Survival of patients with Duchenne muscular dystrophy who underwent spinal deformity correction.

AIM: We investigated survival rates after scoliosis correction in individuals with Duchenne muscular dystrophy (DMD) and evaluated factors that can affect them. METHOD: This was a retrospective cohort study from 2000 to 2022 with a minimum 2-year postoperative follow-up. We reviewed the hospital records/spinal radiographs and analysed data with XLSTAT. Kaplan-Meier and multivariate Cox regression survival analysis was performed. RESULTS: Forty-three patients had a mean age at surgery of 14 years 5 months. Mean postoperative follow-up was 10 years 10 months. There was no operative or 30-day postoperative mortality in this group. Twenty-four patients died because of cardiorespiratory failure. Median survivorship was 14 years 2 months, with the longest observed survival being 22 years 6 months given the limitation of the length of postoperative follow-up. The degree of preoperative coronal imbalance and pelvic obliquity, as well as intraoperative blood loss, were factors that significantly affected survival. The impact of preoperative sagittal imbalance and extension of the fusion to the sacrum/pelvis trended towards significance. In contrast, age at surgery, preoperative/postoperative scoliosis, thoracic kyphosis, lumbar lordosis, scoliosis and pelvic obliquity flexibility or correction indices, postoperative coronal/sagittal balance, need of preoperative non-invasive ventilation, preoperative feeding disorders, development of surgical complications, and length of hospital and intensive care unit stay were exposure variables that did not affect postsurgical survival in patients with DMD. INTERPRETATION: Survival of up to two decades or more was possible among young patients with DMD after scoliosis correction. This was affected by factors that related to disease and deformity severity, as well as surgical morbidity. WHAT THIS PAPER ADDS: There was no operative or 30-day postoperative mortality in this group of patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction. Survival probabilities at 5-year, 10-year, 15-year, and 20-year intervals post-surgery were 92%, 80%, 33%, and 12% respectively. Scoliosis surgery achieved good deformity correction and a balanced spine that was maintained at follow-up. Respiratory failure, severe pneumonia, and left ventricular failure were the leading causes of death in the study participants. Preoperative global coronal imbalance, pelvic obliquity, and intraoperative blood loss significantly predicted survival. Factors that affected survival after scoliosis surgery were associated with perioperative morbidity and disease or deformity severity in the DMD group.

No difference in postoperative complication rates or cardiopulmonary function for early versus late scoliosis correction in Duchenne muscular dystrophy.

BACKGROUND: Given reduced rates of both pulmonary function decline and scoliosis progression with steroid treatment in Duchenne muscular dystrophy (DMD), the role of early scoliosis surgery has been questioned. The purpose of this study was to compare the postoperative complication rates of early versus late scoliosis correction in DMD. METHODS: This study was a retrospective cohort, conducted at an academic tertiary level children's hospital. Patients with DMD who underwent posterior scoliosis correction, with preoperative pulmonary function testing [forced vital capacity (FVC)] were included and divided into two groups by preoperative curve angles: ≤ 45° and > 45°. The primary outcome variable was postoperative complications by Clavien-Dindo classification grading. Secondary outcome variables included postoperative complications occurring after the first 90 days, age at surgery, duration of wheelchair dependency preoperatively, pulmonary function, steroid utilization, shortening fraction by echocardiogram, surgery duration, intensive care unit/hospital length of stay, days intubated, infection, and percent curve correction. Two-tailed t-test and Chi-square testing were used for analysis of patient factors and Clavien-Dindo complication grade, respectively. RESULTS: Thirty-one patients were included with a total follow-up of 8.3 ± 3.2 years, 4.8 ± 2.2 years post-spinal fusion. Steroid treatment (prednisone, deflazacort) was utilized for 21 (67.7%) patients. Primary curve correction was not different between groups (65.0% vs 71.4% [p = 0.37]). There were no significant differences in Clavien-Dindo classification grades between groups (p > 0.05). For the entire cohort, the overall complication rate was higher for patients with steroid treatment (61.9% vs 10.0% [p = 0.008]). Neither forced vital capacity nor fractional shortening on echocardiogram was different between groups at final follow-up (p = 0.6 and p = 0.4, respectively). CONCLUSION: The comparable risk of perioperative complications for early and late scoliosis correction supports a "watchful waiting" approach, whereby curves less than 45° can be carefully followed while cardiopulmonary function is maintained. Patients undergoing steroid treatment should be counseled regarding the higher risk of postoperative blood transfusion and deep wound infection. LEVEL OF EVIDENCE: III Retrospective cohort.

Persistent myocardial atrophy despite LV reverse remodeling in Duchenne cardiomyopathy treated by LVAD.

DCM is the leading cause of death in Duchenne patients. LVADs are considered as therapeutic options as DT in advanced HF. The aim of our study was to evaluate LV remodeling of Duchenne after LVADs and chronic therapy. Demographic and echocardiographic data of 8 Duchenne patients implanted with LVADs were reviewed and analyzed. All measures were collected before LVAD implantation, after 1 month and 1 year. All patients were affected by end-stage DCM, and mean age at implantation was 16.9 ± 2.9 years. Patients were treated with maximal medical therapy. One-year post-implantation HR decreased from a mean of 110 ± 19 bpm to 82 ± 2 bpm (P = .002), and a significant decrease in LV volumes and diameters LVEDD P = .03, LVESD P = .02, EDV P = .01, and ESV P = .02) was noticed together with a significant increase in EF (P = .0036). However, RWT did not change over time, showing an eccentric remodeling pattern pre- and post-LVADs. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function secondary to a significant ventricular unloading due to LVADs coupled with chronic therapy.

The modified Kostuik transilial bar technique has acceptable results in neuromuscular spinal deformity correction.

The aim of this study is to evaluate the results of the modified Kostuik transilial bar technique for neuromuscular scoliosis (NS). We reviewed the records of 21 patients treated for NS with this instrumentation. There were 14 females and seven males, with an average age of 15.6 years (range: 9-21 years). We determined patients' demographics, correction ratio of both curve and pelvic obliquity, loss of correction, screw loosening at first sacral vertebra, and clinical outcomes. Mean follow-up was 56 months (range: 34-96 months). There were no reoperations, no screw breakage, and no significant loss of correction. The mean preoperative coronal Cobb angle was 71.4°±8.7°, the initial postoperative measurements had a mean Cobb angle of 19.2°±7.2°, and at the last follow-up, the mean Cobb angle was 23.6°±6.9° (P<0.001). Pelvic obliquity decreased from 27.7°±12.4° to 9.1°±5.3° at follow-up and to 11.9°±6.3° at the last follow-up (P<0.001). The preoperative pelvic obliquity angle was significantly higher at the patients with screw loosening (P=0.016). There was one established as well as one possible pseudoarthrosis in our patients. The new technique does appear to possibly become an alternative to conventional lumbosacral fixation techniques. Integration of the bar with pipe-type connector onto the long spinal instrumentation with oblique connectors can prevent the most unenviable complications such as wide exposure, hardware prominence, reoperation, and pseudoarthrosis.

Cost-Effectiveness of Ventricular Assist Device Destination Therapy for Advanced Heart Failure in Duchenne Muscular Dystrophy.

Destination ventricular assist device therapy (DT-VAD) is well accepted in select adults with medically refractory heart failure (HF) who are not transplant candidates; however, its use in younger patients with progressive diseases is unclear. We sought to evaluate the cost-effectiveness of DT-VAD in Duchenne muscular dystrophy (DMD) patients with advanced HF. We created a Markov-state transition model (5-year horizon) to compare survival, costs, and quality of life (QOL) between medical management and DT-VAD in DMD with advanced HF. Model input parameters were derived from the literature. We used sensitivity analyses to explore uncertainty around model assumptions. DT-VAD had higher costs ($435,602 vs. $125,696), survival (3.13 vs. 0.60 years), and quality-adjusted survival (1.99 vs. 0.26 years) than medical management. The incremental cost-effectiveness ratio (ICER) for DT-VAD was $179,086 per quality-adjusted life year (QALY). In sensitivity analyses that were widely varied to account for uncertainty in model assumptions, the DT-VAD strategy generally remained more costly and effective than medical management. Only when VAD implantation costs were <$113,142 did the DT-VAD strategy fall below the $100,000/QALY willingness-to-pay threshold commonly considered to be "cost-effective." In this exploratory analysis, DT-VAD for patients with DMD and advanced HF exceeded societal expectations for cost-effectiveness but had an ICER similar to the accepted practice of DT-VAD in adult HF patients. While more experience and research in this population is needed, our analysis suggests that DT-VAD for advanced HF in DMD should not be dismissed solely based on cost.

Segmental Pedicle Screw Instrumentation and Fusion Only to L5 in the Surgical Treatment of Flaccid Neuromuscular Scoliosis.

STUDY DESIGN: A retrospective cohort study was performed. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of stopping segmental pedicle screw instrumentation constructs at L5 in the treatment of neuromuscular scoliosis. SUMMARY OF BACKGROUND DATA: Duchenne muscular dystrophy and spinal muscular atrophy are flaccid neuromuscular disorders in which gradual deterioration is the hallmark and have a lot of characteristics in common despite differences in etiology. Instrumentation and fusion to the sacrum/pelvis has been a mainstay in the surgical treatment of flaccid neuromuscular scoliosis and recommended to correct pelvic obliquity. However, the caudal extent of instrumentation and fusion in the surgical treatment of flaccid neuromuscular scoliosis has remained a matter of considerable debate and there have been few studies on the use of segmental pedicle screw instrumentation for flaccid neuromuscular scoliosis. METHOD: From 2005 to 2007, a total of 27 consecutive patients with neuromuscular disorders (20 Duchenne muscular dystrophy and 7 spinal muscular atrophy), aged 11 to 17 years, underwent segmental pedicle screw instrumentation and fusion only to L5. Assessment was performed clinically and with radiologic measurements. Minimum 2-year follow-up was required for inclusion in this study. RESULTS: Twenty patients were enrolled in this study. No patient was lost to follow-up. All patients had L5 tilt of less than 15° and a coronal curve with apex L2 or higher preoperatively. Preoperative coronal curve averaged 70° (range: 51°-88°), with a postoperative mean of 15° (range: 5°-25°) and 17° (range: 6°-27°) at the last follow-up. The pelvic obliquity improved from 15° (range: 9°-25°) preoperatively to 5° (range: 3°-8°) postoperatively and 6° (range: 3°-8°) at the last follow-up. The L5 tilt improved from 9° (range: 2°-14°) preoperatively to 2° (range: 0°-4°) postoperatively and 2° (range: 0°-5°) at the last follow-up. Physiologic sagittal plane alignment was recreated after surgery and maintained long-term. There was no significant loss of correction of coronal curve and pelvic obliquity. There was no major complication. CONCLUSION: Segmental pedicle screw instrumentation and fusion to L5 was safe and effective in patients with flaccid neuromuscular scoliosis with apex L2 or higher and minimal L5 tilt of less than 15°. Segmental pedicle screw instrumentation ending at L5 offered the ability to correct spinal deformity and pelvic obliquity initially, intermediate and even long-term, with no major complications. This method in appropriate patients can be a viable alternative to instrumentation and fusion to the sacrum/pelvis in the surgical treatment of flaccid neuromuscular scoliosis. LEVEL OF EVIDENCE: N/A.

Perioperative management of gastrostomy tube placement in Duchenne muscular dystrophy adolescent and young adult patients: A role for a perioperative surgical home.

BACKGROUND: In past decades, Duchenne muscular dystrophy patients have been living longer and as the disease advances, patients experience multisystemic deterioration. Older patients often require gastrostomy tube placement for nutritional support. For optimizing the perioperative care, a practice of multidisciplinary team can better anticipate, prevent, and manage possible complications and reduce the overall perioperative morbidity and mortality. AIMS: The aim of this study was to review our experience with perioperative care of adolescent and young adults with Duchenne muscular dystrophy undergoing gastrostomy by various surgical approaches in order to identify challenges and improve future perioperative care coordination to reduce morbidity. METHODS: We retrospectively examined cases of gastrostomy tube placement in patients of ages 15 years and older between 2005 and 2016. We reviewed preoperative evaluation, anesthetic and surgical management, and postoperative complications. RESULTS: Twelve patients were identified; 1 had open gastrostomy, 3 laparoscopic gastrostomies, 5 percutaneous endoscopic guided, and 3 radiologically inserted gastrostomy tubes. All patients had preoperative cardiac evaluation with 6 patients demonstrating cardiomyopathy. Nine patients had preoperative pulmonary consultations and the pulmonary function tests reported forced vital capacity of ≤36% of predicted. Eight patients were noninvasive positive pressure ventilation dependent. General anesthesia with tracheal intubation was administered in 8 patients, and intravenous sedation in 4 patients; 1 received sedation supplemented with regional anesthesia and 3 received deep sedation. One patient had a difficult intubation that resulted in trauma and prolonged tracheal intubation. Three patients developed postoperative respiratory complications. Two patients' procedures were postponed due to inadequate preoperative evaluation and 1 because of disagreement between anesthesia and procedural services as to the optimal approach for airway management. CONCULSION: Optimal management of the perioperative care of Duchenne muscular dystrophy patients requires input from relevant medical specialists, proceduralist and anesthesiologist. This complexity of care coordination presents an opportunity for anesthesiologists to lead a collaborative perioperative team in management of advanced Duchenne patients coming for gastrostomy.

The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rapidly progressive, lethal neuromuscular disorder, present from birth, which occurs almost exclusively in males. We have reviewed contemporary evidence of burden, epidemiology, illness costs and treatment patterns of DMD. This systematic review adhered to published methods with information also sought from the web and contacting registries. Searches were carried out from 2005 to June 2015. The population of interest was individuals with clearly defined DMD or their carers. RESULTS: Nine thousand eight hundred fifty titles were retrieved from searches. Fifty-eight studies were reviewed with three assessed as high, 33 as medium and 22 as low quality. We found two studies reporting birth and four reporting point prevalence, three reporting mortality, 41 reporting severity and/or progression, 18 reporting treatment patterns, 12 reporting quality of life, two reporting utility measures, three reporting costs of illness and three treatment guidelines. Birth prevalence ranged from 15.9 to 19.5 per 100,000 live births. Point prevalence per 100,000 males was for France, USA, UK and Canada, 10.9, 1.9, 2.2 and 6.1 respectively. A study of adult DMD patients at a centre in France found median survival for those born between 1970 and 1994 was 40.95 years compared to 25.77 years for those born between 1955 and 1969. Loss of ambulation occurred at a median age of 12 and ventilation starts at about 20 years. There was international variation in use of corticosteroids, scoliosis surgery, ventilation and physiotherapy. The economic cost of DMD climbs dramatically with disease progression - rising as much as 5.7 fold from the early ambulatory phase to the non-ambulatory phase in Germany. CONCLUSIONS: This is the first systematic review of treatment, progression, severity and quality of life in DMD. It also provides the most recent description of the burden, epidemiology, illness costs and treatment patterns in DMD. There are evidence gaps, particularly in prevalence and mortality. People with DMD seem to be living longer, possibly due to corticosteroid use, cardiac medical management and ventilation. Future research should incorporate registry data to improve comparability across time and between countries and to investigate the quality of life impact as the condition progresses.

Evaluation of the Unit Rod surgical instrumentation in Duchenne scoliosis. A retrospective study.

The article represents a retrospective clinical and radiological study. Objectives. Evaluating the safety and efficiency of the surgical treatment by using the Unit Rod for scoliosis in adolescents and children presenting Duchenne's muscular dystrophy. Summary. Surgical management of myopathic scoliosis still causes controversies regarding the timing of surgery (patient's age), the pelvic inclusion in the arthrodesis or the advantages of surgery over the conservatory treatment. The patients are very fragile and a long surgery with massive blood loss could lead to serious complications. Unit Rod instrumentation is simple, confers excellent stability and has a low rate of complications. Methods. This is a retrospective clinical and radiological study with a medium follow-up of 6.9 years including 13 patients diagnosed with Duchenne myopathy. All investigated patients were non-ambulatory at the time of surgery and have been treated by the Unit Rod technique at the University Hospital of Rouen between 2002 and 2008. Spinal fusion was, in all cases, realized from T2 to pelvis. Galveston technique of pelvic fixation and Luque's sublaminar wire instrumentation of the spine were used. Results. The results obtained with this treatment and post-surgery complications were analyzed and compared with those from literature. The advantages of this technique consist mostly in a good and stable pelvic fixation, a short interventional time, a minimal blood loss and few complications. Cobb angle correction is similar to that obtained by other surgical procedures. Conclusions. Using the Unit Rod instrumentation of scoliosis in Duchenne's muscular dystrophy is safe, has excellent outcomes, brings post-surgery improvements, and has minor intra and post-surgery complications. The low cost of this treatment could make it a first choice for medical health systems with financial problems.

Adenoviral vectors encoding CRISPR/Cas9 multiplexes rescue dystrophin synthesis in unselected populations of DMD muscle cells.

Mutations disrupting the reading frame of the ~2.4 Mb dystrophin-encoding DMD gene cause a fatal X-linked muscle-wasting disorder called Duchenne muscular dystrophy (DMD). Genome editing based on paired RNA-guided nucleases (RGNs) from CRISPR/Cas9 systems has been proposed for permanently repairing faulty DMD loci. However, such multiplexing strategies require the development and testing of delivery systems capable of introducing the various gene editing tools into target cells. Here, we investigated the suitability of adenoviral vectors (AdVs) for multiplexed DMD editing by packaging in single vector particles expression units encoding the Streptococcus pyogenes Cas9 nuclease and sequence-specific gRNA pairs. These RGN components were customized to trigger short- and long-range intragenic DMD excisions encompassing reading frame-disrupting exons in patient-derived muscle progenitor cells. By allowing synchronous and stoichiometric expression of the various RGN components, we demonstrate that dual RGN-encoding AdVs can correct over 10% of target DMD alleles, readily leading to the detection of Becker-like dystrophin proteins in unselected muscle cell populations. Moreover, we report that AdV-based gene editing can be tailored for removing mutations located within the over 500-kb major DMD mutational hotspot. Hence, this single DMD editing strategy can in principle tackle a broad spectrum of mutations present in more than 60% of patients with DMD.

Peripheral nerve blocks as the sole anesthetic technique in a patient with severe Duchenne muscular dystrophy.

General anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are associated with high risks of complications, including rhabdomyolysis, malignant hyperthermia, hemodynamic instability, and postoperative mechanical ventilation. Here, we describe peripheral nerve blocks as a safe approach to anesthesia in a patient with severe Duchenne muscular dystrophy who was scheduled to undergo surgery. A 22-year-old male patient was scheduled to undergo reduction and internal fixation of a left distal femur fracture. He had been diagnosed with Duchenne muscular dystrophy at 5 years of age, and had no locomotive capability except for that of the finger flexors and toe extensors. He had developed symptoms associated with dyspnea 5 years before and required intermittent ventilation. We blocked the femoral nerve, lateral femoral cutaneous nerve, and parasacral plexus under ultrasound on the left leg. The patient underwent a successful operation using peripheral nerve blocks with no complications. In conclusion general anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are unsafe approaches to anesthesia because of hemodynamic instability and respiratory depression. Peripheral nerve blocks are the best way to reduce the risks of critical complications, and are a safe and feasible approach to anesthesia in patients with severe Duchenne muscular dystrophy.

Long-term Follow-up of Pulmonary Function and Scoliosis in Patients With Duchenne's Muscular Dystrophy and Spinal Muscular Atrophy.

BACKGROUND: Spine surgery for neuromuscular scoliosis in patients with Duchenne's Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) remained controversial. This study aimed to review the long-term results of spine surgery and its effect on pulmonary function in these patients. METHODS: A retrospective review was conducted for the above patients who had undergone surgery from 1990 to 2006 in a tertiary hospital. Their yearly lung function tests, clinical records, and x-ray films before and after surgery were reviewed. All patients had at least 2 lung function tests performed before surgery and at least 3 lung function tests performed after surgery. Records of perioperative pulmonary infections that resulted in hospital admissions were also retrieved from the hospital computer system. RESULTS: Forty patients were reviewed: 29 with DMD, 11 with SMA. The mean follow-up period was 11.6 years. For patients with DMD, the mean correction of Cobb's angle from surgery was 34.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 7.80% per year, and was reduced to 4.26% per year postoperatively (P<0.001). For patients with SMA, the mean correction of Cobb's angle from surgery was 44.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 5.31% per year, and was reduced to 1.77% per year postoperatively (P<0.001). For both DMD and SMA patients, the difference between the rate of preoperative and postoperative pulmonary infections that resulted in hospital admission were, however, not significant (P=0.433 and 0.452, respectively). CONCLUSIONS: Scoliosis surgery in patients with DMD and SMA results in a long-term decreased rate of decline in pulmonary function over a follow-up period of more than 10 years. The level of the apical vertebrae of the scoliosis did not demonstrate a significant trend on the pulmonary function. The frequency of chest infections did not improve by scoliosis surgery. LEVEL OF SIGNIFICANCE: Level III­Retrospective study.

Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy.

Intra-arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first-in-human, exploratory, non-randomized open-label phase I-IIa clinical trial of intra-arterial HLA-matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor-derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2-month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor-derived dystrophin in 1. Intra-arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy.

[Mitral valve replacement for a manifesting carrier of duchenne muscular dystrophy].

Duchenne muscular dystrophy (DMD) is an X-linked disease, but female carriers infrequently have some symptoms, who are called manifesting carriers. Here we report a case of a manifesting carrier of DMD with skeletal muscle weakness and cardiac abnormalities such as deterioration of cardiac function and left ventricular dilatation, who successfully underwent cardiac surgery. A 79-year-old female with acute heart failure for severe mitral regurgitation was admitted to our hospital. Surgical replacement of the mitral valve was performed under general anesthesia with intravenous anesthetics and non-depolarizing muscle relaxant. Cardiac surgery on a manifesting carrier of DMD is rare and requires a careful preoperative assessment of the heart function and anesthetic management.

Incidence and risk factors for post-operative complications after scoliosis surgery in patients with Duchenne muscular dystrophy : a comparison with other neuromuscular conditions.

We report the incidence of and risk factors for complications after scoliosis surgery in patients with Duchenne muscular dystrophy (DMD) and compare them with those of other neuromuscular conditions. We identified 110 (64 males, 46 females) consecutive patients with a neuromuscular disorder who underwent correction of the scoliosis at a mean age of 14 years (7 to 19) and had a minimum two-year follow-up. We recorded demographic and peri-operative data, including complications and re-operations. There were 60 patients with cerebral palsy (54.5%) and 26 with DMD (23.6%). The overall complication rate was 22% (24 patients), the most common of which were deep wound infection (9, 8.1%), gastrointestinal complications (5, 4.5%) and hepatotoxicity (4, 3.6%). The complication rate was higher in patients with DMD (10/26, 38.5%) than in those with other neuromuscular conditions (14/84, 16.7% (p = 0.019). All hepatotoxicity occurred in patients with DMD (p = 0.003), who also had an increased rate of deep wound infection (19% vs 5%) (p = 0.033). In the DMD group, no peri-operative factors were significantly associated with the rate of overall complications or deep wound infection. Increased intra-operative blood loss was associated with hepatotoxicity (p = 0.036). In our series, correction of a neuromuscular scoliosis had an acceptable rate of complications: patients with DMD had an increased overall rate compared with those with other neuromuscular conditions. These included deep wound infection and hepatotoxicity. Hepatotoxicity was unique to DMD patients, and we recommend peri-operative vigilance after correction of a scoliosis in this group.

[Current care strategies for Duchenne muscular dystrophy]. / Aktuelle Betreuungsstrategien bei Duchenne-Muskeldystrophie.

BACKGROUND: The medical care of patients with Duchenne muscular dystrophy (DMD) is an interdisciplinary and multifaceted task. The vast majority of those affected show a nearly constant course which is reflected in a corresponding stage-oriented treatment concept. Although there is still no causal therapy available for DMD, the course and in particular the quality of life of patients can be decisively improved by established medical practices. THERAPEUTIC STRATEGIES: The orthopedic problems of DMD patients include contractures of the upper and lower extremities as well as sitting instability due to progressive scoliosis with pelvic imbalance. The orthopedic treatment incorporates conservative measures, such as physiotherapy, provision of orthotic devices and wheelchairs as well as surgery to resolve contractures of the lower extremities and surgical stabilization of the spine. Furthermore, in these patients orthopedic surgeons and trauma surgeons are confronted with the treatment and prophylaxis of fractures induced by osteoporosis. An early onset of glucocorticoid therapy markedly delays the loss of motor abilities. TREATMENT ASPECTS: An important aspect in the care of DMD patients is the timely prophylaxis and treatment of respiratory insufficiency with regular sessions of breathing therapy, learning breathing and coughing techniques and the sufficiently early start of non-invasive mechanically assisted ventilation. Of similar relevance are also the early recognition and cardioprotective treatment of cardiomyopathy. CONCLUSION: The orthopedic surgeon accompanies the patient and family through all stages of the disease and must be appropriately informed on current management and treatment strategies even outside the limits of the personal field of specialization.

Dexmedetomidine and ketamine sedation for muscle biopsies in patients with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) possesses many potential challenges for anesthetic care. Invasive and noninvasive procedures with corresponding sedation or general anesthesia are frequent and necessary for affected patients. There remains a need for a better agent or agents for procedural sedation in patients with comorbid diseases. This study prospectively evaluated a combination of ketamine with two different doses of dexmedetomidine for sedation during muscle biopsy in patients with DMD. METHODS: Dexmedetomidine 1.0 or 0.5 µg·kg(-1) was administered as a loading dose over 3 min followed by a continuous infusion of 1.0 or 0.5 µg·kg·h(-1). Ketamine (1 mg·kg(-1)) was administered along with the dexmedetomidine loading dose. As the procedure commenced, additional doses of ketamine (0.5 mg·kg(-1)) were administered as needed. Sedation scores, hemodynamic data, operative times, and recovery times were recorded. RESULTS: The study cohort included a total of 53 bicep, deltoid, or anterior tibialis muscle biopsies in 19 boys including 24 in the dexmedetomidine 1.0 µg·kg(-1) group and 29 in the dexmedetomidine 0.5 µg·kg(-1) group. Mean age and weight were 9.7 ± 1.4 years and 33.3 ± 7.7 kg in the dexmedetomidine 1.0 µg·kg(-1) group and 8.8 ± 1.8 years and 30.2 ± 10.8 kg in the dexmedetomidine 0.5 µg·kg(-1) group. No significant changes in blood pressure were noted. A decrease in heart rate (HR) occurred after the loading dose of dexmedetomidine in both groups. The HR was significantly lower in the dexmedetomidine 1.0 µg·kg(-1) group compared with the dexmedetomidine 0.5 µg·kg(-1) group. Total recovery time to discharge was significantly shorter in the dexmedetomidine 0.5 µg·kg(-1) group than the dexmedetomidine 1.0 µg·kg(-1) group (146 ± 65 vs 174 ± 58 min; P = 0.03), although the total ketamine dose was significantly greater in the dexmedetomidine 0.5 µg·kg(-1) group (3.7 ± 1.0 vs 2.0 ± 0.5 mg·kg(-1); P < 0.01). There were no episodes of apnea or hypoventilation; however, a jaw thrust was needed in one patient in the dexmedetomidine 1.0 µg·kg(-1) group. CONCLUSION: The combination of dexmedetomidine and ketamine is safe and effective for moderately painful procedures with limited respiratory and cardiovascular effects in a high-risk patient population. Dexmedetomidine 0.5 µg·kg(-1) as a loading dose with ketamine followed by a continuous infusion of dexmedetomidine at 0.5 µg·kg(-1) ·h(-1) achieved an adequate sedation level with shorter total recovery times in the perioperative unit compared with a higher dose regimen of dexmedetomidine (1.0 µg·kg(-1) loading dose followed by an infusion at 1.0 µg·kg(-1) ·h(-1)).