Severe pallid breath-holding spells treated with low-dose theophylline.

BACKGROUND: The medical treatment for severe pallid breath-holding spells accompanied with severe bradycardia or transient cardiac arrest is controversial. Although various medications have been reported to be effective, patients treated with pacemaker insertion are not always evaluated for pharmacological therapy beforehand. CASE REPORT: A 9-month-old boy developed pallid breath-holding spells. At 15 months of age, a Holter electrocardiogram revealed 12 s of asystole during a breath-holding spell. Treatment with low-dose theophylline sustained-release dry syrup (5.3 mg/kg/day) led to complete control of the spells. The peak concentration of theophylline was 4.4 µg/mL which was below the therapeutic range for bronchial asthma. When he turned 3 years and 5 months of age, theophylline treatment was discontinued without recurrence of pallid breath-holding spells. DISCUSSION: Theophylline is now infrequently used to treat pediatric bronchial asthma due to its limited effect coupled with its side effects, which include headache, digestive symptoms, and theophylline-associated convulsions. The effectiveness of theophylline as a treatment for pallid breath-holding spells has been reported in several reports. In our case, the theophylline dosage was approximately half the amount described in previous reports. CONCLUSIONS: In this case, low-dose theophylline was adequate in controlling the pallid breath-holding spells. Because theophylline-associated seizures are a major concern, we suggest an evaluation of low-dose theophylline for treating patients with severe pallid breath-holding spells without febrile convulsions or epilepsy before proceeding with permanent pacemaker insertion. Further development of preventive strategies for theophylline-associated seizures and characterization of patients who respond well to theophylline treatment is required.

Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study.

BACKGROUND: Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents' fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement. METHODS: Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated. RESULTS: The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35-6.04), P =0.01]. CONCLUSION: VPA therapy reduces CBHS' frequency. Mood improvement is a suggestive effective mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04482764.

APOE gene-dependent BOLD responses to a breath-hold across the adult lifespan.

Age and apolipoprotein E (APOE) e4 genotype are two of the strongest known risk factors for sporadic Alzheimer's disease (AD). Neuroimaging has shown hemodynamic response changes with age, in asymptomatic carriers of the APOE e4 allele, and in AD. In this study, we aimed to characterize and differentiate age- and APOE gene-specific hemodynamic changes to breath-hold and visual stimulation. A further aim was to study whether these responses were modulated by 3-day intake of nitrate, a nitric oxide (NO) source. The study was designed as a randomized, double-blinded, placebo-controlled crossover study, and the study cohort comprised 41 APOE e4 carriers (e3/e4 or e4/e4 genotype) and 40 non-carriers (e3/e3 genotype) aged 30-70 years at enrollment. The participants underwent two scanning sessions, each preceded by ingestion of sodium nitrate or sodium chloride (control). During functional magnetic resonance imaging (fMRI) sessions, participants performed two concurrent tasks; a breath-hold task to probe cerebrovascular reactivity and a visual stimulation task to evoke functional hyperemia, respectively. We found that the blood oxygenation level dependent (BOLD) hemodynamic response to breath-hold was altered in APOE e4 carriers relative to non-carriers. Mid-aged (50-60 years of age) e4 carriers exhibited a significantly increased peak time relative to mid-aged e3 carriers, and peak time for younger (30-40 years of age) e4 carriers was significantly shorter than that of mid-aged e4 carriers. The response width was significantly increased for e4 carriers. The response peak magnitude significantly decreased with age. For the visual stimulation task, we found age-related changes, with reduced response magnitude with age but no significant effect of APOE allele type. We found no effect of nitrate ingestion on BOLD responses evoked by the breath-hold and visual stimulation tasks. The APOE gene-dependent response to breath-hold may reflect NO-independent differences in vascular function.

Transient Severe Respiratory Motion Artifacts After Application of Gadoxetate Disodium: What We Currently Know.

BACKGROUND: Gadoxetate disodium is an intracellular contrast agent for magnetic resonance imaging (MRI) of the liver. Recent publications revealed that injection of gadoxetate disodium can lead to imaging artifacts due to transient severe motion (TSM) in the arterial phase of contrast-enhanced liver MRI. In this review we present and discuss published frequencies of TSM, contrast injection and image acquisition protocols, potential risk factors, and proposed strategies to avoid or minimize the effects of TSM. METHOD: Two reviewers independently searched the PubMed search engine for "transient severe motion artifact" and related terms. Reference lists of retrieved articles were also searched. The two reviewers selected in consensus nine studies that reported both frequencies of TSM and potential risk factors. Study data were extracted by both reviewers, and disagreement was resolved by consensus. RESULTS AND CONCLUSION: TSM is caused by impaired breath-hold ability after gadoxetate disodium injection and occurs in 5 - 22 % of patients. The dose of applied contrast agent, repeated exposure to gadoxetate disodium, high BMI and pulmonary disease have been described as potential risk factors for TSM. However, there are only few concordant results on this topic and the pathophysiology of TSM has not been identified. Proposed strategies for the prevention of TSM are slow injection rates and low doses of diluted gadoxetate disodium. Accelerated and free-breathing MRI sequence protocols and breath-hold training may minimize the effects of TSM. Further prospective studies are needed to confirm these strategies and to identify the underlying mechanism of TSM. KEY POINTS: · TSM occurs in 5 - 22 % of patients after gadoxetate disodium injection.. · Potential risk factors of TSM are dose, repeated exposure, BMI, pulmonary disease.. · The underlying mechanism for TSM has not been identified.. · Slow injection rates and diluted gadoxetate disodium may prevent TSM.. · Accelerated image acquisition or free-breathing sequences may mitigate the effects of TSM.. CITATION FORMAT: · Well L, Weinrich JM, Adam G et al. Transient Severe Respiratory Motion Artifacts After Application of Gadoxetate Disodium: What We Currently Know. Fortschr Röntgenstr 2018; 190: 20 - 30.

Effect of iron supplementation in children with breath holding spells.

AIM: The aim of this study was to analyse the effect of iron supplementation in children with breath holding spells, irrespective of their iron status and study the factors associated with the response. METHODS: This was a prospective interventional study. Study population comprised of patients aged 6-36 months, attending a paediatric outpatient department with recurrent episodes (more than three in last 4 weeks) of breath holding spells. Children with loss of consciousness or convulsive movements associated with breath holding spells were considered as severe. After baseline investigations, all enrolled patients were given elemental iron at the dose of 3 mg/kg/day as a single daily dose. Four weekly follow-ups were done until 3 months after initiation of the intervention. At 12 weeks, investigations were repeated and outcome assessed for remission or decrease in severity of breath holding episodes. RESULTS: A total of 100 children with breath holding spells received iron supplementation. Almost 73% of children showed complete response, with another 23% showing greater than 50% reduction in frequency. Frequency of spells at diagnosis and intolerance to oral iron were significantly associated with poor response to iron supplementation. Other factors such as age at onset, age at presentation, severity of spells, anaemia and serum iron parameters had no significant association with the response. Of the 27 children without iron deficiency (serum ferritin ≥ 30 µg/L), 77.7% responded completely to iron supplementation, similar to the iron-deficient group. CONCLUSIONS: Iron supplementation is effective in the management of breath holding spells. Non-anaemic and iron-replete children with breath holding spells also respond well to iron supplementation.

Neuromuscular blockade and inspiratory breath hold during stereotactic body radiation therapy for treatment of heart base tumors in four dogs.

CASE DESCRIPTION 4 dogs were examined because of pleural effusion and ventricular tachycardia, coughing and supraventricular tachycardia, appendicular osteosarcoma, and syncopal episodes. CLINICAL FINDINGS In all 4 dogs, a heart base tumor was identified by means of thoracic CT. TREATMENT AND OUTCOME In all 4 dogs, the heart base tumors were treated by means of stereotactic body radiation therapy. Dogs were anesthetized, and neuromuscular blockade was achieved with atracurium or vecuronium. A circle rebreathing system with 15 m (50 feet) of anesthetic tubing coursing through the vault wall was used to connect the patient to the anesthesia machine, which was located in the control room. After a brief period of hyperventilation, an inspiratory breath was held at 20 cm H2O for the duration of beam delivery. Each beam delivery lasted between 30 and 100 seconds. Immediately following the breath hold, assisted ventilation was resumed. Mean treatment delivery time for each patient was 26 minutes; mean total anesthesia time was 89 minutes. All patients recovered without complications. There was no evidence of hemoglobin desaturation or hypercapnia during the anesthetic procedure. CLINICAL RELEVANCE The technique allowed for control of the respiration cycle from outside the radiation vault and a short overall treatment time. No adverse effects were encountered. This procedure should be considered when delivering radiation to structures within the thoracic cavity.

Effect of Gadoxetate Disodium on Arterial Phase Respiratory Waveforms Using a Quantitative Fast Fourier Transformation-Based Analysis.

OBJECTIVE: The purpose of this study is to investigate the effect of gadoxetate disodium administration on arterial phase respiratory waveforms. SUBJECTS AND METHODS: From 2013 to 2015, 107 subjects undergoing liver MRI with either gadoxetate disodium (10 mL diluted 1:1 with saline; injection rate, 2 mL/s; n = 40) or gadobenate dimeglumine (0.2 mL/kg; maximum, 20 mL; injection rate, 2 mL/s; n = 67) were enrolled. Respiratory waveforms obtained during unenhanced and dynamic contrast-enhanced phases were filtered by a physicist, who was blinded to contrast agent and imaging phase, to eliminate electronic and cardiac noise using fast Fourier transformation. The average root-mean-square difference of two intrasubject control phases (unenhanced and late dynamic) was termed D1, and the root-mean-square deviation of the arterial phase referent to the control record mean was termed D2. D1, D2, and their difference were compared across agents with the Mann-Whitney U test. Bland-Altman plots were generated for D1 and D2 values. RESULTS: D1 values were similar for both agents (mean [± SD], 232 ± 203 for gadoxetate vs 201 ± 230 for gadobenate; p = 0.48), indicating similar intercohort baseline breath-holding capability. D2 was greater and more variable for the gadoxetate cohort (438 ± 381) than for the gadobenate cohort (167 ± 167; p < 0.001), indicating larger and more unpredictable respiratory waveform deviations isolated to the arterial phase (subject-level rate, 48% [19/40] for gadoxetate vs 1% [1/67] for gadobenate; p < 0.001). Aberrant respiratory waveform peaks in the arterial phase were usually associated with transient tachypnea (mean maximum arterial phase respiratory rate for the gadoxetate cohort, 27 breaths/min; range, 11-40 breaths/min). CONCLUSION: Fixed-dose gadoxetate disodium (10 mL; 1:1 dilution with 10 mL of saline; injection rate, 2 mL/s) transiently reduces breath-holding capacity during the arterial phase and is accompanied by brief transient tachypnea.

ß1-Blockade increases maximal apnea duration in elite breath-hold divers.

We hypothesized that the cardioselective ß1-adrenoreceptor antagonist esmolol would improve maximal apnea duration in elite breath-hold divers. In elite national-level divers (n = 9), maximal apneas were performed in a randomized and counterbalanced order while receiving either iv esmolol (150 µg·kg-1·min-1) or volume-matched saline (placebo). During apnea, heart rate (ECG), beat-by-beat blood pressure, stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were measured (finger photoplethysmography). Myocardial oxygen consumption (MV̇o2) was estimated from rate pressure product. Cerebral blood flow through the internal carotid (ICA) and vertebral arteries (VA) was assessed using Duplex ultrasound. Apnea duration improved in the esmolol trial when compared with placebo (356 ± 57 vs. 323 ± 61 s, P < 0.01) despite similar end-apnea peripheral oxyhemoglobin saturation (71.8 ± 10.3 vs. 74.9 ± 9.5%, P = 0.10). The HR response to apnea was reduced by esmolol at 10-30% of apnea duration, whereas MAP was unaffected. Esmolol reduced SV (main effect, P < 0.05) and CO (main effect; P < 0.05) and increased TPR (main effect, P < 0.05) throughout apnea. Esmolol also reduced MV̇o2 throughout apnea (main effect, P < 0.05). Cerebral blood flow through the ICA and VA was unchanged by esmolol at baseline and the last 30 s of apnea; however, global cerebral blood flow was reduced in the esmolol trial at end-apnea (P < 0.05). Our findings demonstrate that, in elite breath-hold divers, apnea breakpoint is improved by ß1-blockade, likely owing to an improved total body oxygen sparring through increased centralization of blood volume (↑TPR) and reduced MV̇o2NEW & NOTEWORTHY The governing bodies for international apnea competition, the Association Internationale pour le Développment de l'Apnée and La Confédération Mondaile des Activités Subaquatiques, have banned the use of ß-blockers based on anecdotal reports that they improve apnea duration. Using a randomized placebo-controlled trial, we are the first to empirically confirm that ß-blockade improves apnea duration. This improvement in apnea duration coincided with a reduced myocardial oxygen consumption.

Acute effects of cannabis on breath-holding duration.

Distress intolerance (an individual's perceived or actual inability to tolerate distressing psychological or physiological states) is associated with cannabis use. It is unknown whether a biobehavioral index of distress intolerance, breath-holding duration, is acutely influenced (increased or decreased) by cannabis. Such information may further inform understanding of the expression of psychological or physiological distress postcannabis use. This within-subjects study examined whether smoked marijuana with 2.7%-3.0% delta-9-tetrahydrocannabinol (THC), relative to placebo, acutely changed duration of breath holding. Participants (n = 88; 65.9% male) were nontreatment-seeking frequent cannabis users who smoked placebo or active THC cigarette on two separate study days and completed a breath-holding task postsmoking. Controlling for baseline breath-holding duration and participant sex, THC produced significantly shorter breath-holding durations relative to placebo. There was a significant interaction of drug administration × frequency of cannabis use, such that THC decreased breath-holding time among less frequent but not among more frequent users. Findings indicate that cannabis may exacerbate distress intolerance (via shorter breath-holding durations). As compared to less frequent cannabis users, frequent users display tolerance to cannabis' acute effects including increased ability to tolerate respiratory distress when holding breath. Objective measures of distress intolerance are sensitive to contextual factors such as acute drug intoxication, and may inform the link between cannabis use and the expression of psychological distress. (PsycINFO Database Record

Hepatic Arterial Phase in Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging: Analysis of Respiratory Patterns and Their Effect on Image Quality.

OBJECTIVE: The aims of this study were to objectively evaluate patient respiration and breathing change after contrast injection and to assess its potential impact on image quality for the hepatic arterial phase in gadoxetic acid-enhanced magnetic resonance imaging. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. One hundred fifty-four patients underwent gadoxetic acid-enhanced liver magnetic resonance imaging with a 13-second breath-hold hepatic arterial phase. During the acquisition of precontrast and hepatic arterial phases, the respiratory motion signal was acquired and graded on a 4-point scale based on the SD of the respiratory waveform, with the highest grade indicating the worst breath-hold. Breath-holding grades 3 and 4 for the hepatic arterial phases were considered as breath-holding difficulty during the hepatic arterial phase. Gadoxetic acid-related dyspnea was defined as when the SD value of respiratory waveform during the hepatic arterial phase was 200 greater than that of the precontrast image. Then, the precontrast and hepatic arterial phase images were evaluated with respect to overall image quality and motion artifact using a 5-point scale, with the highest score indicating the worst image quality. In the hepatic arterial phase, the correlation between breath-holding degree and image quality parameters was evaluated using Pearson correlation. The differences in mean image quality scores between patients with and without gadoxetic acid-related dyspnea were evaluated using Student t test. RESULTS: Based on the analysis of the respiratory waveforms, the incidence of breath-holding difficulty during the hepatic arterial phase was 23.4% (33/154), and the incidence of gadoxetic acid-related dyspnea was 6.5% (10/154). By image analysis, the incidence of a degraded hepatic arterial phase (overall image quality score ≥4) was 5.2% (8/154). During the hepatic arterial phase, the breath-holding degree correlated with overall image quality and motion artifacts (r = 0.564 and 0.578, respectively). Patients with gadoxetic acid-related dyspnea showed significantly worse image qualities of the hepatic arterial phase than patients without gadoxetic acid-related dyspnea (all, P < 0.001), although image qualities for the precontrast image were not statistically significant between the 2 groups (all, P > 0.05). CONCLUSIONS: The objective analysis of respiratory patterns during a breath-hold is feasible and useful for evaluating gadoxetic acid-related dyspnea and its effect on image quality analysis.

Treatment of cyanotic breath-holding spells with oral theophylline in a 10-year-old boy.

Cyanotic breath-holding spells are generally benign and resolve spontaneously by 4 to 5 years of age. Treatment with iron and other drugs has been employed in selected cases with very frequent and severe episodes. We describe a 10-year-old boy with recent-onset cyanotic breath-holding spells that were activity limiting. He was unable to participate in physical activities with his peers as any argument or emotional upset provoked these spells. Treatment with oral iron and piracetam was ineffective. However, treatment with oral theophylline produced dramatic amelioration of symptoms, and he was once again able to participate in play activities with his peers. We believe that general central nervous system stimulant and respirogenic effects of theophylline were instrumental in control of symptoms in our child.

[Gender analysis of efficiency provided by general bath containing antlers of Siberian stags in skiers].

The authors performed gender analysis of efficiency caused by general bath containing antlers of Siberian stags in athletes engaged into winter sports. Male athletes demonstrated increased physical performance, low RBC membrane response to epinephrine, decreased cortisol level, higher testosterone level and longer time of breath-holding in Stange's test. Female athletes demonstrated no reliable changes in the mentioned parameters.

Comparison of methods for determining the partition coefficient of gadolinium in the myocardium using T1 mapping.

PURPOSE: To develop and validate modified Look-Locker (MOLLI) protocols to generate myocardial T1 maps within clinically acceptable breath-hold durations and to compare partition coefficients (λ) of gadolinium (Gd)-DTPA determined from either bolus injection (BI) or continuous infusion (CI) techniques. MATERIALS AND METHODS: T1 mapping was performed in phantoms and in 10 volunteers on a 1.5T scanner using the standard (3-3-5) MOLLI technique and two MOLLI schemes with shorter breath-hold durations. Imaging was performed precontrast and every 5 minutes following a bolus of 0.1 mmol/kg Gd-DTPA and a 15-minute delayed continuous infusion of 0.001 mmol/kg Gd-DTPA until equilibrium T1 in the myocardium was achieved to enable direct comparison of T1 relaxation times between techniques and λ's between the BI and CI methods. RESULTS: There was good agreement of T1 values between the 3-3-5 standard MOLLI protocol and the modified 3-5 MOLLI protocol in both phantom studies over a range of heart rates and in human subjects. Both MOLLI protocols produced similar measurements of λ using both the BI and CI methods. CONCLUSION: A reduced breath-hold MOLLI T1 mapping protocol combined with the BI method can accurately characterize T1 and λ in clinically applicable breath-hold durations without requiring a long equilibrium phase infusion.