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Ketamine is a dissociative anaesthetic; its mechanism of action is primarily an antagonism of the N-methyl-D-aspartate (NMDA) receptor. The role of ketamine, in particular in lower sub-anaesthetic doses, has recently gained increasing interest in pain management. It has been studied in a considerable number of trials and analysed in meta-analyses and systematic reviews. Based on these data, the primary role of ketamine in such low doses is as an 'anti-hyperalgesic', 'anti-allodynic' or 'tolerance-protective' agent. It therefore has a role in the treatment of opioid resistant or 'pathological' pain (central sensitisation with hyperalgesia or allodynia, opioid induced hyperalgesia, neuropathic pain) rather than as an 'analgesic' in its own right. Low dose ketamine also has 'preventive analgesia' properties. Furthermore, in higher doses it provides effective and safe sedation and analgesia for painful procedures. The place of ketamine in the treatment of chronic pain and the effects of long-term medicinal use remain unclear.

Objective: An audit of opioid prescribing in a large teaching hospital across all specialties was conducted to identify areas for improvement., Methods: Opioid medications prescribed for the entire patient admission were recorded and assessed using quality statements., Results and Discussion: Of 334 patients reviewed 209 (62.6%) were prescribed an opioid. Poly-prescribing of 'when required' (p.r.n.) opioids was frequent with 107 (51.2%) patients having more than one 'p.r.n.' opioid. Dosing intervals were too long for 146 (69.8%) patients leaving them at risk of breakthrough pain. The intramuscular route was prescribed for 100 (47.8%) patients, and 49 (23.4%) of prescriptions had an inappropriate variety of administration routes., Conclusion: Although the criteria for assessing opioid prescribing were stringent the prescribing was sub-optimal. This survey will form the basis for future quality initiatives.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Pain management has improved in the past few decades. Opioid analgesics have become the mainstay in the treatment of cancer pain whilst inter-disciplinary pain management programmes are the generally accepted approach to chronic pain of non-malignant origin. Recently some pain specialists have advocated the use of opioids in the long-term management of non-cancer pain. This has raised some fundamental questions about the purpose of pain management. Is it best to opt for maximum pain relief and comfort, or should one emphasise function and activity as higher priorities? Will the use of opioids create more autonomy for pain sufferers or will this add handicaps to lives which are already limited? Until more clinical outcome data are available we advocate caution in the use of opioid analgesia. Such caution can, and does, raise questions about the rights of the patient and the rights of the prescriber in a context where the facts do not point to a clear course of action.

In a prospective study of 167 patients with head and neck cancer, we assessed the causes and mechanisms of pain, as well as the efficacy and side effects of analgesic treatment, along World Health Organization (WHO) guidelines. The majority of patients had pain caused by cancer (83%) and/or treatment (28%), 4% had pain due to debility, and 7% had pain unrelated to cancer. Palliative antineoplastic treatment was performed in 32% of patients. Systemic analgesics were administered on 97% of a total of 8,106 treatment days, and coanalgesics or adjuvant drugs on 100%. The treatment proved to be very successful, as severe pain was experienced only during 5% of the observation period. In the absence of serious side effects, the most frequent symptoms observed were insomnia, dysphagia, anorexia, constipation, and nausea. The use of analgesic and adjuvant drugs along WHO guidelines to treat pain in head and neck cancer is highly effective and relatively safe.

We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case.

A cancer pain management unit can benefit markedly from a well-planned documentation system for administrative and scientific purposes. This article presents the principles of such a computerized system based on relational data base programs. The described system has been used by the authors for the last seven years. The successful documentation of more than 1400 patients over treatment periods of up to 2 years has provided detailed administrative and scientific information.

Cancer pain remains a major cause of suffering. Improvements in its management have made unrelieved cancer pain unacceptable. While pharmacotherapy is the mainstay of cancer pain treatment, other options such as radiotherapy, nerve blocks, etc., have to be considered as well. A comprehensive approach must also address psychosocial issues. A successful pharmacotherapy programme for cancer pain requires careful assessment of the origin and cause of the pain. The selection of analgesics has to be rationalised using a sequential approach such as the WHO stepladder. Oral application by the block in an individually titrated dosage is recommended. Although morphine remains the most useful opioid, it should be used in combination with nonopioids. Co-analgesics, which contribute to analgesia without being classical analgesics, should be used to treat pain of specific origin. Here membrane-stabilizers, antidepressants and steroids play an often underestimated role in the treatment of neurogenic pain. Anxiolytics and major tranquillisers should be avoided because they cause sedation without improving quality of analgesia. Calcitonin, diphosphonates and spasmolytics are of minor importance in this regard. Finally, concomitant medication to treat side effects of the therapy may be necessary in formulating a comprehensive treatment plan.

The efficacy of the World Health Organization's guidelines for cancer pain relief was examined in 401 dying patients. At the time of death, only 3% of the patients experienced severe or very severe pain; whereas 52% had no pain at all, 24% experienced only mild or moderate pain, and 20% were unable to rate their pain intensity. Analgesic drugs were the mainstay of therapy during the last 24 hr of life, being administered by mouth in 47% and parenterally in 44% of the patients. Only 9% of the patients required no systemic analgesics. Nonopioid analgesics alone were effective in 5% and a combination of nonopioids and "weak" opioids were effective in 16% of the patients. In the remaining 70% of the patients "strong" opioids alone or in combination with nonopioid analgesics were necessary to achieve adequate pain reduction. Additional adjuvant drugs to treat special types of pain or other symptoms were prescribed in 90% of the patients. Nonpharmacological measures, such as radiotherapy, nerve blocks or neurosurgery played only a very minor role at this stage of the disease. This study shows that cancer pain can be treated satisfactorily until death.

Inadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction. The management of postoperative pain (perhaps the most common form of acute pain) is traditionally attempted with fixed dosages of analgesics by relatively unpredictable routes (e.g. oral, rectal and intramuscular). Intravenous opioid infusions (an improvement) risk respiratory depression and require close monitoring and titration. Patient-controlled analgesia (PCA), by contrast, permits the most efficacious medication (pure opioid agonist) by the optimal route (intravenous) under direct control of the patient, and provides high levels of satisfaction and safety. Ideally, any opioid use should be integrated with a wide spectrum of other analgesic modalities in an anaesthesiology-based 'acute pain service'. The use of opioids for chronic pain of nonmalignant origin remains controversial. There is a perceived conflict between patients' interests and those of society. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity), anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when opioids are used appropriately to treat pain (so-called 'dual pharmacology'). With sensible guidelines, and in the context of a multidisciplinary pain clinic, opioids may provide the only hope of relief to many sufferers of chronic pain.

Bruce Parsons,1 Rainer Freynhagen,2,3 Stephan Schug,4,5 Ed Whalen,1 Marie Ortiz,1 Pritha Bhadra Brown,1 Lloyd Knapp61Pfizer Inc, New York, NY, USA; 2Department of Anesthesiology, Critical Care Medicine, Pain Therapy & Palliative Care, Pain Center Lake Starnberg, Benedictus Hospital, Tutzing, Germany; 3Department of Anesthesiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; 4Discipline of Anaesthesiology and Pain Medicine, Medical School, University of Western Australia, Perth, WA, Australia; 5Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, WA, Australia; 6Pfizer Inc, Groton, CT, USACorrespondence: Bruce ParsonsPfizer Inc, 235 East 42nd Street, New York, NY, USATel +1 212 573 1649Email bruce.parsons@pfizer.comBackground: Euphoria is a complex, multifactorial problem that is reported as an adverse event in clinical trials of analgesics including pregabalin. The relationship between the reporting of euphoria events and pregabalin early treatment responses was examined in this exploratory post-hoc analysis.Methods: Data were from patients with neuropathic or non-neuropathic chronic pain enrolled in 40 randomized clinical trials, who received pregabalin (75–600 mg/day) or placebo. Reports of treatment-emergent euphoria events were based on the Medical Dictionary of Regulatory Activities preferred term “euphoric mood”. Prevalence rates of euphoria events overall and by indication were assessed. Post-treatment endpoints included ≥30% improvements in pain and sleep scores up to 3 weeks as well as a ≥1-point improvement in daily pain score up to 11 days after treatment.Results: 13,252 patients were analyzed; 8,501 (64.1%) and 4,751 (35.9%) received pregabalin and placebo, respectively. Overall, 1.7% (n=222) of patients reported euphoria events. Among pregabalin-treated patients, a larger proportion who reported euphoria events achieved an early pain response compared with those who did not report euphoria (30% pain responders in week 1 with euphoria events [43.0%], without euphoria events [24.2%]). Results were similar for weeks 2 and 3. For Days 2–11, a larger proportion of pregabalin-treated patients with (relative to without) euphoria events were 1-point pain responders. Findings were similar in pregabalin-treated patients for sleep endpoints (30% sleep responders in week 1 with euphoria events [50.7%], without euphoria events [36.1%]). Similar results were found for weeks 2 and 3. Patients who received placebo showed similar patterns, although the overall number of them who reported euphoria events was small (n=13).Conclusion: In patients who received pregabalin for neuropathic or non-neuropathic chronic pain, those who experienced euphoria events may have better early treatment responses than those who did not report euphoria events.Keywords: euphoria, pain, pregabalin, sleep

Sonya Ting,1 Stephan Schug2,3 1Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, WA, Australia; 2Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; 3Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, University of Western Australia Anaesthesiology Unit, Royal Perth Hospital, Perth, WA, Australia Abstract: Pain is a common symptom that can be complex to treat. Analgesic medications are the mainstay treatment, but there is wide interindividual variability in analgesic response and adverse effects. Pharmacogenomics is the study of inherited genetic traits that result in these individual responses to drugs. This narrative review will attempt to cover the current understanding of the pharmacogenomics of pain, examining common genes affecting metabolism of analgesic medications, their distribution throughout the body, and end organ effects. Keywords: cytochrome P450, COMT, pharmacokinetics, pharmacodynamics, inherited traits

Summary: Tonsillectomy is one of the most frequently performed surgical procedures; however, pain management remains challenging. Procedure‐specific efficacy as well as specific risks of treatment options should guide selection of pain management protocols based on evidence and should optimise analgesia without harm. The aims of this systematic review were to evaluate the available literature and develop recommendations for optimal pain management after tonsillectomy. A systematic review utilising preferred reporting items for systematic reviews and meta‐analysis guidelines with procedure‐specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language up to November 2019 assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Out of the 719 potentially eligible studies identified, 226 randomised controlled trials met the inclusion criteria, excluding the studies examining surgical techniques. Pre‐operative and intra‐operative interventions that improved postoperative pain were paracetamol; non‐steroidal anti‐inflammatory drugs; intravenous dexamethasone; ketamine (only assessed in children); gabapentinoids; dexmedetomidine; honey; and acupuncture. Inconsistent evidence was found for local anaesthetic infiltration; antibiotics; and magnesium sulphate. Limited evidence was found for clonidine. The analgesic regimen for tonsillectomy should include paracetamol; non‐steroidal anti‐inflammatory drugs; and intravenous dexamethasone, with opioids as rescue analgesics. Analgesic adjuncts such as intra‐operative and postoperative acupuncture as well as postoperative honey are also recommended. Ketamine (only for children); dexmedetomidine; or gabapentinoids may be considered when some of the first‐line analgesics are contra‐indicated. Further randomised controlled trials are required to define risk and combination of drugs most effective for postoperative pain relief after tonsillectomy. [ABSTRACT FROM AUTHOR]

Summary: Caesarean section is associated with moderate‐to‐severe postoperative pain, which can influence postoperative recovery and patient satisfaction as well as breastfeeding success and mother‐child bonding. The aim of this systematic review was to update the available literature and develop recommendations for optimal pain management after elective caesarean section under neuraxial anaesthesia. A systematic review utilising procedure‐specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language between 1 May 2014 and 22 October 2020 evaluating the effects of analgesic, anaesthetic and surgical interventions were retrieved from MEDLINE, Embase and Cochrane databases. Studies evaluating pain management for emergency or unplanned operative deliveries or caesarean section performed under general anaesthesia were excluded. A total of 145 studies met the inclusion criteria. For patients undergoing elective caesarean section performed under neuraxial anaesthesia, recommendations include intrathecal morphine 50–100 µg or diamorphine 300 µg administered pre‐operatively; paracetamol; non‐steroidal anti‐inflammatory drugs; and intravenous dexamethasone administered after delivery. If intrathecal opioid was not administered, single‐injection local anaesthetic wound infiltration; continuous wound local anaesthetic infusion; and/or fascial plane blocks such as transversus abdominis plane or quadratus lumborum blocks are recommended. The postoperative regimen should include regular paracetamol and non‐steroidal anti‐inflammatory drugs with opioids used for rescue. The surgical technique should include a Joel‐Cohen incision; non‐closure of the peritoneum; and abdominal binders. Transcutaneous electrical nerve stimulation could be used as analgesic adjunct. Some of the interventions, although effective, carry risks, and consequentially were omitted from the recommendations. Some interventions were not recommended due to insufficient, inconsistent or lack of evidence. Of note, these recommendations may not be applicable to unplanned deliveries or caesarean section performed under general anaesthesia. [ABSTRACT FROM AUTHOR]

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Many patients still suffer severe acute pain in the postoperative period. Although guidelines for treating acute pain are widely published and promoted, most do not consider procedure-specific differences in pain experienced or in techniques that may be most effective and appropriate for different surgical settings. The procedure-specific postoperative pain management (PROSPECT) Working Group provides procedure-specific recommendations for postoperative pain management together with supporting evidence from systematic literature reviews and related procedures at The methodology for PROSPECT reviews was developed and refined by discussion of the Working Group, and it adapts existing methods for formulation of consensus recommendations to the specific requirements of PROSPECT. To formulate PROSPECT recommendations, we use a methodology that takes into account study quality and source and level of evidence, and we use recognized methods for achieving group consensus, thus reducing potential bias. The new methodology is first applied in full for the 2006 update of the PROSPECT review of postoperative pain management for laparoscopic cholecystectomy. Transparency in PROSPECT processes allows the users to be fully aware of any limitations of the evidence and recommendations, thereby allowing for appropriate decisions in their own practice setting. [ABSTRACT FROM AUTHOR]