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Preference: Anaesthesia and Intensive Care

62

News briefs

Parechovirus warning from ASID

The Australasian Society for Infectious Diseases (ASID) has found that more than 100 Australian infants had developed brain damage and developmental delays 1 year after they were hospitalised with the virus in 2013 and 2014, according to a report in The Straits Times. The symptoms include rashes, irritability, muscle twitches and seizures, fever and diarrhoea, said ASID. In severe cases, it can cause hepatitis or encephalitis. Parechovirus is spread like the common cold, by direct contact with nose and throat discharges from sneezing, coughing, saliva, nasal mucus or faeces. There is no vaccine or treatment at present. Starting in December 2013, it spread quickly through parts of Queensland, including Brisbane and the Gold Coast, and over 100 newborn babies were hospitalised. They refused to eat, were lethargic and had high temperatures. The new study followed up on 46 out of 79 of the babies. Half of them showed developmental problems and nearly 20% had significant neurological problems by the time they were 1-year-old. In March, two infants from Toowoomba almost died from the virus. Left fighting for life in intensive care, one of them had to be given painful spinal taps and have her chest cut open.

Soap operas play role in mental health understanding

According to a report in The Guardian, soap operas involving storylines about mental health can play a valuable role in increasing understanding of depression, anxiety and schizophrenia, and in encouraging people with problems to seek help. UK charity Mind conducted a survey of more than 2000 people, which found that half of the respondents who had seen a storyline involving a character with mental health problems said it had helped their understanding of the issues. Nearly a third of people with a mental health problem said they were encouraged to seek help after seeing or reading a news story, while a quarter were prompted to get assistance after seeing a soap opera or drama involving a character with mental illness. Mind, along with Bipolar UK, and Action on Postpartum Psychosis, worked with the soap EastEnders for a storyline over Christmas and the new year about a character with postpartum psychosis, a severe mental illness that normally occurs shortly after giving birth.

[Comment] Offline: The 500-year old cause of the doctors’ strike

For the first time in the history of the UK’s National Health Service (NHS), junior doctors went on strike twice last week. They withdrew their labour from emergency and intensive care, in protest at the UK Government’s decision to impose a new employment contract. Jeremy Hunt, the Conservative Secretary of State for Health, says repeatedly that junior doctors are “the backbone of the NHS”. But he also argues that the strike is not about health. It is, he says, about bringing his government down.

[Comment] Gut microbiome and necrotising enterocolitis: time for intervention?

Despite improvements in neonatal intensive care, the birthweight-specific incidence of necrotising enterocolitis has not changed over the past three decades. However, the total burden of disease is increasing because of increased survival of very low birthweight infants. Mortality remains high and complications include post-surgical short bowel syndrome and its outcomes (prolonged dependence on total parenteral nutrition, recurrent infections, poor growth, and liver failure), long hospital stays, and long-term neurodevelopmental impairments.

New cosmetic surgery guidelines encourage cooling off periods

The Medical Board of Australia has introduced a range of new guidelines in a bid to crackdown on the cosmetic surgery industry.

The guidelines aim to inform medical professionals and the community about the expectations the Board has for doctors who perform cosmetic surgery procedures.

According to Board Chair, Dr Joanna Flynn, “The guidelines will help keep patients safe, without imposing an unreasonable regulatory burden on practitioners.”

Related: Delay implants, women advised

The 6 page guidelines were developed after draft guidelines were circulated in March 2015.

“The Board listened to stakeholder feedback, and responded with a new set of guidelines that will best keep patients safe,” Dr Flynn said.

“The changes prioritise patient safety and reduce some of the regulatory requirements proposed in the previous draft guidelines, when either there was no evidence of improved safety or the costs significantly outweighed the benefits of a proposal,” she said.

Related: Cosmetic clinic under fire over surgeries

9 key points from the guidelines include:

  • There should be a 7 day cooling off period for all adults before any major procedure (anything that involves cutting beneath the skin);
  • Adult patients should be referred to a psychologist, psychiatrist or general practitioner if there are any indications of underlying psychological problems;
  • There should be a 3 month cooling off period for all under 18s before major procedures and a mandatory evaluation from a registered psychiatrist, psychologist or general practitioner;
  • There should be a 7 day cooling off period for all under 18s before minor procedures (cosmetic medical procedures that do not involve cutting beneath the skin but may involve piercing the skin);
  • The treating medical practitioner must take responsibility for any post-operative care;
  • The treating medical practitioner must make sure there are emergency facilities when using sedation, anaesthesia or analgesia;
  • There needs to be a mandatory consultation (either by person or by video conference) before medical practitioner prescribes schedule 4 cosmetic injectables;
  • Medical practioners need to provide detailed, written information to the patient to ensure they are making informed consent. Information should include the range of possible outcomes, complications and recovery times associated with the procedure and the qualifications and experience of the medical practioner;
  • Medical practitioners need to provide patients with detailed written information about costs including any costs for follow-up care or any potential revision surgery or treatment.

The new guidelines will take effect on 1 October 2016. Read the Cosmetic Surgery Guidelines.

Latest news:

Acute pain management: scientific evidence, fourth edition, 2015

In 1999, the first edition of Acute pain management: scientific evidence was written by a multidisciplinary committee under the guidance of Michael Cousins and published by the National Health and Medical Research Council (NHMRC).1 As there has been a substantial increase in the quantity and quality of publications about acute pain management, the Australian and New Zealand College of Anaesthetists (ANZCA) and its Faculty of Pain Medicine (FPMANZCA) have taken responsibility for revising and updating the available evidence every 5 years.2,3 The fourth edition, which became publicly available in December 2015,4 will be available in hardcopy soon, but can already be downloaded for free in pdf format from http://www.anzca.edu.au/resources/college-publications.

Development and methods

As with the first three editions, the document aimed to combine a review of the best available evidence on acute pain management with current clinical and expert practice, rather than to formulate specific recommendations for clinical practice. Accordingly, the document summarises the evidence currently available on the management of acute pain from over 8000 references, and presents it in a concise and easily readable form to aid practising clinicians. The document was prepared by following the methods established over the preceding three editions. All evidence is documented according to NHMRC levels of evidence, from Level I (systematic reviews of randomised controlled trials [RCTs]) to Level IV (case series).5 However, for the first time, this fourth edition scores systematic reviews and RCTs for quality, and reports the numbers of studies included and patients randomised, to allow readers to assess the relevance of the evidence presented. As in previous editions, the document is preceded by a summary list of all key messages (now totalling 669). These key messages provide concise statements on each topic, showing the highest level of evidence, and clinical practice points based on clinical experience or expert opinion. The document also shows the status of each key message in comparison with the previous edition (eg, new, unchanged, strengthened, qualified, or reversed).

The document addresses all aspects of acute pain management. There are sections on:

  • the physiology, psychology and the assessment of acute pain;

  • analgesic medicines and routes and techniques of their administration (eg, regional techniques, patient-controlled analgesia [PCA]); and

  • non-pharmacological techniques (eg, physical therapies, acupuncture and psychological techniques).

Furthermore, specific clinical situations, such as post-operative pain and acute medical and cancer pain, are addressed, as well as acute pain in specific settings (eg, burns units, intensive care units, emergency departments). Pain in children is dealt with for the first time in a detailed section presenting evidence-based management for this complex and challenging group. Other groups covered in detail are pregnant women, older patients, and patients with opioid tolerance or with an addiction. Culturally responsive care for culturally and linguistically diverse patients, with an emphasis on Aboriginal, Torres Strait Islander and Maori peoples, is also addressed.

Post-operative pain management

This brief overview cannot cover all the evidence provided in the document, but focuses on that related to post-operative pain, one of the most common manifestations of acute pain. However, many of the issues related to post-operative pain are translatable to other acute pain scenarios, in particular pain after trauma. Most of the following statements are summaries or direct quotations of the key messages in the fourth edition.4

Multimodal analgesia

The overall concept underlying post-operative (and other) acute pain relief is multimodal or “balanced” analgesia, that is, the use of combinations of analgesics or analgesic techniques with different modes or sites of action. Such an approach (eg, combining a non-opioid with an opioid or a regional analgesia technique with a systemic analgesic) improves pain control compared with mainly opioid-based analgesia, and reduces opioid consumption (ie, is “opioid-sparing”) and thereby reduces adverse effects.

Opioid-sparing analgesic approaches permit earlier mobilisation and earlier enteral feeding after surgery and so may contribute to early recovery overall. However, providing appropriate analgesia is only one of several elements of “enhanced recovery after surgery (ERAS)” protocols aiming to reduce hospital stays and complication rates. Furthermore, different surgical procedures cause different pain states (eg, musculoskeletal versus visceral) of different severity in different locations.

Procedure-specific post-operative pain management

As the efficacy of analgesics can be different in different surgical settings, pooling of data from various post-operative pain states may ignore the specific effects of a specific analgesic or technique in a specific post-operative setting. Therefore, post-operative pain requires a procedure-specific approach to analgesia. The recognition of this need has led to the development of the Prospect (PROcedure-SPECific post-operative pain managemenT) initiative (http://www.postoppain.org), which provides procedure-specific evidence-based recommendations for the treatment of pain after a wide range of operations.6,7

Acute neuropathic pain

In assessing acute pain after surgery and trauma, acute neuropathic pain is often overlooked or its severity underestimated. This has important consequences, as neuropathic pain does not respond to many common analgesics, and requires specific therapeutic approaches. Ketamine, opioids (including tramadol or tapentadol) and α2δ ligands (gabapentin or pregabalin) are the preferred systemic treatment options for acute neuropathic pain, as a rapid onset of effect is needed in this setting. Early recognition of neuropathic pain in an acute setting is also relevant, as chronic post-surgical pain and post-traumatic pain often have a neuropathic component. Risk factors that predispose to the development of such pain include the severity of pre-surgical chronic pain and post-surgical acute pain, and intraoperative nerve injury. Chronic pain after surgery and trauma is more common than generally thought, and can lead to significant disability. Diagnosis and subsequent appropriate treatment of acute neuropathic pain might prevent the development of chronic pain.

Preventive analgesia

Some analgesic interventions have an effect on post-operative pain and/or analgesic consumption that exceeds the expected duration of action of the medicine. Such interventions are defined as preventive analgesia. Ketamine and local anaesthetics have such a preventive effect. There are now also data that show that ketamine, certain regional analgesic techniques and possibly calcium channel α2δ subunit ligands (gabapentin and pregabalin) prevent the development of chronic post-surgical pain. There are significant associations between psychosocial factors such as anxiety, pain catastrophising, depression, psychological vulnerability and stress and the subsequent development of chronic post-surgical pain.

Regional analgesia and continuous peripheral nerve blocks

There is increasing evidence for the role of regional anaesthesia techniques in providing effective post-operative pain relief. Such techniques are not only preventive as outlined above, but provide overall excellent analgesia with minimal systemic adverse effects and can thereby improve and accelerate recovery. The evidence remains strong for continuous epidural analgesia, in particular after major thoracic and abdominal surgery with improved return of bowel function and overall reduced morbidity and possibly even mortality. However, this technique is underutilised in some parts of the world due to the fear of serious complications, in particular in conjunction with use of anticoagulants, and to the perceived increased workload in managing patients with thoracic epidural analgesia. This has led to increased use of continuous peripheral nerve blocks in the post-operative setting, which, compared with single-injection peripheral nerve blocks, result in improved pain control, decreased need for opioid analgesics, reduced nausea and improved patient satisfaction.

Compared with opioid analgesia, continuous peripheral nerve blocks (regardless of catheter location) provide better post-operative analgesia and reductions in opioid use as well as decreased nausea, vomiting, pruritus and sedation. The use of ultrasound guidance to perform blocks increases block success rates, reduces block performance time and the risk of local anaesthetic toxicity and results in faster onset and longer duration of analgesia compared with localisation using a peripheral nerve stimulator.

Techniques for which there is particularly good evidence include continuous thoracic paravertebral analgesia (for unilateral thoracotomies and after rib fractures) and transversus abdominis plane blocks (after abdominal surgery), as well as a broad range of peripheral nerve blocks of the upper and lower limb (after orthopaedic surgery). After total knee joint replacement, femoral nerve blocks are a proven approach, but there is also increasing evidence to support local infiltration analgesia.

With regard to complications, post-operative neurological dysfunction is often related to patient and surgical factors, and the incidence of neuropathy directly related to regional anaesthesia is rare. Continuous peripheral and regional nerve blocks carry a risk of infection; skin preparation with alcohol-based chlorhexidine and full barrier precautions (including face masks) are recommended for insertion of peri-neural catheters.

Patient-controlled analgesia

Opioids remain an important component of systemic analgesia for the relief of severe pain despite the multiple opioid-sparing approaches. In the early post-operative setting, intravenous opioids delivered via PCA provide better analgesia than conventional parenteral opioid regimens and result in greater patient satisfaction. Adding a background infusion to morphine delivered intravenously via PCA in opioid-naive patients increases the incidence of respiratory depression and does not improve pain relief or sleep, or reduce the number of PCA demands. There is little evidence that any particular opioid delivered via PCA is superior to another in regard to analgesic or adverse effects in general, but individual patients may tolerate one opioid better than another. The safety of PCA use can be significantly improved by hospital-wide safety initiatives (“smart pumps”, equipment, guidelines, education, monitoring).

Non-opioid analgesics

There is good evidence to support the use of non-opioid analgesics to complement opioid analgesics for multimodal analgesia; non-steroidal anti-inflammatory drugs (NSAIDs) are superior to paracetamol (and combining both increases efficacy) and COX-2 inhibitors (coxibs) offer safety advantages over non-selective NSAIDs, in particular with regard to platelet dysfunction leading to blood loss. The risk of adverse renal effects of non-selective NSAIDs and coxibs is increased in the presence of factors such as pre-existing renal impairment, hypovolaemia, hypotension and the use of other nephrotoxic agents including angiotensin-converting enzyme inhibitors. Other analgesic options include peri-operative intravenous lignocaine, which has been shown to reduce pain and opioid requirements after abdominal surgery and to decrease nausea, vomiting, duration of ileus and length of hospital stay. Peri-operative intravenous ketamine reduces opioid consumption, time to first analgesic request and post-operative nausea and vomiting compared with placebo. It is particularly helpful in opioid-tolerant patients. Peri-operative administration of α2δ ligands reduce post-operative pain and opioid requirements and reduce the incidence of vomiting, pruritus and urinary retention, but increase the risk of sedation. The peri-operative use of systemic α2-receptor agonists (clonidine and dexmedetomidine) reduces post-operative pain intensity, opioid consumption and nausea without prolonging recovery times, but the frequency and severity of adverse effects (bradycardia and hypotension) sometimes limit their clinical usefulness. Dexamethasone reduces post-operative pain and opioid requirements to a limited extent, but also reduces nausea and vomiting, fatigue, and improves the quality of recovery compared with placebo. Current evidence does not support the use of cannabinoids in acute pain management.

Non-pharmacological strategies

There is some evidence to support non-pharmacological techniques for providing post-operative analgesia. Transcutaneous electrical nerve stimulation (TENS) compared with sham TENS reduces acute pain (procedural and non-procedural), including pain after thoracic surgery. Acupuncture (specifically, auricular acupuncture) reduces post-operative pain and opioid requirements, as well as opioid-related adverse effects compared with a variety of controls. Beneficial effects of acupuncture on post-operative pain have been confirmed in particular after back surgery and ambulatory knee surgery and total knee joint replacement. Psychological (including distraction [music, books, video] and hypnosis), physical (including holding, warming, non-nutritive sucking) and use of sweet solution (sucrose) interventions are particularly beneficial in painful procedures in children and are being used peri-operatively.

Conclusion

The increase in evidence in the area of acute pain management over the past 15 years is impressive. Based on the evidence available, which is summarised in the fourth edition of Acute pain management: scientific evidence,4 physicians can make evidence-based decisions in most acute pain scenarios. Such an approach improves the safety and effectiveness of treatment of patients in acute pain, thereby reducing pain and suffering. These guidelines are even relevant to primary care physicians, who may influence outcomes in these patient populations.

However, a significant gap remains between evidence and practice in the area of acute pain management. It is the challenge for all health care professionals to reduce this gap to benefit our patients.

Using opioids in general practice for chronic non-cancer pain: an overview of current evidence

Chronic non-cancer pain is highly prevalent in our communities and its optimal management is crucial to the health and wellbeing of the community.1 Without good control of chronic pain, our community faces a level of avoidable suffering that cannot be justified, with costs of uncontrolled chronic pain borne across society by individuals, health services and businesses.2,3 At both the level of the individual patient and the community, there needs to be focus on using the best available evidence to assess and manage this overwhelming problem. Part of the appropriate treatment for many people will include opioid analgesics for acute pain at least for days to weeks.4 Simultaneously there is increasing pressure to ensure that prescribing of opioid analgesics is minimised to reduce the risk of dependence and illicit diversion. This is a difficult balance to strike, even with initiatives such as prescription drug monitoring programs.5

This article provides a brief overview of the current evidence to guide opioid use for chronic non-cancer pain in general practice.

Chronic pain: definitions and epidemiology

The International Association for the Study of Pain defines chronic pain as that which has persisted beyond normal tissue healing time; by convention, this is usually interpreted as pain that lasts for more than 3 months.6 Definitions for the duration of pain, intensity and level of interference with daily activities vary around the world. In the adult Australian population, pain has been defined as chronic if experienced daily for three of the past 6 months.1 Prevalence varies with the definition of chronicity.7,8

Chronic non-cancer pain is a major health problem around the world with prevalence rates as high as 33% of the population in western populations.9 It is prevalent across our communities, with up to 17.1% of men and 20.0% of women in Australia likely to experience the problem.1 These rates are comparable to those found in Denmark and Canada.10 Much higher rates have been reported from the United Kingdom, where rates may be as high as 46.5% of the population.11 Pain that interferes markedly with daily functioning has a rate in Australia of 5.0% of the population, with the strongest predictor being a work-related injury in an adjusted model with an odds ratio of 19.3 (95% CI 7.30–51.30; P < 0.001).12

The most frequently identified pains are those affecting the lower back and from osteoarthritis.11 As expected, the prevalence of pain increases with age, with some of the highest rates seen in residential aged care facilities.13 Chronic neuropathic pain is estimated to occur in one in 11 people.14

Chronic prescribing has been defined as 90 days or more of opioid prescribing in the past 120 days;15 this definition is congruent with that of the International Association for the Study of Pain.6

Current guidelines for safe prescribing of opioids for chronic non-malignant pain

The two most current and comprehensive evidence-based guidelines for the use of opioids for chronic non-cancer pain come from the United States and Canada.16,17 They share the stated purpose of ensuring the appropriate management of chronic non-cancer pain while minimising abuse of opioids.

The Canadian guideline is for all practitioners working with chronic non-cancer pain, not just clinicians in specialist pain practice (Box 1).17 Major domains in considering such therapy are outlined in the document: assessing patients for the suitability for opioids; initiating a therapeutic trial of opioids and monitoring long term use. Sections are devoted to particular patient populations. One recurring theme in the clinical recommendations is to treat only “well defined somatic or neuropathic pain conditions when non-opioid alternatives have failed”.17 Care needs to be taken when deciding to initiate or titrate opioids, especially in more vulnerable populations who have relevant comorbid conditions, and great care is necessary if people require more than 200 mg of oral morphine equivalents. Another key theme is the need for the clinicians involved in a patient’s care to have clear lines of accountability with each other and for agreed communication strategies among treating clinicians.

Guidelines from the US stress that the use in the longer term (more than 3 months) of opioids for chronic non-cancer pain has little data to support the practice.16 However, in contrast to the Canadian guideline, the US guidelines suggest that doses of greater than 91 mg of morphine equivalent should be treated with caution and specialist advice sought. There is some evidence to support prescription drug monitoring programs and urine drug testing as mechanisms to reduce abuse potential. Less robust evidence supports a thorough patient assessment, risk-screening tools, controlled-substance agreements, careful dose titration, opioid dose ceilings, and adherence to practice guidelines reduces the risk of aberrant prescription drug-related behaviours.18

With respect to Australian recommendations, most recently the National Prescribing Service (NPS) has released a series of documents providing clinical advice for health professionals engaged in the care of people with chronic pain. This includes a section titled “Best practice opioid analgesic prescribing for chronic pain”, with the Australian recommendations similar to those of the US suggesting that daily doses above 100 mg morphine equivalent should be avoided. Further, recommendations made by the NPS include the fact that when commencing opioids, initial doses should be low with careful and supervised titration.19 A summary of the NPS recommendations is included in Box 2.

Current prescribing trends in Australia

Australia continues to experience rising rates of opioid prescription.20 Between 1992 and 2012, Australian opioid dispensing episodes increased from 0.5 million prescriptions to 7.5 million, with no evidence to suggest that these figures are reaching a plateau.21 There has also been an increase in the number of opioid preparations available (n = 241), including morphine (n = 87), fentanyl (n = 43) and oxycodone (n = 37) as the largest three groups.21 The indication on the Pharmaceutical Benefits Scheme generally includes use for chronic severe disabling pain that is not responsive to non-opioids. The variation in opioid prescribing across Australia has recently been highlighted in the Australian Atlas of Healthcare Variation published by the Australian Commission on Safety and Quality in Health Care (http://www.safetyandquality.gov.au/atlas).

The overall increase in opioids in Australia likely reflects a population that continues to grow rapidly in part because of increasing life expectancy with chronic illnesses of ageing often associated with pain, previous under-prescribing, increasing incidence and survival from cancer, increased numbers of preparations available, poor access to allied health for non-pharmacological interventions, poor undergraduate and postgraduate education about opioid prescribing, aggressive marketing and the imperative for health professionals to better manage pain.20

Clinical consequences of opioid use

Despite the prevalence of pain across the community, overall chronic non-cancer pain generally remains poorly treated, resulting in limitations in activity and diminished quality of life. Although there are a variety of strategies available to help manage chronic non-cancer pain, for many people opioids are prescribed long term. While some patients do achieve effective analgesia, an estimated 40–70% of people with chronic pain do not,22 with the balance towards those who appear not to benefit from opioids in the long term.23 It is important to consider how the long term use is balanced with the risk of short and long term adverse effects of opioids.

Shorter term harms

Typically shorter term side effects are considered unpleasant but unlikely to lead to long term consequences (Box 3). Data from a systematic review suggest that for every four patients commenced on opioids, at least one person would experience at least one of these effects in a 1–8-week period.24

Longer term harms

Longer term harms may include physical and psychological issues and dependence. (Box 4) While most of the adverse effects that occur when opioids are commenced are expected to resolve rapidly,25 the adverse effects of constipation, sedation or dizziness for some people may not settle, all of which can cause significant morbidity. Older patients taking the equivalent of at least 50 mg of morphine daily have a twofold risk of sustaining a fracture as a result of a fall.26

Opioids may contribute to acceleration of loss of bone mineral density in the long term and to hypogonadism because of their suppression of hypothalamic gonadotrophin-releasing hormone. This can lead to amenorrhea or oligomenorrhea in premenopausal women and erectile dysfunction in men.27 There is also a 28% increase in the risk of myocardial infarction for people taking opioids long term.28

Psychological impacts include higher rates of depression after chronic opioid therapy is initiated in people who were not previously depressed. In this same cohort, higher rates of anxiety, lower self-efficacy and a tendency towards catastrophising were seen regardless of the opioid doses.29

People who use opioids long term for chronic non-cancer pain are at greater risk of misusing them, including through psychological dependency and overdose. These problems are prevalent in this cohort, with rates of misuse (21–29%) and addiction (8–12%) a cause for grave concern.30

The risk of sudden death due to opioids is amplified in the context of concurrent benzodiazepine and/or alcohol (mis)use.31

Aside from the direct adverse effects of opioids, there are several other potential negative consequences. There is a subset of people who are not concurrently using other agents such as alcohol, who are on modest doses of opioids and not currently experiencing high levels of pain, for whom driving is likely be to be safe.32 In Australia, recommendations include the suggestion that people should not drive if they feel drowsy or impaired. Further, due to the persistent miotic effects, driving at night is discouraged. If there are concerns regarding capacity, a practical driving assessment may be requested by health professionals with the details as to how to achieve this in each state, dependent on the local driver-licensing authority.33 Proper assessments of capacity are important given that health service use increases with opioid use. Higher rates of hospitalisations, emergency department presentations and even unintentional death have been recorded.31,34 The evidence that supports the benefits outweighing the risks of long term opioids for chronic pain is very poor. There is real need for further research to most clearly define which patients are most likely to benefit from opioids and what are the most suitable precautions to safeguard them from harm.35

GPs’ attitudes to prescribing opioids for chronic non-cancer pain

Despite the development of various guidance documents for the safe and effective use of opioids,17,19,36,37 GPs continue to be concerned about the risk of opioid dependence and misuse for patients with chronic non-cancer pain. There are also concerns expressed by GPs about their capacity to manage the complex physical and psychological needs of this patient cohort, and their role in long term prescribing and the limitations of available treatment approaches.38–41 Regional difference in opioid-prescribing confidence has been noted in a pan-European online survey of primary care pain management practices.41 GPs in Norway (46%), Sweden (43%) and Poland (37%) reported lower levels of opioid-prescribing confidence, which they attributed to fears of addiction and adverse events.41 GPs in the UK, the Netherlands, France and Italy were more confident about prescribing opioids for patients with chronic non-cancer pain, which they attributed to their experience and the therapeutic treatment choices available.41

Opioid prescribing in primary care is complex because of the need to optimise pain management while balancing the risks of tolerance and addiction.37 Inappropriate prescribing is more likely when patients are exposed to repeated consultations that do not meet their needs and if GPs feel powerless to negotiate an alternative plan of care and set appropriate boundaries.38,42 If there is a perceived paucity of treatment alternatives, opioid prescribing can occur as a default decision.38 Variations in opioid prescribing have previously been linked to GPs’ pain management training, experience and exposure to adverse opiate-related events.43

What can be done to reduce inappropriate prescribing?

While there are opportunities to address inappropriate prescribing at the system, provider and patient levels, one of the most immediate changes could be achieved simply by supporting GPs to manage patients’ chronic non-cancer pain in accordance with recommended guidelines.39

Evidence-based guidelines provide GPs with an evidence-based framework for the collaborative development of a treatment plan with the patient.37 There are also opportunities to strengthen safe opioid prescribing by GPs for non-malignant pain through specific education programs.44 Combining clinician education with an opioid dose limitation practice policy45 and implementing a practice policy of not providing repeat opioid prescriptions or authorising a dose increase without a formal medical review may reduce the risk of inappropriate dose escalation.38

High level evidence supports the use of methadone or buprenorphine in patients with chronic non-cancer pain who are addicted to opioids (high level evidence).17

Indications to prescribe or not prescribe chronic opioids

Only carefully selected patients should be considered for long term opioids for chronic non-cancer pain that is moderate to severe, has led to substantial negative impacts on daily living and has failed all other analgesic modalities and adequate allied health assessments.46 Any concerns about the prevalence of opioid prescribing must be balanced with ensuring that people with opioid-responsive pain are adequately treated.47 Evidence is slowly building to refine prescribing guidelines, maximising benefits and minimising harms.48 Many of the more routine pain problems such as chronic back pain or chronic headaches are unlikely to respond to opioids, in contrast to more severe and physically disabling problems such as destructive rheumatoid arthritis.34

Managing aberrant patient behaviour

Aberrant behaviour related to prescription medications includes any behaviour that suggests non-medical use of a drug or evidence of addiction, such as drug-seeking behaviour, alternative routes of delivery, obtaining opioids from other sources or unsanctioned use.39 Preventing aberrant drug-related behaviour requires minimising the risk of opioid misuse while optimising the best evidenced-based treatments for patients with chronic non-cancer pain. In order to minimise harm, these patients require an approach that is similar to other chronic illness interventions, which includes appropriate non-pharmacological and pharmacological approaches, and an individualised evidence-based risk-mitigation plan to optimise adherence.39 There is good evidence that determining the treatment goals of pain relief and improved function can minimise the risk of aberrant behaviour.37 Prescribing tamper-resistant opioids currently offers the highest level of prevention of opioid misuse.18

If a patient with chronic non-cancer pain requests an early opioid prescription, it is important to consider the possibility that the patient may have developed tolerance to the opioid, thus requiring a higher dose to maintain the same level of pain control; developed physical dependence and is experiencing early withdrawal symptoms; diverted some or all of his or her opioids for financial gain; or that a third party may have diverted the prescribed opioids.49 Once aberrant behaviour has developed, management becomes more complex and is likely to require a range of responses including urgent referral to specialist services, urine drug screening and other compliance monitoring, treatment agreements, and patient education. High level evidence suggests that when combined, these measures can reduce substance misuse by 50%.50

Ensuring adequate prescribing when indicated

Promoting and implementing the guidance offered by recently updated guidelines and providing clinicians with point-of-care resources can help to ensure adequate and safe opioid prescribing for patients where opioids are indicated. In patients with acute pain, both the US and Canadian guidelines suggest that opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects.17,48 Further, the US guidelines suggest that in well selected populations, chronic opioid therapy may be continued (≥ 90 days), with continuous adherence monitoring, in conjunction with or after failure of other modalities of treatments, with improvement in physical and functional status and minimal adverse effects.37

In addition to prescribing practices, greater emphasis on chronic pain management during initial medical training programs and access to point-of care pain management guidelines is required to better support GPs to manage opioid prescribing for people with non-malignant pain.40,41 Improved access to allied health services when pain is still acute is crucial if the prevalence of chronic, non-cancer pain is to be reduced substantially.

Box 1 –
Roadmap for safe and effective use of opioids for chronic non-cancer pain: Canadian guideline17

Reprinted with permission.

Box 2 –
Best practice opioid analgesic prescribing for chronic pain: National Prescribing Service19

When trialling an opioid:

  • limit the trial to 4 weeks and only after exploring all other treatment options, both physical and psychological
  • review weekly preferably with a family member
  • encourage the use of a pain diary with a validated pain assessment tool such as the Brief Pain Inventory
  • assess for measureable improvements in quality of life (sleep, mood, libido), function (activities) and pain scores to gauge the effectiveness of opioids during the trial phase
  • along with monitoring physical and mental condition, monitor other key areas of function such as fitness for driving, work and other activities, and check for aberrant drug-related behaviours
  • avoid short-acting opioids

Dosing:

  • start with low doses and titrate according to response and adverse effects
  • doses above the equivalent of 100 mg morphine per day require reassessment, including specialist advice if possible
  • exercise caution with older patients

Management plans and contracts:

  • an opioid contract that summarises conditions of use along with a management plan that outlines other activities can help set realistic goals and expectations of behaviour while undertaking an opioids trial

Box 3 –
Frequently encountered effects of opioids compared with placebo in short term use24

No. of trials

No. of participants

Side effect

Participants experiencing side effect

No. needed to harm*

Opioids

Placebo

8

1114

Constipation

41%

11%

3.4

8

1114

Nausea

32%

12%

5.0

7

1022

Sedation

29%

10%

5.3

7

972

Vomiting

15%

3%

8.1

8

1114

Dizziness

20%

7%

8.2

6

981

Itching

15%

7%

1.3

7

677

Dry mouth

13%

9

–

* Short term; reverses immediately with cessation.

Box 4 –
Definitions of misuse, abuse and addiction30

Term

Definition

Misuse

Opioid use contrary to the directed or prescribed pattern regardless of the presence or absence of harm or adverse effects

Abuse

Intentional use of the opioid for a non-medical purpose such as euphoria or altering of one’s state of consciousness

Addiction

Pattern of continued use with experience of, or demonstrated potential for harm with a psychological dependence

The role of neurosurgery in the treatment of chronic pain

Neurosurgical training should formally incorporate chronic pain management, and future generations will need to direct the development of rational surgical intervention

Until the early 1980s, neurosurgical intervention for intractable pain consisted almost exclusively of targeted neuroablative procedures aimed at disrupting nociceptive pathways at some point between peripheral nerve and cortex.

Used predominantly in the treatment of malignant pain in the trunk, pelvis and lower limbs, the most successful of these — dorsal rhizotomy, spinothalamic cordotomy and myelotomy — were considered to demonstrate, invariably in non-randomised case series, good to excellent results in selected patients with nociceptive cancer pain. Pain relief would usually be maintained through a survival period of 9–12 months but there were risks of operative mortality, post-lesion dysaesthesia, and impaired motor, sensory and sphincter function. Generally confined to use in cancer patients with a life expectancy of less than 1 year and with more widespread use of opiates, hospice care and the development of intrathecal drug delivery, these operations became almost redundant.

Recent advances in image-guided percutaneous cordotomy, a new understanding of the pain pathways within the dorsal columns, and the introduction of minimally invasive punctate myelotomy have led to some resurgence both of cordotomy and myelotomy in treating cancer pain patients.1,2 One ablative procedure yet to be unequivocally surpassed by newer techniques is that of dorsal root entry zone lesioning.3,4 Thermal lesions target the nociceptive fibres of the lateral part of the dorsal rootlets and medial aspect of Lissauer’s tract. Used in its proper context — for intractable upper limb pain following brachial plexus avulsion — it has demonstrated up to 80% long term excellent pain relief with few operative complications.

With the exception of microvascular decompression and ganglionic procedures for trigeminal neuralgia, almost all neurosurgical procedures for chronic pain have, over the past 30 years, moved firmly towards reversible, low risk neuromodulation techniques (electrical stimulation of some part of the nervous system or the use of intrathecal drug delivery to control pain or modify physiological function).

Medial thalamotomy and anterior cingulectomy — used to modify transmission and affective aspects of pain perception (via lateral and medial pain pathways respectively) have been supplanted by the use of deep brain stimulation. Used mostly for treatment of medically and surgically intractable trigeminal neuralgia and other facial pains, cluster headache, post-stroke pain and various painful deafferentation states, convincing data regarding long term effectiveness of deep brain stimulation in large numbers of chronic pain patients remain limited. Evidence for the benefits of motor cortex stimulation is even less compelling.5

Intrathecal infusion of baclofen for spasticity and mini-dose opiates for chronic nociceptive malignant pain consistently produce effective, durable results in appropriate cases. The potential for serious management morbidity coupled with the paucity of useful and safe intrathecal medications direct that extreme caution be exercised in applying this therapy to patients with neuropathic, non-malignant, and generalised pain syndromes. Neurosurgeons deal largely with complications such as catheter tip granuloma, infection, and catheter displacement or extrusion.

Pioneered in 1967 by the neurosurgeon C Norman Shealy using an intradural, radiofrequency-controlled system to relieve intractable malignant pain of the pelvis and lower limbs,6 spinal cord stimulation has evolved massively in terms of technology, technique, safety, and understanding of its uses and limitations. In Australia, percutaneous, epidural electrodes are now implanted predominantly by pain medicine specialists. Neurosurgical input is required for insertion of plate electrodes in cases where epidural access is limited, and for accessing difficult sites such as the cervico-medullary junction.

Advantages of spinal cord stimulation include its low risk, reversibility and straightforward procedural techniques. On this basis, some have advocated earlier neuromodulation so as to avoid or delay major or repeat surgeries such as in the treatment of failed back surgery syndrome, and of pure low back pain with poorly defined pain generators. The downside is the now widespread, often ill-considered and repeated application of an expensive mode of treatment to unsuitable patients and pathologies. Unfortunately, this trend seems matched by a substantial increase in equally ill-considered, minimally invasive, instrumented spinal fixation for back and neck pain. Both forms of surgery as applied to chronic spinal pain are in urgent need of rationalisation.

Evidence-based recommendations for patient selection in spinal cord stimulation in Australia and New Zealand were published in 2011.7 These have remained consistent with all literature reviews to date. The most valid indication is in cases of failed back surgery syndrome. Generalised acceptance of neuromodulation has been limited partly by medical territorialism but also by scepticism generated by the lack of high level evidence for efficacy and of cost benefit. It was not until 20058 and 20089 that level 2 evidence was established in these domains. The ability to provide level 1 evidence has been hampered until very recently by a lack of placebo controls owing to stimulation-induced paraesthesiae, while the very existence of an organic basis to some pain syndromes (eg, complex regional pain syndrome type 1 and non-traumatic occipital neuralgia) that may be treated by neural stimulation has been questioned.

Trials of stimulation using exteriorised leads (time-limited by infection risk) are sometimes too short to allow adequate assessment regarding permanent implantation. There is little commercial incentive to correct this problem. Careful patient selection is paramount, yet in the United States, where trial to permanent implantation may be office based, reported trial to permanent implantation rates vary between 20% and almost 100%. Research and development worldwide are heavily sponsored by industry, which gives rise to inevitable concerns of investigator bias and unseemly haste in publishing case series. All those entering or already working in this field are recommended to read the sobering chapter by Coffey in Surgical management of pain.10

Spinal cord stimulation aims at a spinal level to suppress wide dynamic range neuronal activity in the dorsal horns and suprasegmentally via the dorsal column nuclei to modulate activity in the medial thalamus and cingulate gyrus. It has traditionally entailed tonic stimulation with a frequency of around 40–60 Hz. Recent pragmatic randomised controlled trials suggest that high frequency stimulation at 10 kHz and burst (phasic) stimulation offer superiority in the treatment of chronic back and neuropathic leg pains.11 Each of these provides paraesthesia-free analgesia and has the potential finally to allow sham stimulation. Closed-loop feedback systems promise to even out stimulation efficiency while Wi-Fi and magnetic resonance imaging compatible devices are becoming well established.

Dorsal root ganglion stimulation may hold the key to treating pains less well treated by spinal cord stimulation, including groin pain, foot pain, post-herpetic neuralgia, persistent post-surgical pain (herniorrhaphy, mastectomy, thoracotomy), and in complex regional pain syndrome. Despite multiple positive case series, there is only weak evidence for occipital nerve stimulation benefitting a variety of chronic headaches, although it does appear useful in treating post-craniotomy neuropathic head pain.

Unless results from very necessary, very carefully conducted prospective, randomised, placebo-controlled trials dictate otherwise, neuromodulation is likely to continue as the predominant form of interventional treatment for intractable neuropathic pain for the foreseeable future. If so, incorporation of all these developments within a single system would maximise flexibility and efficacy. Advances in Wi-Fi and miniaturisation technology should simplify implantation beyond current imagination. Improved functional imaging may lead to anatomically discrete electrical or drug micro-implantation or even to highly focussed neuroablative procedures.

Nationally, the quality of intractable pain management remains erratic. Neurosurgeons are well qualified to play a leading research and clinical role in optimising both benign and cancer pain treatment. However, at present, fewer than ten practising neurosurgeons in Australia and New Zealand have a major subspecialist interest in pain surgery. Broader exposure to pain management in neurosurgical and spinal surgical training would be of substantial benefit to recruitment and in the treatment of acute (postoperative) and chronic pain states.

[Comment] Pragmatic trials in critically ill children are CATCHing on

The many barriers impeding performance of clinical trials in critically ill children1 have resulted in a paucity of evidence guiding bedside practice.2 Children admitted to a paediatric intensive care unit are heterogeneous. Not only does age vary (ie, from newborn babies to adolescents), but also the broad causes of illness include congenital disorders, recovery from surgery, neurological emergencies, overwhelming infections, and traumatic injuries. Traditional explanatory trials are designed to test causal research hypotheses by assessing a tightly controlled intervention in a selected subgroup of patients.

[Correspondence] The GAS trial – Authors’ reply

Beverley Orser and colleagues correctly point out the limitations of our study,1 which were also highlighted in our discussion and the accompanying Comment.2 We agree that a more extensive follow-up of the children aged 5 years is essential, that indeed is our primary outcome. We also agree with Markus Weiss and colleagues that there are many other factors besides possible anaesthetic neurotoxic effects that might influence the short-term and long-term outcome of anaesthesia and surgery in infants.