Surgical aspects of pediatric neuromuscular scoliosis: Perioperative bleeding, bone mineral density and health-related quality of life related to spinal fusion

Neuromuscular scoliosis (NMS), the three-dimensional deformity of the spine, has neurologic or muscular origin. Conservative treatment offers limited possibilities for severe deformities in NMS, hence surgical treatment is often ultimately necessary. Fusion surgery is a difficult procedure for the patient and carries substantial risks. In NMS, the surgical risks and complications are considerably higher than in patients with Adolescent idiopathic scoliosis (AIS). The aim of this dissertation was to investigate the characteristics associated with spinal fusion surgery in NMS patients in terms of perioperative bleeding, health-related quality of life (HRQoL) and bone mineral density. Studies I and II examined perioperative bleeding and its risk factors. Perioperative bleeding was significantly higher in NMS patients compared to AIS. The risk factor profile differed between the study groups. Increasing operative time was a risk factor for intraoperative and total bleeding, whereas extent of fusion correlated to amount of drainage bleeding. Study III investigated health-related quality of life changes associated with spinal fusion. NMS patients showed a significant improvement in quality of life at post-operative two-year follow-up, and the improvement of HRQoL was not inferior in comparison to AIS patients. In study IV, the bone mineral density (BMD) of spinal muscular atrophy patients was investigated from spinal CT-imaging taken prior to spinal fusion. Patients pre-treated with growth-friendly spinal implants had poorer bone mineral density in a comparison to patients followed prior fusion without surgical interventions. Bone quality was poorer in both groups in comparison to healthy controls. This study suggests that there are higher risks associated in spinal fusion for neuromuscular scoliosis patients compared to surgical treatment of idiopathic scoliosis. Perioperative bleeding is more extensive, and previous operative treatment further compromises the poorer bone quality of patients with neuromuscular scoliosis. Importantly, despite the risks, quality of life appears to improve significantly after spinal fusion surgery. KEYWORDS: neuromuscular scoliosis, spinal fusion, perioperative bleeding, health-related quality of life, bone mineral densityNeuromuskulaariskolioosissa (NMS) selän kolmiulotteisen virheasennon taustalla on jokin lihas- tai hermosairaus. Konservatiiviset hoitovaihtoehdot tarjoavat rajoitetusti mahdollisuuksia neuromuskulaariskolioosipotilaiden vaikeiden virheasentojen korjauksessa, joten kirurgiset hoitokeinot ovat lopulta usein välttämättömiä. Luudutusleikkaus on potilaalle raskas toimenpide, johon liittyy monia riskejä. Neuromuskulaariskolioosissa leikkausriskit ja komplikaatiot ovat selvästi yleisempiä kuin idiopaattisen skolioosin (AIS) leikkaushoidossa. Tämän väitöskirja-tutkimuksen tavoitteena oli selvittää NMS-potilaiden luudutusleikkauksiin liittyviä erityispiirteitä leikkauksenaikaisen verenvuodon, elämänlaadun muutoksen sekä leikkausta edeltävän luuntiheyden osalta. Osatöissä I ja II tutkittiin leikkauksenaikaista verenvuotoa ja sen riskitekijöitä. Leikkausverenvuoto oli merkittävästi suurempaa NMS-potilailla AIS-potilaisiin verrattuna. Riskitekijäprofiili erosi tutkimusryhmien välillä. Leikkauksen kesto oli vuotoa lisäävä riskitekijä leikkauksenaikaiselle ja kokonaisverenvuodolle ja luudutuksen laajuus korreloi positiivisesti leikkauksen jälkeiseen verenvuotoon. Osatyössä III selvitettiin luudutusleikkauksen aiheuttamaa elämänlaadun muutosta tapaus-verrokkitutkimusasetelmassa. NMS-potilaiden elämänlaatu parani merkittävästi kahden vuoden seurannassa luudutusleikkauksen jälkeen, eikä elämänlaadun paraneminen ollut AIS-potilaita heikompaa. Osatyössä IV tutkittiin SMA (spinaalinen lihasatrofia) potilaiden luuntiheyttä luudutusleikkausta edeltävästi otetuista tietokonetomografiakuvista. Kasvuystävällisillä implanteilla hoidettujen potilaiden luuntiheys oli heikompaa ennen luudutusleikkausta verrattuna potilaisiin, joita ei ollut hoidettu operatiivisesti ennen luudutusleikkausta. Luunlaatu oli molemmissa ryhmissä tervettä verrokkiväestöä heikompaa. Tämän tutkimuksen perusteella neuromuskulaariskolioosipotilaiden luudutusleikkauksiin liittyy suurempia riskejä verrattuna idiopaattisen skolioosin leikkaushoitoon. Perioperatiivinen verenvuoto on runsaampaa, ja aiempi operatiivinen hoito heikentää neuromuskulaaripotilaiden entisestään heikompaa luunlaatua. Huomattavaa on, että riskeistä huolimatta elämänlaatu vaikuttaa parantuvan merkittävästi luudutusleikkauksen jälkeen. AVAINSANAT: Neuromuskulaariskolioosi, luudutusleikkaus, perioperatiivinen verenvuoto, elämänlaatu, luuntihey

Ketamiinin käyttö kivunhoidossa ja PCA

Ketamiini on monipuolinen lääkeaine, jonka pääasiallinen vaikutusmekanismi on N-Metyyli-D-Aspartaatti (NMDA) -reseptorien kilpailematon antagonismi aivojen ja selkäytimen alueella. Tämä vaikutus on annosriippuvainen. NMDA-reseptorit ovat osana kivun transmissiota ja modulaatiota. Yleisimmin ketamiini annostellaan suonensisäisesti, mutta teoriassa se voidaan annostella montaa muutakin reittiä käyttämällä. Perinteisesti ketamiinia on käytetty anesteettina, mutta tässä tarkoituksessa ketamiinin käyttö on kuitenkin varsin ongelmallista sen dissosiatiivisten ominaisuuksien vuoksi. Sen sijaan analgeettinen teho tulee esille jo subanesteettisilla annoksilla. Tämä johtuu siitä, että kiputilanteessa NMDA-reseptorit lisäävät selkäytimen kipua välittävien C-säikeiden aktiivisuutta. Ketamiini on analgeettina monipuolinen vaihtoehto. Sitä voidaan käyttää niin akuutin operatiivisen, kuin kroonistuvankin kivun hoidossa. Intraoperatiivisesti annettu ketamiini vaikuttaa pienentävän myös postoperatiivisen opioidin tarvetta, ja kivun voimakkuus on alhaisempi. Ketamiini on analgesiakäytössä parhaimmillaan postoperatiivisessa kivunhoidossa ja sen vaikutus ovat tehokkain runsaasti kipua aiheuttavien leikkausten jälkeen. Kroonisen kivun hoidossa ketamiini on vaihtoehto niille kipupotilaille potilaille, joilla muut analgeetit ovat riittämättömiä. Tämän vaikutus perustuu sentraaliseen sensitiaatioon. Tehohoidossa ketamiini on mielekäs analgeetti, sillä se ei vaikuta suolen toimintaan, eikä lamaa hengitystä tai verenkiertoa. Lisäksi ketamiini tarjoaa mahdollisuuksia myös masennuslääkekäytössä, sekä addiktioiden ja epilepsian hoidossa. Analgeettisilla annoksilla ketamiinilla ei ole havaittu merkittäviä komplikaatioita. Dysforisia vaikutuksia on havaittu ketamiinin analgesiakäytössä merkittävästi vähemmän kuin anestesiakäytössä, ja niitä voidaan entisestään vähentää kombinoimalla hoitoon bentsodiatsepiineja. PCA eli patient controlled analgesia toteutetaan laitteella, jossa tietokoneistettuun pumppuun on annosteltu ruiskullinen kipulääkettä. Laite yhdistetään potilaaseen tyypillisimmin iv-katetrin kautta. Toimintaperiaate on yksinkertainen: potilaan painaessa laitteeseen yhdistettyä annostelunappia, laite annostelee tietyn suuruisen ennaltamäärätyn lääkeannoksen suoraan potilaan laskimoon. PCA:n käytön yhteydessä on havaittu parempia tuloksia postoperatiivisen kivun hoidossa ja parantunutta potilastyytyväisyyttä verrattuna perinteisiin tapoihin

Distal Femoral Focal Deficiency

Distal femoral focal deficiency is an extremely rare type of congenital femoral deficiency that comprises hypoplasia of the distal femur, with a normally developed hip. We represent a unique case of distal femoral hypoplasia and deficiency of knee extensors, childhood follow-up and final treatment with exarticulation, and a comparison with previous literature.Peer reviewe

Perioperative Risk Factors for Bleeding in Adolescents Undergoing Pedicle Screw Instrumentation for Scoliosis

Progressive scoliosis eventually leads to extensive spinal fusion surgery, which carries a risk for significant bleeding. Neuromuscular scoliosis (NMS) patients have an additional inherent risk of major perioperative bleeding. The purpose of our research was to investigate the risk factors for measured (intraoperative, drain output) and hidden blood loss related to pedicle screw instrumentation in adolescents, divided into adolescent idiopathic scoliosis (AIS) and NMS patient groups. A retrospective cohort study with prospectively collected data of consecutive AIS and NMS patients undergoing segmental pedicle screw instrumentation at a tertiary level hospital between 2009 and 2021 was conducted. In total, 199 AIS (mean age 15.8 years, 143 females) and 81 NMS patients (mean age 15.2 years, 37 females) were included in the analysis. In both groups, levels fused, increased operative time, and smaller or larger size of erythrocytes were associated with perioperative blood loss (p < 0.05 for all correlations). In AIS, male sex (p < 0.001) and the number of osteotomies correlated with more drain output. In NMS, levels fused correlated with drain output, p = 0.00180. In AIS, patients’ lower preoperative MCV levels (p = 0.0391) and longer operation times, p = 0.0038, resulted into more hidden blood loss, but we did not find any significant risk factors for hidden blood loss in NMS patients

Treatment of congenital bipartite patella in pediatric population - a systematic review of the published studies

Bipartite patella is an abnormality where patella is incorrectly ossified resulting in fibrocartilaginous synchondrosis. In most cases bipartite patella is asymptomatic and incidental finding but can also be painful especially in adolescents. The aim of our analysis was to determine the preferable treatment for pediatric bipartite patella. We conducted a systematic review based on PubMed and Embase searches. All original articles with reference to treatment in the population of ≤ 20 years of age, were included. Case reports, and articles without individualized data were excluded. In total, the individual data of 126 knees in 116 patients was analyzed. In 77.8% (98/126) of the analyzed knees the result was excellent, and the majority of the knees, 89.7% (105/126) received surgical intervention, and seven different techniques were used. None of operative methods were superior to others. Excellent treatment outcomes were achieved more often in younger patients (p=0.004), and the median duration of symptoms in operatively treated patients was shorter (p=0.018). If operative treatment is used after unsuccessful conservative treatment, it should be considered early in adolescence and also within a relatively short period after the onset of symptoms. The best operative method could not be found. More research and RCTs are needed concerning the conservative methods and different operative techniques

Distal Femoral Focal Deficiency

Distal femoral focal deficiency is an extremely rare type of congenital femoral deficiency that comprises hypoplasia of the distal femur, with a normally developed hip. We represent a unique case of distal femoral hypoplasia and deficiency of knee extensors, childhood follow-up and final treatment with exarticulation, and a comparison with previous literature

Perioperative Risk Factors for Bleeding in Adolescents Undergoing Pedicle Screw Instrumentation for Scoliosis

Progressive scoliosis eventually leads to extensive spinal fusion surgery, which carries a risk for significant bleeding. Neuromuscular scoliosis (NMS) patients have an additional inherent risk of major perioperative bleeding. The purpose of our research was to investigate the risk factors for measured (intraoperative, drain output) and hidden blood loss related to pedicle screw instrumentation in adolescents, divided into adolescent idiopathic scoliosis (AIS) and NMS patient groups. A retrospective cohort study with prospectively collected data of consecutive AIS and NMS patients undergoing segmental pedicle screw instrumentation at a tertiary level hospital between 2009 and 2021 was conducted. In total, 199 AIS (mean age 15.8 years, 143 females) and 81 NMS patients (mean age 15.2 years, 37 females) were included in the analysis. In both groups, levels fused, increased operative time, and smaller or larger size of erythrocytes were associated with perioperative blood loss (p p p = 0.00180. In AIS, patients' lower preoperative MCV levels (p = 0.0391) and longer operation times, p = 0.0038, resulted into more hidden blood loss, but we did not find any significant risk factors for hidden blood loss in NMS patients

A retrospective cohort study of bleeding characteristics and hidden blood loss after segmental pedicle screw instrumentation in neuromuscular scoliosis as compared with adolescent idiopathic scoliosis

BackgroundProgressive scoliosis in neuromuscular patients often requires a long instrumented spinal fusion. Previous studies have shown larger intraoperative blood loss in these patients than those with adolescent idiopathic scoliosis (AIS), but the total blood loss composed of visible and hidden blood loss has not been described in this patient population. The aim of our study was to investigate the bleeding characteristics and hidden blood loss related to spinal fusion in neuromuscular scoliosis (NMS) as compared to AIS patients.MethodsA retrospective cohort study with prospective data collection of NMS patients undergoing segmental pedicle screw instrumentation at a university hospital between 2009 and 2021. A comprehensive statistical analysis was performed regarding intra- and postoperative blood loss compared to patient characteristics such as age and diagnosis. Hidden blood loss was estimated and compared to the total blood loss. We standardized amount of bleeding with patient weight and fusion level for further analysis. Consecutive AIS patients served as a control population. Eighty-one consecutive patients with NMS (mean age 15.2 years, 37 females) were included and their bleeding characters were compared with 199 AIS patients (mean age 15.8 years, 143 females). The primary outcome was total blood loss including intraoperative, 24-hour drain output and hidden blood loss. Secondary outcome measures included requirement for blood transfusion.ResultsNeuromuscular patients had a significantly larger total blood loss with mean values of 1914 mL in the NMS and 1357 mL in the AIS groups, respectively (pConclusionsHidden blood loss constitutes one-third of total blood loss in children undergoing segmental pedicle screw instrumentation for neuromuscular scoliosis. Hidden blood loss is significantly greater in the neuromuscular as compared with idiopathic scoliosis. Hidden blood loss should be considered in the perioperative management of NMS.</p

S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial

Background Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.Methods We randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.Results Of the 100 patients analyzed, patients receiving 0.75 mg ml(-1) S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml(-1) (74.7 mg) or 0.25 mg ml(-1) (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to -0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml(-1) S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013-0.32, P = 0.033). The occurrence of adverse events was similar among the groups.Conclusions Oxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects

Early Development of Spinal Deformities in Children Severely Affected with Spinal Muscular Atrophy after Gene Therapy with Onasemnogene Abeparvovec—Preliminary Results

Spinal muscular atrophy (SMA) is a rare genetic disorder, with the most common form being 5q SMA. Survival of children with severe SMA is poor, yet major advances have been made in recent years in pharmaceutical treatment, such as gene-therapy, which has improved patient survival. Therefore, clinical problems, such as the development of spinal deformities in these genetically treated SMA children represent an unknown challenge in clinical work. In a retrospective case series, the development of spinal deformities was analyzed in 16 SMA children (9 male, 7 female) treated with onasemnogene abeparvovec in two institutions during the years 2020 to 2022. Ten out of sixteen patients had a significant kyphosis, and nine out of sixteen patients had significant scoliosis, with the mean curvature angles of 24 ± 27° for scoliosis, and 69 ± 15° for kyphosis. Based on these preliminary data, it can be assumed that early-onset kyphosis presents a clinical challenge in gene-therapy-treated SMA children. Larger datasets with longer follow-up times need to be collected in order to verify these preliminary observations