Factors associated with carbon dioxide transfer in an experimental model of severe acute kidney injury and hypoventilation during high bicarbonate continuous renal replacement therapy and oxygenation membrane support.

OBJECTIVE: To investigate the factors influencing carbon dioxide transfer in a system that integrates an oxygenation membrane in series with high-bicarbonate continuous veno-venous hemodialysis in hypercapnic animals. METHODS: In an experimental setting, we induced severe acute kidney injury and hypercapnia in five female Landrace pigs. Subsequently, we initiated high (40mEq/L) bicarbonate continuous veno-venous hemodialysis with an oxygenation membrane in series to maintain a pH above 7.25. At intervals of 1 hour, 6 hours, and 12 hours following the initiation of continuous veno-venous hemodialysis, we performed standardized sweep gas flow titration to quantify carbon dioxide transfer. We evaluated factors associated with carbon dioxide transfer through the membrane lung with a mixed linear model. RESULTS: A total of 20 sweep gas flow titration procedures were conducted, yielding 84 measurements of carbon dioxide transfer. Multivariate analysis revealed associations among the following (coefficients ± standard errors): core temperature (+7.8 ± 1.6 °C, p < 0.001), premembrane partial pressure of carbon dioxide (+0.2 ± 0.1/mmHg, p < 0.001), hemoglobin level (+3.5 ± 0.6/g/dL, p < 0.001), sweep gas flow (+6.2 ± 0.2/L/minute, p < 0.001), and arterial oxygen saturation (-0.5 ± 0.2%, p = 0.019). Among these variables, and within the physiological ranges evaluated, sweep gas flow was the primary modifiable factor influencing the efficacy of low-blood-flow carbon dioxide removal. CONCLUSION: Sweep gas flow is the main carbon dioxide removal-related variable during continuous veno-venous hemodialysis with a high bicarbonate level coupled with an oxygenator. Other carbon dioxide transfer modulating variables included the hemoglobin level, arterial oxygen saturation, partial pressure of carbon dioxide and core temperature. These results should be interpreted as exploratory to inform other well-designed experimental or clinical studies.

Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

OBJECTIVES: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor. METHODS: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls. RESULTS: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples. DISCUSSION: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Detection of Chronic Hypoventilation Among Infants With Robin Sequence Using Capillary Blood Gas Sampling.

OBJECTIVES/HYPOTHESIS: To describe the use of capillary blood gas (CBG) sampling to detect and quantify hypoventilation in infants with Robin sequence (RS). METHODS: Case series with chart review at two institutions. Infants with RS presenting over a 10-year period were identified using departmental databases. CBG values obtained during infancy or until airway intervention (AI) were reviewed. RESULTS: From 2008 to 2018, 111 infants with RS were identified as having had been assessed and managed from birth or transfer until discharge home and having CBG data available. In most cases, CBG sampling was obtained every other day until intervention or discharge. A total of 81 (73%) infants required AI: 72 (89%) underwent mandibular distraction osteogenesis, five (6%) underwent tracheotomy, and four (5%) were discharged home with a nasopharyngeal airway. The mean PCO2 at day of life (DOL) 7-30 for the AI group was 52.7 mmHg (95% confidence interval: 51.7-53.7) and for the no AI group was 45.9 mmHg (44.8-47.0; P < .0001). The mean HCO3 at DOL 7-30 for the AI group was 29.8 mEq/L (29.4-30.1) and for the no AI group was 27.0 mEq/L (26.5-27.4; P < .0001). Receiver operating characteristic curves were created for maximum PCO2 and HCO3 values and cutoffs were established by optimizing a balance of sensitivity and specificity. Infants requiring AI surpassed the PCO2 and HCO3 cutoff at a median of DOL 9. CONCLUSIONS: Among infants with RS and hypoventilation, objective measures of respiratory acidosis may be apparent by DOL 9. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2789-2794, 2021.

Is venous blood a more reliable description of acid-base state following simulated hypo- and hyperventilation?

BACKGROUND: ABGs are performed in acute conditions as the reference method for assessing the acid-base status of blood. Hyperventilation and breath-holding are common ventilatory changes that occur around the time of sampling, rapidly altering the 'true' status of the blood. This is particularly relevant in emergency medicine patients without permanent arterial catheters, where the pain and anxiety of arterial punctures can cause ventilatory changes. This study aimed to determine whether peripheral venous values could be a more reliable measure of blood gases following acute changes in ventilation. METHODS: To allow for characterisation of ventilatory changes typical of acutely ill patients, but without the confounding influence of perfusion or metabolic disturbances, 30 patients scheduled for elective surgery were studied in a prospective observational study. Following anaesthesia, and before the start of the surgery, ventilator settings were altered to achieve a + 100% or - 60% change in alveolar ventilation ('hyper-' or 'hypoventilation'), changes consistent with the anticipation of a painful arterial puncture commonly encountered in the emergency room. Blood samples were drawn simultaneously from indwelling arterial and peripheral venous catheters at baseline, and at 15, 30, 45, 60, 90 and 120 s following the ventilatory change. Comparisons between the timed arterial (or venous) samples were done using repeated-measures ANOVA, with post-hoc analysis using Bonferroni's correction. RESULTS: Arterial blood pH and PCO2 changed rapidly within the first 15-30s after both hyper- and hypoventilation, plateauing at around 60s (∆pH = ±0.036 and ∆PCO2 = ±0.64 kPa (4.7 mmHg), respectively), with peripheral venous values remaining relatively constant until 60s, and changing minimally thereafter. Mean arterial changes were significantly different at 30s (P < 0.001) when compared to baseline, in response to both hyper- and hypoventilation. CONCLUSION: This study has shown that substantial differences in arterial and peripheral venous acid-base status can be due to acute changes in ventilation, commonly seen in the ER over the 30s necessary to sample arterial blood. If changes are transient, peripheral venous blood may provide a more reliable description of acid-base status.

Effects of spinal immobilization at 20° on end-tidal carbon dioxide.

OBJECTIVE: The aim was to determine the effect on end-tidal carbon dioxide (ETCO2) of spinal immobilization (SI) at a conventional 0° angle and to investigate the usefulness of immobilization at a 20° angle for preventing possible hypoventilation. METHODS: The study included 80 healthy volunteers, randomly divided into two groups. Spinal backboards and cervical collars were applied in Group 1 using a 0° angle and in Group 2 using a 20° angle, with the head up. SI was continued for 1 h, and ETCO2 values were measured at the 0th, 30th and 60th minute. RESULTS: There were no significant differences between the groups in 0th and 30th minute ETCO2. However, after 60th minute, results showed a statistically significant increase in ETCO2 in Group 1 (35.5 mmHg [IQR 25-75:35-38]) compared to Group 2 (34 mmHg [IQR 25-75:33-36]) (p < 0.001). During SI, there was a statistically significant increase in ETCO2 in Group 1 (35 mmHg [IQR 25-75:34-36], 35.5 mmHg [IQR 25-75:34-37] and 36 mmHg [IQR 25-75:35-38] respectively at the 0th, 30th and 60th minute after SI) (p < 0.001) and no change in Group 2. Also, we found statistically significant differences between ΔETCO2 levels in Groups 1 and 2 at all 3 time intervals. CONCLUSION: Conventional SI with an angle of 0° led to an increase in ETCO2 while subjects immobilization at a 20° angle maintained their initial ETCO2 values. Immobilization at 20° may prevent decompensation in patients who have thoracic trauma or lung diseases or those who are elderly, pregnant, or obese.

Evaluation of transcutaneous carbon dioxide and saturation monitoring during fiberoptic bronchoscopy.

INTRODUCTION: The aim of the study was to assess the effects of interventions during bronchoscopy on ventilation and determine the risk factors for hypoventilation related to both interventions and patients' demographical and clinical characteristics. MATERIALS AND METHODS: A total of 74 patients who underwent fiberoptic bronchoscopy (FOB) were included in the study. Oxygen saturation (SpO2) and partial carbon dioxide pressure (PCO2) were measured transcutaneously (TcSO2 and TcPCO2) using a sensor consisting of a probe placed on the earlobe. The demographic characteristics and basal, mean, peak and minimum values of TcSO2 and TcPCO2 during FOB were retrospectively analyzed and assessed in terms of the risk factors for hypoventilation. RESULT: During the procedure, the device automatically recorded the TcSO2 and TcPCO2 values. The mean TcPCO2 level was 37.09 ± 5.6 (27.1-60.6) mmHg. The mean increase in the TcPCO2 level from baseline was 3.25 ± 2.12 mmHg. The mean TcSO2 measurement was 95.9 ± 2.27 (80-100%). The measured mean and peak TcPCO2 values were significantly higher in men. In the whole group, the patients with a history of smoking more than 20 packyears also had significantly higher TcPCO2 values compared to the nonsmokers and light smokers. In the patients with endobronchial lesions, the decrease in the TcSO2 level was higher during FOB (p= 0.03), and the mean difference between the lowest and mean TcSO2 levels was significantly greater (6.2 vs 4.55%, p= 0.03). CONCLUSIONS: Changes in ventilation during FOB have multifactorial causes. The best indicator of ventilation is PCO2, and monitorization of PCO2 is very important in detecting hypoventilation. In this study, we determined some risk factors for hypoventilation in order to predict ventilation problems in patients planned to undergo FOB. We recommend that in male patients with endobronchial lesions, those with a longer smoking history, and those with a longer duration of FOB, SpO2 should be monitored together with PCO2.

End-tidal carbon dioxide underestimates plasma carbon dioxide during emergent trauma laparotomy leading to hypoventilation and misguided resuscitation: A Western Trauma Association Multicenter Study.

BACKGROUND: End-tidal carbon dioxide (ETCO2) is routinely used during elective surgery to monitor ventilation. The role of ETCO2 monitoring in emergent trauma operations is poorly understood. We hypothesized that ETCO2 values underestimate plasma carbon dioxide (pCO2) values during resuscitation for hemorrhagic shock. METHODS: Multicenter trial was performed analyzing the correlation between ETCO2 and pCO2 levels. RESULTS: Two hundred fifty-six patients resulted in 587 matched pairs of ETCO2 and pCO2. Correlation between these two values was very poor with an R of 0.04. 40.2% of patients presented to the operating room acidotic and hypercarbic with a pH less than 7.30 and a pCO2 greater than 45 mm Hg. Correlation was worse in patients that were either acidotic or hypercarbic. Forty-five percent of patients have a difference greater than 10 mm Hg between ETCO2 and pCO2. A pH less than 7.30 was predictive of an ETCO2 to pCO2 difference greater than 10 mm Hg. A difference greater than 10 mm Hg was predictive of mortality independent of confounders. CONCLUSION: Nearly one half (45%) of patients were found to have an ETCO2 level greater than 10 mm Hg discordant from their PCO2 level. Reliance on the discordant values may have contributed to the 40% of patients in the operating room that were both acidotic and hypercarbic. Early blood gas analysis is warranted, and a lower early goal of ETCO2 should be considered. LEVEL OF EVIDENCE: Therapeutic, level IV.

Physiological adaptations to repeated sprint training in hypoxia induced by voluntary hypoventilation at low lung volume.

PURPOSE: This study investigated the effects of repeated-sprint (RS) training in hypoxia induced by voluntary hypoventilation at low lung volume (RSH-VHL) on physiological adaptations, RS ability (RSA) and anaerobic performance. METHODS: Over a 3-week period, eighteen well-trained cyclists completed six RS sessions in cycling either with RSH-VHL or with normal conditions (RSN). Before (Pre) and after (Post) the training period, the subjects performed an RSA test (10 × 6-s all-out cycling sprints) during which oxygen uptake [Formula: see text] and the change in both muscle deoxyhaemoglobin (Δ[HHb]) and total haemoglobin (Δ[THb]) were measured. A 30-s Wingate test was also performed and maximal blood lactate concentration ([La]max) was assessed. RESULTS: At Post compared to Pre, the mean power output during both the RSA and the Wingate tests was improved in RSH-VHL (846 ± 98 vs 911 ± 117 W and 723 ± 112 vs 768 ± 123 W, p < 0.05) but not in RSN (834 ± 52 vs 852 ± 69 W, p = 0.2; 710 ± 63 vs 713 ± 72 W, p = 0.68). The average [Formula: see text] recorded during the RSA test was significantly higher in RSH-VHL at Post but did not change in RSN. No change occurred for Δ[THb] whereas Δ[HHb] increased to the same extent in both groups. [Lamax] after the Wingate test was higher in RSH-VHL at Post (13.9 ± 2.8 vs 16.1 ± 3.2 mmol L-1, p < 0.01) and tended to decrease in RSN (p = 0.1). CONCLUSIONS: This study showed that RSH-VHL could bring benefits to both RSA and anaerobic performance through increases in oxygen delivery and glycolytic contribution. On the other hand, no additional effect was observed for the indices of muscle blood volume and O2 extraction.

Anti-Hypothalamus and Anti-Pituitary Auto-antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis.

BACKGROUND: Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a very rare and complex pediatric syndrome characterized by altered hypothalamic thermal regulation, pain threshold, and respiratory control, hyperphagia with rapid weight gain and, often, hypothalamic-pituitary dysfunction. Its etiopathogenesis remains undetermined. We investigated the presence of alterations to target genes and hypothalamic-pituitary autoimmunity in a patient with -ROHHAD syndrome. METHODS: A 3-year-old girl presenting with obesity after rapid weight gain was diagnosed with ROHHAD syndrome based on clinical features and abnormal biochemical and functional testing results. Because of worsening of rapid symptoms and demonstration of oligoclonal bands on cerebrospinal fluid (CSF) analysis, she was treated with plasmapheresis, methylprednisolone, anti-CD20 monoclonal antibodies, and azathioprine. Despite initial partial clinical improvement, the patient soon died of cardiorespiratory arrest. Post-mortem, whole exome sequencing, high-resolution comparative genomic hybridization array, and optimized indirect immunofluorescence (IIF) analysis were performed on blood and CSF. RESULTS: No putative causative genomic variants compatible with dominant or recessive inheritance nor clinically significant structural rearrangement were detected. IIF on serum and CSF demonstrated the presence of anti-pituitary and anti-hypothalamus autoantibodies. CONCLUSIONS: These findings support the involvement of autoimmunity in ROHHAD syndrome. However, response to immunosuppressive treatment was only transient and the patient died. Further cases are required to define the complex disease pathogenesis.

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.

Detection of early nocturnal hypoventilation in neuromuscular disorders.

Objective Nocturnal hypoventilation (NH) is a complication of respiratory involvement in neuromuscular disorders (NMD) that can evolve into symptomatic daytime hypercapnia if not treated proactively with non-invasive ventilation. This study aimed to assess whether NH can be detected in the absence of other signs of nocturnal altered gas exchange. Methods We performed nocturnal transcutaneous coupled (tc) pCO2/SpO2 monitoring in 46 consecutive cases of paediatric-onset NMD with a restrictive respiratory defect (forced vital capacity < 60%). Nocturnal hypoventilation was defined as tcPCO2 > 50 mmHg for > 25% of recorded time, and hypoxemia as tcSpO2 < 88% for > 5 minutes. Daytime symptoms and bicarbonate were recorded after overnight monitoring. Results Twenty-nine of 46 consecutive patients showed NH. Twenty-three patients did not have nocturnal hypoxemia and 18 were clinically asymptomatic. In 20 patients, PaCO2 in daytime blood samples was normal. Finally, 13/29 patients with NH had isolated nocturnal hypercapnia without nocturnal hypoxia, clinical NH symptoms, or daytime hypercapnia. Conclusions Paediatric patients with NMD can develop NH in the absence of clinical symptoms or significant nocturnal desaturation. Therefore, monitoring of NH should be included among nocturnal respiratory assessments of these patients as an additional tool to determine when to commence non-invasive ventilation.

Isolated mild sleep-associated hypoventilation in children with Down syndrome.

INTRODUCTION: Children with Down syndrome (DS) have a high incidence of obstructive sleep apnea (OSA) that is often associated with hypoventilation. Little is known, however, about the prevalence of sleep-associated hypoventilation independent of OSA in these children. METHODS: Retrospective chart review of all children with DS under 18 years of age undergoing polysomnography at a tertiary care paediatric hospital during a 2-year period. Exclusion criteria were as follow: those requiring oxygen or positive-pressure ventilation; with tracheostomy, baseline hypoxia, unrepaired cyanotic heart disease, pulmonary hypertension, and cerebral palsy; or OSA with >5 obstructions/hour. RESULTS: 86 children met inclusion criteria. 68 (79%) had ETCO2values >50 mm Hg during sleep. 37 (43%) ranged 50-55 mm Hg, and 12 (14%) met American Academy of Sleep Medicine criteria for hypoventilation of ETCO2 >50 mm Hg for >25% of total sleep time (TST). Average pulse-oximetry saturation (SpO2) values during sleep were 97.8% (SD ±1; range: 95.1-99.9). Average percentage of TST with SpO2 >92% was 99.89%. CONCLUSION: Mildly elevated ETCO2 in the absence of OSA is common in children with DS. This may reflect underlying differences in autonomic control of ventilation in these children and may be considered a normal variant not necessitating intervention other than close monitoring for pulmonary hypertension.

Effect of Mild Hypercapnia on Lung Oxygenation in Sitting Position During Shoulder Arthroscopy Under General Anesthesia.

BACKGROUND Mild hypercapnia is permitted during surgeries in sitting position under general anesthesia to maintain cerebral regional oxygen saturation (rSO2). However, since hypoventilation may cause gas exchange impairment, we evaluated effects of mild hypercapnia on lung oxygenation during shoulder arthroscopy in sitting position. MATERIAL AND METHODS Forty patients were randomly allocated to a normocapnia group (ETCO2 35 mmHg, n=20) or a hypercapnia group (45 mmHg, n=20). The mean arterial pressure (MAP), heart rate (HR), and rSO2 were measured 5 min after intubation in supine position (T0), and at 2, 4, 6, 8, 10, 20, 30, 40, 50, and 60 min of remaining in sitting position (T1-10). Arterial blood gas was analyzed at T0 and T5. The oxygenation index (PaO2/FiO2) and dead-space ventilation ratio (Vd/Vt) were calculated. RESULTS There were no differences in PaO2/FiO2 at T0 and T5 between the 2 groups. At T5, the Vd/Vt was higher in the normocapnia group than in the hypercapnia group (p=0.04). The Vd/Vt at T5 increased from T0 in the normocapnia group. The incidence of cerebral desaturation in the hypercapnia group (0/20) was lower than in the normocapnia group (5/20) (p=0.047). Among rSO2, MAP, and HR, only changes in rSO2 over time between the 2 groups differed significantly (p=0.048). CONCLUSIONS Mild hypercapnia did not decrease lung oxygenation in sitting position, probably due to attenuation of the increase in dead-space ventilation ratio. Since hypercapnia maintained rSO2 without changes in oxygenation index and hemodynamic parameters, mild hypercapnia should be maintained during shoulder arthroscopy in sitting position under general anesthesia.

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.

Validity of transcutaneous PCO2 in monitoring chronic hypoventilation treated with non-invasive ventilation.

BACKGROUND: Non-invasive ventilation (NIV) is an efficient treatment for patients with chronic hypercapnic respiratory failure (CRF), but requires regular monitoring to detect both diurnal and nocturnal residual hypercapnia. The present study was designed to determine 1) whether transcutaneous PCO2 (PtcCO2) is a valid tool for monitoring PaCO2 in this group of patients, and 2) if overnight instrumental drift of the PtcCO2 sensor is clinically significant. METHODS: Sixty-seven patients with CRF on long term NIV were included. Arterial blood gases (ABG) were sampled from the radial artery during PtcCO2 measurement. PtcCO2 was recorded 2 min after ABG sampling. Instrumental drift was tested by measuring a gas of known CO2 concentration after auto-calibration of the sensor in the evening, and on the following morning. FINDINGS: PaCO2 values ranged from 3.97 kPa to 9.0 kPa. Thirty-six (53%) patients were hypercapnic. Correlation between PaCO2 and PtcCO2 was highly significant (r(2) = 0.9, p < 0.0001), Bias (d) and SD of bias (s) were 0.23 kPa and 0.28 kPa respectively, with a minor underestimation of PaCO2. Limits of agreement (d ± 2s) were; -0.32; 0.79 kPa. None of the paired values of PaCO2/PtcCO2 had a difference exceeding 1 kPa. The mean drift of PtcCO2 was 0.14 ± 0.54 kPa/8 h (p = 0.04; 95% CI: 0.01-0.27). INTERPRETATION: With the device tested, in stable patients under NIV-treatment for CRF, PtcCO2 accurately reflects PaCO2. PtcCO2 can be used to monitor CO2 overnight during NIV without any clinically significant drift. TRIAL REGISTRATION N°: NCT01845233.

High bicarbonate levels in narcoleptic children.

The objective of this study was to evaluate the levels of plasma bicarbonate levels in narcoleptic children. Clinical, electrophysiological data and bicarbonate levels were evaluated retrospectively in children seen in our paediatric national reference centre for hypersomnia. The cohort included 23 control subjects (11.5 ± 4 years, 43% boys) and 51 patients presenting de-novo narcolepsy (N) (12.7 ± 3.7 years, 47% boys). In narcoleptic children, cataplexy was present in 78% and DQB1*0602 was positive in 96%. The control children were less obese (2 versus 47%, P = 0.001). Compared with control subjects, narcoleptic children had higher bicarbonate levels (P = 0.02) as well as higher PCO2 (P < 0.01) and lower venous pH gas (P < 0.01). Bicarbonate levels higher than 27 mmol L(-1) were found in 41.2% of the narcoleptic children and 4.2% of the controls (P = 0.001). Bicarbonate levels were correlated with the Adapted Epworth Sleepiness Scale (P = 0.01). Narcoleptic patients without obesity often had bicarbonate levels higher than 27 mmol L (-1) (55 versus 25%, P = 0.025). No differences were found between children with and without cataplexy. In conclusion, narcoleptic patients had higher bicarbonate plasma levels compared to control children. This result could be a marker of hypoventilation in this pathology, provoking an increase in PCO2 and therefore a respiratory acidosis, compensated by an increase in plasma bicarbonates. This simple screening tool could be useful for prioritizing children for sleep laboratory evaluation in practice.

Carbon dioxide levels during polygraphy in children with sleep-disordered breathing.

PURPOSE: The recent scoring rules of the American Academy of Sleep Medicine (AASM) define hypoventilation in children as a carbon dioxide (CO2) level of >50 mmHg for >25 % of total sleep time (partial pressure of CO2 (PCO2) > 50[>25 %]). As there is no validated level of nocturnal hypoventilation with regard to end-organ damage in children, we evaluated the prevalence of hypoventilation with the AASM definition but also with a lesser degree of elevated CO2 in children with sleep-disordered breathing (SDB). METHODS: Transcutaneous CO2 (PtcCO2) was recorded during overnight polygraphy (PG). Hypoventilation was defined according to four definitions: the AASM score (PCO2 > 50[>25 %]), the peak value of PtcCO2 > 50 mmHg (PtcCO2 > 50[peak]), a percentage of PtcCO2 > 50 mmHg > 2 % of nighttime recording (PtcCO2 > 50[>2 %]) or a nocturnal PtcCO2 > 10 mmHg above waking baseline level (PtcCO2[>10 mmHg]). PtcCO2 indices were correlated to the apnoea-hypopnoea index (AHI) and oxygenation indices. RESULTS: PGs from 221 children with suspicion of obstructive sleep apnoea (72 %), neuromuscular diseases (21 %), and lung diseases (7 %) were analysed. The prevalence of hypoventilation according to PCO2 > 50[>25 %], PtcCO2 > 50[peak], PtcCO2 > 50[>2 %] and PtcCO2[>10 mmHg] were 16, 27, 31 and 52 %, respectively, and did not differ between the three diagnostic groups. Significant but weak correlations were observed between hypoventilation and AHI and oxygenation indices. CONCLUSIONS: Nocturnal hypoventilation occurs in a large number of children referred for SDB, independent of the underlying disease, when more stringent criteria than those of the AASM are used. The poor correlation between hypoventilation and AHI or oxygenation indices is in favour of CO2 being a supplemental index of SDB.

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.

[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.

Sleep hypoventilation and daytime hypercapnia in stable chronic obstructive pulmonary disease.

PURPOSE: To explore the associations between sleep hypoventilation (SH) and daytime arterial pressures of carbon dioxide (PaCO2), sleep stages, and sleep apneas/hypopneas (AHI) in subjects with chronic obstructive pulmonary disease (COPD). SH has previously been found in COPD-subjects with chronic hypercapnic respiratory failure (CHRF) using supplementary oxygen (LTOT), and has been proposed as a possible predictor for CHRF. PATIENTS AND METHODS: A prospectively designed observational study in a pulmonary rehabilitation hospital of 100 (39 male) stable COPD inpatients with a mean forced expiratory volume in 1 second (FEV1) of 1.1 L (42% of predicted) and a mean age of 64 years, using polysomnography with transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2). RESULTS: SH as defined by the American Academy of Sleep Medicine (AASM) was found in 15 of the subjects, seven of whom used LTOT. However, six had SH despite being normocapnic during the daytime (only one on LTOT). Subjects with SH had a greater ΔPtcCO2 increase from nonrapid eye movement (NREM) to rapid eye movement (REM) sleep stages compared to non-SH subjects (mean [standard deviation] between-groups difference =0.23(0.20) kPa, P<0.0005). Subjects with apnea/hypopnea index ≥15 (overlap, N=27) did not differ from those with COPD alone (AHI <5, N=25) in sleep ΔPtcCO2 or daytime PaCO2. A regression model with the variables FEV1, LTOT, and sleep maximum ΔPtcCO2 explained 56% of the variance in daytime PaCO2 (F(3, 94) =40.37, P<0.001). CONCLUSION: In stable COPD, SH as defined by the AASM was found both in normocapnic, non-LTOT subjects and in hypercapnic, LTOT-using subjects. Between-sleep-stage increase in ΔPtcCO2 was higher in subjects with SH. Overlap subjects did not differ from simple COPD subjects in sleep ΔPtcCO2 or daytime PaCO2.