Epidural Fentanyl Research Articles

Fentanyl transdermal patches: overview of cutaneous adverse effects in humans

Using Medline, Embase, and the Science Citation Index, we summarize the cutaneous adverse effects of transdermal and parenteral fentanyl. The fentanyl transdermal therapeutic system (TTS; patch) provides continuous systemic delivery of fentanyl (N-phenyl-N-(1-(2-phenylethyl)-4-piperidinyl) propanamide), a potent opioid analgesic, for 72 hours. Clinical studies of fentanyl TTSs demonstrated varying rates of irritation at the application site, ranging from none to 42%, with a median of 25%. Most descriptions of skin reactions included erythema at the application site, indicating irritant dermatitis. Skin testing in 2 subjects receiving parenteral doses concluded that although immunoglobulin E (IgE) antibodies to fentanyl exist, few cases of immediate-type allergic reactions to fentanyl have been substantiated. Comparing the reactions to anesthetic agents during allergenic testing demonstrated positive “wheal and flare” to fentanyl in only 1 of 50 patients (2%). Pruritus has been frequently reported during administration of epidural fentanyl, but allergenicity has not been shown. The few case reports of possible anaphylactic reactions to fentanyl have not clearly demonstrated fentanyl as the causal agent. In addition, transdermal and intravenous/epidural routes of administration may not be comparable because of large differences in plasma concentrations: When these results are taken together, fentanyl (TTS) has shown limited skin intolerance.

Breastfeeding success rate after vaginal delivery can be high despite the use of epidural fentanyl: an observational cohort study

Background Epidural labor analgesia inclusive of high-dose fentanyl has been thought to affect breastfeeding in multiparous patients. In our experience, this effect is not as significant as quoted in the literature. This study was designed to evaluate breastfeeding success in women receiving epidural analgesia with fentanyl-containing solutions at our institution. Methods Term multiparous women who received epidural analgesia for labor, had previously breastfed, and who intended to breastfeed, were recruited. Baseline demographics, as well as detailed epidural, obstetric and neonatal data, were collected. Epidural analgesia was achieved with a mixture of bupivacaine and fentanyl. Subjects were telephoned both 1 and 6 weeks after delivery, and a breastfeeding questionnaire was completed. Our primary outcome was breastfeeding cessation at 6 weeks. Results One hundred and five women were recruited, with 18 exclusions. The median cumulative epidural fentanyl dose was 151.4 μg (30–570 μg). No neonates developed complications attributable to labor analgesia. Four women stopped breastfeeding because of issues related to the baby (4.6%); only one of them received a fentanyl dose >150 μg. The breastfeeding success rate was therefore >95%. The women had a median maternity leave of 12 months, and 69% received post-partum lactation support. Conclusions The incidence of successful breastfeeding in multiparous women who undergo vaginal delivery with epidural analgesia inclusive of fentanyl is much greater at our institution than previously reported in the literature. This may be due to favorable conditions such as time off work and post-natal support.

Effectivity of epidural fentanyl to provide intraoperative analgesia. Comparison of epidural and intravenous administration

Sadurní, M.; Beltrán de Heredia, S.; Pérez-Ramos, A.; Dürsteler, C.; Puig, M. M. Author Information

Preoperative Stimulation of Erythropoiesis in Patients with Anemia

Objective: to comparatively study different postoperative analgesia modes in patients undergoing reconstructive interventions into the abdominal aorta. Subjects and methods. The impact of analgesia on the course of the early postoperative period was comparatively studied in 98 patients. According to the mode of postoperative analgesia, the patients were divided into 3 groups: 1) 35 patients received traditional analgesia with narcotic analgesics (promedol, morphine i.m.); 2) 32 patients had prolonged epidural infusion of 0.2% ropivocaine solution with fractional epidural administration of fentanyl 0.1 mg twice daily; 3) 31 patients were given a combination of epidural naropine and fentanyl with parenteral ketorolac 90 mg/day and paracetamol 3 g/day. The magnitude of pain syndrome was analyzed using the visual analogue scale. The parameters of central hemodynamics (CHD) were estimated applying thoracic tetrapolar rheocardiography. Autonomic homeostatic changes were studied from the cardiac rhythm variability by computer rhythmocardiography. Results. The least magnitude of pain syndrome, the eutonic type of autonomic regulation of the cardiovascular system, and the highest cardiac index values were recorded in Group 3. Conclusion. The use of mul-timodal postoperative analgesia ensures valid analgesia with the stable parameters of CHD and autonomic homeostasis. Key words: analgesia, epidural infusion, visual analogue scale, central hemodynamics, cardiac rhythm variability.

A Study on Epidural Tramadol Compared with Epidural Fentanyl Combined with Low Dose Bupivacaine for the Control of Metastatic Cancer Pain

Background: Despite advances in the knowledge of pathophysiology of pain and its management, patients continue to suffer from pain in many terminal stage cancer. Tramadol hydrochloride is a weak opioid with analgesic properties, and can be tried for cancer pain management. Objectives: This study was performed to find out the efficacy of the analgesic property of Tramadol through epidural route in cancer patients as an combination with low dose(.125%) Bupivacaine and to compare with Fentanyl, a μ opioid agonist. Methods: 50 Cancer patients with or without previous pain management were randomly allocated to one of the two study regime- Group-A (tramadol 50 mg) and Group-B (Fentanyl 50 mgm) in combination with .125% Bupivacaine. Drugs were administered epidurally 6 hourly, 8 hourly and 12 hourly respectively for the 1st, 2nd and 3rd day. Low dose bupivacaine was added to both groups to enhance quality. Pain scores, blood pressure, respiratory rate, heart rate, side effects and patients' satisfaction score was recorded 6 hourly for 72 hrs. The data yielded from this study were compiled and analyzed by unpaired and paired ‘t' test with 95% confidence limit. A value of P< 0.05 was considered to be significant. ÷ square test was done for some of the data. Results : Pain scores were significantly decreased in both the groups but were not significantly different. The incidence of side effects including nausea and vomiting was found in both the groups and was not significantly different between the two groups. Conclusion: The use of epidural Tramadol in selected cancer pain patients (especially pain in lower abdomen and lower back) may be very useful and is comparable to opioid in certain situations. Key words: Metastatic cancer pain; Epidural tramadol. DOI: 10.3329/bsmmuj.v2i2.4760 BSMMU J 2009; 2(2): 66-72

Effect of Preincisional Epidural Fentanyl and Bupivacaine on Postthoracotomy Pain and Pulmonary Function

This study attempts to determine whether preemptive thoracic epidural analgesia (TEA) initiated before surgical incision would reduce the severity of acute post-thoracotomy pain, its effects on pulmonary function and stress response. Forty patients undergoing posterolateral thoracotomy received TEA either before (preoperative-TEA group) or after (postoperative-TEA group) surgery. Postoperative analgesia was maintained with epidural infusion of bupivacaine and fentanyl. Pain scores, pulmonary functions, arterial blood gases, plasma glucose, cortisol levels and epidural fentanyl consumption were compared for 48 hours after surgery. The preoperative-TEA group demonstrated significantly reduced pain scores at 2, 4, 8, 12, 24, and 48 hours at rest (p = 0.001, p = 0.002, p = 0.004, p = < 0.001, p = 0.006, and p = 0.001, respectively) and at 4, 8, 12, 24, 48 hours on coughing (p = 0.001, p = 0.001, p = 0.001, p = 0.001, p = 0.004, respectively), and a significant reduction in epidural fentanyl consumption (208.6 +/- 49.3 mL, versus 260 +/- 28.8 mL, p = 0.001). The preoperative-TEA group showed significant improvement in pulmonary functions as compared with the postoperative-TEA group (p < 0.05), except forced expiratory volume in one second at 24 hours (p = 0.061) and peak expiratory flow rate at 48 hours (p = 0.188). The postoperative-TEA treated patients were more likely to have a higher arterial carbon dioxide pressure at 4, 8, 12, and 24 hours (p = 0.017, p = 0.001, p = 0.003, p = 0.001), respectively. However, we could not demonstrate a statistical difference in oxygenation, cortisol, or glucose level. Though preemptive TEA appeared to reduce the severity of acute pain, preserve pulmonary function, and reduce analgesic requirements, these statistically significant differences were not enough to conclude a clinical significant difference between groups.

Epidural versus intravenous fentanyl for postoperative analgesia following orthopedic surgery: randomized controlled trial.

Controversy exists regarding the site of action of fentanyl after epidural injection. The objective of this investigation was to compare the efficacy of epidural and intravenous fentanyl for orthopedic surgery. A randomized double-blind study was performed in Hospital São Paulo. During the postoperative period, in the presence of pain, 29 patients were divided into two groups: group 1 (n = 14) received 100 microg of fentanyl epidurally and 2 ml of saline intravenously; group 2 (n = 15) received 5 ml of saline epidurally and 100 microg of fentanyl intravenously. The analgesic supplementation consisted of 40 mg of tenoxicam intravenously and, if necessary, 5 ml of 0.25% bupivacaine epidurally. Pain intensity was evaluated on a numerical scale and plasma concentrations of fentanyl were measured simultaneously. The percentage of patients who required supplementary analgesia with tenoxicam was lower in group 1 (71.4%) than in group 2 (100%): 95% confidence interval (CI) = 0.001-0.4360 (P = 0.001, Fisher's exact test; relative risk, RR = 0.07). Epidural bupivacaine supplementation was also lower in group 1 (14.3%) than in group 2 (53.3%): 95% CI = 0.06-1.05 (P = 0.03, Fisher's exact test; RR = 0.26). There was no difference in pain intensity on the numerical scale. Mean fentanyl plasma concentrations were similar in the two groups. Intravenous and epidural fentanyl appear to have similar efficacy for reducing pain according to the numerical scale, but supplementary analgesia was needed less frequently when epidural fentanyl was used. NCT00635986.

Effects of Epidural Fentanyl on Speed and Quality of Block for Emergency Cesarean Section in Extending Continuous Epidural Labor Analgesia Using Ropivacaine and Fentanyl

We performed a prospective, randomized, and double-blind study comparing the top-up effects of 2% lidocaine/100 µg fentanyl/epinephrine (n=31) and 2% lidocaine/saline/epinephrine (n=30) when extending an epidural labor analgesia using low-dose ropivacaine and fentanyl. Survival analysis for the sensory blocks to the T4 level showed no statistically significant differences in onset time to T4 between the 2 groups. Onset times (min) to T4-sensory blocks for cold and pinprick were not different between the two groups. However, median maximum sensory level in the lidocaine-fentanyl group (T1 for cold and T2 for pinprick) was significantly higher than that in the lidocaine-saline group (T3 and T4, respectively). The lidocaine-fentanyl group exhibited less visceral pain (6.5% vs. 36.7%), less supplementation of lidocaine (6.5% vs. 43.3%), and less nausea (6.5% vs. 26.7%) compared with the lidocaine-saline group during the intraoperative period. It is concluded that adding fentanyl to 2% lidocaine does not speed up the onset of the block when the onset is tested with cold or sharp pinprick but improves the quality of analgesia with fewer side effects in emergency top-up for cesarean section.

Epidural analgesia and breastfeeding: a randomised controlled trial of epidural techniques with and without fentanyl and a non‐epidural comparison group

We compared breastfeeding initiation and duration in 1054 nulliaparae randomised to bupivacaine Control epidural, Combined Spinal Epidural or Low Dose Infusion and 351 matched non-epidural comparisons. Women were interviewed after delivery and completed a postal questionnaire at 12 months. Regression analysis determined factors which independently predicted breastfeeding initiation. Breastfeeding duration was subjected to Kaplan-Meier analysis. A similar proportion of women in each epidural group initiated breastfeeding. Women with no epidural did not report a higher initiation rate relative to epidural groups and those who received pethidine reported a lower initiation rate than control epidural (p = 0.002). Older age groups (p < 0.001) and non-white ethnicity (p < 0.026) were predictive of breastfeeding. Epidural fentanyl dose, delivery mode and trial group were not predictive. Mean duration for breastfeeding was similar across epidural groups (Control 13.3, Combined Spinal Epidural 15.5, Low Dose Infusion 15.0 weeks). Our data do not support an effect of epidural fentanyl on breastfeeding initiation.

Effects of Concomitant Bupivacaine and Infusion Volume on the Analgesic Effect of Epidural Fentanyl After Lower Abdominal Surgery

Effects of Concomitant Bupivacaine and Infusion Volume on the Analgesic Effect of Epidural Fentanyl After Lower Abdominal Surgery

Optimizing Epidural Fentanyl Loading Dose for Early Labor Pain

Sufficient sensory blockade between L1 and T10 is required to relieve visceral pain during early labor. We examined whether the addition of fentanyl to a loading dose of 0.0625% bupivacaine could provide dose-dependent analgesic effects on early-stage labor pain. Sixty parturients who requested epidural analgesia for labor pain were enrolled and randomly allocated to one of three groups. Group A (n = 20) received 10 mL of 0.0625% epidural bupivacaine as a loading dose alone. Group B (n = 20) received the same bupivacaine loading dose in combination with 2 microg/mL fentanyl. Group C (n = 20) received the same loading bupivacaine dose plus 4 microg/mL fentanyl. All patients received diluted bupivacaine plus 2 microg/mL fentanyl at a rate of 10 mL/hr as a maintenance dose. Fifteen minutes later, we recorded the highest cephalic and lowest caudal anesthetized dermatomes, side effects, and the number of patients who asked for supplemental analgesia. The highest anesthetized cephalic dermatome was at the level of T12 (T9-L1) in Group A, T9 (T8-T12) in Group B and T7 (T5-T9) in Group C (p < 0.05 among the three groups). Eleven patients (55%) requested supplemental bupivacaine for inadequate analgesia in Group A, six in Group B (30%), and none in Group C (0%). Pruritus was reported by seven (35%) patients in Group B and eight (40%) patients in Group C, but none in Group A. The addition of fentanyl to epidural bupivacaine dose-dependently increased the analgesic effect and higher loading doses of fentanyl increased the dermatomic coverage. We suggest that 0.0625% bupivacaine plus 4 microg/mL fentanyl is the ideal loading dose to provide the greatest segmental analgesia for early labor pain with minimal side effects.

Are Signposts in the Woods Pointing in the Right Direction?

Editor-in-Chief, Anesthesiology. editor-in-chief@anesthesiology.orgI thank Dr. Barasch for his insightful comments and for this opportunity to clarify my statement regarding the priority for confirmatory research. Actually, we agree that both laboratory and clinical research findings are strengthened, challenged, or refuted by further studies, and that subtle effects or those which are heavily dependent on the exact conditions of the experiment absolutely require confirmation. In my own field of interest, I note that it took very few studies to establish that the analgesic potency of epidural morphine greatly exceeded that of systemic delivery, but dozens of studies to establish that potency of epidural fentanyl differed little from that of systemic delivery. At this point, it would be very unlikely that yet another study comparing epidural to systemic morphine or fentanyl would meaningfully add to our understanding of analgesic potency, although other factors which were not previously examined in depth, such as opioid-induced immune modulation, might justify such a comparison. My point in the editorial1was not that confirmatory research was not wanted in this journal, but rather that we would consider articles addressing the study topics of the retracted papers as being entirely novel rather than confirmatory.I also thank Dr. Barasch for the suggestion regarding electronic publication of selected articles, and we will discuss the advantages and disadvantages of creating this second class of article within our Editorial Board. As I have quickly observed, this journal, like others in medical science, must continuously and critically review its processes and products to better serve the research and clinical practice communities.Editor-in-Chief, Anesthesiology. editor-in-chief@anesthesiology.org

The addition of fentanyl to 1.5 mg/ml ropivacaine has no advantage for paediatric epidural analgesia

Epidural opioids are frequently combined with local anaesthetics for an additive antinociceptive effect. We investigated the efficacy of epidural fentanyl to 1.25 or 1.5 mg/ml ropivacaine for post-operative epidural analgesia in children. One hundred and eight children undergoing hypospadias repair were randomized to receive 1.25 mg/ml ropivacaine (R1.25 group), 1.25 mg/ml ropivacaine with 0.2 mcg/kg/h of fentanyl (R1.25F group), 1.5 mg/ml ropivacaine (R1.5 group) or 1.5 mg/ml ropivacaine with 0.2 mcg/kg/h of fentanyl (R1.5F group) for post-operative epidural analgesia. The epidural catheter was threaded caudally through the L4-5 interspace. The face, legs, activity, cry, consolability (FLACC) score was assessed at every hour and at FLACC score >4, an epidural bolus of 0.5 ml/kg of ropivacaine 1.5 mg/ml was given as the rescue analgesia. The incidence of side effects such as hypoxia, sedation, pruritus, nausea and/or vomiting was recorded. The need for rescue analgesia was higher in the R1.25 group compared with that in the other three groups (all P<0.05). The incidence of side effects was higher in the R1.5F group compared with that in the R1.25 and R1.5 groups (both P=0.010). The addition of 0.2 mcg/kg/h fentanyl to 1.5 mg/ml ropivacaine increased the incidence of side effects without improvement of analgesia in infants and children undergoing hypospadias repair. The use of plain 1.25 mg/ml ropivacaine increased the need for rescue analgesia and this could be compensated by addition of fentanyl.

Practice guidelines for the prevention, detection, and management of respiratory depression associated with neuraxial opioid administration.

Practice guidelines for the prevention, detection, and management of respiratory depression associated with neuraxial opioid administration.

A randomized study of maternal serum cytokine levels following cesarean section under general or neuraxial anesthesia

Cytokines are significant mediators of the immune response to surgery and also play a role in parturition. The aim of the study was to investigate the impact of the anesthetic technique for cesarean section on plasma levels of cytokines IL-6 and TNF-alpha. Thirty-five parturients scheduled for elective cesarean section were randomly assigned to general (n=18) or neuraxial (n=17) anesthesia. The general anesthesia group received thiopental 4 mg/kg, succinylcholine 1-1.5 mg/kg and 1% end-tidal concentration of sevoflurane in nitrous oxide and 50% oxygen. The neuraxial anesthesia group received intrathecal 0.5% levobupivacaine 1.8-2.2 mL and epidural fentanyl 1 microg/kg. Blood samples were taken for IL-6 and TNF-alpha immediately after positioning the parturient on the operating table, after uterine incision and before the umbilical cord clamping and 24h after surgery (T(1), T(2) and T(3) respectively). The two groups did not differ in IL-6 (P=0.15) or TNF-alpha (P=0.73) serum concentrations at any time point. In the general and neuraxial anesthesia groups, IL-6 serum concentrations were significantly higher in the third blood sample, T(3) (12.2+/-5.0 and 15.2+/-4.3 pg/mL), than in T(1) (0.41+/-0.38 and 0.29+/-0.10 pg/mL) and T(2) (0.37+/-0.47 and 0.24+/-0.05) respectively (P<0.001). Within each group, serum TNF-alpha concentrations did not differ significantly over time (P=0.44). Under the present study design anesthetic technique did not affect IL-6 or TNF-alpha concentrations in parturients undergoing elective cesarean section. Serum IL-6 levels increased 24 h postoperatively independently of anesthetic technique.

Efficacy of Addition of Fentanyl to Epidural Bupivacaine on Postoperative Analgesia after Thoracotomy for Lung Resection in Infants

The authors evaluated the efficacy of adding fentanyl to epidural bupivacaine in infants up to 6 months of age after a thoracotomy in a prospective, randomized, double-blind study. The primary outcome was the total amount of rescue doses of intravenous nalbuphine in the first 24 h after surgery. Secondary outcomes included (1) time to first rescue dose of nalbuphine, (2) pain scores, and (3) behavior scores. Thirty-two infants were randomly assigned to receive an epidural infusion containing 0.1% bupivacaine (group B; n = 16) or 0.1% bupivacaine and 2 microg/ml fentanyl (group BF; n = 16). Patients were evaluated up to 24 h after surgery for pain; amount of analgesic rescues and time to first rescue; pain scores; behavior scores (five-item behavior score); and complications, including respiratory depression, oxygen requirement, vomiting, and urinary retention. The two groups had similar demographics. Nalbuphine consumption (P = 0.001) and pain scores (P < 0.001) in the first 24 h were significantly decreased in group BF compared with group B. The time to first analgesic rescue was significantly longer in group BF (P = 0.005). The five-item behavior score was significantly better in group BF than in group B (P = 0.01). The incidence of side effects, the time to first successful feeding, and the time to discharge were similar in both groups. Addition of 2 microg/ml epidural fentanyl to 0.1% bupivacaine results in improved postthoracotomy analgesia without any increase in side effects, compared with 0.1% bupivacaine, in infants up to 6 months of age.

Epidural sufentanil provides better analgesia from 24 h after surgery compared with epidural fentanyl in children

Studies comparing epidural fentanyl and sufentanil in adults reported a similar analgesic effect with variable side effects. We hypothesized that epidural fentanyl and sufentanil will have a similar analgesic effect in children undergoing urological surgery. Sixty-four children undergoing urological surgery were randomized into two groups: fentanyl in ropivacaine (fentanyl group, n=32) and sufentanil in ropivacaine (sufentanil group, n=32). After anaesthesia, an epidural catheter was inserted at the L2-3, L3-4 or L4-5 interspace. For post-operative pain relief, a solution consisting of fentanyl 0.1 mcg/kg/ml or sufentanil 0.015 mcg/kg/ml in 1.5 mg/ml ropivacaine was infused at a rate of 2 ml/h. To assess post-operative pain, the faces pain scale and the face, legs, activity, cry, consolability score were recorded at 1, 6, 24, 48 and 72 h after surgery. The incidence of adverse effects such as hypoxia, sedation, pruritus, nausea and/or vomiting was also evaluated. Pain scores demonstrated no significant difference between the groups. The need for rescue analgesia during 24-72 h was higher in the fentanyl group than in the sufentanil group (6/32 vs. 0/32, P=0.012). The incidence of pruritus was higher in the sufentanil group compared with that in the fentanyl group (5/32 vs. 0/32). Epidural sufentanil provides better analgesia from 24 h after surgery compared with epidural fentanyl in infants and children undergoing urological surgery. The incidence of pruritus in the sufentanil group was higher than that in the fentanyl group.

Comparison of three doses of epidural fentanyl followed by bupivacaine and fentanyl for labor analgesia

Epidural fentanyl 100 microg after lidocaine-epinephrine test dose has been shown to provide adequate analgesia in early labor. This investigation determines the effect of three different bolus doses of epidural fentanyl on duration and quality of analgesia during early first stage of labor. In this prospective, double-blind study, 103 laboring nulliparous at cervical dilation <5 cm were enrolled. After an epidural test dose of lidocaine (60 mg) with epinephrine (15 microg), parturients received, randomly, bolus of epidural fentanyl 50, 75, or 100 microg, followed by a continuous infusion of epidural bupivacaine 0.0625% and fentanyl 3 microg/ml at a rate of 10 ml/h. Pain scores and maternal sedation, pruritus, nausea, and vomiting were recorded 10, 20, and 30 min after fentanyl, and every 30 min thereafter until first request for additional analgesia. Adequate analgesia was achieved in 87% (28/32), 94% (35/38), and 94% (31/33) in the fentanyl 50, 75, and 100 microg groups within 20 min. Mean duration of analgesia before re-dosing was significantly longer in fentanyl 100 and 75 microg groups (185.6+/-82.9 and 188.5+/-82.2 min, respectively) as compared with fentanyl 50 microg group (133.6+/-46.2 min, P<0.016). There was no difference in the incidence of maternal side effects or neonatal Apgar scores among the three groups. After a test dose of lidocaine-epinephrine, the three epidural fentanyl doses produced similar effective labor analgesia. However, epidural fentanyl 75 microg followed by epidural infusion of dilute bupivacaine and fentanyl produced longer duration of analgesia than fentanyl 50 microg followed by the same infusion, with no further prolongation when the dose of fentanyl was increased up to 100 microg.

205. Effects of Epidural Fentanyl on Speed and Quality of Block for Non-Scheduled Cesarean Section in Extending Epidural Labour Analgesia

205. Effects of Epidural Fentanyl on Speed and Quality of Block for Non-Scheduled Cesarean Section in Extending Epidural Labour Analgesia

205: Effects of Epidural Fentanyl on Speed and Quality of Block for Non-Scheduled Cesarean Section in Extending Epidural Labour Analgesia

205: Effects of Epidural Fentanyl on Speed and Quality of Block for Non-Scheduled Cesarean Section in Extending Epidural Labour Analgesia