Research Priorities to Improve Treatment of Patients Exposed to Xylazine-fentanyl: Rapid Communication from a National Institute on Drug Abuse Center for the Clinical Trials Network Meeting.

ABSTRACT: In response to the rapid escalation in the detection of xylazine in the unregulated drug supply, in April 2023, the White House designated fentanyl contaminated with xylazine an "emerging threat." The National Institute on Drug Abuse Center for Clinical Trials Network convened a multidisciplinary meeting of stakeholders, federal staff members, researchers, and clinicians caring for patients with fentanyl and xylazine exposures. This convening focused on the most critical areas of concern with the goal of describing current practices and a xylazine-fentanyl research agenda. Discussions focused on the domains of epidemiology and laboratory detection, xylazine withdrawal and overdose, and dermal manifestations. The authors were involved in planning and moderating the program and providing a summary of the proceedings.

Aloe Vera-Containing Matrix in Transdermal Fentanyl Therapy Improves Adhesion, Skin Tolerance and Quality of Life: Results of a German Multicenter Study with a New Fentanyl Patch.

BACKGROUND: Chronic pain represents a significant and costly healthcare problem especially in the older patient. Transdermal opioid therapy is easy to apply and ensures constant supply of active ingredients. However, skin irritation, poor adhesion and systemic side effects complicate transdermal pain therapy. METHODS: In the Relief study, comprising 54 centers, all in Germany, 252 patients were recruited and data about the general care situation as well as the characteristics, effects and side effects of the Aloe vera fentanyl patch were collected. 92 patients had a prior treatment with fentanyl patch without Aloe vera, allowing a comparative analysis. RESULTS: Compared to patches without Aloe vera, the new fentanyl patch showed better adhesion. Systemic and local tolerance and pain reduction were also significantly better. Patients also reported improvements in side effects and central parameters of quality of life. The data regarding the care situation in Germany showed remarkably low use of coanalgetics and laxatives in pain patients. DISCUSSION: Aloe vera in transdermal pain treatment improves adhesion and local tolerance of the patch. Pain control and quality of life were also improved. Regional care data concerning cotreatment in pain therapy from this study indicate a lack of penetration of existing guidelines in general practitioners' pain therapy.

Fentanyl transdermal patches induced chemical leucoderma.

Chemical leucoderma is defined as hypopigmentation or vitiligo-like hypomelanosis caused by repeated chemical exposure, and the diagnosis can be made clinically. Chemical leucoderma induced by fentanyl transdermal patches is rare. This case report involves a 53-year-old man with chronic back pain caused by herniated nucleus pulposus at the L4-L5 level. The patient had used fentanyl transdermal patches for about 2 years. Depigmented lesions were observed in the areas where fentanyl transdermal patches had been applied. Chemical leucoderma was the most likely diagnosis. There remains a debate regarding whether there is a fentanyl dose-response relationship and whether the duration of exposure is relevant. Spontaneous repigmentation may occur after discontinuing the chemical exposure, and follow-ups are recommended to monitor whether spontaneous repigmentation occurs. Additionally, several treatment options have been proposed as specific treatments for chemical leucoderma, including psoralens, corticosteroids, calcineurin inhibitors, immunosuppressive agents and phototherapy.

A Case of Phenibut Directed Detoxification Leading to Toxicity During the COVID-19 Pandemic.

BACKGROUND: Phenibut is a non-Food and Drug Administration-approved gamma-aminobutyric acid analog marketed in the United States as an anxiolytic, cognitive enhancer, and alcohol withdrawal treatment through online supplement vendors. In this case report, we describe a woman's self-directed detoxification with phenibut used to manage withdrawal symptoms from fentanyl and benzodiazepines in March 2020 during the height of the COVID-19 pandemic. CASE: A 38-year-old woman with severe opioid, benzodiazepine, gabapentin, stimulant use disorders developed altered mental status after oral phenibut ingestion intended to help self-manage opioid and benzodiazepine withdrawal. She chose self-directed detoxification as she feared COVID-19 exposure in detoxification facilities. Her altered mental status drove her to jump out a third-story window causing multiple spinal fractures. After a long hospitalization, she self-directed her discharge home due to concerns about COVID-19. Her premature discharge disrupted opioid and benzodiazepine use disorder treatment plans. CONCLUSION: This case highlights the risks of phenibut use for selfdirected detoxification. With COVID-19 related changes in the drug supply, people may be more likely to use online pharmaceuticals, therefore, substance use assessments should inquire about the online acquisition of new psychoactive drugs. Public health messaging regarding the risks of infectious disease transmission in addiction care settings is needed to guide addiction treatment choices among people who use substances.

Intranasal fentanyl spray versus intravenous opioids for the treatment of severe pain in patients with cancer in the emergency department setting: A randomized controlled trial.

OBJECTIVE: Intranasal fentanyl (INF) quickly and noninvasively relieves severe pain, whereas intravenous hydromorphone (IVH) reliably treats severe cancer pain but requires vascular access. The trial evaluated the efficacy of INF relative to IVH for treating cancer patients with severe pain in an emergency department (ED) setting. METHODS: We randomized 82 patients from a comprehensive cancer center ED to receive INF (n = 42) or IVH (n = 40). Eligible patients reported severe pain at randomization (≥7, scale: 0 "none" to 10 "worst pain"). We conducted non-inferiority comparisons (non-inferiority margin = 0.9) of pain change from treatment initiation (T0) to one hour later (T60). T0 pain ratings were unavailable; therefore, we estimated T0 pain by comparing 1) T60 ratings, assuming similar group T0 ratings; 2) pain change, estimating T0 pain = randomization ratings, and 3) pain change, with T0 pain = 10 (IVH group) or T0 pain = randomization rating (INF group). RESULTS: At T60, the upper 90% confidence limit (CL) of the mean log-transformed pain ratings for the INF group exceeded the mean IVH group rating by 0.16 points (>pain). Substituting randomization ratings for T0 pain, the lower 90% CL of mean pain change in the INF group extended 0.32 points below (

Transient lower cranial nerve palsies following spinal anesthesia with bupivacaine-fentanyl combination for transurethral resection of the prostate.

Spinal anesthesia is a widely used regional anesthesia for many infra-umbilical surgical procedures with proven efficacy and safety. However, although rare, some neurologic complications can occur with potentially life threatening consequences. Among them, lower cranial nerve palsies have been rarely reported in the literature. We report such a case in a 75-year-old man with transient dysphagia, dysphonia and spinal accessory nerve palsy occurring four days after spinal anesthesia for transurethral resection of the prostate. His symptoms completely resolved spontaneously within 2 weeks. The possibility of lower cranial nerve palsies should be added to the potential complications during or following spinal anesthesia with bupivacaine-fentanyl combination. Although transitional, this complication may occur few days after the procedure and need to be promptly recognized, carefully evaluated and treated by conservative measures.

Postoperative nausea and vomiting (PONV) in outpatient repair of inguinal hernia.

PURPOSE: Nausea and vomiting are among the most frequent complications following anesthesia and surgery. Due to anesthesia seems to be primarily responsible for post operative nausea and vomiting (PONV) in Day Surgery facilities, the aim of the study is to evaluate how different methods of anesthesia could modify the onset of postoperative nausea and vomiting in a population of patients undergoing inguinal hernia repair. METHODS: Ninehundredten patients, aged between 18 and 87 years, underwent open inguinal hernia repair. The PONV risk has been assessed according to Apfel Score. Local anesthetic infiltration, performed by the surgeon in any cases, has been supported by and analgo-sedation with Remifentanil in 740 patients; Fentanyl was used in 96 cases and the last 74 underwent deep sedation with Propofol . RESULTS: Among the 910 patients who underwent inguinal hernia repair, PONV occurred in 68 patients (7.5%). Among patients presenting PONV, 29 received Remifentanil, whereas 39 received Fentanyl. In the group of patients receiving Propofol, no one presented PONV. This difference is statistically significant (p < .01). Moreover, only 50 patients of the total sample received antiemetic prophylaxis, and amongst these, PONV occurred in 3 subjects. CONCLUSIONS: Compared to Remifentanil, Fentanyl has a major influence in causing PONV. Nonetheless, an appropriate antiemetic prophylaxis can significantly reduce this undesirable complication. Key words: Day Surgery, Fentanyl, Inguinal, Hernia repair, Nausea, Vomiting.

Effects of three forms of local anesthesia on perioperative fentanyl-induced hyperalgesia.

Both local infiltration analgesia (LIA) and nerve block are common analgesic modalities for pain relief after surgery. The aim of the current study was to investigate the effects of those two modalities on pain behavior and the expression of pro-inflammatory cytokines such as interleukin (IL)-1ß and IL-6 and tumor necrosis factor-α (TNF-α) in the spinal cord and dorsal root ganglion (DRG) in a rat model of perioperative fentanyl induced hyperalgesia. Rats were injected with fentanyl (60 µg/kg) 4 times and received a plantar incision after the second injection or they received pre-incision LIA and sciatic nerve block (SNB) or post-incision LIA with levobupivacaine (0.5%, 0.2 mL). Mechanical and thermal nociceptive thresholds were assessed using the tail pressure test and paw withdrawal test on the day before drug injection, 1 and 4 hours after injection, and 1-7 days later. The lumbar spinal cord and dorsal root ganglia were collected from rats in each group to measure IL-1ß, IL-6, and TNF-α on the day before drug injection, 4 hours after injection, and 1, 3, 5, and 7 days later. Fentanyl and an incision induced a significantly delayed mechanical hyperalgesia in the tail and thermal hyperalgesia in both hind paws and up-regulation of pro-inflammatory cytokines in the spinal cord and dorsal root ganglia. Rats treated with pre-incision LIA and SNB or post-incision LIA had alleviated hyperalgesia and significantly reduced levels of IL-1ß, IL-6, and TNF-α compared to the control group. LIA and SNB partly prevented perioperative fentanyl-induced hyperalgesia and up-regulation of pro-inflammatory cytokines in the spinal cord and dorsal root ganglia.

Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options.

BACKGROUND: Methemoglobinemia is a well-recognized adverse drug reaction related to the use of certain local anesthetic agents. The mainstay of treatment for methemoglobinemia is i.v. methylene blue, along with provision of supplemental oxygen; however, methylene blue is listed as a category X teratogen. This poses an issue should methemoglobinemia develop during pregnancy. CASE REPORT: A 35-year-old, 20-week and 5-day gravid female was transferred from an outpatient oral surgeon's office for hypoxia. She was undergoing extraction of 28 teeth and was administered an unknown, but "large" quantity of prilocaine during the procedure. Given this exposure, the concern was for methemoglobinemia. This was confirmed with co-oximetry, which showed 34.7% methemoglobin. The initial treatment plan was methylene blue; however, this drug is a category X teratogen. Thus, an interdisciplinary team deliberated and decided on treatment with high-dose ascorbic acid and transfusion of a single unit of packed red blood cells. The patient was managed with noninvasive ventilation strategies and a total of 8 g ascorbic acid. She was discharged on hospital day 3 with no obstetric issues noted. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intravenous ascorbic acid appears to be a potential alternative to methylene blue in this patient population. The data surrounding teratogenicity of methylene blue are mostly related to intra-amniotic or intra-uterine administration. In life-threatening cases of methemoglobinemia during pregnancy, the benefits of i.v. methylene blue may outweigh the risks.

Serotonergic medications, herbal supplements, and perioperative serotonin syndrome.

PURPOSE: Perioperative use of serotonergic agents increases the risk of serotonin syndrome. We describe the occurrence of serotonin syndrome after fentanyl use in two patients taking multiple serotonergic agents. CLINICAL FEATURES: Two patients who had been taking multiple serotonergic medications or herbal supplements (one patient taking fluoxetine, turmeric supplement, and acyclovir; the other taking fluoxetine and trazodone) developed serotonin syndrome perioperatively when undergoing outpatient procedures. Both experienced acute loss of consciousness and generalized myoclonus after receiving fentanyl. In one patient, the serotonin syndrome promptly resolved after naloxone administration. In the other patient, the onset of serotonin syndrome was delayed and manifested after discharge, most likely attributed to the intraoperative use of midazolam for sedation. CONCLUSION: Even small doses of fentanyl administered to patients taking multiple serotonergic medications and herbal supplements may trigger serotonin syndrome. Prompt reversal of serotonin toxicity in one patient by naloxone illustrates the likely opioid-mediated pathogenesis of serotonin syndrome in this case. It also highlights that taking serotonergic agents concomitantly can produce the compounding effect that causes serotonin syndrome. The delayed presentation of serotonin syndrome in the patient who received a large dose of midazolam suggests that outpatients taking multiple serotonergic drugs who receive benzodiazepines may require longer postprocedural monitoring.

Impact of Prophylactic Fentanyl Pectin Nasal Spray on Exercise-Induced Episodic Dyspnea in Cancer Patients: A Double-Blind, Randomized Controlled Trial.

CONTEXT: Episodic breathlessness is common and debilitating in cancer patients. OBJECTIVES: In this pilot study, we examined the effect of prophylactic fentanyl pectin nasal spray (FPNS) on exercise-induced dyspnea, physiologic function, and adverse events. METHODS: In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients performed three six-minute walk tests (6MWTs) to induce dyspnea. They were randomized to receive either FPNS (15%-25% of total daily opioid dose each time) or placebo 20 minutes before the second and third 6MWTs. We compared dyspnea Numeric Rating Scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the first and second 6MWTs (T2-T1) and between the first and third 6MWTs (T3-T1). RESULTS: Twenty-four patients enrolled, with 96% completion. FPNS was associated with significant within-arm reduction in dyspnea NRS at rest (T2-T1: -0.9 [95% CI -1.7, -0.1]; T3-T1: -1.3 [95% CI -2.0, -0.5]) and at the end of a 6MWT (T2-T1: -2.0 [95% CI -3.5, -0.6]; T3-T1: -2.3 [95% CI -4.0, -0.7]), and longer walk distance (T2-T1 +23.8 m [95% CI +1.3, +46.2 m]; T3-T1: +23.3 m [95% CI -1.7, +48.2]). In the placebo arm, we observed no significant change in walk distance nor dyspnea NRS at rest, but significant reduction in dyspnea NRS at six minutes (T2-T1: -1.7 [95% CI -3.3, -0.1]; T3-T1: -2.5 [95% CI -4.2, -0.9]). Vital signs, neurocognitive function, and adverse effects did not differ significantly. CONCLUSION: FPNS was safe, reduced dyspnea at rest, and increased walk distance in before-after comparison. The placebo effect was substantial, which needs to be factored in future study designs. TRIAL REGISTRATION: ClinicalTrials.govNCT01832402.

In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile.

BACKGROUND AND PURPOSE: For patients experiencing inadequate analgesia and intolerable opioid-related side effects on one strong opioid analgesic, pain relief with acceptable tolerability is often achieved by rotation to a second strong opioid. These observations suggest subtle pharmacodynamic differences between opioids in vivo. This study in rats was designed to assess differences between opioids in their in vivo profiles. EXPERIMENTAL APPROACH: Male Sprague Dawley rats were given single i.c.v. bolus doses of morphine, morphine-6-glucuronide (M6G), fentanyl, oxycodone, buprenorphine, DPDPE ([D-penicillamine(2,5) ]-enkephalin) or U69,593. Antinociception, constipation and respiratory depression were assessed using the warm water tail-flick test, the castor oil-induced diarrhoea test and whole body plethysmography respectively. KEY RESULTS: These opioid agonists produced dose-dependent antinociception, constipation and respiratory depression. For antinociception, morphine, fentanyl and oxycodone were full agonists, buprenorphine and M6G were partial agonists, whereas DPDPE and U69,593 had low potency. For constipation, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, morphine produced a bell-shaped dose-response curve, whereas DPDPE and U69,593 were inactive. For respiratory depression, morphine, M6G, fentanyl and buprenorphine were full agonists, oxycodone was a partial agonist, whereas DPDPE and U69,593 were inactive. The respiratory depressant effects of fentanyl and oxycodone were of short duration, whereas morphine, M6G and buprenorphine evoked prolonged respiratory depression. CONCLUSION AND IMPLICATIONS: For the seven opioids we assessed, no two had the same profile for evoking antinociception, constipation and respiratory depression, suggesting that these effects are differentially regulated. Our findings may explain the clinical success of 'opioid rotation'. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

ED50 and ED95 of intrathecal isobaric levobupivacaine coadministered with fentanyl for transurethral resections: randomized, double-blind trial.

BACKGROUND: Levobupivacaine use is progressively increased for intrathecal anesthesia in transurethral resections. The aim was to determine ED(50) and ED(95) of intrathecal isobaric levobupivacaine by addition of 25 mcg fentanyl for patients undergoing transurethral resections. METHODS: A total of 100 patients undergoing transurethral resections with ASA I-III, were randomized to groups receiving intrathecal 0.5% isobaric levobupivacaine in doses of 6, 8, 10, 12 or 14 mg in equal volumes with 25 mcg intrathecal fentanyl addition. Sensorial block level was determined by pinprick and motor block by Bromage scale. RESULTS: Mean onset time of sensorial block in 6 mg group was significantly longer than that of sensorial block in 10 mg, 12 mg and 14 mg groups (p<0.01), 8 mg was longer than 12 mg and 14 mg (p<0.01), and 10 mg onset time of sensorial block was significantly longer than 12 mg and 14 mg (p<0.01). Mean onset time of T10 sensory level in 6 mg group was significantly longer than mean onset time of T10 sensory level in 10 mg, 12 mg and 14 mg (p<0.01), the mean onset time of T10 sensory level in 8 mg group was also significantly longer than that of 12 mg, 14 mg groups (p<0.01). ED(50) and ED(95) of levobupivacaine coadministered with 25 mcg fentanyl were 7.32 mg and 10.88 mg, respectively. CONCLUSION: Levobupivacaine with opioid co-administration can be used in doses considerably lower than doses proposed for routine use as it is a safe drug depending on its hemodynamic effects, side effects.

[Effects of assisted-electroacupuncture on recovery of fast tracking anesthesia in mPCNL].

OBJECTIVE: To compare the effects on anesthesia recovery between assisted-electroacupuncture fast tracking anesthesia and simple fast tracking anesthesia in patients with minim ally invasive percutaneous nephrolithotomy (mPCNL). METHODS: Eighty cases of mPCNL were selected and randomly divided into a treatment group and a control group. Fentanyl (1-2 microg/kg), sevoflurane (8%) and rocuronium (0.5 mg/kg) were applied to perform anesthesia induction in both groups, and endotracheal inhalation of sevoflurane and intravenous pump injection of remifentanil were adopted to main anesthesia status during the operation. 20 min before anesthesia induction, bilateral Neiguan (PC 6), Neimadian, Hegu (LI 4), Yangxi (LI 5), Zhongji (CV 3), Qichong (ST 30), Zuwuli (LR 10) were selected and punctured in the treatment group, and elecctroacupuncture was given after arrival of qi until 30 min after the wake-up from anesthesia and withdrawal of endotracheal tube. The dosage for anesthesia maintenance, recovery time of awareness, extubation time, incidences of nausea, vomiting and chill and irritation of urethral catheters were observed and recorded. RESULTS: (1) The dosages of remifentanil and sevoflurane in the treatment group during the operation were obviously less than those in the control group [remifentanil: (5. 27 +/-1.23) micro g/kg h vs (7.35+/-1.70) micro g/kg . h; sevoflurane: (1.12+/-0.43) vol% vs (2.35+/-0.87) vol% , both P<0. 001]. (2) The recovery time of awareness and extubation time in the treatment group were significantly earlier than those in the control group [recovery time of awareness: (5.65 +/- 2.34) min vs (8. 87 +/- 6. 84) min, P<0. 01; extubation time : (7. 23+/-4. 35) min vs (10. 62+/-8. 16) min, P<0. 05]. (3) The incidences of nausea, vomiting and chill in the treatment group were significantly less than those in the control group (all P<0. 05). (4) The irritation of urethral catheters on urethra in the treatment group was significantly less than that in the control group (P<0. 001). CONCLUSION: The assisted-electroacupuncture anesthesia could reduce the dosage of remifentanil and sevoflurane in mPCNL fast tracking anesthesia in urinary surgery, reduce the incidences of nausea, vomiting, chill and irritation of urethral catheters during recovery stage, and prompt recovery of mPCNL patients.

A report on the long-term use of fentanyl pectin nasal spray in patients with recurrent breakthrough pain.

CONTEXT: As patients with cancer are living longer, there is a need to ensure that treatments used for palliative care are well tolerated and effective during long-term use. OBJECTIVES: To investigate the long-term use of fentanyl pectin nasal spray (FPNS) for the treatment of breakthrough pain in cancer (BTPc) in patients receiving regular opioid therapy. METHODS: Adult patients (N = 401) taking at least 60 mg/day oral morphine or equivalent, experiencing one to four episodes of BTPc a day, entered an open-label long-term study (NCT00458510). Patients had either completed an FPNS randomized controlled trial or were newly identified. Of these, 171 patients continued into an extension study. Up to four episodes of BTPc a day were treated with FPNS at 100-800 µg titrated doses. During the extension study, patients visited the clinic every four weeks for assessment and reporting of adverse events (AEs). RESULTS: There were 163 patients with documented FPNS use. The mean duration of use was 325 days; 46 patients used FPNS for ≥360 days; the maximum duration was 44 months. Seventy percent of patients did not change their FPNS dose; 2% of patients withdrew from the study because of the lack of efficacy. The most common AEs, aside from disease progression, were insomnia, 9.9%; nausea, 9.4%; vomiting, 9.4%; and peripheral edema, 9.4%. The overall incidence of FPNS-related AEs was 11.1%, the most common being constipation (4.1%), with no apparent dose relationship. Ten patients (5.8%) experienced nasal AEs, most of which were mild or moderate. CONCLUSION: FPNS appeared to provide sustained benefit and was well tolerated during long-term treatment of BTPc.

A pharmacokinetic assessment of an alternate titration strategy for fentanyl pectin nasal spray.

OBJECTIVE: Fentanyl pectin nasal spray (FPNS) is approved for management of breakthrough pain in cancer. It is available in 100 and 400 µg strength products which allow for doses of 100 - 800 µg (1 or 2 sprays). Existing titration strategies require a transition from the 100 µg product to the 400 µg product when increasing the dose from 200 to 400 µg. This study assessed the pharmacokinetic (PK) profile of FPNS administered as 4 sprays of 100 µg as an alternate titration strategy. METHODS: In this 3-way, crossover study, healthy subjects aged 18 - 65 years were randomized to receive each of 3 dosages of FPNS (4 × 100 µg, 2 × 100 µg, and 1 × 400 µg). PK samples were collected over 24 hours. RESULTS: Of 22 subjects randomized, 20 were included in the PK analysis. Administration of both 400 µg regimens (4 × 100 µg and 1 × 400 µg) provided greater systemic fentanyl exposure compared with the 200 µg dose (C(max): 1,748 and 1,485 pg/ml vs. 1,051 pg/ml; AUC(0-1h): 1,012 and 944 pg×h/ml vs. 665 pg×h/ml; and tmax: 0.25 hours and 0.50 hours vs. 0.25 hours); fentanyl exposure after 4 × 100 µg and 1 × 400 µg regimens was similar. Adverse events (AEs) were all mild or moderate in intensity; most common AEs were nausea (50%) and headache (23%). AE frequency was similar across treatments without reports of nasal effects. CONCLUSIONS: Given that systemic fentanyl exposure from FPNS administered as 4 × 100 µg is similar to that from FPNS as 1 × 400 µg, the 4 × 100 µg regimen provides an alternate titration strategy for patients needing more than 200 µg. This alternate strategy will facilitate a patient's ability to achieve an optimized FPNS regimen and reduce opioid wastage.

Transcutaneous electrical nerve stimulation on acupoints reduces fentanyl requirement for postoperative pain relief after total hip arthroplasty in elderly patients.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is regarded as an effective treatment for various types of pain. However, no randomized controlled trial has investigated TENS on acupoints for postoperative analgesia in elderly patients. This study aim to investigate whether TENS on acupoints has any favorable effect on complementary analgesia after total hip arthroplasty (THA) for elderly patients compared with a sham control treatment. METHODS: Sixty-eight elderly patients requiring THA surgery were enrolled and randomly allocated to one of two groups. Group Acu received true TENS on acupoints (bilateral P6, L14; ST36, GB31 ipsilateral to the surgery site) and Group Sham received sham treatment. All patients received patient-controlled analgesia for two days postoperatively. Analgesia was assessed by postoperative fentanyl requirement and pain intensity using a visual analogue scale (VAS-10 cm). The incidence of analgesia-related side effects, optional medication use and effects of patients' blinding were recorded. RESULTS: Fentanyl consumption in Group Acu was lower than that in Group Sham at 24 h (mean ± SD; 360±117 vs. 572±132 µg; P<0.001) and 48 h (712±184 vs. 1022±197 µg; P<0.001) after surgery. Postoperative pain intensity measured by VAS was similar in both groups. The incidence of opioid-related side effects and rescue medication for postoperative analgesia was significantly higher in Group Sham than in Group Acu. Differences between the groups regarding the effects of patients' blinding were not significant. CONCLUSION: TENS on specific acupoints is an effective and complementary approach to reduce postoperative analgesic requirement in elderly patients after THA.

Single intrathecal fentanyl for combined spinal epidural anesthesia confers no advantage over hemodynamic effects in elderly patients.

BACKGROUND: Neuroaxial blockade for ambulatory transurethral resection of the prostate is a well established technique. Patients in this group are often at high risk for perioperative complications from concurrent diseases. The purpose of this study was to compare the elderly patients who received intrathecal fentanyl alone or intrathecal fentanyl plus bupivacaine or epidural anesthesia for transurethral resection of prostate surgery. MATERIAL AND METHODS: Ninety-nine patients were prospectively randomized to receive fentanyl 25 microg (Group F), fentanyl 25 microg plus hyperbaric bupivacaine 2.5 mg (Group BF), or epidural anesthesia adding fentanyl 50 microg (Group E) by combined spinal epidural anesthesia technique. RESULTS: The amount of local anesthetics used until when the sensorial block reached the level of T10 was significantly lower in the Group BF than in the Group E and the Group F (p < 0.001). Maximum level of sensory block was significantly lower in the Group BF than in the Group E and the Group F (p = 0.01). The time elapsed until the sensory block reached T10, the regression of sensory block to L5 level were significantly lower in the Group BF than in the Group E and the Group F (p = 0.005, p < 0.001, respectively). Compared to the basal values, mean arterial pressures were significantly lower in the Group BF than in the Group E and the Group F (p < 0.05). The occurrence of hypotension was significantly lower in the Group BF (9.4%) than in the Group E (18.2%) and the Group F (24.2%). CONCLUSIONS: Intrathecal hyperbaric bupivacaine 2.5 mg plus fentanyl 25 microg administration provides shorter motor block onset time, less local anesthetic usage and adequate hemodynamic stability in elderly patients.

Utilisation of transdermal fentanyl in Germany from 2004 to 2006.

PURPOSE: Oral morphine is the first-choice opioid for moderate to severe cancer pain. Transdermal fentanyl is an alternative in patients with stable requirements of high-potency opioids (HPO) or if drugs cannot be taken orally. Drug regulatory authorities have issued several alerts to use transdermal fentanyl only for chronic pain and in HPO-tolerant patients to minimise the risk of severe opioid side effects. The aim of this study was to characterise utilisation of transdermal fentanyl in Germany. METHODS: The analysis was based on data from four German statutory health insurances from the years 2004-2006. Descriptive analyses were performed in new users of transdermal fentanyl to assess HPO-naïvety, potential difficulties with the oral route in HPO-naïve patients and the number of transdermal fentanyl dispensations. The initial dose in new users was assessed in 2005-2006 after marketing of transdermal fentanyl 12.5 µg/hour. RESULTS: Of 35 262 patients with new use of transdermal fentanyl, 29 793 (84.5%) were assessed as HPO-naïve. Of those, 21 596 (72.5%) did not have diagnoses indicating difficulties with the oral route. For 71.2% of the HPO-naïve new users of transdermal fentanyl, the first dose exceeded the recommended dose of 12.5 µg/hour, and 49.3% of them received only one prescription of the drug. CONCLUSIONS: Transdermal fentanyl was used as a first-choice opioid, which may increase the risk of serious opioid side effects, in a substantial number of HPO-naïve patients. Inappropriate prescribing included also high initial doses in HPO-naïve patients and possible prescription for acute pain in a considerable proportion of patients.