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De riktlinjer som presenteras här syftar till vägledning i den kliniska vardagen. Även om riktlinjerna i första hand riktar sig till avdelningar som bedriver neonatal intensivvård och/eller intermediärvård fungerar de också som vägledning för andra enheter som arbetar med nyfödda barn. Dokumentet kan användas som underlag vid utformning av regionala riktlinjer och utbildningsprogram på respektive vårdinrättning. Vi rekommenderar att med hjälp av dessa riktlinjer lokalt skapa och implementera PM utifrån den kunskap, erfarenhet och de väl inarbetade rutiner och läkemedel som personalen är förtrogen med. Osäkerhet avseende farmakologisk behandling kan medföra såväl underbehandling som felbehandling och kommer inte det sjuka barnet tillgodo. Efter en genomgång av principerna för smärtskattning görs en genomgång av tillgängliga behandlingsalternativ innefattande optimerad vårdmiljö och beteendestödjande åtgärder samt läkemedel. Därefter presenteras de indikationer – kliniska situationer – som möter den personal som arbetar med nyfödda barn, indelat i olika smärttyper.

Bakgrund: Trots kunskap om hur små barn påverkas negativt av smärtsamma procedurer och tillgången till effektiva motåtgärder genomförs mängder av vaccinationer och andra injektioner utan tillräcklig smärtlindring. Lilla Barnsmärtguiden utvecklades därför som ett webbaserat verktyg till hjälp för personal som injicerar barn i åldern 0-6 år. Material och metod: Med stöd av AbbVie AB genomfördes två workshops med sjuksköterskor med stor vana att ge injektioner till barn. Genom föreläsningar, gruppdiskussioner och s.k. graphic recording formulerades förslag till åtgärder i områdena det späda barnet, det lilla barnet, det stora barnet, föräldrarna samt personalen. Utifrån detta utformade arbetsgruppen text och bild för en webbplats med funktionalitet för såväl dator som läsplatta och mobiltelefon. Innehåll och design testades mot en grupp sjuksköterskor inom barnhälsovården och specialistsjukvården. Samtidigt utformades informationsmaterial för att sprida kännedom om Lilla Barnsmärtguiden. Resultat: Den färdiga webbplatsen publicerades med Örebro universitet som utgivare, på www.lillabarnsmartguiden.se med de fyra sektionerna förberedelser, under besöket, barn i olika åldrar samt vårdnadshavaren. Under dessa rubriker ges förslag på farmakologiska och icke-farmakologiska åtgärder som kan användas för att minska smärta och obehag vid vaccinationer och andra injektioner. Hänvisning till nyckelreferenser görs för de som vill läsa vidare.Lanseringen av Lilla Barnsmärtguiden fick ett bra genomslag i media vilket bl.a. ledde till flera chat-sessioner hos Sveriges television. Under de fyra första månaderna nåddes över 5 500 unika besökare. Slutsats: Barn som genomgår vaccinationer och andra injektioner får otillräcklig smärtlindring. Lilla Barnsmärtguiden möter ett behov av information och stöd till personal som genomför de smärtsamma procedurerna.

The National Tonsil Surgery Register in Sweden collects perioperative data from health care professionals and patient reported outcome measures 30 days and 6 months after surgery. Since 2009, patient-reported outcome measures, include questions related to pain. Objective: To illustrate the process of improvements, efforts, and the use of a quality register in pain, and pain management after tonsil surgery in Sweden. Method: Quantitative and qualitative research. Results: Registry data indicated unrelieved postoperative pain with a high proportion of health care contacts. This resulted in the implementation of the Swedish National Guidelines (2013), and patient information published on the website www.tonsilloperation.se. The guidelines recommend multimodal pain treatment with paracetamol combined with COX-inhibitors, and if necessary, oral clonidine rather than opioids as rescue analgesics. A national survey (2015) showed that Swedish ENT-professionals’ opinions of, and the ENT-departments adherence to the guidelines were good. According to the national registry data (2017), the implementation has resulted in longer use of post-operative analgesic and fewer contacts with healthcare. Simultaneously, registry data showed that operating methods and techniques, age, and indication for surgery affect the pain outcome. Results from age-oriented pain diaries and qualitative interviews (2017-2018) capture the children’s and caregivers’ perspectives on pain, and pain treatment. Preliminary results show that type of pain treatment affects the quality of the postoperative care and recovery. Conclusion: Pain management after tonsil surgery has been, and still is, a challenge for ENT-professionals and constant improvements are necessary.

Background: Pain management in children after tonsil surgery is essential, and optimal pain treatment has been discussed for many years. Data from the National Tonsil Register in Sweden (NTRS) and a national mapping system have demonstrated the need for national pain treatment guidelines for pediatric tonsil surgery. As a result, Swedish national guidelines, together with updated patient information on the website tonsilloperation.se, were developed and implemented in 2013. Objectives The objective of this study was to evaluate the professionals’ opinions of and adherence to pain treatment guidelines for pediatric tonsil surgery patients in a two-year follow-up. Method: This descriptive cross-sectional study was based on data from an inter-professional questionnaire, which was validated by an expert group using a content validity index (S-CVI 0.93). The questionnaire was sent to all Swedish ear, nose and throat (ENT) departments (n=49) that the NTRS identified as performing tonsil surgery on children younger than 18 years of age. In each clinic, we asked for responses from staff in each of the following professions: ENT physicians, anesthesia physicians, registered nurse anesthetists, and registered nurses in the ENT departments. Results: Respondents from 48 ENT departments participated, and 139/163 (85%) completed questionnaires were returned. The guidelines were reported as being clear, ensuring patient safety and providing optimal pharmacological treatment. Treatment was given according to the guidelines: Half of the departments gave pre- or intraoperative treatment with clonidine, betamethasone and high-dose paracetamol (acetaminophen). A multimodal pain approach (paracetamol and COX inhibitors) after hospital discharge was prescribed by all departments after tonsillectomy and, more extensively, after tonsillotomy. One-third of the departments prescribed paracetamol with a higher normal dose for the first three postoperative days. Half of the departments prescri, Funding agencies:Research Committee at Region Örebro CountyÖrebro University Hospital Research Foundation OLL674631, Effective postoperative pain management in children after tonsil surgery: barriers and possible solutions

Objective: As shown by data from the National Tonsil Surgery Register in Sweden, tonsil surgery often causes severe pain that lasts for many days. The register data demonstrate the necessity for better evidence-based pain treatment guidelines for tonsil surgery. The guidelines, introduced in 2013, consist of both pharmacological and non-pharmacological recommendations. In the guidelines, a multimodal analgesic approach and combination of analgesics are recommended to provide effective pain treatment with limited side effects. Two national multi-professional education days on pain, pharmacology and the guidelines were offered. Web-based information about pharmacological treatment (www.tonsililloperation.se) was designed for patients and next-of-kin. The current aims were to describe adherence to the Swedish guidelines for pain treatment in tonsil surgery in pediatric patients < 18 years Method: An inter-professional questionnaire was developed, including questions linked to the relevant guidelines. The questions came from a national mapping before the guidelines were designed. The items were discussed by an expert group, and content validity was evaluated using the content validity index.ENT-and anesthesia physicians and nurses from all 50 ENT clinics in Sweden were enrolled. Results: Most clinics had received the guidelines, but there was a discrepancy between the professions. More than half had perused the literature review performed before the guidelines were designed, and attended themulti-professional education day. Pre- and perioperative treatment usually included paracetamol, clonidine and betamethasone. A multimodal pain approach after discharge from hospital (tonsillectomy and tonsillotomy) was used, combining paracetamol with cox-inhibitors. Most clinics used paracetamol, with a higher dose for the first 3 days (healthy children and acceptable nutrition), and a reduced dose from day 4.In case of inadequate analgesia after tonsillectomy, oral clonidine or

Background: Surgery of the tonsils often causes severe pain lasting for many days as been shown by data from the National Tonsil Surgery Register in Sweden. Tonsillotomy is associated with fewer readmissions due to bleeding, number of days requiring analgesics and health care contacts due to pain compared to tonsillectomy. The register data demonstrate the necessity of better-evidenced based pain treatment guidelines for tonsil-surgery. Objectives: To develop evidenced based pain treatment guidelines for tonsil-surgery in Sweden. Methods: The evidence based guidelines were designed by an updated literature review and from the clinical expertise in the pediatric pain field, which thereafter were reviewed by ENT-doctors and anesthetists from each ENT-clinic in Sweden. Results: A multimodal pain treatment approach is advocated, including premedication and administration during anesthesia, with paracetamol (acetaminophen), clonidine and betamethasone. If not given as a premedication the combination can be administered intravenously in the initial phase of anesthesia. At the end of surgery, if no bleeding problems, cox-inhibitors can be given.After discharge from hospital, the recommendations for pain relief are paracetamol combined with cox-inhibitors (ibuprofen, diclofenac) and if needed oral clonidine in favor of opioids. When pain intensity decreases, discontinue the analgesic treatment in the following order: opioid, clonidine, paracetamol and at last ibuprofen. The need for analgesic treatment after tonsillectomy is usually 5-8 days, after tonsillotomy only 3-5 days.Parents are recommended to contact the hospital if the child has difficulties in drinking or eating adequately and/or suffers from pain despite taking the recommended medication regularly. Conclusions: Swedish guidelines for tonsil-surgery provide practical evidence-based pain treatment recommendations.

Riktlinjerna är framtagna av referensgruppen för Tonsilloperation. Syftet med dessa riktlinjer är att optimera det perioperativa omhändertagandet (premedicinering - peroperativt - postoperativt smärtomhändertagande) i samband med tonsilloperationer på barn och ungdomar. Bakgrund och referenser till riktlinjerna finns i ett separat dokument. Riktlinjerna gäller för friska barn. Finns det riskfaktorer som ex grav sömnapné, kraftig övervikt, komplicerande sjukdomstillstånd eller organpåverkan behöver den farmakologiska behandlingen anpassas efter situationen. Tonsillkirurgi medför svår och långvarig smärta samt hög frekvens av illamående. Smärtan är ofta värst dag 3 till 5 efter tonsillektomi. Tonsillotomi ger generellt upphov till mindre smärta än tonsillektomi. För att uppnå effekt behöver den farmakologiska smärtbehandlingen påbörjas redan vid premedicineringen och fortlöpa under själva anestesin/ingreppet. En multimodal behandling ska eftersträvas och målsättningen är att uppnå en för individen acceptabel smärtnivå i det postoperativa skedet och i hemmet. Den farmakologiska behandlingen ska kombineras med preoperativ information om ingreppet till patienten och vårdnadshavare. En lugn och trygg situation före anestesistart ökar chanserna för ett lugnt postoperativt förlopp., Referensgruppen för tonsilloperation.

I Sverige utförs 13000 tonsilloperationer varje år, över 50 % utförs på barn under 15 år. Tonsilloperation medför svår och långvarig smärta samt hög frekvens av illamående. Smärtan är ofta värst dag 3 till 5 efter tonsillektomi. Tonsillotomi ger generellt upphov till mindre smärta än tonsillektomi. Dehydrering och sämre näringsintag kan vara en orsak till större smärtproblematik vid tonsillektomier. Äldre barn som genomfört tonsilloperation skattar högre postoperativ smärta vilket kräver ökat behov av analgetika. Olika interventioner inklusive farmakologiska används för att behandla och förebygga smärta och illamående. De vanligaste systemiska analgetika som används är paracetamol, COX-hämmare samt opioider. Användande av opioider vid tonsillektomi på barn med och obstruktiv sömnapné kan ge upphov till allvarliga komplikationer 4. Alfa-2 adrenerga agonister som klonidin har en analgetisk effekt utan påverkan på andningsdriven. Klonidin kan vara ett bra komplement då paracetamol i kombination med COX-hämmare inte har tillräcklig analgetisk effekt. Olika regionala metoder med bl.a. lokalbedövningsmedel används också med viss effekt.

Opioids are the mainstay of the treatment of severe nociceptive pain in both children and adults. The studies in this thesis have focused on different aspects of opioid treatment in the pediatric population with special interest in morphine and ketobemidone. Ketobemidone has been in use for a long period of time but there has been very limited published data about the pharmacokinetics and pharmacodynamics of this drug. The aim has been to increase the knowledge of both pharmacokinetic and pharmacodynamic effects of morphine and ketobemidone. In the sequence of studies the first one dealt with the pharmacokinetics of rectally administered morphine. Two different formulations of morphine were used and compared. Secondly the child’s acceptance of the two formulations was examined from a pain perspective. Further on, the potency of ketobemidone in children was compared to morphine in a postoperative setting using PCA as a drug delivery system. Pharmacokinetic studies in children have been scarce despite the long time use of ketobemidone. In two studies the pharmacokinetics were explored in neonates, infants and children. From the results the following conclusions were drawn: • A morphine gel adapted for rectal use, with a higher pH than the regular saline solution, did not show any significant higher bioavailability but a tendency for an improved uptake. Bioavailability of rectally administered morphine is relatively low (about 30 %) and shows a large inter-individual variability in children. • A morphine gel developed for rectal administration induces less pain in children aged 1-6 years. Most children tolerate rectal administration of morphine well when used for premedication. • The opioid ketobemidone is equipotent to morphine when used for postoperative pain treatment. The frequency of adverse effects of ketobemidone and morphine are comparable when PCA is used for postoperative pain relief in children. • The pharmacokinetic characteristics of ketobemidone administe