Combination Of Alfentanil Research Articles

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 1h after injection; a reduction in formalin‑induced flinching was interpreted as an antinociceptive effect. Isobolographic analysis was used to determine the type of antinociceptive interaction (additivity, antagonism or synergism). Extracellular signal‑regulated kinase (ERK) and c‑fos protein levels were also detected by western blot analysis to determine the potential mechanisms of the synergistic effect. Alfentanil, propofol or an alfentanil‑propofol 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 (4.36mg/kg) was different from the observed experimental ED50 value (2.51mg/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 c‑fos 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.

The study aims to investigate the possible mechanism of the synergistic analgesic effect of propofol-alfentanil combination. 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). 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. Propofol and alfentanil exert synergistic analgesic effects through the adenylyl cyclase pathway.

A Response Surface Model Exploration of Dosing Strategies in Gastrointestinal Endoscopies Using Midazolam and Opioids.

Classical midazolam–opioid combination for gastrointestinal endoscopy sedation has been adopted for decades. Dosing regimens have been studied but most require fixed dosing intervals. We intend to use a sophisticated pharmacodynamic tool, response surface model (RSM), to simulate sedation using different regimens. RSM can predict patient's response during different phases of the examination and predict patient's wake-up time with precision and without the need for fixed dosing intervals. We believe it will aid physicians in guiding their dosing strategy and timing.The study is divided into 2 parts. The first part is the full Greco RSMs development for 3 distinct phases: esophagogastroduodenoscopy (EGD), colonoscopy, and intersession (the time lapse between procedures). Observer's Assessment of Alertness Score (OAA/S) is used to assess patient response. The second part simulates 6 regimens with different characteristics using the RSMs: midazolam only, balanced midazolam and opioids, high-dose opioids and midazolam, low-dose midazolam with high-dose opioids, high-dose midazolam and low-dose opioids, and finally midazolam with continuous opioid infusion. Loss of response at 95% probability for adequate anesthesia during examination and return of consciousness at 50% probability during intersession was selected for simulation purposes.The average age of the patient population is 49.3 years. Mean BMI is 21.9 ± 2.3 kg/m2. About 56.7% were females and none received prior abdominal surgery. The cecal intubation rate was 100%. Only 1 patient (3%) developed temporary hypoxemia, which was promptly managed with simple measures. The RSMs for each phase showed significant synergy between midazolam and alfentanil. The balanced midazolam and alfentanil combination provided adequate anesthesia and most rapid return of consciousness. The awakening time from the final drug bolus was 7.4 minutes during EGD and colonoscopy stimulation, and 9.1 minutes during EGD simulation.Simulation of regimens with different characteristics gives insights on dosing strategies. A balanced midazolam–alfentanil regimen is adequate in providing good anesthetic depth and most rapid return of consciousness. We believe with the aid of our RSM, clinicians can perform sedation with more flexibility and precision.

Synergistic antinociception of propofol–alfentanil combination in mice

Drug combination is frequently used in pain treatment, which can produce similar analgesia with reduced dosage and side effects. In the present study, we examined the effects of co-administration of propofol, a general anesthetic, and alfentanil, an opioid analgesic drug, and the types of interactions between them in heat induced acute phasic and acetic-acid induced acute tonic pain models using the up-and-down method. In both pain models, alfentanil was administered in fixed-dose fractions of the 50% effective dose (ED50), and the types of interactions were determined by isobolographic analysis. In hot plate test, alfentanil (35.6–50.0μg/kg, i.v.), propofol (6.5–15.5mg/kg, i.v.), and their combinations (80%, 50%, 30% and 10% of a single drug ED50) produce a significant, dose-dependent antinociception. In the tail-flick test, alfentanil (35.6–50.0μg/kg, i.v.), propofol (5.0–14.3mg/kg, i.v.), and their combination significantly and dose dependently extend the tail-flick latency. In the acetic-acid induced writhing test, alfentanil (12.5–23.2μg/kg, i.p.), propofol (15.0–28.5mg/kg, i.p.), and their combination significantly and dose dependently reduce the frequency of writhing. In all the above pain models, isobolographic analysis revealed a significant synergistic interaction between alfentanil and propofol, with about 4-fold reduction of doses of both drugs, in comparison with each single drug's ED50. These data suggest that the combination of alfentanil and propofol synergistically suppresses acute phasic and tonic pain in mice, indicating a potential application in pain treatment.

A double-blinded randomized evaluation of alfentanil and morphine vs fentanyl: analgesia and sleep trial (DREAMFAST)

Patients using fentanyl patient-controlled analgesia (PCA), the standard first-line choice in our hospitals, commonly complain of postoperative sleep disruption due to pain. The aim of this study was to determine whether the PCA combination of alfentanil and morphine, which provides longer analgesia without compromising onset speed, would improve postoperative pain-related sleep interference. Two hundred and twelve adults undergoing major surgery where PCA was the planned principal postoperative analgesic modality were randomized to either the combination of alfentanil and morphine (Group AM) or fentanyl (Group F). The primary outcome was pain-related awakenings during the second postoperative night as measured by the study questionnaire, based on the St Mary's Hospital Sleep Questionnaire. Analgesic efficacy, other sleep measures, and opioid-related side-effects were also assessed. There was no difference in pain-related sleep disturbance between the groups, with 41% of Group AM and 53% of Group F waking due to pain (P=0.10). Group AM had better rest and dynamic analgesia in the first 24 h with fewer requiring rescue ketamine infusion during the 2 day study period (2 vs 14%, P=0.001). Those in Group AM experienced less nausea and vomiting in the second 24 h (18 vs 35%, P=0.028) but more pruritus (40 vs 23%, P=0.013). Despite better early postoperative analgesia, pain-related sleep interference was not improved by the PCA combination of alfentanil and morphine. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: Ref: ACTRN12608000118303.

Carbon dioxide accumulation during analgosedated colonoscopy: Comparison of propofol and midazolam

To characterize the profiles of alveolar hypoventilation during colonoscopies performed under sedoanalgesia with a combination of alfentanil and either midazolam or propofol. Consecutive patients undergoing routine colonoscopy were randomly assigned to sedation with either propofol or midazolam in an open-labeled design using a titration scheme. All patients received 4 μg/kg per body weight alfentanil for analgesia and 3 L of supplemental oxygen. Oxygen saturation (SpO₂) was measured by pulse oximetry (POX), and capnography (PcCO₂) was continuously measured using a combined dedicated sensor at the ear lobe. Instances of apnea resulting in measures such as stimulation of the patient, a chin lift, a mask maneuver, or withholding of sedation were recorded. PcCO₂ values (as a parameter of sedation-induced hypoventilation) were compared between groups at the following distinct time points: baseline, maximal rise, termination of the procedure and 5 min after termination of the procedure. The number of patients in both study groups who regained baseline PcCO₂ values (± 1.5 mmHg) five minutes after the procedure was determined. A total of 97 patients entered this study. The data from 14 patients were subsequently excluded for clinical procedure-related reasons or for technical problems. Therefore, 83 patients (mean age 62 ± 13 years) were successfully randomized to receive propofol (n = 42) or midazolam (n = 41) for sedation. Most of the patients were classified as American Society of Anesthesiologists (ASA) II [16 (38%) in the midazolam group and 15 (32%) in the propofol group] and ASA III [14 (33%) and 13 (32%) in the midazolam and propofol groups, respectively]. A mean dose of 5 (4-7) mg of IV midazolam and 131 (70-260) mg of IV propofol was used during the procedure in the corresponding study arms. The mean SpO₂ at baseline (%) was 99 ± 1 for the midazolam group and 99 ± 1 for the propofol group. No cases of hypoxemia (SpO₂ < 85%) or apnea were recorded. However, an increase in PcCO₂ that indicated alveolar hypoventilation occurred in both groups after administration of the first drug and was not detected with pulse oximetry alone. The mean interval between the initiation of sedation and the time when the PcCO₂ value increased to more than 2 mmHg was 2.8 ± 1.3 min for midazolam and 2.8 ± 1.1 min for propofol. The mean maximal rise was similar for both drugs: 8.6 ± 3.7 mmHg for midazolam and 7.4 ± 3.2 mmHg for propofol. Five minutes after the end of the procedure, the mean difference from the baseline values was significantly lower for the propofol treatment compared with midazolam (0.9 ± 3.0 mmHg vs 4.3 ± 3.7 mmHg, P = 0.0000169), and significantly more patients in the propofol group had regained their baseline value ± 1.5 mmHg (32 of 41 vs 12 of 42, P = 0.0004). A significantly higher number of patients sedated with propofol had normalized PcCO₂ values five minutes after sedation when compared with patients sedated with midazolam.

Comparison of propofol and the combination of propofol and alfentanil during bronchoscopy: a randomized study

propofol is an excellent sedative agent for use in patients undergoing bronchoscopy. The addition of an opioid to propofol can be advantageous because of the antitussive effect of the opioid and the possible improvement in sedation quality. However, it may increase the risk of hypoxaemia. To investigate the effect of the addition of alfentanil to propofol, we performed a prospective study to compare propofol-only sedation with propofol-alfentanil combination sedation in patients undergoing bronchoscopy. patients were randomly assigned either to the propofol-only (group P, n=32) or to the propofol-alfentanil combination group (group PA, n=32). The average peripheral oxygen saturation (SpO(2) ) and the lowest SpO(2) during the sedation were compared. Patient and bronchoscopist satisfaction as well as the degree of coughing were compared using a 100 mm visual analogue scale, where 0 indicated the least and 100 indicated the most satisfied. group P had the higher average SpO(2) (%) during the procedure than group PA (97.8 ± 1.6 and 96.4 ± 1.1, P<0.01) as well as the lowest SpO(2) (%) (95.4 ± 2.7 and 94.0 ± 2.4, P<0.05). Patient satisfaction (92.2 ± 13.5 and 92.3 ± 18.2), bronchoscopist satisfaction (76.6 ± 18.1 and 72.8 ± 19.1), and degree of cough (73.4 ± 22.7 and 72.2 ± 18.5; group P and group PA, respectively) were not different between the groups. the combination of propofol and alfentanil resulted in a greater respiratory depression than propofol alone; furthermore, the addition of an opioid did not improve the quality of sedation. In conclusion, we do not recommend sedation with propofol and alfentanil during bronchoscopy.

The Effects of Alfentanil and a Combination of Alfentanil and Esmolol on Hemodynamic Responses after Endotracheal Intubation in Hypertensive Patients

Background: This study was desined to determine the efficacy and clincial usefulness of alfentanil and a combined use of alfentanil and esmolol for blunting hemodynamic responses after tracheal intubation in hypertensive patients who needed a rapid sequence induction. Methods: Group 1 received alfentanil 15/kg and group 2 received alfentanil 15/kg and esmolol 1 mg/kg intravenously. Thiopental sodium 5 mg/kg and succinylcholine 1 mg/kg were used for the induction of anesthesia. Changes in blood pressure and herat rate were measured during intubation and induction of anesthesia with enflurane--O2 and vecuronium. Rate pressure products (RPP) was calculated and the frequencies of hypertension, hypotension, tachycardia, bradycardia were measured. Results: In group 1, systolic blood pressure increased significantly at 1, 2 minute and decreased significantly at 4, 5, 10, 15 minute compared to base, and diastolic blood pressure increased significantly at 1 minute and decreased significantly at 4, 5, 10 minute. Heart rate increased significantly at 1, 2 minute. In group 2, systolic blood pressure decrease significantly at 3, 4, 5 minute after tracheal intubation compared to base, and diastolic blood pressure increased at 1 minute and decreased at 4, 5, 10, 15 minute. HR did not change significantly (P /kg and esmolol 1 mg/kg is a useful method to attenuate hemodynamic responses after endotracheal intubation and especially for rapid sequence induction.

Effects of a Combination of Nicardipine and Alfentanil on Hemodynamic Response after Endotracheal Intubation

Background: The present study was designed to examine the effect of a combination of nicardipine and low dose alfentanil on hemodynamic response following endotracheal intubation. Methods: Thirty patients (20-65 yr) were assigned randomly to receive nicardipine (N: /kg) or a combination of nicardipine and low dose of alfentanil (NA: nicardipine /kg and alfentanil /kg). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured at 1, 2 min after anesthetic induction, and every minute for 5 min after intubation. Results: The magnitude of increases in SBP and DBP were non-significantly smaller in the NA group than in the N group, and increase in HR were significantly lower in the NA group. Conclusions: These results indicate that the nicardipine with alfentanil combination was more effective than nicardipine alone at attenuating blood pressure and heart rate increases following intubation.

Rapid tracheal intubation with propofol, alfentanil and a standard dose of vecuronium

We studied 60 ASA I patients with Mallampati grade 1 airways to compare emergency intubating conditions with either alfentanil 20 micrograms kg-1, propofol 2.5 mg kg-1 and vecuronium 0.1 mg kg-1, or with thiopentone 5 mg kg-1 and suxamethonium 1 mg kg-1. Ease of laryngoscopy, vocal cord status and cough response were graded. The trachea of all patients was intubated; 83% of patients in the alfentanil-propofol-vecuronium group and 86% in the thiopentone-suxamethonium group were considered to have satisfactory intubating conditions at 60 s. We conclude that the combination of alfentanil 20 micrograms kg-1, propofol 2.5 mg kg-1 and vecuronium 0.1 mg kg-1 provided adequate conditions for rapid tracheal intubation.

Propofol and alfentanil for sedation during placement of retrobulbar block for cataract surgery

Study Objective: To determine if the addition of alfentanil to propofol is more effective than propofol alone to provide adequate conditions for placement of a retrobulbar block prior to cataract surgery. Design: Randomized, double-blinded study. Setting: Outpatients at a university hospital. Patients: 40 adult ASA physical status I, II, and III outpatients scheduled for elective cataract surgery. Interventions: Patients were randomly assigned to receive one of four drug combinations prior to the placement of a retrobulbar block: Group 1, propofol alone; Group 2, alfentanil 5 μg/kg plus propofol; Group 3, alfentanil 10 μg/kg plus propofol; Group 4, alfentanil 15 μg/kg plus propofol. All patients were preoxygenated by face mask for two minutes prior to drug administration. The quality of conditions for block placement were determined by: (1) assessing the amount of movement by the patients while the block needle was in place, (2) cooperativeness of the patients during the operation, (3) hemodynamic side effects, (4) incidence and severity of respiratory depression, (5) incidence of nausea and vomiting, (6) recall of placement of the block, and (7) time to discharge from the hospital. Measurements and Main Results: The addition of alfentanil to propofol for sedation prior to placement of the retrobulbar block resulted in a dose-dependent reduction in movement by the patients. However, the highest dose of alfentanil (15 μg/kg) resulted in the greatest frequency (40% of the patients in this group) of respiratory depression (SpO 2 < 90%). All patients were cooperative during the operation and responsive to verbal command within 5 minutes of placement of the block. In addition, all of the patients denied being nauseated, having vomited, or recalling block placement in the recovery room or the next day. Conclusions: The combination of alfentanil and propofol may be used to sedate patients in order to limit movement and provide a cooperative, alert patient with stable hemodynamics and limited respiratory depression during placement of retrobulbar block prior to ophthalmic surgery. However, excessive dosage of these drugs may result in hazardous respiratory depression in this patient population.

Modification of the haemodynamic responses to induction of anaesthesia and tracheal intubation with alfentanil, esmolol and their combination

The purpose of this double-blind randomized work was to study the effect of alfentanil and esmolol and their half-dose combination on the increases of heart rate and arterial pressure and on the prolongation of the QTc interval of the ECG occurring during anaesthetic induction. Sixty ASA class I-II patient with mean age ranging from 26 to 32 yr among the groups. Patients were allocated to one of four equal groups to receive saline, esmolol 2 mg.kg-1, alfentanil 0.03 mg.kg-1 and alfentanil 0.015 mg.kg-1+esmolol 1 mg.kg-1. Anaesthesia was induced with thiopentone. Succinylcholine was used to facilitate tracheal intubation. Haemodynamic variables were measured non-invasively and the QTc interval with the aid of a microcomputer. Comparisons between the groups were performed using two-way analysis of variance with repeated measures. Both alfentanil and alfentanil-esmolol prevented the increase of heart rate and arterial pressure caused by intubation whereas esmolol prevented only the increase of the heart rate. None of the treatments prevented prolongation of the QTc interval after intubation and only alfentanil prevented that after succinylcholine. The present results suggest that in the prevention of the haemodynamic responses to tracheal intubation, the half-dose combination of alfentanil and esmolol is as effective as alfentanil and superior to esmolol. The combination is preferable to relatively large doses of either drug in circumstances where side effects, such as respiratory depression due to alfentanil or bradycardia due to both drugs should be minimized.

Sedation for fibre optic bronchoscopy

Most current sedative regimens for fibre optic bronchoscopy use an opioid, a benzodiazepine or a combination of both. This study compares midazolam (M) (a benzodiazepine), alfentanil (A) (an opioid) and a combination of both drugs (M + A). One hundred and three patients were randomized in double-blind manner into groups M(35), A(33) and M + A(35). The number of coughs, number of additional aliquots of lignocaine and duration of the procedures were recorded along with oxygen desaturation. The patient's level of discomfort was assessed by patient and bronchoscopist and expressed as a visual analogue score. There were significantly fewer coughs per minute in Group A compared with Group M ( P=0·0053), and significantly less lignocaine was required in Group A ( P=0·005) and in Groups M + A ( P<0·002) compared with Group M. There was no significant difference in the assessment of discomfort between the groups. There was a trend for Group M + A to desaturate more than the other two with a significant difference between desaturation in Group M + A and Group A ( P=0·033). Alfentanil is a more effective anti-tussive agent than midazolam for outpatient fibre optic bronchoscopy. The combination of alfentanil and midazolam does not provide any better anti-tussive effect and may have the risk of a greater degree of desaturation secondary to increased sedation.

Alfentanil–Kombinationsnarkosen bei der Adeno–Tonsillektomie im Kindesalter – ein Vergleich mit der Ethrane–Inhalationsanästhesie

In two groups, each comprising 25 children undergoing adenotonsillectomy, two different methods of anaesthesia were used. Group I received ethrane inhalations, group II an alfentanil combination anaesthesia

ALFENTANIL AND PROPOFOL INFUSIONS FOR SURGERY IN THE BURNED PATIENT

We have studied combinations of alfentanil and propofol for total i.v. anaesthesia in 24 severely burned patients. No inhalation agents were used. After a loading dose of alfentanil 100 micrograms kg-1, the intraoperative requirement was 1.24 (SEM 0.7) micrograms kg-1 min-1, and after a propofol induction dose of 2 mg kg-1 the maintenance rate was 100 micrograms kg-1 min-1. Initial hypotension occurred after induction of anaesthesia, but during the operation, cardiovascular variables were stable. After adequate antagonism of neuromuscular block, respiratory depression persisted in three patients when the two agents were discontinued simultaneously; this was not seen when alfentanil was discontinued 15 min before propofol. Quality of recovery was good, and satisfactory postoperative analgesia was present in the majority of patients 2 h after operation. This study indicates that total i.v. anaesthesia with a combination of alfentanil and propofol appears to be satisfactory in burned patients.