Voluntary Breathing Research Articles

Positive Expiratory Pressure Improves Oxygenation in Healthy Subjects Exposed to Hypoxia

IntroductionPositive end-expiratory pressure (PEEP) is commonly used in critical care medicine to improve gas exchange. Altitude sickness is associated with exaggerated reduction in arterial oxygenation. We assessed the effect of PEEP and pursed lips breathing (PLB) on arterial and tissue oxygenation under normobaric and hypobaric hypoxic conditions.MethodsSixteen healthy volunteers were exposed to acute normobaric hypoxia (Laboratory study, FiO2=0.12). The protocol consisted in 3-min phases with PEEPs of 0, 5 or 10 cmH2O, PLB or similar ventilation than with PEEP-10, interspaced with 3-min phases of free breathing. Arterial (pulse oximetry) and quadriceps (near-infrared spectroscopy) oxygenation, ventilation, cardiac function, esophageal and gastric pressures and subjects’ subjective perceptions were recorded continuously. In addition, the effect of PEEP on arterial oxygenation was tested at 4,350 m of altitude in 9 volunteers breathing for 20 min with PEEP-10 (Field study).ResultsDuring the laboratory study, PEEP-10 increased arterial and quadriceps oxygenation (arterial oxygen saturation +5.6±5.0% and quadriceps oxyhemoglobin +58±73 µmol.cm compared to free breathing; p<0.05). Conversely, PLB did not increase oxygenation. Oxygenation improvement with PEEP-10 was accompanied by an increase in expiratory esophageal and gastric pressures (esophageal pressure swing +5.4±3.2 cmH2O, p<0.05) but no change in minute ventilation, breathing pattern, end-tidal CO2 or cardiac function (all p>0.05) compared to PEEP-0. During the field study, PEEP-10 increased arterial oxygen saturation by +6.7±6.0% after the 3rd minute with PEEP-10 without further significant increase until the 20th minute with PEEP-10. Subjects did not report any significant discomfort with PEEP. ConclusionsThese data indicate that 10-cmH2O PEEP significantly improves arterial and muscle oxygenation under both normobaric and hypobaric hypoxic conditions in healthy subjects. PEEP-10 could be an attractive non-pharmacological tool to limit blood oxygen desaturation and possibly symptoms at altitude.

Patient machine interface for the control of mechanical ventilation devices.

The potential of Brain Computer Interfaces (BCIs) to translate brain activity into commands to control external devices during mechanical ventilation (MV) remains largely unexplored. This is surprising since the amount of patients that might benefit from such assistance is considerably larger than the number of patients requiring BCI for motor control. Given the transient nature of MV (i.e., used mainly over night or during acute clinical conditions), precluding the use of invasive methods, and inspired by current research on BCIs, we argue that scalp recorded EEG (electroencephalography) signals can provide a non-invasive direct communication pathway between the brain and the ventilator. In this paper we propose a Patient Ventilator Interface (PVI) to control a ventilator during variable conscious states (i.e., wake, sleep, etc.). After a brief introduction on the neural control of breathing and the clinical conditions requiring the use of MV we discuss the conventional techniques used during MV. The schema of the PVI is presented followed by a description of the neural signals that can be used for the on-line control. To illustrate the full approach, we present data from a healthy subject, where the inspiration and expiration periods during voluntary breathing were discriminated with a 92% accuracy (10-fold cross-validation) from the scalp EEG data. The paper ends with a discussion on the advantages and obstacles that can be forecasted in this novel application of the concept of BCI.

Time-frequency methods and voluntary ramped-frequency breathing: a powerful combination for exploration of human neurophysiological mechanisms

We experimentally altered the timing of respiratory motoneuron activity as a means to modulate and better understand otherwise hidden human central neural and hemodynamic oscillatory mechanisms. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations, and muscle sympathetic nerve activity in 13 healthy supine young men who gradually increased or decreased their breathing frequencies between 0.05 and 0.25 Hz over 9-min periods. We analyzed results with traditional time- and frequency-domain methods, and also with time-frequency methods (wavelet transform, wavelet phase coherence, and directional coupling). We determined statistical significance and identified frequency boundaries by comparing measurements with randomly generated surrogates. Our results support several major conclusions. First, respiration causally modulates both sympathetic (weakly) and vagal motoneuron (strongly) oscillations over a wide frequency range-one that extends well below the frequency of actual breaths. Second, breathing frequency broadly modulates vagal baroreflex gain, with peak gains registered in the low frequency range. Third, breathing frequency does not influence median levels of sympathetic or vagal activity over time. Fourth, phase relations between arterial pressure and sympathetic and vagal motoneurons are unaffected by breathing, and are therefore likely secondary to intrinsic responsiveness of these motoneurons to other synaptic inputs. Finally, breathing frequency does not affect phase coherence between diastolic pressure and muscle sympathetic oscillations, but it augments phase coherence between systolic pressure and R-R interval oscillations over a limited portion of the usual breathing frequency range. These results refine understanding of autonomic oscillatory processes and those physiological mechanisms known as the human respiratory gate.

Continuous Real Time Breath Gas Monitoring in the Clinical Environment by Proton-Transfer-Reaction-Time-of-Flight-Mass Spectrometry

Analysis of volatile organic compounds (VOCs) in breath holds great promise for noninvasive diagnostic applications. However, concentrations of VOCs in breath may change quickly, and actual and previous uptakes of exogenous substances, especially in the clinical environment, represent crucial issues. We therefore adapted proton-transfer-reaction-time-of-flight-mass spectrometry for real time breath analysis in the clinical environment. For reasons of medical safety, a 6 m long heated silcosteel transfer line connected to a sterile mouth piece was used for breath sampling from spontaneously breathing volunteers and mechanically ventilated patients. A time resolution of 200 ms was applied. Breath from mechanically ventilated patients was analyzed immediately after cardiac surgery. Breath from 32 members of staff was analyzed in the post anesthetic care unit (PACU). In parallel, room air was measured continuously over 7 days. Detection limits for breath-resolved real time measurements were in the high pptV/low ppbV range. Assignment of signals to alveolar or inspiratory phases was done automatically by a matlab-based algorithm. Quickly and abruptly occurring changes of patients' clinical status could be monitored in terms of breath-to-breath variations of VOC (e.g. isoprene) concentrations. In the PACU, room air concentrations mirrored occupancy. Exhaled concentrations of sevoflurane strongly depended on background concentrations in all participants. In combination with an optimized inlet system, the high time and mass resolution of PTR-ToF-MS provides optimal conditions to trace quick changes of breath VOC profiles and to assess effects from the clinical environment.

Breathing manoeuvre-dependent changes in myocardial oxygenation in healthy humans

CO₂ is an intrinsic vasodilator for cerebral and myocardial blood vessels. Myocardial vasodilation without a parallel increase of the oxygen demand leads to changes in myocardial oxygenation. Because apnoea and hyperventilation modify blood CO₂, we hypothesized that voluntary breathing manoeuvres induce changes in myocardial oxygenation that can be measured by oxygenation-sensitive cardiovascular magnetic resonance (CMR). Fourteen healthy volunteers were studied. Eight performed free long breath-hold as well as a 1- and 2-min hyperventilation, whereas six aquatic athletes were studied during a 60-s breath-hold and a free long breath-hold. Signal intensity (SI) changes in T₂*-weighted, steady-state free precession, gradient echo images at 1.5 T were monitored during breathing manoeuvres and compared with changes in capillary blood gases. Breath-holds lasted for 35, 58 and 117 s, and hyperventilation for 60 and 120 s. As expected, capillary pCO₂ decreased significantly during hyperventilation. Capillary pO₂ decreased significantly during the 117-s breath-hold. The breath-holds led to a SI decrease (deoxygenation) in the left ventricular blood pool, while the SI of the myocardium increased by 8.2% (P = 0.04), consistent with an increase in myocardial oxygenation. In contrast, hyperventilation for 120 s, however, resulted in a significant 7.5% decrease in myocardial SI/oxygenation (P = 0.02). Change in capillary pCO₂ was the only independently correlated variable predicting myocardial oxygenation changes during breathing manoeuvres (r = 0.58, P < 0.01). In healthy individuals, breathing manoeuvres lead to changes in myocardial oxygenation, which appear to be mediated by CO₂. These changes can be monitored in vivo by oxygenation-sensitive CMR and thus, may have value as a diagnostic tool.

Responses to voluntary hyperventilation in children with separation anxiety disorder: Implications for the link to panic disorder

BackgroundBiological theories on respiratory regulation have linked separation anxiety disorder (SAD) to panic disorder (PD). We tested if SAD children show similarly increased anxious and psychophysiological responding to voluntary hyperventilation and compromised recovery thereafter as has been observed in PD patients. MethodsParticipants were 49 children (5–14 years old) with SAD, 21 clinical controls with other anxiety disorders, and 39 healthy controls. We assessed cardiac sympathetic and parasympathetic, respiratory (including pCO2), electrodermal, electromyographic, and self-report variables during baseline, paced hyperventilation, and recovery. ResultsSAD children did not react with increased anxiety or panic symptoms and did not show signs of slowed recovery. However, during hyperventilation they exhibited elevated reactivity in respiratory variability, heart rate, and musculus corrugator supercilii activity indicating difficulty with respiratory regulation. ConclusionsReactions to hyperventilation are much less pronounced in children with SAD than in PD patients. SAD children showed voluntary breathing regulation deficits.

Modification of Electrical Pain Threshold by Voluntary Breathing-Controlled Electrical Stimulation (BreEStim) in Healthy Subjects

BackgroundPain has a distinct sensory and affective (i.e., unpleasantness) component. BreEStim, during which electrical stimulation is delivered during voluntary breathing, has been shown to selectively reduce the affective component of post-amputation phantom pain. The objective was to examine whether BreEStim increases pain threshold such that subjects could have improved tolerance of sensation of painful stimuli.MethodsEleven pain-free healthy subjects (7 males, 4 females) participated in the study. All subjects received BreEStim (100 stimuli) and conventional electrical stimulation (EStim, 100 stimuli) to two acupuncture points (Neiguan and Weiguan) of the dominant hand in a random order. The two different treatments were provided at least three days apart. Painful, but tolerable electrical stimuli were delivered randomly during EStim, but were triggered by effortful inhalation during BreEStim. Measurements of tactile sensation threshold, electrical sensation and electrical pain thresholds, thermal (cold sensation, warm sensation, cold pain and heat pain) thresholds were recorded from the thenar eminence of both hands. These measurements were taken pre-intervention and 10−min post-intervention.ResultsThere was no difference in the pre-intervention baseline measurement of all thresholds between BreEStim and EStim. The electrical pain threshold significantly increased after BreEStim (27.5±6.7% for the dominant hand and 28.5±10.8% for the non-dominant hand, respectively). The electrical pain threshold significantly decreased after EStim (9.1±2.8% for the dominant hand and 10.2±4.6% for the non–dominant hand, respectively) (F[1, 10] = 30.992, p = .00024). There was no statistically significant change in other thresholds after BreEStim and EStim. The intensity of electrical stimuli was progressively increased, but no difference was found between BreEStim and EStim.ConclusionVoluntary breathing controlled electrical stimulation selectively increases electrical pain threshold, while conventional electrical stimulation selectively decreases electrical pain threshold. This may translate into improved pain control.

AROMATIC AMINO ACIDS METABOLISM IN HUMANS EXPOSED TO EXPERIMENTAL SEVERE ACUTE SHORT-TERM NORMOBARIC HYPOXIA

In aviation, acute hypoxia is one of the most dangerous factors affecting humans, and developing new ways of increasing human hypoxic resistance in severe acute hypoxia remains important. In this work we have studied particular features of proteinogenous aromatic amino acids metabolism in volunteers breathing hypoxic gas mixture containing 9 % of O 2. We have shown that the healthy volunteers exposed to experimental hypoxia in postprandial state significantly decreased plasma levels of free tyrosine and phenylalanine in the early recovery period. We hypothesized that these amino acids being precursors for mediators and hormones (dopamine, epinephrine, norepinephrine) can play a significant role in increasing hypoxic resistance in humans.

Relationship between heart rate variability, blood pressure and arterial wall properties during air and oxygen breathing in healthy subjects

Previous studies reported that normobaric hyperoxia influences heart rate, arterial pressure, cardiac output and systemic vascular resistance, but the mechanisms underlying these changes are still not fully understood. Several factors are considered including degeneration of endothelium-derived nitric oxide by reactive oxygen species, the impact of oxygen-free radicals on tissues and alterations of autonomic nervous system function. Recently, new devices for the detailed non-invasive assessment of large and small arteries have been developed. Therefore, the aim of our study was to assess heart rate variability (HRV) as a potential indicator of autonomic balance and its relation to blood pressure and vascular properties during medical air (MAB) and 100% oxygen breathing (OXB) in healthy volunteers. In 12 healthy subjects we assessed heart rate and blood pressure variability, baroreflex sensitivity, respiratory frequency, common carotid artery diameter and its wall distensibility, as well as changes in the digital artery pulse waveform, stroke index and systemic vascular resistance during MAB and OXB. Mean and systolic blood pressure have increased significantly while digital pulse amplitude and carotid artery diameter were significantly lower during hyperoxia. Heart rate variability measures did not differ during MAB and OXB. However, the correlations between spectral HRV components and those hemodynamic parameters which have changed due to hyperoxia varied substantially during MAB (correlated significantly) and OXB (no significant correlations were noted). Our findings suggest that autonomic nervous system might not be the main mediator of the cardiovascular changes during 100% oxygen breathing in healthy subjects. It seems that the direct vascular responses are initial consequences of hyperoxia and other cardiovascular parameter alterations are secondary to them.

The Supplementary Motor Area Exerts a Tonic Excitatory Influence on Corticospinal Projections to Phrenic Motoneurons in Awake Humans

IntroductionIn humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe").MethodsThe SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA.ResultscTBS reduced the amplitude of DiMEPs from 327.5±159.8 µV at baseline to 243.3±118.7 µV, 217.8±102.9 µV and 240.6±123.9 µV at post 1, post 2 and post 3, respectively (F = 6.341, p = 0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7±96.5 µV at baseline to 270.7±135.4 µV at post 3 (F = 4.844, p = 0.009).ConclusionsThe corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe.

Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia

Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO₂) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO₂ is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO₂ on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO₂), and norepinephrine use. The time averaged StO₂ was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO₂ (SC 0.53, p < 0.001) and high risk level (SC 0.06, p = 0.03) were significant independent variables correlated with StO₂. SStO₂ was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO₂ was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO₂ in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO₂.

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

Aerosol Delivery to the Lung Is More Efficient Using an Extension with a Standard Jet Nebulizer than an Open-Vent Jet Nebulizer

Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2). In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2). In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p<0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p<0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p<0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p<0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.

Hypoxic effects on sympathetic vasomotor outflow and blood pressure during exercise with inspiratory resistance

The purpose of the present study was to clarify the influence of inspiratory resistive breathing during exercise under hypoxic conditions on muscle sympathetic nerve activity (MSNA) and blood pressure (BP). Six healthy males completed this study. The subjects performed a submaximal exercise test using a cycle ergometer in a semirecumbent position under normoxic [inspired oxygen fraction (FiO2) = 0.21] and hypoxic (FiO2 = 0.12-0.13) conditions. The subjects carried out two 10-min exercises at 40% peak oxygen uptake [spontaneous breathing for 5 min and voluntary breathing with inspiratory resistance for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were set at 0.5 s each)]. MSNA was recorded via microneurography of the right median nerve at the elbow. A progressive increase in MSNA burst frequency (BF) during leg-cycling exercise with inspiratory resistance in normoxia and hypoxia were accompanied by an augmentation of BP. The increased MSNA BF and mean arterial BP (MBP) during exercise with inspiratory resistive breathing in hypoxia (MSNA BF, 55.7 ± 1.4 bursts/min, MBP, 134.3 ± 6.6 mmHg) were higher than those in normoxia (MSNA BF, 39.2 ± 1.8 bursts/min, MBP, 123.6 ± 4.5 mmHg). These results suggest that an enhancement of inspiratory muscle activity under hypoxic condition leads to large increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise.

Myocardial velocity mapping for the right ventricle in pulmonary arterial hypertension using a novel image-based respiratory self-navigation from a golden-angle spiral acquisition

Background CMR is a recognized method of assessing global RV function in patients with pulmonary arterial hypertension (PAH). Unfortunately, assessment of regional myocardial motion with MRI remains challenging due to the thin RV wall. One solution may be tissue phase mapping (TPM) in which motion can be encoded at a higher spatial resolution. However, one problem is the need for respiratory navigation due to long scan times. We have therefore implemented a novel self-gated golden-angle spiral TPM technique that can acquire high-resolution data efficiently during free breathing in healthy volunteers and in patients with PAH. Methods

Size matters: choosing the right tracheal tube

Size matters: choosing the right tracheal tube

Phase-Dependent Respiratory-Motor Interactions in Reaction Time Tasks During Rhythmic Voluntary Breathing

The study investigated squeezing reaction time (RT) in response to a visual cue during rhythmic voluntary breathing at 0.6 Hz paced by a metronome, breath holding, or at rest in 13 healthy subjects. Rhythmic voluntary breathing slowed down RT, only in the expiratory phase with accompanied changes in the length of respiratory phases, while breath-holding reduced RT. The prolonged RT during voluntary expiratory phases and the absence of changes in RT during voluntary inspiratory phases are most likely related to disproportionally increased cognitive demands during the expiratory phase of voluntary breathing. The absence of changes in RT during voluntary inspiration is likely to be compensated by respiratory-motor facilitation mechanisms in this phase. Shortened RT during breath holding is possibly associated with increased attention.

Using Time-Frequency Analysis of the Photoplethysmographic Waveform to Detect the Withdrawal of 900 mL of Blood

We designed this study to determine if 900 mL of blood withdrawal during spontaneous breathing in healthy volunteers could be detected by examining the time-varying spectral amplitude of the photoplethysmographic (PPG) waveform in the heart rate frequency band and/or in the breathing rate frequency band before significant changes occurred in heart rate or arterial blood pressure. We also identified the best PPG probe site for early detection of blood volume loss by testing ear, finger, and forehead sites. Eight subjects had 900 mL of blood withdrawn followed by reinfusion of 900 mL of blood. Physiological monitoring included PPG waveforms from ear, finger, and forehead probe sites, standard electrocardiogram, and standard blood pressure cuff measurements. The time-varying amplitude sequences in the heart rate frequency band and breathing rate frequency band present in the PPG waveform were extracted from high-resolution time-frequency spectra. These amplitudes were used as a parameter for blood loss detection. Heart rate and arterial blood pressure did not significantly change during the protocol. Using time-frequency analysis of the PPG waveform from ear, finger, and forehead probe sites, the amplitude signal extracted at the frequency corresponding to the heart rate significantly decreased when 900 mL of blood was withdrawn, relative to baseline (all P < 0.05); for the ear, the corresponding signal decreased when only 300 mL of blood was withdrawn. The mean percent decrease in the amplitude of the heart rate component at 900 mL blood loss relative to baseline was 45.2% (38.2%), 42.0% (29.2%), and 42.3% (30.5%) for ear, finger, and forehead probe sites, respectively, with the lower 95% confidence limit shown in parentheses. After 900 mL blood reinfusion, the amplitude signal at the heart rate frequency showed a recovery towards baseline. There was a clear separation of amplitude values at the heart rate frequency between baseline and 900 mL blood withdrawal. Specificity and sensitivity were both found to be 87.5% with 95% confidence intervals (47.4%, 99.7%) for ear PPG signals for a chosen threshold value that was optimized to separate the 2 clusters of amplitude values (baseline and blood loss) at the heart rate frequency. Meanwhile, no significant changes in the spectral amplitude in the frequency band corresponding to respiration were found. A time-frequency spectral method detected blood loss in spontaneously breathing subjects before the onset of significant changes in heart rate or blood pressure. Spectral amplitudes at the heart rate frequency band were found to significantly decrease during blood loss in spontaneously breathing subjects, whereas those at the breathing rate frequency band did not significantly change. This technique may serve as a valuable tool in intraoperative and trauma settings to detect and monitor hemorrhage.

Breathing-controlled electrical stimulation could modify the affective component of neuropathic pain after amputation: a case report

In this case, a 31-year-old male suffered phantom neuropathic pain for more than 3 years after an above-the-knee amputation. His shooting phantom pain disappeared after the first session of breathing-controlled electrical stimulation, and reappeared or was triggered 28 days after an experimental error during which he received sustained electrical stimulation. In other words, painful shooting stimuli may not have been “cured” but forgotten and retriggered by a fearful event due to the experimental error. Therefore, this accidental finding provides a unique opportunity to understand sensory and affective components of neuropathic pain, and a novel intervention could modify the affective component of it.