Six methods to determine expiratory time constants in mechanically ventilated patients: a prospective observational physiology study.

BACKGROUND: Expiratory time constant (τ) objectively assesses the speed of exhalation and can guide adjustments of the respiratory rate and the I:E ratio with the goal of achieving complete exhalation. Multiple methods of obtaining τ are available, but they have not been compared. The purpose of this study was to compare six different methods to obtain τ and to test if the exponentially decaying flow corresponds to the measured time constants. METHODS: In this prospective study, pressure, flow, and volume waveforms of 30 postoperative patients undergoing volume (VCV) and pressure-controlled ventilation (PCV) were obtained using a data acquisition device and analyzed. τ was measured as the first 63% of the exhaled tidal volume (VT) and compared to the calculated τ as the product of expiratory resistance (RE) and respiratory system compliance (CRS), or τ derived from passive flow/volume waveforms using previously published equations as proposed by Aerts, Brunner, Guttmann, and Lourens. We tested if the duration of exponentially decaying flow during exhalation corresponded to the duration of the predicted second and third τ, based on multiples of the first measured τ. RESULTS: Mean (95% CI) measured τ was 0.59 (0.57-0.62) s and 0.60 (0.58-0.63) s for PCV and VCV (p = 0.45), respectively. Aerts method showed the shortest values of all methods for both modes: 0.57 (0.54-0.59) s for PCV and 0.58 (0.55-0.61) s for VCV. Calculated (CRS * RE) and Brunner's τ were identical with mean τ of 0.64 (0.61-0.67) s for PCV and 0.66 (0.63-069) s for VCV. Mean Guttmann's τ was 0.64 (0.61-0.68) in PCV and 0.65 (0.62-0.69) in VCV. Comparison of each τ method between PCV and VCV was not significant. Predicted time to exhale 95% of the VT (i.e., 3*τ) was 1.77 (1.70-1.84) s for PCV and 1.80 (1.73-1.88) s for VCV, which was significantly longer than measured values: 1.27 (1.22-1.32) for PCV and 1.30 (1.25-1.35) s for VCV (p < 0.0001). The first, the second and the third measured τ were progressively shorter: 0.6, 0.4 and 0.3 s, in both ventilation modes (p < 0.0001). CONCLUSION: All six methods to determine τ show similar values and are feasible in postoperative mechanically ventilated patients in both PCV and VCV modes.

Glycaemic Variability and Risk Factors of Pregnant Women with and without Gestational Diabetes Mellitus Measured by Continuous Glucose Monitoring.

Background: The aim of the study was to compare the continuous glucose monitoring (CGM)-determined glycaemic variability (GV) of pregnant women with gestational diabetes mellitus (GDM) and without GDM (CG; control group). The secondary aim was to evaluate the association between risk factors of diabetes in pregnancy and parameters of glyceamic control. Methods: Demographic, biometric and biochemical parameters were obtained for pregnant women (20-38 years old) who after an oral glucose tolerance test were examined by 7-day continuous glucose monitoring using a iPro®2 Professional CGM. Results: The differences in GV between women with GDM and CG compared by total area under glucose curve (total AUC, (mmol·day/L) was statistically significant (p = 0.006). Other parameters of glycaemic control such as mean glucose, standard deviation, coefficient of variation, J-index, % time-above target range 7.8 mmol/L (%TAR), % time-in range 3.5-7.8 mmol/L (%TIR), time-below target range 3.5 mmol/L (%TBR), glycated haemoglobin were not significantly different in the study groups. Risk factors (a family history of diabetes, pre-pregnancy BMI, higher weight gain and age) correlated with parameters of glycaemic control. Conclusions: We found a significant difference in GV of women with and without GDM by total AUC determined from CGM. TIR metrics were close to significance. Our work points at an increased GV in relation to the risk factors of GDM. Pregnant women with risk factors have higher probability of severe GV with its consequences on maternal and fetal health state.

Introducing a core curriculum for respiratory sleep practitioners.

The background and purpose of the HERMES (Harmonising Education in Respiratory Medicine for European Specialists) initiative has been discussed at length in previous articles [1-3]. This article aims to provide more detailed and specific insight into the process and methodology of the Sleep HERMES Task Force in developing a core curriculum in respiratory sleep medicine.

Effects of partially ionised medical oxygen, especially with O2•-, in vibration white finger patients.

A major symptom of hand-arm vibration syndrome is a secondary Raynaud's phenomenon-vibration white finger (VWF)-which results from a vasospasm of the digital arteries caused by work with vibration devices leading to occupational disease. Pharmacotherapy of VWF is often ineffective or has adverse effects. The aim of this work was to verify the influence of inhalation of partially ionized oxygen (O2•-) on peripheral blood vessels in the hands of patients with VWF. Ninety one (91)patients with VWF underwent four-finger adsorption plethysmography, and the pulse wave amplitude was recorded expressed in numeric parameters-called the native record. Next, a cold water test was conducted following with second plethysmography. The patients were divided in to the three groups. First and second inhaled 20-min of ionized oxygen O2•- or oxygen O2 respectively. Thirth group was control without treatment. All three groups a follow-up third plethysmography-the post-therapy record. Changes in the pulse wave amplitudes were evaluated. Inpatients group inhaling O2•- a modest increase of pulse wave amplitude was observed compared to the native record; patients inhaling medical oxygen O2 and the control showed a undesirable decline of pulse wave amplitude in VWF fingers. Strong vasodilatation were more frequent in the group inhaling O2•- compare to O2 (p < 0.05). Peripheral vasodilatation achieved by inhalation of O2•- could be used for VWF treatment without undesirable side effect in hospital as well as at home environment.

Resuscitation and auto resuscitation by airway reflexes in animals.

Various diseases often result in decompensation requiring resuscitation. In infants moderate hypoxia evokes a compensatory augmented breath - sigh and more severe hypoxia results in a solitary gasp. Progressive asphyxia provokes gasping respiration saving the healthy infant - autoresuscitation by gasping. A neonate with sudden infant death syndrome, however, usually will not survive. Our systematic research in animals indicated that airway reflexes have similar resuscitation potential as gasping respiration. Nasopharyngeal stimulation in cats and most mammals evokes the aspiration reflex, characterized by spasmodic inspiration followed by passive expiration. On the contrary, expiration reflex from the larynx, or cough reflex from the pharynx and lower airways manifest by a forced expiration, which in cough is preceded by deep inspiration. These reflexes of distinct character activate the brainstem rhythm generators for inspiration and expiration strongly, but differently. They secondarily modulate the control mechanisms of various vital functions of the organism. During severe asphyxia the progressive respiratory insufficiency may induce a life-threatening cardio-respiratory failure. The sniff- and gasp-like aspiration reflex and similar spasmodic inspirations, accompanied by strong sympatho-adrenergic activation, can interrupt a severe asphyxia and reverse the developing dangerous cardiovascular and vasomotor dysfunctions, threatening with imminent loss of consciousness and death. During progressive asphyxia the reversal of gradually developing bradycardia and excessive hypotension by airway reflexes starts with reflex tachycardia and vasoconstriction, resulting in prompt hypertensive reaction, followed by renewal of cortical activity and gradual normalization of breathing. A combination of the aspiration reflex supporting venous return and the expiration or cough reflex increasing the cerebral perfusion by strong expirations, provides a powerful resuscitation and autoresuscitation potential, proved in animal experiments. They represent a simple but unique model tested in animal experiments.

Reversal of functional disorders by aspiration, expiration, and cough reflexes and their voluntary counterparts.

Agonal gasping provoked by asphyxia can save ~15% of mammals even from untreated ventricular fibrillation (VF), but it fails to revive infants with sudden infant death syndrome (SIDS). Our systematic study of airway reflexes in cats and other animals indicated that in addition to cough, there are two distinct airway reflexes that may contribute to auto-resuscitation. Gasp- and sniff-like spasmodic inspirations (SIs) can be elicited by nasopharyngeal stimulation, strongly activating the brainstem generator for inspiration, which is also involved in the control of gasping. This "aspiration reflex" (AspR) is characterized by SI without subsequent active expiration and can be elicited during agonal gasping, caused by brainstem trans-sections in cats. Stimulation of the larynx can activate the generator for expiration to evoke the expiration reflex (ExpR), manifesting with prompt expiration without preceding inspiration. Stimulation of the oropharynx and lower airways provokes the cough reflex (CR) which results from activating of both generators. The powerful potential of the AspR resembling auto-resuscitation by gasping can influence the control mechanisms of vital functions, mediating reversal of various functional disorders. The AspR in cats interrupted hypoxic apnea, laryngo- and bronchospasm, apneusis and even transient asphyxic coma, and can normalize various hypo- and hyper-functional disorders. Introduction of a nasogastric catheter evoked similar SIs in premature infants and interrupted hiccough attacks in adults. Coughing on demand can prevent anaphylactic shock and resuscitate the pertinent subject. Sniff representing nasal inspiratory pressure and maximal inspiratory and expiratory pressures (MIP and MEP) are voluntary counterparts of airway reflexes, and are useful for diagnosis and therapy of various cardio-respiratory and neuromuscular disorders.

Hypoxic damage to pancreatic beta cells--the hidden link between sleep apnea and diabetes.

Despite a large body of epidemiologic and clinical evidence suggesting that sleep disordered breathing is an independent risk factor for development of type 2 diabetes (T2DM), the underlying pathogenesis of altered glucose metabolism in sleep apnea remains to be unraveled. While previous studies have proposed some causal pathways linking sleep apnea with T2DM through increased insulin resistance and deterioration in insulin sensitivity, there has been a particular lack of research into sleep apnea-related alterations in pancreatic beta-cell function. Drawing upon our previous observation that sleep apnea is independently associated with an increased basal pancreatic beta-cell function in adults with normal glucose metabolism, the idea presented here suggests that sleep apnea imposes an excessive demand for insulin secretion, which may lead to progressive pancreatic beta-cell failure in high-risk individuals. Specifically, we hypothesize that in addition to diabetogenic effects of acute hypoxic activation of the sympathetic nervous system, the chronic intermittent hypoxemia represses the expression of key genes regulating biosynthesis of pancreatic proinsulin convertases with a resultant progressive decrease in their catalytic activity. The long-term hypoxic damage to pancreatic beta-cells may thus contribute to progression of glucose dysregulation in persons with untreated sleep apnea over time. Strategies to prevent and decrease the high prevalence and associated morbidity of T2DM are critically needed. The ideas and hypotheses presented here address the unexplored pathophysiological mechanisms underlying the potential causal link between sleep apnea and T2DM. Future hypotheses-testing will seek to delineate the role of sleep apnea in the development of T2DM, probe the underlying molecular mechanisms for pancreatic beta-cell dysfunction in sleep apnea, and obtain information on clinical, epidemiologic, and other factors responsible for protecting individuals from alterations in insulin-glucose homeostasis. These results could further be utilized in testing genetic susceptibilities and various therapy modalities to prevent pancreatic beta-cell dysfunction and maintain normal glucose status in persons with sleep apnea in the long term.

Do differences in sleep architecture exist between persons with type 2 diabetes and nondiabetic controls?

BACKGROUND: It has been shown previously that the suppression of slow-wave sleep (SWS) markedly reduced insulin sensitivity and led to an impairment of glucose tolerance. We hypothesized that a decreased amount of SWS is a feature peculiar to subjects with type 2 diabetes. METHOD: A retrospective case-control study analyzed polysomnographic recordings and covariate data of 22 type 2 diabetic and 22 nondiabetic subjects [n = 44; 8 women, 36 men, aged 57.5 +/- 5.5 years, body mass index (BMI) 33.8 +/- 5.9 kg/m(2), apnea-hypopnea index (AHI) 29.6 +/- 22.2 episodes/hr] matched individually for sex, race, age, BMI, and severity of sleep-related breathing disorders (SRBD). We assessed differences in sleep architecture between the study group and the control group. Primary end points included the percentage of total sleep time spent in each sleep stage. RESULTS: Despite similar age and severity of SRBD, subjects with type 2 diabetes demonstrated a significantly decreased amount of SWS (3.9 +/- 5.95% vs 8.4 +/- 4.57%; p = 0.012), increased percentage time in rapid eye movement sleep (24.1 +/- 12.14% vs 13.8 +/- 6.96%; p = 0.005), and higher arousal index (44.3 +/- 19.53/hr vs 35.7 +/- 12.67/hr; p = 0.037) compared to nondiabetic controls. After adjustment for sex, BMI, AHI, and smoking, age and presence of type 2 diabetes were independent predictors of the decreased SWS percentage (p = 0.001). Variables in this model accounted for 34% of the variance in the SWS percentage in our cohort. CONCLUSIONS: Results demonstrated distinct differences in sleep architecture in our cohort with decreased amounts of SWS in type 2 diabetes. These findings suggest that polysomnographic recognition of altered sleep architecture may be partially implicated in the early detection of persons with type 2 diabetes.

Reactive oxygen species, especially O2+* in cancer mechanisms.

UNLABELLED: In the nature including the human organism there are 5 reactive oxygen species (ROS): O2, O2-*, O2+*, 1O2, O3 with different electromagnetic characteristics and biological effects. The effects of enrichment of medical oxygen O2 with traces of ROS on various cells were tested in experiments. METHODS: Human embryonic lung fibroblasts WI38 damaged by Radon Rn222 into WI38/ Rn cells and WI38 cells transformed by virus SV40 into VA13 cells were exposed to different ROS gas mixtures, prepared in high - voltage plasma chamber of "Oxygen Ion 3000". Trans-membrane resting potential (TMRP) was measured and cells morphology was visually observed using microscopy during 10 days. RESULTS: Exposition of WI38, WI38/Rn and VA13 to medical O2, alone show no effect in TMRP and in cell morphology. But pico-concentration of O2+* in medical O2 increased the TMRP in WI38/Rn cells from -25mV to -35mV (variance 0.5-2mV) (p < 0.001) with improvement of cells morphology and the TMRP of VA13 cells from -15mV to -32mV (2-3mV) (p < 0.001) with a maximum effect on the 5th day. Later the TMRP strongly decreased and the cell membrane ruptured due to water influx. O2, enriched with O2-* alone or together with O2+* had no significant effect in WI38/Rn and VA13 groups (p > 0.05). CONCLUSION: Radon protective effect on WI38/Rn or destructive effect on VA13 of pico-concentrations of O2+* in medical O2 conforms to the theory of hormesis resp. to hypothesis of cancer induction mechanisms, supporting it's further experimental or clinical use.

Beneficial effects of severe sleep apnea therapy on nocturnal glucose control in persons with type 2 diabetes mellitus.

Given the consequences of sleep apnea and coexisting diabetes, satisfactory treatment of both diseases is required. Our results of continuous glucose monitoring in severe sleep apnea diabetic patients before and during continuous positive airway pressure/CPAP therapy showed significant reduction of nocturnal glucose variability and improved overnight glucose control on CPAP.