Anesthetic Hypersensitivity in a Case-Controlled Series of Patients With Mitochondrial Disease.

BACKGROUND: Children with mitochondrial disease undergo anesthesia for a wide array of surgical procedures. However, multiple medications used for their perioperative care can affect mitochondrial function. Defects in function of the mitochondrial electron transport chain (ETC) can lead to a profound hypersensitivity to sevoflurane in children. We studied the sensitivities to sevoflurane, during mask induction and maintenance of general anesthesia, in children presenting for muscle biopsies for diagnosis of mitochondrial disease. METHODS: In this multicenter study, 91 children, aged 6 months to 16 years, presented to the operating room for diagnostic muscle biopsy for presumptive mitochondrial disease. General anesthesia was induced by a slow increase of inhaled sevoflurane concentration. The primary end point, end-tidal (ET) sevoflurane necessary to achieve a bispectral index (BIS) of 60, was recorded. Secondary end points were maximal sevoflurane used to maintain a BIS between 40 and 60 during the case, and maximum and minimum heart rate and blood pressures. After induction, general anesthesia was maintained according to the preferences of the providers directing the cases. Primary data were analyzed comparing data from patients with complex I deficiencies to other groups using nonparametric statistics in SPSS v.27. RESULTS: The median sevoflurane concentration to reach BIS of 60 during inductions (ET sevoflurane % [BIS = 60]) was significantly lower for patients with complex I defects (0.98%; 95% confidence interval [CI], 0.5-1.4) compared to complex II (1.95%; 95% CI, 1.2-2.7; P < .001), complex III (2.0%; 95% CI, 0.7-3.5; P < .001), complex IV (2.0%; 95% CI, 1.7-3.2; P < .001), and normal groups (2.2%; 95% CI, 1.8-3.0; P < .001). The sevoflurane sensitivities of complex I patients did not reach significance when compared to patients diagnosed with mitochondrial disease but without an identifiable ETC abnormality (P = .172). Correlation of complex I activity with ET sevoflurane % (BIS = 60) gave a Spearman's coefficient of 0.505 (P < .001). The differences in sensitivities between groups were less during the maintenance of the anesthetic than during induction. CONCLUSIONS: The data indicate that patients with complex I dysfunction are hypersensitive to sevoflurane compared to normal patients. Hypersensitivity was less common in patients presenting with other mitochondrial defects or without a mitochondrial diagnosis.

Assessment of muscle oxygenation in children with congenital heart disease.

BACKGROUND: Adaptive responses to congenital heart disease result in altered muscle perfusion and muscle metabolism. Such changes may be detectable using noninvasive spectroscopic monitors. AIMS: In this study we aimed to determine if resting muscle oxygen saturation (MOx) is lower in children with acyanotic or cyanotic congenital heart disease than in healthy children and to identify differences in muscle oxygen consumption in children with cyanotic and acyanotic congenital heart disease. METHODS: Using a custom fiber optic spectrometer system, optical measurements were obtained from the calf or forearm of 49 patients (17 with acyanotic congenital heart disease, 18 with cyanotic congenital heart disease, and 14 control). Twenty additional control patients were used to develop the analytic model. Spectra were used to determine MOx at baseline, during arterial occlusion, and during reperfusion. The rate of muscle desaturation during arterial occlusion was also evaluated. Two-sample t-tests were used to compare each heart disease group with the controls. RESULTS: Patients with acyanotic and cyanotic congenital heart disease had lower baseline MOx than controls. Baseline MOx was 91.3% (CI 85.9%, 96.7%) for acyanotic patients, 91.1% (CI 86.3%, 95.9%) for cyanotic patients, and 98.9% (CI 96.7%, 101.1%) for controls. Similarly, MOx was lower in the acyanotic and cyanotic groups than the controls after reperfusion (84.6% [CI 74.1%, 95.1%] and 82.1% [CI 74.5%, 89.7%] vs 98.9% [96.5%, 101.3%]). The rate of decline in oxygenation was significantly greater in cyanotic patients versus controls (0.46%/s (CI 0.30%, 0.62%/s) vs 0.17%/s (0.13%, 0.21%/s)). CONCLUSION: This study demonstrates that muscle oxygenation is abnormal in children with both cyanotic and acyanotic congenital heart disease. This suggests that noninvasive monitoring of muscle oxygenation may provide valuable information in situations where children with congenital heart disease may be at risk of hemodynamic compromise.

Endoscopic Versus Open Repair for Craniosynostosis in Infants Using Propensity Score Matching to Compare Outcomes: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The North American Pediatric Craniofacial Collaborative Group (PCCG) established the Pediatric Craniofacial Surgery Perioperative Registry to evaluate outcomes in infants and children undergoing craniosynostosis repair. The goal of this multicenter study was to utilize this registry to assess differences in blood utilization, intensive care unit (ICU) utilization, duration of hospitalization, and perioperative complications between endoscopic-assisted (ESC) and open repair in infants with craniosynostosis. We hypothesized that advantages of ESC from single-center studies would be validated based on combined data from a large multicenter registry. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. We analyzed 1382 infants younger than 12 months undergoing open (anterior and/or posterior cranial vault reconstruction, modified-Pi procedure, or strip craniectomy) or endoscopic craniectomy. The primary outcomes included transfusion data, ICU utilization, hospital length of stay, and perioperative complications; secondary outcomes included anesthesia and surgical duration. Comparison of unmatched groups (ESC: N = 311, open repair: N = 1071) and propensity score 2:1 matched groups (ESC: N = 311, open repair: N = 622) were performed by conditional logistic regression analysis. RESULTS: Imbalances in baseline age and weight are inherent due to surgical selection criteria for ESC. Quality of propensity score matching in balancing age and weight between ESC and open groups was assessed by quintiles of the propensity scores. Analysis of matched groups confirmed significantly reduced utilization of blood (26% vs 81%, P < .001) and coagulation (3% vs 16%, P < .001) products in the ESC group compared to the open group. Median blood donor exposure (0 vs 1), anesthesia (168 vs 248 minutes) and surgical duration (70 vs 130 minutes), days in ICU (0 vs 2), and hospital length of stay (2 vs 4) were all significantly lower in the ESC group (all P < .001). Median volume of red blood cell administered was significantly lower in ESC (19.6 vs 26.9 mL/kg, P = .035), with a difference of approximately 7 mL/kg less for the ESC (95% confidence interval for the difference, 3-12 mL/kg), whereas the median volume of coagulation products was not significantly different between the 2 groups (21.2 vs 24.6 mL/kg, P = .73). Incidence of complications including hypotension requiring treatment with vasoactive agents (3% vs 4%), venous air embolism (1%), and hypothermia, defined as <35°C (22% vs 26%), was similar between the 2 groups, whereas postoperative intubation was significantly higher in the open group (2% vs 10%, P < .001). CONCLUSIONS: This multicenter study of ESC versus open craniosynostosis repair represents the largest comparison to date. It demonstrates striking advantages of ESC for young infants that may result in improved clinical outcomes, as well as increased safety.

Perioperative Outcomes and Management in Pediatric Complex Cranial Vault Reconstruction: A Multicenter Study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND: The Pediatric Craniofacial Collaborative Group established the Pediatric Craniofacial Surgery Perioperative Registry to elucidate practices and outcomes in children with craniosynostosis undergoing complex cranial vault reconstruction and inform quality improvement efforts. The aim of this study is to determine perioperative management, outcomes, and complications in children undergoing complex cranial vault reconstruction across North America and to delineate salient features of current practices. METHODS: Thirty-one institutions contributed data from June 2012 to September 2015. Data extracted included demographics, perioperative management, length of stay, laboratory results, and blood management techniques employed. Complications and outlier events were described. Outcomes analyzed included total blood donor exposures, intraoperative and perioperative transfusion volumes, and length of stay outcomes. RESULTS: One thousand two hundred twenty-three cases were analyzed: 935 children aged less than or equal to 24 months and 288 children aged more than 24 months. Ninety-five percent of children aged less than or equal to 24 months and 79% of children aged more than 24 months received at least one transfusion. There were no deaths. Notable complications included cardiac arrest, postoperative seizures, unplanned postoperative mechanical ventilation, large-volume transfusion, and unplanned second surgeries. Utilization of blood conservation techniques was highly variable. CONCLUSIONS: The authors present a comprehensive description of perioperative management, outcomes, and complications from a large group of North American children undergoing complex cranial vault reconstruction. Transfusion remains the rule for the vast majority of patients. The occurrence of numerous significant complications together with large variability in perioperative management and outcomes suggest targets for improvement.

Instillation of liposomes vs dimethyl sulphoxide or pentosan polysulphate for reducing bladder hyperactivity.

OBJECTIVE: To investigate the efficacy of intravesical liposomes against dimethyl sulphoxide (DMSO), and pentosan polysulphate (PPS) in reducing chemically induced bladder hyperactivity in rats. MATERIALS AND METHODS: Bladder reflex activity of female Sprague-Dawley rats was evaluated by continuous cystometry under urethane anaesthesia (1.0 g/kg). After obtaining a control cystometrogram (CMG) with normal saline (0.04 mL/min) for 2 h, bladder hyperactivity was then induced by 1 h infusion of protamine sulphate (10 mg/mL) followed by a 1-h infusion of KCl (500 mm). Six rats each were then infused with KCl-based preparations containing either 50% DMSO, PPS (6 mg/mL), or liposomes (2 mg/mL) for 2 h. The variables measured included the intercontraction interval (ICI), pressure threshold (PT) and baseline pressure (BP). RESULTS: Sequential infusion of protamine sulphate/KCl induced hyperactive bladder with no significant difference in ICI, PT or BP among groups before initiating treatment. ICI was significantly increased after infusion of PPS (58.1% increase) and liposomes (156.8% increase) but there was no increase with DMSO. PT was not significantly affected by liposome infusion but slightly increased with PPS (12.4% increase). There was a large and significant increase in PT and BP with DMSO (116.5% increase) and BP largely remained unchanged after instillation with liposomes or PPS. CONCLUSIONS: Intravesical liposomes and PPS have a beneficial effect in a bladder hyperactivity rat model, while acute instillation of DMSO does not. Intravesical liposomes were effective in doubling the ICI compared with PPS, and might be a new treatment option for bladder hyperactivity.

Measuring proteins with greater speed and resolution while reducing sample size.

A multi-angle light scattering (MALS) system, combined with chromatographic separation, directly measures the absolute molar mass, size and concentration of the eluate species. The measurement of these crucial properties in solution is essential in basic macromolecular characterization and all research and production stages of bio-therapeutic products. We developed a new MALS methodology that has overcome the long-standing, stubborn barrier to microliter-scale peak volumes and achieved the highest resolution and signal-to-noise performance of any MALS measurement. The novel design simultaneously facilitates online dynamic light scattering (DLS) measurements. As National Institute of Standards and Technology (NIST) new protein standard reference material (SRM 8671) is becoming the benchmark molecule against which many biomolecular analytical techniques are assessed and evaluated, we present its measurement results as a demonstration of the unique capability of our system to swiftly resolve and measure sharp (20~25 µL full-width-half-maximum) chromatography peaks. Precise measurements of protein mass and size can be accomplished 10 times faster than before with improved resolution. In the meantime the sample amount required for such measurements is reduced commensurately. These abilities will have far-reaching impacts at every stage of the development and production of biologics and bio-therapeutic formulations.

Development and evaluation of a charge capture program for long-term care providers.

OBJECTIVE: Clinicians often have difficulty determining the appropriate Current Procedural Terminology Evaluation and Management code to assign to the type and intensity of patient care they provide. The purpose of this study was to develop, implement, and evaluate a handheld charge capture program for use by providers in the long-term care setting. DESIGN: Using a pre-post study design, we compared the coding accuracy and user satisfaction of an established paper process with a handheld charge capture program created for this study by means of: (1) preimplementation and postimplementation assessment of coding accuracy, and (2) preimplementation and postimplementation clinician survey. SETTING: We studied an academic division of geriatric medicine. PARTICIPANTS: Participants consisted of six clinicians who currently spend at least 50% of their clinical time practicing in the long-term care setting. INTERVENTION: A handheld charge capture program to replace the current paper-based charge capture process was reviewed. RESULTS: Overall coding accuracy improved by approximately 20% when the handheld program was used instead of a paper coding process. The majority of clinicians found that the handheld program was more widely available, efficient, easier to use, and encouraged the participants to document more completely and accurately in the patient's medical record. CONCLUSION: A handheld billing and coding program used by clinicians who provide care for long-term care residents is not only feasible, but leads to an improvement in coding accuracy when compared with a paper process. In addition, clinician satisfaction toward the billing and coding processes improved with the use of the handheld program.

Mitochondrial Disease and Anesthesia

Abstract It is increasingly common for children with mitochondrial disease to undergo surgery and anesthesia. Although many different anesthetics have been used successfully for these patients, serious, unexpected complications have occurred during and following anesthetic exposure. This has led to the widespread opinion among anesthesiologists that mitochondrial patients are at increased risk from the stress of surgery and anesthesia. Defects in function of the mitochondrial electron transport chain can lead to striking hypersensitivity to volatile anesthetics in children. Despite this striking finding, the connection between mitochondrial function and response to anesthetics is unknown. We review here the anesthetic considerations for patients with mitochondrial defects. In addition, we present an approach to anesthetic care of these patients at our institutions.