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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.

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.

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 PCO 2 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 HCO 3 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 PCO 2 and HCO 3 values and cutoffs were established by optimizing a balance of sensitivity and specificity. Infants requiring AI surpassed the PCO 2 and HCO 3 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., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

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 PCO 2 changed rapidly within the first 15-30s after both hyper- and hypoventilation, plateauing at around 60s (∆pH = ±0.036 and ∆PCO 2  = ±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.

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.

Objective: The aim was to determine the effect on end-tidal carbon dioxide (ETCO 2 ) 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 ETCO 2 values were measured at the 0th, 30th and 60th minute., Results: There were no significant differences between the groups in 0th and 30th minute ETCO 2 . However, after 60th minute, results showed a statistically significant increase in ETCO 2 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 ETCO 2 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 ΔETCO 2 levels in Groups 1 and 2 at all 3 time intervals., Conclusion: Conventional SI with an angle of 0° led to an increase in ETCO 2 while subjects immobilization at a 20° angle maintained their initial ETCO 2 values. Immobilization at 20° may prevent decompensation in patients who have thoracic trauma or lung diseases or those who are elderly, pregnant, or obese., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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. [La max ] 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 O 2 extraction.

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.

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) pCO 2 /SpO 2 monitoring in 46 consecutive cases of paediatric-onset NMD with a restrictive respiratory defect (forced vital capacity < 60%). Nocturnal hypoventilation was defined as tcPCO 2  > 50 mmHg for > 25% of recorded time, and hypoxemia as tcSpO 2  < 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, PaCO 2 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.

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 ETCO 2 values >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 ETCO 2 >50 mm Hg for >25% of total sleep time (TST). Average pulse-oximetry saturation (SpO 2 ) values during sleep were 97.8% (SD ±1; range: 95.1-99.9). Average percentage of TST with SpO 2 >92% was 99.89%., Conclusion: Mildly elevated ETCO 2 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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

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.

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., (© 2015 European Sleep Research Society.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

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.

Glycine receptor (GlyR) antibodies have been identified in patients with rigidity and hyperekplexia, but the clinical phenotype associated with these antibodies has not been fully elucidated. The clinical features in two additional patients with GlyR antibodies are described. A 55-year-old man presented with stimulus-induced hyperekplexia and rigidity in the lower limbs and trunk. He initially responded to benzodiazepines, but presented after 18 months with severe, painful, prolonged spasms associated with supraventricular and ventricular arrhythmias, hypoventilation and oxygen desaturation requiring intubation. He improved following treatment with clonazepam, baclofen and immunomodulatory therapies. A 58-year-old woman presented with stiffness in the legs and hyperekplexia associated with hypoventilation, at times leading to loss of consciousness. She responded to benzodiazepines and has remained in remission. The clinical picture associated with GlyR antibodies includes autonomic dysfunction, cardiac arrhythmias and hypoventilation. It is important to recognise these serious complications early to limit mortality from this treatable condition., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

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.

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.

Rodents are most useful models to study physiological and pathophysiological processes in early development, because they are born in a relatively immature state. However, only few techniques are available to monitor non-invasively heart frequency and respiratory rate in neonatal rodents without restraining or hindering access to the animal. Here we describe experimental procedures that allow monitoring of heart frequency by electrocardiography (ECG) and breathing rate with a piezoelectric transducer (PZT) element without hindering access to the animal. These techniques can be easily installed and are used in the present study in unrestrained awake and anesthetized neonatal C57/Bl6 mice and Wistar rats between postnatal day 0 and 7. In line with previous reports from awake rodents we demonstrate that heart rate in rats and mice increases during the first postnatal week. Respiratory frequency did not differ between both species, but heart rate was significantly higher in mice than in rats. Further our data indicate that urethane, an agent that is widely used for anesthesia, induces a hypoventilation in neonates whilst heart rate remains unaffected at a dose of 1 g per kg body weight. Of note, hypoventilation induced by urethane was not detected in rats at postnatal 0/1. To verify the detected hypoventilation we performed blood gas analyses. We detected a respiratory acidosis reflected by a lower pH and elevated level in CO2 tension (pCO2) in both species upon urethane treatment. Furthermore we found that metabolism of urethane is different in P0/1 mice and rats and between P0/1 and P6/7 in both species. Our findings underline the usefulness of monitoring basic cardio-respiratory parameters in neonates during anesthesia. In addition our study gives information on developmental changes in heart and breathing frequency in newborn mice and rats and the effects of urethane in both species during the first postnatal week.

Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disease that causes an autonomous nervous system dysregulation. Patients are unable to have a correct ventilation, especially during sleep, facing risk of death. Therefore, most of them are mechanically ventilated during night and their blood oxygenation is monitored, while a supervisor keeps watch over them. If low oxygen levels are detected by the pulse-oximeter, an alarm fires; the supervisor deals with the situation and, if there is neither a technical problem nor a false alarm, wakes the subject, as CCHS patients usually recover from hypoxia when roused from sleep. During a single night multiple alarms may occur, causing fractioned sleep for the subject and a lasting state of anxiety for supervisors.

Aim: To characterize the profiles of alveolar hypoventilation during colonoscopies performed under sedoanalgesia with a combination of alfentanil and either midazolam or propofol., Methods: Consecutive patients undergoing routine colonoscopy were randomly assigned to sedation with either propofol or midazolam in an open-labeled design using a titration scheme. All patients received 4 μg/kg per body weight alfentanil for analgesia and 3 L of supplemental oxygen. Oxygen saturation (SpO₂) was measured by pulse oximetry (POX), and capnography (PcCO₂) was continuously measured using a combined dedicated sensor at the ear lobe. Instances of apnea resulting in measures such as stimulation of the patient, a chin lift, a mask maneuver, or withholding of sedation were recorded. PcCO₂ values (as a parameter of sedation-induced hypoventilation) were compared between groups at the following distinct time points: baseline, maximal rise, termination of the procedure and 5 min after termination of the procedure. The number of patients in both study groups who regained baseline PcCO₂ values (± 1.5 mmHg) five minutes after the procedure was determined., Results: A total of 97 patients entered this study. The data from 14 patients were subsequently excluded for clinical procedure-related reasons or for technical problems. Therefore, 83 patients (mean age 62 ± 13 years) were successfully randomized to receive propofol (n = 42) or midazolam (n = 41) for sedation. Most of the patients were classified as American Society of Anesthesiologists (ASA) II [16 (38%) in the midazolam group and 15 (32%) in the propofol group] and ASA III [14 (33%) and 13 (32%) in the midazolam and propofol groups, respectively]. A mean dose of 5 (4-7) mg of IV midazolam and 131 (70-260) mg of IV propofol was used during the procedure in the corresponding study arms. The mean SpO₂ at baseline (%) was 99 ± 1 for the midazolam group and 99 ± 1 for the propofol group. No cases of hypoxemia (SpO₂ < 85%) or apnea were recorded. However, an increase in PcCO₂ that indicated alveolar hypoventilation occurred in both groups after administration of the first drug and was not detected with pulse oximetry alone. The mean interval between the initiation of sedation and the time when the PcCO₂ value increased to more than 2 mmHg was 2.8 ± 1.3 min for midazolam and 2.8 ± 1.1 min for propofol. The mean maximal rise was similar for both drugs: 8.6 ± 3.7 mmHg for midazolam and 7.4 ± 3.2 mmHg for propofol. Five minutes after the end of the procedure, the mean difference from the baseline values was significantly lower for the propofol treatment compared with midazolam (0.9 ± 3.0 mmHg vs 4.3 ± 3.7 mmHg, P = 0.0000169), and significantly more patients in the propofol group had regained their baseline value ± 1.5 mmHg (32 of 41 vs 12 of 42, P = 0.0004)., Conclusion: A significantly higher number of patients sedated with propofol had normalized PcCO₂ values five minutes after sedation when compared with patients sedated with midazolam.

Background: Pulse oximetry alone has been suggested to determine which patients on home mechanical ventilation (MV) require further investigation of nocturnal gas exchange. In patients with neuromuscular diseases, alveolar hypoventilation (AH) is rarely accompanied with ventilation-perfusion ratio heterogeneity, and, therefore, oximetry may be less sensitive for detecting AH than in patients with lung disease., Objective: To determine whether pulse oximetry (S(pO(2))) and transcutaneous carbon dioxide (P(tcCO(2))) during the same night were interchangeable or complementary for assessing home MV efficiency in patients with neuromuscular diseases., Methods: Data were collected retrospectively from the charts of 58 patients with chronic neuromuscular respiratory failure receiving follow-up at a home MV unit. S(pO(2)) and P(tcCO(2)) were recorded during a 1-night hospital stay as part of standard patient care. We compared AH detection rates by P(tcCO(2)), S(pO(2)), and both., Results: AH was detected based on P(tcCO(2)) alone in 24 (41%) patients, and based on S(pO(2)) alone with 3 different cutoffs in 3 (5%), 8 (14%), and 13 (22%) patients, respectively. Using both P(tcCO(2)) and S(pO(2)) showed AH in 25 (43%) patients., Conclusions: Pulse oximetry alone is not sufficient to exclude AH when assessing home MV efficiency in patients with neuromuscular diseases. Both P(tcCO(2)) and S(pO(2)) should be recorded overnight as the first-line investigation in this population., (Copyright 2012 Daedalus Enterprises)

Objectives: Under a constant inspired concentration, the uptake of a volatile anesthetic into the arterial blood should mainly be governed by alveolar ventilation, according to the assumption that the patient's cardiac output remains stable during anesthesia. We investigated whether ventilation volume affects the rate of desflurane uptake by examining arterial blood concentrations., Method: Thirty female patients were randomly allocated into the following three groups: hyperventilation, normal ventilation and hypoventilation. Hemodynamic variables were measured using a Finometer, inspiratory and end-tidal concentrations of desflurane were measured by infrared analysis, and the desflurane concentration in the arterial blood (Ades) was analyzed by gas chromatography., Results: During the first 10 minutes after the administration of desflurane, the Ades was highest in the hyperventilation group, and this value was significantly different from those obtained for the normal and hypoventilation groups. In addition, hyperventilation significantly increased the slope of Ades-over-time during the first 5 minutes compared with patients experiencing normal ventilation and hypoventilation, but there were no differences in these slopes during the periods from 5-10, 10-20 and 20-40 minutes after the administration of desflurane. This finding indicates that there were no differences in desflurane uptake between the three groups after the first 5 minutes within desflurane administration., Conclusions: Hyperventilation accelerated the rate of the rise in Ades following desflurane administration, which was time-dependent with respect to different alveolar ventilations levels.

Eight men performed three series of 5-min exercise on a cycle ergometer at 65% of normoxic maximal O(2) consumption in four conditions: (1) voluntary hypoventilation (VH) in normoxia (VH(0.21)), (2) VH in hyperoxia (inducing hypercapnia) (inspired oxygen fraction [F(I)O(2)] = 0.29; VH(0.29)), (3) normal breathing (NB) in hypoxia (F(I)O(2) = 0.157; NB(0.157)), (4) NB in normoxia (NB(0.21)). Using near-infrared spectroscopy, changes in concentration of oxy-(Delta[O(2)Hb]) and deoxyhemoglobin (Delta[HHb]) were measured in the vastus lateralis muscle. Delta[O(2)Hb - HHb] and Delta[O(2)Hb + HHb] were calculated and used as oxygenation index and change in regional blood volume, respectively. Earlobe blood samples were taken throughout the exercise. Both VH(0.21) and NB(0.157) induced a severe and similar hypoxemia (arterial oxygen saturation [SaO(2)] < 88%) whereas SaO(2) remained above 94% and was not different between VH(0.29) and NB(0.21). Arterialized O(2) and CO(2) pressures as well as P50 were higher and pH lower in VH(0.21) than in NB(0.157), and in VH(0.29) than in NB(0.21). Delta[O(2)Hb] and Delta[O(2)Hb - HHb] were lower and Delta[HHb] higher at the end of each series in both VH(0.21) and NB(0.157) than in NB(0.21) and VH(0.29). There was no difference in Delta[O(2)Hb + HHb] between testing conditions. [La] in VH(0.21) was greater than both in NB(0.21) and VH(0.29) but not different from NB(0.157). This study demonstrated that exercise with VH induced a lower tissue oxygenation and a higher [La] than exercise with NB. This was caused by a severe arterial O(2) desaturation induced by both hypoxic and hypercapnic effects.

Background: Pulse oximetry is a widely accepted procedure for ventilatory monitoring during gastrointestinal endoscopy, but this method provides an indirect measurement of the respiratory function. In addition, detection of abnormal ventilatory activity can be delayed, especially if supplemental oxygen is provided. Capnography offers continuous real-time measurement of expiratory carbon dioxide., Objective: We aimed at prospectively examining the advantages of capnography over the standard pulse oximetry monitoring during sedated colonoscopies., Patients and Methods: Fifty patients undergoing colonoscopy were simultaneously monitored with pulse oximetry and capnography by using two different devices in each patient. Several sedation regimens were administered. Episodes of apnea or hypoventilation detected by capnography were compared with the occurrence of hypoxemia., Results: Twenty-nine episodes of disordered respiration occurred in 16 patients (mean duration 54.4 seconds). Only 38% of apnea or hypoventilation episodes were detected by pulse oximetry. A mean delay of 38.6 seconds was observed in the events detected by pulse oximetry (two episodes of disturbed ventilation were simultaneously detected by capnography and pulse oximetry)., Conclusions: Apnea or hypoventilation commonly occurs during colonoscopy with sedation. Capnography is more reliable than pulse oximetry in early detection of respiratory depression in this setting.

Introduction: Routine monitoring of noninvasive respiratory support relies on nocturnal pulse oximetry and daytime arterial blood gases, without systematic nocturnal carbon dioxide recording. The aim of the study was to assess if overnight pulse oximetry and daytime blood gases are sufficiently accurate to detect nocturnal hypoventilation in children receiving long-term noninvasive respiratory support., Materials and Methods: Pulse oximetry and carbon dioxide pressure measured by capillary arterialized blood gases and a combined transcutaneous carbon dioxide and pulse oximetry (PtcCO(2)/SpO(2)) monitor were compared in 65 patients (asthma, n = 16, recurrent bronchitis, n = 8, lung infection, n = 8, cystic fibrosis, n = 15, interstitial lung disease, n = 6, neuromuscular disease, n = 12). Daytime capillary arterialized blood gases and nocturnal recording of pulse oximetry and carbon dioxide by means of a combined PtcCO(2)/SpO(2) monitor were performed in 50 other patients receiving nocturnal noninvasive respiratory support at home., Results: A correlation was observed between pulse oximetry (r = 0.832, P < 0.0001) and carbon dioxide pressure (r = 0.644, P < 0.0001) measured by capillary arterialized blood gases and the combined PtcCO(2)/SpO(2) monitor. Twenty-one of the 50 patients (42%) on long-term noninvasive respiratory support presented nocturnal hypercapnia, defined by a PtcCO(2) value >50 mmHg, without nocturnal hypoxemia. Daytime capillary arterialized carbon dioxide levels were normal in 18 of these 21 patients., Conclusions: Nocturnal hypercapnia may occur in children receiving nocturnal noninvasive respiratory support at home. Nocturnal pulse oximetry and daytime arterial blood gases are not sufficiently accurate to diagnose nocturnal hypercapnia, underlying the importance of a systematic carbon dioxide monitoring in children receiving noninvasive respiratory support.

Background: Long-term home mechanical ventilation (HMV) is usually initiated in hospital. Admission to hospital has resource implications and may not be reimbursable in some healthcare systems., Methods: Twenty-eight stable neuromuscular and chest wall disease patients with nocturnal hypoventilation (transcutaneous carbon dioxide (TcCO(2) >6.5 kPa), were randomised to start HMV either as an outpatient (n=14, age range 12-62 years) or inpatient (n=14, age range 14-73 years). We compared effects of HMV on nocturnal and diurnal arterial blood gas tensions, ventilator compliance, healthcare professional (HCP) contact time, and time in hospital., Results: Improvements in nocturnal arterial oxygen saturation (SaO(2)) and daytime PaO(2) were equivalent in both groups. Peak nocturnal TcCO(2), improved in both groups; % time TcCO(2) >6.5 kPa fell in the inpatient group and daytime PaCO(2) decreased significantly (p<0.05) in the outpatient group. The mean (SD) inpatient stay was 3.8 (1.0) days, and the outpatient attendance sessions 1.2 (0.4). HCP contact time including telephone calls was: inpatient 177 (99) min; outpatient 188 (60) min (p=not significant); 2 month ventilator compliance was: inpatient 4.32 (7); outpatient 3.92 (8) (p=not significant) hours per night., Conclusion: Outpatient initiation of HMV is feasible with equivalent outcome in the outpatient and the inpatient groups.

Objective: The goal was to assess the time to recognition of apnea in a simulated pediatric sedation scenario, with and without supplemental oxygen., Methods: A pediatric human patient simulator mannequin was used to simulate apnea in a 6-year-old patient who received sedation for resetting of a fractured leg. Thirty pediatricians participating in a credentialing course for sedation were randomly assigned to 2 groups. Those in group 1 (N = 15) used supplemental oxygen, and those in group 2 (N = 15) did not use supplemental oxygen. A third group (N = 10), consisting of anesthesiology residents (postgraduate years 2 and 3 equivalent), performed the scenario with oxygen supplementation, to ensure validity and reliability of the simulation. The time interval from simulated apnea to bag-mask ventilation was recorded. Oxygen saturation and Paco(2) values were recorded. All recorded variables and measurements were compared between the groups., Results: The time interval for bag-mask ventilation to occur in group 1 (oxygen supplementation) was significantly longer than that in group 2 (without oxygen supplementation) (173 +/- 130 and 83 +/- 42 seconds, respectively). The time interval for bag-mask ventilation to occur was shorter in group 3 (anesthesiology residents) (24 +/- 6 seconds). Paco(2) reached a higher level in group 1 (75 +/- 26 mmHg), compared with groups 2 and 3 (48 +/- 10 and 42 +/- 3 mmHg, respectively). There was no significant difference between the groups in oxygen saturation values at the time of clinical detection of apnea (93 +/- 5%, 88 +/- 5%, and 94 +/- 7%, respectively)., Conclusions: Hypoventilation and apnea are detected more quickly when patients undergoing sedation breathe only air. Supplemental oxygen not only does not prevent oxygen desaturation but also delays the recognition of apnea.

Cerebral control of respiration has been extensively studied but at present, no evidence of cerebral laterality or dominance for respiration exists. We examined the ventilatory changes following temporary (20 min) occlusion of the right or left common carotid artery in rabbits. The corresponding groups of sham-operated rabbits were used as controls. The partial pressure of end-tidal carbon dioxide (PET(co2) ) was measured with a microstream capnograph before the operation as well as at 6h, and days 1, 4, 9 and 15 postoperation and was used to indicate the ventilatory status. The results showed that following temporary occlusion of the left common carotid artery, subjects began hypoventilation and had a progressive rise in PET(co2) on day 9 postoperation compared to the sham-operated group. However, animals that underwent occlusion of the right common carotid artery hyperventilated from as early as 6h postoperation to days 1 and 4, an effect that ceased up to day 9 postoperation. It was concluded that respiration might be under differential regulation by the two cerebral hemispheres. While the left hemispheric ischemia-reperfusion injury induced hypoventilation that of the right hemisphere resulted in hyperventilation.

This study investigated the effects of training with voluntary hypoventilation (VH) at low pulmonary volumes. Two groups of moderately trained runners, one using hypoventilation (HYPO, n=7) and one control group (CONT, n=8), were constituted. The training consisted in performing 12 sessions of 55 min within 4 weeks. In each session, HYPO ran 24 min at 70% of maximal O(2) consumption ( [V(02max)) with a breath holding at functional residual capacity whereas CONT breathed normally. A V(02max) and a time to exhaustion test (TE) were performed before (PRE) and after (POST) the training period. There was no change in V(O2max), lactate threshold or TE in both groups at POST vs. PRE. At maximal exercise, blood lactate concentration was lower in CONT after the training period and remained unchanged in HYPO. At 90% of maximal heart rate, in HYPO only, both pH (7.36+/-0.04 vs. 7.33+/-0.06; p<0.05) and bicarbonate concentration (20.4+/-2.9 mmolL(-1) vs. 19.4+/-3.5; p<0.05) were higher at POST vs. PRE. The results of this study demonstrate that VH training did not improve endurance performance but could modify the glycolytic metabolism. The reduced exercise-induced blood acidosis in HYPO could be due to an improvement in muscle buffer capacity. This phenomenon may have a significant positive impact on anaerobic performance.

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre.

Objective: Oxygen desaturation is common among patients with sleep apnea. This study was designed to evaluate the methods used to express the severity of oxygen desaturation in patients with obstructive sleep apnea hypopnea syndrome., Methods: The oxygen saturation data of 215 patients [suspected of having obstructive sleep apnea (OSA)] studied at the Sleep Centre of Peking Union Medical College Hospital were evaluated. Apnea-hypopnea index (AHI) and the following conventional indices of oxygen desaturation were compared: average oxygen saturation (AO(2)), lowest oxygen saturation (LO(2)), oxygen desaturation index (ODI), average desaturation and the percent of the total time with oxygen saturation level lower than 90% (T < 90%)., Results: There was a significant correlation between the oxygen saturation values measured by any method (AO(2), LO(2), ODI, average desaturation, T < 90%) and the severity of sleep AHI (r = -0.610, 0.983, -0.789, 0.782, 0.821, respectively, P = 0.001)., Conclusions: The best method of expressing the severity of oxygen desaturation in patients with obstructive sleep apnea hypopnea syndrome needs the combination of several conventional indices of oxygen desaturation (lowest oxygen saturation, oxygen desaturation index, and the percent of the total time with oxygen saturation level lower than 90%).

Described in the specialty literature for over one century under the name of Pickwick syndrome, the obesity--hypoventilation syndrome (OHS) includes the triad: obesity--hypoventilation--hypersomnia. In Romania, this entity is rarely recognized and, despite the developments in specific investigations, the disease is frequently difficult to differentiate from other respiratory disorders during sleep. The authors try to clarify some issues related to pathophysiologic mechanism and contribution of mechanical factors or of respiratory nervous center etc. References are made about the leptin involvement. Clinical appearance and therapy modalities are added to the description of the disease.

Background: Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels., Objectives: The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations., Method: We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study., Results: The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred., Conclusion: Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

Background: Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV., Methods: Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacity<50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria., Results: Peak nocturnal transcutaneous carbon dioxide tension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months., Conclusion: Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.

Study Objective: This two-part study was designed to determine the effect of supplemental oxygen on the detection of hypoventilation, evidenced by a decline in oxygen saturation (Spo(2)) with pulse oximetry., Design: Phase 1 was a prospective, patient-controlled, clinical trial. Phase 2 was a prospective, randomized, clinical trial., Setting: Phase 1 took place in the operating room. Phase 2 took place in the postanesthesia care unit (PACU)., Patients: In phase 1, 45 patients underwent abdominal, gynecologic, urologic, and lower-extremity vascular operations. In phase 2, 288 patients were recovering from anesthesia., Interventions: In phase 1, modeling of deliberate hypoventilation entailed decreasing by 50% the minute ventilation of patients receiving general anesthesia. Patients breathing a fraction of inspired oxygen (Fio(2)) of 0.21 (n = 25) underwent hypoventilation for up to 5 min. Patients with an Fio(2) of 0.25 (n = 10) or 0.30 (n = 10) underwent hypoventilation for 10 min. In phase 2, spontaneously breathing patients were randomized to breathe room air (n = 155) or to receive supplemental oxygen (n = 133) on arrival in the PACU., Measurements and Results: In phase 1, end-tidal carbon dioxide and Spo(2) were measured during deliberate hypoventilation. A decrease in Spo(2) occurred only in patients who breathed room air. No decline occurred in patients with Fio(2) levels of 0.25 and 0.30. In phase 2, Spo(2) was recorded every min for up to 40 min in the PACU. Arterial desaturation (Spo(2) < 90%) was fourfold higher in patients who breathed room air than in patients who breathed supplemental oxygen (9.0% vs 2.3%, p = 0.02)., Conclusion: Hypoventilation can be detected reliably by pulse oximetry only when patients breathe room air. In patients with spontaneous ventilation, supplemental oxygen often masked the ability to detect abnormalities in respiratory function in the PACU. Without the need for capnography and arterial blood gas analysis, pulse oximetry is a useful tool to assess ventilatory abnormalities, but only in the absence of supplemental inspired oxygen.

Background: There are no published reports identifying an inadequate ventilatory response to metabolic acidosis as a predictor of impending respiratory failure. Metabolic acidosis should induce a respiratory alkalosis in which the partial pressure of carbon dioxide (Paco2) is (1.5 [HCO3-] + 8) +/- 2. This study examined the relation between inadequate ventilatory compensation and intubation among trauma patients., Methods: A retrospective chart review was performed for trauma patients admitted between January 1999 and December 2000. Age, gender, Injury Severity Score and combined Trauma and Injury Severity Score, chest injury, history of cardiac or pulmonary disease, partial pressure of oxygen (Pao2), Paco2, Glasgow Coma Score, respiratory rate, systolic blood pressure, base deficit, and ability to compensate were analyzed with respect to intubation and need for ventilator support., Results: Of 140 patients with metabolic acidosis, 45 ultimately were intubated. The mean Paco2 for the unintubated patients was 34 +/- 7 mm Hg, as compared with 41 +/- 11 mm Hg for the intubated patients (p < 0.001). Only injury severity and ability to compensate for metabolic acidosis were independent predictors of intubation. Patients with inadequate compensation were 4.2 times more likely to require intubation when control was used for the Injury Severity Score (95% confidence interval, 1.8-9.7; p < 0.001)., Conclusions: Inability to mount an adequate hyperventilatory response to metabolic acidosis is associated with an increased likelihood of respiratory failure and a need for ventilatory support. Recognition of this relation should lead to closer monitoring of patients with this condition, and could help to avert unforeseen crisis intubations. This observation needs to be validated in a prospective study.

Objective: To compare the ability of a sidestream capnograph and a mainstream capnograph to measure end-tidal CO2 (ETCO2) and provide accurate estimates of PaCO2 in mechanically ventilated dogs., Design: Randomized, double Latin square., Animals: 6 healthy adult dogs., Procedure: Anesthesia was induced and neuromuscular blockade achieved by IV administration of pancuronium bromide. Mechanical ventilation was used to induce conditions of standard ventilation, hyperventilation, and hypoventilation. While tidal volume was held constant, changes in minute volume ventilation and PaCO2 were made by changing the respiratory rate. Arterial blood gas analysis was performed and ETCO2 measurements were obtained by use of either a mainstream or a sidestream capnographic analyzer., Results: A linear regression model and bias analysis were used to compare PaCO2 and ETCO2 measurements; ETCO2 measurements obtained by both capnographs correlated well with PaCO2. Compared with PaCO2, mainstream ETCO2 values differed by 3.15 +/- 4.89 mm Hg (mean bias +/- SD), whereas the bias observed with the sidestream ETCO2 system was significantly higher (5.65 +/- 5.57 mm Hg). Regardless of the device used to measure ETCO2, bias increased as PaCO2 exceeded 60 mm Hg., Conclusions and Clinical Relevance: RelevancehAlthough the mainstream cas slightly more accurate, both methods of ETCO2 measurement correlated well with PaCO2 and reflected changes in the ventilatory status. However, ETCO2 values > 45 mm Hg may inaccurately reflect the severity of hypoventilation as PaCO2 may be underestimated during conditions of hypercapnia (PaCO2 > 60 mm Hg).

We retrospectively evaluated data from 213 consecutive patients; 152 were affected by obstructive sleep apnea (OSA), 29 had OSA associated with chronic obstructive pulmonary disease (COPD), also known as overlap syndrome, and 32 had COPD. Patients with obesity-hypoventilation syndrome were not included. The aims of the study were to evaluate the anthropometric, pulmonary, and polysomnographic characteristics of patients affected by overlap syndrome compared to "simple" OSA and to COPD subjects and to analyze the determinants of hypercapnia in overlap syndrome. In the comparison between overlap and OSA patients, the overlap group had a significantly higher PaCO2 (44.59 vs. 39.22 mm Hg; p < 0.01), in the presence of a similar AHI (40.46 vs. 41.59/h). Comparing overlap to COPD patients, overlap showed a significantly higher PaCO2 value (44.59 vs. 39.63 mm Hg; p < 0.005) and had significantly less severe obstructive impairment (FEV 162.93 vs. 47.31%; FEV1/FVC ratio 66.71 vs. 59.25%; p < 0.005). Anthropometric, pulmonary function, and polysomnographic data did not differ between normo- and hypercapnic overlap patients. The best model (stepwise multiple regression analysis) for predicting PaCO2 in overlap patients showed r2 value 0.65: PaO2 contributed to 38%, FEV1 to 15%, and weight to 12%. In conclusion, the occurrence of hypercapnia in overlap patients is only partially explained by the combination of overweight and reduced respiratory function, supporting the hypothesis of a multifactorial genesis.

Background: Leptin is a protein hormone produced by fat cells of mammals. It acts within the hypothalamus via a specific receptor to reduce appetite and increase energy expenditure. Plasma leptin levels correlate closely with total body fat mass operating via a central feedback mechanism. In human obesity serum leptin levels are up to four times higher than in lean subjects, indicating a failure of the feedback loop and central leptin resistance. In leptin deficient obese mice (ob/ob mice) leptin infusion reverses hypoventilation. It was hypothesised that a relative deficiency in CNS leptin, indicated by high circulating leptin levels, may be implicated in the pathogenesis of obesity hypoventilation syndrome (OHS)., Methods: Fasting morning leptin levels were measured in obese and non-obese patients with and without daytime hypercapnia (n=56). Sleep studies, anthropometric data, spirometric parameters, and awake arterial blood gas tensions were measured in each patient., Results: In the whole group serum leptin levels correlated closely with % body fat (r=0.77). Obese hypercapnic patients (mean (SD) % body fat 43.8 (6.0)%) had higher fasting serum leptin levels than eucapnic patients (mean % body fat 40.8 (6.2)%), with mean (SD) leptin levels of 39.1 (17.9) and 21.4 (11.4) ng/ml, respectively (p<0.005). Serum leptin (odds ratio (OR) 1.12, 95% CI 1.03 to 1.22) was a better predictor than % body fat (OR 0.92, 95% CI 0.76 to 1.1) for the presence of hypercapnia., Conclusions: Hyperleptinaemia is associated with hypercapnic respiratory failure in obesity. Treatment with leptin or its analogues may have a role in OHS provided central leptin resistance can be overcome.

Study Objectives: To assess the effectiveness of nasal noninvasive mechanical ventilation (NIMV) in patients with obesity hypoventilation syndrome (OHS)., Design: Clinical assay that compares two groups of patients with hypercapnic respiratory failure, one group with OHS and the other group with kyphoscoliosis, in their basal situation and after 4 months of treatment with nocturnal NIMV. Thirty-six patients (22 patients with OHS and 14 patients with kyphoscoliosis) completed the study protocol., Results: The frequency of symptoms, such as morning headache, morning drowsiness, dyspnea, and leg edema, improved in a statistically significant way in both groups of patients. The sleepiness improved only in the group with OHS. The comparison of frequency of symptoms between both groups of patients after NIMV treatment did not present statistically significant differences. In the resting situation and without nasal ventilation in place, the PO(2) (mean +/- SD) changed from 51 +/- 10 to 64 +/- 11 mm Hg (p < 0.001) and PCO(2) from 58 +/- 10 to 45 +/- 5 mm Hg (p < 0.001) when the patients with OHS were treated with NIMV. In the group of patients with kyphoscoliosis, likewise without nasal ventilation in place, PO(2) changed from 53 +/- 6 to 65 +/- 5 mm Hg (p < 0.001) and PCO(2) from 59 +/- 11 to 45 +/- 4 mm Hg (p < 0.001) with NIMV treatment. When we compared PO(2) and PCO(2) in both groups of patients at the beginning and at the end of NIMV treatment, we did not find statistically significant differences between OHS and kyphoscoliosis., Conclusions: NIMV improves the clinical symptoms and the respiratory failure of patients with OHS to a similar degree to that reported for diseases in which its use is completely established, such as kyphoscoliosis. Therefore, NIMV could be an alternative to the treatment of patients with OHS.

Objective: Obese patients demonstrate a variety of biochemical, metabolic, and pulmonary abnormalities. Inflammatory mediators such as tumor necrosis factor-alpha and interleukin-6 (IL-6) may have a direct effect on glucose and lipid metabolism. Hypoxemia in itself induces release of IL-6. The aim of this study was to examine the relationship between IL-6 levels in healthy volunteers (control group) and three different groups of obese patients: patients without obstructive sleep apnea syndrome (OSAS), patients with OSAS, and patients with obesity hypoventilation syndrome (OHS) (daytime baseline oxygen saturation of <93%)., Research Methods and Procedures: We measured serum IL-6 levels in 25 obese patients (body mass index of >35 kg/m2) and 12 healthy women., Results: The results demonstrate statistically significant differences in serum IL-6 levels between the control group (1.28 +/- 0.85 pg/mL) and obese patients without OSAS (7.69 +/- 5.06 pg/mL, p < 0.05) and with OSAS (5.58 +/- 0.37 pg/mL, p < 0.0005). In the patients with OHS, IL-6 concentrations were highest (43.13 +/- 24.27 pg/mL)., Discussion: We conclude that serum IL-6 is increased in obese patients. The highest IL-6 levels were found in the patients with OHS.

Background: While permissive hypercapnia is commonly practised in critical care, it remains unclear if the comparable manoeuvres are clinically acceptable during anaesthesia. This retrospective study aimed at describing the anaesthetic implications of hypercapnia associated with deliberate hypoventilation during thoracic surgery in patients with severe emphysema., Methods: Thirteen patients with emphysema who required thoracic surgery under similar anaesthesia were reviewed: 3 patients were managed to maintain normocapnia (normocapnia group) whereas 10 patients developed hypercapnia (PaCO2 >70 mmHg) as a result of restricting peak airway pressures (hypercapnia group)., Results: In the normocapnia group (PaCO2: 45+/-1 mmHg, mean+/-SD), no event which required therapeutic intervention during the surgery was seen, whereas 2 of 3 patients showed postoperative air leakage which persisted over 5 days. In the hypercapnia group, the maximum PaCO2 during anaesthesia ranged between 70 mmHg and 135 mmHg (98-21 mmHg). During anaesthesia, all 10 patients required inotropic support to prevent hypotension, 4 patients required tracheal gas insufflation of oxygen to the operated lung to avoid hypoxaemia and 3 patients required lidocaine to treat ventricular arrhythmia. However, the trachea was extubated in the operation theatre in 9 of 10 patients and no organ dysfunction was observed postoperatively. Four patients showed postoperative air leak on the first postoperative day, one of which persisted over 5 days., Conclusion: Although there are some limitations, this preliminary study indicates that hypercapnia around 100 mmHg during anaesthesia for thoracic surgery may not be associated with serious consequences.