A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery.

Chronic postoperative pain is common after breast cancer surgery. Peri-operative lidocaine infusion may prevent the development of chronic postoperative pain, but a large-scale trial is required to test this hypothesis. It is unclear whether a pragmatic, multicentre trial design that is consistent with expert guidance, addresses the limitations of previous studies, and overcomes existing translational barriers is safe, effective and feasible. We conducted a double-blind, randomised controlled pilot study in 150 patients undergoing breast cancer surgery across three hospitals in Western Australia. Patients received lidocaine, or equivalent volumes of saline, as an intravenous bolus (1.5 mg.kg-1 ) and infusion (2 mg.kg-1 .h-1 ) intra-operatively, and a subcutaneous infusion (1.33 mg.kg-1 .h-1 ) postoperatively for up to 12 h on a standard surgical ward, with novel safety monitoring tools in place. The co-primary outcomes were: in-hospital safety events; serum levels of lidocaine during intravenous and subcutaneous infusion; and annualised enrolment rates per site with long-term data capture. In-hospital safety events were rare, and similar in the placebo and lidocaine arms (3% vs. 1%). Median (IQR [range]) serum lidocaine levels during intravenous (2.16 (1.74-2.83 [1.12-6.06]) µg.ml-1 , n = 41) and subcutaneous (1.52 (1.28-1.83 [0.64-2.85]) µg.ml-1 , n = 48) infusion were comparable with previous trials reporting improved pain outcomes. Annualised enrolment approximated 50 patients per site per year, with high levels of protocol adherence and ≥ 99% capture of outcomes at 3 and 6 months. The adjusted odds ratio (95%CI) for postoperative pain at 6 months in the lidocaine arm was 0.790 (0.370-1.684). We conclude that this trial, as designed, is safe, effective and feasible in patients undergoing breast cancer surgery, and a larger-scale trial is planned.

New formulations of fentanyl for acute pain management.

Intravenous fentanyl citrate has stood the test of time as a valuable formulation for pain management. The desirable physicochemical properties of fentanyl have allowed the development of several alternative formulations for delivery using less invasive routes, for example, transmucosal (intranasal, oral buccal and oral sublingual) and transdermal. These new formulations have been applied to clinical settings in which rapid onset of analgesia is desired, using convenient but noninvasive methods. Recent commercialization of various formulations has been driven largely by the needs of cancer patients, for whom severe but self-limiting "breakthrough" pain is less suitably treated by parenteral or oral routes of opioid administration. However, these formulations are also used for acute analgesia in prehospital and in-hospital emergency department care, and for pediatric acute pain management. Finally, they are increasingly used by patients with chronic pain of nonmalignant origin, although there is considerable debate about their merit in this group. We searched the databases MEDLINE, PubMed, EMBASE, CINAHL and Cochrane up to October 2011, using search terms "fentanyl AND nasal; intranasal; transmucosal; buccal; sublingual; oral; inhaled; inhalation; transdermal". The characteristics of several formulations of fentanyl are reviewed, detailing their pharmacokinetics, pharmacodynamics and clinical experience with their use for acute pain management.

Evidence-based management of postoperative pain in adults undergoing open inguinal hernia surgery.

BACKGROUND: Open inguinal hernia repair is associated with moderate postoperative pain, but optimal analgesia remains controversial. The aim of this systematic review was to evaluate the available literature on the management of pain after open hernia surgery. METHODS: Randomized studies, in English, published between January 1966 and March 2009, assessing analgesic and anaesthetic interventions in adult open hernia surgery, and reporting pain scores, were retrieved from the Embase and MEDLINE databases. In addition to published evidence, clinical practice was taken into account to ensure that the recommendations had clinical validity. RESULTS: Of the 334 randomized studies identified, 79 were included. Quantitative analysis suggested that regional anaesthesia was superior to general anaesthesia for reducing postoperative pain. Spinal anaesthesia was associated with a higher incidence of urinary retention and increased time to home-readiness compared with regional anaesthesia. CONCLUSION: Field block with, or without wound infiltration, either as a sole anaesthetic/analgesic technique or as an adjunct to general anaesthesia, is recommended to reduce postoperative pain. Continuous local anaesthetic infusion of a surgical wound provides a longer duration of analgesia. Conventional non-steroidal anti-inflammatory drugs or cyclo-oxygenase 2-selective inhibitors in combination with paracetamol, administered in time to provide sufficient analgesia in the early recovery phase, are optimal. In addition, weak opioids are recommended for moderate pain, and strong opioids for severe pain, on request.

Expert panel consensus recommendations for the pharmacological treatment of acute pain in the Middle East region.

The findings of an expert panel convened to review critically how best to apply evidence-based guidelines for the treatment of acute pain in the Middle East region are presented. The panel recommended a three-step treatment protocol. Patients with mild-to-moderate levels of acute pain should be treated with paracetamol (step 1). If analgesia is insufficient after 1-2 days, a selective cyclo-oxygenase-2 inhibitor or, if gastrointestinal safety and bleeding risk are not an issue, a non-specific nonsteroidal anti-inflammatory drug, should be used (step 2). If analgesia remains inadequate, treatment with tramadol, or paracetamol plus codeine/tramadol is recommended (step 3). Patients reporting severe pain should be referred to a pain clinic or specialist for opioid analgesic treatment. Measures of pain and functioning that have been validated in Arabic, with culturally appropriate and easy to understand descriptors, should be used. Early and aggressive acute pain management is important to reduce the risk of pain becoming chronic, especially in the presence of neuropathic features.

[Paracetamol for perioperative analgesia. Old substance - new insights]. / Paracetamol für die perioperative Analgesie. Alte Substanz - neue Erkenntnisse.

Since paracetamol was first synthesized in 1878 it has become one of the most popular and widely used drugs for the first-line treatment of fever and pain. The reasons for this popularity are a wide variety of formulations, an assumed positive safety record and the wide availability as an over-the-counter drug. However, recently several studies questioned the positive risk-benefit ratio of paracetamol for postoperative pain by observing several possible adverse effects and limitations. The aim of the present review is to give an update of the recent literature on the efficacy of paracetamol for postoperative pain and on the value of the clinical relevance of different adverse effects of paracetamol. Finally, based on the current findings the authors try to assess the role of paracetamol for the treatment of postoperative pain.

An observational study of skin conductance monitoring as a means of predicting hypotension from spinal anaesthesia for caesarean delivery.

BACKGROUND: Hypotension after spinal anaesthesia is a common and important complication at caesarean delivery. Skin conductance monitoring has been shown to predict post-spinal hypotension in elderly patients and may be a rapid, non-invasive means of predicting risk in the obstetric population. METHODS: Women having elective caesarean delivery were included in this observational pilot trial. Baseline data were obtained for blood pressure, heart rate and skin conductance variables before administration of spinal anaesthesia and at 1-min intervals for 20 min thereafter. Correlations between baseline data and minimum post-spinal blood pressure were calculated, and the predictive value of baseline variables was estimated by use of receiver operator characteristics. RESULTS: Forty women completed the study. Spinal anaesthesia was followed in most cases by a significant reduction from baseline in systolic blood pressure [0-9% n=2 (5%), 10-20% n=21 (52.5%), 20-30% n=12 (30%), >30% n=5 (12.5%)]. Minimum systolic blood pressure was >100 mmHg in 25 (62%), 80-100 mmHg in 12 (30%) and < 80 mmHg in 3 (7.5%) patients. Fasting times, spinal block distribution, baseline heart rate, blood pressure or baseline skin conductance did not predict post-spinal hypotension or neonatal outcome. CONCLUSION: In contrast to a previous report in elderly patients, we were unable to demonstrate a significant relationship between baseline sympathetic tone, measured by skin conductance, and hypotension following spinal anaesthesia in women undergoing elective caesarean delivery.

The evaluation of anaesthesia-related information on the Internet.

The quality and accessibility of anaesthesia-related information available to patients on the Internet is a growing concern for the specialty. We sought to evaluate the quality of anaesthesia-related websites using a simple scoring system. The scoring system comprised quality and technical scores individually, and these were also combined into a total score. Test-retest reliability was assessed by calculating intraclass correlation coefficients. We employed the four most popular search engines and one meta-search engine, using the search term "general anaesthesia". Only the first 10 sites retrieved were scored. The intraclass correlation coefficients for all terms demonstrated at least moderate agreement and the total scores demonstrated high consistency r = 0.852, 0.774 (P < 0.001, and P < 0.003 respectively). There were 18 duplicate websites and 32 were scored. There was no difference between search engines for any of the three scores awarded. The majority of websites were rated as either 'poor' or fair' across all scores. Our study indicates that quality anaesthesia-related information is unlikely to be retrieved by patients using the Internet.

A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty.

The PROSPECT Working Group, a collaboration of anaesthetists and surgeons, conducts systematic reviews of postoperative pain management for different surgical procedures (http://www.postoppain.org). Evidence-based consensus recommendations for the effective management of postoperative pain are then developed from these systematic reviews, incorporating clinical practice observations, and transferable evidence from other relevant procedures. We present the results of a systematic review of pain and other outcomes following analgesic, anaesthetic and surgical interventions for total knee arthroplasty (TKA). The evidence from this review supports the use of general anaesthesia combined with a femoral nerve block for surgery and postoperative analgesia, or alternatively spinal anaesthesia with local anaesthetic plus spinal morphine. The primary technique, together with cooling and compression techniques, should be supplemented with paracetamol and conventional non-steroidal anti-inflammatory drugs or COX-2-selective inhibitors, plus intravenous strong opioids (high-intensity pain) or weak opioids (moderate- to low-intensity pain).

The assessment of postoperative pain by monitoring skin conductance: results of a prospective study.

The number of fluctuations of skin conductance per second correlates with postoperative pain. The aim of this prospective study was to test the cut-off value for the number of fluctuations of skin conductance per second obtained from a previous study. Seventy-five patients were asked to quantify their level of pain on a numeric rating scale (0-10) in the recovery room. The number of fluctuations of skin conductance per second was recorded simultaneously. The number of fluctuations of skin conductance per second was different between patients with no (0.07), mild (0.16), moderate (0.28) and severe pain (0.33); p < 0.001. The tested cut-off value for the number of fluctuations of skin conductance per second (0.1) distinguished a numeric rating scale 3 with 88.5% sensitivity and 67.7% specificity. The number of fluctuations of skin conductance per second may be a useful means of assessing postoperative pain.

New parameters of skin conductance compared with Bispectral Index monitoring to assess emergence from total intravenous anaesthesia.

BACKGROUND: Arousal after total i.v. anaesthesia (TIVA) has been reported to be detectable by monitoring the number of fluctuations per second (NFSC), a parameter of skin conductance (SC). However, compared with monitoring of the bispectral index (BIS), the predictive probability of NFSC was significantly lower. The aim of this study was to determine the value of the two new, not yet published parameters of SC, area under the curve (AUC) methods A and B, for monitoring emergence from TIVA compared with monitoring of NFSC and BIS. METHODS: Twenty-five patients undergoing surgery were investigated. NFSC, AUC A, AUC B, BIS, and haemodynamic parameters (mean arterial pressure and heart rate) were recorded simultaneously. The performance of the monitoring devices in distinguishing between the clinical states 'steady-state anaesthesia', 'first clinical reaction', and 'extubation' were compared using the method of prediction probability (Pk) calculation. RESULTS: BIS showed the best performance in distinguishing between 'steady-state anaesthesia' vs 'first reaction' (Pk BIS 0.95; NFSC 0.73; AUC A 0.54; AUC B 0.62) and 'steady-state anaesthesia' vs 'extubation' (Pk BIS 0.99; NFSC 0.73; AUC A 0.71; AUC B 0.67). However, the time from first BIS>60/SC>0 to a first clinical reaction was significantly shorter for BIS (median BIS((R)) 180 s; NFSC 780 s; AUC A 750 s; AUC B 690 s; P < 0.001). CONCLUSIONS: AUC A and AUC B did not improve accuracy of SC monitoring in patients waking after TIVA.

PROSPECT: a practical method for formulating evidence-based expert recommendations for the management of postoperative pain.

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

Monitoring of skin conductance to assess postoperative pain intensity.

BACKGROUND: Pain is known to alter the electrogalvanic properties of the skin. The aim of this pilot study was to investigate the influence of postoperative pain on skin conductance (SC) readings. METHODS: After obtaining ethical approval and written informed consent, 25 postoperative patients were asked to quantify their level of pain on a numeric rating scale (NRS, 0-10) at different time points in the recovery room. As a parameter of SC, the number of fluctuations within the mean SC per second (NFSC) was recorded. Simultaneously, the NRS was obtained from patients by a different observer who was blinded to the NFSC values. RESULTS: Data from 110 readings of 25 patients (14 female, 11 male; 21-67 yr) were included. NFSC showed a significant correlation with the NRS (r=0.625; P<0.01), whereas heart rate and blood pressure showed no or very weak correlation with the NRS. NFSC was significantly different between patients with no (NRS=0), mild (NRS=1-3), moderate (NRS=4-5) and severe (NRS=6-10) pain (no: 0.047, mild: 0.089, moderate: 0.242, severe: 0.263; P<0.0001). Post hoc, a cut-off value for NFSC (0.1) was calculated above which a pain score >3 on the NRS was predicted with sensitivity of 89% and specificity of 74%. CONCLUSIONS: The severity of postoperative pain significantly influences SC. Using cut-off values, NFSC may prove a useful tool for pain assessment in the postoperative period.

Skin conductance monitoring compared with Bispectral Index to assess emergence from total i.v. anaesthesia using propofol and remifentanil.

BACKGROUND: Arousal after sevoflurane anaesthesia has been detectable by monitoring changes in skin conductance (SC) with similar accuracy as monitoring Bispectral Index (BIS). As SC monitoring detects changes in sympathetic tone, the measurements might be confounded by the sympatholytic properties of propofol, a component of total i.v. anaesthesia (TIVA). Therefore in this study, monitoring of SC during emergence from TIVA was compared with the monitoring of BIS. METHODS: Twenty-five patients undergoing plastic surgery were investigated. The number of fluctuations of SC per second (NFSC), BIS and haemodynamic variables [systolic blood pressure (SBP) and heart rate (HR)] were recorded simultaneously. The performance of the monitoring devices in distinguishing between the clinical states 'steady-state anaesthesia', 'first clinical reaction' and 'extubation' were compared using the method of prediction probability (Pk) calculation. RESULTS: BIS((R)) showed the best performance in distinguishing between 'steady-state anaesthesia' and 'first reaction' (Pk BIS 0.99 vs NFSC 0.80; P<0.01), and 'steady-state anaesthesia' and 'extubation' (Pk BIS) 1.00 vs NFSC 0.91; P<0.05); the time from first change of BIS or NFSC to a first clinical reaction was significantly longer for NFSC (median BIS 135 s vs NFSC 191 s; P<0.05). BIS and NFSC performed better in distinguishing between the investigated clinical states than SBP and HR. CONCLUSIONS: In this study, BIS was found to predict arousal with a higher probability but slower response times than NFSC in patients waking after TIVA.

The role of ketamine in pain management.

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

Skin conductance monitoring compared with bispectral index monitoring to assess emergence from general anaesthesia using sevoflurane and remifentanil.

BACKGROUND: Changes in skin conductance have previously been reported to correlate well with plasma levels of stress hormones and awakening stimuli. In this study, monitoring of skin conductance during emergence from general anaesthesia was compared with the monitoring of bispectral index (BIS). METHODS: Twenty-five patients undergoing minor elective surgery were investigated. The number of fluctuations in mean skin conductance (NFSC), BIS and haemodynamic parameters were recorded simultaneously. The performance of the monitoring devices to predict and distinguish between the clinical states 'steady-state anaesthesia', 'first reaction' and 'extubation' were compared using the method of prediction probability (P(K)) calculation. RESULTS: Both monitors showed similar performance in distinguishing between 'steady-state anaesthesia' vs 'first reaction' (P(K) NFSC 0.89; BIS 0.94) and 'steady-state anaesthesia' vs 'extubation' (P(K) NFSC 0.96; BIS 0.96). The response times of the monitors, to indicate the likelihood of 'first reaction', were not significantly different. CONCLUSIONS: NFSC, as a parameter of skin conductance, performed similarly to BIS in patients waking after a general anaesthetic.