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

BACKGROUND: A 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. METHODS: Patient'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. RESULTS: Twenty-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. CONCLUSIONS: Our 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

Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

Abstract Background Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia. Methods Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h −1 for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively. Results A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min ( P =0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine ( P =0.009). At three months, no differences between groups were noted. Conclusions Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up

Multicentre, double-blind, randomised, sham-controlled trial of 10 khz high-frequency spinal cord stimulation for chronic neuropathic low back pain (MODULATE-LBP): a trial protocol

Introduction: chronic neuropathic low back pain (CNLBP) is a debilitating condition in which established medical treatments seldom alleviate symptoms. Evidence demonstrates that high-frequency 10 kHz spinal cord stimulation (SCS) reduces pain and improves health-related quality of life in patients with failed back surgery syndrome (FBSS), but evidence of this effect is limited in individuals with CNLBP who have not had surgery. The aim of this multicentre randomised trial is to assess the clinical and cost-effectiveness of 10 kHz SCS for this population.Methods: this is a multicentre, double-blind, randomised, sham-controlled trial with a parallel economic evaluation. A total of 96 patients with CNLBP who have not had spinal surgery will be implanted with an epidural lead and a sham lead outside the epidural space without a screening trial. Patients will be randomised 1:1 to 10 kHz SCS plus usual care (intervention group) or to sham 10 kHz SCS plus usual care (control group) after receiving the full implant. The SCS devices will be programmed identically using a cathodal cascade. Participants will use their handheld programmer to alter the intensity of the stimulation as per routine practice. The primary outcome will be a 7-day daily pain diary. Secondary outcomes include the Oswestry Disability Index, complications, EQ-5D-5 L, and health and social care costs. Outcomes will be assessed at baseline (pre-randomisation) and at 1 month, 3 months and 6 months after device activation. The primary analyses will compare primary and secondary outcomes between groups at 6 months, while adjusting for baseline outcome scores. Incremental cost per quality-adjusted life year (QALY) will be calculated at 6 months and over the lifetime of the patient.Discussion: the outcomes of this trial will inform clinical practice and healthcare policy on the role of high-frequency 10 kHz SCS for use in patients with CNLBP who have not had surgery.Trial registration: Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018.Disclaimer: the views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The NIHR had no role in the study design, writing of the manuscript or the decision to submit for publication.Roles and Responsibilities: AK, SP, DP, SW, RST, AC, SE, LM, RD and JF all contributed to the trial design and to securing trial funding. AK, JR, SP, DP, and SE are involved in the recruitment, the intervention and the follow-up. SW will perform data collection and analysis. RST will be responsible for the statistical analysis, and RD will be responsible for the health economic analysis. All authors read and approved the final manuscript.<br/

General anesthesia impairs muscle microvascular compliance

Introduction Drugs used to induce and maintain general anesthesia have deep effects on the cardiovascular system. To our knowledge there are no studies investigating microvascular compliance during general anesthesia with a noninvasive approach based on near-infrared spectroscopy (NIRS) technology. Methods We randomized 36 healthy subjects undergoing maxillofacial surgery to receive general anesthesia with a sevofluorane–remifentanil (Group S) or a propofol–remifentanil association (Group P). We collected noninvasive measures of hemoglobin concentration from the gastrocnemius muscle of the subjects using a NIRS device (NIMO, NIROX srl, Italy), which performs quantitative assessments of the [HbO2] and [Hb] exploiting precise absorption measurements close to the absorption peak of the water. Data were collected during a series of venous occlusions at different cuff pressures, before and after 30 minutes from induction of general anesthesia. The muscle blood volume and microvascular compliance were obtained with a process previously described elsewhere [1]. Data were analyzed with a one-way analysis of variance test. Results Demographic data of the 36 subjects were similar in both Groups S and P. General anesthesia reduced the heart rate and mean arterial pressure and increased the total muscle blood volume in both groups (Group S: from 2.4 ± 0.9 to 3.2 ± 1.2 ml/ 100 ml; Group P: from 2.4 ± 1.2 to 3.5 ± 1.8 ml/100 ml; P &lt; 0.05). During general anesthesia, despite no differences in muscle blood volume between the two groups, sevofluorane– remifentanil significantly decreased microvascular compliance (from 0.15 ± 0.08 to 0.09 ± 0.04 ml/mmHg/100 ml; P = 0.001) whereas propofol–remifentanil did not (from 0.15 ± 0.08 to 0.16 ± 0.11 ml/mmHg/100 ml; P = 0.39). Conclusion General anesthesia affects the microvascular bed of skeletal muscle. An association between opioid and ipnotic agents increases the muscle blood volume, whereas microvascular compliance is reduced only by the sevofluorane–remifentanil association. Reference 1. De Blasi RA, Palmisani S, Alampi D, et al.: Microvascular dysfunction and skeletal muscle oxygenation assessed by phase modulation near-infrared spectroscopy in patients with septic shock. Intensive Care Med 2005, 31:1661-1668

General anesthesia impairs muscle microvascular compliance

Introduction Drugs used to induce and maintain general anesthesia have deep effects on the cardiovascular system. To our knowledge there are no studies investigating microvascular compliance during general anesthesia with a noninvasive approach based on near-infrared spectroscopy (NIRS) technology. Methods We randomized 36 healthy subjects undergoing maxillofacial surgery to receive general anesthesia with a sevofluorane–remifentanil (Group S) or a propofol–remifentanil association (Group P). We collected noninvasive measures of hemoglobin concentration from the gastrocnemius muscle of the subjects using a NIRS device (NIMO, NIROX srl, Italy), which performs quantitative assessments of the [HbO2] and [Hb] exploiting precise absorption measurements close to the absorption peak of the water. Data were collected during a series of venous occlusions at different cuff pressures, before and after 30 minutes from induction of general anesthesia. The muscle blood volume and microvascular compliance were obtained with a process previously described elsewhere [1]. Data were analyzed with a one-way analysis of variance test. Results Demographic data of the 36 subjects were similar in both Groups S and P. General anesthesia reduced the heart rate and mean arterial pressure and increased the total muscle blood volume in both groups (Group S: from 2.4 ± 0.9 to 3.2 ± 1.2 ml/ 100 ml; Group P: from 2.4 ± 1.2 to 3.5 ± 1.8 ml/100 ml; P &lt; 0.05). During general anesthesia, despite no differences in muscle blood volume between the two groups, sevofluorane– remifentanil significantly decreased microvascular compliance (from 0.15 ± 0.08 to 0.09 ± 0.04 ml/mmHg/100 ml; P = 0.001) whereas propofol–remifentanil did not (from 0.15 ± 0.08 to 0.16 ± 0.11 ml/mmHg/100 ml; P = 0.39)

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 midline thoracotomy on pulse pressure variations during pressure-control ventilation

Objective During mechanical ventilation, the heart–lung interaction induces a cyclic oscillation of the arterial pulse pressure. The measure of this respiratory changes, called pulse pressure variation (PPV), is one of the most reliable index of fluid responsiveness. It is used as a functional hemodynamic monitoring in several conditions (general anesthesia, sepsis, ALI/ARDS). During cardiac surgery, midline thoracotomy significantly alters heart–lung interaction and, consequently, PPV. The aim of the study was the evaluation of the effects of sternotomy on PPV during pressure-control ventilation (PCV). Methods Nineteen patients (age 62 ± 10 years) undergoing elective CABG in a tertiary university hospital were enrolled. A Swan–Ganz catheter, an arterial catheter and a central venous catheter was inserted in order to collect pressure waveforms. After the induction of general anesthesia all the patients were mechanically ventilated (PCV), setting pressure values in order to obtain a tidal volume of 8 ml/kg. Hemodynamic data were collected 5 min before and after sternotomy. PPV was calculated offline from the collected waveforms, according to the formula reported by Michard and colleagues [1]. Results The PPV, cardiac index, stroke volume, mean arterial pressure, airway pressure and tidal volume did not change after sternotomy. We subsequently differentiated patients according to PPV values (Fig. 1). In the subgroup of patients with PPV > 13% (7/19 patients), we found a good correlation between PPV and Paw (Pearson correlation 0.861 P = 0.03; R2 = 0.74 P = 0.049); after sternotomy, PPV was significantly reduced (15.4 ± 2.8% vs 8.2 ± 1.6%, P = 0.043) and it was no more correlated with Paw. In the subgroup of patients with PPV < 13% (12/19 patients), we did not find any correlation between PPV and Paw, and sternotomy had no effects on hemodynamic data. Conclusions During PCV, airway pressure affects PPV only when patients are in a ‘fluid responsive’ status (PPV > 13%); similarly, sternotomy reduces PPV only when baseline is above the hreshold value of 13%. It may thus be possible that midline thoracotomy makes a ‘fluid responsive’ patient unresponsive to a fluid challenge by leading his heart to work on the plateau portion of theFrank–Starling curve. This hypothesis would be confirmed by the lack of correlation between airway pressure and PPV after opening the thorax. Reference 1. Michard F, Boussat S, Chemla D, et al.: Am J Respir Crit Care Med 2000, 162:134-138

Improving Automatic Labelling through RDF Management

Building a shared and widely accessible repository, in order for scientists and end users to exploit it easily, results in tackling a variety of issues

Invasive neurostimulation

Chronic migraine afflicts 1-5% of the global population and poses a substantial burden on subjects’ quality of life and on health services utilization [1]. Although most patients benefit from abortive and preventive drugs, a subgroup of patients remains refractory to treatment. Refractory chronic migraine is one of the greatest chal- lenges in headache medicine and, in these patients, inva- sive techniques should be considered. In the past 20 years neuromodulatory approaches, already proved effective in other chronic pain syndromes, have been increasingly used for refractory primary headaches. Neuromodulation, a reversible and adjustable manipula- tion of pain pathways is an evidence-based invasive treat- ment for chronic pain conditions and it may be applied to any neural structure: spinal cord, deep brain, and periph- eral nerves. Recently, three 12-week follow-up prospective, rando- mised trials have been conducted to validate occipital nerve stimulation in chronic migraine and intractable chronic migraine associated to occipital localization of pain. Considering the primary outcomes (50% reduction in pain intensity, 50% decrease of headache days) all the three trials have failed. In one of these studies [2], although the second follow-up at 52 weeks has shown important effects on pain severity, headache days, HIT-6 and MIDAS scores (60% of patients achieved 30% reduction in headache days and/or pain, 50% achieved 50% reduction in headache days and/or pain, 70% reported excellent or good headache relief and improved QoL, 70% would undergo the procedure again), it has also shown high incidence of adverse events related to the procedure (70% of patients experienced at least one * Correspondence: [email protected] 1Department of Medical-Surgical Sciences and Traslational Medicine, Sapienza University of Rome, Sant’Andrea Hospital, Rome, Italy Full list of author information is available at the end of the article AE, 41% of AEs required supplemental surgery, 8.6% of AEs required hospitalization). A more recent prospective, open-label, exploratory study [3] assessing the long-term (6-months) safety, tolerability and efficacy of cervical high frequency (10 kHz), paresthe- sia-free, spinal cord stimulation in a cohort of 14 refrac- tory chronic migraine patients (refractory also to Onabotulinumtoxin-A) has shown good results on reduc- tion of headache days, medication intake, HIT-6 and MIDAS scores. The patients were carefully selected, for refractory chronic migraine, not considering topographic criteria for localization of pain, and were assessed by two different psychologists before eligibility. A significant reduction in headache days was observed at 24 weeks (average 7.0 days). Seven (50%) subjects recorded a &gt;30% decrease in headache days, while 5 (36%) subjects reported a reduction in headache days greater than 50%. Eight sub- jects (57%) reverted to an episodic pattern of headache (&lt;15 days a month). Medication intake reduced signifi- cantly, and four subjects discontinued triptans. Few adverse events have been reported. HF10-SCS deserves further clinical investigations to evaluate its possible role in the management of rCM