Methadone for the induction of anesthesia: plasma histamine concentration, arterial blood pressure, and heart rate

Despite the widespread use of methadone for the treatment of acute and chronic pain, the hemodynamic effects of methadone administered by IV bolus have not been studied. We compared the hemodynamic effects of an IV bolus of methadone 20 mg with those of fentanyl 10 microg/kg for the induction of anesthesia in combination with etomidate 0.3 mg/kg. Forty-three patients undergoing major surgery were randomized to one of the two treatments in a double-blinded fashion. Plasma concentrations of histamine were measured before and 2 min after opioid administration. Heart rate and arterial blood pressure were measured via an arterial line just before opioid administration, etomidate administration, and tracheal intubation; during intubation; and 1 min after intubation. There were no significant differences in mean heart rate between the methadone and fentanyl groups at any time point. Systolic and diastolic blood pressures were significantly lower (P < 0.05) in the fentanyl group just before intubation, during intubation, and 1 min after intubation. Mean plasma concentrations of histamine before and after the administration of methadone or fentanyl were 1.54 ng/mL (SD, 0.65 ng/mL) and 1.57 ng/mL (SD, 1.37 ng/mL) or 1.00 ng/mL (SD, 0.58 ng/mL) and 1.04 ng/mL (SD, 0.47 ng/mL), respectively. Despite the lack of a significant change in mean plasma concentrations of histamine, substantial increases in plasma histamine occurred in 2 of 23 patients who received methadone. There were no obvious hemodynamic effects associated with histamine concentrations up to 6.2 ng/mL. Methadone appears to have the potential for producing histamine release. Although methadone administration did not produce hemodynamic instability in this study, the possible hemodynamic side effects of histamine release should be considered when IV boluses of methadone are given. IMPLICATIONS: The same dose of IV methadone (20 mg) that is effective for postoperative pain is also suitable for the induction of anesthesia in combination with etomidate. The plasma histamine concentration was notably increased in two patients, without obvious hemodynamic sequelae. Therefore, methadone appears to have the potential for producing histamine release.     

Quantification of serum fentanyl concentrations from umbilical cord blood during ex utero intrapartum therapy

Fetal IM injection of fentanyl is frequently performed during ex utero intrapartum therapy (EXIT procedure). We quantified the concentration of fentanyl in umbilical vein blood. Thirteen samples from 13 subjects were analyzed. Medians and ranges are reported as follows. Weight of the newborn at delivery was 3000 g (2020-3715 g). The dose of fentanyl was 60 μg (45-65 μg). The time between IM administration of fentanyl and collection of the sample was 37 minutes (5-86 minutes). Fentanyl was detected in all of the samples, with a median serum concentration of 14.0 ng/mL (4.3-64.0 ng/mL).     

Cardiovascular, respiratory, and analgesic effects of fentanyl in unanesthetized rhesus monkeys

To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64-micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128-micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)     

The simulation of continuous arteriovenous hemodialysis with a mathematical model

We have developed a mathematical model that predicts the performance of continuous arteriovenous hemodialysis. Given patient (plasma protein concentration, hematocrit, mean arterial pressure, central venous pressure) and circuit (flow resistance, membrane hydraulic permeability, dialyzer mass transfer coefficient, ultrafiltrate column height, dialysate flow rate) characteristics as inputs, predictions of hydraulic and oncotic pressure distribution, filtration rate, blood flow, total, diffusive, and convective urea clearances are provided. The model was tested by perfusing a circuit with bovine blood under conditions of pure ultrafiltration, zero net ultrafiltration and dialysis, or combined ultrafiltration and dialysis (countercurrent dialysate flow at rates of 10, 20, and 30 ml/min). In order to permit computation, membrane hydraulic permeability and flow resistances were measured. Dialyzer mass transfer coefficient for urea could not be measured directly and so was determined by fitting model predictions to measured urea clearances. For all conditions of operation, a urea mass transfer coefficient of 0.014 cm/min successfully simulated the data. Predictions of blood flow, filtrate generation rate, and circuit pressure distribution were accurate. At lower dialysate flow rates, urea clearance approximated the sum of dialysate flow and filtration rate. At higher dialysate flows, however, departure from this ideal blood-dialysate equilibrium was observed. Model predictions regarding the relative contributions of diffusion and convection to urea clearance were explored. Under conditions of nearly perfect equilibration of urea between blood and dialysate at the blood inlet, the model predicts that the diffusive clearance of urea will increase with increasing rate of filtration and may exceed the rate of dialysate inflow.     

Pharmacokinetics of levobupivacaine, fentanyl, and clonidine after administration in thoracic paravertebral analgesia

BACKGROUND AND OBJECTIVES: There is little knowledge of the pharmacokinetics of local anesthetics and adjunctive analgesics after paravertebral blockade. We evaluated the pharmacokinetics of low-dose levobupivacaine, fentanyl, and clonidine after paravertebral analgesia for breast surgery. METHODS: Thirty-eight patients receiving paravertebral analgesia for breast surgery received a 19-mL paravertebral bolus of levobupivacaine 0.25% combined with a 1-mL volume of saline (group L, 13 patients), fentanyl 50 microg (group LF, 13 patients), or clonidine 150 microg (group LC, 12 patients) followed 1 hour later by infusion of levobupivacaine 0.1% (L), levobupivacaine 0.05% with fentany l 4 microg/mL (LF), or levobupivacaine 0.05% with clonidine 3 microg/mL (LC), respectively. Plasma concentrations of study drugs were determined at intervals up to 24 hours after bolus injection. RESULTS: There was rapid absorption of levobupivacaine after bolus with mean (standard deviation) maximum plasma concentration (Cpmax) of 0.51(0.24) microg/mL in a median time to maximum concentration tCpmax of 15 minutes. Mean Cpmax fentanyl and clonidine after bolus were 0.62 (0.37) and 0.79 (0.23) ng/mL, in a median tCpmax of 15 and 22.5 minutes, respectively. Mean Cpmax levobupivacaine after infusion was 0.47 (0.41) microg/mL in a median tCpmax of 24 hours. There was progressive accumulation of fentanyl and clonidine at 24 hours with a mean Cpmax of 0.72 (0.33) and 1.74 (0.70) ng/mL, respectively. CONCLUSIONS: After paravertebral bolus and infusion administration, Cpmax levobupivacaine was within the safe range. Cpmax fentanyl and clonidine were less than the effective levels after IV administration, suggesting that their analgesic effect may be partly attributed to a peripheral mechanism of action.     

Fentanyl concentration in maternal and umbilical cord plasma following intranasal or subcutaneous administration in labour

BackgroundThe effect that the route of maternal fentanyl administration has on placental transfer of drug to the neonate is not well studied. Plasma concentration ratios are an indicator of fetal exposure, relative to the mother.MethodsA cohort study (n=30) was conducted to measure fentanyl concentrations in maternal plasma, and arterial and venous cord blood, among women administered either intranasal or subcutaneous fentanyl for labour pain relief. Maternal and cord blood samples were collected within 30 min of birth to determine the fentanyl plasma concentration and to assess relative neonatal exposure. Neonatal outcomes were assessed by Apgar scores, need for resuscitation and nursery admission.ResultsThirty paired samples were obtained from healthy parturients with uncomplicated term pregnancies. Highest observed umbilical venous and arterial concentrations were 0.71 ng/mL and 0.56 ng/mL, respectively, and fetal to maternal fentanyl plasma concentration ratios ranged between 0.23 and 0.73, indicating low fetal exposure. While the total intranasal fentanyl dose administered was significantly higher than the subcutaneous fentanyl dose, this did not result in a higher fetal to maternal ratio. All neonates in both groups had 5-min Apgar scores >7, two neonates required short-term stimulation and oxygen (unrelated to fentanyl) and no neonate was admitted to the nursery.ConclusionThis study is the first to examine fetal and maternal fentanyl concentrations after subcutaneous administration. This research supports the safe use of fentanyl for labour analgesia for women.     

Effect of fluid preload on maternal haemodynamics for low-dose epidural analgesia in labour

We prospectively studied 30 women in labour who requested epidural analgesia. They were randomly allocated into two groups; one received a preload of 7 mL/kg normal saline and the other no preload. All patients had a standard epidural solution consisting of 0.1% bupivacaine 20 mL containing fentanyl 2 microg/mL. Mean arterial blood pressure and cardiac index were measured serially for 20 min after epidural drug administration. Cardiac index was measured using transthoracic electrical bioimpedance (BOMED). Power calculation showed that a sample size of 30 had 80% power to detect a difference of more than 20% in cardiac index using a two-sided test at a significance level of <0.05. No significant changes in cardiac index or mean arterial pressure occurred at any time in either group. These results suggest that routine fluid preloading is not necessary for 0.1% bupivacaine 20 mL with fentanyl 2 microg/mL as epidural bolus in labour.     

Behavior of the histamine level in induction of anesthesia with propofol and methohexital

In a study of the effect of intravenous anesthetics on plasma histamine levels, propofol and methohexital were administered to patients. Histamine determination was performed using an improved fluometric method specific for imidazole derivatives. As a primary step, the plasma histamine concentration was determined in 60 healthy, fasting probands and used as a comparative value. The mean value obtained from 60 examinations was 0.38 +/- 0.12 ng/ml, the median value was 0.37 ng/ml (Table 1). The next step consisted in determination of plasma histamine values in 20 patients 1 h following premedication with fentanyl. In this group, the mean value was 0.33 +/- 0.11 ng/ml, the median value 0.316 ng/ml (Table 2). In another 20 patients the plasma histamine concentration was determined 1 h following intramuscular injection of 1.4 microgram fentanyl +0.07 mg/kg droperidol (Thalamonal). In this group, the mean value was 0.373 +/- 0.11 ng/ml and the median value was 0.736 ng/ml. Subsequently, the effect of 2.5 mg/kg propofol (Disoprivan) or 1 mg/kg methohexital (Brevimytal) on plasma histamine levels was examined in a randomized, prospective study in 22 patients of ASA class I and II (Table 3, Fig. 2). Two minutes prior to injection of the test substances and 2, 4, 8, and 13 min following injection, plasma histamine levels, blood pressure, and heart rate were examined. In both groups, no changes in plasma histamine levels were observed during the period of examination. Comparison of the individual time columns within a group as well as intergroup comparisons revealed no statistically significant differences in either the t test or the Wilcoxon-Mann-Whitney U test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progression of diabetic nephropathy

BACKGROUND: Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/year. The risk factors of losing filtration power (progression promoters) have not been clearly identified. Furthermore, information on optimal arterial blood pressure, glycemic control, and cholesterol levels are lacking. METHODS: We measured GFR with (51)Cr-EDTA plasma clearance technique, blood pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy recruited consecutively during 1983 through 1997. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. In total, 271 patients received antihypertensive treatment at the end of the observation period. RESULTS: Mean arterial blood pressure was 102 +/- 0.4 (SE) mm Hg. The average decline in GFR was 4.0 +/- 0.2 mL/min/year and even lower (1.9 +/- 0.5 mL/min/year) in the 30 persistently normotensive patients, none of whom had ever received antihypertensive treatment (P < 0.01). A multiple linear regression analysis revealed a significant positive correlation between the decline in GFR and mean arterial blood pressure, albuminuria, glycosylated hemoglobin A(1c), and serum cholesterol during follow-up (R(adj)(2) = 0.29, P < or = 0.001). No threshold level for blood pressure, glycosylated hemoglobin A(1c), or serum cholesterol was demonstrated. A two-hit model with mean arterial blood pressure and glycosylated hemoglobin A(1c) below and above the median values (102 mm Hg and 9.2%, respectively) revealed a rate of decline in GFR of only 1.5 mL/min/year in the lowest stratum compared with 6.1 mL/min/year in the highest stratum (P < 0.001). CONCLUSIONS: The prognosis of diabetic nephropathy has improved during the past decades, predominantly because of effective antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters.     

Reduction by Fentanyl of the Cp sub 50 Values of Propofol and Hemodynamic Responses to Various Noxious Stimuli

Background: Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia.

Methods: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation.

Results: The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp sub 50loss of consciousness, 4.4 micro gram/ml (range, 3.8-5.0); Cp50tetanus, 9.3 micro gram/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 micro gram/ml (range, 8.9-10.8); Cp50skin incision, 10.0 micro gram/ml (range, 8.1-12.2); and Cp50intubation, 17.4 micro gram/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50 s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion.     

The effect of modified ultrafiltration on the amount of circulating endotoxins in children undergoing cardiopulmonary bypass

OBJECTIVE: To determine whether the use of modified ultrafiltration during pediatric cardiopulmonary bypass (CPB) diminishes the load of circulating endotoxins. DESIGN: Single-arm prospective observational study. SETTING: A university hospital operating room and intensive care unit. PARTICIPANTS: Twenty children undergoing CPB for correction of various congenital heart diseases. INTERVENTIONS: The amount of endotoxins in plasma was measured during CPB and before and after modified ultrafiltration. The ultrafiltrate was assayed for the presence of endotoxins. Postoperatively, the children were followed with relevant infectious parameters and cultures. MEASUREMENTS AND MAIN RESULTS: The amount of endotoxins increased significantly during the CPB procedure (from a median of 1.3 ng [range, 0 to 13.7 ng] to 24.2 ng [range, 2.1 to 75.9 ng]). After termination of CPB, modified ultrafiltration was shown to lower the amount of circulating endotoxins in blood (from a median of 24.2 ng [range, 2.1 to 75.4 ng] to 9.0 [range, 0.1 to 40.6 ng]). The major bulk of this reduction in endotoxin load was retrieved in the ultrafiltrate (median of 11.9 ng [range, 0 to 12.1 ng]). CONCLUSION: This study strongly suggests that modified ultrafiltration decreases the amount of circulating endotoxins in children undergoing cardiac surgery.     

Effects of fentanyl on baroreceptor reflex control of heart rate in newborn infants

Baroreceptor reflex control of heart rate was studied in ten neonates and young infants before and after intravenous fentanyl (10 micrograms/kg). All infants were in stable condition while being mechanically ventilated. Mean (+/- SD) corrected gestational age was 40.1 +/- 3.7 weeks, mean weight 3120 +/- 700 g. The pressor response was tested using phenylephrine and the depressor response using nitroglycerin. Changes in heart rate (R-R interval) were plotted against changes in systolic arterial pressure, and the slope of the linear portion of this relationship expresses the baroreflex sensitivity. No significant changes in systolic arterial pressure, heart rate, and blood gas values were observed after fentanyl injection when compared to control values. Mean (+/- SEM) control phenylephrine slope was 8.44 +/- 2.05 msec/mmHg, and mean nitroglycerin slope was 2.54 +/- 0.37 msec/mmHg. Both slopes decreased significantly by 48% and 42%, respectively, after fentanyl injection (P less than 0.02). Mean plasma fentanyl concentrations measured at the end of each test were not statistically different (5.11 +/- 0.65 ng/ml and 4.28 +/- 0.58 ng/ml, respectively). This suggests that the baroreflex control of heart rate is present in term neonates and markedly depressed during fentanyl anesthesia. Changes in blood pressure occurring during fentanyl anesthesia have to be carefully considered, because cardiac output is principally rate-dependent in newborns.     

Effect of modified ultrafiltration on bivalirudin elimination and postoperative blood loss after on-pump coronary artery bypass grafting: assessment of different filtration strategies

Abstract Objective: Bivalirudin has a short elimination half‐life of approximately 25 to 30 minutes, but no antidote is available. We assessed the effect of four different strategies of modified ultrafiltration after cardiopulmonary bypass on the bivalirudin elimination and postoperative blood loss. Methods: Five groups of seven patients undergoing elective “on‐pump” coronary artery bypass grafting were enrolled in this controlled randomized investigation. The filtration strategies varied with regard to the filtration flow, the filtrate volume, the addition of vacuum suction to the filter system, and the performance of hemodiafiltration. Filtration was started after weaning from cardiopulmonary bypass (CPB). The cumulative postoperative blood drainage at 12 hours was recorded. Results: Bivalirudin half‐life in the control group was 0.6 ± 0.11 hours, and the blood loss was 958 ± 472 mL. Hemofiltration with a constant flow of 300 mL/m² body surface area/min and a filtrate volume of 3000 mL reduced the elimination half‐life significantly to 0.47 ± 0.11 hours. Adding the process of dialysis to hemofiltration resulted in a half‐life of 0.52 ± 0.04 hours and reduced the 12‐hour postoperative blood loss significantly, compared to the control group, to 444 ± 220 mL. The other strategies failed to augment the bivalirudin elimination and postoperative drainage effectively. Conclusion: Zero‐balanced modified hemodiafiltration without addition of vacuum suction is effective in improving the elimination of bivalirudin after CPB and reducing the postoperative blood loss. Zero‐balanced hemodiafiltration should be considered for the augmented elimination of bivalirudin in complex surgical procedures with a high risk of bleeding complications. However, larger investigations are warranted to confirm these results.     

Effects of immediately initiating an epidural infusion in the combined spinal and epidural technique in nulliparous parturients

BACKGROUND AND OBJECTIVES: Intrathecal fentanyl with bupivacaine provides rapid labor analgesia of limited duration. We investigated the effect of initiating an epidural infusion of 0.1% ropivacaine with fentanyl 2 microg/mL and epinephrine 1:400,000 (REF) on the duration of analgesia and incidence of side effects after intrathecal injection in the combined spinal and epidural technique. METHODS: Thirty-four nulliparous parturients with a cervical dilation of 3 to 5 cm were randomized to receive epidural saline or REF at 10 mL following the intrathecal injection of fentanyl 25 microg and bupivacaine 2.5 mg. Degree of analgesia, severity of pruritus, motor block, blood pressure, and sensory level to coolness were assessed until the patient requested additional analgesia. RESULTS: Analgesia was significantly longer in the REF group, 158.4 +/- 59.6 minutes versus 103.8 +/- 26.2 minutes. The decrease in blood pressure compared with the blood pressure at intrathecal injection was greater for the REF group at all times, but achieved statistical significance at 60 minutes. There was no difference in ephedrine use, pruritus, or motor block between groups. There was no difference in sensory level to coolness at 90 minutes after intrathecal injection between groups. CONCLUSIONS: Initiating an infusion of REF prolongs the duration of analgesia, but also results in a greater decrease in blood pressure. Despite this effect on blood pressure, there was no difference in ephedrine use.     

Comparison of fentanyl and tramadol in pain therapy with an on-demand analgesia computer in the early postoperative phase

17 patients undergoing cholecystectomy in non-opiate general anaesthesia received tramadol (n = 7) or fentanyl (n = 10) for immediate postoperative pain relief using the on-demand analgesia computer (ODAC). Heart rate, blood pressure, and respiratory rate were monitored at half-hourly intervals during the 6-h trial period. Arterial blood was withdrawn at hourly intervals for blood gas analyses and beta-endorphin plasma level assays. Fentanyl and tramadol serum levels were determined prior to each on-demand bolus injection during the first 2 h of the study. At the end of the trial period, the quality of analgesia was assessed retrospectively using a visual analog scale. Mean opiate consumption was 0.53 +/- 0.1 mg for fentanyl and 412 +/- 11.6 mg for tramadol, resulting in an equipotency ratio of about 1:980 (relating to body wt., consumption/h, and pain score). No correlation was found between body wt.-based opiate requirements and pain score. Heart rate increased slightly but significantly under both opiates. Fentanyl produced a significant drop in mean arterial pressure by a maximum of 16%, while tramadol left mean arterial pressure unchanged. Respiratory rate, which was elevated initially, dropped significantly in both groups. Arterial pO2 and pCO2 were within the normal range throughout the observation period, reflecting the absence of respiratory side effects. Opiate blood levels showed major inter- and intraindividual variations (minimal and maximal levels for fentanyl ranged from 0.44-3.44 ng/ml, for tramadol from 272-1,900 ng/ml) and were thus poor predictors of the quality of analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of fentanyl on peripheral and cerebral hemodynamics in neonatal lambs

The effects of fentanyl or cardiovascular function, regional distribution of cardiac output, and the dose required for producing anesthesia were studied in ten previously catheterized, newborn lambs. In addition, the effects of fentanyl on cerebral blood flow and oxygen utilization were examined. Fentanyl in cumulative doses as high as 4.4 mg/kg (average plasma levels of 646 +/- 95 ng/ml, maximum plasma level of 862 ng/ml) did not reliably produce anesthesia as assessed by tail and foot clamping, although it did cause profound respiratory depression. With normocapnia maintained by mechanical ventilation, fentanyl did not alter cerebral oxygen delivery or consumption, and the two remained coupled. Fentanyl did not affect cardiac output, heart rate, or mean arterial blood pressure at the highest dose level, nor did it reduce blood flow to specific organ beds, other than the kidney. Thus, the hemodynamic stability seen with fentanyl in the lamb does not occur at the expense of reduced blood flow to organs, such as the gastrointestinal tract or brain, that are particularly vulnerable in the neonate.     

Zusatz von Fentanyl zur Bupivacain – Periduralanalgesie bei Sectio Caesarea

Epidural anaesthesia for elective caesarean section can have advantages over general anaesthesia. The anaesthesiologist can avoid endotracheal intubation as well as fetal depression following placental transfer of systemic anaesthetics. However, despite reaching an effective blockade preoperatively, intraoperative discomfort and pain may occur during epidural anaesthesia with local anaesthetics alone, necessitating supplemental systemic analgesics or even conversion to general anaesthesia [21]. Addition of epidural fentanyl has been shown to improve onset and quality of perioperative analgesia without evident side effects for mother or newborn [24]. Nevertheless, administration of epidural opioids before cord clamping is still hotly debated, some fearing maternal and or neonatal depression [6, 26]. The aim of the present study was to investigate the quality of analgesia, associated side effects and the resulting maternal and neonatal plasma opiate concentrations after a single preoperative addition of 0.1 mg fentanyl to epidural bupivacaine analgesia in comparison to epidural bupivacaine analgesia alone. Methods. Following governmental and ethics committee approval, 43 elective consenting patients for caesarean section were randomized to receive double-blind injections of either 8 ml 0.5% bupivacaine+0.1 mg fentanyl (B+F group, n=22) or 8 ml 0.5% bupivacaine +2 ml saline (Bup group, n=21) into an epidural catheter. In both groups additional injections of bupivacaine were given to achieve sensory blockade up to T4. Systolic blood pressure, heart and respiratory rates were measured regularly. Quality of intraoperative pain relief was assessed at delivery, uterine eventration, and during uterine and abdominal closure using a visual analogue scale (VAS). The duration of postoperative analgesia was compared between groups, as well as the incidence of nausea, itching or sedation. Similarly, Apgar scores and umbilical arterial and venous blood gas analyses were compared. Fentanyl concentrations were determined in maternal venous blood sampled before and 20 and 40 min after epidural injection and at birth, and in umbilical venous and arterial blood sampled after delivery. Radioimmunoassay analysis was performed from plasma specimens centrifuged and frozen at ?20° C [19]. The statistical level of significance was defined as P<0.05. Results. Groups were comparable regarding age, weight and time of gestation. Total bupivacaine doses and injection to delivery times were similar in both groups. Figure 1 shows that there were 40% more pain-free (VAS=0) patients in the B+F group during uterine eventration and wound closure (P<0.05). Mean postoperative duration of analgesia was significantly longer in the B+F group (382 vs 236 min). The rate of nausea and mild itching was significantly higher in the B+F group. Respiratory depression was never detected in patients or newborns. Small group differences in blood pressure or respiratory rate were inconstant and clinically irrelevant, as were differences in umbilical venous pCO₂. One hundred and twenty-five blood samples were analysed for fentanyl concentrations. The mean fentanyl concentration before epidural injection was not zero, but 0.25 ng/mg (range 0.02–0.32). Maternal concentrations at 20 and 40 min after injection were 0.55 ng/ml (0.12–1.14) and 0.52 ng/ml (0.26–1.04) (Fig. 3). At delivery, mean maternal fentanyl concentration was 0.58 ng/ml (0.14–1.18); mean umbilical arterial and venous concentrations were 0.51 ng/ml (0.04–1.8) and 0.41 ng/ml (0.18–1.2), respectively. Rare results of fentanyl concentrations >1.0 ng/ml correlated neither with sedation, maternal respiratory rate and side effects, nor with Apgar scores and umbilical blood gas values. No Apgar score at 5 min was below 9, and no umbilical pH was below 7.20. Conclusion. We conclude that preoperative epidural addition of 0.1 mg fentanyl to 0.5% bupivacaine significantly improves intraoperative pain relief during elective caesarean section and prolongs postoperative analgesia. This important advantage of fentanyl is associated with an increased incidence of nausea and mild itching. No clinically significant fentanyl-associated depression of vigilance could be detected in the mother or newborn. The resulting plasma fentanyl concentrations are within safe limits. When administered epidurally and preoperatively for caesarean section, maternal plasma levels of fentanyl do not decrease significantly until birth. In the radioimmunoassay an unknown substance cross-reacts like fentanyl.     

Fentanyl does not alter the "sleep" plasma concentration of thiopental.

Thiopental and fentanyl are commonly combined for induction of anesthesia. The effect of an analgesic concentration of fentanyl on the plasma concentration of thiopental to induce sleep was studied in 46 unpremedicated patients. As a measure of drug effect, sleep (the lack of response to open eyes to a verbal command) was used. Forty-six patients were randomized to receive thiopental infused to one of several predetermined plasma concentrations. Twenty-two of these patients also received a fentanyl infusion to a desired analgesic concentration of 1 ng/mL. Thiopental and fentanyl were infused by means of a pharmacokinetic model-driven infusion device (computer-assisted continuous infusion, CACI). Venous blood samples were taken from the contralateral antecubital fossa at 5 and 10 min after the start of the infusion. At 10 min, the patients' names were firmly spoken, and they were instructed to open their eyes. If they did not respond to this command, they were considered to be asleep. Only patients in whom the 5- and 10-min measured plasma concentrations of thiopental and fentanyl, respectively, were within +/- 30% of each other were used for the determination of the Cp50(asleep), the plasma concentration at which 50% of the patients were asleep. The Cp50(asleep) with and without fentanyl was calculated by logistic regression. The Cp50(asleep) for patients in whom concentrations were maintained within +/- 30% for thiopental alone (n = 17) was 7.32 micrograms/mL (95% confidence interval, 5.53-10.95); for thiopental in the presence of fentanyl (n = 18 with a measured fentanyl concentration of 1.27 +/- 0.5 ng/mL), this was 7.22 micrograms/mL (95% confidence interval, 4.83-10.15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hydroxyethylstarch 6% preload does not prevent the hypotension following induction with propofol and fentanyl

PURPOSE: To study the effects of volume preload with hydroxyethylstarch 6% (HES) on the changes in arterial blood pressure and heart rate following propofol/fentanyl induction of anesthesia. METHODS: Seventy five patients, divided into three groups, scheduled for orthopedic surgery were allocated randomly to receive either no preload or 500 ml, or 1000 ml of 6% HES respectively over 20 minutes period prior to anesthetic induction. Anesthesia was induced with fentanyl 1.5 microg.kg(-1) and propofol 2.5 mg.kg(-1). Cardiovascular parameters were monitored for 5 minutes following induction. RESULTS: Systolic blood pressure (SBP) decreased significantly (P<0.001) in all groups after anesthetic induction. Blood pressure recorded at 5 minutes was 76% of the baseline values in the control group and in the HES 500 group and was 78% in the HES 1000 group. Changes in the diastolic blood pressure (DBP) and mean blood pressure (MBP) were also similar in the three groups. There was no significant difference between the three groups in the HR decline too. CONCLUSION: Administration of 6% HES as a preload did not attenuate the decrease in blood pressure following induction of anesthesia with propofol and fentanyl.     

Combinations of fentanyl and levobupivacaine for post-thoracotomy pain

The aim of the present study is to evaluate the analgesic activity, patient satisfaction, and side effect profile of different concentrations of levobupivacaine plus fentanyl administered through thoracic epidural patient-controlled analgesia in patients undergoing thoracotomy. The study included 60 patients who were randomly divided into three groups. At the end of the surgery, group I (n = 20) received 0.125% levobupivacaine plus 3 mg fentanyl, group II received 0.1% levobupivacaine plus 3 mg fentanyl, and group III received 0.05% levobupivacaine plus 3 mg fentanyl via an epidural catheter placed at the level of T_10-11 or T_11-12. For all groups, the patient-controlled analgesia device was programmed to deliver a loading dose of 14 mL at an infusion rate of 4 mL/h, and a bolus dose of 2 mL/h, with a locked out interval of 15 minutes and 60 mL of a 4-hour limit. The following parameters were evaluated at 5, 10, 15, 20, 30, and 40 minutes and at 1, 2, 4, 8, 16, and 24 hours after admission to the intensive care unit, at which nausea and vomiting scales, Visual Analog Scale I-II, Ramsay sedation scale, Bromage scale, pupil diameter, arterial blood pressure, heart rate, respiratory rate, and SpO₂ were measured and recorded. Any side effect was also documented. As the result of the evaluation, visual Analog Scale I-II scores, patient satisfaction scores, mean arterial blood pressure, and heart rate significantly differed in group I as compared with groups II and III. No side effects were encountered except mild nausea, which was seen in group III and did not require treatment. Motor blockage, pupil size, respiratory rate, and SpO₂ were not monitored in any of the patients in all groups. In conclusion, our study suggested that the use of 0.125% levobupivacaine, together with 3 mg/mL fentanyl, constitutes a good combination, and can be used safely without causing hemodynamic change and motor block.