Intravascular Membrane Oxygenation and Carbon Dioxide Removal with IVOX: Can Improved Design and Permissive Hypercapnia Achieve Adequate Respiratory Support During Severe Respiratory Failure?

Abstract: The intravenacaval oxygenator and carbon dioxide removal device (IVOX) conceived by Mortensen at CardioPulmonics is a diffusion–limited device capable of removing 30% of CO₂ production of an adult at normocapnia with minimal reduction in ventilator requirements. Through mathematical modeling, an ex vivo venovenous bypass circuit to model the vena cava and animal models of severe smoke inhalation injury, the practice of permissive hypercapnia has been established to enhance CO₂ removal by IVOX. By allowing the blood PCO₂ to rise gradually, the CO₂ excretion by IVOX can be linearly increased in a 1: 1 relationship. Experimental and clinical studies have shown that CO₂ removal by IVOX increased from 30–40 ml/min at normal blood PCO₂ to 80–90 ml/min at PCO₂ of 90 mm Hg. In addition, IVOX with permissive hypercapnia allowed a significant reduction in minute ventilation and peak airway pressure. Design changes could also improve the performance of IVOX. Increased surface area and mixing with more fibers and crimping in new prototypes of IVOX significantly increased CO₂ removal and oxygen transfer. Active mixing in the blood to decrease the boundary layer resistance can further enhance gas exchange of IVOX. In conclusion, gas exchange by the current design of IVOX is limited, and improvements in design are needed for it to become a more clinically applicable device. Permissive hypercapnia can significantly enhance CO, removal by IVOX as well as significantly reduce ventilator requirements.     

Sudden Wenckebach Periods and Their Relationship to Neurocardiogenic Syncope

Throughout a 9-month period during which 1, 125 Hoiter tapes were reviewed prospectively we identified 13 non medicated patients with an arrhythmia, which for the purposes of this presentation was categorized, because of their mode of initiation, as sudden Wenckebach periods (WP). The episodes emerged abruptly from a normal (± 200 ms) PR interval with sudden prolongation of PR and PP intervals (and reversed PR-RP relationship that took place over 1–8 cycles. The postpaced PR interval was shorter than that of the last conducted beat. The episodes were separated into two groups. Group I included 11 patients with symptoms other than syncope and Group 11 included 2 patients with syncope. There were 26 episodes of sudden WP in Group 1. Twenty-five terminated in a single (and one in double) blocked P waves. Most episodes occurred between 10 PM and 7 AM. Symptoms did not correlate with the episodes. Mean 24-hour rates were < 90. In Group II there were 22 episodes, all occurring between 6 AM and 10 PM. The mean sinus cycle lengths before the phenomenon started to occur in Group I (861 ± 185 ms) as well as the cycle lengths at the onset of block (1,096 ± 215 ms) were statistically longer than those in Group II (591 ± 40 ms and 747 ± 63 ms, respectively, P < 0.0001). Although the mode of onset in the episodes in Group II was similar to Group I, 16 episodes terminated in 2–6 blocked P waves. Thus, the entire number of episodes could be categorized as an unusual type (because of the PR prolongation) of paroxysmal, or advanced second degree A V block. Because these patients had negative electrophysiological studies, positive tilt tests, and absent syncope after oral propranolol therapy, they were considered as having neurocardiogenic syncope. In addition, the faster than normal (> 100) mean 24-hour rates) suggested that they also had so-called inappropriate sinus tachycardia. In summary. Group I consisted of patients with a normal, benign, vagal-induced second-degree AV block, whereas the Hoiter findings in Group II appeared to refiect unusual (but natural, i.e., nonprovoked) electrocardiographic manifestations of certain patients with neurocardiogenic syncope.     

Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings

Computed tomography (CT) was compared with chest radiography in the assessment of disease severity in 27 patients with sarcoidosis. The CT scans and radiographs were each read twice by two independent observers. Disease extent was assessed on CT scans by visual scoring (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification. The severity of parenchymal changes on the CT scan and on the radiograph was significantly correlated with the severity of dyspnea (r = .61 and .58, respectively; P less than .001), diffusing capacity (r = -.62 and -.52, P less than .01), and vital capacity (r = -.49 and -.51, P less than .01). Patients with predominantly irregular opacities had more severe dyspnea and lower lung volumes than patients with predominantly nodular opacities (P less than .05). The authors conclude that in patients with sarcoidosis, the radiographic and CT assessments of disease severity show similar correlation with clinical and functional impairment.     

Nonclinical Toxicology Studies with Zidovudine: Acute, Subacute, and Chronic Toxicity in Rodents, Dogs, and Monkeys

In single dose acute toxicity studies in CD-1 mice and CD rats,the median lethal dose (MLD) for zidovudlne (ZDV) was >750mg/kg after iv dosing and >3000 mg/kg after po administration(recommended human dose is 100 mg every 4 hr while awake). Becauseof the short half-life in rats (0.8 hr), dogs (1.0 hr), andmonkeys (0.8 hr), the daily dose of ZDV in most studies wasgiven in two equal portions approximately 6 hr apart. Intravenousadministration of ZDV was well tolerated in beagle dogs at doselevels up to 42.5 mg/kg bid for 2 weeks and in CD rats at doselevels up to 75 mg/kg bid for 4 weeks. In a 2-week dose range-findingstudy in beagle dogs, cytostatic effects were noted at po doselevels of 62.5 to 250 mg/kg bid in certain tissues with rapidcell replication rates. In contrast, in 3-to 12-month oral toxicitystudies in CD rats and cynomolgus monkeys, the principal toxicologicfinding was reversible macrocytic normochromic anemia whichoccurred at 225–250 mg/kg bid in rats and 17.5–150mg/kg bid in monkeys. In the 12-month rat study, RBC was decreasedat 25 and 75 mg/kg bid. In the 12-month monkey study WBC wasslightly decreased at 150 mg/kg bid.     

Bacterial and Human Cell Mutagenicity and Mouse Lung Tumorigenicity of the Oxygenated Polynuclear Aromatic Hydrocarbon Phenalenone

Phenalenone (perinaphthenone) is a major oxygenated polynucleararomatic hydrocarbon (oxy-PAH) atmospheric pollutant formedfrom the combustion of fossil fuels. Mutagenicity of phenalenonewas measured in quantitative forward mutation assays with Salmonellatyphimurium TM677 and metabolically competent human B-lymphoblastoidcell lines (MCL-5 and hlAlv2 cells), and its tumorigenicitywas also assessed in a newborn mouse assay. Phenalenone wasmutagenic in Salmonella in the presence of rat liver postmitochondrialsupernatant (PMS) at a minimum detectable mutagen concentration(MDMC) of 12 /µg/ml, but was not mutagenic in the absenceof PMS at concentrations up to 100 /µg/ ml. Phenalenonewas not significantly mutagenic in either human cell line after28 hr treatment, although mutant fractions were increased bynearly fivefold in hlAlv2 cells (at the tk locus) exposed at30 µg/ml. However, after 72 hr treatment, phenalenonewas mutagenic at the hprt locus in hlAlv2 cells with an MDMCof 3 µg/ml Phenalenone was also tumorigenic in male BLU:Hamice with a lung tumor incidence of 33% 6 months after injectionwith 4.2 mg phenalenone, the highest dose tested. Lung tumormultiplicity in this treatment group was 0.5 tumor/mouse. Noincrease in lung tumors in female mice was observed. Indicesof lung tumor incidence (ED₅₀) and multiplicity (TM_1.0) formale mice were 29.3 and 34.9 µxmol, respectively. Thesedata suggest that phenalenone does not contribute significantlyto the mutagenicity or carcinogenicity of combustion emissionextracts.     

Method for identification and classification of single motor unit potentials in diagnostic electromyography

It is important to have an objective method for recording jaw muscle capacity such as EMG before, during and after treatment of muscle dysfunction and also for oral rehabilitation with dentures, implants or other types of restorations. Because measurements of motor unit potentials (MUPs) are needed in several areas of EMG analysis, algorithms have been developed in our laboratory for use in a small computer-aided system for semi-automatic detection and pattern recognition of MUPs. Based upon the test recordings it is suggested that a characteristic 'maximal voltage increase per microsecond during the spike-phase' can be used as a supplement to the more generally used parameter 'rise-time'. Examples are given of how the programs can be useful in the study of the functional anatomy of jaw muscles by recording normative values for MUPs and their recruitment patterns.