Central Neurogenic Hyperventilation and Hyperlactatemia After Resection of a Fourth Ventricle Tumor: A Case Report.

We report a rare case of central neurogenic hyperventilation (CNH) and hyperlactatemia after resection of a fourth ventricle tumor. Our management consisted of close monitoring and exclusion of alternate causes of hyperventilation and hyperlactatemia. We hypothesize that a localized increase in tissue lactate, related to tumor metabolism, may have triggered CNH in our patient through stimulation of the brainstem respiratory centers. CNH should be considered during the differential diagnosis of perioperative hyperventilation with respiratory alkalosis in patients with posterior fossa tumors. Hyperlactatemia can trigger compensatory hyperventilation but will not result in alkalosis.

OTUB1 regulates lung development, adult lung tissue homeostasis, and respiratory control.

OTUB1 is one of the most highly expressed deubiquitinases, counter-regulating the two most abundant ubiquitin chain types. OTUB1 expression is linked to the development and progression of lung cancer and idiopathic pulmonary fibrosis in humans. However, the physiological function of OTUB1 is unknown. Here, we show that constitutive whole-body Otub1 deletion in mice leads to perinatal lethality by asphyxiation. Analysis of (single-cell) RNA sequencing and proteome data demonstrated that OTUB1 is expressed in all lung cell types with a particularly high expression during late-stage lung development (E16.5, E18.5). At E18.5, the lungs of animals with Otub1 deletion presented with increased cell proliferation that decreased saccular air space and prevented inhalation. Flow cytometry-based analysis of E18.5 lung tissue revealed that Otub1 deletion increased proliferation of major lung parenchymal and mesenchymal/other non-hematopoietic cell types. Adult mice with conditional whole-body Otub1 deletion (wbOtub1del/del ) also displayed increased lung cell proliferation in addition to hyperventilation and failure to adapt the respiratory pattern to hypoxia. On the molecular level, Otub1 deletion enhanced mTOR signaling in embryonic and adult lung tissues. Based on these results, we propose that OTUB1 is a negative regulator of mTOR signaling with essential functions for lung cell proliferation, lung development, adult lung tissue homeostasis, and respiratory regulation.

Central neurogenic hyperventilation secondary to suspected metastatic renal cell carcinoma.

Central neurogenic hyperventilation (CNH) is a neurogenic disorder rarely described within Emergency Medicine literature. CNH is a primary cause of hyperventilation, most commonly due to primary central nervous system neoplasms. Patient presentation varies based on the underlying cause, and may present with a sole chief complaint of dyspnea. We present a case of an adult male with a history of deep vein thrombosis, anticoagulated on apixaban, and extensively metastatic renal cell carcinoma who presented with a two-week history of dyspnea. Evaluation in the emergency department showed a primary respiratory alkalosis with a compensatory metabolic acidosis. Diagnostic work-up failed to reveal a cardiac, pulmonary, metabolic, or toxic cause. During the emergency department course, the patient became dysarthric and altered, at which point, computed tomography scan of the head revealed a pontine hemorrhage. The hemorrhage was stabilized with prothrombin complex concentrate, but the patient's dyspnea and mental status deteriorated throughout the course of his hospitalization. While the cause of the patient's hemorrhage was not elucidated, given the patient's widely metastatic disease, it was presumed to be secondary to metastasis. Our case highlights both a unique cause of a rare disorder of hyperventilation, and a diagnostic challenge to the emergency medicine provider. It is important to consider central causes of hyperventilation in patients with dyspnea and neurologic symptoms.

Lessons of the month 2: A forgotten cause of transient T-wave inversion.

A 19-year-old patient presented with severe chest pain, which is not typical for cardiac angina. However, his smoking history and the strong family history of ischaemic heart disease coupled with evidence of progressive T-wave changes on his electrocardiogram (ECG) caused dilemma in deciding further management. His blood tests were normal apart from hypophosphataemia, and he had two negative troponin results. His arterial blood gases showed respiratory alkalosis. He was given analgesia for a diagnosis of musculoskeletal chest pain and the next morning his ECG, arterial blood gases and phosphate levels all normalised. He had a normal echocardiogram and was reviewed by the cardiologist who diagnosed musculoskeletal chest pain which led to distress and hyperventilation causing hypophosphataemia and transient T-wave inversion. This case is a reminder of an under-recognised physiological phenomenon involving the cardiac conduction during hyperventilation.

Hyperventilation Syndrome and Sustained Hyperchloremia After Kidney Transplant: Time-Sequence Swing of Acid-Base Interpretation.

An interaction between regained renal function in a transplanted kidney and hyperventilation syndrome may interfere with correct diagnosis of acid-base status in patients with preoperative nongap acidosis. Here, we present a patient with glomerular nephritis and hyperchloremia who underwent kidney transplant. Progressively increasing bicarbonate reabsorption by the renal graft, which thereby changed the arterial carbon dioxide tension-to-bicarbonate ratio, resulted in a time-sequence swing of an acid-base interpretation despite persistent mixed respiratory alkalosis due to hyperventilation syndrome and nongap metabolic acidosis due to preexisting hyperchloremia. Specifically, the sequence was mixed primary metabolic acidosis and primary respiratory acidosis immediately after surgery, primary metabolic acidosis and secondary respiratory alkalosis on postoperative days 1 and 2, mixed primary hyperchloremic metabolic acidosis and primary respiratory alkalosis on postoperative day 3, and finally primary respiratory alkalosis and secondary hyperchloremic metabolic acidosis on postoperative day 7. This swing in the acid-base interpretation indicates that the acid-base imbalance described here does not fit the empirical relationship for calculating the expected bicarbonate or carbon dioxide tension value, suggesting that "correct" interpretation of acid-base status may not lead to "correct" diagnosis of acid-base status. It should be remembered that not every acid-base imbalance fits the empirical relationship.

Purinergic and adenosine receptors contribute to hypoxic hyperventilation in zebrafish (Danio rerio).

The chemoreceptors involved in oxygen sensing in teleost fish are neuroepithelial cells (NECs) in the gills, and are analogous to glomus cells in the mammalian carotid body. Purinergic signalling mechanisms involving the neurotransmitters, ATP and adenosine, have been identified in mediating hypoxic signalling in the carotid body, but these pathways are not well understood in the fish gill. The present study used a behavioural assay to screen for the effects of drugs, that target purinergic and adenosine receptors, on the hyperventilatory response to hypoxia in larval zebrafish (Danio rerio) in order to determine if the receptors on which these drugs act may be involved in hypoxic signalling. The purinergic receptor antagonist, PPADS, targets purinergic P2X2/3 receptors and inhibited the hyperventilatory response to hypoxia (IC50=18.9µM). The broad-spectrum purinergic agonist, ATPγS, elicited a hyperventilatory response (EC50=168µM). The non-specific adenosine receptor antagonist, caffeine, inhibited the hyperventilatory response to hypoxia, as did the specific A2a receptor antagonist, SCH58261 (IC50=220nM). These results suggest that P2X2/3 and A2a receptors are candidates for mediating hypoxic hyperventilation in zebrafish. This study highlights the potential of applying chemical screening to ventilatory behaviour in zebrafish to further our understanding of the pathways involved in signalling by gill NECs and oxygen sensing in vertebrates.

Investigating hyperventilation syndrome in patients suffering from empty nose syndrome.

OBJECTIVES/HYPOTHESIS: Patients with empty nose syndrome (ENS) following turbinate surgery often complain about breathing difficulties. We set out to determine if dyspnea in patients with ENS was associated with hyperventilation syndrome (HVS). We hypothesized that lower airway symptoms in ENS could be explained by HVS. STUDY DESIGN: Observational prospective study. METHODS: All consecutive patients referred to our center for ENS over 1 year were invited to participate. Patients completed the Nijmegen score and underwent a hyperventilation provocation test (HVPT) and arterial blood gas and cardiopulmonary tests. HVS was defined by a delayed return of the end-tidal partial pressure of carbon dioxide in the expired gas to baseline during HVPT. Patients with HVS were asked to complete the Sinonasal Outcome Test (SNOT)-16 questionnaire before and after a specific eight-session respiratory rehabilitation program. RESULTS: Twenty-two of the 29 patients referred for ENS during the study period were eligible for inclusion and underwent a complete workup. HVS was diagnosed in 17 of these patients (77.3%). In the five patients who completed the SNOT-16, the score was significantly lower after rehabilitation. CONCLUSIONS: This study suggests that HVS is frequent in patients with ENS, and that symptoms can be improved by respiratory rehabilitation. Pathophysiological links between ENS and HVS deserve to be further explored. LEVEL OF EVIDENCE: 2b Laryngoscope, 127:1983-1988, 2017.

Endogenous hydrogen sulfide in the rostral ventrolateral medulla/Bötzinger complex downregulates ventilatory responses to hypoxia.

Hydrogen sulfide (H2S) is now recognized as a new gaseous transmitter involved in several brain-mediated responses. The rostral ventrolateral medulla (RVLM)/Bötzinger complex is a region in the brainstem that is involved in cardiovascular and respiratory functions. Recently, it has been shown that exogenous H2S in the RVLM modulates autonomic function and thus blood pressure. In the present study, we investigated whether H2S, endogenously produced in the RVLM/Bötzinger complex, plays a role in the control of hypoxia-induced hyperventilation. Ventilation (VE) was measured before and after bilateral microinjection of Na2S (H2S donor, 0.04, 1 and 2 pmol/100 nl) or aminooxyacetate (AOA, 0.2, 1 and 2 pmol/100 nl, a cystathionine ß-synthase, CBS, inhibitor) into the RVLM/Bötzinger complex followed by a 60-min period of hypoxia (7% inspired O2) or normoxia exposure. Control rats received microinjection of vehicle. Microinjection of vehicle, AOA or Na2S did not change VE in normoxic conditions. Exposure to hypoxia evoked a typical increase in VE. Microinjection of Na2S (2 pmol) followed by hypoxia exposure attenuated the hyperventilation. Conversely, microinjection of AOA (2 pmol) into the RVLM/Bötzinger complex caused an increase in the hypoxia-induced hyperventilation. Thus, endogenous H2S in the RVLM/Bötzinger complex seems to play no role in the maintenance of basal pulmonary ventilation during normoxia whereas during hypoxia H2S has a downmodulatory function. Homogenates of RVLM/Bötzinger complex of animals previously exposed to hypoxia for 60 min exhibited a decreased rate of H2S production. Our data are consistent with the notion that the gaseous messenger H2S synthesis is downregulated in the RVLM/Bötzinger complex during hypoxia favoring hyperventilation.

Smoking, physical activity and respiratory irregularities in patients with panic disorder.

BACKGROUND: In the past decades different evidences suggested a relationship between panic disorder (PD) and respiration, among which the presence of different respiratory irregularities at rest in PD patients. It has been hypothesized that PD could be characterized by a dysfunction of those areas involved in the central control of respiration. The aim of the present study was to elucidate possible differences in breath-by-breath respiratory function at rest between a sample of PD patients with agoraphobia and healthy controls (HC), with particular attention to smoking and physical activity as possible relevant factors in the understanding of respiratory dynamics in PD. METHODS: Respiratory physiology was assessed in 32 PD patients and 24 HC. Respiratory rate (RR), tidal volume (VT), minute ventilation (VE), and end-tidal CO2 (pCO2) have been assessed. RESULTS: A significant diagnosis-by-smoking interaction was found for mean RR and VT. Mean pCO2 was significantly higher in active than in sedentary patients. Anxiety state did not account for the results. CONCLUSIONS: Our findings suggest an abnormal regulation of the respiratory system as a key mechanism in PD. In future studies it should be useful t o stratify data taking into account level and intensity of physical activity and smoking behaviour, as well as to consider the cardiac profile and the effect of those variables able to modulate the homeostatic brain functioning. .

Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry--a comparison with reference gas chromatography.

The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for measuring VA/Q distributions is based on measurements of the elimination and retention of infused inert gases. Conventional multiple inert gas elimination technique (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures, which requires tonometry of blood samples with a gas that can then be injected into the chromatograph. The method is laborious and requires meticulous care. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) facilitates the handling of blood and gas samples and provides nearly real-time analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3 with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left lower lobe ventilation. The different protocols ensured a large range of normal and abnormal VA/Q distributions. Eight inert gases (SF6, krypton, ethane, cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused; six of these gases were measured with MMIMS, and six were measured with GC. We found close agreement of retention and excretion of the gases and the constructed VA/Q distributions between GC and MMIMS, and predicted PaO2 from both methods compared well with measured PaO2. VA/Q by GC produced more widely dispersed modes than MMIMS, explained in part by differences in the algorithms used to calculate VA/Q distributions. In conclusion, MMIMS enables faster measurement of VA/Q, is less demanding than GC, and produces comparable results.

Eucapnic voluntary hyperventilation in diagnosing exercise-induced laryngeal obstructions.

Exercise-induced laryngeal obstructions (EILOs) cause exercise-related respiratory symptoms (ERRS) and are important differential diagnoses to exercise-induced asthma. The diagnostic method for EILOs includes provocation to induce the obstruction followed by a verification of the obstruction and the degree thereof. The objective of the present study was to examine if a eucapnic voluntary hyperventilation (EVH) test could induce laryngeal obstructions laryngoscopically identical in subtypes and development as seen during an exercise test. EVH and exercise testing with continuous laryngoscopy were performed during a screening of two national athletic teams (n = 67). The laryngoscopic recordings were examined for usability, abnormalities and maximal supraglottic and glottic obstruction using two currently available methods (Eilomea and CLE-score). The participants were asked questions on ERRS, and whether the symptoms experienced during each provocation matched those experienced during regular training. A total of 39 completed both tests. There were no significant differences in subtypes and development thereof, the experience of symptoms, and specificity and sensitivity between the methods. Significantly more recordings obtained during the exercise test were usable for evaluation primarily due to resilient mucus on the tip of the fiber-laryngoscope in the EVH test. Only recordings of six athletes from both provocation methods were usable for evaluation using the Eilomea method (high-quality demand). Amongst these, a linear correlation was found for the glottic obstruction. EVH tests can induce EILOs. However, the present test protocol needs adjustments to secure better visualisation of the larynx during provocation.

Low serum concentrations of vitamin B6 and iron are related to panic attack and hyperventilation attack.

Patients undergoing a panic attack (PA) or a hyperventilation attack (HVA) are sometimes admitted to emergency departments (EDs). Reduced serotonin level is known as one of the causes of PA and HVA. Serotonin is synthesized from tryptophan. For the synthesis of serotonin, vitamin B6 (Vit B6) and iron play important roles as cofactors. To clarify the pathophysiology of PA and HVA, we investigated the serum levels of vitamins B2, B6, and B12 and iron in patients with PA or HVA attending an ED. We measured each parameter in 21 PA or HVA patients and compared the values with those from 20 volunteers. We found that both Vit B6 and iron levels were significantly lower in the PA/HVA group than in the volunteer group. There was no significant difference in the serum levels of vitamins B2 or B12. These results suggest that low serum concentrations of Vit B6 and iron are involved in PA and HVA. Further studies are needed to clarify the mechanisms involved in such differences.

A local risk prediction model for prolonged ventilation after adult heart valve surgery in a Chinese single center.

BACKGROUND AND AIM OF THE STUDY: The aim of this study was to develop a logistic risk prediction model for prolonged ventilation after adult heart valve surgery. MATERIALS AND METHODS: This is a retrospective observational study of collected data on 3965 consecutive patients older than 18 years, who had undergone heart valve surgery between January 2000 and December 2010. Data were randomly split into a development dataset (n = 2400) and a validation dataset (n = 1565). A multivariate logistic regression analysis was undertaken using the development dataset to identify independent risk factors for prolonged ventilation (defined as ventilation greater than 72 h). Performance of the model was then assessed by observed and expected rates of prolonged ventilation on the development and validation dataset. Model calibration and discriminatory ability were analyzed by the Hosmer-Lemeshow goodness-of-fit statistic and the area under the receiver operating characteristic (ROC) curve, respectively. RESULTS: There were 303 patients that required prolonged ventilation (7.6%). Preoperative independent predictors of prolonged ventilation are shown with odds ratio and P value as follows: (1) age, 1.9, P < .0001; (2) hypercholesterolemia, 5.3, P = .001; (3) renal failure, 18.2, P = .004; (4) previous cardiac surgery, 2.4, P = .0002; (5) left bundle branch block, 4.2, P = .011; (6) ejection fraction, 1.4, P = .003; (7) left ventricle weight, 1.5, P = .007; (8) New York Heart Association class III-IV, 1.8, P = .021; (9) critical preoperative state, 4.5, P < .0001; (10) tricuspid insufficiency, 1.2, P = .031; (11) concurrent CABG, 2.2, P = .019; and (12) concurrent other cardiac surgery, 2.1, P = .001. The Hosmer-Lemeshow goodness-of-fit statistic was not statistically significant in both development and validation dataset (P = .202 vs P = .291). The ROC curve for the prediction of prolonged ventilation in development and validation dataset was .789 and .710, respectively. CONCLUSIONS: We developed and validated a local risk prediction model for prolonged ventilation after adult heart valve surgery. This model can be used to calculate patient-specific risk by the logistic equation with an equivalent predicted risk at our center in future clinical practice.

Central neurogenic hyperventilation in anti-NMDA receptor encephalitis.

Central neurogenic hyperventilation (CNH) is a rare condition that is generally associated with infiltrative tumors of the brainstem. Respiratory dysfunction, particularly central hypoventilation, is common in anti-N-methyl D-aspartate (NMDA) receptor encephalitis. CNH, to the best of our knowledge, has not been described previously in this disease. A 24-year-old woman was diagnosed with anti-NMDA receptor encephalitis secondary to ovarian teratoma. In addition to the typical symptoms of the disease, recurrent CNH episodes were observed during the course of the illness, which subsided with midazolam and propofol infusion. Supportive and disease-specific treatments, including oopherectomy, plasmapheresis and intravenous immunoglobulin, provided excellent recovery. These observations suggest that NMDA receptors may play a role in the pathophysiology of CNH.

Factors related with the higher percentage of hospitalizations due to asthma amongst women: the FRIAM study.

INTRODUCTION: The reason why there is a higher hospitalization rate due to asthma exacerbations amongst women is unclear. The objective of this study is to explore the possible causes that may explain this fact. METHODS: A multi-center, prospective study including asthma patients hospitalized in the pulmonary medicine departments during a two-year period. By means of a questionnaire, the following data were collected: demographic characteristics and treatment compliance, anxiety-depression, hyperventilation and asthma control, both prior to and during the hospitalization. RESULTS: 183 patients were included, 115 (62.84%) of whom were women. The women were older (52.4 ± 18.3/43.4 ± 18.7; P=.02), were more frequently prescribed inhaled corticosteroids (63.2%/47.1%; P=.03) and had a higher rate of hyperventilation syndrome (57.3/35.9; P=.02) and a longer mean hospital stay (7.3 ± 3.4/5.9 ± 3.6; P=.02). The percentage of smokers among the women was lower (21.2%/38.8%; p=0.01) and the FEV(1) was lower at admittance (58.2% ± 15.9/67.5% ± 17.4; P=.03). In the 40 to 60-year-old age range, an association was demonstrated between being female and the 'previous hospitalizations' variable (OR, 16.1; 95% CI, 1.6-156.7); sex and obesity were also independently associated (OR, 4.8; 95% CI, 1.06-22). CONCLUSIONS: In this cohort, the rate of hospitalization for asthma was higher in women than in men. Being a woman between the ages of 40 and 60 is associated with previous hospitalizations and is a risk factor for asthma-related hospitalization. This situation could partially be explained by the hormonal changes during menopause, where polyposis and obesity are independent risk factors.

Airway injury during high-level exercise.

Airway epithelial cells act as a physical barrier against environmental toxins and injury, and modulate inflammation and the immune response. As such, maintenance of their integrity is critical. Evidence is accumulating to suggest that exercise can cause injury to the airway epithelium. This seems the case particularly for competitive athletes performing high-level exercise, or when exercise takes place in extreme environmental conditions such as in cold dry air or in polluted air. Dehydration of the small airways and increased forces exerted on to the airway surface during severe hyperpnoea are thought to be key factors in determining the occurrence of injury of the airway epithelium. The injury-repair process of the airway epithelium may contribute to the development of the bronchial hyper-responsiveness that is documented in many elite athletes.

Traumatic brain injury: review of current management strategies.

Head injury is a common condition with a high morbidity and mortality. Serious intracranial haematomas require early recognition and evacuation to maximise chances of independent outcomes. Recent organisational changes have promoted the development of trauma units and major trauma centres where patients can go through triage and be managed in an appropriate environment, and the development of management pathways in intensive treatment units has resulted in improvements in the outcome of traumatic brain injuries. Evidence for the treatment of cerebral perfusion pressure, and management of hyperventilation, osmotherapy, tracheostomy, and leakage of cerebrospinal fluid (CSF) has accumulated during the last decade and is important in the management of patients in all clinical settings. Since head injury is commonly associated with maxillofacial injuries, this review will be relevant to all who deal with this aspect of trauma.