Alba Piroli

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.

Waiting Time and Pain During Office Hysteroscopy

STUDY OBJECTIVE To find a correlation between the waiting time between counseling about and performance of office hysteroscopy and the perception of pain. DESIGN Observational study (Canadian Task Force classification II-2). SETTING Academic environment. PATIENTS Two hundred eighty-four women undergoing hysteroscopy. INTERVENTIONS Diagnostic hysteroscopy with endometrial biopsy. MEASUREMENTS AND MAIN RESULTS Before examination, patients were asked to complete 2 forms, the STAI-S (State-Trait Anxiety Inventory, State) and STAI-T (State-Trait Anxiety Inventory, Trait) anxiety scales, for evaluation of their usual anxiety state and their state of anxiety during the examination. Patients were asked to quantify on a visual analog scale the pain felt during the examination. A statistically significant positive correlation, even if weak, was demonstrated between pain and waiting time (r = 0.45; p < .01) but not with the values for the anxiety state (r = 0.06; p = .56) and anxiety trait (r = -0.05; p = .66). Pain (≥4) was significantly associated with waiting time (≥60 minutes) (odds ratio [OR], 5.21; 95% confidence interval [CI], 1.29-35.50), age (OR, 1.57; 95% CI, 0.40-5.87) and menopause (OR, 2.81; 95% CI, 1.10-7.40) but not with STAI-S level (≥34) (OR, 0.87; 95% CI, 0.26-3.12) or STAI-T level (≥34) (OR, 0.65; 95% CI, 0.19-2.32). CONCLUSION Office hysteroscopy is associated with a level of anxiety that can affect patient tolerability of the procedure. However, factors such as reducing waiting time may have a positive effect on patient compliance, making hysteroscopy easier and thereby increasing its diagnostic and therapeutic potential.

Strong analgesics: Working towards an optimal balance between efficacy and side effects

Inadequately treated chronic pain remains a major cause of suffering. A recent survey found that moderate to severe chronic pain affects 19% of adult Europeans (Breivik et al., 2006). Other large scale surveys in Australia (Blyth et al., 2001), Denmark (Sjogren et al., 2009) and Norway (Rustoen et al., 2004) have given similar results. These also represent a substantial socioeconomic burden (Dunn and Croft, 2004). Moreover, these surveys may underestimate the true incidence, because many patients paradoxically report their analgesia to be satisfactory despite being in pain. One study found that over 75% of patients declared themselves satisfied or very satisfied with their overall pain management, despite almost 50% reporting recent moderate to severe pain (Dawson et al., 2002). The cornerstone of treatment for moderate to severe pain is classical opioid therapy; the WHO Pain Analgesic Ladder recommends weak opioids for Step 2 and strong opioids for Step 3 in the management of chronic pain (WHO, 1996), even if this recommendation has been criticized (Marinangeli et al., 2004). However, the prescription of opioids is still limited by medical, ethical, cultural and legal issues (Bhamb et al., 2006; Jacobsen et al., 2007). One major factor is opiophobia; physicians’ and patients’ concerns about the appropriate use of opioids, and their fears and misunderstandings in connection with these agents. Patients may be reluctant to take opioids because of a perceived association with drug abuse and criminality (Fields, 2007) or with terminal illness. Classic opioid therapy also has shortcomings; specifically, in providing sustained analgesic efficacy over long periods, reliable efficacy in difficult-to-treat pain syndromes, and acceptable levels of tolerability. Balancing adequate pain relief with minimal side effects is difficult, and sometimes impossible. Long term opioid efficacy may be compromised by the development of tolerance and/or hyperalgesia. The current clinical strategy for managing these phenomena is opioid rotation, utilising the incomplete cross-tolerance between opioids in order to recover efficacy (DuPen et al., 2007). However, the evidence for this strategy is largely anecdotal or based on observational and uncontrolled studies, and there are no predictive criteria for the best drug option. A recent approach has been to combine drugs with different modes of action, such as morphine with N-methyl-D-aspartate (NMDA) antagonists, anticonvulsants or antidepressants. A few clinical studies have been undertaken with morphine plus the NMDA antagonist dextromethorphan. The combination has so far failed to demonstrate either enhanced opioid analgesia or reduced tolerance compared to morphine alone, and – in addition – discontinuation rates have been higher with the combination (Galer et al., 2005). Difficult-to-treat pain syndromes are essentially those where the pain is neuropathic in origin or has a neuropathic component. Examples include diabetic peripheral neuropathy, post-herpetic neuralgia and mixed cancer pain. Many different drugs are currently used to treat these syndromes and there is no gold standard for treatment, demonstrated by a review of 105 high-quality, randomised, placebo-controlled clinical trials (Finnerup et al., 2005). Experienced pain therapists use a combination of analgesics (often an opioid and a non-opioid) with different modes of action. Animal studies have suggested that combining morphine with an alpha2 delta ligand such as gabapentin (Matthews and Dickenson, 2002), a tricyclic antidepressant such as amitriptyline (Luccarini et al., 2004), or an NMDA antagonist such as ketamine (Pelissier et al., 2003) all offer some benefit. However, some unresolved issues remain with this approach (such as the safety of polypharmacy and its effect on compliance), while clinical trials suggest that any improvement in efficacy may be outweighed by the increased incidence of side effects (Hanna et al., 2008; Gilron et al., 2005). Tolerability problems are common with opioids, particularly nausea and vomiting during the first one or two weeks, and constipation throughout long term treatment. Anti-emetics and laxatives may be used both for prophylaxis and treatment of these adverse events, but the current pharmacological approach is often unsatisfactory and/or the regimen is too complex, so patients discontinue treatment because of additional and intolerable side effects. One recent alternative is to combine a classical opioid with a systemic mu opioid receptor antagonist (Muller-Lissner et al., 2007), but further studies are needed. Peripheral selective and non-selective mu opioid receptor antagonists have been developed. These act on peripheral receptors, including those located within the GI tract, and do not cross the blood–brain barrier. Some clinical trials has shown that subcutaneous methylnaltrexone rapidly induces laxation in patients with advanced illness and opioid-induced consti-

Comparison of different anaesthetic methodologies for sedation during in vitro fertilization procedures: effects on patient physiology and oocyte competence

The main goal of the present retrospective study is to compare four analgesic methodologies (EMLA cream, propofol, thiopental sodium, sevoflurane) for in vitro fertilization (IVF) oocyte retrieval. We found that most anaesthetic parameters were not significantly different among all treatments. In contrast, significant differences were revealed in all groups for total number of oocytes retrieved per patient, rate of mature oocytes at metaphase II stage (MII) and percentage of fertilization and embryo development. In the EMLA cream and thiopental sodium groups we observed the highest percentage of MII oocytes (P < 0.001). Fertilization rate in the EMLA and sevoflurane groups were similar but significantly higher than the propofol and thiopental sodium groups (P < 0.001). The highest rate of anomalous fertilization was observed in the propofol group. Rate of embryo development was similar in all groups but sevoflurane group had a lower percentage of good embryos. In conclusion, by comparing different anaesthetic techniques with different mechanisms of action and administration, potential negative effects of these drugs on the initial stages of human IVF procedure were revealed. Therefore, a local anaesthetic cream is proposed as an acceptable alternative option for anaesthesia during transvaginal oocyte retrieval.

Duloxetine and Pregabalin for Pain Management in Multiple Rheumatic Diseases Associated with Fibromyalgia

The fibromyalgia syndrome (FMS) is characterized by chronic and widespread musculoskeletal pain and soreness accompanied by sleep disorders, chronic fatigue and affective disorders. FMS is often associated with other forms of immuno‐rheumatic diseases. Although FMS pathophysiology is still not fully understood, a number of neuroendocrine, neurotransmission and neurosensitive disorders might generate a mechanism for the elicitation of pain by “central sensitization,” which is common to many other painful conditions. The present case describes the success of a therapeutic scheme, which associates two different pharmacological classes, anticonvulsants and new‐generation antidepressants, when FMS complicates a rare pathology called Cogans syndrome. The association of two drugs might noticeably affect the molecular mechanisms of difficult pain, thus solving painful conditions of multifactorial origin.

Anaesthesia management in patients with multiple chemical sensitivity syndrome.

Multiple Chemical Sensitivity (MCS) is characterised by the appearance of numerous and sometimes severe symptoms, when subjects are in contact with various chemicals and medicinal substances. Currently there are no useful guidelines for managing clinical issues and, specifically, anaesthesia for patients with MCS. This case report describes anaesthesia management in a patient affected by clinically documented MCS and a latex allergy, a candidate for a laparoscopic cholecystectomy operation.

Intravenous naloxone plus transdermal buprenorphine in cancer pain associated with intractable cholestatic pruritus.

To the Editor: The complex and unpredictable series of symptoms that comes with the terminal stage of neoplastic disease significantly compromises patients’ quality of life, and poses harsh therapeutic challenges for clinicians. Good control of severe cancer-related cholestatic pruritus seems to be hard to achieve and pruritus still undermines the remaining physical and relational capabilities of seriously ill cancer patients. Its pathogenesis remains substantially unknown and its treatment mostly empirical. An increased central opioidergic tone seems to be an important component of cholestatic pruritus, with hyperactivity of the serotoninergic system playing a primary role. These elements were the basis for the therapeutic choice successfully applied in the following clinical case.

Palmitoylethanolamide in the Treatment of Failed Back Surgery Syndrome

Introduction This observational study was designed to evaluate the efficacy of ultramicronized palmitoylethanolamide (um-PEA) (Normast®) administration, as add-on therapy for chronic pain, in the management of pain-resistant patients affected by failed back surgery syndrome. Methods A total of 35 patients were treated with tapentadol (TPD) and pregabalin (PGB). One month after the start of standard treatment, um-PEA was added for the next two months. Pain was evaluated by the Visual Analogue Scale (VAS) at the time of enrollment (T0) and after one (T1), two (T2), and three (T3) months. Results After the first month with TDP + PGB treatment only, VAS score decreased significantly from 5.7 ± 0.12 at the time of enrollment (T0) to 4.3 ± 0.11 (T1) (p < 0.0001); however, it failed to provide significant subjective improvement in pain symptoms. Addition of um-PEA led to a further and significant decrease in pain intensity, reaching VAS scores of 2.7 ± 0.09 (T2) and 1.7 ± 0.11 (T3, end of treatment) (p < 0.0001) without showing any side effects. Conclusions This observational study provides evidence, albeit preliminary, for the efficacy and safety of um-PEA (Normast) as part of a multimodal therapeutic regimen in the treatment of pain-resistant patients suffering from failed back surgery syndrome.

Influence of the menstrual cycle phase on pain perception and analgesic requirements in young women undergoing gynecological laparoscopy

The influence of the gonadal hormones on some aspects of the human physiology has been studied with uncertain results. Still a confusion exists in relation to the real effects of the female hormones on the perception of pain. The existing data refer mainly to experimental studies and have provided results not always useful in the clinical practice.

578 A STRONG OPIOID IN NEUROPATHIC PAIN: HYDROMORPHONE

Results: At the last follow-up control (t45) both groups reported a good pain relief (VAS≤3). More specific: in group A at t30 VAS 4±0.98 at t45 VAS 2±1.17; while in group B at t30 VAS 4 ±0.75 at t45 VAS 2±1.21. Our study failed to show a statistic significative difference (p < 0.05). 3 subjects of group A with DN related sleep difficulties reported the greatest pain relief with improved sleep quality. 2 subjects of group B reported urinary retention and decrease of libido after the treatment. Discussion: According to our data Duloxetin may be considered an effective treatment for neuropatic pain with better tolerability than usual antidepressants.