R. M. Langford

Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

1. The use of opioids in cancer pain:  The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side‐effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision‐making process can change.

Normalization of widespread hyperesthesia and facilitated spatial summation of deep-tissue pain in knee osteoarthritis patients after knee replacement

OBJECTIVE The modest association between radiographic joint damage and pain in osteoarthritis (OA) has led to the suggestion of facilitated central pain processing. This study evaluated the importance of ongoing tissue pathology in the maintenance of enhanced central pain processing. METHODS Pain assessment was performed on 48 patients with symptomatic knee OA and 21 sex- and age-matched pain-free healthy control subjects. Twenty of the OA patients subsequently underwent total knee replacement surgery and were reassessed. Pressure-pain thresholds (PPTs) were recorded using a pressure algometer (both over and distant from the knee) and a double-chamber inflatable cuff mounted around the calf. Spatial summation was assessed by relating PPTs using the dual- and single-chamber cuff. Conditioned pain modulation (CPM) was assessed by recording the increase in PPT in response to experimental arm pain. RESULTS PPTs at the knee and at sites away from the knee were reduced in OA patients as compared with healthy pain-free control subjects (P < 0.0001). Cuff PPTs were decreased in OA patients as compared with the healthy controls (P < 0.05), who also exhibited a greater degree of spatial summation (P < 0.05). Whereas an elevation of PPTs was noted in the healthy controls in response to experimental arm pain (P < 0.0001), no such CPM was observed in the OA patients. Following joint replacement in the OA patients, there was a reduction in the widespread mechanical hyperesthesia, along with normalization of spatial summation ratios and restoration of CPM. CONCLUSION The widespread hyperesthesia and enhanced spatial summation observed in OA patients imply sensitized central pain mechanisms together with the loss of CPM. Normalization of the results following joint replacement implies that these central pain processes are maintained by peripheral input.

Current Knowledge of Buprenorphine and Its Unique Pharmacological Profile

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ‐opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ‐opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compounds favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain.

Acute pain management for opioid dependent patients.

Patients requiring acute pain management may be opioid dependent as a result of either recreational or therapeutic opioid use, including those in opioid addiction programmes. Pain in these patients is often under‐estimated and under‐treated. In addiction, drug‐seeking behaviour differentiates it from simple dependence. With few randomised controlled trials, current evidence predominantly consists of guidelines based on case reports, retrospective studies and expert opinion. Consensus recommendations include maintaining regular provision of the patients pre‐existing opioid requirement, with additional analgesia, ideally multimodal, in appropriate combinations of short‐acting opioid (as required), local anaesthesia, and adjuvant anti‐inflammatory analgesics and paracetamol. Patient controlled analgesia with higher bolus doses and shorter lock‐out intervals is a recommended strategy. Transdermal opioid patches and implantable pumps will continue to deliver opioid, to which non‐opioid and short‐acting opioids may be added. Re‐exposure to opioid is ideally avoided in previously addicted patients, but if not feasible, opioid therapy should be prescribed.

Randomized placebo‐controlled trial of the activity of the morphine glucuronides

Morphine‐6‐glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine‐3‐glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G.

Investigation of oesophageal photoplethysmographic signals and blood oxygen saturation measurements in cardiothoracic surgery patients.

Pulse oximeter probes attached to the finger may fail to estimate blood oxygen saturation (SpO2) in patients with compromised peripheral perfusion (e.g. hypothermic cardiopulmonary bypass surgery). The measurement of SpO2 from a central organ such as the oesophagus is suggested as an alternative to overcome this problem. A reflectance oesophageal pulse oximeter probe and a processing system implemented in LabVIEW were developed. The system was evaluated in clinical measurements on 50 cardiothoracic surgery patients. Oesophageal photoplethysmographic (PPG) signals with large amplitudes and high signal-to-noise ratios were measured from various depths within the oesophagus from all the cardiothoracic patients. The oesophageal PPG amplitudes from these patients were in good agreement with previous oesophageal PPG amplitude measurements from healthy anaesthetized patients. The oesophageal pulse oximeter SpO2 results agreed well with the estimated arterial oxygen saturation (SaO2) values inferred from the oxygen tension obtained by blood gas analysis. The mean (+/- SD) of the differences between the oesophageal pulse oximeter SpO2 readings and those from blood gas analysis was 0.02 +/- 0.88%. Also, the oesophageal pulse oximeter was found to be reliable and accurate in five cases of poor peripheral perfusion when a commercial finger pulse oximeter probe failed to estimate oxygen saturation values for at least 10 min. These results suggest that the arterial blood circulation to the oesophagus is less subject to vasoconstriction and decreased PPG amplitudes than are the peripheral sites used for pulse oximetry such as the finger. It is concluded that oesophageal SPO2 monitoring may be of clinical value.

The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1, 2 and 3 after elective abdominal surgery

OBJECTIVES Patients undergoing abdominal surgery often suffer from morbidity associated with increased protein catabolism. Therapeutic recombinant human insulin‐like growth factor (rhIGF)‐I has been proposed as a means of reversing this process. As IGFBPs modulate the bioavailability of the IGFs, we have studied the changes in the circulating levels of these peptides during surgery.

Pain management today—what have we learned?

Pain is a leading cause of morbidity worldwide, with published data showing its prevalence as high as 50% for chronic pain in the European population. This prevalence is likely to continue to rise, particularly in elderly people with comorbid conditions and complex aetiologies of pain. There is thus a rapidly growing demand for safe and effective pain management. Management of mild-to-moderate pain has traditionally been based upon the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the synthetic non-opioid analgesic paracetamol (acetaminophen), the latter of which acts centrally, inhibiting brain cyclo-oxygenase (COX) and nitric oxide synthase. Both the NSAIDs and paracetamol are effective for mild-to-moderate pain and are widely recommended and used. However, NSAIDs may not be tolerated due to gastrointestinal (GI) symptoms and can result in potentially fatal peptic ulceration and bleeding. Selective COX-2 inhibitors were developed to reduce the GI side effects and complications, but large-scale studies have highlighted another serious potential effect of anti-inflammatory drugs: cardiovascular events. Both the European Medicines Agency (EMEA) and the Food and Drugs Administration (FDA) in the US have issued advice to apply cautions and restrictions when prescribing COX-2 inhibitors, particularly for patients at increased cardiovascular risk and for long-term use. The FDA also applied cardiovascular warnings with regard to nonselective NSAIDs. Both the EMEA and the FDA have recommended using the lowest effective dose for the shortest duration. These concerns and warnings have left physicians seeking safe alternatives to anti-inflammatory drugs for both short- and long-term uses in many patients. These developments have generated a climate of uncertainty in the absence of official guidance on the selection of alternative analgesic regimens. Amongst the possible strategies, combinations of drugs that provide analgesic efficacy at reduced individual doses may confer the optimal risk–benefit ratio for pain management in the long term or in patients at increased cardiovascular risk. Weak opioids devoid of serious organ-damaging effects combined with paracetamol may well be safer for long-term therapy. Fixed-dose combinations of paracetamol with weak opioids, such as codeine, dextropropoxyphene or tramadol are currently available. Paracetamol plus tramadol is an effective and safe multimodal analgesic regimen for the management of both acute and chronic moderate-to-severe pain. Re-evaluating the role of weak opioids, such as tramadol, and combinations in pain management may prove a valuable option for prescribers seeking alternatives to anti-inflammatory drugs.

Esophageal pulse oximetry utilizing reflectance photoplethysmography

Peripheral perfusion is often poor and barely pulsatile in patients undergoing prolonged major surgery. Hence, the arterial blood oxygen saturation (SpO/sub 2/) readings from commercial finger pulse oximeters can become unreliable or cease when they are most needed. To overcome this limitation, the esophagus has been investigated as an alternative measurement site, as perfusion may be preferentially preserved centrally. A reflectance esophageal pulse oximeter probe, and a processing system implemented in Lab VIEW were developed. The system was evaluated in clinical measurements on 49 cardiothoracic surgery patients. The SpO/sub 2/ values from the esophagus were in good agreement with arterial blood oxygen saturation (SaO/sub 2/) values obtained from blood gas analysis and CO-oximetry. The means (/spl plusmn/SD) of the differences between the esophageal SpO/sub 2/ and SaO/sub 2/ results from blood gas analysis and CO-oximetry were 0.02/spl plusmn/0.88% and -0.73/spl plusmn/0.72%, respectively. In five (10.2%) of the patients, the finger pulse oximeter failed for at least 10 min while the esophageal SpO/sub 2/ readings remained reliable. The results confirm that the esophagus may be used as an alternative monitoring site for pulse oximetry even in patients with compromised peripheral perfusion.

Decontamination of laryngoscopes: a survey of national practice.

We conducted a postal questionnaire to survey methods of laryngoscope cleaning in units throughout Great Britain. We found that there was great variation in practice. Most units autoclave laryngoscope blades at some time, but less than one‐quarter do so between each case. A wide range of methods is used to clean the blade in units where autoclaving was not undertaken. Most units had no guidelines relating to laryngoscope treatment between uses.