A Sustainable and Scalable Multidisciplinary Airway Teaching Mission: The Operation Airway 10-Year Experience.

OBJECTIVE: To address whether a multidisciplinary team of pediatric otolaryngologists, anesthesiologists, pediatric intensivists, speech-language pathologists, and nurses can achieve safe and sustainable surgical outcomes in low-resourced settings when conducting a pediatric airway surgical teaching mission that features a program of progressive autonomy. STUDY DESIGN: Consecutive case series with chart review. SETTING: This study reviews 14 consecutive missions from 2010 to 2019 in Ecuador, El Salvador, and the Dominican Republic. METHODS: Demographic data, diagnostic and operative details, and operative outcomes were collected. A country's program met graduation criteria if its multidisciplinary team developed the ability to autonomously manage the preoperative huddle, operating room discussion and setup, operative procedure, and postoperative multidisciplinary pediatric intensive care unit and floor care decision making. This was assessed by direct observation and assessment of surgical outcomes. RESULTS: A total of 135 procedures were performed on 90 patients in Ecuador (n = 24), the Dominican Republic (n = 51), and El Salvador (n = 39). Five patients required transport to the United States to receive quaternary-level care. Thirty-six laryngotracheal reconstructions were completed: 6 single-stage, 12 one-and-a-half-stage, and 18 double-stage cases. We achieved a decannulation rate of 82%. Two programs (Ecuador and the Dominican Republic) met graduation criteria and have become self-sufficient. No mortalities were recorded. CONCLUSION: This is the largest longitudinal description of an airway reconstruction teaching mission in low- and middle-income countries. Airway reconstruction can be safe and effective in low-resourced settings with a thoughtful multidisciplinary team led by local champions.

Effect of anesthesia on evoked auditory responses in pediatric auditory brainstem implant surgery.

OBJECTIVE: Electrically evoked auditory brainstem responses (EABR) guide placement of the multichannel auditory brainstem implant (ABI) array during surgery. EABRs are also recorded under anesthesia in nontumor pediatric ABI recipients prior to device activation to confirm placement and guide device programming. We examine the influence of anesthesia on evoked response morphology in pediatric ABI users by comparing intraoperative with postoperative EABR recordings. STUDY DESIGN: Retrospective review. METHODS: Seven children underwent ABI surgery by way of retrosigmoid craniotomy. General anesthesia included inhaled sevoflurane induction and propofol maintenance during which EABRs were recorded to confirm accurate positioning of the ABI. A mean of 7.7 ± 2.8 weeks following surgery, the ABI was activated under general anesthesia or sedation (dexmedetomidine) and EABR recordings were made. A qualitative analysis of intraoperative and postoperative waveform morphology was performed. RESULTS: Seven subjects (mean age 20.6 months) underwent nine ABI surgeries (seven primary, two revisions) and nine activations. EABRs were observed in eight of nine postoperative recordings. In three cases, intraoperative EABRs during general anesthesia were similar to postoperative EABRs with sedation. In one case, sevoflurane and propofol were used for intra- and postoperative recordings, and waveforms were also similar. In four cases, amplitude and latency changes were observed for intraoperative versus postoperative EABRs. CONCLUSION: Similarity of EABR morphology in the anesthetized versus sedated condition suggests that anesthesia does not have a large effect on far-field evoked potentials. Changes in EABR waveform morphology observed postoperatively may be influenced by other factors such as movements of the surface array. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:507-513, 2020.

Successful Use of High-Flow Nasal Cannula for Concurrent Vocal Cord Electromyography and Tubeless Microlaryngeal Surgery in a Spontaneously Breathing Adult Patient: A Case Report.

Ventilation during microlaryngoscopy previously included jet ventilation, microlaryngeal endotracheal tubes, and extended apnea. Historically, apneic oxygenation provided a tubeless field but limited operative time. Increased utilization of high-flow nasal cannula in intensive care units and operating rooms has created new opportunities to expand tubeless microlaryngoscopy. Although few studies have described high-flow nasal cannula for microlaryngoscopy, there remains much to be explored. In this case report, we describe the unique setting of utilizing high-flow nasal cannula in a spontaneously breathing patient to create an optimal tubeless surgical field for both microlaryngoscopy and vocal cord electromyography.

Nonsurgically induced disuse muscle atrophy and neuromuscular dysfunction upregulates alpha7 acetylcholine receptors.

Previous models of muscle disuse have invariably used surgical methods that require the repetitive application of plaster casts. A method of disuse atrophy that does not require such repetitive applications is described herein. Modified plastic pipette tubing was applied to a single hindlimb (mouse), from thigh to foot, resulting in immobilization of the knee in the extension position, and the ankle in the plantar flexion position. This method resulted in the loss of soleus muscle to 11%, 22%, 39%, and 45% of its original mass at 3, 7, 14, and 21 days, respectively, in association with a significant decrease of tibialis twitch (25%) and tetanic tensions (26%) at 21 days, compared with the contralateral side and (or) sham-immobilized controls. Immunohistochemical analysis of the soleus using fluorescent α-bungarotoxin revealed a significant increase in the number of synapses per unit area (818 + 31 compared with 433 + 16/mm(2)) and an increase in muscle fibers per unit area (117 compared with 83/mm(2)), most likely related to the atrophy of muscle fibers bringing synapses closer. A 3-fold increase in alpha7 acetylcholine receptor (α7AChR) protein expression, along with increased expression of α1AChR subunit in the immobilized side compared with the contralateral side was observed. The physiology and pharmacology of the novel finding of upregulation of α7AChRs with disuse requires further study.

Mitochondria, endoplasmic reticulum, and alternative pathways of cell death in critical illness.

Dying cells are distinguished by their biochemical and morphologic traits and categorized into three subtypes: apoptosis, oncosis (necrosis), and cell death with autophagy. Each of these types of cell death plays critical roles in tissue morphogenesis during normal development and in the pathogenesis of human diseases. Given that tissue homeostasis is controlled by the intricate balance between degeneration and regeneration, it is essential to understand the mechanisms of different forms of cell death to establish and improve therapeutic interventions for prevention and rescue of these cell death-related disorders. Critical illness, including sepsis, trauma, and burn injury, is often complicated by multiple organ dysfunction syndrome and is accompanied by increased cell death in parenchymal and nonparenchymal tissues. Accumulating evidence suggests that augmented cell death plays an important role in the organ failure in critical illness. We discuss possible therapeutic approaches for prevention of cell death, particularly apoptotic cell death.

Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction: the state of functional ischemia. Until now, however, the cause-effect relationship between the pathogenesis of DMD and functional ischemia was unclear. We examined (i) whether functional ischemia is necessary to cause contraction-induced myofiber damage and (ii) whether functional ischemia alone is sufficient to induce the damage. METHODOLOGY/PRINCIPAL FINDINGS: In vivo microscopy was used to document assays developed to measure intramuscular red blood cell flux, to quantify the amount of vasodilatory molecules produced from myofibers, and to determine the extent of myofiber damage. Reversal of functional ischemia via pharmacological manipulation prevented contraction-induced myofiber damage in mdx mice, the murine equivalent of DMD. This result indicates that functional ischemia is required for, and thus an essential cause of, muscle damage in mdx mice. Next, to determine whether functional ischemia alone is enough to explain the disease, the extent of ischemia and the amount of myofiber damage were compared both in control and mdx mice. In control mice, functional ischemia alone was found insufficient to cause a similar degree of myofiber damage observed in mdx mice. Additional mechanisms are likely contributing to cause more severe myofiber damage in mdx mice, suggestive of the existence of a "two-hit" mechanism in the pathogenesis of this disease. CONCLUSIONS/SIGNIFICANCE: Evidence was provided supporting the essential role of functional ischemia in contraction-induced myofiber damage in mdx mice. Furthermore, the first quantitative evidence for the "two-hit" mechanism in this disease was documented. Significantly, the vasoactive drug tadalafil, a phosphodiesterase 5 inhibitor, administered to mdx mice ameliorated muscle damage.

Long-term effects of botulinum toxin on neuromuscular function.

BACKGROUND: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium. METHODS: Rats (n=30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n=9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated. RESULTS: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups. CONCLUSION: Botulinum toxin causes dose-dependent long-term neuromuscular changes. The loss of tension generating capacity is almost exclusively related to muscle atrophy, because the specific tension did not change. The decreased ED10, unaltered ED50, and increased ED90 to atracurium suggest its interactions with different isoforms of receptors having varying sensitivity to atracurium. The absence of fade, despite the persistent botulinum toxin-induced denervation (increased nAChRs), suggests that the up-regulated nAChRs may have compensated for the prejunctional effects of botulinum toxin.

In vivo micro-circulation measurement in skeletal muscle by intra-vital microscopy.

BACKGROUND: Regulatory factors and detailed physiology of in vivo microcirculation have remained not fully clarified after many different modalities of imaging had invented. While many macroscopic parameters of blood flow reflect flow velocity, changes in blood flow velocity and red blood cell (RBC) flux does not hold linear relationship in the microscopic observations. There are reports of discrepancy between RBC velocity and RBC flux, RBC flux and plasma flow volume, and of spatial and temporal heterogeneity of flow regulation in the peripheral tissues in microscopic observations, a scientific basis for the requirement of more detailed studies in microcirculatory regulation using intravital microscopy. METHODS: We modified Jeff Lichtman's method of in vivo microscopic observation of mouse sternomastoid muscles. Mice are anesthetized, ventilated, and injected with PKH26L-fluorescently labeled RBCs for microscopic observation. RESULT & CONCLUSIONS: Fluorescently labeled RBCs are detected and distinguished well by a wide-field microscope. Muscle contraction evoked by electrical stimulation induced increase in RBC flux. Quantification of other parameters including RBC velocity and capillary density were feasible. Mice tolerated well the surgery, injection of stained RBCs, microscopic observation, and electrical stimulation. No muscle or blood vessel damage was observed, suggesting that our method is relatively less invasive and suited for long-term observations.

Adipocyte apoptosis after burn injury is associated with altered fat metabolism.

Burn injury often is associated with the abnormal lipid metabolism, including hyperlipidemia, desensitization to lipolytic responses to catecholamines, and reduction in the size of the white adipose tissue. Understanding the biological mechanisms for the decrease in fat mass despite desensitization to catecholamines is important both for the study of lipid metabolism and for the study of its relationship to concomitant insulin resistance. Using epididymal adipose tissue from adult male Sprague-Dawley rats after burn injury (n = 102) or sham-burn injury (n = 102), we tested the hypothesis that a whole-body burn injury causes apoptosis in that tissue. At 1, 3, and 7 days after 40% to 50% body burn injury to the rat, epidydimal adipose tissue was harvested and studied for apoptotic changes and lipolytic properties. For apoptosis, paraformaldehyde-fixed tissue sections were analyzed by in situ TdT-mediated dUTP-X nick-end labeling (TUNEL) staining, and tissue homogenates were also analyzed for DNA fragmentation by enzyme-linked immunoassay and ligation-mediated polymerase chain reaction ladder assay. Isolated adipocytes were stimulated with isoprotenerol, and glycerol production was measured as a reflector of effectiveness of lipolysis. Epididymal adipose tissue showed increased apoptosis manifested by the positive TUNEL staining and increased DNA fragmentation by enzyme-linked immunoassay at day 3 and 7 after burn injury. The DNA fragmentation was confirmed further by the ligation-mediated polymerase chain reaction ladder assay. This elevated DNA fragmentation persisted in the burned animals from day 3 until day 7 after burn injury, the end of observation period. Increase in apoptosis was correlated with decrease in DNA content and tissue weight in the epidydimis. At the functional level, a significant decrease in isoproterenol-induced lipolytic activity (glycerol production) was observed to almost 50% of control level at day 3 and 7 but was not decreased at day 1. Apoptosis of adipocytes may play a role in the altered lipid metabolism, including hyperlipidemia observed in burned subjects.