An international multidisciplinary consensus statement on the prevention of opioid-related harm in adult surgical patients.

This international multidisciplinary consensus statement was developed to provide balanced guidance on the safe peri-operative use of opioids in adults. An international panel of healthcare professionals evaluated the literature relating to postoperative opioid-related harm, including persistent postoperative opioid use; opioid-induced ventilatory impairment; non-medical opioid use; opioid diversion and dependence; and driving under the influence of prescription opioids. Recommended strategies to reduce harm include pre-operative assessment of the risk of persistent postoperative opioid use; use of an assessment of patient function rather than unidimensional pain scores alone to guide adequacy of analgesia; avoidance of long-acting (modified-release and transdermal patches) opioid formulations and combination analgesics; limiting the number of tablets prescribed at discharge; providing deprescribing advice; avoidance of automatic prescription refills; safe disposal of unused medicines; reducing the risk of opioid diversion; and better education of healthcare professionals, patients and carers. This consensus statement provides a framework for better prescribing practices that could help reduce the risk of postoperative opioid-related harm in adults.

A randomized controlled trial of postoperative analgesia following total knee replacement: transdermal Fentanyl patches versus patient controlled analgesia (PCA).

BACKGROUND: This randomized controlled trial compared a standard patient controlled analgesic (PCA) regime with a transdermal and oral Fentanyl regime for post-operative pain management in patients undergoing total knee replacement. METHODS: One hundred and ninety-six patients undergoing total knee replacement were recruited. Pre- and post-operatively Visual Analogue Score (VAS), Oxford Knee Score, Health Anxiety and Depression Score and Brief Pain Inventory Score were completed. According to the day 1, VAS score patients were randomly allocated to either a PCA regime or a Fentanyl transdermal/oral regime. Patient reported outcomes were measured until the patients were discharged. RESULTS: The results demonstrate that in terms of analgesic effect, day of discharge and side effect profile the two regimes are comparable. CONCLUSIONS: We conclude that a Fentanyl transdermal regime provides adequate analgesic effect comparable to a standard PCA regime in conjunction with a low side effect profile. Using a transdermal analgesic system provides efficient continuous delivery enabling a smooth transition from hospital to home within the first week. Transdermal Fentanyl provides an alternative analgesic regime that can provide an equivalent analgesic effect so as to enable a satisfactory outcome for the patient in terms of function and pain. LEVEL OF EVIDENCE: II.

Pre-exercise screening and health coaching in CHD secondary prevention: a qualitative study of the patient experience.

Secondary prevention programmes can be effective in reducing morbidity and mortality from coronary heart disease (CHD). In particular, UK guidelines, including those from the Department of Health, emphasize physical activity. However, the effects of secondary prevention programmes with an exercise component are moderate and uptake is highly variable. In order to explore patients' experiences of a pre-exercise screening and health coaching programme (involving one-to-one consultations to support exercise behaviour change), semi-structured telephone interviews were undertaken with 84 CHD patients recruited from primary care. The interviews focused on patients' experiences of the intervention including referral and any recommendations for improvement. A thematic analysis of transcribed interviews showed that the majority of patients were positive about referral. However, patients also identified a number of barriers to attending and completing the programme, including a belief they were sufficiently active already, the existence of other health problems, feeling unsupported in community-based exercise classes and competing demands. Our findings highlight important issues around the choice of an appropriate point of intervention for programmes of this kind as well as the importance of appropriate patient selection, suggesting that the effectiveness of health coaching may be under-reported as a result of including patients who are not yet ready to change their behaviours.

Walk or run? Is high-intensity exercise more effective than moderate-intensity exercise at reducing cardiovascular risk?

The benefits of exercise in the prevention of cardiovascular disease are irrefutable. However, the optimum 'dose' of exercise in order to derive the maximum cardiovascular benefit is not certain. Current national and international guidelines advocate the benefits of moderate-intensity exercise. The relative benefits of vigorous versus moderate-intensity exercise have been studied in large epidemiological studies, addressing coronary heart disease and mortality, as well as smaller randomized clinical trials which assessed effects on cardiovascular risk factors. There is evidence that exercise intensity, rather than duration or frequency, is the most important variable in determining cardioprotection. Applying this evidence into practice must take into account the impact of baseline fitness, compliance and the independent risk associated with a sedentary lifestyle. This review aims to evaluate the role of exercise intensity in the reduction of cardiovascular risk, and answer the question: should you be advising your patients to walk or run?

An observational study of perioperative risk associated with aortic stenosis in non-cardiac surgery.

This prospective multicentre observational study investigated the risk of non-cardiac surgery in patients with moderate or severe aortic stenosis (AS). Patients with AS undergoing non-cardiac surgery in five New Zealand hospitals between August 2011 and September 2015 were studied. Preoperative variables were analysed for a significant association with postoperative major adverse cardiac events (MACE) and 30-day mortality. Of the 147 patients recruited, 13 (9%) died within 30 days and 33 (22%) had a MACE. Using univariate analysis, patients with severe AS had four times higher 30-day mortality than patients with moderate AS (16% versus 4%, P=0.007). Other factors associated with increased 30-day mortality included having a smaller aortic valve area, smaller dimensionless severity index, concomitant mitral regurgitation, and higher overall surgical risk. Patients with symptoms attributable to AS had a higher incidence of MACE compared to patients without symptoms (36% versus 16%, P=0.011). Variables significantly associated with both 30-day mortality and MACE were age, American Society of Anesthesiologists physical status, emergency surgery, New York Heart Association classification, preoperative albumin level, frailty, and history of congestive heart failure. Using multivariate analysis, emergency surgery, symptoms attributable to AS, preoperative albumin level, and AVA remained significantly associated with adverse outcome. While these findings should be interpreted with caution due to the observational nature of the study, limited power and multiple simultaneous comparisons, they suggest that patients with severe AS have a higher risk of adverse outcome after non-cardiac surgery than patients with moderate AS.

Oral transmucosal fentanyl citrate versus placebo for painful dressing changes: a crossover trial.

OBJECTIVE: Fentanyl is a potent opioid that is well absorbed via the oral mucosa. It can be given as an oral lozenge. The onset of analgesia is rapid and matches the pain profile observed at dressing changes. METHOD: Patients experiencing pain during daily dressing changes were given entonox plus either placebo or oral transmucosal fentanyl citrate (OTFC) for two consecutive dressing changes in a randomised double-blind placebo-controlled crossover trial. RESULTS: Nine patients were recruited. The mean worst pain score during dressing changes was 7/10 with placebo and 4/10 with OTFC; the reduction in pain achieved with OTFC was significant. The mean number of breaths of entonox taken during the dressing change was 27.67 with placebo and 4.67 with OTFC; the reduction in the number of entonox breaths with OTFC was significant. One patient in the OTFC group suffered nausea. CONCLUSION: Compared with placebo, OTFC improved analgesia during painful dressing changes without an increase in side-effects.

A retrospective observational study of patients with dilated cardiomyopathy undergoing non-cardiac surgery.

The perioperative risks and factors associated with adverse cardiac outcomes in patients with dilated cardiomyopathy undergoing non-cardiac surgery are unknown. Interrogation of the Nelson Hospital transthoracic echocardiogram database identified 127 patients with dilated cardiomyopathy who satisfied the study criteria and underwent non-cardiac surgery between June 1999 and July 2013. Demographic and clinical data along with postoperative death within 30 days or a major adverse cardiac event were retrieved and analysed. The mean age was 75.9 years. Seventy-one percent of the patients had severe impairment of left ventricular function and 35% had a severely dilated left ventricle. A major adverse cardiac event occurred in 18.1% of patients and 5.5% of patients died within 30 days of surgery. Increased surgical risk and absence of cerebrovascular disease were associated with adverse outcome (P <0.001, P <0.05, respectively). Forty-three and a half percent (43.5%) of patients undergoing high-risk surgery had an adverse outcome compared to 36.1% and 5.9% for moderate and low-risk surgery, respectively. A major adverse cardiac event was observed in 26.7% of patients with cardiovascular disease compared to 9.8% of patients without cardiovascular disease. We were unable to exclude an influence of other potential risk factors due to the retrospective observational nature of the study. These findings highlight a potential increase in complications with moderate or high surgical risk, whilst are reassuring in demonstrating the relative safety of low-risk surgery in this group of high-risk patients.

Delivery of local anaesthetic via a sternal catheter to reduce the pain caused by sternal fractures: first case series using the new technique.

Sternal fractures cause considerable pain, and a proportion of patients require admission for analgesia. Local anaesthetic techniques have been used to reduce the pain from chest wall injuries and may reduce complications from these injuries. The use of a local anaesthetic delivered via a sternal catheter over a fractured sternum has been described in a patient whose pain was inadequately controlled with opiates. This technique was recently offered to patients in the emergency department at the Royal Devon and Exeter Hospital, Exeter, UK, and the experiences of patients and doctors are reported. Findings from this first case series suggest that the technique seems to be effective, well tolerated and acceptable to patients.

Age is the best predictor of postoperative morphine requirements.

The dose of opioid prescribed for postoperative pain relief has traditionally been based on the weight of the patient. Although a reduction in dose is often suggested for elderly patients over 70 years of age, age-related alterations to dose are generally not considered for younger patients. The records of 1010 patients, under 70 years old, prescribed morphine via patient-controlled analgesia (PCA) after major operations were examined to see what factors might best predict the amount of morphine used in the first 24 h after surgery. Factors included were age, sex, weight, operative site, verbal numeric pain score (at rest and on movement) and a nausea/vomiting score. In a subgroup of 78 of these patients, the effects of intraoperative and recovery room doses of opioid ('clinical' loading dose) were analysed. Although the interpatient variability in PCA morphine doses was large (differences of up to 10-fold in each age group), the best predictor of PCA morphine requirement in the first 24 h after surgery (the amount required in the 24 h after the initial loading dose) was the age of the patient. An estimate of these requirements for patients over the age of 20 years can be obtained from the formula: average first 24 h morphine requirement (mg) = 100 - age. PCA allows patients the flexibility to titrate their own opioid dose; if conventional analgesic regimens are to become more effective, they too need to allow for the wide interpatient variation in dose requirements. Although previous studies have noted a correlation between patient age and the amount of opioid needed, this study quantifies this correlation and provides guidelines for opioid dosing. Prescriptions for conventional analgesic regimens should include a dose range centred on values obtained from the above formula to allow for the large interpatient variation in each age group. While initial morphine dose should be guided by patient age and not weight, subsequent doses must still be titrated according to effect.

Pharmacokinetic optimisation of opioid treatment in acute pain therapy.

Traditionally, opioids have been administered as fixed doses at fixed dose intervals. This approach has been largely ineffective. Patient-controlled analgesia (PCA) and upgraded traditional approaches incorporating flexibility in dose size and dose interval, and titration for an effect in individual patients with the monitoring of pain and sedation scores, can greatly improve the efficacy of opioid administration. Optimising opioid use, therefore, entails optimising the titration process. Opioids have similar pharmacodynamic properties but have widely different kinetic properties. The most important of these is the delay between the blood concentrations of an opioid and its analgesic or other effects, which probably relate to the delay required for blood and brain and spinal cord (CNS) equilibrium. The half-lives of these delays range from approximately 34 minutes for morphine to 1 minute for alfentanil. The titration is influenced by the time needed after an initial dose before it is safe to administer a second dose and the duration of the effects of a single dose, which varies widely between opioids, doses and routes of administration. To compare opioids and routes of administration, we examined the relative CNS concentration profiles of opioids - the CNS concentration expressed as a percentage of its maximum value. The relative onset was the defined as the time the relative CNS concentration first rose to 80% of maximum, while the relative duration was defined as the length of time the concentration was above 80%. For an intravenous bolus dose, the relative onset varies from approximately 1 for alfentanil to 6 minutes for morphine, while their relative durations are approximately 2 and 96 minutes, respectively. Although all of the common opioids, perhaps with the exception of alfentanil, have kinetic and dynamic properties suitable for use in PCA with intravenous bolus doses, the long relative duration of morphine makes it particularly suited to an upgraded traditional approach using staff administered intramuscular or subcutaneous doses. There is a clear kinetic preference for regimens with a rapid onset and short duration (e.g. intravenous PCA) for coping with incident pain. It is shown that, in general, titration is improved by the more frequent administration of smaller doses, but it is important to use additional doses to initially 'load' a patient. The titration of opioids should always be accompanied by the monitoring of pain and sedation scores and ventilation.

Blind atrial pacing for patients with sinus node disease who develop atrial fibrillation during permanent pacemaker implantation.

During a 6-year period, six of 110 patients implanted with AAI pacemakers for sick sinus syndrome developed atrial fibrillation at the time of pacemaker implantation (5.5%). In all cases a passive fixation lead was sited in the right atrial appendage, its stability being ensured by rotation of the lead and phrenic nerve stimulation excluded by pacing at 10 V. One patient remained in chronic atrial fibrillation. In the other five, who subsequently reverted to sinus rhythm, atrial P-wave sensing and lead threshold values were satisfactory, allowing programming of the pacemaker output down to 2.5 V to conserve the battery. One out of these five patients continued to have intermittent atrial fibrillation. We conclude that in sick sinus syndrome, atrial fibrillation complicates AAI pacemaker implantation procedure in 5.5% of cases. As an alternative to an unplanned general anaesthetic to cardiovert the patient, it is reasonable to implant an atrial lead in the right atrial appendage in the expectation of a spontaneous reversion to sinus rhythm with a good lead threshold and P-wave sensing. In contrast to inappropriate pacing of the right ventricle in VVI mode, this strategy avoids pacemaker syndrome and reduces the risk of subsequent attacks of atrial fibrillation.

Prevalence of HIV among pregnant women in Dundee 1988-1997: evidence to gauge the effectiveness of HIV prevention measures.

OBJECTIVES: During November 1988-July 1990, an HIV prevalence survey of pregnant women in Dundee, which used a combined voluntary diagnostic testing and voluntary unlinked anonymous approach, revealed a rate of 0.3%, the highest recorded prevalence among such a population in the U.K. at the time. To determine if, and why, any changes in HIV prevalence had occurred during the early to mid 1990s, further studies were conducted. METHODS: During January 1993-December 1997, antenatal patients of, and women undergoing therapeutic termination of pregnancy at, Ninewells Hospital, Dundee, were offered a diagnostic HIV antibody test. For those declining, residual sera from rubella specimens were tested for HIV antibodies using an unlinked anonymous approach which did not necessitate the securement of informed consent. Information about injecting drug use was obtained from all women and linked to their HIV test results. RESULTS: For all pregnant women, a significant decline in HIV prevalence (P<0.05) from 0.3% (19/6228) during 1988-1990 to 0.12% (22/17899) during 1993-1997 was observed. For those who injected drugs, prevalence decreased significantly (P<0.05) from 27.5% (11/40) to 7% (6/85), while among women who had never injected drugs prevalence decreased slightly, but not significantly (P>0.05), from 0.13% (8/6188) to 0.09% (16/17814).Prevalence in the non-injectors who reported no sexual intercourse with an injector was low at 0.04% (8/17682) during 1993-1997. No significant trends in HIV prevalence were seen over the 5 years up to 1997. CONCLUSION: The decline in HIV prevalence among pregnant women in Dundee during the early to mid-1990s can be explained predominantly by the control of HIV transmission among the city's injectors, and from them to the wider heterosexual population. It is likely that interventions designed to reduce needle/syringe sharing among injectors have been successful. It is imperative that the preventive effort is not allowed to be weakened.

Epidural catheter tip cultures: results of a 4-year audit and implications for clinical practice.

BACKGROUND AND OBJECTIVES: The aims of this study were to evaluate the clinical relevance of routine microbiological culture of epidural catheter tips after use in acute pain management, and to identify patterns of culture result with respect to both indications for, and duration of, epidural catheterization. METHODS: The Acute Pain Service (APS) reviews all patients under its care at least daily and keeps detailed records on each. Over a 4-year period, when APS protocol required epidural catheter tips to be sent for microbiological culture on removal, the APS saw 1,810 patients who had received epidural analgesia. The records of these patients were reviewed. RESULTS: Culture results were available for 1,443 (79.7%) patients: 1,027 catheter tips (71.2%) were sterile, while 416 (28.8%) were positive for at least 1 type of microorganism. Clinically, no epidural space infections were identified. The highest positive culture rates were found from epidural catheters used in the treatment of pain from fractured ribs or fractured pelves, while the lowest incidences occurred in elective orthopedic and thoracic surgery. The proportion of epidural catheters with positive culture results steadily increased with the duration of catheterization, but there were no clinically significant differences for catheters left in situ for either 3 or 4 days. CONCLUSIONS: We concluded that a significant proportion of epidural catheter tips may be "culture positive" after removal. It is suggested that this probably represents colonization of the skin at the catheter insertion site and subsequent contamination of the catheter tip on removal of the catheter. The large number of "culture positive" tips in the absence of clinically identifiable epidural space infection suggests that routine culture of epidural catheter tips is clinically irrelevant in the vast majority of cases, and that it is not a good predictor of the presence of an epidural space infection.

Costs and consequences: a review of discharge opioid prescribing for ongoing management of acute pain.

Over recent years there has been a growing need for patients to be sent home from hospital with prescribed opioids for ongoing management of their acute pain. Increasingly complex surgery is being performed on a day-stay or 23-hour-stay basis and inpatients after major surgery and trauma are now discharged at a much earlier stage than in the past. However, prescription of opioids to be self-administered at home is not without risk. In addition to the potential for acute adverse effects, including opioid-induced ventilatory impairment and impairment of driving skills, a review of the literature shows that opioid use continues in some patients for some years after surgery. There are also indications that over-prescription of discharge opioids occur with a significant amount not consumed, resulting in a potentially large pool of unused opioid available for later use by either the patient or others in the community. Concerns about the potential for harm arising from prescription of opioids for ongoing acute pain management after discharge are relatively recent. However, at a time when serious problems resulting from the non-medical use of opioids have reached epidemic proportions in the community, all doctors must be aware of the potential risks and be able to identify and appropriately manage patients where there might be a risk of prolonged opioid use or misuse. Anaesthetists are ideally placed to exercise stewardship over the use of opioids, so that these drugs can maintain their rightful place in the post-discharge analgesic pharmacopoeia.

Home blood pressure monitoring in an anaesthetic pre-admission clinic.

We suspected that many high blood pressure measurements taken in our anaesthetic pre-assessment clinic and immediately prior to induction of anaesthesia were unusually elevated due to a 'white coat' effect. These high blood pressure measurements were causing late cancellations of surgery, even though white coat measurements may not be representative of the patient's usual blood pressure or of their risk of end-organ damage due to hypertension. In this audit, patients with high blood pressure in our pre-admission clinic were provided with training and a home blood pressure monitor to use prior to surgery. These were compared to the pre-admission clinic measurements to determine the incidence of white coat hypertension. We also compared home to general practice blood pressure monitoring where possible. Fifty-two patients were provided with monitors. Fifty-one of these took at least five measurements at home. Thirty-four (66%) patients had average measurements at home at least 20 mmHg lower than pre-admission clinic measurements. A total of 33% of general practice clinic measurements were also ≥ 20 mmHg higher than average home measurements. White coat hypertension was common in our audit population. Relying on average home blood pressure measurements rather than 'one off' in-hospital measurements may have helped to prevent the postponement or cancellation of surgery for 13 patients who had recorded blood pressure ≥ 180/110 mmHg in our pre-admission clinic.

Pain relief and opioid requirements in the first 24 hours after surgery in patients taking buprenorphine and methadone opioid substitution therapy.

The number of patients in buprenorphine opioid substitution therapy (BOST) or methadone opioid substitution therapy (MOST) programs is increasing. If these patients require surgery, it is generally agreed that methadone should be continued perioperatively. While some also recommend that buprenorphine is continued, concerns that it may limit the analgesic effectiveness of full mu-opioid agonists have led others to suggest that it should cease before surgery. However, no good evidence exists for either course of action. Therefore, we undertook a retrospective cohort study comparing pain relief and opioid requirements in the first 24 hours after surgery in 22 BOST and 29 MOST patients prescribed patient-controlled analgesia. There were no significant differences in pain scores (rest and movement), incidence of nausea or vomiting requiring treatment, or sedation between the BOST and MOST patient groups overall, or between those patients within each of these groups who had and had not received their methadone or buprenorphine the day after surgery. There were also no significant differences in patient-controlled analgesia requirements between BOST and MOST patient groups overall, or between patients who did or did not receive MOST on the day after surgery. BOST patients who were not given their usual buprenorphine the day after surgery used significantly more patient-controlled analgesia opioid (P=0.02) compared with those who had received their dose. These results confirm that continuation of buprenorphine perioperatively is appropriate.

Pharmacokinetics of oxycodone after subcutaneous administration in a critically ill population compared with a healthy cohort.

This study aimed to characterise and compare the absorption pharmacokinetics of a single subcutaneous dose of oxycodone in critically ill patients and healthy subjects. Blood samples taken at intervals from two minutes to eight hours after a subcutaneous dose of oxycodone in patients (5 mg) and healthy volunteers (10 mg) were assayed using high performance liquid chromatography. Data were analysed using a non-compartmental approach and presented as mean (SD). Parameters were corrected for dose differences between the groups assuming linear kinetics. Ten patients (eight male, two female) and seven healthy male subjects were included. Maximum venous concentration and area under the concentration curve were approximately two-fold lower in the patient group for an equivalent dose, suggesting either reduced bioavailability or increased clearance: maximum venous concentration 0.14 ± 0.06 vs 0.05 ± 0.02 µg/ml (P <0.0001); area under the concentration curve 19.50 ± 9.15 vs 9.72 ± 2.71 µg/ml/minute (P <0.001) respectively. However, time to maximum venous concentration and mean residence time were not different, suggesting similar absorption rates: time to maximum venous concentration 22.10 ± 18.0 vs 20.50 ± 16.10 minutes (P=0.81); mean residence time 353 ± 191 vs 291 ± 80 minutes (P=0.26). Kinetic parameters were less variable in patients than in volunteers. The patients therefore had reduced exposure to subcutaneous oxycodone. This warrants further model-based analysis and experimentation. Dose regimens for subcutaneous oxycodone developed in healthy volunteers cannot be directly translated to critically ill patients.

Opioids, ventilation and acute pain management.

Despite the increasing use of a variety of different analgesic strategies, opioids continue as the mainstay for management of moderate to severe acute pain. However concerns remain about their potential adverse effects on ventilation. The most commonly used term, respiratory depression, only describes part of that risk. Opioid-induced ventilatory impairment (OIVI) is a more complete term encompassing opioid-induced central respiratory depression (decreased respiratory drive), decreased level of consciousness (sedation) and upper airway obstruction, all of which, alone or in combination, may result in decreased alveolar ventilation and increased arterial carbon dioxide levels. Concerns about OIVI are warranted, as deaths related to opioid administration in the acute pain setting continue to be reported. Risks are often said to be higher in patients with obstructive sleep apnoea. However, the tendency to use the term 'obstructive sleep apnoea' to encompass the much broader spectrum of sleep- and obesity-related hypoventilation syndromes and the related misuse of terminology in papers relating to obstructive sleep apnoea and sleep-disordered breathing remain significant problems in discussions of opioid-related effects. Opioids given for management of acute pain must be titrated to effect for each patient. However strategies aiming for better pain scores alone, without highlighting the need for appropriate monitoring of OIVI, can and will lead to an increase in adverse events. Therefore, all patients must be monitored appropriately for OIVI (at the very least using sedation scores as a '6th vital sign') so that it can be detected at an early stage and appropriate interventions triggered.