Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial.

OBJECTIVES: Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation. DESIGN: Randomized clinical trial. SETTING: Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands. PATIENTS: Patients (n = 40) with respiratory failure ventilated in a partially-supported mode. INTERVENTIONS: In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care. MEASUREMENTS AND MAIN RESULTS: Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively. CONCLUSIONS: Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.

A novel noninvasive approach for evaluating work of breathing indices in a developmental rat model using respiratory inductance plethysmography.

Pulmonary function testing (PFT) is an important component for evaluating the outcome of experimental rodent models of respiratory diseases. Respiratory inductance plethysmography (RIP) provides a noninvasive method of PFT requiring minimal cooperation. RIP measures work of breathing (WOB) indices including phase angle (Ф), percent rib cage (RC %), breaths per minute (BPM), and labored breathing index (LBI) on an iPad. The aim of this study was to evaluate the utility of a recently developed research instrument, pneuRIP, for evaluation of WOB indices in a developmental rat model. Sprague Dawley rats (2 months old) were commercially acquired and anaesthetised with isoflurane. The pneuRIP system uses two elastic bands: one band (RC) placed around the rib cage under the upper armpit and another band (AB) around the abdomen. The typical thoracoabdominal motion (TAM) plot showed the abdomen and rib cage motion in synchrony. The plots of phase angle and LBI as a function of data point number showed that values were within the range. The distribution for phase angle and LBI was within a narrow range. pneuRIP testing provided instantaneous PFT results. This study demonstrated the utility of RIP as a rapid, noninvasive approach for evaluating treatment interventions in the rodent model.

Interventions for escalation of therapy for acute exacerbations of asthma in children: an overview of Cochrane Reviews.

BACKGROUND: Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management. OBJECTIVES: Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta2-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'. MAIN RESULTS: We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta2-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta2-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.

Effects of alkaline agents on respiratory characteristics in rabbit models of respiratory failure.

This study aimed to investigate the effects of alkaline agents on reducing strong inspiratory effort. Rabbits with hypercapnia or lung injury, induced via repeated lung lavage following injurious ventilation, were treated with Saline, NaHCO3, or Trometamol. In the hypercapnia, minute ventilation and tidal volume were unchanged during NaHCO3 administration; however, one hour after the end of NaHCO3 these parameters decreased (82.1+/-7.8 %, 90.8+/-6.0 % of the baseline, respectively, p < 0.05). Trometamol reduced minute ventilation, tidal volume, and respiratory rate after infusion (59.8+/-19.0 %, 87.0+/-9.2 %, 68.2+/-18.4 % of the baseline, respectively, p < 0.05). Alkaline agents did not cause a large change in the cerebrospinal fluid acid-base balance. In the lung injury model, NaHCO3 and Trometamol had little effect on ventilation. However, Trometamol reduced transpulmonary pressure. Trometamol exerted more inhibitory effects on ventilation than NaHCO3 in the hypercapnia model, and Trometamol reduced the transpulmonary pressure in the lung injury model.

Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis.

BACKGROUND: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in patients with acute severe tracheal stenosis, yet data supporting the clinical use of H2-O2 are insufficient. OBJECTIVES: To evaluate the efficacy and safety of breathing H2-O2 in acute severe tracheal stenosis. METHODS: Thirty-five consecutive patients with severe acute tracheal stenosis were recruited in this prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4 consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1) for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary endpoint was inspiratory effort as assessed by diaphragm electromyography (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in the ambient environment was obtained with 12 monitors. Adverse reactions during the inhalation were recorded. RESULTS: The mean reduction in the EMGdi under H2-O2 was 10.53 ± 6.83%. The EMGdi significantly decreased during 2 H2-O2 inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3) (52.95 ± 15.00 vs. 42.46 ± 13.90 vs. 53.20 ± 14.74 vs. 42.50 ± 14.12% for Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77 ± 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and resistance parameters of IOS but not vital signs. No adverse reactions occurred. H2 was undetectable in the environment throughout the procedure. CONCLUSIONS: Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe tracheal stenosis and can be used for this purpose safely.

High flow nasal heliox improves work of breathing and attenuates lung injury in a newborn porcine lung injury model.

BACKGROUND: High flow nasal cannula (HFNC) has been shown to improve ventilation and oxygenation and reduce work of breathing in newborns with respiratory distress. Heliox, decreases resistance to airflow, reduces the work of breathing, facilitates the distribution of inspired gas, and has been shown to attenuate lung inflammation during the treatment of acute lung injury. HYPOTHESIS: Heliox delivered by HFNC will decrease resistive load, decrease work of breathing, improve ventilation and attenuate lung inflammation during spontaneous breathing following acute lung injury in the newborn pig. METHODS: Spontaneously breathing neonatal pigs received Nitrox or Heliox by HFNC and studied over 4 hrs following oleic acid injury. Gas exchange, pulmonary mechanics and systemic inflammation were measured serially. Lung inflammation biomarkers were assessed at termination. RESULTS: Heliox breathing animals demonstrated lower work of breathing reflected by lower tracheal pressure, phase angle and phase relationship. Ventilation efficiency index was greater compared to Nitrox. Heliox group showed less lung inflammation reflected by lower tissue interleukin-6 and 8. CONCLUSION: High flow nasal Heliox decreased respiratory load, reduced resistive work of breathing indices and attenuated lung inflammatory profile while ventilation was supported at less pressure effort in the presence of acute lung injury.

Impact of the anesthetic conserving device on respiratory parameters and work of breathing in critically ill patients under light sedation with sevoflurane.

BACKGROUND: Sevoflurane sedation in the intensive care unit is possible with a special heat and moisture exchanger called the Anesthetic Conserving Device (ACD) (AnaConDa; Sedana Medical AB, Uppsala, Sweden). The ACD, however, may corrupt ventilatory mechanics when used during the weaning process of intensive care unit patients. The authors compared the ventilatory effects of light-sedation with sevoflurane administered with the ACD and those of classic management, consisting of a heated humidifier and intravenous sedation, in intensive care unit patients receiving pressure-support ventilation. METHODS: Fifteen intensive care unit patients without chronic pulmonary disease were included. A target Richmond Agitation Sedation Scale level of -1/-2 was obtained with intravenous remifentanil (baseline 1-condition). Two successive interventions were tested: replacement of the heated humidifier by the ACD without sedation change (ACD-condition) and sevoflurane with the ACD with an identical target level (ACD-sevoflurane-condition). Patients finally returned to baseline (baseline 2-condition). Work of breathing, ventilatory patterns, blood gases, and tolerance were recorded. A steady state of 30 min was achieved for each experimental condition. RESULTS: ACD alone worsened ventilatory parameters, with significant increases in work of breathing (from 1.7 ± 1.1 to 2.3 ± 1.2 J/l), minute ventilation, P0,1, intrinsic positive end-expiratory pressure (from 1.3 ± 2.6 to 4.7 ± 4.2 cm H2O), inspiratory pressure swings, and decreased patient comfort. Sevoflurane normalized work of breathing (from 2.3 ± 1.2 to 1.8 ± 1 J/l), intrinsic positive end-expiratory pressure (from 4.7 ± 4.2 to 1.8 ± 2 cm H2O), inspiratory pressure swings, other ventilatory parameters, and patient tolerance. CONCLUSIONS: ACD increases work of breathing and worsens ventilatory parameters. Sevoflurane use via the ACD (for a light-sedation target) normalizes respiratory parameters. In this patient's population, light-sedation with sevoflurane and the ACD may be possible during the weaning process.

[Utility of heliox during treatment of upper airway obstruction secondary to bilateral vocal cord paralysis after thyroidectomy]. / Utilidad del heliox en la obstrucción de vía aérea superior secundaria a disfunción bilateral de cuerdas vocales postiroidectomía.

Helium is a noble gas whose low density decreases airway resistance. This property is utilized when a mixture of helium and oxygen (heliox) is employed in certain clinical situations, particularly in the context of airway obstruction. We report the case of a woman with severe upper airway obstruction due to bilateral vocal cord paralysis after thyroidectomy. Heliox was used temporarily to reduce respiratory effort and avoid the need for tracheal intubation while the obstruction was being treated with antiinflammatory drugs.

Methazolamide does not impair respiratory work performance in anesthetized rabbits.

In human medicine, the carbonic anhydrase (CA) inhibitor acetazolamide is used to treat irregular breathing disorders. Previously, we demonstrated in the rabbit that this substance stabilized closed-loop gain properties of the respiratory control system, but concomitantly weakened respiratory muscles. Among others, the highly diffusible CA-inhibitor methazolamide differs from acetazolamide in that it fails to activate Ca(2+)-dependent potassium channels in skeletal muscles. Therefore, we aimed to find out, whether or not methazolamide may exert attenuating adverse effects on respiratory muscle performance as acetazolamide. In anesthetized spontaneously breathing rabbits (n = 7), we measured simultaneously the CO(2) responses of tidal phrenic nerve activity, tidal transpulmonary pressure changes, and tidal volume before and after intravenous application of methazolamide at two mean (+/- SE) cumulative doses of 3.5 +/- 0.1 and 20.8 +/- 0.4 mg/kg. Similar to acetazolamide, low- and high-dose methazolamide enhanced baseline ventilation by 52 +/- 10% and 166 +/- 30%, respectively (P < 0.01) and lowered the base excess in a dose-dependent manner by up to 8.3 +/- 0.9 mmol/l (P < 0.001). The transmission of a CO(2)-induced rise in phrenic nerve activity into volume and/or pressure and, hence, respiratory work performance was 0.27 +/- 0.05 ml x kg(-1) x kPa x unit(-1) under control conditions, but remained unchanged upon low- or high-dose methazolamide, at 0.30 +/- 0.06 and 0.28 +/- 0.07 ml x kg(-1) x kPa x unit(-1), respectively. We conclude that methazolamide does not cause respiratory muscle weakening at elevated levels of ventilatory drive. This substance (so far not used for medication of respiratory diseases) may thus exert stabilizing influences on breathing control without adverse effects on respiratory muscle function.

[Effects of sedative agents on metabolic demand]. / Effets des agents sédatifs sur la demande métabolique.

Literature about the effects of sedative drugs on the metabolic demand of critically ill patients is relatively old and of relatively poor quality. Most are experimental or observational studies. Level of evidence is therefore relatively low corresponding to "expert opinion". The effects of analgesics and hypnotics on tissue metabolic demand associated remain difficult to be adequately quantified. They are essentially related to a decreased neuro-humoral response to stress. This response involves principally the sympathetic system, which could be effectively blocked by most of the anesthetic agents. Other factors could participate to the observed reduction in tissue metabolic demand, as a decrease in spontaneous muscular activity, a reduction in work of breathing and/or a decrease in body temperature. The relative contribution of these different factors will depend on the clinical situation of the patient. Proper effects of anesthetic agents on cellular metabolism are limited as they can only decrease the functional component of this metabolism especially at the level of the heart and to some extent, at the level of the brain. Although the control of the sympathetic activity may be beneficial in critically ill patient, complete sympathetic blockade could be detrimental. Indeed, when oxygen transport to the tissues is acutely reduced, the sympathetic system plays an important role in the redistribution of blood flow according of local metabolic demand. The complete blunting of the neuro-humoral response to stress and therefore of the sympathetic system alters this physiological mechanism and results in a decrease in tissue oxygen extraction capabilities. An imbalance between tissue oxygen demand and delivery could appear with the development of cellular hypoxia. The institution of sedation in a critically ill patient requires careful evaluation of the sedation level using an appropriate scale. In patients in whom a reduction in metabolic demand is specifically requested, but also in patients with limited oxygen transport, the effects of sedative agents on the oxygen consumption-oxygen delivery relationship must also be monitored. The choice of the different agents to be administered will depend on the predefined objectives. As far as intravenous agents are concerned, there is no evidence than one association is more efficient in reducing patient's metabolic demand.

Effect of inhaled furosemide on air hunger induced in healthy humans.

Recent evidence suggests that inhaled furosemide relieves dyspnoea in patients and in normal subjects made dyspnoeic by external resistive loads combined with added dead-space. Furosemide sensitizes lung inflation receptors in rats, and lung inflation reduces air hunger in humans. We therefore hypothesised that inhaled furosemide acts on the air hunger component of dyspnoea. Ten subjects inhaled aerosolized furosemide (40 mg) or placebo in randomised, double blind, crossover experiments. Air hunger was induced by hypercapnia (50+/-2 mmHg) during constrained ventilation (8+/-0.9 L/min) before and after treatment, and rated by subjects using a 100 mm visual analogue scale. Subjects described a sensation of air hunger with little or no work/effort of breathing. Hypercapnia generated less air hunger in the first trial at 23+/-3 min after start of furosemide treatment (58+/-11% to 39+/-14% full scale); the effect varied substantially among subjects. The mean treatment effect, accounting for placebo, was 13% of full scale (P=0.052). We conclude that 40 mg of inhaled furosemide partially relieves air hunger within 1h and is accompanied by substantial diuresis.

Helium-hyperoxia, exercise, and respiratory mechanics in chronic obstructive pulmonary disease.

RATIONALE: Hyperoxia and normoxic helium independently reduce dynamic hyperinflation and improve the exercise tolerance of patients with chronic obstructive pulmonary disease (COPD). Combining these gases could have an additive effect on dynamic hyperinflation and a greater impact on respiratory mechanics and exercise tolerance. OBJECTIVE: To investigate whether helium-hyperoxia improves the exercise tolerance and respiratory mechanics of patients with COPD. METHODS: Ten males with COPD (FEV(1) = 47 +/- 17%pred [mean +/- SD]) performed randomized constant-load cycling at 60% of maximal work rate breathing air, hyperoxia (40% O(2), 60% N(2)), normoxic helium (21% O(2), 79% He), or helium-hyperoxia (40% O(2), 60% He). MEASUREMENTS: Exercise time, inspiratory capacity (IC), work of breathing, and exertional symptoms were measured with each gas. RESULTS: Compared with air (9.4 +/- 5.2 min), exercise time was increased with hyperoxia (17.8 +/- 5.8 min) and normoxic helium (16.7 +/- 9.1 min) but the improvement with helium-hyperoxia (26.3 +/- 10.6 min) was greater than both these gases (p = 0.019 and p = 0.007, respectively). At an isotime during exercise, all three gases reduced dyspnea and both helium mixtures increased IC and tidal volume. Only helium-hyperoxia significantly reduced the resistive work of breathing (15.8 +/- 4.2 vs. 10.1 +/- 4.1 L . cm H(2)O(-1)) and the work to overcome intrinsic positive end-expiratory pressure (7.7 +/- 1.9 vs. 3.6 +/- 2.1 L . cm H(2)O(-1)). At symptom limitation, tidal volume remained augmented with both helium mixtures, but IC and the work of breathing were unchanged compared with air. CONCLUSION: Combining helium and hyperoxia delays dynamic hyperinflation and improves respiratory mechanics, which translates into added improvements in exercise tolerance for patients with COPD.

Use of heliox in children.

For over 70 years, helium-oxygen mixture (heliox) has been promoted as adjunctive therapy to overcome airflow-obstructive disorders and lesions. In the past 2 decades heliox has gained widespread support in many pediatric emergency departments and intensive care units, in treatment of infants and children with both upper and lower airway obstruction. Because heliox is less dense than air or oxygen, it provides more laminar flow in obstructed airways, and it is purported to reduce work of breathing, respiratory distress, and postextubation stridor. Clinical evidence of the effectiveness of heliox in pediatric patients with airflow obstruction is relatively sparse and appears in the literature primarily as case presentations, case series, and small, uncontrolled studies. This article reviews the rationale and methods for heliox treatment of children with asthma, airway obstruction, bronchiolitis, and croup.

Heliox and noninvasive positive-pressure ventilation: a role for heliox in exacerbations of chronic obstructive pulmonary disease?

Evidence-based respiratory therapy for exacerbations of chronic obstructive pulmonary disease (COPD) includes oxygen, inhaled bronchodilators, and noninvasive positive-pressure ventilation. Examining the physics of gas flow, a case can be made either for or against the use of helium-oxygen mixture (heliox) in the care of patients with COPD. The evidence for the use of heliox in patients with COPD exacerbation is not strong at present. Most of the peer-reviewed literature consists of case reports, case series, and physiologic studies in small samples of carefully selected patients. Some patients with COPD exacerbation have a favorable physiologic response to heliox therapy, but predicting who will be a responder is difficult. Moreover, the use of heliox is hampered by the lack of widespread availability of an approved heliox delivery system. Appropriately designed randomized controlled trials with patient-important outcomes, such as avoidance of intubation, decreased intensive-care-unit and hospital days, and decreased cost of therapy, are sorely needed to establish the role of heliox in patients with COPD exacerbation, including those receiving noninvasive positive-pressure ventilation. Lacking such evidence, the use of heliox in patients with COPD exacerbation cannot be considered standard therapy.

Opportunities and risks of using heliox in your clinical practice.

Helium-oxygen mixture (heliox) has been advocated for clinical use since 1934, and there has been a growing array of clinical applications. Until recently, administering heliox has required jury-rigging by modifications and/or extension of available devices not designed for use with heliox. This paper reviews devices required to administer heliox and considers how devices designed to deliver air and/or oxygen have been adapted for use with heliox. Use of devices outside of their design limits adds risk and liability, whereas using Food-and-Drug-Administration cleared devices for heliox administration reduces the risk and liability.

Helium-oxygen decreases inspiratory effort and work of breathing during pressure support in intubated patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the impact of helium-oxygen (He/O2) on inspiratory effort and work of breathing (WOB) in intubated COPD patients ventilated with pressure support. DESIGN AND SETTING: Prospective crossover interventional study in the medical ICU of a university hospital. PATIENTS AND PARTICIPANTS: Ten patients. INTERVENTIONS: Sequential inhalation (30 min each) of three gas mixtures: (a) air/O2, (b) He/O2 (c) air/O2, at constant FIO2 and level of pressure support. MEASUREMENTS AND RESULTS: Inspiratory effort and WOB were determined by esophageal and gastric pressure. Throughout the study pressure support and FIO2 were 14+/-3 cmH2O and 0.33+/-0.07 respectively. Compared to Air/O2, He/O2 reduced the number of ineffective breaths (4+/-5 vs. 9+/-5 breaths/min), intrinsic PEEP (3.1+/-2 vs. 4.8+/-2 cmH2O), the magnitude of negative esophageal pressure swings (6.7+/-2 vs. 9.1+/-4.9 cmH2O), pressure-time product (42+/-37 vs. 67+/-65 cmH2O s(-1) min(-1)), and total WOB (11+/-3 vs. 18+/-10 J/min). Elastic (6+/-1 vs. 10+/-6 J/min) and resistive (5+/-1 vs. 9+/-4 J/min) components of the WOB were decreased by He/O2. CONCLUSIONS: In intubated COPD patients ventilated with pressure support He/O2 reduces intrinsic PEEP, the number of ineffective breaths, and the magnitude of inspiratory effort and WOB. He/O2 could prove useful in patients with high levels of PEEPi and WOB ventilated in pressure support, for example, during weaning.

Language of dyspnea in panic disorder.

Dyspnea is a key symptom in panic attacks. This study investigated different types of dyspnea induced by the 35% CO2 challenge test given to patients with panic disorder (PD). The types of dyspnea provide room for possible conjectures on neurophysiological pathways involved in the experience of breathing discomfort in PD and in the panic-respiration connection. Factor analysis applied to the Dyspnea Questionnaire identified three main factors: breathing effort, sense of suffocation, and rapid breath. Factor scores for breathing effort and sense of suffocation significantly discriminated between patients who did and those who did not report CO2-induced panic attacks. Factor scores for breathing effort significantly discriminated between patients whose reaction resembled their unexpected panic attacks and those whose reaction did not. A dissociation between an increased central respiratory command and a decreased mechanical efficiency of the respiratory response in patients with PD may underlie the breathing effort factor during the CO2 challenge. The sense of suffocation factor was found to be linked to chemosensitivity. Although involved in CO2 reactivity, it may not be a central factor in unexpected panic attacks.

Helium-oxygen reduces work of breathing in mechanically ventilated patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate whether helium-oxygen mixture reduces inspiratory work of breathing (WOB) in sedated, paralyzed, and mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN AND SETTING: Open, prospective, randomized, crossover study in the medical intensive care unit in a university hospital. PATIENTS AND PARTICIPANTS: 23 patients admitted for acute exacerbation of COPD and mechanically ventilated. MEASUREMENTS: Total WOB (WOBt), elastic WOB (WOBel), resistive WOB (WOBres), and WOB due to PEEPi (WOBPeepi) were measured. Static intrinsic positive end expiratory pressure (PEEPi), static compliance (Crs), inspiratory resistance (Rins), inspiratory (tinsp) and expiratory time constant (texp) were also measured. These variables were compared between air-oxygen and helium-oxygen mixtures. RESULTS: WOBt significantly decreased with helium-oxygen (2.34+/-1.04 to 1.85+/-1.01 J/l, p<0.001). This reduction was significant for WOBel (1.02+/-0.61 J/l to 0.87+/-0.47, p<0.01), WOBPeepi (0.77+/-0.38 J/l to 0.54+/-0.38, p<0.001), and WOBres (0.55+/-0.19 J/l to 0.44+/-0.24, p<0.05). PEEPi, Rins, tinsp and texp significantly decreased. Crs was unchanged. CONCLUSIONS: Helium-oxygen mixture decreases WOB in mechanically ventilated COPD patients. Helium-oxygen mixture could be useful to reduce the burden of ventilation.