Roberto Arcioni

Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-ht3 Spinal Receptor Involvement in Acute Pain in Humans

To investigate a possible antinociceptive role of serotonin receptor subtype 3 (5-HT3), we evaluated the effects of a coadministration of ondansetron, a 5-HT3 selective antagonist, and tramadol, a central analgesic dependent on enhanced serotonergic transmission. Fifty-nine patients undergoing ear, throat, and nose surgery, using tramadol for 24-h postoperative patient-controlled analgesia (bolus = 30 mg; lockout interval = 10 min) were randomly allocated either to a group receiving ondansetron continuous infusion (1 mg · mL−1 · h−1) for postoperative nausea and vomiting (Group O) or to a control group receiving saline (Group T). Pain and vomiting scores and tramadol consumption were evaluated at 4, 8, 12, and 24 h. Pain scores were never >4, according to a 0–10 numerical rating scale, in both groups. Group O required significantly larger doses of tramadol at 4 h (213 versus 71 mg, P < 0.001), 8 h (285 versus 128 mg, P < 0.002), and 12 h (406 versus 190 mg, P < 0.002). Vomiting scores were higher in Group O at 4 h (P < 0.05) and 8 h (P = 0.05). We conclude that ondansetron reduced the overall analgesic effect of tramadol, probably blocking spinal 5-HT3 receptors.

Neuromodulation of chronic headaches: position statement from the European Headache Federation

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases.Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches.In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile.

Combined intrathecal and epidural magnesium sulfate supplementation of spinal anesthesia to reduce post-operative analgesic requirements : a prospective, randomized, double-blind, controlled trial in patients undergoing major orthopedic surgery

Background:  New ways of decreasing post‐operative analgesic drug requirements are of special interest after major surgery. Magnesium sulfate (MgSO4) alters pain processing and reduces the induction and maintenance of central sensitization by blocking the N‐methyl‐d‐aspartate (NMDA) receptor in the spinal cord. We investigated whether supplementation of spinal anesthesia with combined intrathecally and epidurally infused MgSO4 reduced patients’ post‐operative analgesia requirements.

Emerging treatment for chronic migraine and refractory chronic migraine

Introduction: Chronic migraine (CM), the suffering of 15 or more headache days with at least 8 of these migraine days, afflicts 1.3% - 5.1% of the global population. CM is the most common disorder faced by experts in tertiary headache centers. When resistant to conventional medical treatment and prophylactic medication this condition is known as refractory chronic migraine (RCM). RCM is one of the greatest challenges in headache medicine. Areas covered: State-of-the-art and future medical treatments of chronic migraine include: OnabotulinumtoxinA, antiepileptic drugs (Levetiracetam, Magnesium valproate hydrate, Lacosamide, BGG-492), 5-HT agonists (Lasmiditan, NXN-188, novel delivery systems of Sumatriptan, a well-established drug treatment for acute migraine), CGRP receptor antagonists (BMS-927711), ML-1 agonists (Ramelteon), orexin receptor antagonist (MK-6096), plant-derived compound (LLL-2011) and other multitarget drugs such as Tezampanel, Tonabersat, intranasal carbon dioxide and BOL-148. The role for neuromodulation, the application of targeted electrical stimulation, will be examined. Expert opinion: Medication overuse headache (MOH) is now recognized to be a major factor in many cases of both chronic and refractory chronic migraine. MOH must be addressed prior to evaluating the effectiveness of new preventative and prophylactic treatment approaches. Innovative new drugs and electrical neuromodulation are promising CM treatments. Future studies must carefully screen patients and acquire data that can lead to personalized, tailored treatment strategies.

A six year retrospective review of occipital nerve stimulation practice - controversies and challenges of an emerging technique for treating refractory headache syndromes

BackgroundA retrospective review of patients treated with Occipital Nerve Stimulation (ONS) at two large tertiary referral centres has been audited in order to optimise future treatment pathways.MethodsPatient’s medical records were retrospectively reviewed, and each patient was contacted by a trained headache expert to confirm clinical diagnosis and system efficacy. Results were compared to reported outcomes in current literature on ONS for primary headaches.ResultsTwenty-five patients underwent a trial of ONS between January 2007 and December 2012, and 23 patients went on to have permanent implantation of ONS. All 23 patients reached one-year follow/up, and 14 of them (61%) exceeded two years of follow-up. Seventeen of the 23 had refractory chronic migraine (rCM), and 3 refractory occipital neuralgia (ON). 11 of the 19 rCM patients had been referred with an incorrect headache diagnosis. Nine of the rCM patients (53%) reported 50% or more reduction in headache pain intensity and or frequency at long term follow-up (11–77 months). All 3 ON patients reported more than 50% reduction in pain intensity and/or frequency at 28–31 months. Ten (43%) subjects underwent surgical revision after an average of 11 ± 7 months from permanent implantation - in 90% of cases due to lead problems. Seven patients attended a specifically designed, multi-disciplinary, two-week pre-implant programme and showed improved scores across all measured psychological and functional parameters independent of response to subsequent ONS.ConclusionsOur retrospective review: 1) confirms the long-term ONS success rate in refractory chronic headaches, consistent with previously published studies; 2) suggests that some headaches types may respond better to ONS than others (ON vs CM); 3) calls into question the role of trial stimulation in ONS; 4) confirms the high rate of complications related to the equipment not originally designed for ONS; 5) emphasises the need for specialist multidisciplinary care in these patients.

Effects of remifentanil-based general anaesthesia with propofol or sevoflurane on muscle microcirculation as assessed by near-infrared spectroscopy

BACKGROUND Although anaesthetics are known to alter microcirculation no study has, to our knowledge, documented changes in human skeletal microcirculatory function during general anaesthesia. METHODS Forty-four patients undergoing maxillofacial surgery at a university hospital were prospectively randomized to receive general anaesthesia with remifentanil combined with propofol or sevoflurane. Muscle microcirculation was investigated with near-infrared spectroscopy (NIRS) before general anaesthesia was induced and 30 min later. An NIRS device (NIMO, Nirox) was used to quantify calf deoxyhaemoglobin [HHb], oxyhaemoglobin [HbO2], and total haemoglobin [HbT] concentrations, coupled to a series of venous and arterial occlusions to measure calf blood flow, muscle oxygen consumption, calf vascular resistance, microvascular compliance, and haemoglobin resaturation rate (RR). RESULTS In both the groups, general anaesthesia induced marked changes in muscle microcirculation: the tissue blood volume increased (+33% in remifentanil-sevoflurane and +45% with remifentanil-propofol groups), microvascular resistance decreased (-31% and -38%, respectively), and the post-ischaemic haemoglobin RR decreased (-48% and -36%, respectively). In the remifentanil-propofol group, the muscle blood flow increased (P<0.001), whereas in the remifentanil-sevoflurane group microvascular compliance and muscle oxygen consumption decreased (P<0.01). CONCLUSIONS Remifentanil-based general anaesthesia with propofol or sevoflurane altered the muscle microcirculation in different ways. Quantitative NIRS, a technique that takes into account the optical tissue properties of the individual subject, can effectively measure these changes non-invasively.

Lateral popliteal sciatic nerve block: a single injection targeting the tibial branch of the sciatic nerve is as effective as a double-injection technique

Background:  Evidence indicating that single‐ and double‐injection techniques for inducing a sciatic nerve block via a posterior subgluteal approach yield a similar success rate prompted us to investigate whether the two anesthetic techniques yield a similar success rate via a lateral approach. We also hypothesized that, owing to the peculiar anatomic features of the sciatic nerve at the popliteal level, a single injection via the lateral approach might induce effective anesthesia by targeting the tibial nerve only.

Cervical 10 kHz spinal cord stimulation in the management of chronic, medically refractory migraine: A prospective, open-label, exploratory study

A significant minority of chronic migraine (CM) subjects fail conventional medical treatment (rCM), becoming highly disabled. Implantation of an occipital nerve stimulator is a therapeutic option for these subjects. Paresthesia‐free cervical 10 kHz spinal cord stimulation (HF10 SCS) may provide an alternative. We report the results of a prospective, open‐label, exploratory study assessing the long‐term safety, tolerability and efficacy of cervical HF10 SCS in cohort of rCM subjects.

Does local anesthetic dilution influence the clinical effectiveness of multiple-injection axillary brachial plexus block?: a prospective, double-blind, randomized clinical trial in patients undergoing upper limb surgery.

Objectives: The relationship between the dose, volume, and concentration of local anesthetic and the quality and success of regional anesthesia remains unclear. Our aim was to test whether using 3 different volumes of the same local anesthetic dose influences the success rate of an axillary brachial plexus block with a multiple-injection technique in patients undergoing upper limb surgery. Methods: One hundred sixty-five patients were prospectively randomized to 1 of 3 groups. Each group received an axillary block with mepivacaine 400 mg, diluted in 3 different volumes (20, 30, and 40 mL). Outcome measures recorded were the block success rate at 30 mins, sensory and motor onset times, and length of postoperative sensory and motor blockade. Results: No difference was found in the rate of successful axillary plexus blocks determined when the 30-min follow-up ended among the 3 groups: 94% for 20-mL volume, 94% for 30-mL volume, and 98% for 40-mL volume. The median sensory and motor onset times of anesthesia did not differ. However, postoperative motor blockade and sensory analgesia lasted significantly longer in the patients receiving mepivacaine 400 mg diluted in a volume of 30 mL than in the other groups. Conclusions: An axillary brachial plexus block induced with a multiple-injection technique with mepivacaine 400 mg yields a high success rate regardless of the volume of anesthetic injected.

Effects of sternotomy on heart-lung interaction in patients undergoing cardiac surgery receiving pressure-controlled mechanical ventilation

Background:  The key concept underlying the dynamic indexes of preload dependence is the physiological heart–lung interaction. During sternotomy this interaction undergoes various changes, some of which remain unclear. Our primary aim was to investigate how the interaction changes during sternotomy by evaluating pulse pressure variations (PPV) with the chest closed and after sternotomy in patients ventilated using the pressure‐controlled mode.