Moderate hypercapnia exerts beneficial effects on splanchnic energy metabolism during endotoxemia.

PURPOSE: Low tidal volume ventilation and permissive hypercapnia are required in patients with sepsis complicated by ARDS. The effects of hypercapnia on tissue oxidative metabolism in this setting are unknown. We therefore determined the effects of moderate hypercapnia on markers of systemic and splanchnic oxidative metabolism in an animal model of endotoxemia. METHODS: Anesthetized rats maintained at a PaCO(2) of 30, 40 or 60 mmHg were challenged with endotoxin. A control group (PaCO(2) 40 mmHg) received isotonic saline. Hemodynamic variables, arterial lactate, pyruvate, and ketone bodies were measured at baseline and after 4 h. Tissue adenosine triphosphate (ATP) and lactate were measured in the small intestine and the liver after 4 h. RESULTS: Endotoxin resulted in low cardiac output, increased lactate/pyruvate ratio and decreased ketone body ratio. These changes were not influenced by hypercapnia, but were more severe with hypocapnia. In the liver, ATP decreased and lactate increased independently from PaCO(2) after endotoxin. In contrast, the drop of ATP and the rise in lactate triggered by endotoxin in the intestine were prevented by hypercapnia. CONCLUSIONS: During endotoxemia in rats, moderate hypercapnia prevents the deterioration of tissue energetics in the intestine.

Pulmonar recruitment in acute respiratory distress syndrome. What is the best strategy?

Supporting patients with acute respiratory distress syndrome (ARDS), using a protective mechanical ventilation strategy characterized by low tidal volume and limitation of positive end-expiratory pressure (PEEP) is a standard practice in the intensive care unit. However, these strategies can promote lung de-recruitment, leading to the cyclic closing and reopening of collapsed alveoli and small airways. Recruitment maneuvers (RM) can be used to augment other methods, like positive end-expiratory pressure and positioning, to improve aerated lung volume. Clinical practice varies widely, and the optimal method and patient selection for recruitment maneuvers have not been determined, considerable uncertainty remaining regarding the appropriateness of RM. This review aims to discuss recent findings about the available types of RM, and compare the effectiveness, indications and adverse effects among them, as well as their impact on morbidity and mortality in ARDS patients. Recent developments include experimental and clinical evidence that a stepwise extended recruitment maneuver may cause an improvement in aerated lung volume and decrease the biological impact seen with the traditionally used sustained inflation, with less adverse effects. Prone positioning can reduce mortality in severe ARDS patients and may be an useful adjunct to recruitment maneuvers and advanced ventilatory strategies, such noisy ventilation and BIVENT, which have been useful in providing lung recruitment.

Effect of ventilation on systemic blood flow evaluated by echodopplercardiography

Systemic blood flow (Q) was measured by echodopplercardiography in 5 normal young adult males during apnea, eupnea and tachypnea. Measurements were made in a recumbent posture at 3-min intervals. Tachypnea was attained by doubling the respiratory frequency at eupnea at a constant tidal volume. An open glottis was maintained during apnea at the resting respiratory level. The Q values were positively correlated with the respiratory frequency, decreasing from eupnea to apnea and increasing from eupnea to tachypnea (P<0.05). These data demonstrate that echodopplercardiography, a better qualified tool for this purpose, confirms the positive and progressive effects of ventilation on systemic blood flow, as suggested by previous studies based on diverse technical approaches

Lung tissue mechanics in the early stages of induced paracoccidioidomycosis in rats

Pulmonary dysfunction represents the most important cause of death in patients with paracoccidioidomycosis (PBM). In order to investigate the functional changes of the lungs in the early stages of PBM, a model of benign disease was developed by intratracheal challenge of 12-week old isogenic Wistar rats with 1 x 106 yeast forms of Paracoccidioides brasiliensis. Animals were studied 30 and 60 days after infection, when fully developed granulomas were demonstrable in the lungs. Measurements of airway resistance, lung elastance and tissue hysteresis were made during sinusoidal deformations (100 breaths/min, tidal volume = 2 ml) with direct measurement of alveolar pressure using the alveolar capsule technique. Infection caused a significant increase in hysteresis (infected: 1.69, N = 13; control: 1.13, N = 12, P = 0.024, ANOVA), with no alterations in airway resistance or lung elastance. Histopathological analysis revealed the presence of fully developed granulomas located in the axial compartment of the lung interstitial space. These results suggest that alterations of tissue mechanics represent an early event in experimental PBM

Cardiovascular and respiratory changes during slow-wave sleep in rats are associated with electrocorticogram desynchronization

In awake rats a single recurrent larger tidal volume (deep breaths) occurs at regular intervals, followed by oscillations in arterial pressure and heart rate. In the present study we recorded the changes in blood pressure, heart rate and ventilation during the wakefulness-sleep cycle identified by electrocorticographic records in order to determine whether the deep breaths and cardiovascular oscillations were associated with changes in the electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats the deep breaths and oscillations in arterial pressure and heart rate were preceded by SWS desynchronization. The interval between deep breaths during SWS was 71 ± 4 s, the period between initial desynchronization and the generation of deep breaths was 3.98 ± 0.45 s and the duration of SWS desynchronization was 11 ± 0.65 s. Hypotension (-16 ± 1 mmHg) and tachycardia (+15 ± 5 bpm) were observed during deep breaths in the SWS state. These data indicate that the oscillations in arterial pressure and heart rate during SWS are associated with deep breaths, which in turn are preceded by desynchronization of the electrocorticogram in this state of sleep

Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat

Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.

Participation of nitric oxide in the nucleus isthmi in CO2-drive to breathing in toads

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain. It has been reported that NI plays an important role in integration of CO2 chemoreceptor information and glutamate is probably involved in this function. However, very little is known about the mechanisms involved. Recently, it has been shown that nitric oxide synthase (NOS) is expressed in the brain of the frog. Thus the gas nitric oxide (NO) may be involved in different functions in the brain of amphibians and may act as a neurotransmitter or neuromodulator. We tested the hypothesis that NO plays a role in CO2-drive to breathing, specifically in the NI comparing pulmonary ventilation, breathing frequency and tidal volume, after microinjecting 100 nmol/0.5 µl of L-NAME (a nonselective NO synthase inhibitor) into the NI of toads (Bufo paracnemis) exposed to normocapnia and hypercapnia. Control animals received microinjections of vehicle of the same volume. Under normocapnia no significant changes were observed between control and L-NAME-treated toads. Hypercapnia caused a significant (P<0.01) increase in ventilation only after intracerebral microinjection of L-NAME. Exposure to hypercapnia caused a significant increase in breathing frequency both in control and L-NAME-treated toads (P<0.01 for the control group and P<0.001 for the L-NAME group). The tidal volume of the L-NAME group tended to be higher than in the control group under hypercapnia, but the increase was not statistically significant. The data indicate that NO in the NI has an inhibitory effect only when the respiratory drive is high (hypercapnia), probably acting on tidal volume. The observations reported in the present investigation, together with other studies on the presence of NOS in amphibians, indicate a considerable degree of phylogenetic conservation of the NO pathway amongst vertebrates.

Breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises

The objective of the present study was to evaluate breathing pattern, thoracoabdominal motion and muscular activity during three breathing exercises: diaphragmatic breathing (DB), flow-oriented (Triflo II) incentive spirometry and volume-oriented (Voldyne) incentive spirometry. Seventeen healthy subjects (12 females, 5 males) aged 23 ± 5 years (mean ± SD) were studied. Calibrated respiratory inductive plethysmography was used to measure the following variables during rest (baseline) and breathing exercises: tidal volume (Vt), respiratory frequency (f), rib cage contribution to Vt (RC/Vt), inspiratory duty cycle (Ti/Ttot), and phase angle (PhAng). Sternocleidomastoid muscle activity was assessed by surface electromyography. Statistical analysis was performed by ANOVA and Tukey or Friedman and Wilcoxon tests, with the level of significance set at P < 0.05. Comparisons between baseline and breathing exercise periods showed a significant increase of Vt and PhAng during all exercises, a significant decrease of f during DB and Voldyne, a significant increase of Ti/Ttot during Voldyne, and no significant difference in RC/Vt. Comparisons among exercises revealed higher f and sternocleidomastoid activity during Triflo II (P < 0.05) with respect to DB and Voldyne, without a significant difference in Vt, Ti/Ttot, PhAng, or RC/Vt. Exercises changed the breathing pattern and increased PhAng, a variable of thoracoabdominal asynchrony, compared to baseline. The only difference between DB and Voldyne was a significant increase of Ti/Ttot compared to baseline. Triflo II was associated with higher f values and electromyographic activity of the sternocleidomastoid. In conclusion, DB and Voldyne showed similar results while Triflo II showed disadvantages compared to the other breathing exercises.

Breathing pattern and thoracoabdominal motion during exercise in chronic obstructive pulmonary disease

Subjects with chronic obstructive pulmonary disease (COPD) present breathing pattern and thoracoabdominal motion abnormalities that may contribute to exercise limitation. Twenty-two men with stable COPD (FEV1 = 42.6 ± 13.5% predicted; age 68 ± 8 years; mean ± SD) on usual medication and with at least 5 years of diagnosis were evaluated at rest and during an incremental cycle exercise test (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and abdominal motion contribution to tidal volume and the phase angle that measures the asynchrony were analyzed by inductive respiratory plethysmography at rest and during three levels of exercise (30-50, 70-80, and 100% maximal work load). Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni corrections were used for analyses. As expected, the greater the exercise intensity the higher the tidal volume and respiratory frequency. Abdominal motion contributed to the tidal volume increase (rest: 49.82 ± 11.19% vs exercise: 64.15 ± 9.7%, 63.41 ± 10%, and 65.56 ± 10.2%, respectively, P < 0.001) as well as the asynchrony [phase angle: 11.95 ± 7.24° at rest vs 22.2 ± 15° (P = 0.002), 22.6 ± 9° (P < 0.001), and 22.7 ± 8° (P < 0.001), respectively, at the three levels of exercise]. In conclusion, the increase in ventilation during exercise in COPD patients was associated with the major motion of the abdominal compartment and with an increase in the asynchrony independent of exercise intensity. It suggests that cycling exercise is an effective way of enhancing ventilation in COPD patients.

Effects of different levels of positive airway pressure on breathing pattern and heart rate variability after coronary artery bypass grafting surgery

The application of continuous positive airway pressure (CPAP) produces important hemodynamic alterations, which can influence breathing pattern (BP) and heart rate variability (HRV). The aim of this study was to evaluate the effects of different levels of CPAP on postoperative BP and HRV after coronary artery bypass grafting (CABG) surgery and the impact of CABG surgery on these variables. Eighteen patients undergoing CABG were evaluated postoperatively during spontaneous breathing (SB) and application of four levels of CPAP applied in random order: sham (3 cmH2O), 5 cmH2O, 8 cmH2O, and 12 cmH2O. HRV was analyzed in time and frequency domains and by nonlinear methods and BP was analyzed in different variables (breathing frequency, inspiratory tidal volume, inspiratory and expiratory time, total breath time, fractional inspiratory time, percent rib cage inspiratory contribution to tidal volume, phase relation during inspiration, phase relation during expiration). There was significant postoperative impairment in HRV and BP after CABG surgery compared to the preoperative period and improvement of DFAα1, DFAα2 and SD2 indexes, and ventilatory variables during postoperative CPAP application, with a greater effect when 8 and 12 cmH2O were applied. A positive correlation (P < 0.05 and r = 0.64; Spearman) was found between DFAα1 and inspiratory time to the delta of 12 cmH2O and SB of HRV and respiratory values. Acute application of CPAP was able to alter cardiac autonomic nervous system control and BP of patients undergoing CABG surgery and 8 and 12 cmH2O of CPAP provided the best performance of pulmonary and cardiac autonomic functions.

Étude multicentrique sur les stratégies de ventilation mécanique employées chez les enfants avec un œdème pulmonaire lésionnel

Des études adultes sur l’œdème pulmonaire lésionnel et le Syndrome de Détresse Respiratoire Aiguë ont mené à l’établissement de recommandations sur les stratégies de ventilation mécanique à employer chez ces patients. Cependant, il n’est pas clair si les recommandations adultes sont également bénéfiques pour l’enfant. Objectif Décrire les stratégies de ventilation mécanique employées chez les enfants atteints d’un œdème pulmonaire lésionnel. Méthodes Étude épidémiologique transversale tenue dans 59 unités de Soins Intensifs Pédiatriques de 12 pays en Amérique du Nord et en Europe. Six jours d’étude ont eu lieu entre juin et novembre 2007. Les enfants atteints d’un œdème pulmonaire lésionnel étaient inclus et des données sur la sévérité de leur maladie, les paramètres de ventilation mécanique et les thérapies adjuvantes employées ont été recueillies. Résultats Des 3823 enfants dépistés, 414 (10.8%) avaient un œdème pulmonaire lésionnel et 165 (40%) ont été inclus dans l’étude (124 étaient sous ventilation mécanique conventionnelle, 27 sous ventilation à haute fréquence par oscillation et 14 sous ventilation non invasive). Dans le groupe sous ventilation conventionnelle, 43.5% étaient ventilés avec un mode contrôlé à pression, le volume courant moyen était de 8.3±3.3 ml/kg et l’utilisation de la PEP et FiO2 était hétérogène. Conclusions Cette étude démontre une hétérogénéité dans les stratégies de ventilation mécanique employées chez les enfants souffrant d’un œdème pulmonaire lésionnel. Celle-ci pourrait être en partie reliée à la robustesse des critères diagnostiques actuellement utilisés pour définir l’ALI/SDRA. Une évaluation rigoureuse de ces stratégies est nécessaire pour guider la standardisation des soins et optimiser l’issue de ces patients.

Comparative safety respiratory pharmacology : validation of a head-out plethysmograph – pneumotachometer testing device in male Sprague–Dawley rats, Beagle dogs and Cynomolgus monkeys

Le but de cette étude était d’évaluer les qualifications de performance du système FlexiWare® chez le rat male Sprague Dawley et le singe Cynomolgus éveillés, ainsi que chez le chien Beagle éveillé et anesthésié, suite à l’administration de produits ayant une activité pharmacologique connue. Les produits utilisés incluaient l’albutérol administré par inhalation, la méthacholine, et le rémifentanil administrés par voie intraveineuse. Une solution saline administré par voie intraveneuse, a été utilisée comme substance témoin. Différentes variables ont servi à évaluer la réponse des animaux (rats, chien, singe). Ces dernières comprenaient la fréquence respiratoire (RR), le volume courant (TV), la ventilation minute (MV). Des paramètres additionnels ont été évalués chez le rat, soit les temps d’inspiration (IT) et d’expiration (ET), le temps du pic de débit expiratoire, les pics de débits inspiratoire et expiratoire, le ratio inspiratoire:expiratoire (I:E), le ratio inspiratoire sur respiration totale (I:TB), et l’écoulement expiratoire moyen (EF50). Les résultats obtenus ont démontré que le système FlexiWare® était suffisamment sensible et spécifique pour dépister, chez les espèces animales utilisées, les effets bronchodilateur, bronchoconstricteur et dépresseur central des substances testées. Il pourrait faire partie des méthodes (ICH 2000) utilisées en pharmacologie de sécurité lors de l’évaluation de substances pharmacologiques sur le système respiratoire des animaux de laboratoire. Les espèces animales utilisées ont semblé s’adapter aisément aux procédures de contention. Les paramètres évalués, RR, TV et MV ont permis de caractériser la réponse des animaux suite à l’administration de produits pharmacologiques à effets connus, judicieusement complétés par les variables de débit. L’ajout de paramètres du temps n’était pas primordiale pour détecter les effets des drogues, mais offre des outils complémentaires d’interpréter les changements physiologiques. Cependant, chez le rat conscient, la période d’évaluation ne devrait pas s’étendre au-delà d’une période de deux heures post traitement. Ces études constituent une évaluation des qualifications de performance de cet appareil et ont démontré de manière originale, la validation concurrentielle, en terme de précision (sensibilité et spécificité) et fiabilité pour différentes variables et sur différentes espèces.

Dispositivo de no reinhalación NRMASK, pruebas de eficacia, desempeño y seguridad

Objetivo del estudio: comparar las mediciones realizadas en el dispositivo de entrega de agente halogenado, con un modelo matemático donde se encontraron los valores ideales de fracción espirada de agente halogenado para cada evento. Diseño del estudio: diseño de tecnología. Lugar de desarrollo: salas de cirugía de un Hospital Universitario, Bogotá, Colombia. Intervenciones y medidas: luego de diseñar y ensamblar un circuito anestésico semiabierto tipo mascara facial con dos válvulas unidireccionales (una inspitratoria y otra espiratoria), se procedió a tomar las medidas de Concentración inspirada de sevofluorane, y fracción inspirada de oxigeno, con volúmenes espiratorios de 70 a 170 mL con intervalos de 10 mL, y con el dial de sevoflorane a 2, 2.2, 2.4, 2.6 vol%, los resultados consignados fueron comparados con los valores matemáticamente calculados para cada evento. Resultados: las mediciones realizadas en la máscara son concordantes con los cálculos realizados en el modelo matemático. La concentración espirada de sevoflorane es ligeramente superior en cada evento con respecto a lo encontrado en el modelo matemático, no es posible asegurar la no reinhalación con las mediciones realizadas.

Preoxigenacion con volumen corriente y capacidad vital en voluntarios sanos a 2600 metros

En la literatura existen descritas varias técnicas de preoxigenación aplicadas a diferentes pacientes y realizadas con diferentes flujos o fracciones inspiradas de oxigeno, sin embargo no se encuentran descripciones ni estudios realizados con respecto a este tópico en pacientes ubicados por encima de los 1000 mts sobre el nivel del mar. El objetivo del presente estudio es describir el patrón de saturación con oxigeno al 100% obteniendo fracción espirada de oxígeno (EtO2) >90% y Saturación de oxígeno (SaO2) > 99%, así como el patrón de normalización de la saturación de oxigeno con una fracción inspirada del 21% con cuatro técnicas estandarizadas de preoxigenación, en personas voluntarias sanas pertenecientes a la Fundación Cardio Infantil a 2600 metros sobre el nivel del mar. Materiales y métodos: Este es un estudio cuasiexperimental en personas adultas voluntarias sanas pertenecientes a la Fundación Cardio Infantil, los cuales son sometidos a toma de saturación de oxígeno basal y luego se les aplica preoxigenación con fracción inspirada oxigeno (FiO2) al 100% con un flujo de 10Lt/min, mediante sello de máscara facial con arnés: Simultáneamente se realiza una medición de la fracción espirada de oxígeno (ETO2) y oximetría de pulso (SaO2) cada 15 segundos con cada una de las cuatro pruebas de preoxigenación (volumen corriente por 3 minutos, 8 capacidades vitales, volumen corriente hasta ETO2 de =90% y capacidades vitales hasta ETO2 =90%) y luego medición del tiempo de normalización de la saturación respirando al oxígeno con FiO2 al 21 % hasta alcanzar nuevamente la SaO2 basal, con cada técnica. Resultados: No existe diferencia significativa en la aplicación de las técnicas de preoxigenación ni tampoco en el tiempo de normalización de la saturación de oxígeno con FiO2 al 21 % al nivel de Bogotá con las cuatro técnicas de preoxigenación aplicadas a nuestros pacientes. Conclusión: Las cuatro técnicas de preoxigenación son efectivas, sin embargo recomendamos el uso de técnicas que buscan una ETO2=90%. Por otra parte encontramos que el tiempo de recuperación de la saturación basal es de 3,9 minutos en personas voluntarias sanas a 2600 mts sobre el nivel del mar, la cual es inferior comparada con los 10 minutos que toma la normalización de la saturación de oxígeno a 0 mts sobre el nivel del mar descritos previamente en la literatura. Hace falta realizar estudios de preoxigenación y apnea en pacientes a nuestra altura (2600 mts sobre el nivel del mar) para confirmar que el tiempo de desaturación es significativamente menor que a nivel del mar. Palabras Claves: Preoxigenación, Fracción espirada de O2 (EtO2), saturación de oxígeno (SaO2).

Efectos de la ventilación mecánica con heliox en niños y adolescentes con patología bronquial obstructiva

Evaluar si el Heliox reduce la resistencia en la vía aérea en niños y adolescentes con patología bronquial obstructiva que requieren ventilación mecánica. Materiales y Métodos: Estudio prospectivo observacional descriptivo en niños y adolescentes con patología bronquial obstructiva y ventilación mecánica con Fi02 ≤ 0,5. Medición de variables: resistencia, presión pico, presión media de la vía aérea, presión meseta, volumen corriente, autoPEEP, distensibilidad, PetCO2, ventilación de espacio muerto antes de inicio de heliox y a los 30 minutos, 2, 4, 6, 12, 18 y 24 horas y diariamente hasta suspenderlo por extubación o FiO2 > 0,5. Resultados: Resultados parciales, incluyó 9 pacientes encontrando descenso significativo de resistencia espiratoria a los 30 minutos (51,2 vs 32,3; p=0,0008 ), 2 horas ( 51,2 vs 33,4; p=0,0019) y 4 horas (51,2 vs 30,7; p=0,0012) así como de la resistencia inspiratoria a la hora 2 (48,6 vs 36,2; p = 0,013) y hora 4 (48,6 vs 30 ; p=0,004). Se observó tendencia al descenso de la PetCO2 que no fue significativa (52,3 vs 34,3: p=0,06). No se evidenció cambios en las variables; autoPEEP, presión pico, presión media de la vía aérea, distensibilidad, ventilación de espacio muerto, presión meseta y volumen corriente antes y después del inicio del Heliox. Conclusión: La ventilación mecánica con Heliox en niños con patología bronquial obstructiva parece ser que reduce de manera significativa la resistencia de la vía aérea, con tendencia al descenso de la PetC02. Se necesitan estudios prospectivos al menos observacionales analíticos que corroboren estos hallazgos.