Baseline Ventilation Research Articles

RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO₂ insensitive brown Norway rat.

Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague-Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague-Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex.

Rebuttal from Magdy Younes.

There is really little disagreement in the two accounts (Orr et al. 2014; Younes, 2014) if one considers that I addressed the increase in loop gain (LG) when the upper airway (UA) is unstable (hereafter called Actual LG) whereas Orr et al. addressed only that component of LG that is measured when UA is stabilized, the component I called Chemical LG. To put these two loop gains in the proper perspective I refer to several investigations from the laboratory of the opposing authors. Wellman et al. (2011) and Edwards et al. (2012) measured the Actual LG in obstructive sleep apnoea (OSA) patients by relating the increase in ventilation at airway opening to the reduction in ventilation during the event. The values reported ranged from 1.4 to 14.0 (average 4.4). This is an order of magnitude greater than the Chemical LG (∼0.4; Younes et al. 2001; Wellman et al. 2004, 2008; Jordan et al. 2005). As indicated earlier (Younes, 2014), this difference results from an increased delay in getting a ventilatory response because the airway refuses to open until a threshold chemical drive, the ‘effective recruitment threshold’, is reached (Younes et al. 2007, 2012). Clearly, this increase in LG is a consequence of OSA. What is called a high LG in the absence of UA instability, and what is emphasized as a cause of OSA by Orr et al. is a Chemical LG of 0.7 with a maximum of 0.9 (Wellman et al. 2008). Even this relatively small increase in Chemical LG is the result of untreated OSA since it disappears with treatment (Loewen et al. 2009; Salloum et al. 2010). Orr et al. argue that this modest increase nonetheless contributes to the severity of OSA. I have no problem with this, and have in fact indicated so in my article (Younes, 2014). However, I believe that Orr et al. have exaggerated this clinical importance. They cite two papers in support of effectiveness of oxygen. The paper by Chowdhuri et al. (2010) simply demonstrated a reduction, with oxygen, in hypocapnic ventilatory response to CO2 in normal subjects. The study by Wellman et al. (2008) found >50% reduction in the apnoea–hypopnoea index (AHI) when breathing oxygen in only three out of six patients selected from a base of 43 patients because they had a high LG (range 0.4–0.9). Some of this AHI reduction was due to prolongation of apnoeic events and to disappearance of central/mixed events, which contributed ∼15% of baseline events. Thus the number of true obstructive events that were eliminated by oxygen must have been small. The acetazolamide evidence is also quite unconvincing. The 2013 study by Edwards et al. did not address the severity of OSA. In the 2012 study by Edwards et al. acetazolamide caused a reduction in AHI in patients already treated by continuous positive airway pressure (CPAP) and in whom Chemical LG was probably normal (Loewen et al. 2009; Salloum et al. 2010). So, it is not possible to attribute the improvement in AHI to a reduction in Chemical LG. It is important to note that both acetazolamide (Edwards et al. 2012) and oxygen breathing (Chowdhuri et al. 2010) increase baseline ventilation, and hence respiratory drive. Their helpful effects in some patients need not reflect a reduction in Chemical LG but may be because chemical drive needs to increase less to reach the effective recruitment threshold for UA opening.

Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a sign of improved animal welfare or the adverse effects of an opioid drug?

The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4–7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation.

G113(P) The effects of sleeping position and maternal smoking on the ventilatory response to hypoxia

AimsBoth prone sleeping and maternal antenatal smoking are known risk factors for Sudden Infant Death Syndrome (SIDS). The aim of this study was to determine whether the two factors could...

Respiratory activity in the 6-hydroxydopamine model of Parkinson's disease in the rat.

Respiratory disturbances accompany Parkinson's disease. Weakness of the respiratory muscles or lowering of central respiratory drive might be responsible for respiratory disability. Striatal injection of 6-hydroxydopamine (6-OHDA) simulates motor symptoms of Parkinson's disease in the rat. Present study investigated whether unilateral infusion of 6-OHDA into the striatum may evoke respiratory disorders and therefore be a model for the study of the respiratory aspects of Parkinson's disease. Two weeks after the infusion the animals were anesthetized, vagotomized, paralyzed and artificially ventilated. Neural respiratory activity in the vehicle and 6-OHDA treated groups of animals was assessed from the peak amplitude of the phrenic and hypoglossal bursts, frequency of bursts and minute activity during baseline ventilation and acute intermittent hypoxia composed of five 1.5 minute long episodes of 11 percent oxygen introduced every 3 minutes. An impairment of dopaminergic pathways by 6-OHDA evoked separate effects on phrenic and hypoglossal activity. Under baseline conditions the respiratory parameters taken from the integrated phrenic nerve activity unchanged, while the preinspiratory part of the hypoglossal activity (pre-I HG) was reduced both in terms of its onset and amplitude. 6-OHDA did not affect the phrenic response to acute intermittent hypoxia but it increased the hypoglossal response (Fig. 2). Hypoxia activated the pre-I HG in both experimental groups. Although the pre-I HG increased strongly during hypoxic stimulation, the ratio of the pre-inspiratory hypoglossal amplitude to the inspiratory hypoglossal amplitude never achieved similar values as in the sham group. This ratio decreased significantly during secondary decline of the hypoxic respiratory response. A decline of the hypoxic response was more intense in the hypoglossal activity than in the phrenic activity and moved into hypoxic apnoea more frequently in the Parkinson's disease model. The results indicate a differential modulation of the phrenic and hypoglossal neural output with increased chemical drive when dopaminergic pathways were impaired by 6-OHDA suggesting that such a mechanism may contribute to respiratory insufficiency in Parkinson's disease. An involvement of a modified mechanism of dopamine efflux and of serotonin and orexin during hypoxia is suggested in the observed changes in the hypoglossal activity in the 6-OHDA model of PD.

Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin-deficient (ob/ob) mice.

Leptin, an adipocyte-derived hormone, is suggested to participate in the central control of breathing. We hypothesized that leptin may facilitate ventilatory responses to chemoreflex activation by acting on respiratory nuclei of the ventrolateral medulla. The baseline ventilation and the ventilatory responses to CO2 were evaluated before and after daily injections of leptin into the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) for 3 days in obese leptin-deficient (ob/ob) mice. Male ob/ob mice (40-45 g, n = 7 per group) received daily microinjections of vehicle or leptin (1 μg per 100 nL) for 3 days into the RTN/pFRG. Respiratory responses to CO2 were measured by whole-body plethysmography. Unilateral microinjection of leptin into the RTN/pFRG in ob/ob mice increased baseline ventilation (VE ) from 1447 ± 96 to 2405 ± 174 mL min(-1) kg(-1) by increasing tidal volume (VT ) from 6.4 ± 0.4 to 9.1 ± 0.8 mL kg(-1) (P < 0.05). Leptin also enhanced ventilatory responses to 7% CO2 (Δ = 2172 ± 218 mL min(-1) kg(-1) , vs. control: Δ = 1255 ± 105 mL min(-1) kg(-1) ), which was also due to increased VT (Δ = 4.71 ± 0.51 mL kg(-1) , vs. control: Δ = 2.27 ± 0.20 mL kg(-1) ), without changes in respiratory frequency. Leptin treatment into the RTN/pFRG or into the surrounding areas decreased food intake (83 and 70%, respectively), without significantly changing body weight. The present results suggest that leptin acting in the respiratory nuclei of the ventrolateral medulla improves baseline VE and VT and facilitates respiratory responses to hypercapnia in ob/ob mice.

Leptin and the control of pharyngeal patency during sleep in severe obesity

Obesity imposes mechanical loads on the upper airway, resulting in flow limitation and obstructive sleep apnea (OSA). In previous animal models, leptin has been considered to serve as a stimulant of ventilation and may prevent respiratory depression during sleep. We hypothesized that variations in leptin concentration among similarly obese individuals will predict differences in compensatory responses to upper airway obstruction during sleep. An observational study was conducted in 23 obese women [body mass index (BMI): 46 ± 3 kg/m(2), age: 41 ± 12 yr] and 3 obese men (BMI: 46 ± 3 kg/m(2), age: 43 ± 4 yr). Subjects who were candidates for bariatric surgery were recruited to determine upper airway collapsibility under hypotonic conditions [pharyngeal critical pressure (passive PCRIT)], active neuromuscular responses to upper airway obstruction during sleep, and overnight fasting serum leptin levels. Compensatory responses were defined as the differences in peak inspiratory airflow (ΔVImax), inspired minute ventilation (ΔVI), and pharyngeal critical pressure (ΔPCRIT) between the active and passive conditions. Leptin concentration was not associated with sleep disordered breathing severity, passive PCRIT, or baseline ventilation. In the women, increases in serum leptin concentrations were significantly associated with increases in ΔVImax (r(2) = 0.44, P < 0.001), ΔVI (r(2) = 0.40, P < 0.001), and ΔPCRIT (r(2) = 0.19, P < 0.04). These responses were independent of BMI, waist-to-hip ratio, neck circumference, or sagittal girth. Leptin may augment neural compensatory mechanisms in response to upper airway obstruction, minimizing upper airway collapse, and/or mitigating potential OSA severity. Variability in leptin concentration among similarly obese individuals may contribute to differences in OSA susceptibility.

Physiological comparison of breathing patterns with neurally adjusted ventilatory assist (NAVA) and pressure-support ventilation to improve NAVA settings

Neurally adjusted ventilator assist (NAVA) assists spontaneous breathing in proportion to diaphragmatic electrical activity (EAdi). Here, we evaluate the effects of various levels of NAVA and PSV on the breathing pattern and, thereby, on PaCO2 homeostasis in 10 healthy volunteers. For each ventilation mode, four levels of support (delivered pressure 0 i.e. baseline, 5, 8, and 10cmH2O) were tested in random order. EAdi, flow, and airway pressure were recorded. Optoelectronic plethysmography was used to study lung volume distribution. During both PSV and NAVA, EAdi decreased with the level of assistance (P<0.01). Tidal volume (VT) increased and PtCO2 decreased with increased levels of PSV (P=0.044 and P=0.0004; respectively) while no change was observed with NAVA. Subject–ventilator synchronization was better with NAVA than with PSV. NAVA and PSV similarly decreased the abdominal contribution to VT. No airflow profile similarities were observed between baseline and mechanical ventilation. Diaphragmatic activity can decrease during NAVA without any change in VT and PaCO2. This suggests that NAVA adjustment cannot be based solely on VT and PCO2 criteria.Registered by Frédéric Lofaso and Nicolas Terzi on ClinicalTrials.gov, #NCT01614873.

Alveolar recruitment manoeuvre is safe in children prone to pulmonary hypertensive crises following open heart surgery: a pilot study

To test the tolerance and safety of an alveolar recruitment manoeuvre performed in the immediate postoperative period of corrective open heart surgery in children with congenital heart disease associated with excessive pulmonary blood flow and pulmonary arterial hypertension due to left-to-right shunt. Ten infants aged 1-24 months with congenital heart disease associated with excessive pulmonary blood flow and pulmonary artery hypertension (mean pulmonary artery pressure ≥ 25 mmHg) were evaluated. The alveolar recruitment manoeuvre was performed in the operating theatre right after skin closure, and consisted of three successive stages of 30 s each, intercalated by a 1-min interval of baseline ventilation. Positive end-expiratory pressure was set to 10 cmH2O in the first stage and to 15 cmH2O in the two last ones, while the peak inspiratory pressure was kept at to 30 cmH2O in the first stage and at 35 cmH2O in the latter ones. Haemodynamic and respiratory variables were recorded. There was a slight but significant increase in mean pulmonary artery pressure from baseline to Stage 3 (P = 0.0009), as well as between Stages 1 and 2 (P = 0.0001), and 1 and 3 (P = 0.001), with no significant difference between Stages 2 and 3 (P = 0.06). Upon completion of the third stage, there were significant increases in arterial haemoglobin saturation as measured by pulse oximetry (P = 0.0009), arterial blood partial pressure of oxygen (P = 0.04), venous blood oxygen saturation of haemoglobin (P = 0.03) and arterial oxygen partial pressure over inspired oxygen fraction ratio (P = 0.04). A significant reduction in arterial blood partial pressure of carbon dioxide (P = 0.01) and in end tidal carbon dioxide also occurred (P = 0.009). The manoeuvre was well tolerated and besides a slight and transitory elevation in mean pulmonary artery, no other adverse haemodynamic or ventilatory effect was elicited. The alveolar recruitment manoeuvre seemed to be safe and well tolerated immediately after open heart surgery in infants liable to pulmonary hypertensive crises.

Acquiring basic life support skills in a self-learning station

To develop a self-learning station combining a video with computer exercises to learn cardiopulmonary resuscitation (CPR) to novices, and to assess the efficacy of these two components on CPR acquisition. One hundred and twenty-five pharmacy students were trained using learning-while-watching video instructions followed by exercises with voice feedback. The proportion of students with adequate CPR skills (≥ 70% compressions with depth ≥ 50 mm, ≥ 70% compressions with complete release <5 mm, a compression rate between 100 and 120/min, ≥ 70% ventilations with a volume between 400 and 1000 ml) was measured at baseline, after video training and after subsequent voice-feedback training. Complete datasets were obtained for 104 students. After video training, the 70% cut-off for compression depth was achieved in 29/104 students, for complete release in 75/104, for ventilation volume in 44/104. Mean compression rate 100-120/min was adequate in 77/104 students. Compared with baseline results, only rate (29/104 vs. 77/104) and ventilation volume (6/104 vs. 44/104) improved. After subsequent training with voice feedback the proportions were: compression depth 88/104, compression rate 77/104, ventilation volume 74/104 and complete release 90/104. Compared with the skill level after video training only compression rate did not further improve. A score combining the three compression skills resulted in the following success rates: 6/104 (baseline), 15/104 (after the video), 59/104 (after voice feedback). Although in a self-learning station video training can introduce CPR skills to novices, additional voice-feedback exercises were needed to achieve acceptable CPR quality.

The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia

The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is an autosomal recessive disorder in humans in which there is impaired oxygen-dependent degradation of HIF, resulting in long-term systemic elevation of HIF levels at normal oxygen tensions. CP patients demonstrate the characteristic features of ventilatory acclimatization to hypoxia, namely, an elevated baseline ventilation and enhanced acute hypoxic ventilatory response (AHVR). We investigated the ventilatory and carotid-body phenotype of a mouse model of CP, using whole-body plethysmography, immunohistochemistry, and electron microscopy. In keeping with studies in humans, CP mice had elevated ventilation in euoxia and a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by electron microscopy, which also revealed that the type I cells contained an increased number of mitochondria, enlarged dense-cored vesicles, and markedly expanded rough endoplasmic reticulum. The morphological and ultrastructural changes seen in the CP mouse carotid body are strikingly similar to those observed in animals exposed to chronic hypoxia. Our study demonstrates that the HIF pathway plays a major role, not only in regulating both euoxic ventilatory control and the sensitivity of the response to hypoxia, but also in determining the morphology of the carotid body.

Effects of fluid load on cardiovascular function during stepwise lung recruitment manoeuvre in healthy dogs

The aim of this study was to evaluate the effects of a stepwise lung recruitment manoeuvre (RM) on cardiac output (CO) in mechanically ventilated dogs, with or without a previous fluid load. Eight healthy adult Beagle dogs were enrolled in a prospective crossover study. Following sedation with dexmedetomidine and methadone, anaesthesia was induced with propofol and maintained with isoflurane. CO (thermodilution method) and direct arterial blood pressure were monitored. The dogs were mechanically ventilated in a volume-controlled mode (tidal volume, VT=10mL/kg; positive end-expiratory pressure [PEEP]=0cm H2O) until normocapnia was achieved (end tidal CO2 35–45mmHg). The RM was then performed in a pressure-controlled mode, with progressive increases of the PEEP and end-inspiratory pressure of 5cm H2O, until 15cm H2O and 30cm H2O were reached, respectively. After the RM, the ventilatory mode was returned to volume-control, and the PEEP was sequentially decreased to 10, 5 and 0cm H2O. Baseline ventilation was maintained for 30min. Next, 10mL/kg of lactated Ringer’s solution was administered within 10min, prior to a second RM. The CO was determined before each RM (baseline) and at each pressure step. A repeated measures ANOVA test was used to compare data.Compared to baseline, CO decreased during the RM in both groups. However, there was a significantly higher CO during the second RM at the highest pressure step (P<0.05) and during all decreasing pressure steps (P<0.05). In conclusion, a previous crystalloid fluid load could reduce the impact of a RM on CO in healthy dogs.

Heat stress does not augment ventilatory responses to presyncopal limited lower body negative pressure

Simulated haemorrhage, e.g. lower body negative pressure (LBNP), reduces central blood volume and mean arterial pressure, while ventilation increases. Passive whole-body heat stress likewise increases ventilation. The objective of this project was to test the hypothesis that ventilatory responses to reductions in central blood volume and arterial pressure during simulated haemorrhage are enhanced when individuals are heat stressed rather than normothermic. Eight healthy men (34 ± 9 years old, 176 ± 6 cm tall and 80.2 ± 4.2 kg body weight) underwent a simulated haemorrhagic challenge via LBNP until presyncope on two separate occasions, namely normothermic control and whole-body heat-stress trials. Baseline ventilation and core and mean skin temperatures were not different between trials (all P > 0.05). Prior to LBNP, heat stress increased core (from 36.8 ± 0.2 to 38.2 ± 0.2°C, P < 0.05) and mean skin temperatures (from 33.9 ± 0.5 to 38.1 ± 0.6°C, P < 0.05), as well as minute ventilation (from 8.01 ± 2.63 to 13.68 ± 6.68 l min(-1), P < 0.01). At presyncope, mean arterial pressure and middle cerebral artery blood velocity decreased in both trials (P < 0.05). At presyncope, ventilation increased to 23.22 ± 6.78 (P < 0.01) and 25.88 ± 10.16 l min(-1) (P < 0.01) in the normothermic and hyperthermic trials, respectively; however, neither the increase in ventilation from the pre-LBNP period nor the absolute ventilation was different between normothermic and hyperthermic trials (P > 0.05). These data suggest that the increase in ventilation during simulated haemorrhage induced via LBNP is not altered in heat-stressed humans.

GAL‐021 increases CO2‐chemosensitivity at doses that do not stimulate minute ventilation

GAL‐021 is a novel chemical entity that inhibits BK channels on carotid body glomus type 1 cells and dose‐dependently stimulates ventilation in mice, rats, non‐human primates, and healthy human subjects. As such, GAL‐021 is being developed as a new therapeutic agent to reverse opioid‐induced respiratory depression (OIRD) in people. Here, we evaluated the effects of GAL‐021 on CO2 chemosensitivity at non‐stimulatory plasma concentrations. Minute ventilation was measured using direct tracheal spirometry from urethane‐anesthetized adult rats at three different levels of PaCO2 – baseline, and two levels of hypercapnia: +10 and +20 mmHg above baseline. The slope of the hypercapnic ventilatory responses (HcVR) represented CO2 chemosensitivity. HcVR and CO2 chemosensitivity were measured in each animal before and again during a constant intravenous infusion of GAL‐021, where the dose was titrated in each animal to remain below the threshold that stimulates baseline ventilation. The magnitude of each HcVR and CO2 chemosensitivity was significantly increased during GAL‐021 infusion compared to vehicle control (p&lt;0.001). CO2 chemosensitivity did not change in a time control cohort that received vehicle infusion. Thus, GAL‐021 enhances CO2 chemosensitivity at plasma exposures that do not stimulate baseline breathing. These results suggest that GAL‐021 may have utility as preventative treatment for OIRD and also in the treatment of breathing disorders characterized by intermittent central apneas, such as sleep disordered breathing.

Evaluation of the minute ventilation recovery time as a predictor of weaning in mechanically ventilated COPD patients in respiratory failure

BackgroundThere is still difficulty in discontinuing mechanical ventilation (MV) in chronic obstructive pulmonary disease (COPD) patients with respiratory failure and more than 50% of the time is spent for weaning. A large spectrum of weaning indices is used. In this study we evaluated minute ventilation recovery time (MVRT) that may be a new practical measure of the ability to predict weaning outcome. MethodsThe study was conducted on 50 mechanically ventilated Acute exacerbation of COPD patients admitted to the Zagazig University Hospitals intensive care units (ICUs) with a mean age of 61.8±7.6years, They were divided into 2 groups; group I: successful weaning, included 42 patients and group II: failed weaning, included 8 patients. Minute ventilation (VE) was recorded 30min just after the institution of mechanical ventilation, then every 2h for 24h. Minute ventilation just before the spontaneous breathing trial (SBT) was recorded, and is compared to the previous recordings of minute ventilation, if this value (pre successful weaning VE) was about 110% of one of the recorded VE values, it is now considered as the baseline VE of the patients and the time passed from institution of M.V till such reading is considered as the MVRT of the patient. ResultsAmong 42 successfully weaned mechanically ventilated COPD patients, when compared between different weaning parameters, MVRT was significantly better as a predictor of weaning success (P=0.002). MVRT had high sensitivity and specificity of 76% and 85%, respectively at a cutoff value of 11.7h. MVRT had a strong correlation with weaning outcome in comparison to other weaning parameters used in the study. ConclusionThe minute ventilation recovery time is a good, reliable predictor of weaning success and it is the most independent parameter among other weaning predictors that can predict a successful spontaneous breathing trial (SBT).

Early application of high frequency oscillatory ventilation in ‘H1N1 influenza’ related ARDS is associated with better outcome: a retrospective study

Dear Editor, High frequency oscillatory ventilation (HFOV) is an accepted therapy for refractory hypoxemia in acute respiratory distress syndrome (ARDS). There is a paucity of data for use of HFOV for 2009 H1N1 influenza ARDS and whether early application of HFOV decreases mortality in this subgroup of patients with severe ARDS. We performed a retrospective analysis of 19 patients who received HFOV as a rescue therapy for 2009 H1N1 influenza with severe ARDS to study the outcome predictors. Deenanath Mangeshkar Hospital ethics committee has approved use of HFOV as a rescue therapy in severe ARDS and consent was obtained from next of kin. Inclusion criteria were the presence of severe ARDS (PaO2/FiO2 100) due to H1N1 influenza virus infection, the application of a maximal support of conventional mechanical ventilation (PEEP equal or greater than 12 cm H2O), and the use of HFOV as a rescue therapy. Patients who received HFOV treatment for less than 24 h were excluded from the analysis. Out of the 19 patients studied, 10 survived (52 %). Patients were divided into survivors and non-survivors Demographic variables, baseline gas exchange and ventilation variables were comparable. Average age and APACHE II score were 30.21 ± 9.60 years 13.25 ± 1.90, respectively. Average tidal volume and plateau pressure on conventional ventilation prior to initiation of HFOV were 6.12 ± 1.26 ml/kg of predicted body weight and 27.21 ± 3.85 cm H2O, respectively. In the whole cohort there was a significant improvement in PaO2/FiO2 at 24 h, after initiation of HFOV (77.89 ± 32.50 vs. 121.78 ± 37.94, p = 0.005). Earlier application of HFOV was the only significant independent predictor of survival (p = 0.045) on multivariate logistic regression analysis. Survival odds ratio was 7.05 (95 % CI, 1.04–47.78) for every day of reduced conventional ventilation. Cox regression analysis of survival rates adjusted for APACHE II score, oxygenation index and time from symptom onset to hospital contact indicated a decrease in survival with increasing duration of conventional ventilation (Fig. 1, Table 1). Our findings are in general agreement with the literature on ARDS in adults. Terragni et al. [1] has shown that even with a lung protective strategy, ventilator induced lung injury is possible. Matthias David et al., had suggested that, an increased conventional ventilation period of more then 3 days prior to HFOV was associated with higher mortality [2]. A recent meta-analysis had reaffirmed this suggestion [3]. However, Casper Bollen et al, [4] had suggested that prolonged conventional ventilation prior to HFOV is not associated with higher mortality. Patients in this case series, randomized to the HFOV group had received conventional ventilation at higher tidal volumes (9.30 ± 2.20 ml/kg of predicted body weight), prior to initiation of HFOV. Limiting the duration of volume controlled ventilation before HFOV may confer a benefit by pre-empting ventilator induced lung injury in these patients. A limitation of our case series is a small sample size. However, it may provide useful insight into management of severe ARDS related to

Implementation of 24/7 intensivist presence in the SICU

Staffing of attending intensivists 24 hours per day, 7 days per week (24/7) in the surgical intensive care unit (SICU) has unknown benefits. We hypothesized that 24/7 attending intensivist staffing in the SICU would improve outcomes and processes of care. We retrospectively reviewed 26 months of admissions to our 20-bed SICU, comparing 13 months before and 13 months after addition of an in-house night intensivist to the existing day intensivist with a nighttime on-demand model. Primary outcomes were mortality, complications, SICU length of stay, and ventilator days. Secondary outcomes were use of intensivist-directed ancillary testing and therapies, as well as physician billing (relative value units per full-time equivalent [RVU/FTE]). A total of 2,829 patients were included: 1,408 before and 1,421 after 24/7 staffing. Baseline characteristics, mortality, complications, ventilation days, ICU and hospital length of stay, and readmission rate were similar between groups (all p > 0.05). Use of blood products and imaging tests (computed tomographic scans) were significantly reduced. Total RVU increased, as did the RVU/FTE ratio. Implementation of 24/7 staffing did not improve SICU morbidity or mortality but was associated with decreased blood product use and fewer axial imaging studies. The RVU/FTE ratio was improved. Overall health care value may be decreased under this model. Care management study, level IV.

Continuous Noninvasive Monitoring of Lung Recruitment during High-Frequency Oscillatory Ventilation by Electrical Impedance Measurement: An Animal Study

Background: Ventilatory pressures should target the range between the upper and lower inflection point of the pressure volume curve in order to avoid atelecto- and volutrauma. During high-frequency oscillatory ventilation (HFOV), this range is difficult to determine. Quadrant impedance measurement (QIM) has recently been shown to allow accurate and precise measurement of lung volume changes during conventional mechanical ventilation. Objectives: To investigate if QIM can be used to determine a static pressure-residual impedance curve during a recruitment-derecruitment manoeuvre on HFOV and to monitor the time course of alveolar recruitment after changing mean airway pressure (MAP). Methods: An incremental and decremental MAP trial (6 cm H₂O to 27 cm H₂O) was conducted in five surfactant-depleted newborn piglets during HFOV. Ventilatory, gas exchange and haemodynamic parameters were recorded. Continuous measurement of thoracic impedance change was performed. Results: Mean residual impedance (RI) increased with each stepwise increase of MAP resulting in a total mean increase of +26.5% (±4.0) at the highest MAP (27 cm H₂O) compared to baseline ventilation at 6 cm H₂O. Upon decreasing MAP levels, RI fell more slowly compared to its ascent; 83.4% (±19.1) and 84.8% (±16.4) of impedance changes occurred in the first 5 min after an increase or decrease in airway pressure, respectively. Conclusions: QIM could be used for continuous monitoring of thoracic impedance and determination of the pressure-RI curve during HFOV. The method could prove to be a promising bedside method for the monitoring of lung recruitment during HFOV in the future.

Measurement of tidal volume using Respiratory Ultrasonic Plethysmography in anaesthetized, mechanically ventilated horses

ObjectiveTo compare tidal volume estimations obtained from Respiratory Ultrasonic Plethysmography (RUP) with simultaneous spirometric measurements in anaesthetized, mechanically ventilated horses. Study designProspective randomized experimental study. AnimalsFive experimental horses. MethodsFive horses were anaesthetized twice (1 week apart) in random order in lateral and in dorsal recumbency. Nine ventilation modes (treatments) were scheduled in random order (each lasting 4 minutes) applying combinations of different tidal volumes (8, 10, 12 mL kg−1) and positive end-expiratory pressures (PEEP) (0, 10, 20 cm H2O). Baseline ventilation mode (tidal volume = 15 mL kg−1, PEEP = 0 cm H2O) was applied for 4 minutes between all treatments. Spirometry and RUP data were downloaded to personal computers. Linear regression analyses (RUP versus spirometric tidal volume) were performed using different subsets of data. Additonally RUP was calibrated against spirometry using a regression equation for all RUP signal values (thoracic, abdominal and combined) with all data collectively and also by an individually determined best regression equation (highest R2) for each experiment (horse versus recumbency) separately. Agreement between methods was assessed with Bland-Altman analyses. ResultsThe highest correlation of RUP and spirometric tidal volume (R2 = 0.81) was found with the combined RUP signal in horses in lateral recumbency and ventilated without PEEP. The bias ± 2 SD was 0 ± 2.66 L when RUP was calibrated for collective data, but decreased to 0 ± 0.87 L when RUP was calibrated with individual data. Conclusions and clinical relevanceA possible use of RUP for tidal volume measurement during IPPV needs individual calibration to obtain limits of agreement within ± 20%.

Effect of progesterone on respiratory response to moderate hypoxia and apnea frequency in developing rats

We used whole-body plethysmography and pulse oximetry to assess the effects of acute administration of progesterone (4mg/kg, i.p.) on normoxic ventilation, hypoxic ventilatory response (HVR: FiO2=12% over 20min), metabolism, and apnea frequency in rats on postnatal (P) days P1, P4, P7, and P12. Arterial oxygen saturation was continuously measured, and apneas were discriminated based on the degree of associated desaturation, at least 5 units less than the value before the desaturation. In normoxia, progesterone did not alter ventilation, metabolism or the coefficient of variation of minute ventilation at any age studied when compared with the control group (saline). However, it decreased apnea frequency and apnea associated with desaturation only in P1 rats. In hypoxia: progesterone increased the peak HVR in P4 and P7 rats, increased the steady-state HVR (mean at 15–20min of exposure) in P1, P4 and P7 without affecting the rats’ metabolic rate, decreased the coefficient of variation of minute ventilation in P4 and P7 rats, and finally, decreased apnea frequency only in the P1 rats with no effect on apnea associated with desaturation at any age. We conclude that acute administration of progesterone has no effect on baseline ventilation, but it increases HVR in rats younger than 7days, and decreased the frequency of apnea only in P1 rats.