What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain (BTcP): Expert Opinion.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

Hydromorphone does not influence the immune response in patients affected by chronic pain.

Hydromorphone (HMP) is a semisynthetic opioid that has been widely used over many years in the treatment of chronic moderatesevere pain. A number of studies have demonstrated the use of HMP in patients with cancer pain as safe and affective, and more recently HMP has been also utilised in the treatment of chronic degenerative pain (CDP). Then, some opioids are able to influence several immune parameters. Aim of our study was to assess HMP in patients with CDP in terms of safety and efficacy, to evaluate effects of HMP, within 2 months of observation, on cutaneous cell-mediated immunity (CCMI) as well as other basic immune parameters, and the production of interleukin-2 (IL-2) and interleukin-6 (IL-6). Results have shown that HMP does not influence CCMI nor the sieric levels of immunoglobulins or other immune parameters. Furthermore, it also has no effects on the 3rd and 4th complement fractions, on white blood cells count and T-lymphocyte subpopulations, on presence of seric autoantibodies, nor on production of IL-2 and IL-6. Therapy with HMP has not effects on the studied parameters of the immune system and does not seem to have any influence on the immune competence and immune response in patients with chronic pain.

Fibromyalgia syndrome: preventive, social and economic aspects.

There many open questions concerning the concept of primary prevention in FM. Diagnostic or classification criteria are not universally accepted, and this leads to difficulties in establishing the onset and duration of the disease. In the case of FM, primary prevention may consist of the immediate care of acute pain or treatment for affective disturbances as we do not have any specific laboratory or instrumental tests to determine risk factors of the disease. The goal of secondary prevention is early detection of the disease when patients are largely asymptomatic and intervention improves outcome. Screening allows for identification of an unrecognized disease or risk factor, which, for potential FM patients, includes analysis of tender points, Fibromyalgia Impact Questionnaire (FIQ), pain location and intensity, and fatigue and sleep complaints. Tertiary prevention inhibits further deterioration or reduces complications after the disease has developed. In FM the aim of treatment is to decrease pain and increase function via multimodal therapeutic strategies, which, in most cases, includes pharmacological and non-pharmacological interventions. Patients with FM are high consumers of health care services, and FM is associated with significant productivity-related costs. The degree of disability and the number of comorbidities are strongly associated with costs. An earlier diagnosis of FM can reduce referral costs and investigations, thus, leading to a net savings for the health care sector. However, every social assessment is closely related to the socio-economic level of the general population and to the legislation of the country in which the FM patient resides.

Fibromyalgia syndrome: definition and diagnostic aspects.

Ever since it was first defined, fibromyalgia (FM) has been considered one of the most controversial diagnoses in the field of rheumatology, to the point that not everybody accepts its existence as an independent entity. The sensitivity and specificity of the proposed diagnostic criteria are still debated by various specialists (not only rheumatologists), whose main criticism of the 1990 American College of Rheumatology criteria is that they identify subsets of particular patients that do not reflect everyday clinical reality. Furthermore, the symptoms characterising FM overlap with those of many other conditions classified in a different manner. Over the last few years, this has led to FM being considered less as a clinical entity and more as a possible manifestation of alterations in the psychoneuroendocrine system (the spectrum of affective disorders) or the stress reaction system (dysfunctional symptoms). More recently, doubts have been raised about even these classifications; and it now seems more appropriate to include FM among the central sensitisation syndromes, which identify the main pathogenetic mechanism as the cause of skeletal and extra-skeletal symptoms of FM and other previously defined "dysfunctional" syndromes.

Etiopathogenetic mechanisms of fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskeletal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. FMS is often triggered by negative environmental influences, especially if they occur in childhood. In a fetus, these environmental triggers may influence the development of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal axis (HPA). Increasing evidence supports the comorbidity of psychological conditions including depression, panic disorders, anxiety, and post-traumatic stress disorder (PTSD). Recent evidence suggests that genetic factors may play a role in the pathogenesis of FMS. Central sensitization has long been associated with FMS pain. It describes enhanced excitability of dorsal horn neurons, which leads to transmission of altered nociceptive information to the brain. Understanding of pathogenetic pathways in FMS has advanced beyond observing patient responses to neurophysiologically targeted therapies and basic research.

Non pharmacological treatments in fibromyalgia.

Fibromyalgia is a complex syndrome associated with significant impairment in quality of life and function and with substantial financial costs. Once the diagnosis is made, providers should aim to increase patients' function and minimize pain. Fibromyalgia patients frequently use alternative therapies, strongly indicating both their dissatisfaction with and the substantial ineffectiveness of traditional medical therapy, especially pharmacological treatments. At present, pharmacological treatments for fibromyalgia have a rather discouraging cost/benefit ratio in terms of poor symptom control and high incidence of side effects. The interdisciplinary treatment programs have been shown to improve subjective pain with greater success than monotherapy. Physical therapies, rehabilitation and alternative therapies are generally perceived to be more "natural," to have fewer adverse effects, and in some way, to be more effective. In this review, physical exercise and multimodal cognitive behavioural therapy are presented as the more accepted and beneficial forms of nonpharmacological therapy.

Symptoms and signs in fibromyalgia syndrome.

Fibromyalgia syndrome (FM) is a common chronic pain condition that affects at least 2% of the adult population. Chronic widespread pain is the defining feature of FM, but patients may also exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headaches, and mood disorders. The etiology of FM is not completely understood and the syndrome is influenced by factors such as stress, medical illness, and a variety of pain conditions. Establishing diagnosis may be difficult because of the multifaceted nature of the syndrome and overlap with other chronically painful conditions. A unifying hypothesis is that FM results from sensitization of the central nervous system; this new concept could justify the variety of characteristics of the syndrome. FM symptoms can be musculoskeletal, non-musculoskeletal, or a combination of both; and many patients will also experience a host of associated symptoms or conditions. The ACR classification criteria focus only on pain and disregard other important symptoms; but three key features, pain, fatigue and sleep disturbance, are present in virtually every patient with FM. Several other associated syndromes, including circulatory, nervous, digestive, urinary and reproductive systems are probably a part of the so called central sensitivity or sensitization syndrome. A minority subgroup of patients (30-40%) has a significant psychological disturbance. Psychological factors are an important determinant of any type of pain, and psychological comorbidity is frequent in FM. Psychiatric disorders most commonly described are mood disorders, but psychiatric illness is not a necessary factor in the etiopathogenesis of FM.

Fibromyalgia syndrome: the pharmacological treatment options.

Pharmacological treatment has been gradually enriched by a variety of compounds; however, no single drug is capable of fully managing the constellation of fibromyalgia (FM) symptoms. Currently, it is not possible to draw definite conclusions concerning the best pharmacological approach to managing FM because results of randomized clinical trials present methodological limitations and therapeutic programs are too heterogeneous for adequate comparison. However, a variety of pharmacological treatments including antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, sedatives, muscle relaxants and antiepileptics have been used to treat FM with varying results. In this review, we will evaluate those pharmacological therapies that have produced the most significant clinical results in treating FM patients. The nature of FM suggests that an individualized, multimodal approach that includes both pharmacologic and nonpharmacologic therapies seems to be the most appropriate treatment strategy to date.

The evaluation of the fibromyalgia patients.

Fibromyalgia (FM) is a rheumatic disease characterized by musculoskeletal pain, chronic diffuse tension and/or stiffness in joints and muscles, easy fatigue, sleep and emotional disturbances, and pressure pain sensitivity in at least 11 of 18 tender points. At present, there are no instrumental tests or specific diagnostic markers for FM; in fact, many of the existing indicators are significant for research purposes only. Many differential diagnoses may be excluded by an extensive clinical examination and patient history. Considering overlap of FM with other medical conditions, the treating physicians should be vigilant: chest-X-rays and abdominal ultrasonography are the first steps of general evaluation for all the patients with suspected FM. Functional neuroimaging methods have revealed a large number of supraspinal effects in FM, a disorder mediated by mechanisms that are essentially unknown. Many treatments are used in FM patients, but evaluating their therapeutic effects in FM is difficult because the syndrome is so multifaceted. To address the identification of core outcome domains, the Initiative on IMMPACT and OMERACT workshop convened a meeting to develop consensus recommendations for chronic pain clinical trials.

Anxiolysis and postoperative pain in patients undergoing spinal anesthesia for abdominal hysterectomy.

AIM: The relationship between pain and psychological factors is well known. The aim of the study was to evaluate the influence of lorazepam, given before total abdominal hysterectomy, on postoperative pain control. METHODS: Sixty patients, enrolled in the study, were defined as either anxious or not anxious when the State/Trait Anxiety Inventory (STAI) score was =/>51 or =/< 50, respectively. The anxious patients were randomly assigned to receive oral lorazepam 0.035 mg/kg the night and 2 h before surgery (Group A), or placebo at the same time (Group B). The not anxious patients were assigned to receive oral lorazepam 0.035 mg/kg the night and 2 h before surgery (Group C), or placebo at the same time (Group D). Anesthesia was performed with subarachnoidal block. Ketorolac was used for postoperative pain. As rescue drug, tramadol was administered using a patient controlled analgesia (PCA) modality. Postoperative pain was assessed during the 24 h after surgery by tramadol consumption. RESULTS: Tramadol consumption was significantly greater in Group B (216.3+/-58.9 mg) than in Groups A, C and D respectively (150.9+/-28.9 mg; 153.6+/-39.9 mg; 154.4+/-39.9 mg). Group B showed a significantly higher pain score compared to the other groups during the first 8 h. No difference in patient satisfaction with perioperative treatment was noted. CONCLUSION: Preoperative lorazepam reduced perioperative anxiety. This could explain the better postoperative pain control in patients undergoing hysterectomy, a very stressful surgical procedure.

Cervical pain and headache in patients with facial asymmetries: the effect of orthognathic surgical correction.

AIM: Facial asymmetries are often associated with cervicobrachial pain and headache. The aim of the study was to evaluate the influence of surgical orthognathic correction of facial asymmetries on the intensity of cervicobrachial pain and headache in the short and long term. METHODS: Thirty-two patients affected by maxillomandibular asymmetries associated with pain referred to occipital, cervical, dorsal and scapulohumeral areas who were undergoing orthodontic surgical correction were enrolled in the study. The pain intensity at rest and on fibromyalgia trigger points was assessed using a 0-10 Visual Analogue Scale (VAS) preoperatively (T(0)) and 5 days (T(1)), 6 months (T(2)) and 12 months (T(3)) after surgery. Functional limitation was evaluated by the same method at T(0),T(2) and T(3). RESULTS: VAS scores at rest were significantly lower at T(1), T(2) and T(3) compared to T0 in every area to which pain was referred. After 12 months (T(3)), pain at rest was completely absent in 23 patients (71.8%) in the occipital region, in 23 patients (71.8%) in the cervical area, in 22 patients (68.7%) in the dorsal area, and in 28 patients (87.5%) in the scapulohumeral area. In the other patients, the pain scores in all areas were < 1 (0.77, 0.83, 0.95, 0.5 in the occipital, cervical, dorsal, and scapulohumeral areas respectively). The VAS at neck fibromyalgia points were significantly reduced at T(1), T(2), T(3) and functional limitation was improved at T(3) and T(4) (P=0.00). CONCLUSION: This study appears to demonstrate the utility of orthognathic surgery when facial asymmetry is associated with cranial-cervicobrachial pain syndrome, presumably through a new musculoskeletal rearrangement of stomatognathic apparatus. Indeed, the surgical correction has resulted in morphological, functional and symptomatic effects.

Hemodynamic variations during thoracic and abdominal stop-flow regional chemotherapy.

AIMS: The aim of this study was to study hemodynamic modifications during thoracic and abdominal stop-flow regional chemotherapy and to evaluate the need for routine hemodynamic monitoring during such kind of procedures. METHODS: Thirty patients, aged 17-67 years, ASA physical status II-III, scheduled for thoracic (group A, n = 15), and abdominal (group B, n = 15) stop-flow regional chemotherapy were enrolled. Heart rate (HR), electrocardiogram lead I and V(5), end tidal carbon dioxide (ETCO(2)), arterial oxygen saturation (SaO(2)), systolic, diastolic and mean arterial pressure (SBP, DBP, MAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), left cardiac work (LCW), right cardiac work (RCW), left cardiac work index (LCWI), right cardiac work index (RCWI), cardiac index (CI), and body O(2) consumption (VO(2)) were recorded. RESULTS: After aortic and inferior vena cava endovascular occlusion (T(1)), a significant reduction of CO and SV, associated with an increase of CVP, MAP, PAPM and PCWP were observed. A concomitant reduction of CI and increase of SVR and PVR were registered. The VO(2) was significantly reduced compared to basal values in both groups. After deflating aortic and vena cava balloons (T(2)), CO, SV and CI increased with respect to basal value p < 0.05) whereas MAP, CVP, PAPM, PCWP and calculated parameters (SVR, PVR) showed a significant reduction compared to T(1). The oxygen consumption was significantly higher than that of basal values p < 0.05. After hemofiltration (T(3)), all hemodynamic variables were comparable with the basal values. Modifications of direct and calculated parameters, during the stop-flow period, showed a similar trend in both study groups, without any statistically significant difference. No ST modifications at ECG were noted during all perioperative period. CONCLUSIONS: The results of this study have confirmed in both groups, the safety of stop-flow regional chemotherapy procedure, despite endovascular occlusion of the aorta and inferior cava vein. The hemodynamic and oxygenation changes are reversible and did not produce any ST modifications at ECG during all perioperative period. Routine pulmonary artery catheterization is thus unnecessary, except in high cardiac risk patients.

[Use of remifentanil in ambulatory obstetric-gynecologic surgery. A dose-effect study]. / Uso del remifentanil in chirurgia ambulatoriale ostetrico-ginecologica. Studio dose-effetto.

BACKGROUND: Remifentanil, a recently commercialised opioid, is characterised by a predictable and non cumulative effect which vanishes rapidly without determining side effects in the long term. These characteristics make remifentanil an ideal opioid in continuous infusion for the ambulatory surgery setting. Aim of this study was to assess the ideal dose of remifentanil, administered in bolus before propofol, in patients undergoing uterine curettage and assisted by mask ventilation in 100% oxygen. METHODS: Sixty patients, ASA status I-II, scheduled for uterine curettage, were divided into three study groups according to the bolus dose of remifentanil received before the induction agent: group A (n = 20) 1 microgram/kg; group B (n = 20) 2 micrograms/kg; group C (n = 20) 2 micrograms/kg. All patients were assisted by 100% oxygen ventilation with facial mask. During surgery the following were recorded: time to spontaneous ventilation (in case of post induction apnea); incidence of somatic and autonomic responses to surgical stress (treated with remifentanil in bolus). At the end of surgery the times to response to simple verbal commands, to discharge from the recovery room (by Aldrete score every 5') and to discharge from hospital (by PADSS score every 30') were registered. RESULTS: All patients presented post-induction apnea with a significantly more rapid return to spontaneous ventilation in group A. Six patients of group A responded to surgical stress while in groups B and C there was no need for supplementary boluses (p < 0.05). Five patients of group C were treated with atropine for bradycardia, in four of group C it was necessary to administer succinylcholine for thoracic rigidity. No significant differences regarding the anesthesia recovery times were observed. All patients were discharged from the recovery room after 10' from the end of surgery. Overall, the qualification for discharge from hospital was obtained at the second PADSS score control, except for one group A patient who incurred in metrorrhagia. CONCLUSIONS: The administration in bolus of remifentanil, before the inducing agent, permits short-term surgery in ambulatory surgery settings thanks to the rapid recovery of vital functions. Compared to the other doses, the 1.5 micrograms/kg dose guaranteed a good control over surgical stress without influencing the speed of awakening and without determining uncomfortable side effects.

A double-blinded evaluation of propacetamol versus ketorolac in combination with patient-controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery.

UNLABELLED: We assessed the relative morphine consumption in a combined analgesic regimen (on-demand morphine plus the nonopioids propacetamol or ketorolac) after gynecologic surgery. Two hundred women randomly received two i.v. doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded, double-dummy trial. Patients were monitored for 12 h, and the following efficacy variables were assessed: total dose of morphine, pain intensity, and global efficacy. Safety and tolerability were evaluated by the occurrence of adverse events, especially the presence and intensity of gastrointestinal symptoms. Hemostatic variables were measured 30 and 60 min after the first infusion; arterial blood pressure, heart and respiratory rates, sedation scores, and renal and hepatic function were also assessed. Total morphine requirements were not significantly different between the propacetamol (10.6 +/- 4.8 mg) and ketorolac (10.2 +/- 4.4 mg) groups. The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups: 70.2% of patients in the propacetamol group rated the efficacy as "good/ excellent" compared with 68.2% in the ketorolac group. There were no clinically significant changes in vital signs or laboratory values and no observed differences between the two groups, although ketorolac slightly, but not significantly, prolonged the bleeding time. Epigastric pain was present in 9% and 15% of patients receiving propacetamol and ketorolac, respectively. There were two adverse events in the propacetamol group and four in the ketorolac group. Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery. IMPLICATIONS: Propacetamol and ketorolac, combined with patient-controlled analgesia morphine, show similar analgesic efficacy after gynecologic surgery. Morphine consumption and pain scores were comparable in the two studied groups. Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery.

Intra-articular buprenorphine after knee arthroscopy. A randomised, prospective, double-blind study.

BACKGROUND: Demonstration of peripheral opioid receptors in inflamed synovia supports the concept of peripheral opioid analgesia. The aim of this study was to evaluate the analgesic effect of intra-articular administration of buprenorphine after knee arthroscopy. METHODS: In a double-blind randomised trial, 48 patients were assigned to four groups: group A patients received buprenorphine 100 micrograms i.a. and NaCl 0.9% i.m., group B patients received bupivacaine 0.25% 50 mg i.a. and NaCl 0.9% i.m., group C patients received NaCl 0.9% i.a. and buprenorphine 100 micrograms i.m., and group D patients received NaCl 0.9% i.a. and NaCl 0.9% i.m. Intensity of postoperative pain was evaluated by VAS at recovery (T0) and 1, 3, 6, 12, 24 h after operation (T1, T2, T3, T4, T5), at rest and during passive 10 degrees knee flexion. Total analgesic requirements and side effects related to study drugs were recorded. RESULTS: The VAS scores were significantly higher in groups C and D than in group A and B patients. The differences were significant at T0, T1, T2 and T3. At T1, group C and D patients had greater analgesic requirement than groups A and B. No patients developed side effects. CONCLUSION: Intra-articular buprenorphine and i.a. bupivacaine, both produced equally good postoperative pain control and allowed a significant reduction of analgesic requirement after knee arthroscopy.

The effects of perioperative ketorolac infusion on postoperative pain and endocrine-metabolic response.

We designed a randomized, double-blind study to assess the analgesic efficacy and safety of perioperative ketorolac infusion in 95 patients undergoing cholecystectomy. The ketorolac group (n = 48) received premedication, combined with ketorolac 30 mg intramuscularly (IM), followed by a ketorolac continuous infusion (2 mg/h). The control group (n = 47) received an IM bolus of NaCl 0.9% (1 mL) followed by continuous saline infusion (2 mL/h) for 24 h. Operative blood losses, postoperative pain, sedation, and on-demand morphine consumption (patient-controlled analgesia [PCA]) were measured. The effects on plasma catecholamines, cortisol, potassium, creatinine, skin bleeding time, prothrombin time (PT), and partial thromboplastin time (PTT) were also evaluated. Ketorolac improved pain scores (P < 0.05) and reduced plasma cortisol concentrations between 2 and 6 h (P < 0.05). No significant differences were observed concerning operative blood losses, glucose concentration, and renal and hemostatic functions. The ketorolac group required less morphine (not significant [NS]) than the control group and had less adverse effects (P = 0.002). Thus, perioperative ketorolac infusion improved the quality of postoperative pain relief, and had no major influence on endocrine-metabolic response and no negative influences on hemostatic and renal functions. This study suggests that preventive ketorolac administration, followed by a continuous infusion, is an easy, useful, and safe method for pain control after abdominal surgery.