Barriers to adequate analgesia in paediatric burns patients.

BACKGROUND: All children with burn injuries experience pain at some time during their management and recovery. Burn pain is challenging to manage, owing to a combination of factors. The process of achieving adequate analgesia involves the correct scripting of medication based on the doctor's knowledge, the correct fulfilling of that script, and patient compliance. OBJECTIVES: To assess two components of this process, correct scripting of medication based on the doctor's knowledge and the correct filling of that script, to highlight potential barriers to adequate analgesia for burn-injured patients being followed up at an outpatient department. Patient compliance was out of the scope of this study. METHODS: The study was conducted in the Pietermaritzburg Burn Service (PBS) in Pietermaritzburg, South Africa, and was undertaken in two parts. The first part was conducted through an anonymous, voluntary questionnaire completed by doctors working in hospitals referring to the PBS. The aim of the questionnaire was to identify deficits in knowledge of doctors regarding background analgesia for burn-injured children. The second part was conducted through an audit of the outpatient folders of children attending the PBS outpatient clinic to identify discrepancies between analgesia prescribed and analgesia supplied to the patient. RESULTS: Thirty-six doctors completed the questionnaire. While nearly all the doctors prescribed background analgesia, just over half (58%) prescribed paracetamol, and of those, only half prescribed the correct dose. Half of the doctors prescribed tilidine, and only half of them knew the correct dose. Forty-seven percent of the doctors prescribed both paracetamol and tilidine for background analgesia. The outpatient folders of 59 children attending the outpatient clinic were audited. Fifty-three patients were prescribed paracetamol. There was a statistically significant difference between the paracetamol volume prescribed and the volume supplied (p<0.0001). Twenty-four patients were prescribed ibuprofen. There was a statistically significant difference between the ibuprofen volume prescribed and the volume supplied (p<0.0001). CONCLUSIONS: Burn-injured children commonly receive inadequate analgesia in our setting. The reasons for this are multifactorial. The correct dose and the correct drugs for burn-related background pain are deficits in the knowledge of doctors who deal with this common problem. Furthermore, even if the correct drug and dose are prescribed, the correct volume of medication is often not issued by the pharmacy. This study highlights barriers to achieving adequate analgesia in children with burns being managed as outpatients. Potential strategies to overcome barriers include improving education with regard to pain management and burns at an undergraduate and postgraduate level, and improved supply chain management.

[Basic Knowledge of Drug Pain Therapy in the Palliative Situation]. / Basiswissen zur medikamentösen Schmerztherapie in der Palliativsituation.

This review provides an overview of the basic knowledge of drug pain therapy in the palliative situation. Pain is one of the main symptoms in 60 to 90 % of cancer patients. Pain also develops with neurological and other diseases that occur in end-of-life situations. To address this symptom, a holistic strategy is required that encompasses all physical, psychological, social, and spiritual aspects of the multi-dimensional pain experience ("total pain" concept).Drug treatment for cancer pain has been based on a stepwise approach for many years, starting with non-opioid analgesics, followed by moderate and strong opioids. In contrast, today's pain management is determined more by the actual intensity of this aversive event.The pain assessment should be tailored to identify a nociceptive vs. neuropathic pain component that needs to be challenged by the most appropriate drug therapies. Non-opioid analgesics are ideal substances for relieving nociceptive pain. Antidepressants and anticonvulsants reduce the intensity of new neuropathic pain. Opioids are suitable for all types of pain, but are restricted to a second line choice. Among all opioids are tilidine and tramadol prodrugs, which only relieve pain after activation in the liver. Drug-drug interactions may also block this activation. Rapid release opioids should be used for cancer breakthrough pain. Transdermal opioid applications are recommended for swallowing disorders, but usually not to initiate pain control. An opioid switch can be performed if side effects such as hallucinations for the selected opioid are more pronounced than the pain reduction.

[Management of chronic pain using extended release tilidine : Quality of life and implication of comedication on tilidine metabolism]. / Management von chronischem Schmerz mit retardiertem Tilidin : Lebensqualität und Bedeutung der Komedikation für den Tilidinmetabolismus.

BACKGROUND AND OBJECTIVES: The synthetic opioid tilidine is often used in chronic pain treatment. However, the activation via metabolism in patients with concomitant medication and reduced liver or kidney function is not thoroughly investigated. We therefore studied pain treatment efficacy, health-related quality of live and the metabolism of tilidine in patients with chronic pain. METHODS AND MATERIALS: In all, 48 patients, who were on a stable dose of oral prolonged release tilidine for at least 7 days, were included in this observational multicenter study. Liver and kidney function were assessed in routine blood samples, concentrations of tilidine, nortilidine and bisnortilidine were determined using a validated LC/MS/MS method. Comedication was registered and patients experience with regard to quality of life, pain, gastrointestinal symptoms and adverse events was assessed in standardised questionnaires. RESULTS: On average a daily dose of 180 mg tilidine was taken. Dose normalized plasma concentrations of the active metabolite nortilidine ranged between 1.6 ng/ml and 76.5 ng/ml (mean 29.2 ± 25.1 ng/ml). Ratios between tilidine and nortilidine were on average 0.28 (median = 0.13, standard deviation = 0.67). Patients were on 1 to 14 different concomitant medications. About 66% of the patients had sufficient pain treatment. Almost no opioid-induced constipation was observed. Only few patients had decreased kidney or liver function which did not result in elevated nortilidine concentrations. CONCLUSION: Pain treatment using tilidine resulted in variable nortilidine concentrations which are obviously not strongly influenced by comedication or reduced liver or kidney function. Only a few side effects were observed with almost no opioid-induced constipation.

Treatment Options for Central Sleep Apnea: Comparison of Ventilator, Oxygen, and Drug Therapies.

Central sleep apnea (CSA) is a sleep-related disorder characterized by pauses in breathing during sleep when the brain respiratory network momentarily interrupts transmission of impulses to the respiratory musculature. CSA presents significant problems being an independent risk factor for cardiovascular events and death. There are several available treatment options according to CSA severity. Currently, adaptive servo-ventilation is considered best for CSA patients. The goal of the present study was to retrospectively investigate different treatment methods employed for CSA, such as different modes of ventilation, oxygen therapy, and drugs to determine the most effective one. Data were obtained from hospital records during 2010-2015. The diagnosis of CSA and the optimal treatment method were supported by polysomnography examinations. Devices used during sleep to support breathing included continuous positive airway pressure, bi-level positive airway pressure, or adaptive servo-ventilation. We classified 71 (2.9 %) patients as having CSA from 2,463 patients with sleep-disordered breathing. Of those 71 patients, 54 (76.1 %, 95 % CI 66.2-86.0 %) were male and 17 (23.9 %, 95 % CI 14.0-33.8 %) were female, and they had a mean age of 67.1 ± 14.1. Four (5.6 %) patients underwent a combination therapy, 39 (54.9 %) received a ventilator in proper ventilation mode, 25 (35.2 %) received oxygen therapy, 7 (9.9 %) received medication, and 4 (5.6 %) received no treatment. We conclude that although the majority of patients needed treatment for central sleep apnea, a clear advantage in using ventilators when compared to oxygen therapy or drug therapy could not be found.

[Efficacy of epidural steroid injections for chronic lumbar pain syndromes without neurological deficits. A randomized, double blind study as part of a multimodal treatment concept]. / Wirksamkeit periduraler Steroidinjektionen in der Therapie von nichtradikulären chronischen Rückenschmerzen. Eine randomisierte, doppelverblindete Vergleichsstudie im Rahmen eines multimodalen Behandlungskonzeptes.

BACKGROUND: Chronic lumbar pain syndromes without neurological deficits are generated by a multitude of causes. Functional, morphological and psychosocial factors are discussed. In many cases a diseased intervertebral disc is found on radiological examination but the clinical relevance of these findings is not clear. For this study it was postulated that a diseased disc results in a local inflammatory reaction therefore causing pain and impairing treatability of patients. An epidural injection of steroids can reduce inflammation and therefore improve treatability and ultimately treatment outcome. METHODS: A double blind randomized prospective trial was carried out. Patients treated in hospital for a chronic lumbar pain syndrome without neurological deficits within a multimodal treatment program were screened for indications for an epidural steroid injection (e.g. diseased lumbar disc and intention to treat). Patients eligible for the study were randomized into two groups. The treatment group received an epidural injection of 80 mg triamcinolone and 8 ml bupivacaine 0.25 %. The control group received only an epidural injection of 8 ml bupivacaine 0.25 %. RESULTS: In both groups pain intensity and treatability showed a statistically significant improvement after the epidural injection. The differences between the control and treatment groups were small and not clinically relevant. A small subgroup might profit from the steroid injection. In addition the treatability was dependent on psychometric values and the long-term outcome from a reduction of muscular skeletal dysfunctions. DISCUSSION: After the epidural injection the decrease in pain and increase in treatability was statistically significant. The mechanism of the improvement is not clear and should be examined further. The epidural injection of a steroid in this subgroup of patients did not lead to a clinical improvement in the outcome.

Topical review on the abuse and misuse potential of tramadol and tilidine in Germany.

BACKGROUND: Tramadol and tilidine (in combination with naloxone) are used as weak opioid analgesics in Germany. Tramadol is not scheduled in the German Narcotic Drugs Act. Tilidine is scheduled, whereas Tilidine in fixed combinations with naloxone is exempt from some of the provisions of the Narcotic Drugs Act. Recent reports on misuse of both substances led to an evaluation of their potential for misuse, abuse, and dependency by the expert advisory committee established by the German Federal Government, resident at the Federal Institute for Drugs and Medical Devices. METHODS: A subcommittee formulated key questions and identified available data sources for each of these questions. Additional information was solicited where necessary, including a survey among a panel of pharmacists, a survey in an addiction clinic, analysis of prescription patterns, and information from the boards of pharmacists of the federal states and the Federal Bureau of Criminal Investigation. RESULTS: Analgesic efficiency in the treatment of acute and chronic pain has been proven for both tramadol and tilidine/naloxone. For tramadol, high evidence has been confirmed in systematic reviews, and tramadol is listed in national and international guidelines on acute and chronic pain management. Animal and human studies found a low potential for misuse, abuse, and dependency for both substances. Information from 2 tramadol safety databases allowed calculation of the incidence of abuse or dependency as 0.21 and 0.12 cases per million defined daily dosages (DDDs), with lower incidences in recent years. For tilidine/naloxone, the incidence was calculated as 0.43 cases per million DDDs for oral solution and 0.18 for slow-release tablets. In an online survey among German pharmacies as well as in the reports from state pharmacy boards, fraud attempts were repeated more frequently with tilidine/naloxone than with tramadol in the last 2 years. The Federal Bureau of Criminal Investigations reported prescription fraud only with tilidine/naloxone and predominantly in the region of Berlin. Dependency on tramadol or tilidine/naloxone is reported only rarely from addiction counseling centers. One third of the patients surveyed in an addiction clinic reported experiences with tramadol or tilidine/naloxone, but mostly with duration of less than 4 weeks and with a medical prescription based on a reasonable indication. Also, occasional illegal use of opioid analgesics as a substitute of heroin was reported. An evaluation of pooled data from statutory health insurance companies found 2.5% of persons receiving at least 1 prescription of tramadol or the combination of tilidine and naloxone in 2009 (1.6% with tramadol and 1.0% with tilidine/naloxone). High usage with more than 180 DDDs per year was found in 8.6% of patients treated with tramadol and 17.2% of patients with tilidine/naloxone. CONCLUSIONS: In conclusion, the subcommittee of the expert advisory committee found a low potential for misuse, abuse, and dependency for tramadol, and a low prevalence in clinical practice. Considerable less information is available for the combination of tilidine and naloxone. However, the cumulation of evidence indicated a higher risk of misuse, abuse, and dependency for tilidine/naloxone solution, but not for slow-release tablets.

[Acute pain management in proximal femoral fractures: femoral nerve block (catheter technique) vs. systemic pain therapy using a clinic internal organisation model]. / Akutschmerztherapie bei Patienten mit hüftgelenknahen Frakturen : N.-femoralis-Katheter-Analgesie vs. systemische Schmerztherapie unter Anwendung eines klinikinternen Organisationsmodells.

BACKGROUND: The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management. METHODS: In a prospective randomised trial of patients attending the emergency department, 100 individuals were selected with a clinically diagnosed proximal femoral fracture. Patients were divided into two equal groups A and B. Group A (n=50) received a catheter-mediated femoral nerve block with 1% prilocaine (40 ml) and post-operatively 0.2% ropivacaine (30 ml) 6 hourly. Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg). Patients aged 90 years or more received a reduced dose (tilidine 75 mg + naloxone 6 mg). In the post-operative period regular oral ibuprofen (400 mg, 8 hourly) in addition to oral tilidine (50 mg) + naloxone (4 mg) was given as required for break through pain. Pain intensity was measured using a verbal rating scale (VRS) from 1 to 5: pain free (=1), mild pain (=2), moderate pain (=3), severe pain (=4), excruciating pain (=5). Pain scores were recorded at rest (R), during passive anteflection (30 degrees) of the hip (PA) on arrival and at 15 and 30 min after initial administration of analgesia. Thereafter, recordings were made 4 times a day up to the third post-operative day. RESULTS: Pain scores were comparable for both groups on admission (VRS in R 2.50 vs. 2.46; VRS during PA 4.30 vs. 4.34). Significant pain relief was achieved in both groups following initial administration of analgesia, but the total pain scores in group A were significantly lower than in group B (VRS in R 1.22 vs. 1.58, p<0.01 and VRS during PA 2.66 vs. 3.26; p<0.001). No difference was noted between the two groups during the first 3 post-operative days. No severe complications occurred as a result of analgesia, however, the catheter was dislodged in 20% of patients in group A resulting in the need for systemically administered analgesia. CONCLUSION: All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging. Femoral nerve block should be considered as the method of choice. The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management. The cumbersome logistics inherent in this technique within the clinical setting limits its practical application. An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative. The execution of safe, consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocols as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice.

[Postoperative pain therapy with tilidin and tilidin retard as an oral patient-controlled analgesia after uncomplicated myocardial revascularization]. / Die postoperative Schmerztherapie mit Valoron-N-Lösung und Valoron-N-retard. Tabletten als orales Patienten-kontrolliertes Analgesieverfahren nach herzchirurgischen Routine-Bypassoperationen.

OBJECTIVE: The purpose of this study was to evaluate whether or not the combination of tilidin and tilidin retard as oral patient-controlled analgesia provide a suitable pain management in patients after uncomplicated myocardial revascularization. METHODS: We conducted a randomised phase IV study to evaluate the effectiveness of postoperative analgesia with tilidin and tilidin retard. Patients with a baseline tilidin retard and tilidin liquid demand medication (group B, 42 patients) were compared with a base line paracetamol and tramadol-HCl liquid demand medication (group A, 44 patients). All patients received the first dose of study medication at the second postoperative day after evaluation of the individual pain score using NRS (numeric rating scale). RESULTS: Pain relief in group B was significantly better only at the second postoperative day (NRS 1,8 compared to 3,3 in group A), associated with tolerable side effects and comfortable handling. CONCLUSION: The combination of sustained release with immediate release drugs as a patient controlled analgesia provides suitable and comfortable analgesia after myocardial bypass surgery.

Adverse effects of opioid analgesic treatment are correlated with a significant elevation in plasma epinephrine in healthy humans.

OBJECTIVE: The purpose of this study was to elucidate the relationship of plasma catecholamine concentrations with experienced pain intensity and analgesic effects in the setting of an experimental pain study with human volunteers. METHODS: Plasma norepinephrine and epinephrine concentrations of 12 healthy human volunteers were analysed before and during painful electrical tooth-pulp stimulation under medication using the highly potent opioid analgesic tilidine in a fixed tilidine/naloxone combination and with the non-steroidal anti-inflammatory agent bromfenac. Catecholamine levels were compared with pharmacodynamic effects and reported adverse effects. RESULTS: Catecholamine levels revealed a statistically significant increase in plasma epinephrine concentrations (but not norepinephrine concentrations) 60-90 min after administration of tilidine/naloxone. This was correlated with the onset of adverse effects involving vertigo episodes in all reported cases. In contrast, there was no obvious correspondence of epinephrine or norepinephrine plasma concentrations to the experience of pain and analgesia. For comparison, under medication with the non-opioid analgesic bromfenac, only one mild adverse effects were noted, and no changes in plasma epinephrine or norepinephrine could be determined during the experimental sessions. CONCLUSIONS: It is proposed that elevated plasma epinephrine concentrations are a newly determined response to opioid-induced vertigo; this has possible clinical implications.

Comparison of tilidine/naloxone, tramadol and bromfenac in experimental pain: a double-blind randomized crossover study in healthy human volunteers.

AIM: The analgesic efficacy and safety of single oral doses of two centrally acting compounds, the combination of 50 mg tilidine and 4 mg naloxone (Valoron N) and 50 mg tramadol (Tramal), were compared to 25, 50 and 75 mg of the non-steroidal antiinflammatory bromfenac in experimental pain. SUBJECTS AND METHODS: It was a placebo-controlled double-blind 6-way crossover study design with 12 human volunteers. Acute pain was generated by electrical tooth pulp stimulation. Treatment effects were determined by recording somatosensory-evoked potentials and by subjective pain rating. RESULTS: The tilidine/naloxone combination clearly was the most potent medication in this study, followed by bromfenac 75 mg, which produced an early pain relief. Tramadol produced poor analgesia, as did bromfenac 25 and 50 mg. There was no dose-response relationship for bromfenac. Control of plasma levels revealed pronounced interindividual differences in peak plasma concentrations for bromfenac, but not for tramadol. Tilidine/naloxone exerted adverse effects in 9, tramadol in 3 volunteers. Under medication with 25 and 50 mg bromfenac, respectively, only one subject reported adverse effects. No adverse effects were experienced with 75 mg bromfenac or placebo. CONCLUSION: The results support previous conclusions about the analgesic efficacy of tilidine/naloxone and tramadol in experimental pain. Moreover, the findings suggest that 75 mg bromfenac might be suitable for fast but short relief of pain of non-inflammatory genesis.