With the advent of fast-track pathways after cardiac surgery, there has been a renewed interest in regional anesthesia due to its opioid-sparing effect. This paradigm shift, looking to improve resource allocation efficiency and hasten postoperative extubation and mobilization, has been pursued by nearly every specialty area in surgery. Safety concerns regarding the use of classical neuraxial techniques in anticoagulated patients have tempered the application of regional anesthesia in cardiac surgery. Recently described ultrasound-guided thoracic wall blocks have emerged as valuable alternatives to epidurals and landmark-driven paravertebral and intercostal blocks. These novel procedures enable safe, effective, opioid-free pain control. Although experience within this field is still at an early stage, available evidence indicates that their use is poised to grow and may become integral to enhanced recovery pathways for cardiac surgery patients. Cardiac surgery (CS) generates a unique set of challenges compared to non-cardiac surgery. Postoperative outcomes and quality of life result from several factors, including demographic characteristics, comorbidities, type and quality of surgical intervention, the extent of the systemic inflammatory response, range of organ dysfunction and pain ,2,3,4. CPain management is a crucial element of cardiac ERAS. Adequate analgesia is a prerequisite to ensure patient comfort, low morbidity, early mobilization, and cost effectiveness. Postoperative pain is multifaceted and may result from various interventions, including sternotomy, thoracotomy, chest drains and leg vein harvesting. One study found that maximal pain intensity in CS was usually moderate , but sevTraditionally, opioids were considered the mainstay for pain management after CS based on a predictable hemodynamic profile. Acknowledged risks associated with their use  fueled that which now represents a central tenet in the ERAS paradigm–multimodal analgesia (MA) . MA builLM) constituted the standard regional approach to ensure chest wall pain relief before ultrasound (US) virtually revolutionized RA. Bleeding complications ) were the primary concern regarding the use of TEA and PVBLM in CS [Regional anesthesia/analgesia (RA) represents a valid alternative for the MA repertoire. It obviates many of the drawbacks of drug-based MA strategies, albeit with its particular challenges . ClassicLM in CS . This maLM in CS . DeliverRA of the chest wall may be performed at various points along an arch coursing anteriorly from the posterior midline. With TEA as gold standard regarding the breadth of somatic and sympathetic blockade, CWFPB exhibit a variable decrement in their effect as they approach the anterior midline. Autonomic effects are retained proportionally to the extent of LA spread into the epidural space, and the area of sensory loss is inversely related to the distance between the injection spot and spine. A considerable inter-individual variation in the extent and intensity of CWFPB exists, and several reasons may represent the root cause of this: (1) existence of differential sensory blockade ; (2) relThe role of TEA in cardiac ERAS programs remains an intensely debated topic. TEA produces robust chest wall pain relief, yet it repeatedly failed to improve perioperative morbidity and mortality in CS populations . PotentiCardiac sympatholysis was shown to benefit myocardial blood flow  but alsoThe calculated maximum risks of SEH in CS after TEA were 1:1500 with 95% confidence and 1:1000 with 99% confidence, respectively . In a reOverall, minimization of risks outweighs maximization of analgetic potential. Adequate patient selection, risk factors, and anesthesiologist’s expertise must be carefully balanced before pursuing TEA or any other type of neuraxial technique. Until more evidence becomes available, the risk-benefit ratio of neuraxial analgesia remains prohibitive.LM is highly variable because the LA spread is unpredictable [US). Later, Uppal et al. [US are equivalent regarding coverage and pain relief duration. Conveniently, the single-level PVBUS are markedly faster and better tolerated by patients, two prerequisites of any ERAS strategy.PVB involves LA injection into the thoracic paravertebral space (TPVS) to block the spinal nerve roots as they emerge from the intervertebral foramina. TPVS is a triangular-shaped space on both sides of the vertebrae bounded anterolaterally by the parietal pleura, medially by the posterolateral parts of the vertebral body and posteriorly by the superior costotransverse ligament (SCTL) see also . TPVS codictable . Consequdictable ,24. Thisdictable  and Marhdictable  who usedl et al.  demonstrLM, PVBUS are more reliable and safer [US. Still, the latter proves itself ineffectual in CS with sternotomy since this surgery requires bilateral nerve blockade.Compared to PVBnd safer . Two assnd safer ,32,33,34LM and PVBUS, and between single-shot PVB and PVB with catheters. New data suggests that US guidance during paravertebral blockade could virtually abrogate spinal injury risk even with the large heparin dosing needed in cardiopulmonary bypass (CPB) [US with catheter to TEA to manage pain after on-pump CS [US were non-inferior to TEA regarding pain relief, and bleeding complications were not reported in either group.As with TEA, hemorrhagic complications represent a crucial factor to consider. In contrast to TEA, risk quantification of SEH after PVB is less evident and intensely debated. The latest American Society of Regional Anesthesia and Pain Medicine (ASRA) Practice Advisory on RA and anticoagulation maintains the same recommendations for PVB as for any other neuraxial block . Equivocss (CPB) . El Shor-pump CS . CatheteUS. The first is concerned with single-shot PVB being safer than PVB with TPVS catheters because catheter misplacement, including epidurally, is still possible even with US [US established after surgery, preemptive PVBUS may be better tailored to fast-tracking as it would also mitigate the intraoperative opioid consumption.Future studies will have to address two aspects to maximize the benefits and minimize the potential risks associated with PVB with US ,38. The  with US . CompareUS has yet to be established. Further research is needed before the routine use of paravertebral blockade in CS is either supported or refuted.The best strategy to implement PVBUS have superseded PVBLM in every aspect. A comprehensive review described at least nine approaches, all of which share the same three sonoanatomical landmarks circumscribing TPVS—rib, pleura, and transverse process (TP) [US do not exist. Instead, personal factors relating to skill, experience and perceived safety seem to play a decisive role. An objective comparative evaluation of currently used PVBUS techniques is essential to enable an informed PVB-based MA.PVBess (TP) . At presTPVS scanning breaks down to 4 elements: (1) plane of US beam orientation ; (2) needling technique ; (3) direction of angulation  and (4) safety limit for needle tip  . ChoosinScanning starts with the linear-array transducer placed in a parasagittal plane to identify the adjacent TP, recognizable as flat, rectangular hypoechoic structures see also . Anti-clPost-mortem data challenge the traditional view that TPVS is a discrete anatomical space and suggest that the SCTL is permeable to LA drugs . Hence, US guidance has facilitated the emergence of several more superficial needle placement techniques, all collectively labelled as “paraspinal blocks”  or “PVB The ESPB target for LA deposition is the plane between the erector spinae muscle (ESM) and the thoracic TP tip. Correct single-level LA injection should lift the ESM off the TP and allow the ipsilateral craniocaudal volume-dependent  LA spreap = 0.0001). Macaire et al. used a before-and-after design to show that in open CS a preemptive strategy with bilateral ESPB catheters is associated with reduced intra- and postoperative opioid consumption. Consequently, several ERAS endpoints were favorably altered, including postoperative adverse events  and times to chest tube removal and first mobilization. The authors found no differences in extubation time and pain during the first mobilization. Another RCT showed comparable postoperative pain scores between bilateral continuous ESPB and TEA in 50 patients undergoing open CS [Krishna et al. compared bilateral single-shot ESPB with control  in CS with sternotomy and found reduced postoperative pain, time to extubation, time to ambulation, opioid usage and total length of intensive care unit (ICU) stay . Interes open CS . Finally open CS  given th open CS . This du open CS . These fAlthough promising, results from these clinical studies are not generalizable. There is a potential bias concerning the small patient populations, blinding and randomization. Further studies are mandated to fully understand the benefits and extent of incorporating ESPB into routine clinical practice.Scanning starts with the linear-array transducer set 5–6 cm away from the dorsal midline in a parasagittal orientation. The ribs are then displayed as rounded acoustic shadows with an interceding hyperechoic pleural line see A. SlidinAnterolateral CWFPB provide ipsilateral somatic anesthesia of the upper anterolateral hemithorax but may spare the anterior branches of the intercostal nerves and hence do not consistently provide anesthetic coverage to the ipsilateral parasternal region . This thA 40-patient RCT compared PECS II with no block as part of a postoperative MA strategy in patients undergoing CS with sternotomy. PECS group patients were extubated earlier, had lower pain scores and fewer episodes of rescue analgesia .SAPB was studied in minimally invasive heart valve surgery (MIHVS) with right thoracotomy and minimally invasive direct coronary artery bypass (MIDCAB) with left thoracotomy. Berthoud et al. compared postoperative single-shot deep SAPB to continuous wound infiltration (CWI) and reported significantly lower morphine consumption, reduced length of ICU stay and improved pain control during the first 48 h following MIHVS . AnotherAnterolateral CWFPB have an excellent safety profile that will allow their ongoing integration in cardiac ERAS pathways. Their impact relies markedly on adequate timing  and indication.PECS I targets the lateral (C5–C7) and medial (C8–T1) pectoral nerves travelling within the fascial plane between the pectoralis minor and major muscles. SAPB targets the plane either above or below the serratus anterior muscle (SAM). Although some authors favor the latter , the difThese blocks complement the anterolateral CWFPB by providing anesthesia confined to the parasternal region . DependiBoth parasternal variants have been evaluated in CS with sternotomy. Two small RCTs looked at bilateral single-shot PIFB as part of a postoperative MA regimen. Adverse effects were not recorded, and pain scores were significantly reduced in both trials ,74. TherPreemptive single-shot bilateral TTMPB was compared with placebo in an RCT of 48 adult patients undergoing CS with median sternotomy. Several ERAS-specific outcomes were significantly improved, including first 24 h opioid requirement, rescue analgesia, pain scores, and ICU discharge time . SimilarThe linear-array probe is placed in the parasagittal plane, 1 cm lateral from sternum’s edge in the fourth or fifth intercostal space see . StructuLM is highly probable, especially with continuous catheter infusions [US-assistance has dramatically increased the safety and efficiency of RA techniques resulting in improved outcomes. Reports of complications are scarce and unsystematic. Although local anesthetic systemic toxicity (LAST) is virtually a shared complication of all blocks, it may be more often reported with blocks performed in highly vascular compartments. That was the case with PVB in a case series of eight patients undergoing coronary artery bypass grafting (CABG), where potentially toxic ropivacaine concentrations were reportedly common . Of notenfusions . Such finfusions .Sympathectomy varies in extent and intensity and is common with posterior nerve blocks, mostly bilateral PVB. Compared to PVB, posterior CWFPB seem less associated with hypotension and bradycardia , probablPerformance of PVB and CWFPB can, in theory, result in iatrogenic pneumothorax. Nevertheless, the incidence of this will remain undefined given that chest tubes are invariably present in CS with median sternotomy.Although PVB are formally contraindicated with CPB anticoagulation regimens, the same recommendations may not apply to the more superficial CWFPB. To date, there are no reported hemorrhagic complications after any of the CWFPB, with anecdotal evidence supporting their use in contexts otherwise prohibitive for classical neuraxial techniques .The best way to provide RA as part of cardiac ERAS strategies has become a topic of considerable interest. Future trials are needed to compare currently available USRA techniques , establish the optimum time to start the nervous blockade  and understand the role of various perineural adjuvants. This last issue could have momentous consequences as it may enable prolonged duration of single-injection nerve blocks and circumvent the use of catheters . CatheteMonitoring regional blockade can be difficult under general anesthesia. With conscious, awake patients, preemptive blockades could be assessed by sensory testing , but this would delay the operation by at least twenty minutes. Intraoperative nociception monitors could help run an individualized and precise opioid-sparing strategy starting with induction. One trial is currently underway to evaluate the efficacy of ESPB on perioperative opioid consumption in CS with sternotomy during goal-directed anti-nociception using the Nociception Level (NOL) index (NCT04338984).USRA favors improved outcomes coupled with an excellent safety profile and has gained considerable momentum in fast-track cardiac surgery over the last decade. Young adults  undergoing elective cardiac surgeries with relatively short aortic cross clamp times seem to derive the greatest benefits, including opioid sparing, reduced time to extubation, earlier mobilization and improved perioperative pain control. Upcoming trials are expected to provide the missing links needed to standardize the integration of RA in cardiac ERAS pathways. Until such time, USRA remains a valuable adjunct in cardiac perioperative care that calls for a personalized application encompassing both anesthesiologist’s expertise and patient’s characteristics.


After 24 h, they required less ibuprofen  and paracetamol . Mean pain according to VAS or FPS-r at 24 h was 3.1 with hypnosis vs. 4.3 with distraction (p < 0.001). Overall satisfaction was higher in the hypnosis group . Conclusions: Hypnoanalgesia in children undergoing dermatological outpatient surgery could not only reduce sedation and analgesia requirements, but also improve child and guardian(s) satisfaction.Background and objective. Stress in surgical settings has subtle psychological and physiological repercussions in children. The objective is to evaluate whether hypnosedation is effective in reducing the doses of sedation and analgesia required during the periprocedural period in children undergoing dermatological surgery, without negatively affecting pain and satisfaction. Patients and methods: A prospective, longitudinal, observational study where paediatric patients (aged 5–16 years) scheduled for dermatological surgery were analysed according to whether they received hypnosis or distraction during surgery (both common procedures at the centre). As outcome measurements we used sedation doses (propofol) during surgery and the need for analgesia; pain assessment post-surgery and at 24 h using a visual analogue scale (VAS) or revised face pain scale (FPS-r) (both 0–10) depending on age, as well as patient and guardian satisfaction . Results: Of the 68 patients eligible during the follow-up period, 65 were included. Of these, 33 were treated with hypnosis and 32 with distraction. Children who underwent hypnosis required less total propofol (45.5 ± 11.8 mg vs. 69.3 ± 16.8 mg;  The diagnostic and therapeutic procedures involved in a child’s hospitalisation create fear and anxiety, and may lead to adverse changes in the child’s behaviour, which sometimes continue in the postoperative period ,2. ThereThe use of pharmacological interventions, such as benzodiazepines or midazolam, seeks to reduce preoperative anxiety in children. However, this may be associated with undesirable effects, such as paradoxical reactions, prolonged sedation and adverse changes in behaviour ,4,5.Some non-pharmacological techniques encourage the patient’s attention to be directed away from anxiogenic stimuli and towards a ‘safe place’ . These tMost high-quality studies on pain and hypnosis have been conducted in adults. Studies on pain and hypnosis, such as Thompson et al. , demonstFurthermore, hypnosis during anaesthesia has been shown to help reduce analgesic and sedative doses during and post-surgery, thereby facilitating recovery . This isA prospective, longitudinal, observational study on the comparative effectiveness of interventions, in this case sedation, was conducted. The observation period covered the surgical procedure, immediate postoperative period and 24 h following surgery. The study was approved by the Clinical Research Ethics Committee at the Complejo Hospitalario de Toledo [Toledo Hospital Complex] and was carried out in accordance with the WHO code of ethics (Declaration of Helsinki) on human experimentation.This study followed STROBE recommendations, as shown in Children scheduled for outpatient dermatological surgery at Centro Nacional de Parapléjicos [National Paraplegic Centre] in order to perform a diagnostic or therapeutic biopsy, exeresis of benign and malignant lesions and the infusion of the botulinum toxin were selected based on the following inclusion criteria:(1) having been classified as anaesthetic risk class I or II according to the American Society of Anaesthesiologists (ASA); (2) being in a height and weight percentile between P3 and P97; (3) having no known drug allergies; (4) fasting for 6 h (solids) and 2 h (liquids); and (5) having Spanish as their mother tongue. Those with: a diagnosed intellectual disability, attention deficit disorder, behavioural disorders, previous treatment with hypnosis, a history of neurological pathology or psychomotor delays, previous painful pathology and obstructive sleep apnoea (OSA) were excluded from the study.The exclusion of patients was carried out bearing in mind that children suffering from an attention deficit disorder are incapable of selecting and concentrating on the relevant stimuli, those with prior pain or neurological disorders could disrupt the use of low doses of sedatives, those who have previously received hypnosis could have a preconceived idea; the obese could disrupt the distribution of propofol and moderate-severe asthmatics might need additional medication and present respiratory complications.Recruitment was undertaken by the main researcher based on the surgery waiting list over a three-year period (November 2016 to November 2019). All patients who met the inclusion criteria received an informed consent form together with an information sheet on both the anaesthetic procedure and hypnosis as an adjuvant treatment technique.I Preoperative: recruitment of patients: II Intraoperative: depending on the day with hypnosis (intervention), the day with no hypnosis (attention distraction techniques), application in both arms of induction and maintenance anaesthesia by means of intravenous and/or inhalation agents or local anaesthetic and elimination; awakening (no hypnosis)/return to normal alertness (hypnosis) III. PACU control of vital signs and pain. IV Postoperative monitoring 24 h: pain control.® anaesthetic cream on the back of both hands at least 60 min before peripheral venous cannulation.On the day of the intervention, the children were in the pre-operative room where we interacted with them to learn about their sensory capabilities, reduce anxiety and fear, and initiate the hypnosis technique with focus of attention consistent with the child’s preferences and appropriate to the neurocognitive level or focus of attention on images or music with the digital tablet. At that time, we gave the children fruit-scented markers to colour the anaesthetic face mask inside and out, in addition to applying EMLAIn the hypnosis group, we used suggestion through metaphor that relies on the child’s imaginary thinking to change their perception. This is an excellent moment to use the expression “as if” within the imaginary world of the metaphor. In order to explain the therapeutic act to a seven-year-old child, we could say, for example, that we are going to use a “magic or special mask”, through which the scent of mint, apple or strawberry will enter the airway as if they were sweets that make you laugh while you travel to the moon.Besides facilitating the emergence of hypnosis in the patient, this process enables the child to participate in the surgery. Following standard sedation, therapeutic suggestions are maintained throughout the surgical procedure and the posthypnotic period before returning the patient to the alert state of anaesthesia.The distraction technique used was a digital tablet, on which a cartoon or a music video was passively played as chosen by the child. As with hypnosis, it was maintained throughout the perioperative process, until post-anaesthesia awakening.In the pre-anaesthetic consultation, a therapeutic relationship was established with all children, regardless of the group. This was done by letting them choose their favourite experience of therapeutic suggestion, according to age, preference, and level of cognitive maturation. Furthermore, behavioural interventions were carried out with patients and guardians to reduce the anxiety and fear associated with the procedure, and eliminate any negative connotations associated with medical hypnosis. We explained to the child and guardians that the objective of these interventions was to reactivate the patient’s resources as a method of innate adaptation, creating a “safe place” in the surgical environment. In the case of hypnosis, we used the child’s visual, aural, kinaesthetic, olfactory and gustatory sensorial realities to create this “safe place”, which also helped them to concentrate on their interior world, their imaginary world which becomes their virtual reality. We must observe what the child’s main, predominant sensorial channel is, thus giving us a natural vision of how they perceive reality. The clinician who carries out the hypnosis will accompany the patient using obvious and trivial phrases (truisms), talking in a calm tone and rhythm of voice. In this way the patient shares their same reality and feels orientated in the “here and now”, in order to achieve their medical care objective. The patient’s autonomy is respected throughout the whole process. In essence, hypnosis is a type of therapeutic communication which improves adherence to medical care. When using the distraction technique by means of a digital tablet, it will be the child who chooses their distraction, which may be visual and/or aural and, once the tablet has been handed over, the procedure will be passive.(1)Anaesthetic InductionOnce the patient was in the operating theatre, they were monitored as per the Spanish Anaesthesia and Reanimation Society (SEDAR) for this procedure and ASA state, regardless of the technique used to focus attention, i.e., hypnosis or no hypnosis (distraction technique).® paediatric external circuit was used for inhalation of this mixture connected to the MaquetFlow-i C20 anaesthesia machine and a scented face mask , which had to be maintained throughout a 3-min induction period prior to any intervention. This mask was connected to a 1 L reservoir bag with a pressure limiting valve (APL) enabling extraction of exhaled anaesthetic gases via the scavenging system. Fresh gas flow is 8 to 10 L as per the patient’s weight i.e., equal to 2–3 times their volume/minute, essential to prevent re-inhalation in Mapleson® circuits. This system maintains spontaneous breathing throughout the procedure. Had the child not wanted inhalational anaesthetic induction, we would have used the local anaesthesia provided by the EMLA cream.The child was allowed to choose between inhalational induction of a nitrous oxide and oxygen mixture (60%/40%) and intravenous induction. All but three children chose inhalational induction. A MaplesonDuring inhalational or intravenous anaesthetic induction, only one person should interact with the child verbally, rather than the entire team, to prevent attention dispersion in both the distraction and hypnosis technique groups.Once the peripheral venous cannula had been inserted and fluid-therapy commenced with Ringer’s lactate, standard intravenous induction was started with propofol at 1.5 mg/kg. Next, the surgeon injected 2% lidocaine local anaesthetic subcutaneously, followed by surgical incision and subsequent extraction of the skin lesion, haemostasis and suture.(2)MaintenanceInhalation of the nitrous oxygen/oxygen mixture was maintained throughout the intervention, and the patient was told to just breathe normally.An additional 1.5 mg/kg propofol was administered based on vital signs during surgery which might lead to activation of the autonomous nervous system in response to a sympathetic nociceptive stimulation as a primary indicator of a second dose of propofol being required; moreover, if pain control was insufficient, short-acting opioids (Alfentanil 10–20 mcg/kg) were administered until stabilisation of vital parameters.(3)EliminationThe nitrous oxide concentration is reduced by 25% near the end of the procedure to prevent nausea and vomiting. The patient wakes up in the operating theatre after surgery and gradually returns to a state of alertness when they are moved to the PACU (post-anaesthesia care unit).The mean duration of the surgical interventions was 30–40 min.The PACU not only controls the patient’s vital signs but also assesses pain using adapted scales (see variables and measurements below), and analgesia was administered where necessary. Paracetamol, magnesium metamizole or intravenous tramadol were used.The nurse monitoring the amount of drugs administered in both groups as per adapted pain scale assessment performed the 24 h post-operation check. Paracetamol and ibuprofen were administered orally.The primary endpoint of the study was the total propofol dose (mg) and additional opioid requirement during surgery, measured in mg/kg body weight, as recorded intraoperatively.Furthermore, the impact on pain and analgesic needs were compiled, both in the immediate postoperative period and 24 h post-surgery. These were measured using pain scales adapted to age and cognitive maturation, in this case the visual analogue scale (VAS) from age 10 and revised face pain scale (FPS-r) from five to 9 years , as well as the need for paracetamol, ibuprofen or other analgesic. The scales were given to the children by the head PARU nurse, who was also responsible for the 24-h post-surgery telephone follow-up, and was unaware of the group to which each patient belonged. Analgesic need was recorded in the patient’s history.Prior to discharge, the child and their guardian(s) were given a satisfaction questionnaire on the overall care provided by the healthcare staff during the outpatient paediatric dermatological procedure, with six questions on a Likert scale (1–4) and an overall satisfaction scale (0–10).For the descriptive analysis, mean and standard deviation were used for quantitative variables, and frequency tables (percentage distribution) were used for qualitative variables. The outcome measurements for the intervention control groups were compared using parametric tests for variables with a normal distribution, chi-square or Fisher’s exact test for qualitative variables, depending on the number of cases, and Student’s t-test for quantitative variables. The Mann-Whitney U test was used for quantitative variables that do not follow a normal distribution.p < 0.05 and analysis was carried out with Stata 12.1 .The significance level was set at a value of A total of 68 children were recruited between November 2016 and November 2019. 65 of these children met the selection criteria and were included in the study, while three patients were excluded from the total, two due to obesity and one due to asthma. All patients who were included completed the study .Indications for surgery were: nevus (n = 35), local neoplasms (n = 6), and other lesions (n = 24). Ages ranged from five to 16 years, with 50% aged eight or younger. All weighed 22 kg or more. No significant differences in baseline patient characteristics were observed between the two study groups .p < 0.001) in both cases. In addition to propofol, three patients (5%) required alfentanil on one occasion in the control group (3%) and two children in the hypnosis group (6%). The difference in proportions was not statistically significant.During surgery, a significant reduction of the intraoperative propofol dose is shown both in absolute value (24 mg less on average) as well as per kg of body weight (0.8 mg/kg less) in the hypnosis group, meaning it achieved statistical significance (p = 0.039). Regarding the drugs used, both paracetamol and metamizole magnesium were administered; only one child required tramadol (in the distraction group). Nevertheless, immediate postoperative pain measured by VAS or FPS-r was similar in both groups.During the stay in the PARU, which was statistically shorter for children in the hypnosis group, 45 children (69%) required some analgesic. The overall need was lower in the hypnosis group .However, during the stay in the PARU, nine children (28%) in the distraction group and two (6%) in the hypnosis group required antiemetics (p = 0.05) generally and statistically different in favour of the hypnosis group in terms of paracetamol or ibuprofen use. The total score on the surgical procedure satisfaction questionnaires did not differ between groups  nevertheless, the overall scale favoured the hypnosis group (p < 0.01)41 children (63%) required analgesia in the 24 h following surgery. This requirement was 25% lower in the hypnosis group  was also shown to be effective for anxiety and pain with regard to invasive procedures in children . As an iThe dimensions of the real and virtual worlds are present in hypnosis. The child focuses their attention on what interests them in such a way that the suggestion hinges on the imaginary thoughts of the child, and their imaginary world fluidly becomes their virtual reality . The spoAs opposed to hypnosis, distraction techniques, whether they be active or passive, focus the attention, in this case, on images or music on the tablet. In the case of medical care, this attention is not maintained in the same way over time and there is no permanent doctor-patient relationship. Unlike the accompaniment carried out during hypnosis, it does not use the patient’s resources and the cerebral areas implicated in the brain areas involved in neuromatrix pain.Focusing solely on dermatology helped us to eliminate the methodological ‘noise’ of procedures, complications, the surgeon and technique. The surgical procedure corresponded to moderate pain, and preventive analgesia was used in both groups during the peri-procedure as were non-pharmacological techniques. Studies by Talour et al.  and JonePain is more complex than simply a stimulus-response action. In the surgical process, we must consider the A delta fibres responsible for acute pain, and the C fibres, which are slow-conduction, non-myelinated nerve fibres. These fibres initially transmit pain, while cognitive and emotional aspects are involved in producing the painful sensation. The painful experience is initiated and maintained in specific brain structures, and its final outcome is determined by memory, cognitive state and emotional situation, hence the importance of acting on this sensory and emotional dimension. Initial studies by Faymonville et al. and more recent controlled studies in invasive procedures in adults  have demHypnosis is developed as a process that takes place in different stages, and begins with inviting the patient to a new experience, followed by the disassociation of consciousness where a change occurs in the patient’s perception, and ending with a return to their usual state of alertness.The hypnotic state is a natural one  which a clinician using hypnosis can facilitate via suggestion. It draws on the patient’s resources and specific needs to encourage a change in perception. Hypnosis involves a change in the child’s perception until they return to their normal alert state. The hypnotic trance, which can be achieved immediately or within minutes, depends on the suggestibility of the individual, the clinician’s hypnosis skills, and the context . In receHowever, comprehensive therapies do not necessarily work the same way in adults and children, likely due both to developmental effects as well as pharmacokinetic and pharmacodynamic differences. Based on these differences, we prioritised the use of short-acting drugs with a dissociative  and analThe limitations of this study are those inherent to the hypnosis process; the patient’s collaboration is required, given that they are autonomous. We would have preferred to have conducted a clinical trial; however, as already mentioned, group assignation was quasi-randomised. Another study limitation was the fact that only one anaesthetist was in charge of both hypnosis and medication, but the hospital would not allow two anaesthetists to be involved. On the other hand, the sedation and analgesic protocol is very strict and the whole team was careful to avoid any deviation.This study and the conclusions drawn from it would benefit from replication, which we hope others will undertake.The use of hypnoanalgesia in paediatric outpatient surgical settings improves perioperative pain perception, decreases drug consumption, decreases recovery time and increases patient responsiveness, resulting in less physiological stress and greater patient satisfaction.


The effects differed significantly (p < 0.001) among the groups . The mean improvement  at the endpoint was 86.8% for trigeminal neuralgia, 80.8% for myofascial pain, and 75.4% for oromandibular dystonia. Injection of the botulinum toxin can be a highly effective and safe method to treat trigeminal neuralgia, myofascial pain, and oromandibular dystonia.The differences in analgesic effects of botulinum toxin type A were compared in 28 patients with trigeminal neuralgia, 53 patients with myofascial temporomandibular disorders, and 89 patients with the jaw closing oromandibular dystonia. The patients were treated by injection of botulinum toxin type A into the masseter, temporalis, medial pterygoid, and other muscles based on the symptoms of each patient. The pain severity was evaluated using the visual analog scale, pain frequency, and pain scale of the oromandibular dystonia rating scale. Botulinum toxin injection was performed 1068 times in all patients without significant adverse effects. The visual analog, pain frequency, and pain scales at baseline were reduced ( Clostridium botulinum [The botulinum toxin, which can exert a paralytic effect by binding to presynaptic cholinergic nerve terminals at the neuromuscular junction, is produced by the Gram-positive, rod-shaped, spore-forming, anaerobic bacterium otulinum . It inteotulinum ,3,4,5. Totulinum ,10,11,12otulinum ,18,19,20otulinum ,29,30,31otulinum ,33,34. Hotulinum ,26,29,31Trigeminal neuralgia (TN) is characterized by sudden, unilateral, electric shock-like pain that is limited to the distribution of one or more divisions of the trigeminal nerve . SeveralTemporomandibular disorders (TMDs) are a heterogeneous group of chronic pain conditions that affect the temporomandibular joint, masticatory muscles, and related structures. Despite the inconsistency of published data concerning the application of persistent myofascial pain with BoNT/A ,29,30,31Dystonia is a movement disorder characterized by sustained, intermittent, or task-specific muscle contractions that result in abnormal repetitive movements and/or postures . Oromandp < 0.001) and OMD . Patients with OMD were significantly (p < 0.003) older than those with myofascial TMD  showed bilateral symptoms, while 11 patients (20.8%) had unilateral symptoms. Symptomatic muscles included the masseter, temporalis, medial pterygoid, lateral pterygoid, posterior belly of the digastric, and sternocleidomastoid muscles.Eighty-one patients with OMD (91.0%) showed bilateral symptoms, while eight patients (9.0%) had unilateral symptoms.Symptomatic muscles included the masseter, temporalis, medial pterygoid, lateral pterygoid, orbicularis oris, posterior belly of digastric, sternocleidomastoid, risorius, mentalis, genioglossus, platysma, anterior belly of digastric, depressor anguli, trapezius, and zygomatic major muscles.p < 0.001) in patients without psychiatric treatment  than with it . A significant (p < 0.005) negative correlation (−0.238) was observed between the number of injected sites and improvement of the visual analog scale at the endpoint. The pain frequency (p = 0.155) and pain scales of the oromandibular dystonia rating scale (0.244) showed no significant correlations. The mean follow-up duration was 24.2 ± 9.1 months.BoNT/A  injections were performed 1068 times for all patients. Adverse effects included tenderness and pain at the injection site and temporary muscle weakness after BoNT/A injection. These side effects disappeared spontaneously, and no major side effects were observed. The results of the visual analog scale, pain frequency, and pain scale of the oromandibular dystonia rating scale at baseline the after lidocaine and BoNT/A injections are summarized in p < 0.001) after the lidocaine injection, at two, four, eight, and 12 weeks after the first botulinum toxin therapy, and at the endpoint (p < 0.001) higher in TN (89.3 ± 7.5) than in TMD (70.2 ± 19.3) and OMD (70.3 ± 19.1) patients . A post hoc test was performed at each follow-up. Significant differences are shown in The visual analog scale at baseline was reduced (endpoint . The vispatients . Therefop < 0.001) after lidocaine injection, two, four, eight, and 12 weeks after the first botulinum toxin therapy, and at the endpoint (p < 0.005) and OMD . The Greenhouse–Geisser correction was performed to adjust for the lack of sphericity. The effects were significantly different among the groups . The significant differences analyzed by the post hoc test are shown in The pain frequency at baseline was reduced (endpoint . The paip < 0.001) after the lidocaine injection, two, four, eight, and 12 weeks after the first botulinum toxin therapy, and at the endpoint (p < 0.001) higher in TN (28.6 ± 3.6) than in TMD (21.6 ± 7.5) and OMD (20.3 ± 7.4). After the Greenhouse–Geisser correction, the effects were significantly different among the groups . Significant differences are shown in The pain scale at baseline was reduced (endpoint . The paip < 0.05) higher in patients injected using the CAD/CAM needle guide  than in those that were not .In 16 patients with third-division TN, BoNT/A was injected submucosally or subcutaneously into the trigger zone. Twelve patients with second-division TN required sphenopalatine block using a customized computer-aided design/computer-aided manufacturing (CAD/CAM)-derived needle guide . BoNT/A BoNT/A was injected a total of 195 times  without any adverse effects. The average dose per injection into the muscles was 56.3 ± 7.2 units. The injected jaw-closing muscles were the masseter (92.5%), temporalis (58.5%), and medial pterygoid (32%) muscles. Other injected muscles included the lateral pterygoid (30.2%), posterior belly of the digastric (24.5%), and sternocleidomastoid muscles (18.9%).BoNT/A was injected a total of 737 times  without any significant complications. The average dose per injection into the muscles was 58.2 ± 6.7 units. Injected muscles were the masseter, temporalis, and medial pterygoid, each at 85.4%, 52.8%, and 10.1%, respectively. Other injected muscles were the lateral pterygoid (18%), orbicularis oris (6.7%), posterior belly of digastric (6.7%), sternocleidomastoid (5.6%), risorius (4.5%), mentalis (4.5%), genioglossus (4.5%), platysma (3.4%), anterior belly of digastric (2.2%), depressor anguli (1.1%), trapezius (1.1%), and zygomatic major (1.1%) muscles.The present study is the first to compare the differences in analgesic effects of BoNT/A on pain among TN, myofascial TMD, and OMD subjects.The botulinum toxin has been studied as a promising option for the treatment of various types of pain ,33,34. TN-ethylmaleimide-sensitive factor attachment protein receptor proteins . BoNT/A binds to the membrane and a receptor at the neuromuscular junction, followed by internalization into endosomes. Subsequently, the light chain translocates across the membrane into the cytosol. The light chain cleaves synaptosomal-associated protein-25, which inhibits acetylcholine release at the motor endplate.Synaptic vesicles, which contain neurotransmitters, dock and fuse with the plasma membrane through interactions with soluble Animal studies have proven that subcutaneous BoNT/A inhibits formalin-induced pain by preventing the release of inflammatory mediators such as glutamate, substance P, and calcitonin gene-related peptides from nociceptive nerve endings ,45. BoNTThis study had several limitations. In it the retrospective results of botulinum toxin therapy for pain were compared among the three groups. No control group was set up for ethical reasons. The author has launched a website on involuntary movements of the stomatognathic system . Many paThe difficulty in objectively assessing pain has already been discussed ,49. ManyIn this study, the results were compared at baseline and after lidocaine and BoNT/A administration. Before botulinum toxin therapy, local anesthetic was injected into the muscles, which are postulated to be the cause of pain or involuntary movements. The procedure can help to predict the effect of the botulinum toxin therapy and whether the muscles are the cause of patients’ symptoms. If the symptoms disappear, even if only during the anesthetic effect, the injected muscles must be the cause of the symptoms, and botulinum toxin will help . On the Women were more prevalent than men in all three types of diseases analyzed in this study. However, the age of onset was the youngest in the TMD group and the highest in the TN group. In other words, TMD is more common in individuals in their 20s and 30s, OMD is normally observed in those in their 50s and older, and TN is seen in those in their 60s and older. In this study, patients with TMD were older than the average age of patients with general TMD because other conservative therapies have been ineffective for many years. However, there was a significant age difference among the three groups .Local injections of lidocaine and ethanol can block afferents in the muscle spindle. Muscle afferent block therapy was used effectively in patients with OMD and masticatory muscle spasms ,51,52. CTN pain can occur after stimulation of the trigger zone. Although TN is most commonly related to microvascular compression, the pathophysiological mechanism underlying its development is not fully understood . PharmacThe most common symptom in TMD is masticatory myofascial pain, which often refers to pain in the neck, face, or preauricular regions. It is often accompanied by headaches and limited mouth opening. This disorder has a complex pathogenesis and is expressed as a multifactorial etiology, as well as with various systemic and local risk factors . A multiBoNT/A may have an analgesic effect which is independent of its muscle-relaxing effects, because pain reduction can precede muscle relaxation and last for a longer period, and it is also present outside injected sites. In a recent randomized clinical trial, BoNT/A revealed almost the same effect on myofascial pain as an occlusal splint . Taking Dystonia is manifested by sustained, intermittent muscle, or task-specific contractions that cause abnormal movements or postures . OMD is Patients with OMD have very variable symptoms from patient to patient, such as masticatory disturbance, dysarthria, dysphasia, pain, and esthetic problems. In this study, task-specificity was observed in 49.4% of the patients, and muscle hyperactivity was observed only during specific tasks. Pain is not always the chief complaint in patients with OMD. Patients without complaints of pain were excluded from the study. Recently, the OMDRS has been developed and validated . It can p < 0.005) negative correlation (−0.238) was observed between the number of injected sites and improvement of the visual analog scale at the endpoint. Furthermore, in 12 patients, the author used a customized CAD/CAM-derived needle guide during the injection of BoNT/A to the sphenopalatine ganglion for the treatment of second-division TN [BoNT/A has two main effects. The first is muscle relaxation, and the other is pain relief. In TMD, hyperactive masticatory muscles often result in pain in the muscles or temporomandibular joints. Patients with arthrogenous pain were excluded from the study. In OMD, dystonic contraction in the muscles of the stomatognathic system can result in pain. In the present study, only the jaw closing type of patients was analyzed to compare the results with those of patients with TMD. Based on the two effects of BoNT/A, it may be reasonable to consider that BoNT/A is more effective in patients with TMD or OMD than in those with TN. However, the results were contrary. Although the reason for the results is uncertain, a possible explanation might be more limited injection sites in TN than in TMD or OMD. The patients with TN in this study were unilateral, except for one patient. Only one case had symptoms in the second and third divisions of the trigeminal nerve. One 50-unit vial of BoNT/A was sufficient in all cases. Compared to the myofascial TMD and OMD groups, a sufficient amount of BoNT/A can be injected into the localized area. Indeed, a significant  are summarized in Twenty-eight patients  with classical TN based on the beta version of the third edition of the International Classification of Headache Disorders  were enrTMD involves a number of clinical conditions of the temporomandibular joint, masticatory muscles, and related structures. TMD was diagnosed based on the diagnostic criteria for TMD (DC/TMD) . Fifty-tOMD was diagnosed according to the characteristic clinical features of focal dystonia and electromyographic findings ,38,75. TThe patients received an explanation of the treatment plan and provided written informed consent. This study was performed in accordance with the Declaration of Helsinki after obtaining approval from the institutional review board and ethics committee of the Kyoto Medical Center (15-031).Before the BoNT/A was injected, 3–5 mL of 0.5% lidocaine  was injected into the hyperactive or painful muscles in patients with TMD and OMD and into trigger points in patients with TN. Changes in pain and involuntary movements were carefully observed after the lidocaine injection. If the patients showed changes at all, no BoNT/A injections were administered. If the patients showed improvement of symptoms under the effects of the local anesthetic, we made their next appointments for the BoNT/A injections. Some patients claimed exacerbation of pain at the injection site after the lidocaine injection, which may be related to the injection itself. Pain was evaluated during the next visit.BoNT/A was reconstituted with isotonic sodium chloride solution to reach a concentration of 2.5 to 5 units/0.1 mL. A disposable hypodermic needle electrode  was inserted into the target muscles ,11,12. TFor patients with third-division TN, BoNT/A was injected submucosally or subcutaneously into the trigger zone. A CAD/CAM-derived injection guide was used for patients with second-division TN . The guiFor patients with TMD and OMD, the author administered 50 units of BoNT/A that were reconstituted with 1–2 mL of isotonic sodium chloride solution into the masseter, temporal, and medial pterygoid muscles ,12 basedPain severity was evaluated using the visual analog scale, pain frequency, and OMDRS . The vist-test was used. Differences among the three groups were statistically compared using one-way analysis of variance. Fisher’s exact test and unpaired t-tests were applied to assess the statistical significance of the differences in the distributions. All analyses were conducted using the statistical software package SPSS for Windows . The null hypothesis was rejected at the 5% level (p < 0.05). Improvements and changes in the visual analog scale, pain frequency, and pain scales of the OMDRS were statistically analyzed with 2-way repeated measures analysis of variance (ANOVA) with the groups  and times  as factors. When the sphericity was significant, the Greenhouse–Geisser correction was used to adjust for the lack of sphericity in the repeated measure ANOVA. The Bonferroni method was used as a post-hoc test when the ANOVA revealed significant differences.A two-tailed paired


Oral mucositis (OM) associated with cancer treatment not only impairs patients’ quality of life but also causes treatment delays or changes. This prospective exploratory study was conducted to evaluate the efficacy of Episil® oral liquid, which is an approved protective formulation for the oral mucosa in patients with OM. The extent of the pain-relieving effect, feeling during use, and adverse events or problems were evaluated.In total, 10 Japanese cancer patients with OM receiving chemotherapy, pretreatment therapy for hematopoietic stem cell transplantation, or radiation therapy for head and neck cancer were enrolled.p = 0.264). A significant decrease was observed in the pain score after using Episil® compared with that before using Episil®, and this effect lasted up to 120 min. The protective effects of Episil® were observed 3–5 min after application. Some patients felt slight soreness or discomfort when applying Episil®. However, this discomfort due to Episil®’s stimulation was within the allowable range and transient. No adverse events were observed in any of the cases.A numerical rating scale (NRS) was used to assess oral pain intensity due to OM. Compared to baseline, the mean NRS began to decrease at 5 min after using Episil® .University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) ( Oral mucositis (OM) is a debilitating side effect frequently observed in patients undergoing high-dose chemotherapy, pretreatment therapy for stem cell transplantation, or in patients with head and neck malignancies undergoing radiation therapy , 2. OM cThe management of OM during cancer treatment is difficult. Although the Multinational Association of Supportive Care in Cancer , NationaOne of the most important strategies in managing OM is reducing oral pain. Unrelenting oral pain due to severe OM causes subsequent inability to eat and drink, leading to secondary malnutrition and dehydration. Prolonging this condition makes patients’ performance status poorer and potentially interrupts cancer treatments , 11, 12.Some coating agents have been designed to form oral mucosal barriers that reduce irritation and OM pain. Various agents, such as viscous liquid mucoadhesive hydrogels, have been suggested –15; howeThe European Oral Care in Cancer Group and the United Kingdom Oral Management in Cancer Group recommend Episil® for relieving OM pain.Although Episil® is highly likely to relieve the pain of mucositis, there are few reports of its use in Japanese patients with OM , and itsThis was a single-center, single-arm, open-label, prospective study. In total, 10 patients being treated at the National Cancer Center Hospital were enrolled from April 2, 2018, to April 25, 2018. Episil® was applied on the mucositis lesions of eligible patients. It comprises soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO), which are natural lipids, and contains no medicinal ingredients. The lipid components SPC and GDO self-assemble upon contact with moisture and form a thin bioadhesive liquid crystalline film. The film acts as a protective barrier and exerts a pain-relieving effect. It is an extremely simple device: a few drops of Episil®’s solution are dropped into the oral cavity  and subsequently spread over the affected area with the tongue or the finger. It reacts with water in the saliva and forms an adhesive protective film on the surface of the ulcer within minutes. It comprises soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO), which are natural lipids, and contains no medicinal ingredients. The lipid components SPC and GDO self-assemble upon contact with moisture and form a thin bioadhesive liquid crystalline film. The film acts as a protective barrier and exerts a pain-relieving effect. Data were collected on pain and other outcomes at baseline and 5, 30, 60, and 120 min after application. Similarly, data on adverse events were collected during Episil® use. This study was conducted in accordance with the Declaration of Helsinki, and the study protocol was reviewed and approved by the National Cancer Center Ethics Committee . Written informed consent was obtained from all individual participants included in the study.Eligibility criteria are summarized in Table The primary outcome of this study was the oral pain NRS score. Secondary outcomes included perception, oral-related functions and adverse events.Perception and oral-related functions were evaluated using the method used in the clinical study conducted by Camurus (HS-05–160 study). This questionnaire included nine questions. Seven questions were related to the feeling during use as follows: “ease of use of Episil®” ; “the feeling and comfort in the mouth when using Episil®” ; “the time Episil® takes to form a protective film” ; “changes in taste sensation” ; “stimulation of mucous membrane” ; “Uncomfortable feeling” ; and “acceptance and willingness to continue using Episil®” . The remaining two questions were about oral-related functions: “Speaking difficulties” and “eating difficulties” .Oral mucosal damage using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0 (diagnostic findings)  and adveEpisil® is in a special container with a pump. The pump was pressed three times to apply Episil® solution to the affected area of the oral cavity. After evaluating the efficacy profile over 120 min following the use of Episil®, continuous use of Episil® was allowed if the patient wished to continue, and the investigator considered it usable and necessary. The use of Episil® was limited to approximately 30 days from the start of its use or until one bottle was used up, whichever was shorter. Adverse events and problems were monitored throughout the period of use  that may affect the evaluation of oral pain, only regular use of the same dose and frequency, as in the previous study enrollment, was allowed on the first day of using Episil®. If unbearable oral pain developed and the daily doses of these drugs were increased on the day of using Episil®, they were considered rescue treatments.The oral pain NRS score was evaluated before applying Episil® (baseline), and 5, 30, 60, and 120 min after application. The feeling during use was evaluated 5, 30, 60, and 120 min after applying Episil®. Speaking and eating difficulties were evaluated before Episil® application and 120 min after application. The time until Episil® formed a protective film was evaluated at 1 to 5 min or more after the application of Episil®. Ease of use of Episil® and feeling and comfort in the mouth were evaluated 5 min after Episil® application. Furthermore, 120 min after the application of Episil®, patients were asked whether they wanted to use it repeatedly. Adverse events were evaluated throughout the period of the patients’ use of Episil®. These are summarized in Fig. p ≤ 0.05 were considered statistically significant. Statistical analyses were performed using GraphPad Prism software  and BellCurve for Excel .Data are represented as mean ± standard deviation for continuous variables or number (frequency) for categorical variables. Oral pain NRS was compared using Friedman’s test, followed by Dunn’s multiple comparisons test. Differences with a The patients’ characteristics are summarized in Table At baseline, nine patients had Grade 2, and one patient had Grade 3 OM according to the NCI-CTCAE Version3.0 . The details of concomitant analgesic use are shown in Table p = 0.264), 3.9 ± 1.920 at 10 min (p = 0.0036), 3.55 ± 1.795 (p = 0.0004) at 60 min, and 3.65 ± 1.844 at 120 min (p = 0.0009) after the application of Episil® , and 5-min (10%). , 60 min (90%), and 120 min (80%)  or device failures were observed in any of the cases. Patients’ free comments on the use of Episil®; 1)it will be easier to use in form of mist, 2)the bottle is small and easy to carry, 3)the nozzle is hard to push, 4)the nozzle is too short; hence, it is difficult to deliver the contents to the affected area, 5)there is dripping from the top of the nozzle; thus, it is difficult to use, 6)Immediately after application, there was irritation; however, after a while, I became accustomed to it, and the pain disappeared, 7)Pain relief duration was shorter than 8 h, and it became painful in about 5 h, 8)The gel is tattered in the mouth, 9)Effective when used early on before oral mucositis becomes severe, 10)There is a sense of incongruity in the oral cavity, and 11)Episil® tastes too sweet for me, and it is quite uncomfortable. Many comments contained suggestions for improvements of the Episil® device.The results of this study showed that Episil® is an effective device to relieve oral pain in Japanese patients with moderate to severe treatment-related OM, and its duration of action was determined to be long enough to support the patients’ oral intake. According to Hadjieva et al., who investigated the pain-relieving effect of Episil® in patients undergoing radiation therapy for head and neck cancer with OM, the mucositis pain score decreased rapidly 5 min after application, and this effect appeared to last for eight hours. It has been reported that even though the adhesive film gradually peels off over time due to abrasion, its effect is not totally diminished by a single meal . The preTo alleviate the pain of OM associated with cancer treatment, in clinical practice, systemic administration of analgesics  is prescribed according to the severity of the mucositis. Similarly, it has become common practice to apply a local anesthetic, such as lidocaine, directly to the pain site to reduce pain .However, there have been some challenges with the conventional methods for alleviating the pain associated with OM. Administration of systemic analgesics is good for controlling resting pain; however, it is less effective for contact pain or movement pain during eating and speaking. Moreover, the therapeutic effect following the intake of these analgesics can be delayed. In addition, systemic administration of analgesics has adverse effects, such as renal dysfunction, NSAID-induced gastric mucosal disorder, and constipation and nausea due to opioid use, which might negatively affect the performance of the cancer treatment itself , 20. The.Episil® has some major advantages as a pain relief formulation because, based on its mechanism of action, it does not elicit a pharmacological effect; rather, it simply offers physical wound protection. It is effective for breakthrough pain, such as contact pain during meals or talking, unlike systemic analgesics. Episil® neither causes discomfort nor disturbs the pleasure of eating, and its effect is immediate and persistent. Although systemic side effects and drug-drug interactions were not investigated in this study, Episil® does not contain any medicinal components; therefore, it is thought that there should be less concern about its side effects due to systemic interactions with other drugs. Thus, Episil® may safer as a supportive therapy during cancer treatment than other treatments, such as opioids or NSAIDsIn particular, Episil® may also be valuable in patients with mild OM who have not yet been treated aggressively. The active management of mild OM cases is sometimes difficult. Although the patients had a slight tingling sensation or discomfort in their mouth, making eating slightly more difficult, it was not as painful as when local anesthetics or systemic analgesics were used. Therefore, in many cases, only oral care and simple gargling or no treatment at all had been provided for mild OM patients. This suggests that Episil® could be a new formulation to facilitate eating and drinking without causing discomfort to such mild OM patients and contribute to improving their QOL during cancer treatment.The use of Episil® itself is simple, and its use relies on the patient’s self-management. Therefore, some precautions or considerations may be required for safer and more effective use. First, it takes little time for patients to gain experience in the use of Episil®. In the present study, the protective effects of Episil® were observed 3–5 min after its application. Thus, it seemed better to evaluate the effect after a while rather than immediately after application. Second, patients tended to apply more than the recommended quantities of Episil® into the oral cavity because it took some time for the effects of Episil® to manifest, and all patients wanted an immediate effect. However, excessive dosing may cause discomforts, such as nausea, vomiting, and even treatment interruption. Episil® is designed to drip enough to cover the entire oral cavity in a single press. The recommended dose is 1–3 pump strokes, starting with 1 pump stroke and applying more as needed. However, if the patient feels uncomfortable, it is important to limit the drip to approximately three times, even if they feel the drip is inadequate. Based on the recommended dosing, the patient should start with one pump stroke and apply more if needed. Third, some patients felt slight soreness or discomfort when applying Episil®. However, this slight soreness due to Episil®’s stimulation was usually within the allowable range and transient in nature. If patients feel strong stimulation after the application of Episil®, it can be managed by having the patients gargle with local anesthetics, such as lidocaine, before using Episil®. Fourth, Episil® should not simply be squirted, but also spread over painful mucous membranes using the optimal amount. Severe OM causes extensive and deep pain. It was difficult for most of the patients who cannot move their tongues because of severe OM to spread Episil® properly in their mouth. In such cases, it was necessary to spread the liquid using a safe alternative method, such as using a finger. In addition, severe OM disturbs proper oral cleaning and gargling, which causes the patient’s mouth to become filled with viscous, dirty saliva and results in worse oral hygiene. The viscous saliva in the mouth clings to the mucous membranes and prevents Episil® from effectively forming a protective film. In these patients who cannot receive proper oral cleaning and gargling, Episil® may not work effectively, and the patients may feel discomfort. In fact, they may feel strong discomfort. Thus, it is desirable to start Episil® at the stage of mild to moderate OM, before the symptoms become severe. Using Episil® at the early stage of OM, before severe OM occurs, makes it easier for patients to experience its actual efficacy. This may facilitate the patients’ continuous usage of Episil® effectively even if OM becomes more severe. Finally, an unhealthy oral cavity may cause local infections, increase the grade of OM, exacerbate pain, and prolong the time to heal. During immunosuppression by chemotherapy, local infections with OM cause a high risk of spreading and systemic infections, which is one of the major concerns. To control the risk of infection in the oral cavity, professional dental care should be provided by dental hygienists and dentists, and appropriate self-care instruction should be given. In the present study, all patients were provided with adequate basic oral care by a dental care team, and no patients developed oral infections during the study period. To safely use Episil®, it is important that professional dental care be continued to provide oral care to patients with OM.Although it was not a direct feeling during use, several patients reported that the pump of the container was difficult to push down firmly; therefore, it was difficult to dose/squirt the contents in their mouths. Patients with poor general conditions may have difficulty applying Episil® by themselves and may require the assistance of a healthcare professional, their family, or others.The study has several limitations. It was conducted as a preliminary study (the sample size was 10 casees), which makes difficult to indicate decisive conclusion. The modest sample size makes it difficult to draw decisive conclusions. This study doesn’t consider that the difference of the pathogenic mechanism of mucositis. Episil® has no medicinal properties and only physical protection of the ulcer, therefore we had thought that there was no difference in the effectiveness of Episil® depending on the pathogenic mechanism of mucositis. However, it cannot be denied that the effect of Episil® may differ depending on the pathophysiology of mucositis yet. In addition, the questionnaire used in this study was prepared with reference to the Camurus test (HS-05–160). As this test is not generally used in the clinical evaluation of OM, it is not easy to compare the results of this study to other studies previously reported. In assessing QOL in cancer patients, in particular, regarding the oral functions, a validated questionnaire on oral health may be more meaningful in further research.We did not aim to compare Episil® with other treatments in this study, and we were not be able to set up an appropriate control arm in this study because there was no device that protects the mucous membranes, such as Episil®, had been approved for use in Japan. Since the mechanism of action is completely different between Episil® and other treatments, a simple comparison may be difficult; however, it will be necessary to continue investigation, exploring the synergistic effect of combined use.Despite these limitations, Episil® seems to be effective in Japanese patients suffering from OM pain. Future research is warranted to explore Episil®’s efficacy.Episil® is effective for relieving pain in a rapid and long-acting manner in Japanese patients suffering from OM; it might help cancer treatment continue smoothly without interruptions, and it may improve the QOL of cancer patients.


Thoracoscopic surgery has greatly alleviated the postoperative pain of patients, but postsurgical acute and chronic pain still exists and needs to be addressed. Indwelling drainage tubes are one of the leading causes of postoperative pain after thoracic surgery. Therefore, the aim of this study was to explore the effects of alternative drainage on acute and chronic pain after video-assisted thoracoscopic surgery (VATS).Ninety-two patients undergoing lung wedge resection were selected and randomly assigned to the conventional chest tube (CT) group and the 7-Fr central venous catheter (VC) group. Next, the numeric rating scale (NRS) and pain DETECT questionnaire were applied to evaluate the level and characteristics of postoperative pain.NRS scores of the VC group during hospitalization were significantly lower than those of the CT group 6 h after surgery, at postoperative day 1, at postoperative day 2, and at the moment of drainage tube removal. Moreover, the number of postoperative salvage analgesics  and postoperative hospitalization days were notably reduced in the VC group compared with the CT group. However, no significant difference was observed in terms of NRS pain scores between the two groups of patients during the follow-up for chronic pain at 3 months and 6 months.In conclusion, a drainage strategy using a 7-Fr central VC can effectively relieve perioperative pain in selected patients undergoing VATS wedge resection, and this may promote the rapid recovery of such patients after surgery.ClinicalTrials.gov, NCT03230019. Registered July 23, 2017. Favourable pain management after thoracic surgery is of great significance to prevent chronic pain and complications –3. The cIn recent years, with the popularization of enhanced recovery after surgery (ERAS), the tubeless strategy , 16 has Intriguingly, we speculated that the alternative conventional chest drainage strategy of 7-Fr double-lumen CVC may reduce postoperative pain after lung wedge resection through VATS in the present study. To verify this hypothesis, we designed a single-centre, prospective, and randomized controlled trial to explore the effects of different drainage methods on acute and chronic pain in patients after lung wedge resection under VATS.www.clinicaltrials.gov on July 23, 2017 (registration number: NCT03230019). All participants signed written informed consent forms before enrolment in the study.This prospective, single-centre, open-label, and randomized controlled trial was approved by the Ethics Committee of Guangdong Provincial People’s Hospital (No. GDREC 2017261H) and registered before patient enrolment at The subjects for the screening included patients who received lung wedge resection through VATS at Guangdong Provincial People’s Hospital, and their age was above 18 years. The preoperative exclusion criteria were as follows: (1) any unstable systemic diseases such as active infection, poorly controlled hypertension within 3 months, diabetes or unstable angina; 2) history of ipsilateral chest surgery; (3) preoperative chest X-ray showing pneumonia or atelectasis; (4) bleeding tendency; (5) administration of anticoagulant drugs; or (6) history of other chronic chest pain. Patients were excluded if they needed to receive segmentectomy or lobectomy, if they showed severe adhesions during the surgery, if they required further exploratory surgery, or if air leaks were detected during leak examinations , one surgical team member randomly generated codes by using simple random sampling and SAS statistical software  to randomly assign patients to the VC group or conventional CT group in a 1:1 ratio. It was easy to identify the grouping of patients during follow-up, and the patients and investigators were not blinded to the group assignment.For all patients, general anesthesia was induced with midazolam, sufentanil, propofol and cisatracurium, then double lumen endobronchial tube intubation was performed, and maintained with sevoflurane inhalation, remifentanil infusion, and cisatracurium. Non-steroidal drug flurbiprofen axetil 50 mg and antiemetic drugs were given before skin incision. In the post-anaesthesia care unit (PACU), each patient received intravenous analgesia: sufentanil 150 μg, flurbiprofen 300 mg and antiemetic agents with a total of 75 ml and a background dose of 1 ml/h. Rescue analgesics were administered according to the patient’s pain level after returning to the ward. Salvage analgesic measures indicated that patients with mild pain were given nonsteroidal anti-inflammatory drugs (NSAIDs) (such as Celebrex 200 mg and flurbiprofen axetil injection 50 mg), patients with moderate pain were treated with tramadol (50–100 mg), and patients with severe pain were treated with morphine (7–10 mg).2O suction via the CT. In the scenario of massive pneumothoraxes in the VC group, a syringe was applied to perform a prophylactic air-extraction approximately 3 times a day through the CVC or the reinserted CT. CT/CVC extraction was considered upon indications of blood oxygen saturation (≥) 95%, fully dilated lungs, and no air leakage in the CT group.Before skin incision, 2% lidocaine was used for local infiltration anaesthesia along the incision. A three-centimetre-long incision was made between the anterior axillary line and the fourth or fifth intercostal line of the axillary line. Participants were excluded from the study in the case of severe adhesions or necessity of lobectomy due to insufficient surgical margins during the exploratory process. They were subjected to CT drainage, and all wedge resections were performed using a linear cutting stapler . After completion of wedge resection, a 20-Fr chest tube was inserted for drainage in the CT group Fig. A, conducChronic pain was defined as postoperative pain lasting longer than 3 months according to the International Association for the Study of Pain , and a nThe major endpoint of this study was the level of acute pain after surgery on the first day. The secondary observation indicators mainly included the duration of postoperative intravenous analgesia use, the frequency of postoperative salvage analgesics, the NRS score of extubation, the duration of postoperative drainage, postoperative hospitalization days, the NRS score of postoperative 1 month, and the level and characteristics of chronic pain of patients 3 and 6 months after surgery.t-test, and data with a skewed distribution were compared using the Mann-Whitney U test. Count data are presented as the actual number of cases and percentages, which were processed by the chi-square and Fisher’s exact tests. All the data were analysed by SPSS 25 software , with P < 0.05 indicating statistical significance.Quantitative data are presented as the mean ± standard deviation (mean ± SD). Normally distributed data were compared between two groups using the unpaired n = 9), air leakage (n = 1), and severe adhesion (n = 2) were excluded. Finally, 42 patients were included in the CT group, and 38 patients were assigned to the VC group , postoperative day 1 , postoperative day 2 , and CT removal .The results of the primary outcome mainly focused on NRS scores of hospitalization. NRS scores of the VC group were considerably lower than those of the CT group at 6 h after surgery  and postoperative hospitalization days  were remarkably reduced in the VC group compared with the CT group. No statistically significant difference was observed regarding the pain level of the two groups of patients at discharge  , days of postoperative venous analgesia .It seems that the postoperative average NRS score was less than 3 in both groups. In fact, the proportion of patients with NRS scores≥3 on the first day and the second day Table  in the CPostoperative complications included pneumothorax, pleural effusion, chest tube reinsertion and subcutaneous emphysema. There were no differences between the two groups in these outcomes. Pneumothorax occurred in 4 patients (10.5%) in the VC group, and all patients recovered well after air extraction and did not need reinsertion of the CT. One patient (2.5%) in the CT group required CT reinsertion because of pleural effusion, and this patient was discharged on postoperative day 13.P = 0.182) in VC group and CT group (Tables NRS scores of postoperative at 1 month was (0.9 ± 0.5 vs. 1.1 ± 0.5, p Tables . In the p Tables . The degThoracotomy has been reported to cause trauma and severe pain, while surgical trauma has been considerably reduced due to the development of VATS . MoreoveThe population baseline of the two groups were balanced and same was for surgical procedure, while the postoperative NRS score and hospital stay were decreased in the VC group. This is mainly due to the fact that patients in the alternative drainage group received a 7-Fr central VC, which is small in diameter, greatly reduces the discomfort associated with chest tube. Patients in the VC group undergoing lung wedge resection could even get out of bed on the day of the operation. On the other hand, the VC group patients did not need to carry a chest drainage bottle after surgery, promoting early postoperative activity, which in turn was beneficial for wound healing . In termWith regard to chronic pain, our research results suggested only that there was no difference in the effects of the two kinds of tubes on abnormal skin sensation within half a year after the operation. It is hard to conclude that thoracic drainage tubes have nothing to do with postoperative chronic pain. We need more conclusive evidence to explain the connection between CTs and postoperative chronic pain.We acknowledge that the present study has limitations and that its restrictive inclusion criteria may impede the universality and applicability of the results. First, the diameter of the catheter is small, the drainage capacity for pleural effusion is limited, and the tube is easily blocked. To prevent pneumothorax and massive pleural effusion after surgery, postoperative X-ray examination and dynamic observation of the patients’ reactions were very important, especially at the beginning of the study. Second, our investigation focused on the data and observations at a single research centre, and the sample size was relatively limited. Last, to directly explain the contribution of CTs to postoperative acute and chronic pain, it is necessary to further explore the difference between patients without CTs and the control group of patients in a follow-up study.In conclusion, a drainage strategy using a 7-Fr central VC can effectively relieve perioperative pain in selected patients undergoing VATS wedge resection, and this may be beneficial to the rapid recovery of such patients after surgery.