Showing papers on "Hypoventilation published in 2014"

Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders

Abstract: Background Chronic alveolar hypoventilation is a common complication of many neuromuscular and chest wall disorders. Long-term nocturnal mechanical ventilation is commonly used to treat it. This is a 2014 update of a review first published in 2000 and previously updated in 2007. Objectives To examine the effects on mortality of nocturnal mechanical ventilation in people with neuromuscular or chest wall disorders. Subsidiary endpoints were to examine the effects of respiratory assistance on improvement of chronic hypoventilation, sleep quality, hospital admissions and quality of life. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 10 June 2014. We contacted authors of identified trials and other experts in the field. Selection criteria We searched for quasi-randomised or randomised controlled trials of participants of all ages with neuromuscular or chest wall disorder-related stable chronic hypoventilation of all degrees of severity, receiving any type and any mode of long-term nocturnal mechanical ventilation. The primary outcome measure was one-year mortality and secondary outcomes were unplanned hospital admission, short-term and long-term reversal of hypoventilation-related clinical symptoms and daytime hypercapnia, improvement of lung function and sleep breathing disorders. Data collection and analysis We used standard Cochrane methodology to select studies, extract data and assess the risk of bias in included studies. Main results The 10 eligible trials included a total of 173 participants. Roughly half of the trials were at low risk of selection, attrition or reporting bias, and almost all were at high risk of performance and detection bias. Four trials reported mortality data in the long term. The pooled risk ratio (RR) of dying was 0.62 (95% confidence interval (CI) 0.42 to 0.91, P value = 0.01) in favour of nocturnal mechanical ventilation compared to spontaneous breathing. There was considerable and significant heterogeneity between the trials, possibly related to differences between the study populations. Information on unplanned hospitalisation was available from two studies. The corresponding pooled RR was 0.25 (95% CI 0.08 to 0.82, P value = 0.02) in favour of nocturnal mechanical ventilation. For most of the outcome measures there was no significant long-term difference between nocturnal mechanical ventilation and no ventilation. Most of the secondary outcomes were not assessed in the eligible trials. Three out of the 10 trials, accounting for 39 participants, two with a cross-over design and one with two parallel groups, compared volume- and pressure-cycled non-invasive mechanical ventilation in the short term. From the only trial (16 participants) on parallel groups, there was no difference in mortality (one death in each arm) between volume- and pressure-cycled mechanical ventilation. Data from the two cross-over trials suggested that compared with pressure-cycled ventilation, volume-cycled ventilation was associated with less sleep time spent with an arterial oxygen saturation below 90% (mean difference (MD) 6.83 minutes, 95% CI 4.68 to 8.98, P value = 0.00001) and a lower apnoea-hypopnoea (per sleep hour) index (MD -0.65, 95% CI -0.84 to -0.46, P value = 0.00001). We found no study that compared invasive and non-invasive mechanical ventilation or intermittent positive pressure versus negative pressure ventilation. Authors' conclusions Current evidence about the therapeutic benefit of mechanical ventilation is of very low quality, but is consistent, suggesting alleviation of the symptoms of chronic hypoventilation in the short term. In four small studies, survival was prolonged and unplanned hospitalisation was reduced, mainly in participants with motor neuron diseases. With the exception of motor neuron disease and Duchenne muscular dystrophy, for which the natural history supports the survival benefit of mechanical ventilation against no ventilation, further larger randomised trials should assess the long-term benefit of different types and modes of nocturnal mechanical ventilation on quality of life, morbidity and mortality, and its cost-benefit ratio in neuromuscular and chest wall diseases.

Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation

Abstract: We aimed to characterise the association of pulmonary hypertension due to hypoventilation and exercise capacity, and the haemodynamic and functional changes under noninvasive ventilation. A retrospective analysis was carried out to assess haemodynamics and functional capacity in 18 patients with daytime pulmonary hypertension, due to hypoventilation, at baseline and after 3 months of noninvasive ventilation. Patients presented with a mean±SD pulmonary artery pressure of 49±13 mmHg, preserved cardiac index (3.2±0.66 L·min(-1)·m(-2)), 6-min walking distance of 303±134 m and severely elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Mean pulmonary artery pressure correlated negatively with maximum work rate (R= -0.72; p=0.03) and 6-min walking distance (R= -0.62; p=0.01). Following noninvasive ventilation we found a significant reduction of mean pulmonary artery pressure (-18 mmHg; p<0.001) and NT-proBNP levels (-2110 pg·mL(-1); p=0.001), and improvement in the 6-min walking distance (+66 m; p=0.008) and maximum work rate (+18 W; p=0.028). Changes in work rate correlated inversely with pulmonary artery pressure (R= -0.75; p=0.031). In this specific cohort with hypoventilation and severe pulmonary hypertension, pulmonary hypertension was associated with reduced exercise capacity. Following noninvasive ventilation, haemodynamics and exercise capacity improved significantly.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: review and update

Abstract: Purpose of review The focus of this review is to compare and contrast two orphan disorders of late-onset hypoventilation. Specifically, rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) and congenital central hypoventilation syndrome (CCHS) are distinct in presentation, pathophysiology, and etiology. Recent findings While limited new information is available, appreciation and understanding of rare disorders can be attained through case reports. Recent literature in ROHHAD has included case reports with new findings that may provide insight into pathophysiology involving possible aberrant immune process and dysregulation at the level of the orexinergic system. Summary The etiology of ROHHAD continues to be elusive. The hope is that, with growing recognition, discussion, and investigation into the overlap of ROHHAD with disorders outside congenital central hypoventilation syndrome, further advancement will be made.

Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis.

Abstract: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome (ROHHADS) is a rare, but potentially lethal, pediatric disorder. To date, nearly 80 patients have been reported in the literature; however, the etiopathogenesis is still unclear and debated. Both genetic and paraneoplastic or immune-mediated causes have been supposed to be involved in this syndrome. Nonetheless, at this time, a diagnostic biomarker is not available and diagnosis is based exclusively on clinical criteria. Aiming to establish the immune-mediated pathogenesis, we report 2 children with a clinical picture consistent with ROHHADS and whose cerebrospinal fluid analysis disclosed an intrathecal synthesis of oligoclonal bands. Even if many aspects remain to be explained, this finding suggests that ROHHADS could share similar pathogenetic mechanisms with other immune-mediated central nervous system disorders, and even more important, it might pave the way to a therapeutic chance for these patients by means of immunotherapy.

Does the supplementary motor area keep patients with Ondine's curse syndrome breathing while awake?

Abstract: Background Congenital central hypoventilation syndrome (CCHS) is a rare neuro-respiratory disorder associated with mutations of the PHOX2B gene. Patients with this disease experience severe hypoventilation during sleep and are consequently ventilator-dependent. However, they breathe almost normally while awake, indicating the existence of cortical mechanisms compensating for the deficient brainstem generation of automatic breathing. Current evidence indicates that the supplementary motor area plays an important role in modulating ventilation in awake normal humans. We hypothesized that the wake-related maintenance of spontaneous breathing in patients with CCHS could involve supplementary motor area. Methods We studied 7 CCHS patients (5 women; age: 20–30; BMI: 22.1±4 kg.m−2) during resting breathing and during exposure to carbon dioxide and inspiratory mechanical constraints. They were compared with 8 healthy individuals. Segments of electroencephalographic tracings were selected according to ventilatory flow signal, from 2.5 seconds to 1.5 seconds after the onset of inspiration. After artefact rejection, 80 or more such segments were ensemble averaged. A slow upward shift of the EEG signal starting between 2 and 0.5 s before inspiration (pre-inspiratory potential) was considered suggestive of supplementary motor area activation. Results In the control group, pre-inspiratory potentials were generally absent during resting breathing and carbon dioxide stimulation, and consistently identified in the presence of inspiratory constraints (expected). In CCHS patients, pre-inspiratory potentials were systematically identified in all study conditions, including resting breathing. They were therefore significantly more frequent than in controls. Conclusions This study provides a neurophysiological substrate to the wakefulness drive to breathe that is characteristic of CCHS and suggests that the supplementary motor area contributes to this phenomenon. Whether or not this “cortical breathing” can be taken advantage of therapeutically, or has clinical consequences (like competition with attentional resources) remains to be determined.

Respiratory determinants of diurnal hypercapnia in obesity hypoventilation syndrome. What does weight have to do with it

Abstract: Rationale: Among morbidly obese individuals, obstructive sleep apnea (OSA) is highly prevalent, with up to 20% suffering from hypoventilation syndrome. An increased diurnal PaCO2, the signature of obesity hypoventilation syndrome (OHS), implies diminished global ventilation, hence the term hypoventilation.Objectives: We hypothesized that hypercapnic patients with OSA have lower Ve than eucapnic patients with OSA.Methods: In this prospective study we recorded respiratory variables to determine the pathophysiological mechanisms of steady-state diurnal hypercapnia of 12 consecutive hypercapnic and 20 consecutive eucapnic patients with OSA, matched for apnea–hypopnea index. Patients with any known causes of hypercapnia were not included.Measurements and Main Results: Comparing hypercapnic to eucapnic patients, the mean value (±SD) for PaCO2 (52 ± 5 vs. 40 ± 3 mm Hg) was significantly higher, and the mean PaO2 (59 ± 8 vs. 75 ± 10 mm Hg) was significantly lower, in the hypercapnic patients. Surprisingly, the me...

Residual chemosensitivity to ventilatory challenges in genotyped congenital central hypoventilation syndrome

Abstract: Congenital central hypoventilation syndrome (CCHS) is a neurodevelopmental disorder characterized by life-threatening hypoventilation, possibly resulting from disruption of central chemosensory int...

Obesity hypoventilation syndrome: does the current definition need revisiting?

Abstract: Obesity hypoventilation syndrome (OHS) has been conventionally (and to some extent arbitrarily) defined by the combination of obesity (body mass index (BMI) >30 kg/m2), daytime hypercapnia (arterial partial pressure of carbon dioxide (PaCO2) ≥45 mm Hg or 6 kPa) during wakefulness, and usually (but not always) the presence of ‘sleep disordered breathing’, such as obstructive sleep apnoea, rapid eye movement sleep hypoventilation or both.1 The survival curve for untreated OHS is significantly reduced compared with the non-obese,2 and so early identification and treatment for these patients is likely to be beneficial. Little is currently known about the true prevalence of OHS in ambulatory obese individuals, with estimates range from 0.3–0.4% of the general population,3 to around 30% of hospitalised patients with a BMI >35 kg/m …

Respiratory involvement in neuromuscular disease

Abstract: #### Key points In neuromuscular disease (NMD), respiratory muscle weakness (RMW) is common and death often results from respiratory failure. RMW initially causes sleep-related hypoventilation, with sleep disruption. With progression, daytime respiratory failure ensues. Bulbar muscle weakness

Obstructive sleep apnea and other sleep-related syndromes.

Abstract: Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by repetitive episodes of breathing cessation due to complete or partial collapse of the upper airway therefore affecting ventilation. It is quite common, with a prevalence of about 2-4%, has a strong genetic component, and creates a proinflammatory state with elevated TNFα and other cytokines. If untreated, OSA can lead to significant neurological problems that include stroke, cognitive decline, depression, headaches, peripheral neuropathy, and nonarteritic ischemic optic neuropathy (NAION). Treatment reverses some of these neurological problems. Treatment includes continuous positive airway pressure and its variants, oral appliances, weight loss, upper airway surgery, and rarely maxillofacial procedures. Other sleep breathing disorders such as hypoventilation, central sleep apnea, complex sleep apnea, and Cheyne-Stokes respiration are less common and are sometimes associated with neuromuscular disorders causing diaphragmatic paralysis, but can also be seen in opiate exposure and severe obesity.

Ventilatory response to nitrogen multiple-breath washout in infants.

Abstract: BACKGROUND Nitrogen multiple-breath washout (N2 MBW) using 100% oxygen (O2 ) has regained interest to assess efficiency of tracer gas clearance in, for example, children with Cystic Fibrosis (CF). However, the influence of hyperoxia on the infants' respiratory control is unclear. We assessed safety and impact on breathing pattern from hyperoxia, and if exposure to 40% O2 first induces tolerance to subsequent 100% O2 for N2 MBW. METHODS We prospectively enrolled 39 infants aged 3-57 weeks: 15 infants with CF (8 sedated for testing) and 24 healthy controls. Infants were consecutively allocated to the protocols comprising of 100% O2 or 40/100% O2 administered for 30 breaths. Lung function was measured using an ultrasonic flowmeter setup. Primary outcome was tidal volume (VT ). RESULTS None of the infants experienced apnea, desaturation, or bradycardia. Both protocols initially induced hypoventilation. VT temporarily declined in 33/39 infants across 10-25 breaths. Hypoventilation occurred independent of age, disease, and sedation. In the new 40/100% O2 protocol, VT returned to baseline during 40% O2 and remained stable during 100% O2 exposure. End-tidal carbon dioxide monitored online did not change. CONCLUSION The classical N2 MBW protocol with 100% O2 may change breathing patterns of the infants. The new protocol with 40% O2 induces hyperoxia-tolerance and does not lead to changes in breathing patterns during later N2 washout using 100% O2 . Both protocols are safe, the new protocol seems an attractive option for N2 MBW in infants. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity.

Abstract: A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction.

"Permissive hypoventilation" in a swine model of hemorrhagic shock.

Abstract: BACKGROUND Many penetrating trauma patients in severe hemorrhagic shock receive positive pressure ventilation (PPV) upon transport to definitive care, either by intubation (INT) or bag-valve mask (BVM). Using a swine hemorrhagic shock model that simulates penetrating trauma, we proposed that severely injured patients may have better outcomes with "permissive hypoventilation," where manual breaths are not given and oxygen is administrated passively via face mask (FM). We hypothesized that PPV has harmful physiologic effects in severe low-flow states and that permissive hypoventilation would result in better outcomes. METHODS The carotid arteries of Yorkshire pigs were cannulated with a 14-gauge catheter. One group of animals (n = 6) was intubated and manually ventilated, a second received PPV via BVM (n = 7), and a third group received 100% oxygen via FM (n = 6). After placement of a Swan-Ganz catheter, the carotid catheters were opened, and the animals were exsanguinated. The primary end point was time until death. Secondary end points included central venous pressure, cardiac output, lactate levels, serum creatinine, CO2 levels, and pH measured in 10-minute intervals. RESULTS Average survival time in the FM group (50.0 minutes) was not different from the INT (51.1 minutes) and BVM groups (48.5 minutes) (p = 0.84). Central venous pressure was higher in the FM group as compared with the INT 10 minutes into the shock phase (8.3 mm Hg vs. 5.2 mm Hg, p = 0.04). Drop in cardiac output (p < 0.001) and increase in lactate (p < 0.05) was worse in both PPV groups throughout the shock phase. Creatinine levels were higher in both PPV groups (p = 0.04). The FM group was more hypercarbic and acidotic than the two PPV groups during the shock phase (p < 0.001). CONCLUSION Although permissive hypoventilation leads to respiratory acidosis, it results in less hemodynamic suppression and better perfusion of vital organs. In severely injured penetrating trauma patients, consideration should be given to immediate transportation without PPV.

Neural Respiratory Drive and Ventilation in Patients with Chronic Obstructive Pulmonary Disease during Sleep

Abstract: To the Editor: Patients with chronic obstructive pulmonary disease (COPD) experience sleep-related hypoventilation (1, 2) However, there is controversy as to whether this occurs due to an increase in upper airway resistance or a reduction in neural respiratory drive Elevated neural respiratory drive in wakefulness is well documented in COPD (3) O’Donoghue and coworkers (4) reported in patients with COPD that a sleep-related hypoventilation was due to increased upper airway resistance, and Ballard and coworkers (5) reported an increase in upper airway resistance moving from wakefulness to sleep, although upper airway resistance was not consistently greater during sleep (see Figure 3 of their article [5]) Moreover, in healthy young adults, a poor correlation was observed between changes in ventilation and upper airway resistance (6) Morrell and coworkers (7) addressed the question directly in tracheotomized subjects, confirming hypoventilation during sleep, thus excluding an obligate contribution from upper airway resistance To further address the question, we performed diaphragm electromyography (EMGdi) using a multipair esophageal electrode as an index of neural respiratory drive (8–11) Some of the data have been previously reported in abstract form (12) A total of 17 stable patients with moderate to very severe COPD and 14 age-matched normal subjects participated All subjects were free from obstructive sleep apnea (OSA; apnea–hypopnea index < 50 events/h) and snoring confirmed by prior overnight polysomnography, and were free from clinically significant coexisting diseases, including neuromuscular disorders The study was approved by the Ethics Committee of the Chinese State Key Laboratory of Respiratory Disease, and all patients gave their informed consent to participate A multipair esophageal electrode catheter (Yinghui Medical Technology Co, Ltd, Guangzhou, China) was used as previously described (8) to record the EMGdi during overnight polysomnography (9–11) Airflow was recorded with a pneumotachograph connected to a full facemask Maximal EMGdi was recorded from maximal voluntary inspiratory maneuvers Polysomnography was manually analyzed based on standard criteria (13) The root mean square (RMS) of the EMGdi (RMSEMGdi) was calculated by computer with a time constant of 100 milliseconds Efficacy of neural respiratory drive was defined as the ratio of minute ventilation to peak RMSEMGdi of each breath Data were selected during stable breathing without respiratory events Data collected for 10 minutes before sleep and for at least 15 minutes during non–rapid eye movement (NREM) and REM in the supine position were selected for analysis Two-way ANOVA was used to test differences between wakefulness, NREM, and REM sleep; data are presented as means (±SD), and statistical significance was determined as a P value of less than 005 Some subjects could not tolerate the full facemask, and satisfactory measurements were therefore obtained in 10 male patients with COPD (age, 593 ± 115 yr; body mass index, 208 ± 31 kg/m2; FEV1, 342 ± 158% predicted; FEV1/FVC, 378 ± 116%; oxygen saturation <90%, 20 ± 40% of total sleep time) and 10 control subjects (nine males and one female, age, 581 ± 90 yr; body mass index, 228 ± 28 kg/m2; FEV1 978 ± 95% predicted) The maximal RMSEMGdi measured from patients with COPD was similar to control subjects (1807 ± 920 μV vs 1617 ± 536 μV) RMSEMGdi, as a percent maximal, in patients with COPD was significantly higher than that in normal subjects during wakefulness, NREM, and REM (Table 1) Compared with wakefulness, the RMSEMGdi decreased by 31 (±12)% in NREM, and further decreased by 49 (±12)% in REM sleep in patients with COPD Similarly, ventilation decreased by 30 (±14)% in NREM and 44 (±11)% in REM As shown in Table 1, the reduction in ventilation was principally mediated by tidal volume The reductions in the RMSEMGdi and ventilation were of smaller magnitude in normal subjects The efficacy of neural respiratory drive in normal subjects was significantly higher than that in patients with COPD during both wakefulness and sleep However, sleep did not change the efficacy of neural respiratory drive in either patients with COPD or normal subjects (Table 1 and Figure 1) Table 1 The Root Mean Square of the Diaphragm Electromyography and Ventilation during Wakefulness and Sleep and Their Change Compared with Wakefulness Figure 1 Polysomnography including five-channel diaphragm electromyography (EMGdi; 1–5) from a multipair esophageal electrode, airflow from pneumotachograph, end-tidal CO2, electroencephalogram (EEG; C3A2 and C4A1), and left and right electrooculograms This is the first study to simultaneously accurately record ventilation with a pneumotachograph connected to a full facemask and EMGdi, during wakefulness, NREM, and REM sleep, in patients with COPD without coexisting OSA The efficacy of neural respiratory drive reflects upper airway resistance if lung mechanics and lower airway resistance remain the same Because this is considered to be the case (4, 5), we speculate that the unchanged efficacy of neural respiratory drive between wakefulness and sleep argues against a substantial increase in upper airway resistance during sleep in either nonobese patients with COPD or normal subjects This result is consistent with the work of Meurice and coworkers (14), who reported that upper airway resistance changed little in some patients with COPD during sleep Although O’Donoghue and colleagues (4) concluded that sleep-related hypoventilation in patients with COPD was because of a threefold increase in upper airway resistance, the subjects they studied may have had mild OSA, because an apnea–hypopnea index up to 10 events/h was permitted Our results are consistent with the results reported by Morrell and coworkers (7), who showed that the development of sleep-related hypoventilation is independent of upper airway resistance, because the reduction of ventilation from wakefulness to NREM sleep in subjects who were breathing through the upper airway was similar to that in laryngectomized subjects who were breathing through a tracheal stoma Our conclusions are also consistent with other data supporting the case that reduction of neural respiratory drive is important in sleep-related hypoventilation For example, when continuous positive airway pressure is applied in patients with COPD to eliminate upper airway resistance (1), or to normalize upper airway resistance to waking levels in normal subjects (15), sleep-related hypoventilation is still evident Naturally, our study has some limitations We had a relatively small sample size, and all patients were from one ethnic group and were not in respiratory failure, which could modify pharyngeal behavior (15) Our data are only representative of those who could sleep while instrumented Thus, our findings should not be extended uncritically to all patients with COPD However, in contrast to the previous hypothesis that hypoventilation is principally due to upper airway resistance, our study suggests that sleep-associated hypoventilation in patients with COPD is mainly related to reduction of neural respiratory drive This observation suggests that noninvasive positive-pressure ventilation is a more logical approach than continuous positive airway pressure to the treatment of nocturnal hypoventilation in COPD

The effect of ketamine on hypoventilation during deep sedation with midazolam and propofol: a randomised, double-blind, placebo-controlled trial.

Abstract: Background Hypoventilation is a major cause of morbidity and mortality in patients having procedures under sedation. Few clinical strategies have been evaluated to reduce intraoperative hypoventilation during surgical procedures under deep sedation. Objective The primary objective of this investigation was to examine the effect of ketamine on hypoventilation in patients receiving deep sedation for surgery with midazolam and propofol. Design The study was a randomised, placebo-controlled, double-blind clinical trial. Setting Intraoperative. Patients Healthy women undergoing breast surgery. Intervention Randomised to receive ketamine (0.5 mg kg bolus, followed by an infusion of 1.5 μg kg min) or isotonic saline. Main outcome measure Duration of hypercapnia measured continuously with a transcutaneous carbon dioxide (TCO2) monitor. Results Fifty-four participants were recruited. Patient and surgical characteristics were similar between the study groups. The median percentage of the sedation time with TCO2 more than 6.7 kPa in participants in the ketamine group, 1.2% (95% confidence interval, CI, 0 to 83), was less than that in the isotonic saline group (65%, 95% CI, 0 to 88; P = 0.01). Severe hypoventilation (TCO2 >8.0 kPa) was also less in the ketamine group, median 0% (95% CI, 0 to 11.7) compared with 28% (95% CI, 0 to 79.3; P = 0.0002) for the isotonic saline group. The ketamine group required less airway manoeuvres (chin lift) to keep the SaO2 greater than 95% median (95% CI) [0 (0 to 3) compared with 3 (0 to 16) in the isotonic saline group] (P = 0.004). Conclusion Ketamine decreased the duration and severity of hypercapnia in patients undergoing deep sedation with propofol. The addition of ketamine may reduce hypoventilation and adverse effects in patients having procedures under sedation. Trial registration clinicaltrials.gov identifier: NCT01535976.

Sleep-related disorders in chronic obstructive pulmonary disease

Abstract: Sleep may have several negative consequences in patients with chronic obstructive pulmonary disease (COPD). Sleep is typically fragmented with diminished slow wave and rapid-eye-movement sleep, which likely represents an important contributing factor to daytime symptoms such as fatigue and lethargy. Furthermore, normal physiological adaptations during sleep, which result in mild hypoventilation in normal subjects, are more pronounced in COPD, which can result in clinically important nocturnal oxygen desaturation. The co-existence of obstructive sleep apnea and COPD is also common, principally because of the high prevalence of each disorder, and there is little convincing evidence that one disorder predisposes to the other. Nonetheless, this co-existence, termed the overlap syndrome, typically results in more pronounced nocturnal oxygen desaturation and there is a high prevalence of pulmonary hypertension in such patients. Management of sleep disorders in patients with COPD should address both sleep quality and disordered gas exchange. Non-invasive pressure support is beneficial in selected cases, particularly during acute exacerbations associated with respiratory failure, and is particularly helpful in patients with the overlap syndrome. There is limited evidence of benefit from pressure support in the chronic setting in COPD patients without obstructive sleep apnea.

Nasal high-flow oxygen therapy system for improving sleep-related hypoventilation in chronic obstructive pulmonary disease: a case report

Abstract: Introduction: Sleep-related hypoventilation should be considered in patients with chronic obstructive pulmonary disease, because appropriate respiratory management during sleep is important for preventing elevation of PaCO2 levels. A nasal high-flow oxygen therapy system using a special nasal cannula can deliver suitably heated and humidified oxygen at up to 60 L/min. Since the oxygen concentration remains a constant independent of minute ventilation, this system is particularly useful in patients with chronic obstructive pulmonary disease who have hypercapnia. This is the first report of sleep-related hypoventilation with chronic obstructive pulmonary disease improving using a nasal high-flow oxygen therapy system. Case presentation: We report the case of a 73-year-old Japanese female who started noninvasive positive-pressure ventilation for acute exacerbation of chronic obstructive pulmonary disease and CO2 narcosis due to respiratory infection. Since she became agitated as her level of consciousness improved, she was switched to a nasal high-flow oxygen therapy system. When a repeat polysomnography was performed while using the nasal high-flow oxygen therapy system, the Apnea Hypopnea Index was 3.7 times/h, her mean SpO2 had increased from 89 to 93%, percentage time with SpO2 ≤ 90% had decreased dramatically from 30.8 to 2.5%, and sleep stage 4 was now detected for 38.5 minutes. As these findings indicated marked improvements in sleep-related hypoventilation, nasal high-flow oxygen therapy was continued at home. She has since experienced no recurrences of CO2 narcosis and has been able to continue home treatment. Conclusions: Use of a nasal high-flow oxygen therapy system proved effective in delivering a prescribed concentration of oxygen from the time of acute exacerbation until returning home in a patient with chronic obstructive pulmonary disease, dementia and sleep-related hypoventilation. The nasal high-flow oxygen therapy system is currently used as a device to administer high concentrations of oxygen in many patients with type I respiratory failure, but may also be useful instead of a Venturi mask in patients like ours with type II respiratory failure, additionally providing some positive end-expiratory pressure.

ROHHADNET Syndrome Presenting as Major Behavioral Changes in a 5-Year-Old Obese Girl

Abstract: Behavioral issues are a frequent problem in the pediatric population. Often, these are evaluated and considered to be psychiatric in origin. We report on a pediatric patient who presented with severe behavioral disturbance and developed organic symptoms including hypoventilation and dysautonomia and who was ultimately diagnosed with ROHHADNET syndrome, a syndrome of rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated with a neuroendocrine tumor. Autopsy findings revealed novel findings of the syndrome, including hypothalamic encephalitis.

Frequency and predictors of obesity hypoventilation in hospitalized patients at a tertiary health care institution

Abstract: Objectives: Patients with obesity hypoventilation syndrome (OHS) have significant morbidity and mortality. Early diagnosis and treatment is important and there are limited data on its prevalence and predictive factors. The objective of this observational study was to determine the frequency and predictors of OHS in hospitalized patients at a tertiary health care institution. Materials and Methods: All blood gas analyses of hospitalized adult (age over 18 years) patients were prospectively recruited from the biochemistry laboratory at a tertiary health care center between August 2009 and July 2010. Patients who had hypercapnia (PaCO 2 ≥ 45 mmHg) while breathing room air were included and clinical and laboratory data were obtained from hospital records. A standard questionnaire was also filled by face-to-face interview with patients and/or relatives. Results: A total of 9480 patients' arterial blood gases were evaluated and 330 patients (3.4%) who met the selection criteria were included in the analysis during the study period. Hypoventilation was associated with acute diseases in 64.2% and chronic diseases in 35.8% of the patients. Of the chronic hypoventilation patients, 24.4% had OHS. Univariate logistic regression analysis showed that, female gender, body mass index (BMI), smoking, PaO 2 , SaO 2 and a PaCO 2 /BMI 35 kg/m 2 , SaO 2 Conclusions: OHS is a common cause of chronic alveolar hypoventilation. A careful examination PaCO 2 /BMI ratio may prevent misdiagnoses among hypercapnic patients.

Pulmonary hypertension in hypoventilation syndromes

Abstract: The object that presented itself to the eyes of the astonished clerk, was a boy – a wonderfully fat boy – habited as a serving lad, standing upright on the mat, with his eyes closed as if in sleep. – Dickens [1] In this issue of the European Respiratory Journal , Held et al. [2] report on 18 patients with severe pulmonary hypertension due to alveolar hypoventilation, who were markedly improved after 3 months of noninvasive bi-level positive-pressure ventilation (NIPPV). Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were 50 mmHg and 6–7 Wood units, respectively, at baseline, and decreased to 30 mmHg and 3–4 Wood units with NIPPV; this was accompanied by improved catherisation and echocardiographic indices of right ventricular (RV) function. The N-terminal pro-brain natriuretic peptide (NT-proBNP) levels also decreased, and the 6-min walk distance (6MWD) improved by 80 m. These results are in striking contrast with the “borderline” (mPAP 20–25 mmHg) or mild (mPAP 25–30 mmHg) pulmonary hypertension generally seen, but with rare exceptions, in patients with respiratory conditions. Borderline or mild pulmonary hypertension due to respiratory conditions is of uncertain clinical relevance, exhibits slow progression controlled by supplemental oxygen and is refractory to drugs targeting the pulmonary circulation [3, 4]. 12 of the 18 patients reported by Held et al. [2] fulfilled the criteria of obesity hypoventilation syndrome (OHS), defined by a combination of awake hypercapnia (arterial carbon dioxide tension ( P aCO2) >45 mmHg), a body mass index >30 kg·m−2 and exclusion of other causes that could account for hypoventilation, such as lung or neuromuscular disease [5, 6]. Three of the OHS patients had concomitant chronic obstructive pulmonary disease (COPD) and five patients had COPD without obesity. …

[Nocturnal monitoring of home non-invasive ventilation: Contribution of simple tools such as pulse-oximetry, capnography, built-in ventilator software and autonomic markers of sleep fragmentation].

Abstract: Complex respiratory events, which may have a detrimental effect on both quality of sleep and control of nocturnal hypoventilation, occur during sleep in patients treated by non-invasive ventilation (NIV). Among these events are patient-ventilator asynchrony, increases in upper airway resistance with or without increased respiratory drive, and leaks. Detection of these events is important in order to select the most appropriate ventilator settings and interface. Simple tools can provide important information when monitoring NIV. Pulse-oximetry is important to ensure that an adequate SpO2 is provided, and to detect either prolonged or short and recurrent desaturations. However, the specificity of pulse-oximetry tracings under NIV is low. Transcutaneous capnography discriminates between hypoxemia related to V/Q mismatch and hypoventilation, documents correction of nocturnal hypoventilation, and may detect ventilator-induced hyperventilation, a possible cause for central apnea/hypopnea and glottic closure. Data provided by ventilator software helps the clinician by estimating ventilation, tidal volume, leaks, rate of inspiratory or expiratory triggering by the patient, although further validation of these signals by independent studies is indicated. Finally, autonomic markers of sympathetic tone using signals such as pulse wave amplitude of the pulse-oximetry signal can provide reliable information of sleep fragmentation.

Latin America's first case of Perry syndrome and a new treatment option for respiratory insufficiency

Abstract: Dear Sirs, Perry syndrome is an autosomal dominant disorder characterized by rapidly progressive Parkinsonism, depression, weight loss, and central hypoventilation [1]. Since the original publication in 1975, only 52 patients from ten families have been found, but no case had been reported from Latin America. The mean age of symptom onset is 48 years, and the mean disease duration is 5 years. Patients usually die of respiratory complications. Genome-wide linkage analysis identified disease-segregating mutations located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13 [4]. A 56-year-old Colombian female was admitted to the Hospital Universitario San Ignacio, in Bogota, Colombia, with acute deterioration of her respiration. On clinical examination, the patient displayed generalized anxiety and a severe depressive episode. She reported a weight loss of 15 kg in 6 months. The patient had a 2-year history of Parkinsonism, which comprised hypomimia, cogwheel rigidity in all extremities, and low-frequency postural and intention tremor of the upper extremities that was more pronounced on the left side. Levodopa at a maximum daily dosage of 1,000 mg combined with 100 mg of carbidopa slightly improved the tremor. Brain MRI, EEG, and muscle biopsy did not show any relevant abnormalities. A gas blood analysis on admission showed the following values: FiO2 21 %, pH 7.32, pCO2 60 mmHg, PO2 20 mmHg, HCO3 31 mmol/l, SatO2 88 % with a supply of 2 l of O2 per minute via nasal cannula. This demonstrated severe respiratory acidosis with acidemia. There was no history of chronic obstructive pulmonary disease. The patient's body max index was 16.6. Diagnostic procedures to clarify the etiology of the respiratory insufficiency included diaphragm electromyography (EMG), the mouth pressure generated 100 ms after the onset of an occluded inspiratory effort (P0.1), and the transdiaphragmatic pressure (Pdi) measured with a transesophageal probe. Their results were as follows: normal EMG, 9 cm H2O (P0.1), and 5 cm H2O (Pdi), which suggested a central etiology. Due to unstable and deteriorating respiratory conditions, no polysomnography could be performed. Instead, the patient was placed on mechanical ventilation following tracheostomy. Numerous attempts to treat her with noninvasive respiratory support over a period of 2 months prior to the hospital admission had been unsuccessful. Efforts to wean the patient off a ventilator during other 2 months following the admission failed. Thus, the patient was fitted with a bilateral diaphragmatic pacemaker with direct stimulation of the phrenic nerve (Mark IV Breathing Pacemaker System, Avery Biomedical Devices, Inc.) following a bilateral anterior thoracotomy with a 6-cm transverse incision over the third intercostal space. The surgery was complicated by a mild right hematothorax and subcutaneous emphysema. The patient was stimulated with a pulse train of 20 Hz. The most common pacemaker settings were an amplitude of 1.6 mA and a respiratory frequency of 15 breaths per minute. Two-year-follow-up examinations have displayed a good function of the diaphragmatic pacemaker. The patient became independent in her everyday life. There have been no episodes of acute respiratory failure, albeit the patient has occasionally developed pneumonia. This has successfully been treated with antibiotics. Implantation of a diaphragmatic pacemaker also enabled to avoid the very high costs of permanent ventilatory support. Family history revealed the same symptoms in her mother and another nine relatives on her mother's side, including four uncles, two sisters, and three cousins. All died of respiratory insufficiency. Molecular genetic testing for Perry syndrome confirmed this diagnosis revealing the c.211 G > A (p.G71R) mutation in exon 2 of the DCTN1 gene on chromosome 2p13.1. Our patient is Latin America's first genetically confirmed case of Perry syndrome. Contrary to other cases, our patient presented with mild extrapyramidal symptoms and pronounced respiratory insufficiency as the main complaint. However, the latter has successfully been treated with the use of a diaphragmatic pacemaker. Our case is the first successful attempt to apply a diaphragmatic pacemaker in a patient with Perry syndrome, although diaphragmatic pacemakers in the form of direct phrenic nerve pacing (Diaphragmatic/Phrenic Nerve Stimulator) have already been applied in the symptomatic treatment of different conditions such as congenital central hypoventilation syndrome [5] or medullary trauma [6]. Diaphragmatic pacemakers with the direct stimulation of the diaphragm (Diaphragm Pacing Systems) have been approved by the US Food and Drug Administration in the treatment of ventilator failure in amyotrophic lateral sclerosis [7], spinal cord injuries, and congenital central hypoventilation syndrome. We conclude that implantation of a diaphragmatic pacemaker should be considered as a safe, effective, and cost-reducing treatment option for respiratory insufficiency in patients with Perry syndrome. Early diagnosis significantly improves the patient's quality of life and prevents life-threatening acute respiratory failure. Parkinsonian features, although always present in Perry syndrome, may not be disabling in some cases. Perry syndrome is not geographically constrained. New cases from South America are expected to be diagnosed.

A case of congenital central hypoventilation syndrome with a novel mutation of the PHOX2B gene presenting as central sleep apnea.

Abstract: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by abnormal autonomic control of breathing resulting in hypoventilation. We report an infant girl with CCHS who pr...