Practice variation in opioid prescribing for non-cancer pain in Dutch primary care: A retrospective database study.

BACKGROUND: Prescription opioid use has increased steadily in many Western countries over the past two decades, most notably in the US, Canada, and most European countries, including the Netherlands. Especially the increasing use of prescription opioids for chronic non-cancer pain has raised concerns. Most opioids in the Netherlands are prescribed in general practices. However, little is known about variation in opioid prescribing between general practices. To better understand this, we investigated practice variation in opioid prescribing for non-cancer pain between Dutch general practices. METHODS: Data from 2017-2019 of approximately 10% of all Dutch general practices was used. Each year included approximately 1000000 patients distributed over approximately 380 practices. The primary outcome was the proportion of patients with chronic (>90 days) high-dose (≥90 oral morphine equivalents) opioid prescriptions. The secondary outcome was the proportion of patients with chronic (<90 oral morphine equivalents) opioid prescriptions. Practice variation was expressed as the ratio of the 95th/5th percentiles and the ratio of mean top 10/bottom 10. Funnel plots were used to identify outliers. Potential factors associated with unwarranted variation were investigated by comparing outliers on practice size, patient neighbourhood socioeconomic status, and urbanicity. RESULTS: Results were similar across all years. The magnitude of variation for chronic high-dose opioid prescriptions in 2019 was 7.51-fold (95%/5% ratio), and 15.1-fold (top 10/bottom 10 ratio). The percentage of outliers in the funnel plots varied between 13.8% and 21.7%. Practices with high chronic high-dose opioid prescription proportions were larger, and had more patients from lower income and densely populated areas. CONCLUSIONS: There might be unwarranted practice variation in chronic high-dose opioid prescriptions in primary care, pointing at possible inappropriate use of opioids. This appears to be related to socioeconomic status, urbanicity, and practice size. Further investigation of the factors driving practice variation can provide target points for quality improvement and reduce inappropriate care and unwarranted variation.

Quality of recovery after day care surgery with app-controlled remote monitoring: study protocol for a randomized controlled trial.

BACKGROUND: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. METHODS: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. DISCUSSION: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. TRIAL REGISTRATION: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772).

Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands.

Pain is one of the main complaints of trauma patients in (pre-hospital) emergency medicine. Significant deficiencies in pain management in emergency medicine have been identified. No evidence-based protocols or guidelines have been developed so far, addressing effectiveness and safety issues, taking the specific circumstances of pain management of trauma patients in the chain of emergency care into account. The aim of this systematic review was to identify effective and safe initial pharmacological pain interventions, available in the Netherlands, for trauma patients with acute pain in the chain of emergency care. Up to December 2011, a systematic search strategy was performed with MeSH terms and free text words, using the bibliographic databases CINAHL, PubMed and Embase. Methodological quality of the articles was assessed using standardized evaluation forms. Of a total of 2328 studies, 25 relevant studies were identified. Paracetamol (both orally and intravenously) and intravenous opioids (morphine and fentanyl) proved to be effective. Non-steroidal anti-inflammatory drugs (NSAIDs) showed mixed results and are not recommended for use in pre-hospital ambulance or (helicopter) emergency medical services [(H)EMS]. These results could be used for the development of recommendations on evidence-based pharmacological pain management and an algorithm to support the provision of adequate (pre-hospital) pain management. Future studies should address analgesic effectiveness and safety of various drugs in (pre-hospital) emergency care. Furthermore, potential innovative routes of administration (e.g., intranasal opioids in adults) need further exploration.

Pain relief and quality-of-life improvement after spinal cord stimulation in painful diabetic polyneuropathy: a pilot study.

BACKGROUND: Painful diabetic polyneuropathy (PDP) is associated with high pain scores and is difficult to treat. Therefore, spinal cord stimulation (SCS) has been suggested as second-line treatment. In this study, the feasibility and efficacy of SCS in PDP were investigated, as well as the predictive value of clinical sensory testing for the treatment outcome. METHODS: Fifteen patients with intractable PDP in the lower limbs were recruited. During lead implantation, the feasibility of achieving adequate paraesthesia coverage using one stimulation lead was investigated. If trial stimulation was successful, a definitive neurostimulator was implanted. Pain intensity was scored using an 11-point numeric rating scale and patients' global impression of change scale. Additionally, neuropathic pain characteristics, quality of life, sleep quality and mood were assessed. The predictive value of clinical sensory testing for the treatment outcome was analysed. RESULTS: Adequate paraesthesia coverage was achieved in 14 out of 15 patients. Clinically relevant pain relief was present in 11 patients after trial stimulation and 10 patients at 12 months. The quality of life was significantly increased at 2 weeks and 3 months in patients with successful SCS treatment. Several neuropathic pain characteristics and quality of sleep were improved at 2 weeks and 12 months. Preoperative clinical sensory testing did not differentiate between treatment responders from non-responders. CONCLUSIONS: SCS seems to be an efficacious and feasible treatment for intractable PDP. In this exploratory study, it was not possible to predict the treatment outcome using clinical sensory testing. These results justify performing a randomized clinical trial.

[Ketamine as a party drug]. / Ketamine als partydrug.

Ketamine is a new party drug, which is easy to obtain. For this reason, it is possible that physicians will be increasingly confronted with users that have medical problems. Relatively few cases of ketamine intoxication with a fatal outcome have been reported thus far. Ketamine is very hallucinogenic; people can experience unpleasant flashbacks even weeks after the drug has been eliminated from the body. Ketamine has a short half-life; the elimination half-life is about 2.5 h. A serious intoxication can lead to aspiration, acidosis, rhabdomyolysis, epileptic seizures, respiratory depression, and cardiac arrest. Ketamine is frequently used as a party drug in combination with other substances. As a result, the chance of untoward effects is increased. Anaesthetists use ketamine for short surgical procedures, sedation and analgesia. It is also used more and more often as an analgesic in patients who do not respond well to opioids.

Minimally invasive placement of epidural plate electrodes under local anaesthesia in spinal cord stimulation.

In the treatment of pain syndromes of different aetiologies a change has occurred from destructive interventions to stimulation procedures. Spinal cord stimulation is the best known example of this treatment strategy. It is used often in patients with persistent neuropathic pain syndromes in an extremity, for instance following low back surgery. This treatment is most frequently performed by a percutaneous placement of a single electrode, with the aid of a specially designed Tuohy needle to reach the epidural space. In cases where, for different reasons, a larger, plate electrode is needed, this has to be placed surgically by a small laminectomy. The general anaesthesia mostly needed for this procedure prevents trial stimulation necessary to check the correct electrode position. Besides this, the laminectomy procedure can subsequently result in new pain complaints due to the invasiveness of the procedure. To solve both problems we have modified the implantation technique. By using a tubular retractor system (METRx system, Medtronic Sofamor Danek, Memphis, TN), originally developed for minimally invasive degenerative disc surgery, it is possible to reach the epidural spinal space and introduce the plate electrode with a small approach under local anaesthesia both allowing trial stimulation and avoiding severe postoperative backache related to the approach in these patients.

Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of 173 ng/ml is described. For pain relief an epidural infusion at the level T1-2 with bupivacaine was started. Immediate pain relief was accompanied by short lasting respiratory depression and drowsiness.

Codeine analgesia is due to codeine-6-glucuronide, not morphine.

Eighty per cent of codeine is conjugated with glucuronic acid to codeine-6-glucuronide. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the mu-receptor to result in analgesia, codeine-6-glucuronide in analogy to morphine-6-glucuronide must be the active constituent of codeine. Poor metabolisers of codeine, those who lack the CYP450 2D6 isoenzyme for the O-demethylation to morphine, experience analgesia from codeine-6-glucuronide. Analgesia of codeine does not depend on the formation of morphine and the metaboliser phenotype.

Intrathecal coadministration of bupivacaine diminishes morphine dose progression during long-term intrathecal infusion in cancer patients.

OBJECTIVE: To determine the difference in intrathecal morphine dose progression between a continuous intrathecal infusion of a morphine/bupivacaine mixture and morphine for pain relief in patients with cancer. DESIGN: Patients were treated with intrathecal drugs in a randomized study and followed prospectively until death. SETTING: Institute for Anesthesiology, Department of Pain Treatment, University Hospital Nijmegen, St Radboud, The Netherlands. PATIENTS: Twenty patients with cancer were selected for intrathecal treatment because of either side effects or inadequate relief during conventional pain treatment. INTERVENTIONS: Intrathecal drug infusion rates and medication were adjusted according to pain relief and side effects. OUTCOME MEASURES: Progression of intrathecal morphine dose during a phase of adequate analgesia in both groups following regression analysis and analysis of possible treatment related side effects. RESULTS: The combination of intrathecal morphine and bupivacaine resulted in a diminished progression of the intrathecal morphine dose (slope of regression line = 0.0003 vs. 0.005, p = 0.0001) during a phase of stable analgesia in comparison with the morphine group. No serious side effects presented. CONCLUSION: The diminished intrathecal morphine dose increase in the combination group is considered to be due to a synergistic effect of bupivacaine on the intrathecal morphine-induced antinociception. A dose increment during long-term intrathecal infusion in cancer patients appears to be related to both disease progression and tolerance phenomena.

Topical use of local anesthetics in neonates.

INTRODUCTION: Various local anesthetics as in lidocaine ointment, amethocaine cream and EMLA cream are used topically for minor invasive interventions, such as venipuncture, both in children and adults. Since neonates have a nervous system that, albeit immature, enables them to feel pain, analgesia for these procedures is also indicated. Several studies in neonates have been carried out to establish effectiveness and safety of topically applied local anesthetics. These studies are reviewed in order to assess effectiveness and safety. METHODS: A Medline search was made in order to review all studies on effectiveness and safety of topical use of local anesthetics in neonates. Effectivity or safety studies using local anesthetics for circumcision were rejected. RESULTS: Seven studies on effectiveness were found: Three studies examined lidocaine ointment and four examined EMLA cream. Effectiveness of lidocaine ointment was questionable in two studies and negative in one. Effectiveness of EMLA cream was positive in two studies and negative in the other two. Four studies were found on safety of EMLA cream. All studies indicated that use of EMLA cream was safe. DISCUSSION: The poor effectiveness found in the reviewed studies is possibly due to too long an application time, a lipophilic carrier used and difficulties in assessing pain. The time of application is often based upon studies in children. Since the skin of neonates acts more as a mucosa than as mature skin the local anesthetics are able to cross this barrier more rapidly. Also a high bloodflow in the heel enhances the uptake of the drug. The application time in neonates should therefore be reduced compared to children. The use of a lipophilic carrier should be avoided since a lipophilic carrier impedes the local anesthetic to be absorbed, leading to reduced effect. Various methods of pain assessment were being used. Since not all methods used are validated it is difficult to obtain an objective end point. CONCLUSION AND RECOMMENDATION: The articles reviewed are non conclusive in their results of effective analgesia. Due to a lipophilic base form and a hydrophilic matrix EMLA cream is most effective. An application time of 30 minutes is recommended. In spite of the present precautions due to fear of methemoglobinemia, use of EMLA cream proved to be safe when used once a day. Since the clinical situation often requires more than one application a day, more research is needed to establish a safe and effective local anesthetic which can be applied topically several times a day in the neonate.

Safety of lidocaine-prilocaine cream application four times a day in premature neonates: a pilot study.

UNLABELLED: Although safety is established for lidocaine-prilocaine cream application to the heel once a day in neonates, it is often necessary to repeat heel lances several times a day in the clinical situation. A pilot safety study applying 0.5 g lidocaine-prilocaine cream to the heel covering an area of 5 cm2 with an occlusive dressing during 30 min four times a day was carried out. Twelve neonates (5 male, 7 female) with a gestational age of 30.1-36.3 weeks (mean 31.6 weeks) and a birth weight of 1100-2910 g (mean 1665 g) were enclosed. To establish safety, methaemoglobin levels and plasma concentrations of lidocaine, prilocaine and o-toluidine were measured until 24 h after the final application. Methaemoglobin levels were no different from baseline measurements, ranging from 0.2-1.1% and 0.1-0.7% respectively. Plasma concentrations of lidocaine and prilocaine were very low, maxima at 0.230 and 0.223 mg/l respectively. Plasma o-toluidine concentrations remained below the detection limit (0.025 mg/l). CONCLUSION: Application of 0.5 g lidocaine-prilocaine cream to the heel under occlusion four times a day during 30 min is safe in preterm neonates. Establishing safety by measuring the methaemoglobin level by daily application is recommended.

Neurological impairment during long-term intrathecal infusion of bupivacaine in cancer patients: a sign of spinal cord compression.

Adequate pain relief in patients with far advanced cancer sometimes requires intrathecal (IT) administration of a combination of opioids and local anesthetics. Tumor progression as well as the IT administration of local anesthetics can lead to neurologic dysfunction during treatment. Five patients showed symptoms of compression of the cauda equina or spinal cord shortly after the start of combined IT administration of morphine and bupivacaine in a dosage usually not associated with neurologic symptoms. Unexpectedly, neurologic evaluation suggested compression of the cauda equina and spinal cord, which was confirmed radiographically. Manifestation of new neurologic symptoms during low dose bupivacaine infusion intrathecally might therefore be an early indicator of space-occupying processes within the spinal canal in cancer patients.

[Intrathecal administration of morphine and bupivacaine in the treatment of severe pain in chronic pancreatitis]. / Intrathecale toediening van morfine en bupivacïne ter behandeling van ernstige pijn bij chronische pancreatitis.

A 25-year-old male with idiopathic chronic pancreatitis suffered from severe pain not reacting to medical therapy. Intractable pain persisted after the following procedures: subtotal resection of the pancreas, interpleural administration of bupivacaine, epidural administration of bupivacaine, and thoracoscopic sympathectomy. Eventually, adequate pain relief was achieved with intrathecal administration of morphine and bupivacaine. An infusion pump, externally controlled by radiotelemetry, was implanted subcutaneously for intrathecal drug administration. With this pump the patient was fully ambulant. Intrathecal administration of morphine and bupivacaine through an implanted pump is a possible new technique for pain management in chronic pancreatitis.

Morphine and morphine-glucuronide concentrations in plasma and CSF during long-term administration of oral morphine.

Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid (CSF) samples from 16 patients with cancer receiving oral (controlled-release) morphine. There was a close correlation between plasma and CSF morphine concentrations (r = 0.94, P = 0.0001) and both correlated with drug dosage (r = 0.61, P = 0.013 and r = 0.74, P = 0.0001, respectively). M3G and M6G in plasma and CSF were correlated (r = 0.81 and r = 0.82, both P = 0.0001). No relationship was apparent between M plus M6G concentrations in the CSF and pain scores.