Charles I. Yang

Effects on lung function of multiple expansion thoracoplasty in children with thoracic insufficiency syndrome: a longitudinal study.

Study Design. Longitudinal study of intraoperative pulmonary function in young children with thoracic hypoplasia and scoliosis undergoing multiple expansion thoracoplasty using the vertical expandable prosthetic titanium ribs (VEPTRs). Objective. To test the long-term efficacy of VEPTR multiple expansion thoracoplasty. Summary of Background Data. To our knowledge, no direct measurements of pulmonary function have been reported with VEPTR expansion thoracoplasty. Methods. There were 10 children with thoracic insufficiency syndrome, secondary to thoracic hypoplasia with progressive scoliosis, studied. A mobile pulmonary function laboratory unit was used to study forced vital capacity (FVC), maximum expiratory flow volume curves, and respiratory system compliance (Crs) with the patient under general anesthesia immediately before and after expansion thoracoplasty. Studies were repeated every 6 months at each subsequent operation for expansion thoracoplasty for the duration up to 33 months. Results. At the baseline studies, FVC showed a moderate-to-severe decrease (69% of predicted values), indicating the presence of significant restrictive lung defect. Only 1 of 10 children had severe airway obstruction. The baseline Crs was markedly decreased in part because of the presence of significant atelectasis. Crs increased with an average of 42% after repeated hyperinflation (deep sighs). There was no change in lung volume or function immediately before versus after completion of expansion thoracoplasty. FVC increased significantly over time, with an average rate of 26.8% per year, the rate of increase similar to that of healthy children of comparative ages. In terms of percent-predicted values, FVC did not change significantly between the baseline and last test, indicating that in most children studied, lung growth kept up with body growth. Conclusion. Although it is difficult to assess the extent of the efficacy without a proper or historical control group for comparison, the present study indicates that in children with severe thoracic insufficiency syndrome, the insertion of VEPTRs with multiple expansion thoracoplasties is beneficial over time, by allowing the lungs to expand with body growth without further deterioration in lung function.

Thoracic malformation with early-onset scoliosis: Effect of serial VEPTR expansion thoracoplasty on lung growth and function in children

The effect on pulmonary function of serial VEPTR expansion thoracoplasty was studied longitudinally in anesthetized children with spondylothoracic dysplasia using a special mobile unit. The median age of 24 children at the start of surgery was 4.6 years (1.8-10.8) and most exhibited a moderate-to-severe restrictive lung defect. After a median of 3.2 years (1.0-6.5), their forced vital capacity (FVC) was found to have increased by an average of 11.1%/year. The rate of increase was greater in children who were younger than 6 years at the start of the study than in older children (14.5% versus 6.5%, p<0.01). The average specific respiratory system compliance (C(rs)) was mildly-to-moderately decreased at the start, and over the study it decreased on average to 56% of the initial value in spite of clinically successful expansion thoracoplasty and lung growth, indicating increasing stiffness of the thorax with growth.

Pulmonary and Radiographic Outcomes of VEPTR (Vertical Expandable Prosthetic Titanium Rib) Treatment in Early-Onset Scoliosis

BACKGROUND VEPTR (vertical expandable prosthetic titanium rib) expansion thoracoplasty is used to manage thoracic insufficiency syndrome in early-onset scoliosis. Literature regarding the effects of this technique on pulmonary function is scarce. The aim of this study was to report the intermediate-term results of VEPTR expansion thoracoplasty. METHODS Twenty-one children with thoracic insufficiency syndrome underwent VEPTR expansion thoracoplasty from 2002 to 2012 and had complete chart data, preoperative and follow-up radiographs, and pulmonary function tests performed at the index implantation, first expansion, and last expansion. Pulmonary function tests with forced and passive deflation techniques developed for children under general anesthesia were performed prior to the index implantation and each expansion surgery under the same anesthetic conditions. Pulmonary and radiographic parameters were analyzed longitudinally. RESULTS Mean follow-up was six years, and mean age at implantation was 4.8 years. The mean number of expansion procedures per patient was eleven, and the mean number of pulmonary function tests was ten. The mean interval between surgical procedures was 6.4 months. Mean forced vital capacity (FVC) increased from 0.65 to 0.96 L (p < 0.0001). However, the percentage of the predicted FVC decreased from 77% to 58%. Respiratory system compliance normalized on the basis of body weight, Crs/kg, decreased by 39%, from 1.4 to 0.86 mL/cm H2O/kg. The mean Cobb angle before treatment was 80°, and the mean maximum thoracic kyphosis angle was 57° (range, 7° to 107°). The initial coronal correction was maintained at the time of final follow-up (67°); however, there was a trend toward a decrease in the maximum thoracic kyphosis angle (to 66°, p = 0.08). Clinically apparent proximal thoracic kyphosis occurred in four patients, and spinal imbalance occurred in seven. The mean gain in T1-T12 height during the treatment period was 18 mm (2.9 mm/year). CONCLUSIONS FVC improved over time; however, this increase in lung volume did not keep up with the growth of the child, as the percentage of the predicted FVC decreased, and the chest wall stiffness increased. Coronal correction was maintained, but the increase in proximal thoracic kyphosis is concerning. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Neuroselective sensory electrodiagnostic evaluation of 4% liposomal topical lidocaine.

We used a neuroselective transcutaneous electrical stimulus to determine the onset time of cutaneous anesthesia with 4% liposomal lidocaine under occluded and nonoccluded conditions. The pain tolerance threshold (PTT) was used to atraumatically evaluate nociception. Twenty adult volunteers had liposomal lidocaine applied to the volar surface of each forearm for durations ranging from 0 through 30 min (at 5-min intervals) under occluded and nonoccluded conditions. The PTT was determined using three different frequencies (2000 Hz, 250 Hz, 5 Hz) stimulating A&bgr;, A&dgr;, and C fibers, respectively. The time to reach the maximum PTT achieved defined the anesthetic onset time for each frequency. A differential onset of cutaneous anesthesia among the three frequencies was clearly demonstrated, however there was no significant difference in onset time between occluded and nonoccluded conditions. Blockade of C fiber transmission occurred significantly earlier than that of A&dgr; (P = 0.029), which occurred earlier than that of A&bgr; (P = 0.001) as determined using the Wilcoxon’s signed rank test. We conclude that a mean onset time of approximately 4 ± 2 min for blockade of C fiber transmission and 6 ± 4 min for A&dgr; fiber transmission suggests that painful stimuli such as venipuncture may be attenuated as early as 7 min.

Artemin growth factor increases nicotinic cholinergic receptor subunit expression and activity in nociceptive sensory neurons

BackgroundArtemin (Artn), a member of the glial cell line-derived growth factor (GDNF) family, supports the development and function of a subpopulation of peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is elevated in inflamed tissue and its injection in skin causes transient thermal hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute to Artn-induced sensitivity. Here we have used gene expression, immunolabeling, patch clamp electrophysiology and behavioral testing assays to investigate the link between Artn, nicotinic subunit expression and thermal hypersensitivity.ResultsReverse transcriptase-PCR validation showed increased levels of mRNAs encoding the nAChR subunits α3 (13.3-fold), β3 (4-fold) and β4 (7.7-fold) in trigeminal ganglia and α3 (4-fold) and β4 (2.8-fold) in dorsal root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased immunoreactivity for nAChRα3 and exhibited increased overlap in labeling with GFRα3-positive neurons. Patch clamp analysis of back-labeled cutaneous afferents showed that while the majority of nicotine-evoked currents in DRG neurons had biophysical and pharmacological properties of α7-subunit containing nAChRs, the Artn-induced increase in α3 and β4 subunits resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or hexamethonium. Complete Freund’s adjuvant (CFA) inflammation of paw skin, which causes an increase in Artn in the skin, also increased the level of nAChR mRNAs in DRG. Finally, the increase in nAChRs transcription was not dependent on the Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated in ganglia of TRPV1/TRPA1 double knockout mice.ConclusionsThese findings suggest that Artn regulates the expression and composition of nAChRs in GFRα3 nociceptors and that these changes contribute to the thermal hypersensitivity that develops in response to Artn injection and perhaps to inflammation.

Bilateral Paravertebral Blockade (T7-10) Versus Incisional Local Anesthetic Administration for Pediatric Laparoscopic Cholecystectomy: A Prospective, Randomized Clinical Study.

BACKGROUND:Single-injection paravertebral nerve blocks (PVBs) provide effective postoperative analgesia after adult laparoscopic cholecystectomy (LC). We sought to compare PVBs with local anesthetic injections at laparoscopic port sites in a pediatric population. METHODS:Eighty-three patients (8–17 years old) scheduled for LC were randomized prospectively to 2 treatment groups: the PVB group received ropivacaine 0.5% injected in the paravertebral space and normal saline injections at laparoscopic instrument sites, and the port infiltration group received normal saline in the paravertebral space and ropivacaine 0.5% at instrument sites. Postoperative analgesia was provided with hydromorphone via patient-controlled analgesia for up to 12 hours, followed by oxycodone and hydromorphone. The total amount of analgesic, serial visual analog scale scores for pain and subject pain control satisfaction, type and characteristics of pain, and complications were recorded for 24 hours. RESULTS:The intraoperative fentanyl requirement (ng/kg/min) was lower in the PVB group than in the port infiltration group (12.81 vs 16.57, P = 0.007). Total postoperative analgesic consumption and mean visual analog scale scores were not different between the groups. Baseline pain recorded before surgery correlated with self-reported postoperative pain scores only in the port infiltration group. The rate of complications was low and similar between groups. There was no difference in incidence of patient-reported incisional, visceral, or gas pain. Shoulder pain, however, was 49% less (95% confidence interval, 0.269–0.893) in the port infiltration group. CONCLUSIONS:PVBs did not reduce postoperative pain associated with pediatric LC but decreased intraoperative fentanyl requirements.

Coagulation Profile of Patients with Adolescent Idiopathic Scoliosis Undergoing Posterior Spinal Fusion.

BACKGROUND Blood loss and transfusion requirements during posterior spinal fusion for adolescent idiopathic scoliosis remain a concern. The mechanism of bleeding in these patients is poorly characterized. Thromboelastography is a comprehensive test of a patients coagulation system commonly used in cardiac surgical procedures. It has not been well studied for use in patients with adolescent idiopathic scoliosis. METHODS A prospective, observational study of the coagulation profile of patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion is presented. Healthy patients with adolescent idiopathic scoliosis without a bleeding abnormality were analyzed during posterior spinal fusion. Standard coagulation laboratory and thromboelastogram measures were obtained at the time of the incision and at 1-hour intervals during the surgical procedure. Laboratory values were analyzed in relation to outcomes such as bleeding, transfusion, and a fibrinolysis score. RESULTS Fifty-eight patients were observed. Eighty-one percent of patients were female, the mean age was 13.5 years, a mean of 11.1 levels were fused, the median estimated blood loss was 645 mL, and 47% of patients received blood products. Overall, laboratory values remained stable throughout the surgical procedure. Mild increases in prothrombin time and partial thromboplastin time were observed, and platelets remained stable. From thromboelastogram analysis, an acceleration of clot formation (decreased reaction time) and a slight increase in clot lysis (increased lysis percentage at 30 minutes) were observed. A fibrinolysis score compiled from the presence of fibrin degradation products, the presence of D-dimers, and increased prothrombin time rose steadily over surgical time. The fibrinolysis score was predictive of both transfusion and greater estimated blood loss per level. CONCLUSIONS The stress of posterior spinal fusion induces a hypercoagulable state in patients with adolescent idiopathic scoliosis. Over the first 2 hours of a surgical procedure, varying degrees of fibrinolysis develop. Platelets and coagulation factors are not depleted. Our data support the use of antifibrinolytic therapy for patients with adolescent idiopathic scoliosis.

The effect of cisatracurium and rocuronium on lung function in anesthetized children.

BACKGROUND: Neuromuscular blocking drugs have been implicated in intraoperative bronchoconstrictive episodes. We examined the effects of clinically relevant doses of cisatracurium and rocuronium on the lung mechanics of pediatric subjects. We hypothesized that cisatracurium and rocuronium would have bronchoconstrictive effects. METHODS: We studied ASA physical status I and II pediatric subjects having elective dental or urological procedures, requiring general anesthesia with endotracheal intubations with either cisatracurium or rocuronium. Pulmonary function tests were performed before and after neuromuscular blocking drug dosing and again after albuterol administration. Using forced deflation and passive deflation techniques, forced vital capacity (FVC) and maximum expiratory flow rate at 10% (MEF10) of FVC were obtained. Fractional changes from the baseline were used to compare subjects. Changes in MEF10 of >30% were considered clinically significant. A Shapiro-Wilk test, paired t test, and Wilcoxon rank sum test were used to analyze the data. RESULTS: Twenty-five subjects (median age = 5.25 years; range = 9 months–9.9 years) were studied; 12 subjects received cisatracurium and 13 subjects received rocuronium. Data are shown as mean proportional change ± SD or, in the case of not normally distributed, median proportional change (first, third quartile) with P values. In the cisatracurium group, there were no differences between baseline and postneuromuscular blocker administration in the fractional change from the baselines of FVC (1.00 ± 0.04, P = 0.5), but there was a significant decrease in MEF10 (0.80 ± 0.18, P = 0.002). In the rocuronium group, there were small yet significant decreases of FVC (0.99 [first quartile 0.97, third quartile 1], P = 0.02) and significant decreases in MEF10 (0.78 ± 0.26, P = 0.008). After administration of albuterol in the cisatracurium group, FVC increased slightly but significantly from baseline values (1.02 ± 0.02, P = 0.005). MEF10 increased significantly beyond baseline values (1.24 ± 0.43, P =0.04). In the rocuronium group, there were also significant differences between baseline and postalbuterol administration from the baseline value of FVC (1.02 ± 0.02, P = 0.004) and MEF10 (1.23 ± 0.29, P = 0.01). CONCLUSIONS: At clinically relevant doses, both cisatracurium and rocuronium caused changes in lung function, indicating constriction of smaller airways. In general, these changes were mild and not clinically detectable. However, in the rocuronium group, 3 of 13 patients showed more noticeable decreases in MEF10 (⩽50%), demonstrating the potential for significant broncho-bronchiolar constriction in susceptible patients.

Case Study of High-Dose Ketamine for Treatment of Complex Regional Pain Syndrome in the Pediatric Intensive Care Unit

Complex regional pain syndrome (CRPS) is a life-altering and debilitating chronic pain condition. The authors are presenting a case study of a female who received high-dose ketamine for the management of her CRPS. The innovative treatment lies not only within the pharmacologic management of her pain, but also in the fact that she was the first patient to be admitted to our pediatric intensive care unit solely for pain control. The primary component of the pharmacotherapy treatment strategy plan was escalating-dose ketamine infusion via patient-controlled-analgesia approved by the pharmacy and therapeutics committee guided therapy for this patient. The expertise of advanced practice nurses blended exquisitely to ensure patient and family-centered care and the coordination of care across the illness trajectory. The patient experienced positive outcomes.