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Transdermal fentanyl in opioid-naive cancer pain patients: an open trial using transdermal fentanyl for the treatment of chronic cancer pain in opioid-naive patients and a group using codeine.

To treat cancer pain, physicians often decide to jump directly from step 1 of the World Health Organization (WHO) analgesic ladder to step 3. The use of transdermal fentanyl in patients with cancer pain who had either used no opioid before, or only codeine, is evaluated in the present trial. Both opioid-naive (N = 14) and codeine-using (N = 14) patients started with transdermal fentanyl in the lowest available delivery rate (25 microg/hr). Immediate-release oral morphine was present as "rescue" medication. Transdermal fentanyl provided good to excellent pain relief in the majority (68%) of these patients. During the study, 5 patients continued with 25 microg/hr, and the others used a higher dose. Clinically relevant respiratory depression was not observed. The common side effects of opioids were found; constipation was mentioned by 3 patients (11%). Transdermal fentanyl appeared a safe analgesic in these opioid-naive cancer pain patients. In this study, WHO step 2 could be skipped without untoward complications.

Administration, Cutaneous↗

Propofol-fentanyl versus isoflurane-fentanyl anesthesia for coronary artery bypass grafting: effect on myocardial contractility and peripheral hemodynamics.

To avoid intraoperative awareness and postoperative respiratory depression from high-dose opioid anesthesia, propofol (P), or isoflurane (I) has been combined with moderate-dose opioid with varying results. However, the effects of both P and I on myocardial contractility and left ventricular afterload have not been completely quantified. The end-systolic pressure-diameter relationship (ESPDR) of the left ventricle (LV) is a reliable method to quantitatively assess LV contractility because it is relatively independent of changes in preload and incorporates afterload changes. The purpose of this study was to quantify the cardiodynamic effects of propofol-fentanyl (PF) anesthesia in comparison with isoflurane-fentanyl (IF) anesthesia in patients undergoing coronary artery bypass grafting (CABG). Thirty patients with normal or moderately impaired LV function (ejection fraction > or = 40% with LV end-diastolic pressure < or = 18 mmHg, no preoperative akinesia or dyskinesia) undergoing elective CABG were studied. After premedication with flunitrazepam, 2 mg orally, all patients were induced with thiopental, 1 mg/kg, fentanyl, 20 micrograms/kg, and vecuronium, 0.1 mg/kg, and were ventilated with oxygen/air (F(1)O2 0.6). Anesthesia was maintained throughout the procedure with a zero-order intravenous (IV) continuous infusion of P, 3 mg/kg/h (PF group), or with isoflurane inhalation of 0.6% (IF group), supplemented by intermittent boluses (5 micrograms/kg) of fentanyl (up to a total maintenance dose of 30 micrograms/kg). After intubation, a cross-section of the LV was visualized by two-dimensional transesophageal echocardiography and an m-mode echocardiogram was obtained at the maximum anterior-posterior diameter. The radial artery pressure tracing and the ECG were simultaneously recorded with the M mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of extradural fentanyl, bupivacaine and two fentanyl-bupivacaine mixtures of pain relief after abdominal surgery.

Fentanyl 50 micrograms, bupivacaine 50 mg and two mixtures containing fentanyl 50 micrograms and bupivacaine 25 mg or 12.5 mg (0.25 and 0.125%), respectively, in a volume of 10 ml were administered via thoracic extradural catheters to 24 patients after major abdominal surgery. All patients received all four treatments, in a randomized order, so that each patient received one of the 24 possible combinations of the four treatments. Pain relief was assessed by a linear analogue pain scale and the Prince Henry Hospital pain score. The duration of pain relief, effects on ventilatory frequency, heart rate, arterial pressure and central venous pressure were also recorded. Mean reductions in the analogue pain scale for fentanyl, bupivacaine, and fentanyl in 0.25% and 0.125% bupivacaine were 80 (SEM 5) %, 87 (4) %, 86 (5) % and 77 (5) %, respectively (ns). Pain scores decreased by 62 (6) %, 83 (5) %, 77 (6) % and 72 (6) %, respectively (ns). Mean arterial pressure decreased to 90 (2) %, 70 (2) %, 81 (2) % and 82 (3) %, respectively, of pretreatment values. In this respect, bupivacaine alone was significantly different from the three other treatments (P < 0.001). Hypotension (reduction in arterial pressure greater than 25% of pretreatment mean arterial pressure) was also more frequent after bupivacaine alone (P < 0.01). Effects on ventilation, heart rate and central venous pressure did not differ between the four treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗

The comparison of epidural fentanyl, epidural lidocaine, and intravenous fentanyl in patients undergoing gastrectomy.

This study was conducted prospectively to compare the effect of epidural fentanyl (EP-F), epidural lidocaine (EP-L), and intravenous fentanyl (IV-F) on hemodynamic and hormonal responses to surgery and postoperative analgesic requirement in 30 patients undergoing gastrectomy during isoflurane anesthesia. An epidural catheter was placed via the T8-9 interspace. Group EP-F received fentanyl 2 micrograms/kg in 10 mL saline, and Group EP-L, 10 mL 1.5% lidocaine, epidurally; Group IV-F was given fentanyl, 2 micrograms/kg, IV. Fifty percent of the original dose was repeated every hour. Hemodynamic data and plasma hormonal levels were compared between those before and those at 1 h after skin incision. The total number of analgesic administrations within the first 48 h postoperatively were compared. Group EP-L developed more frequent episodes of hypotension. Group IV-F required higher isoflurane concentrations and the plasma epinephrine levels increased more than in Groups EP-F and EP-L. In Groups EP-L and IV-F, the plasma antidiuretic hormone (ADH) level increased more than in Group EP-F. In Groups EP-F and IV-F, the plasma cortisol and adrenocorticotropic hormone (ACTH) levels increased more than in Group EP-L. The use of postoperative analgesics was significantly less in Group EP-F. In conclusion, in Group EP-F, attenuated hormonal responses to surgery was accompanied with less hypotension and postoperative analgesic requirements were reduced.

Adjuvants, Anesthesia↗

Chest wall rigidity during fentanyl- and midazolam-fentanyl induction: ventilatory and haemodynamic effects.

In a double-blind randomised study, we examined if pretreatment with small doses of midazolam, given before anaesthesia induction with fentanyl, influences the occurrence of fentanyl-induced thoracic rigidity (FITR). At the same time, the effect of rigidity on the cardiovascular and respiratory system was assessed. Sixteen patients undergoing coronary artery bypass surgery were divided into two groups. The midazolam group (M) received 0.075 mg/kg midazolam i.v. and the placebo group (P) NaCl 0.9% 3 min before the start of fentanyl induction. During the induction period, FITR was assessed clinically on a 3-point scale. Haemodynamic and respiratory variables were collected before anaesthesia induction, at the end of the fentanyl infusion and 3 min after intubation. The incidence of FITR was high in both groups: 63% in Group M and 75% in Group P (n.s.); however, its severity was less in Group M. The appearance of rigidity affected the cardiovascular and the respiratory system: central venous and pulmonary capillary wedge pressures showed a sharp increase in patients with FITR accompanied by CO2 retention, due to an inability to ventilate these patients adequately. We conclude that small doses of midazolam do not prevent, but may attenuate, FITR and that the appearance of rigidity causes alterations of haemodynamic and respiratory variables during induction.

Clinical Trials as Topic↗

Premedication for nonemergent neonatal intubations: a randomized, controlled trial comparing atropine and fentanyl to atropine, fentanyl, and mivacurium.

OBJECTIVE: The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure. PATIENTS/METHODS: This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of < or = 85%, < or = 75%, < or = 60%, and < or = 40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium. RESULTS: Analysis of 41 infants showed that incidence of oxygen saturation < or = 60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration < or = 85%, 75%, and 40%; cumulative time > or = 30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in < or = 2 attempts significantly more often in the mivacurium group (35% vs 71%). CONCLUSIONS: Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.

Adjuvants, Anesthesia↗

Comparison of equivalent doses of fentanyl buccal tablets and arteriovenous differences in fentanyl pharmacokinetics.

BACKGROUND: The fentanyl buccal tablet (FBT) is designed to enhance the rate and extent of fentanyl absorption through the buccal mucosa. AIM: To evaluate the bioequivalence of microg-equivalent doses of FBT administered as single and multiple tablets and assess differences in the arterial and venous pharmacokinetics of FBT in healthy volunteers. METHODS: Twenty-seven healthy adults, aged 19-45 years, participated in the randomised, open-label, three-period, crossover study. In the first two periods, FBT was administered as four 100 microg tablets simultaneously or one FBT 400 microg to assess bioequivalence. Venous blood samples were obtained over a 72-hour period to measure plasma fentanyl concentrations. In the third period, arterial and venous blood samples were obtained simultaneously from before administration of one FBT 400 microg through 4 hours after administration to evaluate the impact of arterial versus venous sampling on the pharmacokinetic profile. As subjects were not opioid tolerant, naltrexone was administered to block opioid receptor-mediated effects of fentanyl. Adverse events were recorded throughout. RESULTS: Maximum plasma concentration (C(max)) and area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) on average were approximately 12% and 13% higher, respectively, for FBT administered as four 100 microg tablets simultaneously compared with one FBT 400 microg. Maximum plasma concentrations in the arterial circulation were approximately 60% higher and occurred 15 minutes earlier than those measured from the venous circulation. No serious adverse events were reported during the study. CONCLUSION: Despite small differences in C(max) and AUC(infinity) (on average 12% and 13%, respectively), FBT administered as four 100 microg tablets simultaneously compared with one 400 microg tablet did not meet the criteria for bioequivalence. An increased surface area exposure with four tablets compared with one tablet may account for the slightly higher maximum concentrations observed with four 100 microg tablets. A substantially higher C(max) was reached earlier in the arterial than in the venous circulation.

Administration, Buccal↗

Comparison of propofol-fentanyl or midazolam-fentanyl intravenous anaesthesia for carotid endarterectomy.

Carotid endarterectomy has become a standard surgical operation in the therapy of cerebrovascular insufficiency. The cardiovascular status of the patients needs special attention, since the long-term prognosis is predominantly influenced by concomitant coronary artery disease. General anesthesia techniques are raising the challenge of maintaining cardiovascular stability and establishing adequate cerebral monitoring. Randomly selected 30 patients gave informed consent to this approved study. Fifteen patients were anaesthetised with propofol-fentanyl or midazolam-fentanyl combined with N2O-O2. Haemodynamic parameters (mean arterial pressure, heart rate) showed not significant changes during anaesthesia. Recovery profil proved to be significantly better after propofol-fentanyl compared to midazolam-fentanyl anaesthesia.

Anesthesia Recovery Period↗

Propofol and fentanyl compared with midazolam and fentanyl during third molar surgery.

PURPOSE: The purpose of this study was to measure the safety and efficacy of propofol combined with fentanyl as sedative agents during third molar outpatient surgery. PATIENTS AND METHODS: A double-blind, prospective, randomized clinical trial involving 57 patients undergoing removal of third molars under intravenous sedation between November 1994 and December 1995 was performed. Patients randomly received either propofol and fentanyl (P + F, th = 24) or midazolam and fentanyl (M + F, M = 33). Patient demographics, Corah anxiety scores, and physiologic parameters were determined preoperatively. All medications were titrated to the same clinical end point for sedation. Intraoperative physiologic parameters, cooperation, alertness, and pain scores were assessed. Postoperative recovery and degree of amnesia also were determined. RESULTS: There were no significant differences in either patient demographics or surgical characteristics between groups. The P + F group was significantly less cooperative than the M + F group. Pain during injection of propofol was a significant adverse side effect. Both groups experienced a small percentage of apneic episodes, but mechanical ventilation was never required. There were no differences in recovery between groups as measured by the Treiger dot test and psychomotor recovery scores. The degree of anterograde amnesia was greater for the M + F group, although the difference was not statistically significant. Sedation was rated good to excellent by the patient, surgeon, and observer, and there were no statistically significant differences between groups. CONCLUSION: Propofol appears to be a safe and efficacious drug for use during outpatient oral surgical procedures.

Adolescent↗

Thoracic epidural infusions for post-thoracotomy pain: a comparison of fentanyl-bupivacaine mixtures vs. fentanyl alone.

A randomised double-blind clinical trial was conducted on 106 patients scheduled for pulmonary resection. Patients received an epidural infusion containing 0.1%, 0.2% bupivacaine or saline in combination with fentanyl 10 microgram.ml -1. Adequacy of analgesia was assessed at rest and during movement over 24 h. Analgesic efficacy was assessed using visual analogue scores and an observer/verbal ranking scale. Pain scores were higher in the fentanyl-only group at the 2 h assessment (p < 0.05). Otherwise, there were no between-group differences in pain scores or in the total amounts of epidural solution used. All patients received continuous haemodynamic monitoring. There were no between-group differences in the number of episodes of hypotension or in the number of interventions for hypotension. However, the use of intra-operative vasopressor and the incidence of temporary neurological complications was higher in the 0.2% bupivacaine group (p < 0.05). We conclude that, in the early postoperative period, the addition of bupivacaine 0.1% improves fentanyl epidural analgesia in patients undergoing lung resection and is not associated with the disadvantages seen with the addition of bupivacaine 0.2%.

Adult↗

Sevoflurane-fentanyl versus etomidate-fentanyl for anesthetic induction in coronary artery bypass graft surgery patients.

OBJECTIVE: To compare the hemodynamic effects of sevoflurane-fentanyl with etomidate-fentanyl during anesthetic induction in patients with coronary artery disease with good left ventricular function. DESIGN: A prospective randomized trial. SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were allocated randomly to receive either 4% sevoflurane/nitrous oxide 67%/oxygen 33% (sevoflurane group) or etomidate, 0.2 mg/kg, for induction (intravenous group). Both techniques were supplemented by 10 microg/kg of fentanyl and muscle relaxation with pancuronium. Anesthesia was maintained in both groups with 2% sevoflurane/nitrous oxide 67%/oxygen 33%. MEASUREMENTS AND MAIN RESULTS: Time to loss of consciousness and airway complications during induction were assessed. Hemodynamics were recorded at 1-minute intervals during the induction period up to 5 minutes postintubation. Induction of anesthesia was significantly faster in patients given etomidate compared with patients who received sevoflurane; loss of eyelid reflex was 45 seconds (standard deviation 17 seconds) versus 97 seconds (standard deviation 20 seconds). None of the patients who received sevoflurane had airway complications during the induction period. Both anesthetic induction techniques provided cardiostability with little change in cardiac index (2%). The decrease in mean arterial blood pressure was greater in the patients who received sevoflurane induction (maximal decrease 28% v 14%). The heart rate and filling pressure changes were insignificant. CONCLUSION: Sevoflurane inhalation induction produced minimal changes in cardiac index and no airway complications in patients with coronary artery disease with good left ventricular function. Induction was faster with etomidate, however, and blood pressure remained higher.

Anesthesia, General↗

Propofol and fentanyl anaesthesia for patients with low cardiac output state undergoing cardiac surgery: comparison with high-dose fentanyl anaesthesia.

We have compared the haemodynamic effects of an infusion of propofol 8 mg kg-1 h-1 followed by 4 mg kg-1 h-1 and fentanyl 15 micrograms kg-1 (group 1) with midazolam 3-6 mg and fentanyl 60 micrograms kg-1 (group 2) in patients with a low cardiac output state undergoing cardiac surgery. Heart rate was lower in group 1 throughout the period before cardiopulmonary bypass. There were no significant differences between the groups in other measured variables. Arterial pressure decreased in both groups after induction, by 21% in group 1 and 18% in group 2. Thermodilution assessment of right ventricular ejection fraction was unchanged. Myocardial contractility was not affected adversely. Patients in group 1 who received an infusion of propofol and a smaller dose of fentanyl awakened sooner and the trachea was extubated earlier.

Adult↗

Hemodynamic effects of anesthetic induction with eltanolone-fentanyl versus thiopental-fentanyl in coronary artery bypass patients.

We evaluated the hemodynamic profile of eltanolone and fentanyl versus thiopental and fentanyl anesthetic induction in patients with documented coronary artery disease. Fifty patients scheduled for coronary artery bypass grafting were randomly assigned to two treatment groups (25 patients each). Anesthesia was induced by eltanolone (0.5 mg/kg) or by thiopental (3 mg/kg). Each patient also received 3 micrograms/kg fentanyl and 0.1 mg/kg vecuronium. Heart rate, arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, and cardiac output were determined in the awake state, 2 min after induction of anesthesia, and at 1 and 5 min after intubation, which was performed 3 min after induction. Between-group statistics showed significantly (P < 0.05) lower mean arterial pressure and systemic vascular resistance for eltanolone-treated patients at all measuring points. Pulmonary capillary wedge pressure was lower at 1 min after intubation; left ventricular stroke work index was lower at 1 and 5 min after intubation in the eltanolone group. We conclude that the lower mean arterial pressure with eltanolone as compared to thiopental is a result of greater peripheral vasodilation.

Adult↗

Haemodynamic comparison of propofol-fentanyl anaesthesia with midazolam-fentanyl anaesthesia in CABG patients without preoperative heart failure.

This study was designed to compare prebypass haemodynamics under total intravenous anaesthesia (TIVA) using midazolam-fentanyl (group M) and propofol-fentanyl (group P) combinations. Sixteen adult patients undergoing CABG were studied with patients in group M and P (n = 8 each) given intravenous midazolam 0.1 mg.kg-1.h-1 and propofol 4 mg.kg-1.h-1 with fentanyl 25 micrograms.kg-1 until sternotomy, respectively. Following induction of anaesthesia, cardiac index and heart rate decreased significantly (30% and 20% in both groups, p < 0.05) these variables returned to baseline on completion of sternotomy. In addition, in group P mean arterial pressure decreased significantly (about 15%) following induction and there were no ischaemic signs. Overall for MAP there was no significant difference between the two groups. LVSWI and RVSWI were reduced by around 25% in both groups. Only the change in LVSWI reached statistical significance (p < 0.05). This reduction may have exert a caridioprotectant action by decreasing myocardial oxygen consumption. We conclude that both TIVA techniques represent an acceptable anaesthetic regimen for use in cardiac anaesthesia.

Aged↗

Comparison of the length of stage II labor and incidence of forceps and cesarean delivery after epidural infusion of 0.125% bupivacaine with 2 mu/mL fentanyl as compared with 0.0625% bupivacaine with 2 mu/mL fentanyl.

A large, retrospective chart review was conducted to analyze the length of stage II labor and instrumental and cesarean-section delivery rates in nulliparous women who received either 0.0625% bupivacaine with 2 mu/mL fentanyl or 0.125% bupivacaine with 2 mu/mL fentanyl. Data collected included length of stage II labor, incidence of operative or instrumental delivery rates, concentration of bupivacaine used, and demographic data. Demographics obtained included maternal age, weight, and height, as well as neonatal gestational age, weight, and Apgar scores. Further investigated were additional analgesic requirements of supplemental boluses of local anesthetic between the groups. No differences in demographics were noted between the groups. Instrumental delivery rates were similar between the groups with an incidence of 17.5% in the 0.125% bupivacaine group versus a 15% incidence in the 0.0625% bupivacaine group. Cesarean delivery rate was 17% in the 0.125% bupivacaine group versus a 21% ratio in the 0.0625% bupivacaine group. Duration of stage II labor was noted to be prolonged in the 0.125% bupivacaine group but was not statistically significant. Based on this data, it can be concluded that the use of 0.125% bupivacaine with 2 mu/mL fentanyl does not cause a statistically significant increase in instrumental or cesarean delivery rates, nor does it have a detrimental effect on length of stage II labor.

Adjuvants, Anesthesia↗

Epidural for labour analgesia--bupivacaine + fentanyl vs bupivacaine + fentanyl + epinephrine.

A prospective and randomized study was conducted on 50 full term parturients undergoing labour analgesia at Panna Dai Hospital, R.N.T. Medical College, Udaipur. The parturients were allocated in two groups: group BF (n = 25) received an epidural injection of bupivacaine (0.15%; 15 mg) + Fentanyl (0.0002%); 2 microg/ml); group BEF (n = 25) bupivacaine (0.15%; 15 mg) + Fentanyl (0.0002%; 2microg/ml) + Epinephrine (1.7 microg/ml; 1:600,000). Subsequent top up (same as bolus) was administered at VAS > or = 3. Comparison between the two groups showed no significant difference in onset of analgesia, number of top up doses, degree of motor block and parturients acceptance. The difference in duration of analgesia with addition of epinephrine (93.00 +/- 29.00 min : BEF group; V/S 86.00 +/- 27.00 Min : BF group) did not show any statistical significance between the two groups. Ambulation was achieved in 100% of parturients from both study groups. The incidence of spontaneous delivery was 92% in each group. Parturients in group BEF demonstrated a higher incidence of side effects like nausea and vomiting (4% v/s 0%); hypotension (4% v/s 0%); paresis (8% v/s 0%) and retention of urine (12% v/s 8%) as compared to BF group. To conclude, the addition of epidural epinephrine (1:600,000) to bupivacaine and fentanyl does not affect the duration or quantity of labour analgesia.

Adjuvants, Anesthesia↗

Epidural anaesthesia for caesarean section: a comparison of 0.5% bupivacaine plain, 0.5% bupivacaine plus 100 micrograms fentanyl and 0.5% bupivacaine plus 50 micrograms fentanyl.

Thirty-one healthy women who underwent Caesarean section were studied in a double-blind trial to compare the effectiveness of epidural 0.5% bupivacaine plain, 0.5% bupivacaine plus 100 micrograms fentanyl and 0.5% bupivacaine plus 50 micrograms fentanyl in the prevention of intraoperative pain. There was no difference in the quality of analgesia between the three groups. The incidence of complications was significantly higher in the 0.5% bupivacaine plus 100 micrograms fentanyl group compared with the other two groups.

Adult↗

[Repeated addition of fentanyl to bupivacaine peridural analgesia in labor. Clinical action and fentanyl plasma level].

A combination of epidural opioids with local anaesthetics has been used to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alone. The addition of epidural fentanyl (F) produces highly effective analgesia, the only side effect being mild itching. Initial trials investigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain perception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for fear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100 micrograms F to be safe and the investigators speculated that repeated addition of epidural/F to injection of local anaesthetic may prove beneficial for the parturient without exposing the mother or fetus to risk. We therefore studied maternal analgesia, maternal and umbilical plasma levels and associated side effects following repeated addition of 100 micrograms F to bupivacaine epidural analgesia during labor. METHODS. Following institutional and governmental approval 53 parturients were randomly assigned to receive either 8 ml bupivacaine 0.25% + 0.1 mg fentanyl (B + F group; n = 28) or 8 ml bupivacaine 0.25% + 2 ml saline (BUP group; n = 25) in an epidural catheter at L2/3. The same dose was reinjected upon the patients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effects were recorded before and following each epidural injection. Pain relief was determined at each injection and following cord clamping using the visual analogue pain scale (VAS; 0-100 mm). Maternal venous blood samples were collected to measure plasma F concentrations before and 20 and 40 min after each injection and at birth when umbilical venous and arterial blood was obtained. After centrifugation the samples were maintained at -20 degrees C and then analyzed by radioimmunoassay. At delivery, Apgar scores and umbilical venous and arterial blood gas values were determined. RESULTS. Both groups were comparable for age, weight, height, gestational age and parity. A total of 48 epidural injections were evaluated in the B + F group, 43 in the BUP group. No statistically significant group difference was found between the frequency of injections per delivery (B + F: 2.2; BUP: 1.8); regarding the time between the initial and the first top-up dose (B + F: 144 min; BUP: 140 min) or regarding the interval between the last injection and birth (B + F: 94 min; BUP; 90 min). However, the quality of pain relief during labor and particularly at birth was significantly improved by F (mean VAS in B + F group: 6 mm; mean VAS in BUP group: 42 mm). Mild itching was observed in 43% of patients receiving F, moderate shivering in 13% versus 40% in patients not receiving F. At control mean maternal F plasma levels were not zero but 0.25 ng/ml. After the initial injection and following the first and second top-up dose mean maximum maternal F plasma concentrations were 0.54 ng/ml (+/-0.32; +/-SD), 0.88 ng/ml (+/-0.62) and 1.06 ng/ml (+/-0.4) (range 0.18-2.76 ng/ml), respectively. The increase in maternal F concentrations with increasing injection frequency was statistically significant (P < 0.02). Mean umbilical venous and arterial F concentrations at birth were 0.72 ng/ml (+/-1.16) and 0.62 ng/ml (+/-0.52). No significant group differences were found regarding Apgar scores or umbilical blood gas analyses. In one newborn, radioimmunoassay resulted in unexplainably high umbilical F concentrations without any clinical signs of sedation, depressed vigilance and without any sequellae. DISCUSSION. Repeated addition of 100 micrograms F to epidural anaesthesia with bupivacaine significantly improves analgesia and provides pain relief not only during the fir

Adult↗