Intravenous lidocaine in the management of chronic peripheral neuropathic pain: a randomized-controlled trial.

PURPOSE: Neuropathic pain, resulting from injury to the peripheral or central nervous system, is due to upregulation of aberrant sodium channels with neuronal hyperexcitability. Lidocaine blocks these channels and several studies show that intravenous (IV) lidocaine infusion provides significant relief in patients with chronic peripheral neuropathic pain in the short term (for up to six hours). Our objective was to determine if IV lidocaine provides significant pain relief and overall improvement in quality of life in the longer term (for up to four weeks). METHODS: This single site randomized double-blind, crossover trial compared IV lidocaine infusion (5 mg·kg-1) with active placebo infusion containing diphenhydramine (50 mg) in patients with chronic neuropathic pain of peripheral nerve origin of at least six months duration. The primary outcome was average pain intensity reduction from IV lidocaine relative to placebo at four weeks post-infusion. Secondary outcome measures included parameters of physical function, mood, and overall quality of life. RESULTS: We enrolled 34 subjects in this trial-mostly with painful diabetic neuropathy and post-herpetic neuralgia. There were no significant differences between IV lidocaine and placebo infusions at any time point involving any of the outcome measures. Mean (standard deviation) pain intensity at week 4 for the placebo and lidocaine groups were not different [6.58 (1.97) vs 6.78 (1.56), respectively; between-group difference, 0.17; 95% confidence interval, - 0.50 to 0.84]. CONCLUSION: We found no significant long-term analgesic or quality of life benefit from IV lidocaine relative to control infusion for chronic peripheral neuropathic pain. TRIAL REGISTRATION: clinicaltrials.gov (NCT01669967); registered 22 June, 2012.

RéSUMé: OBJECTIF: La douleur neuropathique, résultat d'une lésion du système nerveux périphérique ou central, est due à l'augmentation de canaux sodiques aberrants accompagnée d'une hyperexcitabilité neuronale. La lidocaïne bloque ces canaux et plusieurs études ont démontré qu'une perfusion intraveineuse (IV) de lidocaïne offrait un important soulagement à court terme (pour une durée maximale de six heures) aux patients atteints de douleur neuropathique périphérique chronique. Notre objectif était de déterminer si la lidocaïne IV procurait un soulagement significatif de la douleur et une amélioration globale de la qualité de vie à plus long terme (pour une durée maximale de quatre semaines). MéTHODE: Cette étude randomisée croisée à double insu et mono-site a comparé une perfusion de lidocaïne IV (5 mg·kg−1) à une perfusion de placebo actif contenant de la diphenhydramine (50 mg) chez des patients atteints de douleur neuropathique chronique provenant du système nerveux périphérique et durant depuis au moins six mois. Le critère d'évaluation principal était la réduction moyenne de l'intensité de la douleur procurée par la lidocaïne IV par rapport au placebo à quatre semaines post-perfusion. Les critères d'évaluation secondaires comprenaient divers paramètres pour mesurer la capacité physique fonctionnelle, l'humeur et la qualité de vie globale. RéSULTATS: Nous avons recruté 34 patients pour cette étude, la plupart souffrant de neuropathie diabétique douloureuse et de névralgie post-herpétique. Aucune différence significative n'a été observée entre les perfusions de lidocaïne IV et de placebo, quel que soit le point de mesure dans le temps, pour aucun de nos critères d'évaluation. L'intensité de la douleur moyenne (écart type) à la semaine 4 était similaire dans les groupes placebo et lidocaïne [6,58 (1,97) vs 6,78 (1,56), respectivement; différence intergroupe, 0,17; intervalle de confiance 95 %, − 0,50 à 0,84]. CONCLUSION: Nous n'avons trouvé aucun bienfait significatif sur l'analgésie à long terme ou la qualité de vie d'une perfusion de lidocaïne IV par rapport à une perfusion témoin pour soulager la douleur neuropathique périphérique chronique. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT01669967); enregistrée le 22 juin 2012.

Sensitivity of the DN4 in Screening for Neuropathic Pain Syndromes.

OBJECTIVES: Several tools have been developed to screen for neuropathic pain. This study examined the sensitivity of the Douleur Neuropathique en 4 Questions (DN4) in screening for various neuropathic pain syndromes. MATERIALS AND METHODS: This prospective observational study was conducted in 7 Canadian academic pain centers between April 2008 and December 2011. All newly admitted patients (n=2199) were approached and 789 eligible participants form the sample for this analysis. Baseline data included demographics, disability, health-related quality of life, and pain characteristics. Diagnosis of probable or definite neuropathic pain was on the basis of history, neurological examination, and ancillary diagnostic tests. RESULTS: The mean age of study participants was 53.5 years and 54.7% were female; 83% (n=652/789) screened positive on the DN4 (≥4/10). The sensitivity was highest for central neuropathic pain (92.5%, n=74/80) and generalized polyneuropathies (92.1%, n=139/151), and lowest for trigeminal neuralgia (69.2%, n=36/52). After controlling for confounders, the sensitivity of the DN4 remained significantly higher for individuals with generalized polyneuropathies (odds ratio [OR]=4.35; 95% confidence interval [CI]: 2.15, 8.81), central neuropathic pain (OR=3.76; 95% CI: 1.56, 9.07), and multifocal polyneuropathies (OR=1.72; 95% CI: 1.03, 2.85) compared with focal neuropathies. DISCUSSION: The DN4 performed well; however, sensitivity varied by syndrome and the lowest sensitivity was found for trigeminal neuralgia. A positive DN4 was associated with greater pain catastrophizing, disability and anxiety/depression, which may be because of disease severity, and/or these scales may reflect magnification of sensory symptoms and findings. Future research should examine how the DN4 could be refined to improve its sensitivity for specific neuropathic pain conditions.

The reciprocal associations between catastrophizing and pain outcomes in patients being treated for neuropathic pain: a cross-lagged panel analysis study.

Catastrophizing is recognized as a key psychosocial factor associated with pain-related negative outcomes in individuals with chronic pain. Longitudinal studies are needed to better understand the temporal relationship between these constructs. The aim of this study was to determine if changes in catastrophizing early in treatment predicted subsequent changes in pain intensity and interference later in treatment, or alternately, if early changes in pain intensity and interference predicted subsequent changes in catastrophizing. A total of 538 patients with neuropathic pain were recruited from 6 multidisciplinary pain clinics across Canada. Study participants were asked to complete measures of catastrophizing, pain intensity, and interference when first seen in the clinic and then again at 3- and 6-month follow-ups. Cross-lagged panel analyses were used to determine the temporal associations among the study variables. The results showed that decreases in catastrophizing early in treatment prospectively predicted improvement in both pain intensity and interference later in treatment. Converse temporal relationships were also found, where a reduction in pain intensity and interference early in treatment predicted a subsequent diminishing of catastrophizing. All 4 unique cross-lagged correlations significantly accounted for an additional 4% to 7% of the total variance. The findings are consistent with theoretical models hypothesizing a causal impact of catastrophizing on pain, suggesting a mutual causation between these factors. The results support that treatments targeting catastrophizing may influence other pain-related outcomes, and conversely that treatments aiming to reduce pain could potentially influence catastrophizing. There may therefore be multiple paths to positive outcomes.

Long-Term Outcome of the Management of Chronic Neuropathic Pain: A Prospective Observational Study.

This prospective observational cohort study addressed the long-term clinical effectiveness of the management of chronic neuropathic noncancer pain at 7 Canadian tertiary pain centers. Patients were treated according to standard guidelines and were followed at 3, 6, 12, 18, and 24 months. Standard outcome measures for pain, mood, quality of life, and overall treatment satisfaction were administered, with the primary outcome measure designated as the composite of 30% reduction in average pain intensity and 1-point decrease in the mean Interference Scale Score (0-10) of the Brief Pain Inventory at 12 months relative to baseline. Of 789 patients recruited, mean age was 53.5 ± 14.2 years (55% female) and mean duration of pain was 4.88 ± 5.82 years. Mean average pain intensity (0-10) at baseline was 6.1 ± 1.9. All standard outcome measures showed statistically significant improvement at 12 months relative to baseline (P < .001). However, only 23.7% attained clinically significant improvement in pain and function at 12 months as the primary outcome measure. Univariable analyses showed poorer outcomes at 12-month follow-up with longer duration of pain (P = .002), greater cigarette use (P = .01), more disability compensation (P = .001), and higher opioid doses at baseline and at 12 months (P < .02). Our present treatment modalities provide significant long-term benefit in only about a quarter of patients with neuropathic pain managed at tertiary care pain clinics. Opioid therapy may not be beneficial for the long term. Perspective: Evidence-based treatment of chronic neuropathic pain provides long-term benefit in only about one-quarter of patients seen in tertiary care centers. Opioid therapy may not be beneficial.

Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society.

BACKGROUND: Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians. OBJECTIVE: To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management. METHODS: RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013. Medications were recommended in the consensus statement if their analgesic efficacy was supported by at least one methodologically sound RCT (class I or class II) showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment were based on the degree of evidence of analgesic efficacy, safety and ease of use. RESULTS: Analgesic agents recommended for first-line treatments are gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors. Tramadol and controlled-release opioid analgesics are recommended as second-line treatments for moderate to severe pain. Cannabinoids are now recommended as third-line treatments. Recommended fourth-line treatments include methadone, anticonvulsants with lesser evidence of efficacy (eg, lamotrigine, lacosamide), tapentadol and botulinum toxin. There is support for some analgesic combinations in selected NeP conditions. CONCLUSIONS: These guidelines provide an updated, stepwise approach to the pharmacological management of NeP. Treatment should be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Additional studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes and treatment of pediatric, geriatric and central NeP.

Mitigating the risk of opioid abuse through a balanced undergraduate pain medicine curriculum.

Chronic pain is highly prevalent in the United States and Canada, occurring in an estimated 30% of the adult population. Despite its high prevalence, US and Canadian medical schools provide very little training in pain management, including training in the safe and effective use of potent analgesics, most notably opioids. In 2005, the International Association for the Study of Pain published recommendations for a core undergraduate pain management curriculum, and several universities have implemented pilot programs based on this curriculum. However, when outcomes have been formally assessed, these initiatives have resulted in only modest improvements in physician knowledge about chronic pain and its treatment. This article discusses strategies to improve undergraduate pain management curricula and proposes areas in which those efforts can be augmented. Emphasis is placed on opioids, which have great potency as analgesics but also substantial risks in terms of adverse events and the risk of abuse and addiction. The authors conclude that the most important element of an undergraduate pain curriculum is clinical experience under mentors who are capable of reinforcing didactic learning by modeling best practices.

Influence of injection rate of hyperbaric bupivacaine on spinal block in parturients: a randomized trial.

PURPOSE: A prospective, randomized, double-blind clinical trial was undertaken to determine whether a tenfold difference in the rate of intrathecal injection of bupivacaine would affect sensory block level in parturients. Secondary outcomes included onset of block and the incidence of hypotension and nausea. METHODS: Following Research Ethics Board approval, 90 ASA I and II term parturients scheduled for Cesarean delivery were randomized to receive either fast injection (over four seconds, Group F) or slow injection (over 40 sec, Group S) of 0.75% hyperbaric bupivacaine 12 mg plus morphine 200 microg. Sensory block, motor block, and blood pressure were assessed every minute for the first 15 min, then every five minutes for the next 20 min. All occurrences of nausea, hypotension (decrease in systolic blood pressure > 30%) and ephedrine requirements were recorded. RESULTS: Forty-three patients in Group F and 42 patients in Group S completed the study. No differences in maximum sensory block height (Group F = median T2, interquartile range [T2-T4], Group S = T3 [T2-T4], P = 0.077) or time to achieve block height (F = 9.3 +/- 4.3 min, S = 9.7 +/- 4.7, P = 0.64) were observed. The frequencies of hypotension (Group F = 35/43, Group S = 32/42, P = 0.56), ephedrine utilization (Group F = 32/43, Group S = 26/42, P = 0.21) and nausea (Group F = 15/43, Group S = 16/42, P = 0.76) were similar. CONCLUSION: Rapid intrathecal injection of hyperbaric bupivacaine does not affect spread of spinal anesthesia or the incidence of hypotension and nausea in parturients.

Brief review: perioperative management of the patient with chronic non-cancer pain.

PURPOSE: Both opioid and non-opioid medications are being utilized increasingly in the treatment of chronic non-cancer pain, and the number of surgical patients receiving large regular doses of opioids is ever-expanding. The perioperative pain control of these patients is often challenging, and is broadening the role of the anesthesiologist as 'perioperative physician'. These patients need to be identified before surgery to plan optimal pain control postoperatively. The purpose of this review is to provide an update on the important considerations in managing the chronic non-cancer pain patient receiving high dose opioids and other adjunctive medications/analgesics. SOURCE: English language articles published between June 1980 and May 2006 were identified by a computerized Medline search using keywords (1/2)chronic pain(1/2), (1/2)opioid dependent(1/2) and (1/2)perioperative(1/2). This same search strategy was repeated and updated using both Medline and Embase. All relevant publications were retrieved and their bibliographies were scanned for additional sources. PRINCIPAL FINDINGS: Although an increasingly common problem for the acute pain service, there is very little published on this topic. Key points include the concept of opioid equivalency, tolerance, the role of adjunctive medications, and the need for good communication between the surgical team, the acute pain service and the patient who is often anxious about the upcoming procedure due to previous unpleasant experiences with poor pain control in hospital. CONCLUSION: Clinical care of the opioid-dependent patient in the perioperative period can be a daunting task. Education to all staff involved in this area needs to be enhanced to improve outcome and patient satisfaction.

The effect of epidural needle type on postdural puncture headache: a randomized trial.

PURPOSE: A prospective, randomized trial in labouring parturients was undertaken to assess whether the 18G Special Sprotte epidural needle is associated with a lower incidence of accidental dural puncture (ADP) in comparison with the 17G Tuohy needle. A secondary purpose was to determine if the incidence of postdural puncture headache (PDPH ) differed between groups when ADP occurred. METHODS: Following Institutional Review Board approval 1,077 parturients requesting epidural analgesia at three tertiary obstetrical units were randomized to epidural catheter insertion with a 17G Tuohy or 18G Special Sprotte needle. Patients were followed for seven days by a blinded assessor to determine the occurrence of PDPH using standardized criteria. If postural headache or neck ache presented, an ADP was diagnosed even if cerebrospinal fluid (CSF) was not observed at insertion. This subgroup was followed daily to assess headache characteristics and response to blood patch. RESULTS: Six Tuohy group patients, and two patients in the Sprotte group were excluded. One of the six excluded in the Tuohy group had an ADP. Twenty-eight ADPs occurred, nine unrecognized by CSF visualization (1.8% Tuohy, 3.4% Sprotte, P = 0.12). The incidence of unrecognized ADPs was higher in the Sprotte group (40% Sprotte vs 20% Tuohy, P < 0.05). If ADP occurred, the incidence of PDPH was lower in the Sprotte group (100% Tuohy vs 55% Sprotte, P = 0.025). The ease of use, and user satisfaction were higher in the Tuohy group (84 +/- 17.3% Tuohy vs 68.2 +/- 25.3% Sprotte, P < 0.001). CONCLUSION: The incidence of ADP was not reduced with the Special Sprotte epidural needle in comparison with the Tuohy needle, but PDPH after ADP occurred less frequently in the Sprotte group.

Targeted thoracic epidural blood patch placed under electrical stimulation guidance (Tsui test).

PURPOSE: This case report describes the use of electrical epidural stimulation (Tsui test) to confirm accurate placement of a thoracic epidural catheter when administering an epidural blood patch for headache management in a patient suffering from spontaneous intracranial hypotension. CLINICAL FEATURES: A 41-yr-old female presented to the Chronic Pain Clinic with a history of postural headache symptoms worsening in severity over several years. Two previous blood patches performed at T11-12 and T10-11 respectively provided short-term relief only. The presumed diagnosis of a spontaneous dural tear was confirmed by a nuclear flow test to be at T2-T4. The epidural site was accessed at T6 with a Tuohy needle. To accurately place the epidural blood patch at the level of the dural tear, the Arrow catheter with electrode adapter was advanced under nerve stimulation guidance to T4. Ten millilitres of autologous blood injected through the catheter was confirmed on magnetic resonance imaging, one hour postprocedure, to lie between T3 and T9. Sustained headache relief was achieved. CONCLUSION: The use of electrical stimulation guidance may be useful when precise epidural blood patch placement is required.

Opioids in the parturient with chronic nonmalignant pain: a retrospective review.

The purpose of this research was to determine the neonatal outcomes of women who had been taking medically prescribed opioids throughout their pregnancy. A retrospective case study was done of 15 pregnancies associated with maternal opiate use between January 1, 1999, and September 30, 2002. Two cases were excluded due to coaddiction. Neonatal data were collected including gestational age, head circumference, length, birth weight, Apgar score at one and five minutes, details of resuscitation required, and Neonatal Abstinence Score. There were 13 pregnancies, which resulted in 13 live births; opioids prescribed included oxycodone, codeine, meperidine, fentanyl, dilaudid, morphine, and methadone. There were four babies with one-minute Apgar score = -5, and two babies with five-minute Apgar score = 5. It was concluded that neonatal growth markers in this population were within normal limits as plotted on the standard growth and development record of Gairdner-Pearson. Five out of 13 (38.5 percent) neonates were diagnosed with opioid discontinuation syndrome.

Attitudes toward opioid use for chronic pain: a Canadian physician survey.

OBJECTIVES: To measure chronic pain patient volumes seen in primary care practice; to determine what medications physicians choose for the treatment of moderate to severe chronic pain; to identify barriers to the use of opioids in the treatment of chronic pain; and to assess physicians' attitudes toward the current management of chronic pain in Canada. DESIGN: A computer-assisted telephone survey of 100 regionally representative Canadian physicians with a defined interest in palliative care (PC, n=30) or noncancer pain (GP, n=70). SETTING: A survey was conducted by Ipsos-Reid in June 2001. Only physicians who met the eligibility criteria of having written 20 or more prescriptions for moderate to severe pain in the preceding four weeks or having devoted 20% of time to palliative care were eligible to participate. RESULTS: In one month, the average number of patients with moderate to severe chronic pain seen by PCs was 94.2; the average seen by GPs was 44.7. The pain experienced by 83.3% of GP patients was noncancer related. For chronic cancer pain, an opioid analgesic was the treatment of choice of 79% of physicians (48% preferred morphine, 21% codeine, 10% other). For moderate to severe chronic noncancer pain, opioids were the first-line treatment of only 32% of physicians (16% preferred codeine, 16% major opioids) because a significant number preferred either non-steroidal anti-inflammatory drugs (29%) or acetaminophen (16%). Thirty-five per cent of GPs and 23% of PCs would never use opioids for noncancer pain, even when described as severe. Chronic pain was deemed by 68% of physicians to be inadequately managed. Almost 60% thought that pain management could be enhanced by improved physician education. Identified barriers to opioid use included addiction potential (37%) and side effects (25%). Seventeen per cent of GPs and 10% of PCs thought that regulatory sanctions limited opioid prescribing. CONCLUSIONS: Even among physicians experienced in chronic pain treatment, there is a reluctance to use opioids for severe nonmalignant pain. One-half of the survey participants believed that there was a need for improved physician education in pain management, including the use of opioids.

Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia.

PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.

Chronic pain in Canada--prevalence, treatment, impact and the role of opioid analgesia.

OBJECTIVE: To assess the prevalence, treatment and impact of chronic pain in Canada. METHODS: A stratified random sample of 2012 adult Canadians (weighted by sex, age and region according to 1996 census data) was surveyed by telephone in 2001 to determine the prevalence of chronic pain, defined as continuous or intermittent pain for at least six months. A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain. RESULTS: Chronic noncancer pain was reported by 29% of the respondents, with increased frequency in women and older age groups. The average duration of pain was 10.7 years and the average intensity was 6.3 (on a scale from 1 to 10), with 80% reporting moderate or severe pain. Anti-inflammatory agents were prescribed for 49% of respondents and opioid analgesics were prescribed for 22% (two-thirds of these were codeine). Almost 70% were worried about addiction potential, and one-third felt that strong analgesics should be reserved for terminal illnesses. Almost one-half were unable to attend social and family events, and the mean number of days absent from work in the past year due to chronic pain was 9.3. INTERPRETATION: Chronic noncancer pain is common in Canadian adults and has a major social and economic impact. Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain, less than 10% of chronic pain patients taking prescription medication were treated with a major opioid. Chronic pain is undertreated in Canada, and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program.