What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study) : Adaptive servo-ventilation in real-life conditions.

BACKGROUNDS: As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. METHODS: The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. RESULTS: 177/214 patients were analysed (87.57% male) with a median (IQ25-75) age of 71 (65-77) years, an ASV-treatment duration of 2.88 (1.76-4.96) years, an ASV-usage of 6.52 (5.13-7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6-13.5) to 6 (3-9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38-62)/h to a residual device index of 1.9 (0.7-3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05). CONCLUSIONS: In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management. TRIAL REGISTRATION: The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986 ) on 1 April 2015.

Low leptin concentration may identify heart failure patients with central sleep apnea.

Low leptin concentration has been shown to be associated with central sleep apnea in heart failure patients. We hypothesized that low leptin concentration predicts central sleep apnea. Consecutive ambulatory New York Heart Association (NYHA) classes I-IV heart failure patients were studied prospectively, including measurement of serum leptin, echocardiography and polysomnography. Sleep apnea was defined by type (central/mixed/obstructive) and by apnea-hypopnea index ≥5 by polysomnography. Subjects were divided into four groups by polysomnography: (1) central sleep apnea, (2) mixed apnea, (3) no apnea and (4) obstructive sleep apnea. Fifty-six subjects were included. Eighteen subjects were diagnosed with central sleep apnea, 15 with mixed apnea, 12 with obstructive apnea and 11 with no sleep apnea. Leptin concentration was significantly lower in central sleep apnea compared to obstructive apnea (8 ± 10.7 ng mL-1 versus 19.7 ± 14.7 ng mL-1 , P Ë‚ 0.01) or no sleep apnea (8 ± 10.7 ng mL-1 versus 17.1 ± 8.4 ng mL-1 , P Ë‚ 0.01). Logistic regression showed leptin to be associated independently with central sleep apnea [odds ratio (OR): 0.19; 95% confidence interval (CI): 0.06-0.62; area under the curve (AUC): 0.80, P < 0.01]. For the detection of central sleep apnea, a cut-off value for leptin concentration 5 ng mL-1 yielded a sensitivity of 50% and specificity of 89%. In conclusion, a low leptin concentration may have utility for the screening of heart failure patients for central sleep apnea.

Ventilation Parameters under Adaptive Servo Ventilation: A Comparison on Behalf of CSA-Pattern, BNP/NT-pro-BNP, and Ejection Fraction.

BACKGROUND: The SERVE-HF study has raised questions concerning the higher mortality under adaptive servoventilation. The ventilatory mode was discussed as a possible aggravating factor. OBJECTIVES: We wondered if the data recorded by the adaptive servo-ventilation (ASV)-devices in heart failure patients with CSA-CSR ± OSA are different in terms of respiratory parameters and therapeutic pressures compared to patients with CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP. METHODS: Patients were included, if ASV had normalized respiratory disturbance index in the first night of application and after at least 6 weeks. ASV-device data were analyzed in terms of respiratory rate (RR), min ventilation (MV), endexpiratory (EEP), peak inspiratory pressure (Ppeak) and median pressure. RESULTS: Compared to CPAP-resistant/emergent-CSA with normal BNP/NT-pro-BNP (n = 25), CSA-CSR- (n = 13) CSA-CSR+OSA-patients (n = 32) with elevated BNP/NT-pro-BNP had higher RR (p < 0.01) in the first night of ASV therapy and during follow-up (15.3 ± 1.3 vs. 17.3 ± 2.4/min) with similar MV (6.5 ± 1.3 vs. 6.6 ± 1.3 L), resulting in significantly lower tidal volumes. EEP (5.6 ± 1.1 vs. 5.5 ± 1.1 hPa), Pmedian and Ppeak (9.8 ± 1.5 vs. 9.7 ± 1.2 hPa) were comparable. Ventilatory parameters were not different between LVEF < 40, 40-49, and ≥50%, neither within the whole group nor the group of CSA-CSR ± OSA and heart failure. CONCLUSION: Patients with heart failure and CSA-CSR ± OSA have higher RRs but similar MV under ASV-therapy than patients with CSA and normal BNP. This indicates higher dead space ventilation. EF was not found to have an influence on the ventilatory parameters.

Cross-Correlation of Heart Rate and Oxygen Saturation in Very Low Birthweight Infants: Association with Apnea and Adverse Events.

BACKGROUND: Analysis of subtle vital sign changes could facilitate earlier treatment of acute inflammatory illnesses. We previously showed that high cross-correlation of heart rate and oxygen saturation (XCorr-HR-SpO2) occurs in some very low birthweight (VLBW) infants with sepsis, and hypothesized that this corresponds to apnea. METHODS: In 629 VLBW infants, we analyzed XCorr-HR-SpO2 in relation to central apnea with bradycardia and desaturation (ABD), BD with or without central apnea (BD), and percent time in periodic breathing (PB) throughout the neonatal intensive care unit (NICU) stay (75 infant-years). We reviewed 100 days with extremely high XCorr-HR-SpO2 (>0.7) and control days for clinical associations. Next, we identified all cases of late-onset septicemia (LOS) and necrotizing enterocolitis (NEC) and analyzed change in XCorr-HR-SpO2 before diagnosis. RESULTS: Mean XCorr-HR-SpO2 was ∼0.10, and increasing XCorr-HR-SpO2 was associated with increasing ABD, BD, and PB (correlation coefficients >0.93). Days with maximum XCorr-HR-SpO2 >0.7 were more likely to have an adverse event than control days (49% versus 13%). In 93 cases of LOS or NEC, there was a 67% increase in XCorr-HR-SpO2 in the 24-hour period prior to diagnosis compared with the previous day (p < 0.01). CONCLUSION: High XCorr-HR-SpO2 is associated with apnea and adverse events including LOS and NEC.

Unbound unconjugated hyperbilirubinemia is associated with central apnea in premature infants.

OBJECTIVE: To evaluate whether jaundice, indexed by unbound bilirubin (UB), is associated with central apnea in premature infants. STUDY DESIGN: A prospective observational study was performed with 27-33 weeks' gestational age infants who were not requiring either mechanical ventilation or noninvasive ventilation with continuous positive airway pressure beyond 24 hours after birth. Infants with congenital infections, chromosomal disorders, craniofacial anomalies, and/or family history of hearing loss were excluded. Total serum bilirubin and UB were measured twice daily during the first postnatal week and then when clinically indicated. Central apnea was evaluated by visual inspection of continuous, electronic cardiorespiratory recordings until 2 weeks of age. RESULTS: One hundred infants were subdivided into 2 groups via median peak UB level: the high UB group (greater than median) and low UB group (less than median). The high UB group had an increased frequency of apnea events during the first 2 weeks compared with infants in the low UB group. After we controlled for confounders, the high UB group had more events of apnea during the first 2 postnatal weeks compared with the low UB group (incidence rate ratio: 1.9, 95% CI 1.2-3.2). CONCLUSIONS: Our findings suggest that jaundice, as indexed by UB, is associated with central apnea in premature infants.

C-reactive protein is elevated in heart failure patients with central sleep apnea and Cheyne-Stokes respiration.

BACKGROUND: Manifestation of central sleep apnea (CSA) with Cheyne-Stokes respiration is of major prognostic impact in chronic heart failure (CHF). Inflammatory processes have been linked to a progression of cardiovascular diseases, including heart failure. While an association of C-reactive protein (CRP) levels to obstructive sleep apnea has been documented before, there is a lack of information regarding variation of CRP levels in patients with CSA. OBJECTIVES: The objective of this study was to investigate a potential association of CRP levels to CSA severity in CHF patients. METHODS: High sensitivity CRP levels were analyzed in 966 patients with CHF (BMI 26.3 ± 4.6, New York Heart Association class 2.6 ± 0.5, left ventricular ejection fraction 29.4 ± 7.9%, N-terminal pro-brain natriuretic peptide, NT-proBNP, level 2,209 ± 3,315 pg/ml) without sleep-disordered breathing (SDB; Apnea-Hypopnea Index, AHI, <5/h) or various degrees of CSA, documented by in-hospital cardiorespiratory polygraphy or polysomnography. RESULTS: The CRP concentration in CHF patients was 0.550 ± 0.794 mg/dl in patients without SDB (AHI 0-4/h, n = 403) versus 0.488 ± 0.708 mg/dl in patients with mild CSA (AHI 5-14/h, n = 123, p = n.s.) and 0.660 ± 0.963 mg/dl in patients with moderate CSA (AHI 15-29/h, n = 160, p = n.s.). In patients with severe CSA (AHI ≥ 30/h, n = 280), significantly higher CRP concentrations were documented (0.893 ± 1.384 mg/dl, p < 0.05). Stepwise regression analysis revealed AHI, NT-proBNP and heart rate to be independently associated with elevated CRP levels. CONCLUSION: Severe CSA in CHF patients is associated with elevated levels of CRP, a systemic marker of inflammation and cardiovascular risk. This might explain in part the negative prognostic impact of CSA in these patients.

Increased propensity for central apnea in patients with obstructive sleep apnea: effect of nasal continuous positive airway pressure.

RATIONALE: There is increasing evidence of increased ventilatory instability in patients with obstructive sleep apnea (OSA), but previous investigations have not studied whether the hypocapnic apneic threshold is altered in this group. OBJECTIVES: To compare the apneic threshold, CO2 reserve, and controller gain between subjects with and without OSA matched for age, sex, and body mass index. METHODS: Hypocapnia was induced via nasal mechanical ventilation for 3 minutes. Cessation of mechanical ventilation resulted in hypocapnic central hypopnea or apnea depending upon the magnitude of the hypocapnia. The apnea threshold (Pet(CO2)-AT) was defined as the measured Pet(CO2) at which the apnea closest to the last hypopnea occurred. The CO2 reserve was defined as the change in Pet(CO2) between eupneic Pet(CO2) and Pet(CO2)-AT. Controller gain was defined as the ratio of change in Ve between control and hypopnea or apnea to the DeltaPet(CO2). MEASUREMENTS AND MAIN RESULTS: Eleven pairs of subjects were studied. There was no difference in the Pet(CO2)-AT between the two groups. However, the CO2 reserve was smaller in the subjects with OSA (2.2 +/- 0.6 mm Hg) compared with the control subjects (4.5 +/- 1.4 mm Hg; P < 0.001). The controller gain was increased in the subjects with OSA (3.7 +/- 1.3 L/min/mm Hg) compared with the control subjects (1.6 +/- 0.5 L/min/mm Hg; P < 0.001). Controller gain decreased and CO2 reserve increased in seven subjects restudied after using continuous positive airway pressure for 1 month. CONCLUSIONS: Ventilatory instability is increased in subjects with OSA and is reversible with the use of continuous positive airway pressure.

Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea.

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remede System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden. Graphical Abstract.

Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

Dysregulated glucose homeostasis in congenital central hypoventilation syndrome.

Background Congenital central hypoventilation syndrome (CCHS) is a rare disorder of autonomic control. A hypoglycaemic seizure in a 4-year-old girl with CCHS led to a more detailed examination of glycaemic control in a cohort of children with CCHS. Methods We conducted an observational cohort study of glucose homeostasis in seven children (3 months to 12 years) with genetically confirmed CCHS using a combination of continuous glucose monitoring (CGM), fasting studies and oral glucose tolerance test (OGTT). CGM was used to compare the effect of diazoxide and dietary intervention in the index patient. Results Hypoglycaemia was not elicited by fasting in any of the patients. Increased postprandial glycaemic variability was evident in all patients using CGM, with seven of seven patients demonstrating initial postprandial hyperglycaemia (plasma-glucose concentration >7.8 mmol/L), followed by asymptomatic hypoglycaemia (plasma-glucose concentration ≤2.8 mmol/L) in two of seven patients that was also demonstrated on OGTT. Both diazoxide and low Glycaemic Index (GI) dietary intervention reduced the proportion of CGM readings <4 mmol/L; however, diazoxide also increased the proportion of readings in the hyperglycaemic range. Conclusions Glucose variability associated with autonomic dysfunction may be unrecognised in CCHS, particularly in children with more severe phenotypes. This report highlights the occurrence of hyperglycaemia as well as hypoglycaemia in CCHS. Given the challenges of recognising hypoglycaemia based on clinical symptomatology, the use of CGM may facilitate its identification allowing appropriate management. The observed normoglycaemia during fasting combined with increased postprandial plasma blood glucose level (BGL) variability is more consistent with dumping syndrome than persistent hyperinsulinism. Dietary modifications therefore may be more effective than diazoxide in managing hypoglycaemia.

Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism.

CONTEXT: The aldosterone to renin ratio (ARR) is recommended to screen for primary aldosteronism (PA). OBJECTIVE: To evaluate whether dietary sodium restriction results in misinterpretation of PA screening. PARTICIPANTS: Untreated hypertensives with ARR more than 20 on a high dietary sodium intake (HS) were also evaluated on a low dietary sodium intake (LS) (n = 241). Positive screening for PA was defined as: plasma renin activity (PRA) less than or equal to 1.0 ng/mL · h with serum aldosterone more than or equal to 6 ng/dL. PA was confirmed by a 24-hour urinary aldosterone excretion more than or equal to 12 mcg with urinary sodium more than 200 mmol. RESULTS: Only 33% (79/241) of participants with an ARR more than 20 had a positive PA screen on HS. On LS, 56% (44/79) of these participants no longer met criteria for positive PA screening. When compared with participants with positive PA screening on both diets, participants with a positive screen on HS but negative on LS exhibited a significantly higher PRA on both diets. Remarkably, of the 48/79 participants who had PA confirmed, 52% had negative PA screening on LS. The distinguishing feature of these participants with "discordant" screening results was a larger rise in PRA on LS resulting in normalization of the ARR and higher Caucasian race prevalence. CONCLUSIONS: Sodium restriction is recommended in hypertension; however, it can significantly raise PRA, normalize the ARR, and result in false interpretation of PA screening. Milder phenotypes of PA, where PRA is not as suppressed, are most susceptible to dietary sodium influences on renin and ARR. Optimal screening for PA should occur under conditions of HS.

Brain natriuretic peptide in patients with congestive heart failure and central sleep apnea.

STUDY OBJECTIVE: To assess the possible relationship between Cheyne-Stokes respiration (CSR) associated with central sleep apnea (CSA) syndrome and brain natriuretic peptide (BNP) in an outpatient population presenting with stable congestive heart failure (CHF). MEASUREMENTS AND RESULTS: Ninety patients with CHF due to systolic dysfunction (left ventricular ejection fraction

Precordial compression without airway management induces lung injury in the rodent cardiac arrest model with central apnea.

To investigate whether the lung injury induced by precordial compression without ventilation or not, in the cardiac-arrest animal model with central apnea. Thirty male Sprague-Dawley rats were anesthetized with halothane. The cardiac arrest was induced by 100 mg/kg ketamine (IV) and accompanied with central apnea. They were allocated to four groups by means of resuscitation. Group A was treated with only precordial compression without the other treatments. In group B with tracheotomy and precordial compression. In group C was performed tracheotomy, oxygenation, and precordial compression. The animals in group D were treated with tracheotomy, oxygen administration, artificial ventilation, and precordial compression. Four minutes after cardiac arrest, the resuscitation was started and continued for 20 min. PaCO(2) in the group without mechanical ventilation increased significantly after the start of the resuscitation. All animals were sacrificed after resuscitation procedure. The wet/dry weight ratio of lung in group A (6.9+/-0.8) was significantly higher than that of the other groups B, C and D (5.9+/-0.6, 5.7+/-0.4 and 5.6+/-0.4, P<0.05 in each). The pathological findings also demonstrated the lung injuries, such as edema, migration, and destruction of structure in group A. The precordial compression alone did not improve CO(2) elimination in the gasping-less cardiac arrest model, as well as maybe inducing more severe lung injury than that with the protective management. This experimental model raises the possibility that chest compressions without airway management might result in lung injury.

An assistive device for congenital central hypoventilation syndrome outpatients during sleep.

Congenital Central Hypoventilation Syndrome is a genetic disease characterized by alveolar hypoventilation and autonomic dysregulation. Patients have hypoventilations, especially during sleep, conditioning hypercapnia which can lead to neurological damage and death. They therefore need mechanical ventilators, that provide sufficient gas exchange, and pulse-oximeters that monitor oxy-hemoglobin blood concentration. Due to the restrictions regarding domiciliary assistive devices, the presence of a caregiver is required all night long. Currently, the only alarm systems available are the ones integrated in the ventilators and monitoring systems. During the night, multiple false alarms may occur, interrupting the sleep and causing anxiety. In this work we describe an assistive device that acquires real-time data from a pulse-oximeter, provides a multisensory stimulation if oxygen saturation falls under a certain threshold, and wakes up the patient if the hypoxia is severe. Tests on healthy subjects have shown that the device guarantees rapid awakenings, with a stimulator-dependent efficacy, and that it does not affect sleep efficiency. The purpose of the device is to determine a gentle awakening if mild hypoxia conditions persist, and to assure rapid awakening when a severe hypoxia occurs, reducing false alarms, improving the quality of sleep and increasing the self-sufficiency of the patients.

Leptin deficiency promotes central sleep apnea in patients with heart failure.

BACKGROUND: Leptin-deficient animals hyperventilate. Leptin expression by adipocytes is attenuated by atrial natriuretic peptide (ANP). Increased circulating natriuretic peptides (NPs) are associated with an increased risk of central sleep apnea (CSA). This study tested whether serum leptin concentration is inversely correlated to NP concentration and decreased in patients with heart failure (HF) and CSA. METHODS: Subjects with HF (N = 29) were studied by measuring leptin, NPs, CO2 chemosensitivity (Δminute ventilation [V.e]/Δpartial pressure of end-tidal CO2 [Petco2]), and ventilatory efficiency (V.e/CO2 output [V.co2]) and were classified as CSA or no sleep-disordered breathing by polysomnography. CSA was defined as a central apnea-hypopnea index ≥ 15. The Student t test, Mann-Whitney U test, and logistic regression were used for analysis, and data were summarized as mean ± SD; P < .05 was considered significant. RESULTS: Subjects with CSA had higher ANP and brain natriuretic peptide (BNP) concentrations (P < .05), ΔV.e/ΔPetco2 (2.39 ± 1.03 L/min/mm Hg vs 1.54 ± 0.35 L/min/mm Hg, P = .01), and V.e/V.co2 (43 ± 9 vs 34 ± 7, P < .01) and lower leptin concentrations (8 ± 10.7 ng/mL vs 17.1 ± 8.8 ng/mL, P < .01). Logistic regression analysis (adjusted for age, sex, and BMI) demonstrated leptin (OR = 0.07; 95% CI, 0.01-0.71; P = .04) and BNP (OR = 4.45; 95% CI, 1.1-17.9; P = .05) to be independently associated with CSA. CONCLUSIONS: In patients with HF and CSA, leptin concentration is low and is inversely related to NP concentration. Counterregulatory interactions of leptin and NP may be important in ventilatory control in HF.

Acetazolamide attenuates Hunter-Cheyne-Stokes breathing but augments the hypercapnic ventilatory response in patients with heart failure.

RATIONALE: Acetazolamide has been used to attenuate Hunter-Cheyne-Stokes breathing with central sleep apnea (CSA) associated with heart failure. However, the mechanisms underlying this improvement remain to be fully elucidated. OBJECTIVES: We hypothesized that acetazolamide stabilizes CSA by attenuating the ventilatory sensitivity to CO2, which is increased in patients with heart failure and is thought to be the major mechanism mediating CSA. METHODS: Six consecutive male patients with stable systolic heart failure and CSA (apnea-hypopnea index [AHI] ≥ 15 episodes/h) were randomized to a double-blind crossover protocol with acetazolamide or placebo received 1 hour before bedtime for six nights with 2 weeks of wash-out. Under both conditions, we measured the hypercapnic ventilatory response (HCVR), arterial blood Pco2, steady-state metabolic CO2 production, overnight attended polysomnography, and also assessed cardiac and pulmonary function. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, acetazolamide significantly decreased the AHI (65 ± 32 vs. 31 ± 19 events/h, mean ± SD). Acetazolamide increased the HCVR slope by 55% (3.3 ± 1.7 vs. 5.1 ± 2.4 L/min/mm Hg; P = 0.03), an increase that far exceeded the 12% fall in arterial Pco2 (P = 0.02). The acetazolamide-induced change in the balance of these effects (ΔHCVR × Pco2) was inversely associated with the reduction in AHI (r = 0.8; P = 0.045). CONCLUSIONS: This placebo-controlled study indicates that acetazolamide improves CSA in patients with heart failure despite an increase in the slope of the HCVR. However, because the degree of HCVR elevation inhibits the improvement in unstable breathing, an increased CO2 chemosensitivity may be a key mechanism underlying an incomplete resolution of CSA with acetazolamide.

[Non-invasive mechanical ventilation in a child with central hypoventilation syndrome: one year follow-up].

OBJECTIVE: To investigate clinical features and therapeutic methods of late-onset central hypoventilation syndrome. METHOD: A nine-year old boy was trachea-intubated and mechanically ventilated because of pneumonia, respiratory and heart failure and pulmonary hypertension. It was found that hard to extubate the patient as he was breathing normally while awake but had shallow breathing, oxygen desaturation and CO2 retention when falling asleep. Nocturnal polysomnography together with transcutaneous CO2 supported the diagnosis of central hypoventilation. The final diagnosis was late-onset congenital central hypoventilation syndrome as the patient gained weight rapidly since 3 years of age and the brain magnetic resonance imaging (MRI) and genetic screening were unremarkable. RESULT: The patient was treated with bi-level positive air pressure ventilation via nasal mask which showed good oxygen saturation and CO2 dropped down. The follow up study done one year later showed normal brain MRI, relief of pulmonary hypertension and better CO2 level in both awaken and sleeping status. CONCLUSION: The late-onset congenital central hypoventilation syndrome in this case had onset of symptoms at 2 years of age, he had normal breathing while he was awake but had oxygen desaturation and CO2 retention during sleep, therefore, respiratory support is required in severe cases. Mechanical ventilation via tracheotomy and non-invasive ventilation via mask are the major choice.

[Transplacental or breast milk intoxication to clonidine: a case of neonatal hypotonia and drowsiness]. / Intoxication transplacentaire ou par lait maternel à la clonidine : un cas de somnolence et d'hypotonie néonatale.

We report a case of clonidine poisoning in a breastfed newborn. At 2 days of life, this boy presented a consciousness deficit with drowsiness, hypotonia, and suspected generalized seizures. There were no cardiorespiratory problems outside of progressive central apneas beginning the 5th day. Further initial investigations were normal (extensive biological exams, cranial ultrasonography and transfontanellar Doppler, electroencephalography, and brain MRI study), excluding the main causes of neonatal hypotonia (encephalitis, infection, metabolic disorder). However, new medical questioning revealed maternal daily intake of 0.15 mg clonidine for hypertension during and after pregnancy. Since it was impossible to quantify clonidine quantification in newborn serum and breast milk, a weaning test was performed the 9th day. Twenty-four hours after cessation of breastfeeding, complete regression of symptoms was obtained. Poisoning by clonidine after fetal and neonatal exposure through breast milk is rare but severe enough to simulate a neurological disease. Diagnosis is based on the search for drug use and the cessation of breastfeeding if doubt persists. Recovery of normal examination results is then rapid and complete.