Alfentanil Infusion Research Articles

Lung compliance during laparoscopic surgery in paediatric patients.

Insufflation of CO2 and positioning of patients induces changes in cardiovascular and respiratory function during laparoscopic procedures. This study was initiated to assess respiratory mechanics such as lung compliance and peak airway pressure (PIP) during laparoscopic surgery in paediatric patients. Ten consecutive patients (age 1-15 years) scheduled for laparoscopic procedure were included in this open prospective single-group study. Anaesthesia was induced and maintained with intravenous infusions of propofol and alfentanil. Vecuronium was administered to maintain muscle relaxation. Head down tilt induced a mean decrease of 17% in lung compliance, which was further decreased by 27% from the baseline during insufflation of intraabdominal CO2 (intraabdominal pressure 12 mmHg). Coincidently, PIP increased by 19% and 32% from the baseline during Trendelenburg position and peritoneal insufflation. Lung compliance and PIP returned to their respective baseline values after removal of CO2 from the peritoneal cavity. Endtidal CO2 increased from a baseline value of 4.3 kPa to 5.4 kPa (33-42 mmHg) during surgery when ventilator settings were not altered. We conclude that insufflation of CO2 induces significant increases in peak airway pressure with simultaneous decreases in lung compliance.

The changing role of monitored anesthesia care in the ambulatory setting.

The changing role of monitored anesthesia care in the ambulatory setting.

Thoracic epidural anaesthesia for coronary artery bypass graft surgery. Effects on postoperative complications.

We have performed a retrospective analysis of the peri-operative course of 218 consecutive patients who underwent routine coronary artery bypass graft surgery in this institution. All patients received a standardised general anaesthetic using target-controlled infusions of alfentanil and propofol. One hundred patients also received thoracic epidural anaesthesia with bupivacaine and clonidine, started before surgery and continued for 5 days after surgery. The remaining 118 patients received target-controlled infusion of alfentanil for analgesia for the first 24 h after surgery, followed by intravenous patient-controlled morphine analgesia for a further 48 h. Using computerised patient medical records, we analysed the frequency of respiratory, neurological, renal, gastrointestinal, haematological and cardiovascular complications in these two groups. New arrhythmias requiring treatment occurred in 18% of the thoracic epidural anaesthesia group of patients compared with 32% of the general anaesthesia group (p = 0.02). There was also a trend towards a reduced incidence of respiratory complications in the thoracic epidural anaesthesia group. The time to tracheal extubation was decreased in the epidural group, with the tracheas of 21% of the patients being extubated immediately after surgery compared with 2% in the general anaesthesia group (p < 0.001). There were no serious neurological problems resulting from the use of thoracic epidural analgesia.

Remifentanil versus alfentanil in a balanced anesthetic technique for total abdominal hysterectomy

Study Objectives: To compare the intraoperative effects and recovery characteristics of remifentanil hydrochloride and alfentanil when administered as part of balanced anesthesia, and to assess the effects of an additional remifentanil infusion administered as analgesic pretreatment before removal of the uterus. Design: Multicenter, double-blind, randomized, parallel-group study. Setting: Two university hospitals. Patients: 35 ASA physical status I, II, and III women scheduled for elective total abdominal hysterectomy with general endotracheal anesthesia. Interventions: Patients were premedicated with midazolam 0.05 mg/kg intravenously (IV). Anesthesia was induced with thiopental 2 mg/kg, vecuronium 0.15 mg/kg, and a single dose of opioid over 60 seconds (Pump 1): remifentanil 2 μg/kg (Remi/Placebo and Remi/Remi groups) or alfentanil 50 μg/kg (Alf/Placebo group). Anesthesia was maintained with a nitrous oxide/oxygen mixture (66:34 ratio) and a continuous opioid infusion: remifentanil 0.25 μg/kg/min (Remi/Placebo and Remi/Remi) or alfentanil 0.5 μg/kg/min (Alf/Placebo). At skin incision, a second blinded drug infusion was also initiated (Pump 2): remifentanil 0.25 μg/kg/min (Remi/Remi) or saline placebo (Remi/Placebo and Alf/Placebo). Intraoperative responses were controlled with single doses of opioid and/or rate titrations via Pump 1. Pump 2 was terminated on removal of the uterus. Pump 1 was terminated at skin closure. Measurements and Main Results: The mean (±SD) opioid infusion rates administered for the duration of Pump 2 to suppress responses to removal of the uterus were 0.49 ± 0.27 μg/kg/min, 1.99 ± 1.34 μg/kg/min, and 0.49 ± 0.07 μg/kg/min for the Remi/ Placebo, Alf/Placebo, and Remi/Remi groups, respectively. At these rates, similar proportions of patients in the Remi/Placebo (67%) and the Alf/Placebo (60%) groups had responses. Fewer patients had responses in the Remi/Remi group (8%) compared with the Remi/Placebo and Alf/Placebo groups ( p < 0.05). The mean total opioid doses used during maintenance were 84.6 μg/kg (Remi/Placebo), 393 μg/kg (Alf/Placebo), and 68. 7 μg/kg (Remi/Remi). Awakening times were significantly shorter ( p < 0.05) in the remifentanil population compared with the alfentanil population, but discharge times were similar. More patients received naloxone to reverse opioid effects in the alfentanil population (60%) than in the remifentanil population (20%) ( p < 0.05). Conclusions: A mean remifentanil infusion of 0.49 μg/kg/min is as effective as a mean alfentanil infusion of 1.99 μg/kg/min in suppressing intraoperative responses. Doubling of the remifentanil infusion to 0.5 μg/kg/min before the major stress event improves suppression of responses and lowers intraoperative use of remifentanil without prolonging recovery times. Remifentanil allows faster awakening times than alfentanil, but preemptive administration of postoperative analgesics is recommended to facilitate discharge.

Use of Alfentanil and Propofol for Outpatient Monitored Anesthesia Care

Propofol and alfentanil are both rapid and short-acting drugs that can be used for sedation and analgesia during monitored anesthesia care (MAC). This study was designed to determine the optimal infusion rates of propofol and alfentanil when administered during local anesthesia. In this randomized, double-blind study, we evaluated the effects of different propofol infusion rates on the alfentanil requirement, level of sedation, intraoperative recall, respiratory and cardiovascular variables, and recovery. Seventy-two consenting ASA physical status I or II female outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to one of four treatment groups. All patients received midazolam, 2 mg intravenously (IV) for premedication. Propofol was infused at 0, 25, 50, or 75 micro g [center dot] kg-1 [center dot] min-1 during the operation. Sedation was evaluated using the Observer's Assessment of Alertness/Sedation (OAA/S) scale at 5-min intervals by a blinded observer. Two minutes before the infiltration of the local anesthetic solution, a bolus of alfentanil, 2.5 micro g/kg IV, was administered, followed by a maintenance infusion of 0.5 micro g [center dot] kg-1 [center dot] min-1. The alfentanil infusion rate was subsequently varied to maintain patient comfort and stable cardiovascular and respiratory function. Pictures were shown at the start of the propofol infusion, upon initiating the alfentanil infusion, and at 45 min after the skin incision to evaluate recall of intraoperative events. Propofol produced dose-dependent increases in the level of sedation (with median OAA/S scores of 2-4, P < 0.05). Higher infusion rates of propofol (50-75 micro g [center dot] kg-1 [center dot] min-1) produced significant amnesia, opioid-sparing effects (alfentanil 0.3 +/- 0.2 vs 0.6 +/- 0.2 micro g [center dot] kg-1 [center dot] min-1), and less postoperative nausea and vomiting (P < 0.05). However, episodes of transient hemoglobin oxygen desaturation were more common in the deeply sedated patients. Thus, in healthy outpatients premedicated with midazolam, 2 mg IV, a propofol infusion of 25-50 micro g [center dot] kg-1 [center dot] min-1 in combination with an alfentanil infusion of 0.2-0.4 micro g [center dot] kg-1 [center dot] min (-1) is recommended for sedation and analgesia during MAC in the ambulatory setting. Implications: Sedation is often given during local anesthesia. This study demonstrated that administration of an intravenous anesthetic, propofol, in combination with an opioid infusion (i.e., alfentanil) to provide sedation analgesia and amnesia with a low incidence of side effects, such as nausea and vomiting and respiratory depression in outpatients premedicated with midazolam. (Anesth Analg 1997;85:566-72)

Effects of alfentanil on cerebral haemodynamics in an experimental model of traumatic brain injury

Alfentanil is reported to increase intracranial pressure (ICP) after neurotrauma. A direct cerebral vasodilator effect has been postulated. We studied 17 Sprague-Dawley rats allocated to one of three groups. Animals were anaesthetized and their lungs ventilated, and arterial pressure, ICP and/or regional cerebral blood flow (CBF) measurements were undertaken. Group 1 (n = 6) received a severe closed head injury while group 2 (n = 5) received no injury. ICP and mean arterial pressure (MAP) were measured before, during and after rapid infusion of alfentanil 250, 500 and 750 micrograms kg-1. CBF was measured by hydrogen clearance before rapid infusions and at 30-min intervals after starting a subsequent slow infusion of alfentanil 500 micrograms kg-1 h-1. Group 3 (n = 6) underwent CBF measurement only, for comparison with those of groups 1 and 2. They received an injury but no alfentanil. ICP or MAP values did not differ significantly between groups 1 and 2. Rapid i.v. doses of alfentanil produced increases in ICP and reductions in MAP. ICP changes were consistent with a drug effect (P < 0.001) but were small. Reductions in MAP were significant (P < 0.05) and preceded changes in ICP. CBF values were similar and unaffected by slow alfentanil infusion in groups 1 and 2, and did not differ significantly between groups 1 and 3. We conclude that alfentanil did not appear to exert a direct effect on the cerebral circulation. Changes in ICP after rapid infusion were secondary to reductions in SAP. Slow infusion did not cause such changes.

Safe anesthetic management of patients undergoing a novel method of treating human hepatocellular cancer

Study Objective: To evaluate the safety and efficacy of monitored anesthesia care (MAC) in patients who undergo a novel treatment for hepatocellular cancer in which procedure-related hemodynamic instability is problematic. Design: Nonrandomized open study. Setting: University cancer center operating room. Patients: Nine patients scheduled for hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration (no more than 3 procedures per patient). Interventions: Hepatic venous isolation was achieved with a dual-balloon inferior vena cava catheter connected to an extracorporeal circuit containing chemofilters. Doxorubicin was infused through the hepatic artery and filtered from the venous blood, which was returned to the patient through an internal jugular venous catheter. Each patient received a bolus of propofol (200 μg/kg) and one of alfentanil (2 μg/kg) followed by simultaneous infusions of propofol and alfentanil for percutaneous placement of the catheters and operation of the extracorporeal circuit. Drug rates were varied to maintain a sedative-analgesic state of calm, comfort, minimal movement, and adequate respiratory function. Prior to circuit initiation, patients were preloaded with crystalloid. During circuit operation, hypotension was treated with intravenous (IV) phenylephrine and crystalloid. Measurements and Main Results: End-tidal CO 2 (P ETCO 2), respiratory rate, oxygen saturation (SaO 2), arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic, diastolic, and mean arterial pressure (MAP), and HR were compared before, during, and after hepatic venous isolation and chemofiltration. Doses and infusion rates of propofol, alfentanil, and phenylephrine were recorded for each treatment. Hypotension occurred in 11 of 13 procedures when blood was directed through the chemofilters and was successfully treated with phenylephrine (dose range 40 to 5,733 μg) and crystalloid. Blood pressure returned to the baseline value on termination of the circuit. Throughout the sedation, patients were easily arousable, analgesia was adequate, and P ETCO 2 level of 38 ± 4 mmHg and SaO 2 greater than 94 % were maintained. Mean doses and infusion rates of MAC drugs were, respectively: propofol, 261 ± 88 mg and 23.7 ± 3.6 μg/kg/min; alfentanil, 3,350 ± 1,468 μg and 0.32 ± 0.14 μg/kg/min. Conclusions: Patients undergoing this novel cancer treatment are safely and effectively managed by MAC achieved with simultaneous infusions of alfentanil and propofol. Procedure-associated hypotension is easily treated with IV phenylephrine and crystalloid.

A Multicenter Study of Bispectral Electroencephalogram Analysis for Monitoring Anesthetic Effect

Bispectral analysis (BIS) of the electroencephalogram (EEG) has been shown in retrospective studies to predict whether patients will move in response to skin incision. This prospective multicenter study was designed to evaluate the real-time utility of BIS in predicting movement response to skin incision using a variety of general anesthetic techniques. Three hundred patients from seven study sites received an anesthetic regimen expected to give an approximately 50% movement response at skin incision. EEG was continuously recorded via an Aspect B-500 monitor and BIS was calculated in real time from bilateral frontocentral channels displayed on the monitor. Half of the patients were randomized to a treatment group in which anesthetic drug doses were increased to produce a lower BIS. In the control group, BIS was recorded, but no action taken on the data displayed. A determination of movement in response to skin incision was made in the 2 min succeeding incision. Retrospective pharmacodynamic modeling was performed using STANPUMP to estimate effect-site concentrations of intravenously administered anesthetics. BIS values were significantly higher in the control group (66 +/- 19) versus the BIS-guided group, in which additional anesthesia was administered to produce a lower BIS (51 +/- 19). The movement response rate was significantly higher in the control group at 43% compared with 13% in the BIS-guided group, but response rates were low at sites which used larger doses of opioids. Logistic regression analysis showed that BIS, estimated opioid effect-site concentrations, and heart rate (in that order) were the best predictors of movement at skin incision. This study demonstrates that dosing anesthetic drugs to lower BIS values achieves a lower probability of movement in response to surgical stimulation. BIS is a significant predictor of patient response to incision, but the utility of the BIS depends on the anesthetic technique being used. When drugs such as propofol or isoflurane are used as the primary anesthetic, changes in BIS correlate with the probability of response to skin incision. When opioid analgesics are used, the correlation to patient movement becomes much less significant, so that patients with apparently "light" EEG profiles may not move or otherwise respond to incision. Therefore, the adjunctive use of opioid analgesics confounds the use of BIS as a measure of anesthetic adequacy when movement response to skin incision is used as the primary end point.

Remifentanil Compared with Alfentanil for Ambulatory Surgery Using Total Intravenous Anesthesia

The purpose of this study was to test the hypothesis that using a 1:4 ratio of remifentanil to alfentanil, a remifentanil infusion would provide better suppression of intraoperative responses and comparable recovery profiles after ambulatory laparoscopic surgery than an alfentanil infusion, as part of total intravenous anesthesia. Two hundred ASA physical status I, II, or III adult patients participated in this multicenter, double-blind, parallel group study. Patients were randomly assigned 2:1 to either the remifentanil-propofol or alfentanil-propofol regimens. The anesthesia sequence was propofol (2 mg/kg intravenously [IV] followed by 150 micro g [centered dot] kg (-1) [centered dot] min-1), and either remifentanil (1 micro g/kg IV followed by 0.5 micro g [centered dot] kg-1 [centered dot] min-1) or alfentanil (20 micro g/kg IV followed by 2 micro g [centered dot] kg-1 [centered dot] min (-1)), and vecuronium. After trocar insertion, infusion rates were decreased (propofol to 75 micro g [centered dot] kg-1 [centered dot] min-1; remifentanil to 0.25 micro g [centered dot] kg-1 [centered dot] min-1; alfentanil to 1 micro g [centered dot] kg-1 [centered dot] min-1). Alfentanil and propofol were discontinued at 10 and 5 min, respectively, before the anticipated end of surgery (last surgical suture); remifentanil was discontinued at the end of surgery. Recovery times were calculated from the end of surgery. The median duration of surgery was similar between groups (39 min for remifentanil versus 34 min for alfentanil). A smaller proportion of remifentanil patients than alfentanil patients had any intraoperative responses (53% vs 71%, P = 0.029), had responses to trocar insertion (11% vs 32%, P < 0.001), or required dosage adjustments during maintenance (24% vs 41%, P < 0.05). Early awakening times were similar. Remifentanil patients qualified for Phase 1 discharge later and were given postoperative analgesics sooner than alfentanil patients (P < 0.05). Actual discharge times from the ambulatory center were similar between groups (174 min for remifentanil versus 204 min for alfentanil) (P = 0.06). In conclusion, remifentanil can be used for maintenance of anesthesia in a 1:4 ratio compared with alfentanil, for total IV anesthesia in ambulatory surgery. This dose of remifentanil provides more effective suppression of intraoperative responses and does not result in prolonged awakening. (Anesth Analg 1997;84:515-21)

Remifentanil Compared with Alfentanil for Ambulatory Surgery Using Total Intravenous Anesthesia

The purpose of this study was to test the hypothesis that using a 1:4 ratio of remifentanil to alfentanil, a remifentanil infusion would provide better suppression of intraoperative responses and comparable recovery profiles after ambulatory laparoscopic surgery than an alfentanil infusion, as part of total intravenous anesthesia. Two hundred ASA physical status I, II, or III adult patients participated in this multicenter, double-blind, parallel group study. Patients were randomly assigned 2:1 to either the remifentanil-propofol or alfentanil-propofol regimens. The anesthesia sequence was propofol (2 mg/kg intravenously [IV] followed by 150 micrograms.kg-1.min-1), and either remifentanil (1 microgram/kg IV followed by 0.5 microgram.kg-1.min-1)of alfentanil (20 micrograms/kg IV followed by 2 micrograms.kg-1.min-1), and vecuronium. After trocar insertion, infusion rates were decreased (propofol to 75 micrograms.kg-1.min-1; remifentanil to 0.25 microgram.kg-1.min-1; alfentanil to 1 microgram.kg-1.min-1). Alfentanil and propofol were discontinued at 10 and 5 min, respectively, before the anticipated end of surgery (last surgical suture); remifentanil was discontinued at the end of surgery. Recovery times were calculated from the end of surgery. The median duration of surgery was similar between groups (39 min for remifentanil versus 34 min for alfentanil). A smaller proportion of remifentanil patients than alfentanil patients had any intraoperative responses (53% vs 71%, P = 0.029), had responses to trocar insertion (11% vs 32%, P < 0.001), or required dosage adjustments during maintenance (24% vs 41%, P < 0.05). Early awakening times were similar. Remifentanil patients qualified for Phase 1 discharge later and were given postoperative analgesics sooner than alfentanil patients (P < 0.05). Actual discharge times from the ambulatory center were similar between groups (174 min for remifentanil versus 204 min for alfentanil) (P = 0.06). In conclusion, remifentanil can be used for maintenance of anesthesia in a 1:4 ratio compared with alfentanil, for total IV anesthesia in ambulatory surgery. This dose of remifentanil provides more effective suppression of intraoperative responses and does not result in prolonged awakening.

Target-controlled infusion of alfentanil for postoperative analgesia: a feasibility study and pharmacodynamic evaluation in the early postoperative period

We have examined the feasibility of target-controlled infusion of alfentanil (TCIA) and the pharmacodynamics of alfentanil in the early postoperative period. Patients were allocated randomly to one of the three groups to receive balanced anaesthesia with bolus injections of fentanyl (group F), sufentanil (group S) or alfentanil (group A). In the recovery room all patients received the same analgesic regimen, comprising TCIA. To evaluate the efficacy of postoperative analgesia, pain scores were measured on a visual analogue scale (VAS) and patients indicated a need for additional analgesia. EC50, the concentration at which, with a 50% probability, patients reported adequate analgesia, was estimated using logistic regression. Six patients did not complain of pain. The time from the last intraoperative bolus injection of opioid until patients complained of postoperative pain was shorter (P < 0.05) in group A (mean 68 min) than in group F (101 min) and group S (136 min). The time to onset of satisfactory analgesia was comparable in the three groups (median 18 min in group F, 15 min in group S and 14 min in group A). EC50 of alfentanil was determined in 28 patients; mean values were 26 ng ml-1 (group F), 39 ng ml-1 (group S) and 52 ng ml-1 (group A). We conclude that TCIA, under the conditions studied, resulted in a fast onset of adequate analgesia, irrespective of the opioid administered during operation. Also, there was no effect of opioids administered during operation on postoperative pharmacodynamics of alfentanil.

Comparison of Recovery Period Characteristics of Propofol Alfentanil And Isoflurane Anaesthesiapropofol

The recovery periods of propofol alfentenil anaesthesia isoflurane anasesthesia were compared clinically. This study was peiformed on 60 patients in groups of ASA 1-II. The patients were divided in two groups After giving propofol 2mglkg IV to the first group; the intubation was made and then a bolus of alfentanil (25mcg/kg ) was given via IV Anaesthesia was maintained by propofol alfentanil infusion. Two mg /kg propofol was given by bolus to the second group and then 0.1 mg/kg vecuronium was given. When neuromuscular blockade was achieved, intubation was made. The anaesthesia was maintained with 02N02 (33%-67% ), and isoflurane inhalation (1-2%).The recovery period of the patients were assessed clinically by awakening, responsiveness to the commands, orientation times. The Stewart scores were evaluated. Statistical analysis were made by using student-t and Mann Whitney-U tests. Awakening responsiveness to commands and orientation times were shorter in the first group than the second (p&lt;0.05). ln both groups the 15 minutes postanaesthesia recovery was foundfull (6 points) according to the Steward Score. ln the recovery period nausea, euphoria, itching in the first group and emesis, coughing in the second group were found. We observed some advantages of propofol alfentanil infusion such as faster recovery, less air pullationjust as the inhalation anaesthetics had. We conclude that the propofol alfentanil infusion can be preferred to isoflurane anaesthesia as an alternative agent.

Propofol-alfentanil versus fentanyl-midazolam in coronary artery surgery

To compare intraoperative hemodynamics profiles and recovery characteristics of propofol-alfentanil with fentanyl-midazolam anesthesia in elective coronary artery surgery. Prospective, randomized study. University hospital. Fifty patients with impaired or good left ventricular function. In group 1, (n = 25) anesthesia was induced with an infusion of propofol, 3 to 4 mg/kg/h, alfentanil, 500 micrograms, and pancuronium 0.1 mg/kg, and maintained with propofol, 3 to 6 mg/kg/h (variable rate), and alfentanil infusions, 30 micrograms/kg/h (fixed rate). Additional boluses of alfentanil, 1 mg, were administered before noxious stimuli; group 2 (n = 25) received a loading dose of fentanyl, 25 micrograms/kg, midazolam, 1.5 to 3 mg, and pancuronium, 0.1 mg/kg for induction, followed by an infusion of fentanyl, 7 micrograms/kg/h, for maintenance. Additional boluses of midazolam (1.5 to 3 mg) and fentanyl (250 micrograms) were administered before noxious stimuli. MEASUREMENTS AND MAIN RESULTS. Cardiovascular parameters at eight intraoperative time points as well as time to extubation, morphine consumption, and pain scores were recorded. Induction of anesthesia was associated in both groups with a small but significant decrease in mean arterial pressure (1: 15 mmHg (15%); 2: 8 mmHg (8%) with significant decreases in cardiac index (1: 8%; 2: 8%) and left ventricular stroke work index (1: 24%; 2: 21%). Throughout surgery, hemodynamic profiles were comparable between groups except after intubation when the MAP was significantly lower in group 1 (75 +/- 12 mmHg) than in group 2 (89 +/- 17 mmHg). Group 1 required less inotropic support. Extubation was performed faster in group 1 (7.6 h) than in group 2 (18.0 h). Morphine requirements and pain scores were comparable between groups. Propofol-alfentanil anesthesia provides good intraoperative hemodynamics and allows early extubation after coronary artery surgery.

Local anaesthesia to the airway reduces sedation requirements in patients undergoing artificial ventilation

Patients in the intensive care unit require large doses of sedative/analgesic drugs to tolerate the presence of a tracheal tube and other unpleasant stimuli. The ideal regimen for sedatives and analgesics has not yet been found. We have investigated the effects of topical local anaesthesia to the pharynx and airway on sedative/analgesic requirements in 30 ICU patients (25-75 yr old) with no obvious brain injury, undergoing mechanical ventilation. Oral tracheal tubes were changed to a modified tube which allowed instillation of local anaesthetic solutions onto the pharyngeal, laryngeal and tracheal mucosa. Lignocaine 1% (5 ml) or 5 ml of 0.9% saline were instilled hourly for 12 h each for a total of 24 h, in a double-blind, randomized crossover design. Baseline sedation was maintained with propofol or alfentanil infusions, or both, which were titrated to patient comfort and to maintain an optimum sedation score throughout. Twenty-five patients completed the study. Mean total propofol and alfentanil requirements were 766 (SD 524) mg and 17 (7.6) mg, respectively, during 12 h of lignocaine instillation, and 1321 (862) mg and 25 (11.4) mg, respectively, during 12 h of saline instillation. There was a significant reduction (P < 0.05) in the requirements for both agents during the period of lignocaine instillation.

Administration of propofol by target-controlled infusion in patients undergoing coronary artery surgery

To study the predictive performance of a target-controlled infusion (TCI) system of propofol in patients undergoing coronary bypass graft (CABG) surgery, using a referenced pharmacokinetic set derived from healthy patients. Also, to determine the propofol concentrations required for clinically acceptable induction and maintenance of anesthesia when combined with midazolam as premedication and a continuous alfentanil infusion and to study the hemodynamic stability of this technique. Prospective noncomparative study analysis. Operating room at a university hospital. Twenty-on patients with good left ventricular function undergoing coronary artery surgery. Patients were anesthetized using a continuous infusion of alfentanil (mean infusion rate: 1 microgram/kg/min) and propofol administered by TCI. The predictive performance of the TCI system (212 arterial samples) was measured at specified time points before, during, and after bypass. The TCI system underestimated the measured blood propofol concentrations with a bias of +21.2% and +9.6% during the prebypass and the bypass periods, respectively. The predictive inaccuracy, expressed by the median absolute prediction error, was 23% and 18.5%, respectively. Mean target propofol concentrations required to induce and maintain anesthesia before bypass were 0.92 microgram/mL and 3.64 micrograms/mL, respectively. In the period during and after bypass, the mean target concentrations required to maintain anesthesia was 2.22 micrograms/mL. The administration of propofol by TCI was still associated with some short episodes of hemodynamic instability that were easily controlled by adjusting the target concentration in the majority of the patients. Therefore, the overall quality and ease of control of anesthesia were considered as being good or adequate. In this group of patients undergoing CABG surgery, the TCI system used underestimated the measured propofol concentrations. However, the predictive performance of the selected mean pharmacokinetic parameters derived from healthy patients was acceptable during the whole surgical procedure.

Clonidine for Major Vascular Surgery in Hypertensive Patients

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable.Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micro gram/kg per os 120 min before induction of anesthesia and 3 micro gram/kg intravenously (IV) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micro gram/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 micro gram centered dot kg-1 centered dot min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures. (Anesth Analg 1996;83:687-95)

Postoperative Epidural Opioid Analgesia

Postoperative Epidural Opioid Analgesia

Time course characteristics of acute tolerance development to continuously infused alfentanil in rats.

The time course of the development of acute tolerance to alfentanil was characterized in rat experiments using various algorithms of continuous infusion of the drug. To maintain analgesia at a constant level (tail compression test), alfentanil use was steadily increased: Time to 50% increase in alfentanil use was 255 +/- 98 min with analgesia maintained at a level of 50% increase in the pressure threshold, and 203 +/- 116 min with analgesia maintained at a level of 200% increase. With the use of the alfentanil infusion regimen designed to rapidly achieve and maintain the constant alfentanil plasma concentration (120 ng/mL), the rate of development of acute tolerance, measured in terms of time to 50% recovery during continuing infusion, was 81 +/- 26 min with the compression test and 88 +/- 38 min with the hot-plate test, but 374 +/- 46 min with the rotarod test (P < 0.0001). Thus we demonstrated rapid development of acute tolerance to continuously infused alfentanil with different methods of tolerance assessment. The results also indicate that the time course of tolerance development does not depend on the type of noxious stimulation (mechanical versus thermal) if the response is organized predominantly supraspinally, and that acute tolerance to the direct effect of alfentanil on motor functions does not mask the rapid development of tolerance to its analgesic effect.

Influence of Escherichia coli Endotoxin on the Pharmacokinetics and Respiratory Depressant Effect of Alfentanil in Rabbits

Postoperative fever occurs in many surgical patients, due to release of pyrogens into the circulation. Pyrogens and fever may influence the pharmacokinetics and effects of drugs. The aim of this study was to investigate the interactions of a pyrogen with the opioid analgesic alfentanil in an animal model. Alfentanil was infused over 10min into 17 conscious rabbits and over 120min in another 12 animals. Some of them had been randomized to pretreatment with Escherichia coli endotoxin. Arterial plasma concentrations of alfentanil were determined repeatedly, and arterial blood gas values were recorded. Endotoxin antagonized the respiratory depressant effect of the 10-min infusion of alfentanil by increasing drug distribution clearance during the infusion. In addition, endotoxin raised the total volume of distribution of alfentanil from 0.70 to 1.4 L/kg. Plasma protein binding and elimination clearance were not affected. The increase in volume of distribution and the lack of effect of endotoxin on elimination clearance were confirmed in the 120-min infusion experiments. Apparent concentration–effect relationships for the actions of alfentanil on arterial CO2, O2, and pH were not influenced by the endotoxin. Circulating pyrogens can thus influence the pharmacokinetics and, indirectly, the effects of alfentanil.

Pharmacokinetics of propofol in adult patients undergoing coronary revascularization. The Multicenter Study of Perioperative Ischemia Research Group.

Propofol is increasingly used for cardiac anesthesia and for perioperative sedation. Because pharmacokinetic parameters vary among distinct patient populations, rational drug dosing in the cardiac surgery patient is dependent on characterization of the drug's pharmacokinetic parameters in patients actually undergoing cardiac procedures and cardiopulmonary bypass (CPB). In this study, the pharmacokinetics of propofol was characterized in adult patients undergoing coronary revascularization. Anesthesia was induced and maintained by computer-controlled infusions of propofol and alfentanil, or sufentanil, in 41 adult patients undergoing coronary artery bypass graft surgery. Blood samples for determination of plasma propofol concentrations were collected during the predefined study periods and assayed by high-pressure liquid chromatography. Three-compartment model pharmacokinetic parameters were determined by nonlinear extended least-squares regression of pooled data from patients receiving propofol throughout the perioperative period. The effect of CPB on propofol pharmacokinetics was modeled by allowing the parameters to change with the institution and completion of extracorporeal circulation and selecting the optimal model on the basis of the logarithm of the likelihood. Predicted propofol concentrations were calculated by convolving the infusion rates with unit disposition functions using the estimated parameters. The predictive accuracy of the parameters was evaluated by cross-validation and by a prospective comparison of predicted and measured levels in a subset of patients. Optimal pharmacokinetic parameters were: central compartment volume = 6.0 l; second compartment volume = 49.5 l; third compartment volume = 429.3 l; Cl1 (elimination clearance) = 0.68 l/min; Cl2 (distribution clearance) = 1.97 l/min1; and Cl3 (distribution clearance) = 0.70 l/min. The effects of CPB were optimally modeled by step changes in V1 and Cl1 to values of 15.9 and 1.95, respectively, with the institution of CPB. Median absolute prediction error was 18% in the cross-validation assessment and 19% in the prospective evaluation. There was no evidence for nonlinear kinetics. Previously published propofol pharmacokinetic parameter sets poorly predicted the observed concentrations in cardiac surgical patients. The pharmacokinetics of propofol in adult patients undergoing cardiac surgery with CPB are dissimilar from those reported for other adult patient populations. The effect of CPB was best modeled by an increase in V1 and Cl1. Predictive accuracy of the derived pharmacokinetic parameters was excellent as measured by cross-validation and a prospective test.