Stellate ganglion block (STGB) is commonly indicated in painful conditions like reflex sympathetic dystrophy, malignancies of head and neck, Reynaud’s disease and vascular insufficiency of the upper limbs. The sympathetic blockade helps to relieve pain and ischaemia. Diagnostic STGB is usually performed with local anaesthetics followed by therapeutic blockade with steroids, neurolytic agents or radiofrequency ablation of ganglion. There is increasing popularity and evidence for the use of adjuvants like opioid, clonidine and N Methyl d Aspartate (NMDA) receptor antagonist – ketamine – for the regional and neuroaxial blocks. The action of ketamine with sympatholytic block is through blockade of peripherally located NMDA receptors that are the target in the management of neuropathic pain, with the added benefit of counteracting the “wind-up” phenomena of chronic pain. We studied ketamine as an adjuvant to the local anaesthetic for STGB in 20 cases of peripheral vascular disease of upper limbs during the last 5 years at our institution. STGB was given for 2 days with 2 ml of 2% lignocaine + 8 ml of 0.25% bupivacaine, followed by block with the addition of 0.5 mg/kg of ketamine for three consecutive days. There was significant pain relief of longer duration with significant rise in hand temperature. We also observed complete healing of the gangrenous fingers in 17/19 patients. The most common approach for stellate ganglion block (STGB) is paratracheal, at the level of C6th Chassaignac’s tubercle.[1The sympathetic supply to the head, neck and upper limb is derived from T1-9 segments, and passes through the stellate ganglion (C5-T1). The stellate ganglion is 2.5 cm×1 cm×0.5 cm and lies over the neck of the 1ubercle.1Besides chronic regional pain syndrome (CRPS), sympathetic blockade is found to be useful in circulatory problems of the upper limbs, such as arterial embolism, accidental intra-arterial injection of drugs and Meniere’s syndrome. It has been indicated as immediate therapy for pulmonary embolism.5 Repeate7Due to non-availability/affordability of RF ablation and to avoid the potential complications of chemical neurolysis, we decided to study the efficacy of ketamine as an adjuvant in enhancing the effects of STGB. Ketamine is known to manipulate the NMDA receptors that trigger the aberrant brain activity in neuropathic pain and control the autonomic dysregulation. Besides A prospective analytical study was performed in 20 patients of PVD of upper limbs during the last 5 years. Approval by the institutional ethical committee and informed consent were obtained. The chief complaints were severe throbbing pain with cold fingers and dry gangrene of 8 days to 1 month duration. Patients were thoroughly assessed and investigated. Laser Doppler flowmetry of the affected extremity was carried out. Patients with h/o recent myocardial infarction /heart blocks and with International normalized ratio (INR) >1.5 were excluded. Pre-block vital parameters, temperature of the normal and affected hand and visual analogue scale (VAS) score for pain were recorded. Diagnostic STGB was carried out with local anaesthetic for 2 days. Patients having pain relief of 50% in the initial magnitude and increase in temperature of the affected hand by 1.5°C were subjected to therapeutic sympatholysis with ketamine. Pre-medication with intravenous midazolam 0.5 mg/kg was given for anxiolysis.th level, patient was lying supine with extension of head at the A-O joint and mouth partially open so as to relax the muscles in the neck [th tubercle approximately at a depth of 2–2.5 cm. The needle withdrawn for 2 mm to prevent periosteal or injection into the longus colli muscles. After −ve aspiration test, lignocaine 2% 2 ml+8 ml of 0.25% bupivacaine was injected in increments. Monitoring of vital parameters during the block, after the block for 30 min and, later, hourly for 4 h was carried out in the recovery room. The block was repeated in a similar way on the 2nd day to confirm the benefits. Later, for three successive days, STGB was repeated with 1.5 ml of 2% lignocaine +8 ml of 0.25% bupivacaine +0.5 mg/kg of ketamine. Intramuscular Diclofenac 2 mg/kg or Tramadol 2 mg/kg was given as soon as VAS reached >6.For classical anterior paratracheal approach at C-6the neck . After sFor pain relief – (0–10 point) VAS 2-hourly for 8 h and later 4-hourly up to16 h and at 24 h.Baseline axillary temperature and temperature of the affected hand before and after block, then 2-hourly for 8 h, later 4-hourly up to16 h and at 24 h.S/O improved circulation – vasodilatation, skin texture and colour.Horner’s syndrome.Immediate complications like hoarseness, weakness in the limb, respiratory insufficiency, etc.Weekly follow-up for 1 month, then monthly for 6 months and later 6-monthly for pain relief, sense of warmth, appearance of line of demarcation, healing of gangrenous lesion and return of peripheral pulsations.For any delayed complications.t”-test for unequal variance, for comparison of mean VAS score, temperature, duration of analgesia, pulse rate and mean blood pressure. Differences are considered as statistically significant if probability  is <0.05 and as highly significant if P<0.001, whereas probability of >0.05 is considered as insignificant. Level of significance is 0.001, 0.01 and 0.05, as appropriate. Power of the test is almost 1 whereever it is significant.Statitistical analysis of the data is performed using data analysis Tool Park in Microsoft Excel. As the sample size of the study group is 20, analysis of the quantitative data is carried out using Student’s unpaired “STGB was performed on 20 patients (M/F=19/1) of age 25–65 years, weighing 40–70 kg. The affecting pathologies are mentioned in P<0.001). The mean duration of analgesia observed was 7 h. Later, the STGB was performed for three successive days with LA+ketamine 0.5 mg/kg. The pre-block mean VAS of days 3, 4 and 5 was 4.7 whereas the post-block mean VAS was 1.6, which was significantly less. The temperature rise obtained was mean 1.73°C. Duration of analgesia was significantly more after the addition of ketamine, with a mean of 14 h (P<0.001). There was no significant variation in the mean pulse rate (PR) and mean blood pressure (MBP) before and after block following STGB and with the addition of ketamine.P<0.001). At 12 and 16 h, there was significant rise in VAS as 6.7 (0.9) and 6.8 (1.2), respectively, following LA block (P>0.05). However, the pre-block VAS of days 3, 4 and 5 achieved was mean (SD) 4.67 (0.7). There was a significant drop in the VAS record as 1.62 (0.73), 1.23 (0.68), 1.39 (0.5) and 2.22 (0.78) at 2, 6, 12 and 16 h, respectively, and it was highly significant (P<0.001).th week in (18/20) 94.7% of the patients. Later, few patients were lost to follow-up (LF) from 6 to 24 months. Warmth in the hand was maintained in (19/20) 95% of the cases. Greater than 90% healing of the fingers was observed in (18/19) 94.7% of the patients at the 12th week. The STGB was repeated in two cases, but a diabetic case required amputation of the 2 phalynx at 8th week due to poor response. Repeat Doppler flow study was not possible in all the cases. At 6 months, 17 patients underwent laser Doppler flowmetry, showing improvement in flow from 50% to 90%. At 24 months, 10 patients had 50–100% improvement in the circulation of the hand.et al. observed incidence of minor and short-lived complications in 1.7/1,000 patients, with no major complications in the series of 45,000 cases.[STGB is a well-accepted therapeutic technique. Wolf 00 cases. The loca00 cases.et al. advocated the injection of 3% phenol  at the stellate ganglion level via the C7 approach under fluoroscopy. They have not observed any long-term Horner’s syndrome.[et al. in 2006 reported profound pain relief following local application with buprenorphine at the stellate ganglion for head and face pain, supporting the presence of endogenous opioids on sympathetic ganglion.[53Racz syndrome. Harris eganglion. For longganglion. For prolanglion.5 Alternatanglion.55 Howevernglion.53Many opioid and non-opioid drugs are tried by different routes to treat chronic pain syndromes. Among th19For neuropathic pain, ketamine is reported to be helpful in a dose range of 0.1–7 mg/kg and by infusion for 30 min to 8 h in both CRPS Type I/II patients. Long-ter+ and Ca2+ channels in neuropathic pain, a combination of a Na+ channel blocker  and NMDA receptor antagonists appears to be rational for the treatment of neuropathic pain. The effect of opioid is decreased in patients with neuropathic pain.[PVD of the upper limbs present with either acute intractable or chronic ischaemic pain, with discolouration and gangrene of the fingers. To achieve prolonged sympathetic blockade for pain relief and to maintain circulation for healing, ketamine appears to be a good adjuvant for STGB. Its action may be supraspinal by systemic absorption and peripheral through NMDA receptors located on the somatic nerve and dorsal root ganglion. Blockade of peripherally located NMDA receptors is a potential target in the management of neuropathic pain due to vascular insufficiency as well. As therehic pain. Ketaminehic pain.et al.,[rd week in 17 patients and 100% pain relief in 15 patients over 4 weeks duration and also accelerated healing of the gangrenous fingers, as observed in 18/19 patients.The aim of our study was to evaluate the effects of ketamine with STGB. For the first 2 days, STGB was given with 10 ml of local anaesthetic. The mean pre-block VAS score was 7 and post-block score attained at 6 h was 3.2, which was significantly less. Following block with the LA agents, duration of analgesia  noted was 7 h (mean of days 1 and 2). After the first record of duration of analgesia, patients received intramuscular Diclofenac 2 mg/kg or Tramadol 2 mg/kg as soon as VAS reached >6. For the first 2 days, intensity of pain was higher in spite of parenteral analgesics. Later, for three successive days, STGBs with the addition of 0.5 mg/kg of ketamine resulted in a pre-block mean VAS of days 3, 4 and 5 of 4.7, showing better response to the parenteral analgesics, and the post-block VAS attained was 1.2 with significantly prolonged duration of analgesia of mean 14 h. The results were similar to the observations noted by Rani sunder et al., who obseet al.,–28 Thereet al., and as aet al., There arSTGB using local anaesthetic with an adjuvant ketamine is a safe and effective technique. Ketamine enhances the effect of sympathetic blockade with relief of pain, ischaemia and maintains circulation. Thus, ketamine is a useful adjuvant to STGB and it obviates the need of permanent destruction of the ganglion by chemical/RF neurolysis in patients with PVD.


Anal pain is a well-known sequel of rubber band ligation (RBL). A plastic device, the anal cooler which can be frozen in a freezer, has been developed to reduce anal pain. It contains a mixture of glycols and has a minimum temperature of 4 °C. This study was designed to investigate the efficacy of the anal cooler in pain relief after RBL.n = 50) or a control group (n = 50). The anal cooler group was instructed to use the cooler when they had pain. All patients were asked to keep a pain diary , and follow-up was performed after 3–6 weeks.Between 2009 and 2010, 100 patients who underwent RBL were prospectively randomized into an anal cooler group (P < 0.001).It was found that 24/50 patients (48 %) in the anal cooler group and 31/50 (62 %) in the control group needed oral analgesics (NS). In total, 36/50 patients (72 %) used the anal cooler. Of these, 9/36 patients (25 %) noticed improvement. Of the remaining 27/36 patients (75 %) who did not notice improvement, 5/36 patients (14 %) found the insertion of the cooler uncomfortable and 1/36 patients (3 %) experienced nausea. No complications occurred during or after the use of the cooler. The 14/50 patients (28 %), who did not use the cooler, had a lower post-banding pain score compared with patients who used the cooler (1.4 vs 6.4; Although post-banding pain after RBL is usually mild, the anal cooler seems to relieve anal pain in 25 % of the patients who used the device. Symptomatic hemorrhoids are a common anorectal disorder , 2. HoweOf all the non-surgical procedures, RBL seems to be the preferred first-line treatment for internal hemorrhoids . This prApplication of cold has been used for many years as a non-pharmacological treatment for pain relief, particularly in acute soft tissue injury . Benefitn = 50) and the control group (n = 50). Patients in the anal cooler group were instructed to keep the anal cooler in the freezer for at least 3 h prior to use and to use the anal cooler whenever they experienced anal pain for at least 10 min. If necessary they were allowed to use additional oral analgesics, such as paracetamol. The anal cooler was lubricated with vaseline and inserted into the anal canal and kept in place for up to 10–15 min (or for as long as it remained cold). The bulky part of the anal cooler remained outside the canal. Patients in the placebo/control group were also instructed to use oral analgesics when necessary. The patients kept a diary, which included a visual analog scale (VAS) regarding post-banding anal pain and use of oral analgesics where no pain was recorded as zero (0) and extreme pain as ten (10). All patients completed structured self-administered questionnaires regarding post-banding anal pain and analgesic requirements, and patient satisfaction was recorded. After 3–6 weeks, patients returned to the clinic for a new proctoscopic examination and evaluation of their diary. Ethics committee approval for the study was obtained from the Medical Ethical Commission of the VU University Medical Center (2009/19).Between 2009 and 2010, 100 consecutive patients who were treated with RBL were included in the study. All patients had symptomatic hemorroids and normal colonoscopies. The patients were prospectively randomized into two groups: the anal cooler group .Results are presented as means and proportions. Differences between the mean pain levels were analyzed using Student’s n = 74). Other symptoms included prolapse (n = 64), anal pain (n = 33) and itching (n = 26). Thirty-three patients had undergone previous treatments including RBL (n = 27), excisional hemorrhoidectomy (n = 4) and sclerotherapy (n = 1).The mean age of the 100 patients was 54 years (range 22–88 years); there were 55 men and 45 women. The most frequent symptom at presentation was bleeding (The mean number of bands applied per patient was 4 (range 1.8). After the treatment, 50 patients were randomized to the anal cooler group and 50 patients to the control group Fig. . The demP = 0.11). In total, 3 patients, who noticed an improvement with the cooler, also used analgesics and 2 of these patients used pre-emptive analgesia due to fear of pain and 1 patient required additional analgesics on days 1 and 2 after RBL because the cooler was deemed ineffective. Of the remaining 27 patients (75 %), who did not have symptomatic improvement with the use of the cooler, 5 (14 %) found insertion uncomfortable and 1 (3 %) complained of nausea which was related to the insertion of the anal cooler.Fifty-four patients had a VAS-score ≥6. Nine of them sought medical advice prior to the planned follow-up visit. The mean VAS-score for post-banding anal pain on the day of the procedure was 5.5 and was similar in the anal cooler and the control groups . Twenty-four of the fifty patients in the cooler group (48 %) and 31/50 patients (62 %) in the control group required oral analgesics to relieve pain (NS)  who did not use the anal cooler had a significantly lower post-banding VAS-score when compared with patients who used the anal cooler. Two of these patients needed pain medication and did not try the anal cooler, because of fear of pain during insertion.Besides post-banding pain, other complications included rectal bleeding (3 %), localized infection without abscess formation or fever (1 %), post-infection ‘polyp’ (1 %) and urinary retention (1 %). Two patients required hospitalization for rectal bleeding which was treated conservatively without the need for blood transfusion.Anal pain is a well-known sequel of RBL. In this study, 54 % of the patients had a VAS-score ≥6 with 55 % requiring oral analgesics. The anal cooler relieved anal pain in 25 % of the patients. Its use tended to decrease the analgesic requirement; however, this effect failed to reach statistical significance due to the small sample size. The use of the anal cooler had no serious side-effects.In the last few decades, local cooling has been used with some frequency in the management of acute local tissue injury, including perianal trauma as well as after minor surgical interventions and in the treatment anal fissure –19. FurtNotwithstanding these effects, the anal cooler was only effective in 25 % of the patients who used it consistently. In some cases, the potential benefit was mitigated by a reportedly painful insertion of the device. For a beneficial effect, an application time of at least 10–15 min is necessary and it is necessary that the patient continue to insert the cooler despite initial discomfort. In this respect, a beneficial effect may potentially occur if the anal cooler is lubricated with lidocaine gel rather than vaseline. The second most likely reason for the limited efficacy of the anal cooler was that it was not cool enough and that the time that the cooler stayed cold was probably too short. In this regard, it might be useful to add water to the mixture of the anal cooler so as to improve its freezing characteristics and reduce its temperature. The third reason for a relative lack of efficacy is the ease of use of the device. The anal cooler needs to be kept in the freezer and requires an application time of 10–15 min which may be inconvenient for working patients.In conclusion, the results of this prospectively randomized trial show that post-banding pain is usually mild and although there is no statistical advantage that there may be clinical benefit in the use of an anal cooler following RBL.


As pain is the cardinal symptom of fibromyalgia (FM), strategies directed towards pain relief are an integral component of treatment. Opioid medications comprise a category of pharmacologic treatments which have impact on pain in various conditions with best evidence for acute pain relief. Although opioid therapy other than tramadol has never been formally tested for treatment of pain in FM, these agents are commonly used by patients. We have examined the effect of opioid treatments in patients diagnosed with FM and followed longitudinally in a multidisciplinary pain center over a period of 2 years. In this first study reporting on health related measures and opioid use in FM, opioid users had poorer symptoms and functional and occupational status compared to nonusers. Although opioid users may originally have had more severe symptoms at the onset of disease, we have no evidence that these agents improved status beyond standard care and may even have contributed to a less favourable outcome. Only a formal study of opioid use in FM will clarify this issue, but until then physicians must be vigilant regarding the multiple adverse consequences of opioid therapy. Chronic widespread pain is the pivotal symptom of fibromyalgia (FM). In the composite score that has been proposed for the new 2010 diagnostic criteria for FM, pain has been weighted to signify two thirds of the symptom component, with other symptoms including fatigue, sleep disturbance, cognitive changes, and somatic symptoms combined to represent the remaining one third of the symptom complex [Even in the absence of evidence for effect in FM, about 30% of Canadian and American FM patients reportedly using opioids . OpioidsThe aims of this study were to prospectively examine disease related measures in FM patients attending a multidisciplinary pain clinic, stratified according to opioid use at followup, and to evaluate the associations of opioid use including health related effects and psychosocial status. We have examined opioid use and recorded outcome in a cohort of FM patients who are followed prospectively in a multidisciplinary pain clinic. This study, wherein drug use was openly observed, received ethics approval by the Ethics Committee of the Montreal General Hospital. The study cohort has previously been described . All patients in this cohort were referred to the Alan Edwards Pain Management Unit from January 2005 with continued entry. Patients were entered into the cohort once the diagnosis of FM was confirmed by the study rheumatologist. All patients received information regarding good health lifestyle practices with recommendations for regular exercise activity and good eating habits with attention to weight control and were encouraged to develop a strong internal locus of control by being active participants in their healthcare. They were assessed and counselled by a psychologist experienced in the care of patients with chronic pain. Specific treatment strategies, including further psychological/behavioural interventions, rehabilitation program participation, and pharmacological interventions, were tailored according to individual patient symptoms and needs, taking into account previous treatment interventions. The frequency of follow-up visits for individual patients was dependent upon physician judgement.Baseline data included demographic, disease related, and psychosocial information. Demographic information included age, gender, education level, marital status, current employment status, and current disability payments. Information regarding symptom and functional status was recorded at entry and at a study followup during which all questionnaires were completed on a second occasion, which occurred at least 1 year after the baseline visit. The number of medications used was recorded and, if opioids were used, the morphine equivalent dose was calculated. Symptom and disease related information included measurements of pain, quality of life, function, and mood. Current pain was measured by a 10 cm visual analog scale (VAS). Pain quality was measured with the McGill Pain Questionnaire (MPQ) . This isA patient global assessment (PGA) of disease was measured by a 10 cm VAS. Quality of life and function was measured by the Fibromyalgia Impact Questionnaire (FIQ) . This is Mood was assessed using the Arthritis Impact Measurement Scale (AIMS) for anxiety and depression . CatastrOpioid use was recorded at baseline and at followup, with calculation of the morphine equivalent dose for opioids using the following morphine equivalent conversion factor: 10 mg morphine was equivalent to tramadol 100 mg, codeine 100 mg, hydromorphone 2 mg, oxycodone 5 mg, and meperidine 100 mg. The conversion for fentanyl patch was calculated as 25 mcg/hour being equivalent to morphine 75 mg per day. Methadone in a dose of <30 mg/day was calculated at 2.5 mg equivalent to morphine 10 mg and >30 mg/day as 1.5 mg equivalent to morphine 10 mg. Patients were categorized into 2 groups according to opioid usage at followup: Group 1 comprised all patients who were using opioids at the follow-up visit which included patients who entered the study on opioids and continued opioid treatments as well as those who initiated and continued opioids during the study period; Group 2 comprised all patients who were not using opioids at the follow-up visit which included those who at entry were not on opioids, those who discontinued opioids during the course of followup, and those who used opioids for a short time during the study period, but did not continue opioid treatment. The baseline data of the groups were tested to establish lack of methodological bias for pain, function, and psychological variables, by comparing between group mean differences for continuous variables and using chi-square tests for categorical variables. General linear model mixed repeated measures ANOVAs were conducted to assess whether there were significant differences in opioid status and pain, function, or psychological variables among patients at followup and whether there were significant interactions among these variables at two levels of the dependent variables (on opioids at followup and off opioids at followup). Multivariate Wilk's Lambda tests were used to assess the main effects of time. Between subject ANOVAs were used to test the main effects of opioid status followed by tests of opioid status by time interaction effects. Binary logistic regression tests were carried out to determine the statistical significance and degree of change in odds of group membership (on or off opioids) at followup for outcome variables. IBM SPSS Statistics version 19.0 was used to carry out the analyses.Of the 159 patients who entered the study, 131 (82%) had at least one followup visit at a mean ± SD of 26 ± 15 months. Their mean age was 50 ± 10 and 92% were females. The demographic and disease related variables of the 28 patients not seen in followup were not significantly different from the 131 patients in this study cohort. Demographic and disease related information for all 131 patients, as well as for the subdivision into Group 1 (opioid users) and Group 2 (nonopioid users), is shown in At entry, 34 patients were using an opioid. Fifteen were using a weak opioid, either codeine or tramadol, and 19 were using strong opioids with an average morphine equivalent dose of 50 mg. Twelve patients in Group 2 were given a trial of opioids, followed by discontinuation. At the recorded follow-up visit, 43  patients were on opioids, 20 of whom had continued treatment from entry and 23 of whom had an opioid treatment initiated during the follow-up period, and 88  patients were not using opioids at followup.Sixteen of the 43 opioid users were on either tramadol or codeine, and 27 were on a strong opioid. Four patients were using 2 different opioids, each were on a long acting and a short acting agent. The mean morphine equivalent dose of opioid at followup was 48 mg a day. When opioid users were categorized according to use of tramadol or methadone in one group (23 patients) and other opioids in a second group (20 patients), there was a trend for those using tramadol or methadone to score better for all outcome measures even though the morphine equivalent dose of 48 mg versus 47 mg was similar (data not shown). F = 6.72, P = 0.011, Eta = 0.22).There was a significant main effect of change over time for pain, function, and mood variables within the total cohort . ChanginThe results of the binary logistic regressions showed that, compared to those not on opioids at followup, patients who took opioids were significantly more likely to be on disability  and more than twice as likely to be unemployed .We have observed that one third of FM patients followed longitudinally in a multidisciplinary pain clinic were maintained on opioid drug therapy. Over time, there was an improvement recorded for the total cohort for measures of pain, function, and mood, irrespective of opioid status. However, opioid users scored consistently higher for all measures of symptom severity with significance noted for higher pain scores and more functional impairment. The only significant interaction between time and opioid status was noted for the single measurement of physical function, the HAQ, with a small effect size. These results suggest that although function, pain, and psychological variables improved during care in a multidisciplinary pain clinic, these measures were independent of opioid use. Importantly, opioid use was not associated with disease status improvements beyond that seen for standard care in a multidisciplinary setting. Additionally, work status of opioid users was less favourable with more unemployment and disability payments noted for the opioid group. The findings of this open observational study raise questions and concerns regarding the rational use of opioid treatments in FM patients. There is currently no optimal treatment for FM, although the current concept is to direct treatments towards specific symptoms, with the ideal pharmacotherapy addressing more than one symptom . Pain isUse of opioids has been entrenched in the management of chronic pain conditions. Our findings of 30% prevalence in use of opioids in FM patients are in line with reports of opioid use in patients with chronic nonmalignant painful conditions . Indeed,While the place of opioid therapy, particularly the use of strong opioids, in the management of FM pain remains controversial, the known analgesic properties of these agents should encourage further study in FM. Opioid medications offer the best available short-term pharmacologic analgesia for almost any pain, although opioids are frequently discontinued in treatment trials of the management of chronic pain . In our In that patients on opioid treatments fared worse than those not on opioids, a number of factors require consideration. It is possible that those patients maintained on opioids had an overall more severe disease process or had more comorbidities contributing to continued opioid use as has been previously reported . AlthougBecause FM symptoms tend to persist over time and only rarely are completely resolved, pharmacologic therapies will necessarily be used over prolonged periods requiring rigorous evaluation of risk benefit ratio. There has been increased concern regarding the immediate as well as the long term side effects of opioid treatments in an individual patient and also societal concerns about the misuse and abuse of prescription opioids. The long term effects of chronic opioid use in nonmalignant pain are not yet fully clarified, but effects on mood, cognitive function, hormonal effects, and increased pain due to hyperalgesia need to be constantly reevaluated . We haveThe progressive increase in opioid prescriptions has seen a parallel increase in their use as drugs of abuse , 25–27. A number of limitations of this study are acknowledged. Firstly, most patients recruited to this study already had symptom duration for over 10 years. We are therefore unable to make any comment regarding the severity of symptoms either at onset of disease or in the absence of treatments. Secondly, as this is a real life study with patient tailored treatments, there was no predetermined protocol to dictate treatment choices; treatments were selected according to individual physician judgement, depending on the predominant symptoms in an individual patient. Thirdly, the duration of opioid treatments for those entering the study on opioids is unknown and, although opioid status at endpoint was recorded, we did not have sufficient information to report on overall duration of opioid use for individual patients. Finally, although wisdom suggests that opioid treatments may be less favourable for patients with FM, patient choices regarding treatments were respected and may have led to continued opioid treatments for some patients which may have been contrary to the recommendation of the multidisciplinary treating team. In this first study reporting on health related measures and opioid use in FM patients, followed longitudinally over a two year period, opioid treated patients were more symptomatic and were more likely to be unemployed and to be receiving disability benefits. While opioids remain a treatment choice for management of pain, we are concerned that our patients using opioids failed to show any advantage in overall health status. Although opioids may have been initiated due to more severe symptoms, we have no evidence that the addition of these agents to the standard care received in a multidisciplinary pain clinic improved disease status or function. Only a formal clinical trial of opioid use in FM will clarify this issue, but until then, we advise physicians to be vigilant regarding the need for continued treatment.


Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC). Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO) measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited.To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL), semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI) scale from the McGill Pain Questionnaire (MPQ), and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF) was also assessed.Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP) were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS) of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients.Study findings support the importance of PRO measures of pain severity as key endpoints for evaluating the efficacy of treatments for CRPC, particularly for patients with bone metastases where episodes of BTcP are common. Qualitative evidence from CRPC patients supports the content validity of the BPI-SF ''Worst Pain' item and promotes use of this item for measuring pain severity in this population. Prostate cancer is the second most common cancer in men with a worldwide age-standardised incidence rate (ASR) of 28.1 per 100,000 . The devBone metastases occur in more than 90% of men with CRPC  and, as Pain has been identified as an important indicator of overall survival in men with metastatic CRPC ,12. DespWhile it is widely recognized that pain is a multi-dimensional construct , a unidiTwo of the most commonly implemented self-completed measures of pain severity in clinical research are the McGill Pain Questionnaire Short-Form (MPQ-SF) ,20 and TWhen selecting a PRO measure for use in clinical trials to document treatment benefit, it is necessary to demonstrate that the selected measure is fit for its intended use in a specific context of use . A key cRecent research has provided insight into the experiences of patients with CRPC, however there is a need to further understand the experiences of CRPC patients with bone metastases, particularly with regard to patients' experience of pain ,27. FurtThe present study, therefore, had two main aims: 1.) To investigate, via qualitative research, the experiences of patients with CRPC and bone metastases, particularly in regards to patient experiences of bone pain and resulting HRQL impact 2.) To assess the content validity of the MPQ-SF PPI and the BPI-SF 'Average Pain' and 'Worst Pain' items within this population.Face-to-face in-depth qualitative interviews were conducted with 17 patients with CRPC and confirmed bone metastases. A combined approach was taken whereby the interviews included a detailed concept elicitation phase followed by thorough cognitive debriefing of the selected pain measures.Patients eligible for participation in the study were recruited in the United States with the help of clinicians from two clinical practices and advertisements from a commercial recruitment agency. To be eligible for participation in the study, patients had to have a clinician-confirmed diagnosis of CRPC with documented evidence of bone metastases (CRPC M1) and be at least 18 years or age. Participants were also expected to be currently experiencing bone pain or to have experienced bone pain recently. Exclusion criteria included evidence of central nervous system metastases, severe or uncontrolled systemic disease, or any other significant clinical disorder.The study was conducted in accordance with the Declaration of Helsinki, and was approved by an Independent Review Board. Written informed consent was obtained from all patients prior to entry into the study.All interviews were conducted by trained interviewers using a semi-structured interview guide. The interview guide was informed by consideration of prostate cancer literature as well as published articles documenting the development and validation of the MPQ-SF and BPI-SF. During the initial 'concept-elicitation' phase of the interview, patients were asked a series of open-ended questions (e.g. could you describe for me your experiences of prostate cancer?) designed to investigate their experience of symptoms related to CRPC and bone metastases (with particular focus on pain). At this stage, care was taken to avoid the use of leading questions, in order to ensure that patients' spontaneous responses were captured.In the second 'cognitive debriefing' phase of the interview, patients were asked to complete the MPQ-SF PPI, and the BPI-SF Average Pain and Worst Pain items as part of a 'think-aloud' exercise in which patients were encouraged to vocalize their decision making process when selecting response choices for each of the measures. Patients were then asked detailed questions designed to verify the relevance and level of clarity  of the measures, and to confirm that the items and response options measured pain intensity adequately (e.g. in your own words what is this question asking? How did you decide which answer to give?). Patients were also asked to identify which of the three PRO measures best documented their experience of bone pain. Again the line of questioning was designed so to not lead or bias patient responses.A pilot interview was conducted with one patient and, based on that patient's feedback, the interview guide was shortened and refocused. An interim analysis of the data collected from this interview and the subsequent 10 interviews was also conducted (Round I), after which the interview guide was revised to incorporate additional questions designed to further explore the terminology that patients used to describe the pain that they experienced and patient understanding and interpretation of the selected PRO measures in the final 6 interviews (Round II).All interviews were audio-taped and transcribed verbatim for the purpose of qualitative analysis. Written interview transcripts were then entered into a qualitative software package (Atlas.Ti) which was used to facilitate the analysis of interview transcripts.priori theory or understanding  prevents me from doing many things that I would do, or would like to do, and normally would do, but I don't do.'; 'I can't seem to do things that I've always done for myself and things that I like to do for other people...at the present time, it's more of a burden to me than at any time in my life. Right now pain is affecting my daily lifestyle.'The pain associated with bone metastases had debilitating consequences on patients' lives with patients reporting impairments in daily functioning from a physical, emotional and social perspective. The physical impact of bone pain typically manifested in patients' experiences of difficulties with walking or even standing: The pain can immobilize you, where it brings on depression. It brings on fear. It brings on anxiety. It brings doubt...stress.'; 'When you have pain that strong, you can't help but have some fears and worries about it'.Further to these physical impairments, patients reported being unable to sleep, feeling tired, and feeling irritable because of bone pain. Patients also described feeling depressed, anxious and stressed, particularly in relation to BTcP when it was evident that pain was getting worse: 'Based on collective feedback from patients, a disease model outlining patients' experiences of living with CRPC with bone metastases in the context of disease pathology was developed Figure .Responses to open-ended questions regarding the perception of 'Current Pain', 'Worst Pain' and 'Average Pain' revealed that patients were able to distinguish between these three distinct concepts. Patients talked about 'Current Pain' as representing the intensity of their pain 'right now' whereas 'Worst Pain' represented the highest intensity of their pain within a given time frame. Patients, however, provided two alternate explanations of 'Average Pain'. For example, some patients considered 'average pain' to represent a value in-between the most and least severe pain that they had experienced over a given time frame, while others described 'average pain' as representing the level of pain experienced 'most of the time'.Well I was thinking that that was when it hurt at its worst, perhaps, not necessarily now it was hurting at this particular moment, but how it hurts at its worst time'. Hardly any difficulties were reported when patients were asked how hard it was to select an appropriate response option for this item. However, some patients had difficulty understanding the meaning of the pain descriptors  and the relation of these descriptors to the bone pain they experienced. Patients also found it difficult to differentiate between the pain descriptors used by the MPQ-PPI, with some descriptors seen to be very similar, if not synonymous: 'Yeah, the words mild and discomforting - what's the difference between those? And then discomforting and distressing? Distressing is more of a psychological thing, I would think, than a measurement of pain. Horrible is a fear type thing instead of a measurement of pain. Excruciating - that's probably a pretty accurate measurement of pain. But some of the words there - discomforting, distressing, and horrible I don't care for.' To further investigate patients' perceptions of the response continuum, as part of the revised interview guide, the final 6 patients interviewed were asked to assign numerical values (from 0-10) to each pain descriptor. Patient answers revealed that there was no standard response continuum and that the distance between individual response options were not interpreted as being equal, as would be expected in a truly linear scale  while 6 patients based their decision on the level of pain that they experienced 'most of the time' . Recall time for average pain varied between patients  and patients recommended including a clear timeframe for clarity. Again patients indicated that increments or decrements of 2 to 3 points for average pain would be considered meaningful. When asked, patients identified scores of 1-3 as representing an acceptable level of pain, and scores of 7-9 as representing an unacceptable level of pain.In deciding on their average pain, 11 patients based their decision on the value between their worst pain and least pain over the specified recall period , while others preferred the BPI-SF Worst Pain item because it was easier to recall . A similar number of patients considered that, because of fluctuating pain levels, the BPI-SF Average Pain item was a better indicator of pain experienced: 'I think average, probably, for the simple reason that I don't think I have that many episodes of really bad pain. I think mine is more on the same level or plane most of the time'.When asked which of the presented items they preferred, one patient had no preference while all other patients preferred the items from the BPI-SF: 'Based on qualitative evidence from CPRC patients with bone metastases, a disease model outlining the experiences of such patients in the context of disease pathology has been developed. Such models are valuable in terms of identifying key measurement concepts which can be used to demonstrate treatment benefit, providing insight into how best to measure these particular concepts and providing a contextual basis for interpreting study findings . As evidGiven the fluctuating nature of pain associated with bone metastases, subjective reporting of pain is time dependent. Multiple reports of pain over time allow integration of symptom evolution in the assessment of patients' pain severity. For repeated use, the PRO measure selected for pain assessment should be short and easy for patients to complete. In this study cognitive debriefing of three single-item measures of pain severity commonly included as endpoints in oncology clinical trials, the MPQ-SF PPI item and 'Average Pain' and 'Worst Pain' items of the BPI-SF, was conducted to determine content validity in patients with CRPC.Whilst the majority of patients were able to accurately interpret the concept of 'current pain' (assessed by the MPQ-SF PPI item), due to the fluctuating nature of pain experienced by CRPC patients with bone metastases, assessments of 'current pain' may not be the most accurate or informative way of assessing pain severity in this population. Indeed, previous research has highlighted that ratings of current pain, among patients experiencing persistent pain, are often lower than ratings of recalled worst or average pain over a given time-period .The concept of 'worst pain' appeared to be interpreted correctly and consistently among patients. By contrast, however, there appeared to be some variability in the way in which patients interpreted the concept 'average pain'. Without consensus among patients regarding the definition of average pain, it would be difficult to determine whether differences among patients are a true reflection of individual differences in pain experience or a result of variations in interpretation of the concept by patients, ultimately limiting the validity of such assessments. As such, 'worst pain' may be the most appropriate measure of pain severity for use in clinical trials. Furthermore, there is evidence to suggest that ratings of 'worst' pain are more representative of the burden experienced by patients in relation to pain and may be more reliable to report; given that when a patient with persistent pain thinks back to their pain over a period of time, they tend to focus their response on their 'worst pain' even when asked about their 'average pain ,39. ReduFeedback from patients regarding the different rating scales adopted by the MPQ-SF PPI (0-6 VRS) and BPI-SF (0-10 NRS) highlighted the superiority of NRS ratings scales for the assessment of pain severity. It appeared to be challenging for patients to define and distinguish between the pain descriptors used in the MPQ-SF PPI scale and there was little or no consensus among patients regarding the grading of each response option. As a result, the MPQ PPI scale could be expected to demonstrate limited sensitivity to changes in the level of pain experienced by patients. Indeed, the limited sensitivity of VRS scales to clinical changes is a commonly held weakness of the use of such measures in pain assessment .By contrast, patients experienced little or no difficulty rating the worst or average pain using a 0-10 NRS. From a measurement perspective, the use of an 11-point NRS scale to measure pain severity provides a simple, non-burdensome response format that is likely to be reliable and sensitive to change ,41. NRS One limitation, attributable to both the MPQ-SF and BPI-SF is that they do not provide opportunity for patients to differentiate the different forms of pain that they may experience. Feedback from the patients interviewed suggested that they were able to distinguish bone pain from other types of pain such as that associated with CIPN based on the location and nature of this pain, however it is not clear when completing an overall pain assessment whether patients would take into account only the pain associated with bone metastases or all types of pain experienced. There is a chance therefore, that in the context of a clinical trial, improvements in patients' experiences of bone pain may be "washed out" by accompanying neurotoxic side-effects such as CIPN.Nonetheless, however, from a content validity perspective, evidence supports the use of the BPI-SF 'Worst Pain' item as the most appropriate measure of pain severity in CRPC patients. In addition to demonstrating acceptable content validity in patients with CRPC, a review of evidence in relation to the BPI-SF 'Worst Pain' item also suggests that this item fulfils much of the key criteria specified in the recent FDA PRO Guidance for Industry ,44. In pAmong the constellation of symptoms experienced by CRPC patients with bone metastases, bone pain is of key concern. There is, therefore, the need for a reliable and valid measure of pain severity within this population. To this end, the BPI-SF Worst Pain item has demonstrated strong content validity in these patients and, whilst psychometric validity of this item in CRPC patients is to be confirmed, there is considerable evidence from comparable disease areas to support the psychometric properties of this item. A culmination of available evidence suggests, therefore, that the BPI-SF 'Worst Pain' item is an appropriate measure of pain severity for use as a clinical trial endpoint for evaluating treatment efficacy in patients with CRPC and bone metastases.ASR: Age-standardised incidence rate; BPI-SF: Brief Pain Inventory Short-Form; BTcP: Breakthrough cancer pain; CIPN: Chemotherapy-induced peripheral neuropathy; CRPC: Castration-resistant prostate cancer; FDA: Food and Drug Administration; HRQL: Health-related quality of life; IMMPACT: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trial; MPQ-SF: McGill Pain Questionnaire Short-Form; NRS: Numerical rating scale; PPI: Present pain intensity; PRO: Patient reported outcome; VRS: Verbal rating scale.Astrazeneca has commissioned Mapi Values, a health outcomes agency with specialist experienced personnel in the field of patient-reported outcomes, to conduct, analyse and communicate findings from this research on their behalf. AG, LA and EP have no other competing interests to declare. CB, BP, SM and FN were all employees of Astrazeneca at the time of the study.ECP designed the study and led the conduct of the qualitative patient interviews and analysis. BP participated in the design of the study and reviewed study findings. AG conducted analysis of the study findings and developed the manuscript. LA, CB, SM and FN were involved in interpretation of study findings and critical review of the manuscript. All authors read and approved the final manuscript.


Withholding analgesics in acute abdomen for fear of masking clinical features and impairing diagnosis and decision-making is still being practiced despite recent evidence to the contrary. This study assesses the effect of preoperative analgesia on clinical findings, clinical diagnosis, and decision-making in patients with non-trauma acute abdomen.n = 46) or placebo (n = 49). The pain score, clinical findings, provisional diagnosis, and treatment plan were noted before and 15–20 min after administration of the analgesic or placebo. The final diagnosis arrived at after adequate investigation or operation was considered the gold standard. The pain scores, diagnosis, treatment plan, and decision between the two groups were compared. Statistical analysis was by SPSS 16. Results were considered statistically significant at p < 0.05.This is a randomized, double-blind, placebo-controlled study using Tramal, a brand of tramadol, at the ED of LAUTECH Teaching Hospital Osogbo, Nigeria. Ninety-five patients between 18–60 years received Tramal (p = 0.001). The abdominal palpation findings were also better in the Tramal group (p = 0.02). There were more changes in the diagnosis after use of Tramal (p = 0.01). There were more changes in the decision in the Tramal group (p = 0.03). Most of the changes in diagnosis and decision in the Tramal group were for the better.Demography and case distribution were similar in both groups. The improvement in pain was greater in the Tramal group (The preoperative use of Tramal in acute abdomen improved the experience of pain and did not adversely affect the accuracy of the diagnosis or decision-making. Acute abdomen is the presence of clinical features of intra-abdominal disease that is likely to require surgical intervention for its resolution -3. BecauPain is often the dominant complaint in patients with acute abdomen ,3,6,7. PThe issue of the safety of providing analgesia for patients with acute abdomen is marked by longstanding controversy over the possible masking of clinical findings and delaying diagnosis -10. In “This study aims at assessing the effect of preoperative analgesia on the clinical findings, diagnosis, and decision-making in patients presenting with non-trauma acute abdomen at the emergency department of our hospital. We hypothesize that preoperative analgesia does not affect the clinical features.This was a prospective, randomized, double-blind placebo study using a synthetic opioid analgesic, the Tramal brand of Tramadol , as the active agent and water for injection (WFI) as placebo. It was carried out in the emergency department (ED) of our hospital between October 2008 and May 2010.The institution’s ethical approval was obtained before commencement of the study, and all randomized patients gave informed consent. All the randomized patients were first seen by the casualty officer, who invited the primary investigator. The primary investigator reviewed the patient’s clinical findings, scored the initial pain (P1) on a numerical rating scale of zero to ten where zero is no pain and ten is the worst pain ever experienced, made a provisional diagnosis (D1), and then proposed the treatment plan (T1).A third party who was not involved in the patient management presented the patient with an opaque paper bag from which the patient randomly picked an envelope containing the grouping letters ‘A’ for active agent and ‘P’ for the placebo. The third party administered either 2 ml (100 mg) of tramadol (TRA) or 2 ml of water for injection (WFI) intravenously, depending on the group picked by the patient. The group picked and the agent administered were unknown to both the patient and the primary investigator. Fifteen to 20 minutes after the administration of the study agent, the primary investigator reviewed the patient again. The residual pain score was recorded as P2, the new provisional diagnosis as D2, and the new treatment plan as T2. The final diagnosis (D3) was determined postoperatively or after adequate investigation if the patient did not undergo an operation. The definitive treatment (T3) given to the patients was based on the demands of their illness. The diagnosis D3 and the treatment T3 were considered the gold standard against which the D1 and D2 and T1 and T2 were compared. Documentation was stopped for all patients upon discharge from inpatient care. Un-blinding was done after randomization had been closed, and collation and analysis were commenced.The analysis of treatment, either conservative or operative, and the incision types were based on intention to treat .The change in clinical diagnosis was considered the primary outcome, and this was used to calculate the sample size because the observed clinical features led to the clinical diagnosis, and the treatment decision was a function of the clinical diagnosis.N = 242) managed for acute abdomen was 60% (145/242). This information was used to find the sample size (n) for this study using the modified Kirkwood formula for comparison of two groups  and P2 as 0.85 .The desired level of significance, v, for this study was 5% (0.05) v = 1.96 . The chance of detecting an actual difference, that is, the power of the study (u), was set at 75%, 0.67. How large should the difference be between the proportion in one group and the proportion in the other group , Mann–Whitney U-test, and chi-square or Fisher’s exact test as appropriate. Exclusion criteria included abdominal symptoms more than 7 days before presentation, hypotensive or obtunded patients, inability to comprehend the pain scoring method, reaction to tramadol or opiates, and prior treatment with analgesics in the course of the illness. Patients below 18 and above 60 years were also excluded to ensure homogeneity of the patient pool and dosing of the active agent. During randomization, no attempt was made to match the groups for age, sex, or clinical diagnosis. Randomization was done only when both the primary investigator and the third party were available; this was to eliminate interobserver differences.Data analysis was done using SPSS version 16. Statistical analyses were performed using Student’s n = 46) or WFI (n = 49). The median age in the two groups was 30.0. Males were 54.3% and 47% in the tramadol and placebo groups, respectively. The sex proportions in the two groups were not statistically different (p = 0.47).Ninety-five patients aged between 18 and 60 years received either Tramal injection (p = 0.56). Also the proportion of patients with acute appendicitis in the two groups was not statistically different (p = 0.39); see Table The distribution of the definitive diagnosis (D3) is shown in Table p = 0.02). After administration of the study agents, there were more cases of discordance between the D1 and D2 in the tramadol group than in the placebo group  (see Table The reduction in pain after administration of the study agents is shown in Table p = 0.03).Operative treatment was proposed for 28 and 32 patients after the D1 in the tramadol and placebo groups, respectively. After the administration of tramadol, changes in decision were more frequent (9/28) compared to the placebo group (2/32) (p = 0.19). All the reported symptoms were non-severe. No patient had respiratory difficulty or hypotension. In the tramadol group 40 patients were discharged, 3 died, and 3 discharged themselves against medical advice (DAMA). Forty-four patients in the placebo group were discharged, and 5 patients died. The median duration of admission was 6 days in both groups.The rate of complications or appearance of new symptoms was not different: five in the tramadol group and two in the placebo group (Several studies indicated inadequate perioperative analgesia and inadequate analgesia for acute and chronic pain worldwide ,22,23. IIn this study, acute appendicitis was the most common cause of acute abdomen, similar to other documentations, and postoperative adhesion the most common cause of intestinal obstruction. The latter is attributed to the increased rate of laparotomy ,24-27.The improvement in pain score after the injection of tramadol being greater than after the use of the placebo is expected. Also, the improvement in abdominal pain demonstrated after the injection of tramadol is similar to the documentation by Mahade et al. on the use of intramuscular tramadol in acute abdominal pain . Some stIn this study, in the tramadol group, there was better improvement in the abdominal palpation findings with respect to localization of area of inflammation and disposition of the patients to palpation; the patients were more comfortable and less evasive of abdominal palpation after injection of tramadol. This is an objective confirmation of the subjective pain symptom improvement. The comfort brought to the patient and the acceptance of abdominal examination are very desirable events in the management of patients with acute abdomen because they make gathering information easier. The improvements in pain score and examination findings support the hypothesis that analgesics improve the clinical features against the view that the clinical signs are not affected by pain relief . In thisThe change in clinical finding in the tramadol group translated into a significant change in the clinical diagnosis in 17% of the patients in this group. The change in diagnosis was for the better more than 75% of the times, but it led to diagnostic confusion in the remainder. Even though this suggests that the use of analgesic has the potential to make the clinical diagnosis better, similar to the report by Zoltie et al. , this stThe pattern of side effects was similar in the two groups; the side effects were non-severe and not unexpected for the tramadol group. There were no life-threatening events, and the pattern of side effects was similar to that reported by McHale et al.  on the uThis study shows that preoperative use of analgesia in patients with acute abdomen will not mask clinical signs while alleviating the pain experienced by patients. Rather, it may improve the gathering of clinical signs and may potentially help in decision-making.ED: Emergency department; TRA: Tramadol; WFI: Water for injection.There are no competing interests. The study was not supported or funded by any organization, institution or individual. The materials used, including the active agent, were funded solely by the authors.AS was involved in the conception of the study, design of the study, literature search, collection of data, statistical analysis, drafting of the manuscript, and review of the manuscript. OA was involved in the conception of the topic, design of the study, data analysis, and drafting of the manuscript. AM was involved in the conception of the study, literature search, analysis of the data, drafting of the manuscript, and review. AA was involved in the design of the study, data analysis, and the drafting and review of the manuscript. OK was involved in the design of the study, data collection, statistical analysis, and drafting of the manuscript. OB was involved in data collection, drafting and review of the manuscript. All authors were involved in the review of the available literature and review of the manuscript, and all have agreed that the manuscript be sent to the International Journal of Emergency Medicine for possible publishing.


A few studies are available actually comparing the clinical efficacy of intravenous acetaminophen with other medications such as dexamethasone to inhibit postoperative adverse events in children.This randomized blinded controlled trial was designed to compare controlling status of postoperative events in children after tonsillectomy randomized to receive either intravenous acetaminophen or dexamethasone.Eighty four children aged between 4 to 13 undergoing tonsillectomy were randomized using a computer-generated schedule to double-blind treatment with intravenous acetaminophen (15 mg/kg) or intravenous dexamethasone (0.1 mg/kg). Children were post-operatively assessed for swallowing pain, pain while opening mouth, ear pain, and postoperative sore throat in recovery room (within one hour after surgery), at the time of admission to the ward, as well as at 12 and 24 hours after surgery, assessed by the objective pain scoring system .There were no significant differences between the two groups with regard to the severity of postoperative pain due to swallowing or opening mouth measured at the different study time points from postoperative recovery to 24 hours after the surgery. There was no difference in ear pain severity at the time of postoperative recovery, at the admission time to ward and also at 12 hours after surgery; however mean score of ear pain severity was significantly higher in those who administered acetaminophen 24 hours after operation. Also, the mean score severity of sore throat was significantly higher in the acetaminophen compared with the dexamethasone group within 12 hours of surgery. Postoperative vomiting and bleeding were similarly observed between the two study groups. The severity of swallowing pain, pain while opening mouth, ear pain, as well as postoperative sore throat as gradually assuaged within 24 hours of tonsillectomy in both groups, however no between-group differences were observed in the trend of the severity of these events.The dexamethasone-based regimen may have more advantage over the intravenous acetaminophen regimen for inhibiting pain and PONV following tonsillectomy in children. Tonsillectomy is one of the most frequent surgical procedures carried out in children which is commonly associated with increased risk of some complications such as severe pain while swallowing and postoperative nausea and vomiting (PONV) . Poorly Dexamethasone is the other drug used for diminishing postoperative pain and PONV in various operations. The effects of the dexamethasone on decreased edema and fibrosis have been clearly substantiated. The anti-inflammatory mechanism of corticosteroids is considered to be a result of the inhibition of phospholipase A2, the crucial membrane enzyme regulating the cascade for the production of hyperalgesic leukotrienes and prostaglandins from arachidonic acid in response to inflammatory stimuli -14, the There are few studies truely comparing the clinical efficacy of intravenous acetaminophen with other medications such as dexamethasone. This randomized blinded controlled trial was designed to compare controlling status of postoperative events in children after tonsillectomy randomized to receive either intravenous acetaminophen or dexamethasone.This randomized blinded controlled trial was designed to compare controlling status of postoperative events in children after tonsillectomy randomized to receive either intravenous acetaminophen or dexamethasone.This study was a randomized controlled trial with blinded assessment of postoperative pain severity and nausea and vomiting (PONV). Children were eligible if they were undergoing tonsillectomy, aged between 4 and 13 years and of ASA physical status I to II. Exclusion criteria were any renal or hepatic impairment, neurological disorder impairing accurate pain assessment, sensitivity to any trial drug, requirement for premedication and other analgesics administered on the day of surgery. After institutional Ethics Committee approval and informed consent from a parent in each case, 84 patients were randomized using a computer-generated schedule to double-blind treatment with intravenous acetaminophen 15 mg/kg (Acetaminophen 1gr/6.7mL - UNIPHARMA S.A manufactured in E.U) or intravenous dexamethasone 0.1 mg/kg (8mg/2mL – DAROU PAKHSH IRAN). Drugs were administered in 50 ml normal saline while using micro set and infused over 30 minutes. Study drugs were marked only with coded number labels and administered within the last 30 minutes of the surgical procedure.At operation room and after setting ECG monitoring, non-invasive blood pressure, capnography, and pulse oxymetry, intravenous line was secured with 22G i.v canula and ringer lactate infusion (8 to 10 cc/kg) was started. All patients were uniformly premedicated with Midazolam 0.05 mg/kg, and Fentanyl 2 µg/kg IV. After preoxygenation with 100% O2, anesthesia was induced with sodium thiopental (5 mg/kg) and Cisatracurium (0.15 mg/kg) and maintained with Sevofluran 2.5%. After the three minutes, patients were intubated endotracheal tube without cuff but tailored to the patients’ age and weight. All intubations were performed by an experienced anesthesiologist. After surgery, all patients were transferred to the recovery room. The mean duration of surgery was 45 minutes.Study Parameters Measurement: Children were postoperatively assessed for swallowing pain, pain when opening mouth, ear pain, and postoperative sore throat in recovery room (within one hour after surgery), on the time of admission to the ward, as well as at 12 and 24 hours after surgery, assessed by the Objective pain scoring system . The incidence of PONV and postoperative bleeding was also assessed postoperatively. Our study outcome measure was the incidence of postoperative pain severity as well as PONV and bleeding. After surgery and in the ward, children with OPS ≥ 5 medicated with meperidine PRN (0.3 mg/kg). In the cases with the appearance of vomiting, ondansetron PRN (0.1 mg/kg) was administered. Also, after establishment of oral feeding, Ibuprofen syrup (6 mg/kg/q8h) was administered.A sample size calculation was performed using a change in OPS mean values of 2.0 with a SD of 1.5. Calculations were performed to determine the number of patients required in this study to have 80% power to detect as statistically significant (P < 0.05). By accepting a type I error of 0.05 and a type II error of 0.20, the study size needed was 40 patients per group. Results were reported as mean ± standard deviation (SD) for the quantitative variables and percentages for the categorical variables. The groups were compared using the Student’s t-test or the Mann-Whitney U test for the continuous variables and the chi-square test (or Fisher’s exact test if required) for the categorical variables. Trend of the changes in continuous variables was compared between the groups using the repeated measure for ANOVA test. This study was done with the power of 80%. P values of 0.05 or less were considered statistically significant. All the statistical analyses were performed using SPSS version 16.0 .From a total of 84 eligible patients that were invited to participate, all of them completed the trial (42 patients in the Acetaminophen group and 42 cases in the dexamethasone group). Average age of all participants was 7.07 ± 2.22 years, median 7.00 years, ranged 4-13 years). The two interventional groups received acetaminophen or dexamethasone were matched in terms of mean age  and frequency of male gender . As summarized in Considering trend of the changes in the severity of pointed postoperative events showed that the severity of swallowing pain, pain when opening mouth, ear pain, as well as postoperative sore throat as gradually reduced within 24 hours of tonsillectomy in both groups, but no between-group differences were observed in the trend of the severity of these events . RegardiIn a total of seven patients in the dexamethasone groups and five cases of the acetaminophen groups, Amp mepridine 0.3 mg/kg PRN were used once in order to reduce pain during 24 hours after the surgery however, it didn’t cause any significant difference. . And a case of the acetaminophen group had vomited three times during 24 hours (Amp ondansetron 0.1 mg/kg PRN was used once) in which the P value = 0.314 was not significant.Postoperative pain and PONV remains a significant problem for children undergoing tonsillectomy, and is the commonest reason for readmission after procedures. The present study compared two different analgesic regimens including intravenous acetaminophen and dexamethasone. Although we could demonstrate a significant deceasing trend of pain severity within 24 hours of surgery in both groups, but between-group difference was not observed regarding trend of the changes in swallowing pain and pain when opening mouth. Also, more pain removing effect of dexamethasone was observed in dexamethasone group compared with acetaminophen group at 24 hours after surgery. Moreover, those who administered dexamethasone experienced severer postoperative sore throat compared to another group within 12 hours after surgery. In fact, our study emphasizes more efficacy of dexamethasone administration than intravenous acetaminophen with respect to controlling postoperative complications in children undergoing tonsillectomy. Much discomfort after tonsillectomy is potentially due to local inflammation, edema and nerve irritation. Dexamethasone is one of the most potent glucocorticoids available that can effectively suppress a basic inflammatory response to tissue injury , 16. DexMalde  studied In our study, although the appearance of PONV was scarce after tonsillectomy, but its rate was more observed in the group which received dexamethasone in comparison with acetaminophen administration. It has been shown that in patients with a high risk of postoperative PONV, a single prophylactic dose of dexamethasone can effective compared with placebo, without evidence of any clinically relevant toxicity , 27. AltThere has been limitations in our study, for instance IV acetaminophen was given once and the half-life is 2-4 hours and duration effect 4-6 hours; we did not control for other medication use that impacts post-op pain and PONV ; even though there is a statistical difference in post op sore throat at the first three time points, one wonders if this is really clinically significant.


Chronic lumbar radicular pain can be described as neuropathic pain along the distribution of a particular nerve root. The dorsal root ganglion has been implicated in its pathogenesis by giving rise to abnormal impulse generation as a result of irritation, direct compression and sensitization. Chronic lumbar radicular pain is commonly treated with medications, physiotherapy and epidural steroid injections. Epidural steroid injections are associated with several common and rarer side effects such as spinal cord infarction and death. It is essential and advantageous to look for alternate interventions which could be effective with fewer side effects.Pulse radio frequency is a relatively new technique and is less destructive then conventional radiofrequency. Safety and effectiveness of pulse radio frequency in neuropathic pain has been demonstrated in animal and humans studies. Although its effects on dorsal root ganglion have been studied in animals there is only one randomized control trial in literature demonstrating its effectiveness in cervical radicular pain and none in lumbar radicular pain. Our primary objective is to study the feasibility of a larger trial in terms of recruitment and methodology. Secondary objectives are to compare the treatment effects and side effects.This is a single-center, parallel, placebo-controlled, triple-blinded , randomized control trial. Participants will have a history of chronic lumbar radicular pain for at least 4 months in duration. Once randomized, all patients will have an intervention involving fluoroscopy guided needle placement to appropriate dorsal root ganglion. After test stimulation in both groups; the study group will have a pulse radio frequency treatment at 42°C for 120 s to the dorsal root ganglion, with the control group having only low intensity test stimulation for the same duration. Primary outcome is to recruit at least four patients every month with 80% of eligible patients being recruited. Secondary outcomes would be to assess success of intervention through change in the visual analogue scale measured at 4 weeks post intervention and side effects. Allocation to each group will be a 1:1 ratio with allocation block sizes of 2, 4, and 6.ClinicalTrials.gov NCT01117870 Chronic lumbar radicular pain (CLR) refers to symptoms of neuropathic pain in the territory of the affected lumbar nerve root. More precisely, the pathology in this condition affects a particular nerve root after it exists from the spinal canal, and before it becomes a part of the somatic nerve. The quality of this pain is usually sharp, lancinating, or burning. Clear distinction must be made between radicular pain (as described above) and radiculopathy. Radiculopathy refers to objective loss of sensory and/or motor function as a result of conduction block and leads to features of numbness, motor loss, wasting, weakness, and loss of reflexes . The patet al.[et al.[et al.[et al.[et al. is the only RCT concerning the application of PRF-DRG for cervical radicular pain. Its main limitation was inadequate number of subjects. There has not been any RCT involving PRF-DRG for lumbosacral radicular pain.Pulsed radio frequency (PRF) is a relatively new technique derived from a well established and proven intervention called thermal radiofrequency (RF) denervation (ablation) . Conventet al. and Tekil.[et al. on facetl.[et al. on PRF ol.[et al. and Simol.[et al. for radiThe resulting articles were then studied and grouped into categories: A, basic science and animal experiments-demonstrating its efficacy, safety and mechanisms of action ’? With this rationale and purpose, a feasibility study is being done to assess whether a larger scale clinical study with the same methodology can be done. This pilot study would also help in assessing the actual number of patients to be involved in the larger clinical study to give a statistically significant difference. With positive outcomes (treatment success), we could also determine the length of follow-up necessary in a full-scale clinical study in order to study the duration of effects.Is it feasible to do a larger scale clinical study to study the effectiveness of ‘PRF treatment of DRG as compared to placebo’ in CLR? Feasibility (outcome) parameters studied: (1) recruitment rate; (2) percentage of patients who go on to complete the full study after enrolling as participants.1. Is pulsed radiofrequency of DRG effective for pain relief - measured as a decrease in VAS, measured at 4 weeks?2. Is application of PRF associated with any short-term (at 4 weeks) or long-term persisting (beyond 3 months) side effects?3. Is there any improvement in Oswestry Disability Index (ODI) in patients of CLR after PRF; measured at 4 weeks, 2 months, and 3 months?4. Is there any decrease in analgesic (medications) use in patients with CLR after application of PRF; measured at 1 week, 4 weeks, 2 months, and 3 months?Patients would be screened at St Joseph Hospital, Hamilton, Canada, at their-East End Pain Clinic for CLR of at least 4 months’ duration. Based on the history and clinical examination, a diagnosis of CLR involving one or more spinal segments is made and noted. The patient is considered eligible for the study if a CT or MRI of lumbar spine done within the last 4 months demonstrates pathology that is concordant with the patient’s clinical symptoms. The spinal level(s) targeted for treatment will be based on clinical findings, for example if a patient exhibits signs and symptoms of right L4 radiculopathy, and the MRI demonstrates right paracentral disc herniations at both L4-5 and L5-S1, only the L4 DRG will be targeted. Patients fulfilling the inclusion criteria will be fully explained about the nature of study, interventions involved and the possible complications after which an informed consent will be taken. Enrolled patients would be randomized according to the method described and included in the study according to previously randomized order. He/she will also meet the assessor (blind to intervention), who would note down the baseline parameters of the patient and also collect a baseline ODI score along with noting down other parameters. A patient having bilateral radiculopathy will be treated for his most affected side in the trial. A patient having CLR of more than one segment on one side shall be treated for all the involved segments with the same technique and counted as a single procedure or intervention for the study. After checking for the informed consent and other safety checklist, patient will only be revealed as belonging to the study . All operating room (OR) personnel, including the physician performing the intervention and the patient, shall be blind to the randomization and treatment. The grouping code, hence the actual treatment will only be known by the person operating the RF machine. Only the RF technician shall be in view of the working details of the RF machine and the noise of the machine is cut by playing out a music or song. This ensures blinding of all involved, except the RF technician. All interventions will be done as day-care procedures in the OR. Patients would continue to use their medications as before. If the pain relief obtained necessitates decrease in the usage of medications that shall be recorded. Similarly unsatisfactory pain relief obtained necessitating increase in the dose or change of medications shall be recorded. The other parameters to be used for statistical analysis are collected as mentioned under data analysis. The patient will have an established IV access. He would be put in prone position. The involved area of back would be made sterile using chlorohexidine 2% and draped. The patient would be connected to continuous monitoring of 3 lead ECG, NIBP, and pulse oximetry. Sedation, if used will be minimal (Grade I or II) to obtain the necessary response of the patient. Under fluoroscopy guidance particular spinal segment(s) affected is (are) identified and confirmed. LA using 2% lidocaine is infiltrated to the skin at entry site. For both groups a RF needle  is used. With an appropriate fluoroscopy view the needle is inserted to the target location in both the groups.Target location: the DRG, which is an enlargement formed by the dorsal nerve root just proximal to its junction with the spinal nerve, lies within the dural sleeve and occupies the upper, medial part of the intervertebral foramen . It is cTarget confirmation : approprTreatment: once positioned the physician shall indicate to the RF technician as ‘treatment’ only, at which time either PRF or placebo (only continuing sensory stimulation at a low frequency of 0.2 V is applied) without revealing. Application of intervention: in Group A, PRF; PRF would be applied for 120 s at 42°C. Group B, placebo; the needle would be continuously stimulated at a low voltage to give a sensation of PRF application and also to obtain the necessary noise to blind the patients. In both groups the same procedure is done at all the involved spinal segmental levels. After the procedure the patient is shifted to recovery area to be monitored, observed and managed for any side effects. The observer, blind to the interventions, will record the pain scores and also check for side effects observed before the patient is discharged home.Blinding and bias control: in our study, the patient, the treating physician, and the assessor for the actual intervention are all blinded. The randomization code, hence the actual treatment, will only be known and administered by the person operating the RF machine. The randomization will be concealed in sealed envelopes. Blinding of patients will be achieved by randomization, use of similar technique and fluoroscopy, stimulating the DRG in both groups, and continuing non-PRF stimulation in placebo group, use of audio to mask the treatment sound. Blinding of the treating physician and assessor will be achieved by not knowing the randomization order and hence not aware of the actual treatment.Suitable patients older than 18 years, suffering from CLR of at least 4 months or more and with concordant findings on either MRI or CT are included. Included patients must also have a VAS score of at least 6/10 (at presentation) and must be ready to provide informed patient consent for participating in the study as a blind subject.Exclusion criteria would include any patient having an absolute contraindication to neuraxial injection in the form coagulation disturbance anticoagulant therapy, bleeding disorder, or infection at the site of injection; patients with anatomical deformity or derangement, either congenital or acquired such as extreme scoliosis, previous implant or instrumentation, making it difficult to access the foramen as evidenced by MRI, CT, or plain X-rays; patients with cancer to account for their symptoms; patients with known significant psychiatric history; patients unable to communicate effectively in English; patients with allergy to local anesthetics or radiographic dye; patients with a history of acute neurological weakness or neurodeficit in the affected limb in terms of measurable motor weakness or abnormal reflexes.Duration of treatment period will involve approximately 30 to 60 min of actual intervention done in the OR. The duration of complete follow-up will be for 3 months after the intervention with the following interval follow-up assessments: (1) 30 min post-procedure in recovery, (2) 24 h after - by a phone call (only VAS and side effects); (3) at 1 week post-procedure visit to the assessor ; (4) at 4 weeks post-procedure visit to the observer for assessment for success ; (5) at 2 months post-procedure-visit to observer ; (6) at 3 months post-procedure visit to the observer - last follow-up visit .n = 32) must have been enrolled. Criteria for success would be as expected recruitment of at least four patients per month after fulfilling the selection criteria and with full informed consent with at least 80% of eligible patients fulfilling the selection criteria being recruited.1. Recruitment rate: percentage of suitable patients fulfilling the inclusion–exclusion criteria, recruited for the actual study after informed consent. The final assessment will be after the complete recruitment, at which time all the expected number of subjects .1. Effectiveness of PRF treatment of DRG, when compared to placebo, as a treatment in patients with CLR: outcome measured as decrease in VAS scores (0 to 10) from baseline measured at recruitment. For definition of success we would consider at least 50% decrease in VAS scores assessed at 4 weeks.2. Assessment of short-term side effects: percentage of patients having side effects after PRF treatment assessed at 1 week, compared with the placebo group. Assessment of persisting side effects: percentage of patients having side effects after PRF treatment, beyond 1 week, compared with placebo group. Short-term side effects (within 1 week – recorded at the first visit):NauseaHeadacheTransient increase in painFever (temperature in°C)Transient paresis/paraesthesiaDysesthesiaLong-term side effects (persisting side effects assessed at visits 1 week and at 6 weeks):Infection at the siteMeningitisEpidural abscessHyposensibilityParalysis/paresisDysesthesiaeAny other3. Improvement in ODI: success defined as at least 50% improvement (or decrease) in ODI measured at 4 weeks, compared with placebo group.4. Decrease in the analgesic medications used: percentage of patients with increase or decrease in their medication use , compared with placebo group.1. Four weeks can be considered as the optimum time at which the therapeutic effect of PRF would be at its maximum.2. There is a theoretical possibility of local anesthetic action in either group, which can be eliminated at 4 weeks.3. Even if there has been a placebo effect it is important to know whether it is sustained at 4 weeks, in comparison to the actual treatment effect.4. To allow appropriate time for a decrease in ODI  to happen as a result of decreasing pain.Sample size has been determined based on feasibility considerations. Total duration of recruitment planned is 8  months. The proposed target is recruitment for 8 months, with an expectation of at least four patients every month, with a total of 32 patients for the study. Potential to recruit patients, as four patients every month has been calculated based on the transforaminal steroid injections (TFESI) performed in the last 3 to 6 months and booked for the next 3 to 6 months  at St Joseph’s Healthcare; data obtained from St Joseph’s Healthcare, Department of Anesthesia and Pain. TFESI represents a well-accepted, presently performed intervention for patients of CLR and most patients suitable for that are potential recruits for this study.Patients will be randomly allocated to each group using a 1:1 ratio. The allocation will be done in blocks using block sizes of 2, 4, and 6.The characteristics of the trial participants will be described using mean (standard deviation) or counts as appropriate. We will use a flow diagram to summarize the flow of patients in the trial. Feasibility outcomes will be reported as counts (proportions).et al.[The results of this pilot study would primarily give us information about the patient recruitment and study methodology. This is being done as there are no previous studies (RCTs) to indicate the successful effects of PRF in CLR. The initial study proposal was to conduct an RCT comparing PRF-DRG with TFESI, which have proven to be more successful than midline ESIs for lumbar radiculopathy , and areet al. on cerviIt is very challenging to devise and conduct a placebo controlled trial in interventional pain medicine. Because of the nature of the problem, which involves significant suffering for a long time, patients may be unwilling to participate as blind participants. CLR patients would have had a trial of most medications and simple interventions before they go on to have complex spinal interventions, such as PRF-DRG. It may also be difficult to have such patients to be under long periods of follow-up after a blind intervention, especially if it is not of benefit to the patient. This trial would be able to tell us whether we were able to recruit patients as expected for the trial and also whether they continue to be participants of the study for the whole duration. The other important and novel aspect of this study which merits attention is the technique of patient blinding during the procedure. Although we will not be formally evaluating the blinding process, it will be interesting to know if we faced significant challenges and if such a methodology needs to be appropriately modified for a future trial. The study would also assess the outcomes of pain relief from PRF compared to placebo. Apart from telling us if PRF is successful, the study would also indicate the difference in pain relief in terms of absolute reduction in VAS scores. This is necessary to assess the number of study participants for a future trial. The assessment of side effects is included to understand if there are major or minor side effects and risks which need to be better studied and informed to the patients.We are presently recruiting study participants. The trial is registered on clinicaltrials.gov with the unique identifier NCT01117870. We only require two more participants to complete the recruitment process. We have also completed interventions on 28/32 patients.CLR: Chronic lumbar radiculopathy; DRG: Dorsal root ganglion; ESI: Epidural steroid injection; PRF: Pulse radiofrequency; RF: Radiofrequency; C-Fos-Proto-oncogene: Protein coded by FOS gene; RCT: Randomized control trial; VAS: Visual analogue scale; ODI: Oswestry Disability Index; OR: Operating room; IVF: Inter-vertebral foramen; TFESI: Transforaminal epidural steroid injection; LA: Local anesthetic; CRPS: Complex regional pain syndrome; TENS: Trans-cutaneous electrical nerve stimulation.No financial or non-financial competing interest exists concerning any authors.HS: Lead investigator, corresponding author of the manuscript, and treating physician for the study patients. PC: Local primary investigator and treating physician involved in patient recruitment, treatment, and follow-up of patients. JMC: Co-investigator and treating physician involved in patient recruitment, treatment, and follow-up of patients. JP: Co-investigator involved in methodology planning, original protocol drafting, and supervision. LT: Co-investigator, statistical assistance, and supervision for the study. All authors read and approved the final manuscript.