disease.

Auditory-evoked potentials in bispectral index-guided anaesthesia for cardiac surgery.

BACKGROUND AND OBJECTIVE: Midlatency auditory-evoked potentials, as measures of the anaesthetic state, were evaluated at similar levels of bispectral index in cardiac surgical patients maintained with either propofol or isoflurane anaesthesia. METHODS: Twenty-four patients were randomly allocated to anaesthesia with propofol (n = 12) or isoflurane (n = 12). Bispectral index was maintained below 60 during surgery. Auditory-evoked potentials were collected before induction of anaesthesia, 10 min after intubation, 30 min after sternotomy, during cardiopulmonary bypass at the time of cross-clamping of the aorta and during stable mild hypothermia, after de-clamping of the aorta, and after the operation. RESULTS: At the pre-determined time points, bispectral index values showed comparable depth of hypnosis in both groups. The latency of the Nb component of midlatency auditory-evoked potentials was significantly increased in the isoflurane group after intubation (P < 0.001) and that of both the Nb and the Pa components after sternotomy (P < 0.001) compared with the propofol group. No differences between the groups were detected with respect to haemodynamic variables. No patient reported recall of intraoperative events. CONCLUSION: After intubation and surgical stimulation, when bispectral index was at a constant level, there was a difference in the Nb and Pa components of the midlatency auditory-evoked potentials between the two anaesthetic regimens, indicating a distinction in the state of anaesthesia. Our results suggest that the parallel use of these two electrophysiological methods can show differences in the components of anaesthesia between various anaesthesia methods in cardiac surgical patients.

Negative inotropic effects of tumour necrosis factor-alpha and interleukin-1beta are ameliorated by alfentanil in rat ventricular myocytes.

BACKGROUND AND PURPOSE: Serum levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) increase during an inflammatory response and have been reported to induce a negative inotropic effect on the myocardium. Alfentanil, an opioid analgesic often used in the critical care of patients with sepsis, has been shown to enhance ventricular contractility. This study characterised the effects of TNF-alpha and IL-1beta on contraction and the Ca(2+) transient and investigated whether depressed ventricular function was ameliorated by alfentanil. EXPERIMENTAL APPROACH: Isolated rat ventricular myocytes were loaded with fura-2 and electrically stimulated at 1 Hz. Contraction and Ca(2+) transients were measured after 60, 120 and 180 min incubations in TNF-alpha (0.05 ng ml(-1)) and IL-1beta (2 ng ml(-1)). The effects of 10 microM alfentanil on contractility and Ca(2+) transients of TNF-alpha and IL-1beta treated cells were determined. KEY RESULTS: After 180 min of TNF-alpha and IL-1beta treatment, the amplitude of contraction, the Ca(2+) transient and sarcoplasmic reticulum (SR) Ca(2+) content were significantly reduced. Alfentanil significantly increased contraction of TNF-alpha and IL-1beta treated cells via a small increase in the Ca(2+) transient and a larger increase in myofilament Ca(2+) sensitivity, effects that were not blocked by 10 microM naloxone, a broad spectrum opioid receptor antagonist. CONCLUSIONS AND IMPLICATIONS: TNF-alpha and IL-1beta induce a significant negative inotropic effect on ventricular myocytes in a time dependent manner through disruption of SR Ca(2+) handling and the Ca(2+) transient. This negative inotropic effect was ameliorated by alfentanil, but this response may not be mediated via opioid receptors.

Performance of AEP Monitor/2-derived composite index as an indicator for depth of sedation with midazolam and alfentanil during gastrointestinal endoscopy.

BACKGROUND AND OBJECTIVE: The A-Line auditory evoked potential index (AAI) (AEP Monitor/2, Danmeter A/S, Odense, Denmark) is a newly developed composite parameter representing the degree of hypnosis. We conducted a prospective, observational study to explore the performance and validity of the AAI during conventional sedation for gastrointestinal (GI) endoscopy. METHODS: Thirty adults of either sex, age <65, scheduled for combined oesophagogastroduodenoscopy (OGD) and colonoscopy under sedation with intravenous (i.v.) midazolam and alfentanil were enrolled. The sedative end-point was set at the Observer's Assessment of Alertness/Sedation (OAA/S) score less than 4. An AEP Monitor/2 was used in all patients. AAI, sedation scores, heart rate (HR), blood pressure (BP) and SPO2 were recorded every 2 min up to the end of the procedure. Receiver operator characteristic analysis was used to test validity and to select optimal sedation. RESULTS: There was a significantly positive correlation between AAI and OAA/S scores (rho = 0.886; P < 0.001). The AAI also showed significant differences between subsequent levels of sedation scores (P < 0.001). AAI greater than 54 indicated fully awake or minimal sedation and values between 54 and 42 were suggestive of moderate sedation. Values between 42 and 34 were associated with moderate to deep sedation and readings below 34 were associated with deep sedation. The relative risk of SPO2 < 95% for OAA/S = 2 compared with 3 was 15.98 (95% confidence interval (CI): 3.94-64.81). CONCLUSIONS: AAI is an effective tool for monitoring sedation during GI endoscopy induced by i.v. midazolam and alfentanil.

Reflex pupillary dilatation in response to skin incision and alfentanil in children anaesthetized with sevoflurane: a more sensitive measure of noxious stimulation than the commonly used variables.

BACKGROUND: Estimation of analgesia in anaesthetized children is often imprecise, and consequently, anaesthesiologists commonly evaluate children's response to surgical stimulation by movement or haemodynamic changes. In adults reflex pupillary dilatation has been demonstrated to be a very sensitive measure of noxious stimulation, correlated with opioid concentrations. The autonomic nervous control changes with age, raising the hypothesis that mechanisms involved in pupillary autonomic functions regarding both sympathetic and parasympathetic components may also differ between adults and children. In this pilot study, we tested the hypothesis that the pupillary reflex dilatation might allow assessment of noxious stimulation and analgesic effect of alfentanil in children under sevoflurane anaesthesia, as an alternative to haemodynamic and bispectral measures. METHODS: After sevoflurane induction, 24 children were maintained in steady-state conditions at 1.5 MAC of sevoflurane in O(2)-N(2)O (50-50). An intense noxious stimulation was provided by standardized skin incision on the lower limb. A bolus of alfentanil (10 microg kg(-1)) was administered either 1 min (n=16) or 2 min (n=8) after skin incision. Haemodynamic values, bispectral index (BIS) and pupillary diameter (PD) were recorded just before stimulation and at 30-60 s intervals during 4 subsequent minutes. RESULTS: In all children PD increased significantly after noxious stimulation [+200 (40)%, at 60 s]. In contrast, mean heart rate and blood pressure increased only 11 (7)% and 10 (8)% respectively, 60 s after stimulation. BIS did not change significantly. In all children, alfentanil injection induced a rapid decrease of PD and restored pre-incision values in 2 min. CONCLUSION: PD is a more sensitive measure of noxious stimulation than the commonly used variables of heart rate, arterial blood pressure and BIS in children anaesthetized with sevoflurane.

Electroencephalogram monitoring during anesthesia with propofol and alfentanil: the impact of second order spectral analysis.

Bispectral analysis of the electroencephalogram (EEG) has been used for monitoring anesthesia. The estimation of bicoherence allows us to determine whether a given time series represents a linear random process in cases where the bicoherence is trivial, i.e., a mere constant independent of frequency. In this study, we investigated the proportion of EEG epochs with nontrivial bicoherence during surgical anesthesia with propofol and alfentanil as an indicator for the degree of nonlinearity in the EEG. We reanalyzed 90 h of EEG recorded from 20 patients undergoing abdominal surgery using the Hinich procedure, which provides a statistical test for the following hypothesis: the EEG is a linear random process. In approximately 90% of all artifact-free, stationary EEG epochs, the bicoherence was found to be zero or a mere constant. Under these conditions, the EEG can be considered as a linear random process. Our findings suggest that the spectral information in the frequency domain delivered by the EEG monitoring during anesthesia is largely contained in the power spectrum of the signal. This calls into question the benefit of EEG bispectral analysis for monitoring anesthesia effect.

Effect of alfentanil on intracranial pressure during propofol-fentanyl anesthesia for craniotomy. A randomized prospective dose-response study.

BACKGROUND: The effect of alfentanil on intracranial pressure (ICP) in patients with supratentorial cerebral tumors has only been sparsely examined and with somewhat contradictory results. METHODS: Thirty-one patients were anesthetized with propofol and fentanyl. After removal of the bone flap a bolus-dose of alfentanil 10 (group 1), 20 (group 2), or 30 microg kg(-1) (group 3) was administered followed by an infusion of 10, 20, or 30 microg.kg(-1).h(-1) to patients in groups 1, 2, and 3, respectively. A control group received no alfentanil. Subdural ICP, mean arterial blood pressure (MAP), and cerebral perfusion pressure (CPP) were monitored and arterial and jugular bulb blood were sampled before and every minute for 5 min after the bolus administration of alfentanil and again after 5 min of hyperventilation to be able to calculate cerebral arterio-venous oxygen content difference (AVDO2) and carbon dioxide reactivity (CO2-reactivity). RESULTS: No changes in subdural ICP or AVDO2 from alfentanil in the study period were observed within the groups. However, alfentanil decreased MAP and CPP. The maximum CPP decrease (mean value of each group) was 4 mmHg, 8 mmHg, and 18 mmHg in groups 1, 2, and 3, respectively. There was no difference between groups as regards the CO2-reactivity. CONCLUSION: We conclude that administration of alfentanil to propofol-fentanyl anesthetized patients with supratentorial cerebral tumors decreases MAP and CPP in a dose-related way, but does not influence subdural ICP, AVDO2 or the CO2-reactivity.

The effects of remifentanil and alfentanil-based total intravenous anesthesia (TIVA) on the endocrine response to abdominal hysterectomy.

STUDY OBJECTIVE: To compare the effects of remifentanil with alfentanil as a part of total intravenous anesthesia (TIVA) on plasma concentrations of cortisol, insulin, and glucose, and hemodynamic responses in patients undergoing abdominal hysterectomy. DESIGN: Randomized, double-blind study. SETTING: University hospital. PATIENTS: 24 ASA physical status I female patients scheduled for abdominal hysterectomy. INTERVENTIONS: Premedicated patients were randomly allocated to receive either remifentanil-propofol (Group R) or alfentanil-propofol (Group A). The loading dose of the study drug was administered over 60 seconds (remifentanil l microg kg(-l) or alfentanil 10 microg kg(-l)) followed by a continuous infusion (remifentanil 0.2 microg kg(-l) min(-l) or alfentanil 0.5 microg kg(-l) min(-l)). In both groups, propofol was administered until loss of consciousness and maintained with a propofol infusion rate of 100 microg kg(-l) min(-l). After induction of anesthesia, all patients were manually ventilated by mask with O2-air mixture for 20 minutes. Then rocuronium 0.6 mg kg(-l) was given for tracheal intubation. MEASUREMENTS: Mean arterial pressure (MAP) and heart rate (HR) were recorded. Plasma concentrations of cortisol, insulin, and glucose were measured during anesthesia and in the recovery room. MAIN RESULTS: In Group R, MAP and HR were lower after tracheal intubation and skin incision than in Group A (p < 0.05). Plasma cortisol concentrations decreased from baseline values at 20 minutes after induction, after tracheal intubation, and skin incision in Group R (p < 0.001). Plasma concentrations of cortisol and glucose increased from baseline values at 30 minutes after skin incision and continued to increase in both groups (p = 0.001). Plasma concentrations of cortisol, insulin, and glucose did not differ between groups at all sampling times. CONCLUSION: Remifentanil provided better hemodynamic stability than alfentanil during anesthesia and surgery. However, both remifentanil and alfentanil had similar effects on the stress endocrine response to abdominal hysterectomy.

No effect of cardiopulmonary bypass on hypnosis in patients anaesthetized with propofol and alfentanil.

BACKGROUND: The effect of cardiopulmonary bypass (CPB) on the level of anaesthetic depth has not been studied previously in a randomized way. METHODS: We assessed the effect of CPB on the propofol needed to maintain a fixed bispectral index score, and on the recovery from anaesthesia in 22 patients undergoing coronary artery bypass graft surgery with CPB (on-pump) compared with 18 patients operated on without CPB (off-pump). Anaesthesia was induced and maintained with propofol and alfentanil. Throughout the procedure, the infusion rate of propofol was adjusted to keep the BIS value at 40 +/- 5. RESULTS: With the off-pump technique, the duration of surgery and anaesthetic administration were significantly greater. The need for propofol in proportion to time was exactly the same in both groups. During anaesthesia and the first 3 h thereafter, the BIS recordings were similar in both groups. No differences were detected in the time to awakening or tracheal extubation. CONCLUSIONS: CPB does not affect propofol requirements or immediate postoperative recovery compared with the off-pump technique.