Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids.

BACKGROUND: Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. PATIENT AND METHODS: In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). RESULTS: Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. CONCLUSION: The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. CLINICAL TRIAL REGISTRATION: NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).

Laparoscopic management of left paraduodenal hernia. Case report and review of literature.

We report a rare case of left paraduodenal hernia in patient with symptoms of abdominal subobstruction treated successful with laparoscopic management in urgent situation that have reduced the length of stay and postoperative pain. Internal hernia is only 1% of the causes of abdominal obstruction and the left paraduodenal hernia about 50% of them; it is a congenital defect that derive from malrotation and abnormal mesenteric adhesion. The modern imaging techniques help for the correct diagnosis despite difficult identification of the pathology for the various clinical presentation. The treatment of choice is the surgical intervention; the laparoscopic approach is rarely described in literature but it can reduce the morbidity, postoperative pain and the length of hospital stay.

Total intravenous anesthesia using remifentanil in extracorporeal shock wave lithotripsy (ESWL). Comparison of two dosages: a randomized clinical trial.

BACKGROUND: Extracorporeal Shock Wave Lithotripsy is usually performed in day surgery setting, consequently people who undergo to this procedure need a safe and fast recovery. Conscious sedation with remifentanil can relieve from pain and keep patients in touch with anaesthesiologists. Few publications tell about infusion rates administered to perform this procedure7. The aim of this study is to assess which is the most appropriate infusion rate. METHODS: Patients were randomly assigned to two groups. Two different infusion rates were compared: 0,05 mcg/kg/min, GROUP A (N.=114), vs. 0.1 µg/kg/min, GROUP B (N.=114). Patients' vital signs, additional analgesic requests, PONV (postoperative nausea and vomiting) and other side effects were registered. The deepness of sedation and patient's satisfaction were evaluated referring to Obsever's Assessment of Alertness and Sedation scale (O/ASS) and using a Likert's scale respectively. Pain intensity was assessed with a 11-points VAS (visual analogue scale). Differences between groups were analyzed using Student t test for independent variables. The χ2 test was used to analyze categorical variables. RESULTS: The study enrolled 228 patients and assigned them to two groups (N.=114). No significant differences were found regarding Likert's scale values (P=0.20), additional analgesic request (P=0.30) and mean VAS values (P>0.05) between the two groups. The difference between the two groups about PONV, hypotension, oxygen desaturation and respiratory depression was statistically significant (P<0.05), as a matter of fact in group A these side effects occurred less frequently. The fifth degree of O/ASS was estimated in about 1.61±0.19 min and 2.987±0.20 min in group A and in group B respectively (P<0.05). CONCLUSION: According with previous results remifentanil at the infusion rate of 0.05 µg/kg/min provides an effective analgesia, causing a lower incidence of side effect than 0.1 µg/kg/min, granting a fast and safe recovery.

Safety and efficacy of transdermal buprenorphine and transdermal fentanyl in the treatment of neuropathic pain in AIDS patients.

BACKGROUND: Multifactor neuropathic pain is one of the most frequent symptoms in AIDS patients and analgesic treatment is primarily based on the use of drug combination of opioids, tricyclic antidepressants and antiepileptics. However, the chronic use of opioids in AIDS patients presents a risk due to the immunosuppressive action of these drugs. Until now, buprenorphine has been regarded as one of the safest opioid analgesics for the treatment of patients with compromised immune systems. To assess the suitability of transdermal fentanyl for the treatment of neuropathic pain in AIDS patients, the present study compares the efficacy, tolerability and the immunosuppressive effects of transdermal buprenorphine vs. fentanyl. METHODS: Forty advanced AIDS patients (28 male and 12 female) with chronic peripheral neuropathic pain were enrolled onto this clinical trial. Neuropathic pain was assessed for its constituent types of pain (burning, stabbing and shooting), its overall intensity and allodynia; scores were awarded using the Neuropathic Pain Scale, expressed as 10 item VAS scores. RESULTS: Both treatment groups showed statistically significant reductions in each of the individual types of neuropathic pain and allodynia (P<0.05; 95% CI: -14.7, -3.1) and significant improvements in Karnofsky Performance Status (P<0.05; mean value, 69; range: 40-90). Both buprenorphine and fentanyl were well tolerated. Neither buprenorphine nor fentanyl affected CD4+ or CD8+levels and both treatments, but particularly buprenorphine group, resulted in more stable CD4+ concentrations. CONCLUSION: The high efficacy, tolerability and patient compliance of both buprenorphine and fentanyl make both these two opioids valid therapeutic options for the treatment of neuropathic pain in patients with AIDS.

Neuromuscular block in Italy: a survey of current management.

BACKGROUND: Little is known about current use of neuromuscular blocking agents by Italian anesthetists. This paper reports the results of a survey conducted to obtain information about current management of neuromuscular block in Italy. METHODS: A questionnaire was given to Italian Anesthetists attending the 64nd National Congress of the Italian Society of Anesthesia, Intensive Care, Analgesia and Intensive Therapy S.I.A.A.R.T.I. (Parma, 13th-16th October 2010). Collected data were stratified by age, geographical location, and the total number of surgical procedures performed in the hospitals concerned. RESULTS: One thousand four hundred forty patients correctly compiled questionnaires were collected. 50% of respondents used clinical tests to monitor the level of neuromuscular blockade. The main clinical tests cited for the evaluation were: keeping the head lifted up for 5 seconds, protruding the tongue and opening the eyes. Train-of-four was used by 50% of respondents on a routine basis. Only 33% of anesthetists reply that a train-of-four ratio of 90% or more is the safe level prior to extubation. CONCLUSION: Clinical signs are used by most of the Italian anesthetists to assess the recovery from neuromuscular blockade. There is poor awareness about their inability to indicate even a significant degree of residual neuromuscular block. A more extensive use of quantitative instrumental monitoring is required for the more rational use of neuromuscular blocking agents.

Prevalence study of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: preliminary data.

PURPOSE: This study aimed to evaluate the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS). MATERIAL AND METHODS: From November 2009 to February 2010, 74 participants (40 MS patients and 34 healthy controls) were enrolled in a randomised singleblind prospective study. All participants underwent ultrasonography (US) to detect signs of CCSVI. RESULTS: CCSVI was detected in 55% of patients in the MS group and 35% in the control group; the difference was not statistically significant (p=0.089). CONCLUSIONS: In our experience, a slight difference exists in the prevalence of CCSVI between MS and healthy controls, but it is not as yet clear which parameters may be most significant. This preliminary study failed to show a statistically significant difference in the prevalence of CCSVI among patients affected by MS. It did, however, reveal a tendency that requires a larger number of patients to achieve statistically significant results.

The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation. The brain MRI abnormality consists of T2 hypointensity in the globus pallidus with a small hyperintensity in its medial part, called the "eye-of-the-tiger" sign. We report on 2 patients affected by PKAN, in whom MRI examination did not demonstrate the "eye-of-the-tiger" sign in the early stages; the typical abnormalities were detected only in the following examinations. Case 1 is a 4-year-old boy first studied at age 2 years for psychomotor delay. The brain MRI was normal. In the following 2 years, the motor impairment progressed. The second brain MRI at age 4 years demonstrated the "eye-of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense mutation F228S in exon 2 in homozygosis. Case 2 is a 6-year-old boy first studied at age 2 years because of psychomotor delay. His brain MRI did not demonstrate abnormalities in the globus pallidus. In the following years spastic-dystonic tetraparesis became evident. A brain MRI at age 4 years demonstrated the "eye-of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense mutation in exon 5 (N501I). Our 2 cases demonstrate that the observation of a normal globus pallidus in the early stage of the disease does not exclude the diagnosis of classic PKAN.

Knowledge of residual curarization: an Italian survey.

BACKGROUND: The use of neuromuscular blocking agents (NMBAs) is widespread in anesthetic practice; little is known about the current use of these drugs in Italy. This survey was conducted to obtain information about the most commonly used clinical tests and the train-of-four (TOF) ratios that are considered as being reliable for assessing recovery from neuromuscular blockade at the end of anesthesia and the estimated occurrence rates of post-operative paralysis in Italian hospitals. METHODS: The questionnaire was given to Italian anesthesiologists attending the 62nd National Congress of the Italian Society of Anesthesia, Analgesia and Intensive Therapy. Collected data were stratified by age and the total number of surgical procedures performed in the hospitals concerned. RESULTS: Seven hundred and fifty-four correctly compiled questionnaires were collected (response rate 88.7%). Seventy three percent of the respondents only used clinical tests for monitoring the level of neuromuscular blockade. The main clinical tests cited for the evaluation of residual paralysis were keeping the head lifted up for 5 s, protruding the tongue and opening the eyes. TOF was used by 35% of the respondents on a routine basis. Only 24% of the interviewed anesthesiologists reported that before extubation, a TOF ratio of at least 0.9 should be reached. CONCLUSIONS: Most Italian anesthetists assess the recovery from neuromuscular blockade only by clinical signs. There is poor awareness about the inability of such techniques to indicate even a significant amount of residual neuromuscular block. A more extensive use of quantitative instrumental monitoring is required for the more rational use of NMBAs.

Carotid artery stenting: findings based on 8 years' experience.

PURPOSE: Carotid artery stenting (CAS) may be an alternative to surgical endarterectomy not only in high-risk patients. Few data are available regarding the long-term clinical efficacy of CAS with the use of cerebral protection devices and the incidence of restenosis. Our experience demonstrates that if certain requirements are fulfilled, CAS can be considered a safe and effective treatment with high short-and long-term success rates. MATERIALS AND METHODS: In the past 8 years, we treated 1,003 patients (1,096 arteries) affected by internal carotid artery stenosis, 93 with bilateral stenosis. Of these, 567 (51.74%) were symptomatic and 529 (48.26%) asymptomatic lesions. The preprocedural evaluation was performed with Doppler ultrasound (US), magnetic resonance (MR) angiography/computed tomography (CT) angiography and a neurological evaluation. Antiplatelet therapy was administered before and after the procedure. RESULTS: Technical success was achieved in 1,092 cases (99.6%), and a cerebral protection device was successfully used in 1,019 procedures (92.9%). The 30-day transient ischaemic attack (TIA)/stroke/death rate was 2.16%: death (0.18%) major stroke (0.45%) and minor stroke/TIA (1.53%). During a follow-up up to 8 years, restenoses occurred in 39 cases (3.57%), of which 28 were post-CAS (2.57%) and 11 post-CAS performed for restenosis after carotid endarterectomy (1%). Only five symptomatic restenoses>80% were treated with a repeated endovascular procedure. CONCLUSIONS: A retrospective analysis of our experience suggests that CAS is a safe and effective procedure with better results than endarterectomy. In up to 8 years of follow-up, CAS seems to be effective in preventing stroke, with a low restenosis rate.

Fibrinolysis or hypercoagulation during radical prostatectomy? An evaluation of thrombelastographic parameters and standard laboratory tests.

BACKGROUND AND OBJECTIVES: Radical prostatectomy is at high risk for intraoperative and postoperative bleeding due to surgical trauma, release of urokinase and tissue type plasminogen activator. We conducted this prospective, observational multi-centre study to assess the degree of systemic fibrinolysis or hypercoagulation in the perioperative period. We studied serial changes in standard laboratory values and in thrombelastographic (TEG; Haemoscope Corporation, Skokie, IL, USA) parameters including lysis at 30 and 60 min (LY-30, LY-60), alpha-angle (alpha) and maximum amplitude. METHODS: In all, 49 patients undergoing radical retropubic prostatectomy in five Italian University Hospitals were included. Blood samples were taken before surgery (T1), at the removal of the prostate (T2), 4 h after surgery (T3) and then 1 day after surgery (T4). Native blood samples were analysed using a thrombelastograph Haemoscope 5000 (Haemoscope Corporation). RESULTS: We did not see any relevant activation of fibrinolysis during any stage. Intraoperatively, we showed even more activated blood coagulation with consumption of fibrinogen and a reduced TEG percentage clot lysis. Only at the first postoperative sample point we saw a trend towards a more fibrinolytic state indicated by increasing partial thromboplastin time, LY-30 and LY-60 values, and a peak of the fibrin degradation product D-dimers. This is consistent with a normal reaction to the hypercoagulable state before and is unlikely to be due to an intraoperative tissue type plasminogen activator release. We found no evidence of an uncontrolled activation of fibrinolysis on the day after surgery. On the contrary, alpha-values which indicate the rate of clot formation and which increase during hypercoagulation showed the tendency to rise slightly compared with the preoperative value. CONCLUSION: Neither standard coagulation parameters nor TEG values showed any significant activation of fibrinolysis or of hypercoagulation in the preoperative period. Nevertheless, hypercoagulation seems to have a substantial clinical impact as it has been shown that cardiovascular complications and pulmonary embolism were the most common causes of death after retropubic prostatectomy.

Advantages of totally implanted port over impromptu short-term central venous catheter in oncological pain therapy.

The aim of this paper is to determine if patient controlled analgesia (PCA) by means of programmable pumps improves patients' autonomy and to verify if the short-term central venous catheter - implanted when pain is first evident - makes the quality of life worse in comparison with an early implanted port. Forty non-terminally ill patients affected by urinary malignant pathologies with visceral and bone metastases were enrolled in a prospective and randomised study at the Urology Department of 'La Sapienza' University in Rome, Italy. Intensity of pain and tolerability of venous access were assessed for the first 7 days, and weekly for 3 months. Such data were used to adjust drug therapy. In this study we hypothesized that a delayed central venous catheter implant, when the pain is at first considerably evident, can interfere negatively with drug treatment. The visual analogue scale (VAS) and the brief pain inventory (BPI) were administered to the patients, and these showed good levels of analgesia in both groups and a greater comfort to the patients with the previously implanted port in comparison with a short-term central venous catheter. In conclusion, PCA achieves a constant level of drugs and enables the patient to voluntary control the pain by means of supplemental boluses. Both central devices seem to provide similar technical benefits, but the port is much more easily tolerated and the quality of life is increased if it is already available when pain is first evident.

Antalgic treatment of pain associated with bone metastases.

Pain from metastases of primitive cancer is the first symptom of disease in 15--20% of patients and remains the most common cause of cancer-related pain. 30--70% of patients have metastases at diagnosis, and 80% of them at the moment of death. Functional impairment of skeleton, neurologic symptoms, pathological fractures and pain are the most important indications for palliative treatment which should result in tumor regression, relief in cancer-related symptoms and maintainance of functional integrity. Bone metastases are treated with the systemic therapies including radiotherapy, hormonal manipulation, biphosphonates, calcitonin, surgical treatment, and chemotherapy. Conventional use of opioids or non-steroidal anti-inflammatory drugs does not always produce satisfactory analgesic result in treated patients because of incidental and intermittent nature of pain and unacceptable side effects. Alternative strategies (peripheric and central nerve blocks, neurolysis) are frequently required. A proper use of different modalities of treatment enhances the probability of achieving relief of pain and maintaining an acceptable quality of life.

Epidural steroids as a pharmacological approach.

Cervicogenic headache is a relatively common pain syndrome related to functional and/or degenerative alterations of the cervical spine tract. Administration of steroid represents an effective therapy for this headache, due to the anti-inflammatory effects combined with its direct analgesic effects on the C fibers. The epidural injection of steroids, while requesting skilled personnel for its execution, gives short term (2-month) pain relief with few risks or side effects. Moreover, epidural steroids allow reduction of analgesic drug consumption.

Epidural corticosteroid blockade in cervicogenic headache.

Cervicogenic headache (CGH) is a relatively common form of headache stemming from the neck structures which presents some pathophysiological condition probably linked together with various pain-producing factors. This report presents a series of 9 patients suffering from cervicogenic headache and the results achieved by means of epidural steroid (methylprednisolone 40 mg) injection into the epidural cervical space (C6-C7 or C7-T1) level. The effectiveness of this diagnostic blockade was compared with the results obtained using the same procedure in 6 chronic tension headache (CTH) patients. A sharp decrease in the Numeric Intensity Scale (NIS) and in the Drug Consumption Index (DCI) values were observed after the diagnostic procedure in CGH patients. The short-term (12 hours) and medium-term (4 weeks) marked clinical improvement obtained in CGH patients may increase the number of available diagnostic tools which can be used to identify these underestimated patients population. The long-term effectiveness of this approach in cervicogenic patients is being evaluated over time.

[Anesthetic infiltration of the spermatic cord in surgery for voluminous hydrocele]. / Infiltrazione anestetica del funicolo spermatico nella chirurgia dell'idrocele voluminoso.

The use of a new technique in spermatic cord block in surgical treatment of large hydroceles is reported. Identification of the cord in these cases is often difficult due to the presence of the hydrocele. The reported technique consists in the percutaneous drainage of the hydrocele prior to the block, in order to allow an easier identification of the cord. The block is then performed by the usual method. 108 patients with large hydroceles (above 250 mls) underwent surgical repair employing this approach. In only one case the cord was not identified even after drainage due to the effects of a previous hernioplasty. In the remaining 107 patients the cord was easily identified and blocked. The excellent results obtained with this approach, show that cord block is possible in all patients, even when a large hydrocele is present.

[Neopterin and interleukin 2 soluble receptors as biochemical markers of cellular immune response to surgical trauma]. / Neopterina e recettore solubile dell'interleuchina 2 come indicatori biochimici della risposta immunitaria cellulare al trauma chirurgico.

In 67 patients submitted to surgical procedures serum neopterin (NPT) and Interleukin 2 soluble receptors (IL2R) were evaluated at the end of the operation as well as 24, 48, 72 hours later. Thirty seven of the subjects (Group B) had undergone minor surgery (average time of operation: 40 +/- 10 min.), thirty (Group A) had undergone major surgery (average time: 180 +/- 30 min.). The results showed elevated NPT and IL2R levels in the latter cases and, in particular, 48 and 72 h after surgery. Neopterin levels were positively correlated with IL2R (r = 0.548 p < 0.01). These data suggest an activation of the cellular immune response which parallels the magnitude and length of surgical trauma. Thus NPT and IL2R levels could represent biochemical markers of postoperative disorders of the immune homeostasis.