Prescription of Opioid Analgesics for Chronic Non-Cancer Pain in Germany despite Contraindications: Administrative Claims Data Analysis.

In Germany, long-term opioid treatment (L-TOT) for chronic non-tumor pain (CNTP) is discussed as not being performed according to the German guideline on L-TOT for CNTP. In the present analysis, the occurrence and predictors of inappropriate care/overuse in a cohort of German insureds with L-TOT for CNTP by the presence of a contraindication with concurrent opioid analgesic (OA) therapy were investigated. We also analyzed whether prescribing physicians themselves diagnosed a contraindication. The retrospective cohort study was based on administrative claims data from a German statutory health insurance. Eight contraindication groups were defined based on the German guideline. Logistic regressions were performed in order to identify predictors for OA prescriptions despite contraindications. The possible knowledge of the prescribing physician about the contraindication was approximated by analyzing concordant unique physician identification numbers of OA prescriptions and contraindication diagnoses. A total of 113,476 individuals (75% female) with a mean age of 72 years were included. The most common documented contraindications were primary headaches (8.7%), severe mood disorders (7.7%) and pain in somatoform disorders (4.5%). The logistic regressions identified a younger age, longer history of OA therapy, opioid related psychological problems, and outpatient psychosomatic primary care as positive predictors for all contraindication groups.

Management of chronic orofacial pain: a survey of general dentists in german university hospitals.

AIM: This survey assessed procedures performed by general dentists in German university hospitals treating patients with chronic orofacial pain (COP). METHODS: A standardized questionnaire was sent to dentists at all 42 German universities. Doctors were asked to describe demographics, diagnoses, etiologies, diagnostic, and treatment procedures for their patients seen over a 3-month period. RESULTS: A total of 34,242 patients from 19 responding university hospitals were enrolled. COP of greater than 6 months duration was identified in 1,767 patients (5.2%), of whom 64% were female, 76% were between 20 and 59 years old, 66.3% frequently changed doctors, and 29.5% demonstrated psychological comorbidities. The most common causes of COP were temporomandibular disorders, atypical odontalgia, and atypical facial pain accounting for 83.4% of the sample, with purported etiologies of surgery or trauma (52.4%), musculoskeletal disorders (24.2%), prosthetics (11.4%), or psychosomatic causes (11.7%). A secondary pain syndrome was found in 25% of patients. Before admission to the universities, 59.4% of patients reported inadequate pain control. Following admission, the number of patients receiving specialized therapies significantly increased from 40.6% to 88.2% (chi(2) test; P < 0.001), and improved pain was reported in 71.4% of patients. Multimodal therapy included treatment of malocclusion (47.1%), surgery (37.7%), analgesics (27.5%), and physiotherapy (22%). Specialized pain assessment (26.5%) or visual analog scales (16.9%) were applied irregularly and pain therapists were rarely consulted (8.9%). Despite the high psychological comorbidity (29.5%), psychological treatments were obtained for only 11%. CONCLUSIONS: The prevalence of COP is 5% in German University dental practices, where current guidelines of COP treatment are followed incompletely, and patients with psychological disorders are usually not treated. Interdisciplinary practice principles should be encouraged.

Effects of spinal anaesthesia versus epidural anaesthesia for caesarean section on postoperative analgesic consumption and postoperative pain.

BACKGROUND AND OBJECTIVE: Regional anaesthesia is commonly used for elective caesarean section. The aim of this study was to investigate whether there is a positive effect of either spinal or epidural anaesthesia on postoperative analgesic requirements and pain relief. METHODS: The analgesic effect of either spinal or epidural induction of perispinal anaesthesia have been compared in 132 women (ASA I or II) scheduled for elective caesarean section, all having epidural catheterization for perioperative anaesthesia and postoperative analgesia. The patients were randomized into two groups. To achieve a sensory block height to the level of the sixth thoracic dermatome, the parturients received isobaric bupivacaine 0.5% and 5 microg sufentanil intrathecally or ropivacaine 0.75% and 10 microg sufentanil epidurally. For postoperative analgesia, all patients used patient-controlled epidural analgesia at identical settings [bolus of ropivacaine 0.133% (11-15 mg according to patient's height), lock-out time 1 h]. Intraoperative and postoperative pain was recorded using a visual analogue pain score as well as analgesic requirements over the first 24 h after surgery. RESULTS: One hundred and twenty-five patients completed the study. There were no differences in patient-controlled epidural analgesic requirements between groups. During surgery, the pain score on a visual analogue scale was more intense with epidural anaesthesia than with spinal anaesthesia (P < 0.05). For the whole 24 h observation period, the area under the curve for pain was lower with spinal anaesthesia (P < 0.0005). At almost all postoperative time points, visual analogue scale scores at rest and during mobilization were lower with spinal anaesthesia (P < 0.05), which was accompanied by less motor blockade and lower frequency of adverse effects. More patients with epidural anaesthesia received supplemental analgesic medication. CONCLUSION: In parturients undergoing elective caesarean section, postoperative use of epidural ropivacaine via patient-controlled epidural analgesia is similar after spinal and epidural anaesthesia. Spinal anaesthesia is, however, accompanied with less postoperative pain, use of additional analgesics and side-effects.

Gastrointestinal symptoms under opioid therapy: a prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine.

INTRODUCTION: The purpose of this trial was to evaluate the effect of long-term treatment with oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine on nausea, emesis and constipation. PATIENTS AND METHODS: Randomly selected outpatients with cancer pain receiving one of the study medications were enrolled in a prospective, open-labeled, controlled trial (n=174). Mobility, pain, and gastrointestinal symptoms were assessed directly and per selected item on the ECOG (Eastern Cancer Oncology Group), EORTC (European Organisation for Research and Treatment of Cancer) questionnaires, NRS (Numerical Rating Scales), and analyzed statistically. RESULTS: Demographic and medical data were comparable in all groups. Only 15% of patients suffered from constipation. 59% took the prescribed laxatives. The incidence of stool free periods >72 h was significantly higher with transdermal opioids (transdermal fentanyl: 22%; transdermal buprenorphine: 21%; oral hydromorphone: 2%; p=0.003). 21% of patients revealed nausea and emesis. The mean NRS for nausea (transdermal fentanyl:1.3; transdermal buprenorphine: 1.2; oral hydromorphone: 1.5; p=0.6), the consumption of antiemetics (transdermal fentanyl: 42%; transdermal buprenorphine: 33%; oral hydromorphone: 36%; p=0.6) and laxatives (transdermal fentanyl:53%; transdermal buprenorphine:66%; oral hydromorphone: 61%; p=0.2) did not differ significantly, in contrast to the score for emesis (transdermal fentanyl: 16%; transdermal buprenorphine:13%; oral hydromorphone: 33%; p=0.02). Morphine equivalent opioid doses differed (mg/d transdermal fentanyl: 183; transdermal buprenorphine: 89; oral hydromorphone: 143; p=0.001), because of obvious tolerance varying after long-term treatment. CONCLUSIONS: Gastrointestinal symptoms of cancer pain patients undergoing an opioid therapy are related to multifactorial causes. Transdermal opioids showed no benefit over oral controlled-release hydromorphone with regard to gastrointestinal symptoms. The conversion ratios for transdermal fentanyl, transdermal buprenorphine, and oral hydromorphone did not accord to the literature, because of differing occurrences of opioid tolerance after long-term therapy.

A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

BACKGROUND: Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised, double-blinded study evaluated the analgesic efficacy of prolonged-release (PR) oral oxycodone when co-administered with PR oral naloxone, and its impact on opioid-induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone. METHODS: A total of 202 patients with chronic pain (mainly non-cancer related, 2.5% of patients had cancer-related pain) under stable oral oxycodone therapy (40, 60 or 80 mg/day) were randomised to receive 10, 20, 40 mg/day naloxone or placebo. After a 4-week maintenance phase, patients received oxycodone only for 2 weeks. Pain intensity was evaluated using a numerical analogue scale and bowel function was assessed using the bowel function index. RESULTS: No loss of analgesic efficacy with naloxone was observed. Mean pain intensity scores on randomisation were comparable for placebo, 10mg, 20mg and 40 mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo (p<0.05). Overall, the combination was well tolerated, with no unexpected adverse events. There was a trend towards an increased incidence of diarrhoea with higher doses of naloxone. The 2:1 oxycodone/naloxone ratio was identified as the most suitable for further development. CONCLUSION: Co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.

Temperament and character personality profiles and personality disorders in chronic pain patients.

In his psychobiological model of personality, Cloninger developed a novel approach concerning the relationships between psychopathological syndromes and personality. We investigated 207 chronic pain patients (CPPs) and compared them to 105 pain-free control subjects. Participants were assessed using the Temperament and Character Inventory (TCI), the Structured-Clinical-Interview-II, the Beck Depression Inventory and the Spielberger Anxiety Inventory. The CPPs scored higher on the depression and state anxiety scales and 41% fulfilled the criteria of having at least one personality disorder (PD). We used a covariance analysis to control for depression and state anxiety and found that the CPPs scored higher on the Harm Avoidance Temperament Dimension and lower on the Self-Directedness and Cooperativeness Character Dimensions. In CPPs, the symptom counts of all PD subtypes were significantly related to low Self-Directedness and, to a lesser degree, low Cooperativeness. The PD symptoms in Cluster A were related to low Reward Dependence, those in Cluster B were related to high Novelty Seeking and the PD symptoms in Cluster C were related to high Harm Avoidance. In multiple hierarchical regression analyses, controlling for age, gender, depression and state anxiety, TCI scales predicted on average 23% in PD symptom counts. The Self-Directedness and Cooperativeness personality traits appeared to be significant predictors in determining the presence or absence of a PD by correctly classifying 75.8% of CPPs. The TCI provides further insight into the mechanisms underlying the development of chronic pain. This useful diagnostic instrument helps to economically and validly facilitate the identification of core PD features.

Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial.

PURPOSE: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. METHODS: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical Rating Scales (NRS)], or as categorical parameters, and analyzed by descriptive and confirmatory statistics (ANOVA, Wilcoxon, chi). RESULTS: Rotation was successful in 64% of patients experiencing pain (60%), and gastrointestinal (32%) and central (26%) symptoms under oral morphine (38%), transdermal fentanyl (22%), tramadol (20%), oxycodone (12%), or sublingual buprenorphine (8%). NRS of pain (4.1 to 3.2; P=0.015), gastrointestinal symptoms, especially defecation rates (P=0.04), and incidence of insomnia improved after an increase in morphine-equivalent doses from 108.9 to 137.6 mg/d without modifying concomitant analgesics or coanalgesics. CONCLUSIONS: Switching the opioid to oral hydromorphone may be a helpful technique to alleviate pain and several symptoms, but it is still not clear to what extent the underlying mechanisms, such as the technique of rotation itself, better dose adjustment, or using a different opioid have an impact.

Pain management procedures used by dental and maxillofacial surgeons: an investigation with special regard to odontalgia.

BACKGROUND: Little is known about the procedures used by German dental and maxillofacial surgeons treating patients suffering from chronic orofacial pain (COP). This study aimed to evaluate the ambulatory management of COP. METHODS: Using a standardized questionnaire we collected data of dental and maxillofacial surgeons treating patients with COP. Therapists described variables as patients' demographics, chronic pain disorders and their aetiologies, own diagnostic and treatment principles during a period of 3 months. RESULTS: Although only 13.5% of the 520 addressed therapists returned completely evaluable questionnaires, 985 patients with COP could be identified. An orofacial pain syndrome named atypical odontalgia (17.0 %) was frequent. Although those patients revealed signs of chronification, pain therapists were rarely involved (12.5%). For assessing pain the use of Analogue Scales (7%) or interventional diagnostics (4.6%) was uncommon. Despite the fact that surgical procedures are cofactors of COP therapists preferred further surgery (41.9%) and neglected the prescription of analgesics (15.7%). However, most therapists self-evaluated the efficacy of their pain management as good (69.7 %). CONCLUSION: Often ambulatory dental and maxillofacial surgeons do not follow guidelines for COP management despite a high prevalence of severe orofacial pain syndromes.

Individual value of brain tissue oxygen pressure, microvascular oxygen saturation, cytochrome redox level, and energy metabolites in detecting critically reduced cerebral energy state during acute changes in global cerebral perfusion.

The authors assessed the diagnostic value of brain tissue oxygen tension (PbrO2), microvascular oxygen saturation (SmvO2), cytochrome oxidase redox level (Cyt a+a3 oxidation), and cerebral energy metabolite concentrations in detecting acute critical impairment of cerebral energy homeostasis. Each single parameter as well as derived multimodal indices (arteriovenous difference in oxygen content [AVDO2], cerebral metabolic rate for oxygen [CMRO2], fractional microvascular oxygen extraction [OEF]) were investigated during controlled variation of global cerebral perfusion using a cisternal infusion technique in 16 rabbits. The objective of this study was to determine whether acute changes between normal, moderately, and critically reduced cerebral perfusion as well as frank ischemia defined by local cortical blood flow (lcoBF), brain electrical activity (BEA), and brain stem vasomotor control can be reliably identified by SmvO2, PbrO2, Cyt a+a3 oxidation, or energy metabolites (glutamate, lactate/pyruvate ratio). PbrO2, SmvO2, and Cyt a+a3 oxidation, but not cerebral perfusion pressure, were closely linked to lcoBF and BEA and allowed discrimination between normal, moderately reduced, and critically reduced cerebral perfusion (P < 0.01). Glutamate concentrations and the lactate/pyruvate ratio varied significantly only between moderately reduced cerebral perfusion and frank ischemia (complete loss of BEA and brain stem vasomotor control). Therefore, PbrO2, SmvO2, and Cyt a+a3 oxidation, but not glutamate and the lactate/pyruvate ratio, reliably predict the transition from moderately to critically reduced cerebral perfusion with impending energy failure.

Monitoring of cerebral perfusion pressure during intracranial hypertension: a sufficient parameter of adequate cerebral perfusion and oxygenation?

OBJECTIVE: A cerebral perfusion pressure (CPP) oriented treatment is a widely accepted standard for patients with intracranial hypertension. In an animal model of controlled intracranial hypertension we investigated whether CPP is a reliable parameter of sufficient cerebral perfusion and oxygenation. Using near-infrared reflexion spectroscopy the effect of decreasing CPP due to increasing intracranial pressure (ICP) on cerebral tissue oxygenation was studied. METHODS: Ten rabbits were subjected to artificially elevated ICP using the cisterna-magna infusion technique. Regional cerebral O(2) saturation of hemoglobin (tiSO(2)), regional tissue concentration of hemoglobin (tiHb), and CPP were recorded continuously. CPP was investigated with respect to tiSO(2). Electrocortical activity was simultaneously recorded by two-channel EEG to determine the onset of ischemia. RESULTS: Reduced CPP due to increased ICP led to a continuous decrease in tiSO(2.) There was progressive suppression of EEG frequency and amplitude with decreasing CPP in all animals. Onset of EEG-silence due to elevated ICP was observed in a wide range of CPP-values between 9 and 42 mmHg. At the same time tiSO(2) varied merely between 0 and 5%. CONCLUSIONS: Regarding the EEG effects due to increased ICP (EEG silence), CPP values showed a wide interindividual variability, in contrast to tiSO(2). In our animal model the sole calculation of CPP did not reflect adequate cerebral perfusion.

S(+)-ketamine attenuates myogenic motor-evoked potentials at or distal to the spinal alpha-motoneuron.

UNLABELLED: We investigated the effect of S(+)-ketamine on spinal cord evoked potentials (ESCPs) and myogenic motor-evoked potentials after electrical stimulation of the motor cortex in a rabbit model. This study was designed to characterize the relationship between ESCP characteristics and corresponding changes in compound muscle action potentials (CMAPs) derived from fore and hind limbs. Direct (D) and indirect (I) corticospinal volleys (ESCP) from the upper and lower thoracic spinal cord, recorded by two bipolar epidural electrodes, were assessed during IV administration of 0.02, 0.05, 0.1, and 0.2 mg. kg(-1) x min(-1) of S(+)-ketamine, each before and after neuromuscular blockade (0.4 mg/kg of cisatracurium), in 16 New Zealand White rabbits after single-pulse bipolar electrical stimulation of the motor cortex at 50 (threshold), 60, and 70 V. CMAP amplitudes at fore and hind limbs were significantly suppressed (P < 0.01) during infusion at 0.1 and 0.2 mL x kg(-1) x min(-1), whereas neither corresponding D- nor I-waves were altered. Similar findings were obtained during variation of stimulus amplitude (50-70 V). Multivariate regression analysis of CMAP amplitudes and various ESCP characteristics demonstrated no apparent interparametric association. These findings indicate that S(+)-ketamine modulates CMAP independent from corticospinal D- and I-wave-mediated facilitation at or distal to the spinal alpha-motoneuron. IMPLICATIONS: S(+)-Ketamine combines several anesthetic properties suitable for total IV neuroanesthesia, including minimal effects on neurophysiological monitoring. Recording of neural and myogenic responses after electrical stimulation of the motor cortex indicates that S(+)-ketamine modulates myogenic motor-evoked potentials by a peripheral mechanism at or distal to the spinal alpha-motoneuron.