Capnography monitoring during procedural sedation and analgesia: A systematic review protocol

Background An important potential clinical benefit of using capnography monitoring during procedural sedation and analgesia (PSA) is that this technology could improve patient safety by reducing serious sedation-related adverse events, such as death or permanent neurological disability, which are caused by inadequate oxygenation. The hypothesis is that earlier identification of respiratory depression using capnography leads to a change in clinical management that prevents hypoxaemia. As inadequate oxygenation/ventilation is the most common reason for injury associated with PSA, reducing episodes of hypoxaemia would indicate that using capnography would be safer than relying on standard monitoring alone. Methods/design The primary objective of this review is to determine whether using capnography during PSA in the hospital setting improves patient safety by reducing the risk of hypoxaemia (defined as an arterial partial pressure of oxygen below 60 mmHg or percentage of haemoglobin that is saturated with oxygen [SpO2] less than 90 %). A secondary objective of this review is to determine whether changes in the clinical management of sedated patients are the mediating factor for any observed impact of capnography monitoring on the rate of hypoxaemia. The potential adverse effect of capnography monitoring that will be examined in this review is the rate of inadequate sedation. Electronic databases will be searched for parallel, crossover and cluster randomised controlled trials comparing the use of capnography with standard monitoring alone during PSA that is administered in the hospital setting. Studies that included patients who received general or regional anaesthesia will be excluded from the review. Non-randomised studies will be excluded. Screening, study selection and data extraction will be performed by two reviewers. The Cochrane risk of bias tool will be used to assign a judgment about the degree of risk. Meta-analyses will be performed if suitable. Discussion This review will synthesise the evidence on an important potential clinical benefit of capnography monitoring during PSA within hospital settings. Systematic review registration: PROSPERO CRD42015023740

From the guest editors: Urban acupuncture

The term urban acupuncture refers to a concept where a localised intervention or treatment is used for the revitalisation and (re)creation of cities by targeting strategic points, poking or activating networks into action. These actions impart stimuli for further responses and opportunity through small projects rather than large developments. Urban Acupuncture activates dynamic transformative forces of the place and focuses on the maintenance of a healthy situation rather than on the cure of problems, and thus metaphorically resonates with the principles of the practice of acupuncture in traditional Chinese medicine...

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension band castrated with or without analgesia: 2. Responses related to stress, health and productivity

Tension banding castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the banders as a humane castration method. Two experiments were conducted, under tropical conditions using Bos indicus bulls comparing tension banding (Band) and surgical (Surgical) castration of weaner (7–10 months old) and mature (22–25 months old) bulls with and without pain management (NSAID (ketoprofen) or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a range of measures; this paper reports on some physiological, morbidity and productivity-related responses to augment the behavioural responses reported in an accompanying paper. Blood samples were taken on the day of castration (day 0) at the time of restraint (0 min) and 30 min (weaners) or 40 min (mature bulls), 2 h, and 7 h; and days 1, 2, 3, 7, 14, 21 and 28 post-castration. Plasmas from day 0 were assayed for cortisol, creatine kinase, total protein and packed cell volume. Plasmas from the other samples were assayed for cortisol and haptoglobin (plus the 0 min sample). Liveweights were recorded approximately weekly to 6 weeks and at 2 and 3 months post-castration. Castration sites were checked at these same times to 2 months post-castration to score the extent of healing and presence of sepsis. Cortisol concentrations (mean ± s.e. nmol/L) were significantly (P < 0.05) higher in the Band (67 ± 4.5) compared with Surgical weaners (42 ± 4.5) at 2 h post-castration, but at 24 h post-castration were greater in the Surgical (43 ± 3.2) compared with the Band weaners (30 ± 3.2). The main effect of ketoprofen was on the cortisol concentrations of the mature Surgical bulls; concentrations were significantly reduced at 40 min (47 ± 7.2 vs. 71 ± 7.2 nmol/L for saline) and 2 h post-castration (24 ± 7.2, vs. 87 ± 7.2 nmol/L for saline). Ketoprofen, however, had no effect on the Band mature bulls, with their cortisol concentrations averaging 54 ± 5.1 nmol/L at 40 min and 92 ± 5.1 nmol/L at 2 h. Cortisol concentrations were also significantly elevated in the Band (83 ± 3.0 nmol/L) compared with Surgical mature bulls (57 ± 3.0 nmol/L) at weeks 2–4 post-castration. The timing of this elevation coincided with significantly elevated haptoglobin concentrations (mg/mL) in the Band bulls (2.97 ± 0.102 for mature bulls and 1.71 ± 0.025 for weaners, vs. 2.10 ± 0.102 and 1.45 ± 0.025 respectively for the Surgical treatment) and evidence of slow wound healing and sepsis in both the weaner (0.81 ± 0.089 not healed at week 4 for Band, 0.13 ± 0.078 for Surgical) and mature bulls (0.81 ± 0.090 at week 4 for Band, 0.38 ± 0.104 for Surgical). Overall, liveweight gains of both age groups were not affected by castration method. The findings of acute pain, chronic inflammation and possibly chronic pain in the mature bulls at least, together with poor wound healing in the Band bulls support behavioural findings reported in the accompanying paper and demonstrate that tension banding produces inferior welfare outcomes for weaner and mature bulls compared with surgical castration.

A comparison of welfare outcomes for weaner and mature Bos indicus bulls surgically or tension band castrated with or without analgesia: 1. Behavioural responses

Tension-band castration of cattle is gaining favour because it is relatively simple to perform and is promoted by retailers of the devices as a humane castration method. Furthermore, retailers encourage delaying castration to exploit the superior growth rates of bulls compared with steers. Two experiments were conducted, under tropical conditions, comparing tension banding and surgical castration of weaner (7–10 months old) and mature (22–25 months old) Bos indicus bulls with and without pain management (ketoprofen or saline injected intramuscularly immediately prior to castration). Welfare outcomes were assessed using a wide range of measures; this paper reports on the behavioural responses of the bulls and an accompanying paper reports on other measures. Behavioural data were collected at intervals by direct observation and continuously via data loggers on the hind leg of the bulls to 4 weeks post-castration. Tension-banded bulls performed less movement in the crush/chute than the surgically castrated bulls during the procedures (weaner: 2.63 vs. 5.69, P < 0.001; mature: 1.00 vs. 5.94; P < 0.001 for tension-band and surgical castration, respectively), indicating that tension banding was less painful then surgical castration during conduct. To 1.5 h post-castration, tension-banded bulls performed significantly (all P < 0.05) more active behavioural responses indicative of pain compared with surgical castrates, e.g., percentage time walking forwards (weaner: 15.0% vs. 8.1%; mature: 22.3% vs. 15.1%), walking backwards (weaner: 4.3% vs. 1.4%; mature: 2.4% vs. 0.5%), numbers of tail movements (weaner: 21.9 vs. 1.4; mature: 51.5 vs. 39.4) and leg movements (weaner: 12.9 vs. 0.9; mature: 8.5 vs. 1.5), respectively. In contrast, surgically castrated bulls performed more immobile behaviours compared with tension-banded bulls (e.g., standing in mature bulls was 56.6% vs. 34.4%, respectively, P = 0.002). Ketoprofen administration appeared effective in moderating pain-related behaviours in the mature bulls from 1.5 to 3 h, e.g., reducing abnormal standing (0.0% vs. 7.7%, P = 0.009) and increasing feeding (12.7% vs. 0.0%, P = 0.048) in NSAID- and saline-treated bulls, respectively. There were few behavioural differences subsequent to 24 h post-castration, but some limited evidence of chronic pain (3–4 weeks post-castration) with both methods. Interpretation, however, was difficult from behaviours alone. Thus, tension banding is less painful than surgical castration during conduct of the procedures and pain-related behavioural responses differ with castration method (active restlessness in response to tension banding and minimisation of movement in response to surgical castration). Ketoprofen administered immediately prior to castration was somewhat effective in reducing pain, particularly in the mature bulls.

Clinical Studies on Epidural and Spinal Postoperative Analgesia : With Special Reference to Continuous Techniques of Administration and Adjuvant Drugs

Continuous epidural analgesia (CEA) and continuous spinal postoperative analgesia (CSPA) provided by a mixture of local anaesthetic and opioid are widely used for postoperative pain relief. E.g., with the introduction of so-called microcatheters, CSPA found its way particularly in orthopaedic surgery. These techniques, however, may be associated with dose-dependent side-effects as hypotension, weakness in the legs, and nausea and vomiting. At times, they may fail to offer sufficient analgesia, e.g., because of a misplaced catheter. The correct position of an epidural catheter might be confirmed by the supposedly easy and reliable epidural stimulation test (EST). The aims of this thesis were to determine a) whether the efficacy, tolerability, and reliability of CEA might be improved by adding the α2-adrenergic agonists adrenaline and clonidine to CEA, and by the repeated use of EST during CEA; and, b) the feasibility of CSPA given through a microcatheter after vascular surgery. Studies I IV were double-blinded, randomized, and controlled trials; Study V was of a diagnostic, prospective nature. Patients underwent arterial bypass surgery of the legs (I, n=50; IV, n=46), total knee arthroplasty (II, n=70; III, n=72), and abdominal surgery or thoracotomy (V, n=30). Postoperative lumbar CEA consisted of regular mixtures of ropivacaine and fentanyl either without or with adrenaline (2 µg/ml (I) and 4 µg/ml (II)) and clonidine (2 µg/ml (III)). CSPA (IV) was given through a microcatheter (28G) and contained either ropivacaine (max. 2 mg/h) or a mixture of ropivacaine (max. 1 mg/h) and morphine (max. 8 µg/h). Epidural catheter tip position (V) was evaluated both by EST at the moment of catheter placement and several times during CEA, and by epidurography as reference diagnostic test. CEA and CSPA were administered for 24 or 48 h. Study parameters included pain scores assessed with a visual analogue scale, requirements of rescue pain medication, vital signs, and side-effects. Adrenaline (I and II) had no beneficial influence as regards the efficacy or tolerability of CEA. The total amounts of epidurally-infused drugs were even increased in the adrenaline group in Study II (p=0.02, RM ANOVA). Clonidine (III) augmented pain relief with lowered amounts of epidurally infused drugs (p=0.01, RM ANOVA) and reduced need for rescue oxycodone given i.m. (p=0.027, MW-U; median difference 3 mg (95% CI 0 7 mg)). Clonidine did not contribute to sedation and its influence on haemodynamics was minimal. CSPA (IV) provided satisfactory pain relief with only limited blockade of the legs (no inter-group differences). EST (V) was often related to technical problems and difficulties of interpretation, e.g., it failed to identify the four patients whose catheters were outside the spinal canal already at the time of catheter placement. As adjuvants to lumbar CEA, clonidine only slightly improved pain relief, while adrenaline did not provide any benefit. The role of EST applied at the time of epidural catheter placement or repeatedly during CEA remains open. The microcatheter CSPA technique appeared effective and reliable, but needs to be compared to routine CEA after peripheral arterial bypass surgery.

Optimizing perioperative analgesia for patients undergoing operative fixation of hip fractures

This PhD thesis describes work carried out on investigation of various interventions with the aim to optimise the anaesthetic management of patients scheduled to undergo operative fixation of hip fractures. We analysed the perioperative effects of continuous femoral nerve block, single preoperative dose of i.v. dexamethasone, the intention to deposit local anaesthetic in different locations around the femoral nerve during ultrasound guided femoral nerve block, continuous spinal anaesthesia and peri-surgical site infiltration with local anaesthetic after surgical fixation of hip fractures. Continuous femoral nerve block provided more effective preoperative analgesia six hours after the insertion of the perineural catheter compared to a standard opiate-based regimen in patients undergoing operative fixation of fractured hip. A single low dose of preoperative dexamethasone in the intervention group decreased pain scores by 75% six hours after the surgery. Both interventions had no major effect on the functional recovery in the first year after the surgical fixation of fractured hip. The results of the ultrasound guided femoral nerve block trial showed no clinical advantage of intending to deposit local anaesthetic circumferentially during performing femoral nerve block. Using the Dixon and Massey’s “up- and-down” method, we demonstrated that intrathecal 0.26 ml of 0.5% bupivacaine provided adequate surgical anaesthesia within 15 minutes in 50% of patients undergoing operative fixation of hip fracture. Finally, we demonstrated that local anaesthetic infiltration had no effect on pain scores 12 hours after the surgical fixation of fractured neck of femur. In addition to this original body of work, a review article was published on femoral nerve block highlighting the use of ultrasound guidance. In conclusion, the results of this thesis offer an insight into interventions aimed at optimising perioperative analgesia in patients scheduled to undergo operative fixation of hip fractures.

Patient-based outcome assessment instruments in acupuncture research.

BACKGROUND: Outcome assessment can support the therapeutic process by providing a way to track symptoms and functionality over time, providing insights to clinicians and patients, as well as offering a common language to discuss patient behavior/functioning. OBJECTIVES: In this article, we examine the patient-based outcome assessment (PBOA) instruments that have been used to determine outcomes in acupuncture clinical research and highlight measures that are feasible, practical, economical, reliable, valid, and responsive to clinical change. The aims of this review were to assess and identify the commonly available PBOA measures, describe a framework for identifying appropriate sets of measures, and address the challenges associated with these measures and acupuncture. Instruments were evaluated in terms of feasibility, practicality, economy, reliability, validity, and responsiveness to clinical change. METHODS: This study was a systematic review. A total of 582 abstracts were reviewed using PubMed (from inception through April 2009). RESULTS: A total of 582 citations were identified. After screening of title/abstract, 212 articles were excluded. From the remaining 370 citations, 258 manuscripts identified explicit PBOA; 112 abstracts did not include any PBOA. The five most common PBOA instruments identified were the Visual Analog Scale, Symptom Diary, Numerical Pain Rating Scales, SF-36, and depression scales such as the Beck Depression Inventory. CONCLUSIONS: The way a questionnaire or scale is administered can have an effect on the outcome. Also, developing and validating outcome measures can be costly and difficult. Therefore, reviewing the literature on existing measures before creating or modifying PBOA instruments can significantly reduce the burden of developing a new measure.

Auriculotherapy for pain management: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Side-effects of standard pain medications can limit their use. Therefore, nonpharmacologic pain relief techniques such as auriculotherapy may play an important role in pain management. Our aim was to conduct a systematic review and meta-analysis of studies evaluating auriculotherapy for pain management. DESIGN: MEDLINE,(®) ISI Web of Science, CINAHL, AMED, and Cochrane Library were searched through December 2008. Randomized trials comparing auriculotherapy to sham, placebo, or standard-of-care control were included that measured outcomes of pain or medication use and were published in English. Two (2) reviewers independently assessed trial eligibility, quality, and abstracted data to a standardized form. Standardized mean differences (SMD) were calculated for studies using a pain score or analgesic requirement as a primary outcome. RESULTS: Seventeen (17) studies met inclusion criteria (8 perioperative, 4 acute, and 5 chronic pain). Auriculotherapy was superior to controls for studies evaluating pain intensity (SMD, 1.56 [95% confidence interval (CI): 0.85, 2.26]; 8 studies). For perioperative pain, auriculotherapy reduced analgesic use (SMD, 0.54 [95% CI: 0.30, 0.77]; 5 studies). For acute pain and chronic pain, auriculotherapy reduced pain intensity (SMD for acute pain, 1.35 [95% CI: 0.08, 2.64], 2 studies; SMD for chronic pain, 1.84 [95% CI: 0.60, 3.07], 5 studies). Removal of poor quality studies did not alter the conclusions. Significant heterogeneity existed among studies of acute and chronic pain, but not perioperative pain. CONCLUSIONS: Auriculotherapy may be effective for the treatment of a variety of types of pain, especially postoperative pain. However, a more accurate estimate of the effect will require further large, well-designed trials.

Effect of ritonavir-induced cytochrome P450 3A4 inhibition on plasma fentanyl concentrations during patient-controlled epidural labor analgesia: a pharmacokinetic simulation.

BACKGROUND: Ritonavir inhibition of cytochrome P450 3A4 decreases the elimination clearance of fentanyl by 67%. We used a pharmacokinetic model developed from published data to simulate the effect of sample patient-controlled epidural labor analgesic regimens on plasma fentanyl concentrations in the absence and presence of ritonavir-induced cytochrome P450 3A4 inhibition. METHODS: Fentanyl absorption from the epidural space was modeled using tanks-in-series delay elements. Systemic fentanyl disposition was described using a three-compartment pharmacokinetic model. Parameters for epidural drug absorption were estimated by fitting the model to reported plasma fentanyl concentrations measured after epidural administration. The validity of the model was assessed by comparing predicted plasma concentrations after epidural administration to published data. The effect of ritonavir was modeled as a 67% decrease in fentanyl elimination clearance. Plasma fentanyl concentrations were simulated for six sample patient-controlled epidural labor analgesic regimens over 24 h using ritonavir and control models. Simulated data were analyzed to determine if plasma fentanyl concentrations producing a 50% decrease in minute ventilation (6.1 ng/mL) were achieved. RESULTS: Simulated plasma fentanyl concentrations in the ritonavir group were higher than those in the control group for all sample labor analgesic regimens. Maximum plasma fentanyl concentrations were 1.8 ng/mL and 3.4 ng/mL for the normal and ritonavir simulations, respectively, and did not reach concentrations associated with 50% decrease in minute ventilation. CONCLUSION: Our model predicts that even with maximal clinical dosing regimens of epidural fentanyl over 24 h, ritonavir-induced cytochrome P450 3A4 inhibition is unlikely to produce plasma fentanyl concentrations associated with a decrease in minute ventilation.

Selected Gamma Aminobutyric Acid (GABA) Esters may Provide Analgesia for Some Central Pain Conditions.

Central pain is an enigmatic, intractable condition, related to destruction of thalamic areas, resulting in likely loss of inhibitory synaptic transmission mediated by GABA. It is proposed that treatment of central pain, a localized process, may be treated by GABA supplementation, like Parkinson's disease and depression. At physiologic pH, GABA exists as a zwitterion that is poorly permeable to the blood brain barrier (BBB). Because the pH of the cerebral spinal fluid (CSF) is acidic relative to the plasma, ion trapping may allow a GABA ester prodrug to accumulate and be hydrolyzed within the CSF. Previous investigations with ester local anesthetics may be applicable to some GABA esters since they are weak bases, hydrolyzed by esterases and cross the BBB. Potential non-toxic GABA esters are discussed. Many GABA esters were investigated in the 1980s and it is hoped that this paper may spark renewed interest in their development.

Exercise and Auricular Acupuncture for Chronic Low Back Pain: A Feasibility Randomised Controlled Trial

Objectives: To evaluate the feasibility of a randomized-controlled trial (RCT) investigating the effects of adding auricular acupuncture (AA) to exercise for participants with chronic low-back pain (CLBP). Methods: Participants with CLBP were recruited from primary care and a university population and were randomly allocated (n=51) to 1 of 2 groups: (1) "Exercise Alone (E)"-12-week program consisting of 6 weeks of supervised exercise followed by 6 weeks unsupervised exercise (n=27); or (2) "Exercise and AA (EAA)"-12-week exercise program and AA (n=24). Outcome measures were recorded at baseline, week 8, week 13, and 6 months. The primary outcome measure was the Oswestry Disability Questionnaire. Results: Participants in the EAA group demonstrated a greater mean improvement of 10.7% points (95% confidence interval, -15.3,-5.7) (effect size=1.20) in the Oswestry Disability Questionnaire at 6 months compared with 6.7% points (95% confidence interval, -11.4,-1.9) in the E group (effect size=0.58). There was also a trend towards a greater mean improvement in quality of life, LBP intensity and bothersomeness, and fear-avoidance beliefs in the EAA group. The dropout rate for this trial was lower than anticipated (15% at 6 mo), adherence with exercise was similar (72% E; 65% EAA). Adverse effects for AA ranged from 1% to 14% of participants. Discussion: Findings of this study showed that a main RCT is feasible and that 56 participants per group would need to be recruited, using multiple recruitment approaches. AA was safe and demonstrated additional benefits when combined with exercise for people with CLBP, which requires confirmation in a fully powered RCT.

No evidence of morphine analgesia to noxious shock in the shore crab, Carcinus maenas

A number of criteria have been suggested for testing if pain occurs in animals, and these include an analgesic effect of opiates (Bateson, 1991). Morphine reduces responses to noxious stimuli in crustaceans but also reduces responsiveness in a non-pain context. Here we use a paradigm in which shore crabs receive a shock in a preferred dark shelter but not if they remain in an unpreferred light area. Analgesia should thus enhance movement to the preferred dark area because they should not experience 'pain'. However, morphine inhibits rather than enhances this movement even when no shock is given. Morphine produces a general effect of non-responsiveness rather than a specific analgesic effect and this could also explain previous studies claiming analgesia. However, we question the utility of this criterion of pain and suggest instead that behavioural criteria be employed. (C) 2011 Published by Elsevier B.V.

Exercise and manual auricular acupuncture:a pilot assessor-blind randomised controlled trial. (The acupuncture and personalised exercise programme (APEP) trial)

Evidence supports the use of exercise for chronic low back pain (CLBP); however, adherence is often poor due to ongoing pain. Auricular acupuncture is a form of pain relief involving the stimulation of points on the outer ear corresponding with specific body parts. It may be a useful adjunct to exercise in managing CLBP; however, there is only limited evidence to support its use with this patient group.