Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis.

BACKGROUND AND OBJECTIVE: Recent studies showed that both sepsis and antibiotic therapy are associated with cell death and linked to reactive oxygen species generation. This study investigated the effects of intratracheal administration of combinations of antioxidants (n-acetyl cysteine (NAC), vitamins C and E) in the treatment of sepsis-induced lung injury. METHODS: Ninety-six male Wistar rats subjected to sepsis were treated with ceftriaxone plus NAC with or without vitamins C and E and compared to appropriate controls. As an index of oxidative damage protein carbonyls, sulfhydryl groups, lipid peroxidation and superoxide anion were measured, as well as superoxide dismutase and catalase. Histopathological alterations and mortality rate were also analyzed. RESULTS: Twenty-four hours after sepsis induction, markers of oxidative stress increased in all lungs examined. Ceftriaxone plus intratracheal combination of NAC, vitamins C and E decreased lung injury in infected animals by reducing superoxide anion production (54%), lipid peroxidation (53%) and protein carbonyl (58%) and restored the redox status (7.5 times). This therapy also reduced the imbalance of antioxidant enzymes activities and attenuated the alveolar architectural disorganization, inflammatory cell infiltration and pulmonary oedema. Survival increased from 66.6% with ceftriaxone to 83.2% with ceftriaxone plus antioxidants. CONCLUSIONS: Ceftriaxone plus intratracheal co-administration of antioxidants provides better protection, by decreasing pulmonary oxidative stress, limiting histophatological alterations and improving survival. Antioxidants should be explored as a co-adjuvant in the treatment of severe lung injury.

Scintigraphic assessment of radio-aerosol pulmonary deposition with the acapella positive expiratory pressure device and various nebulizer configurations.

BACKGROUND: The Acapella device produces high-frequency oscillations and positive expiratory pressure to promote bronchial secretion clearance. Its performance during aerosol delivery has not been described. We evaluated the effect of nebulizer and Acapella configuration on pulmonary deposition of radio-tagged aerosol in healthy subjects. METHODS: Ten healthy male subjects (mean age 24.4 ± 2.2 y) participated in a crossover study that compared pulmonary delivery of 4 mL of technetium-99m-labeled diethylene triamine penta-acetic acid (25 mCi) and 0.9% saline solution via jet nebulizer. We tested 3 configurations: nebulizer attached to the distal end of the Acapella; nebulizer placed between the mouthpiece and the Acapella; and nebulizer alone (control). With scintigraphy we measured radio-aerosol deposition in 6 lung regions: upper, middle, lower, central, intermediate, and peripheral. RESULTS: Deposition was similar between the right and left lungs, with no significant differences between device configurations. Lung deposition was less with the nebulizer attached to the Acapella than with nebulizer between the mouthpiece and the Acapella (P = .001, for both lungs) or without the Acapella (P = .003 and P = .001 for the right and left lungs, respectively). There was no significant difference between the setup without Acapella and the setup with the nebulizer between the mouthpiece and the Acapella (P = .001, for both lungs). On the vertical axis, deposition was lower with the nebulizer attached to the distal end of the Acapella than with the nebulizer between the mouthpiece and the Acapella (upper region P < .001, middle region P = .001, lower region P = .003), and lower with the nebulizer attached to the distal end of the Acapella than with the setup without Acapella (upper and middle region both P = .001, lower region P = .002), with up to a 3-fold difference in the middle and lower regions. On the central-peripheral axis, deposition was lower with the nebulizer attached to the distal end of the Acapella than with the nebulizer between the mouthpiece and the Acapella (central region P < .001, peripheral region P < .001), and lower with the nebulizer attached to the distal end of the Acapella than with the setup without Acapella (central and peripheral regions both P = .002), with differences of 3-4-fold between the central and peripheral regions. CONCLUSIONS: Placing the nebulizer distal to the Acapella, as recommended by the manufacturer, decreased intrapulmonary deposition, compared to placing the nebulizer between the Acapella and the patient airway, or delivering aerosol without the Acapella in the circuit. (ClinicalTrials.gov NCT01102166).

Influence of change in lateral decubitus on pulmonary aerosol deposition.

BACKGROUND: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. OBJECTIVES: To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. METHODS: Eight healthy male volunteers, mean age 23.6±2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of interest (ROI) were investigated in the longitudinal and cross-sectional divisions of the lungs. Statistical analysis included a paired Student's t-test with a significance level of p≤0.05. RESULTS: Inhalation in the right lateral decubitus position presented higher counts (p≤0.04) in posterior ROI of the right lung than in the posterior ROI of the left lung. In the left lateral decubitus position, the count was higher in the left lung (p≤0.02) than in the posterior ROI of the right lung. CONCLUSIONS: The deposition of aerosol particles during inhalation was position-dependent in the two phases of the study, which confirms the validity of technical and therapeutic resources based on the physiology of position-dependent ventilation and suggests that body positioning can be used to advantage in routine therapy.

Influência da variação dos decúbitos laterais na deposição pulmonar de aerossol / Influence of change in lateral decubitus on pulmonary aerosol deposition

CONTEXTUALIZAÇÃO: O decúbito lateral apresenta as maiores mudanças em relação à ventilação pulmonar regional e é utilizado na rotina da fisioterapia respiratória. OBJETIVOS: Avaliar a influência do decúbito lateral na deposição pulmonar de radioaerossol durante a inalação em indivíduos jovens e relacionar os efeitos desse decúbito na rotina terapêutica. MÉTODOS: Em estudo randomizado em duas fases, foram incluídos oito homens voluntários saudáveis, com média de idade de 23,6±2,5 anos. Na primeira fase, inalou-se aerossol durante nove minutos no decúbito lateral sorteado e, após intervalo de cinco a sete dias, realizou-se a segunda fase. Para a cintilografia, inalou-se uma dose média de ácido dietilnotriaminopentacético marcado com tecnécio (DTPA - TC99m), com uma atividade radioativa em média de 25 milicuries (mCi). Ao final da inalação, as imagens foram adquiridas em câmaras de cintilação e analisadas por meio da divisão longitudinal e transversal dos pulmões em regiões de interesse (ROI). Para análise estatística, utilizou-se o teste t de Student pareado, considerando significativo p<0,05. RESULTADOS: A inalação em decúbito lateral direito apresentou, na ROI posterior do pulmão direito, um maior número de contagem (p<0,04) quando comparada à ROI posterior do pulmão esquerdo. No decúbito lateral esquerdo, observou-se um maior número de contagem no pulmão esquerdo (p<0,02) do que na ROI posterior do pulmão direito. CONCLUSÕES: A deposição das partículas de aerossol durante inalação apresentou um comportamento decúbito dependente nas duas fases do estudo, ratificando técnicas e recursos terapêuticos baseados na fisiologia da ventilação decúbito dependente e sugere a utilização do posicionamento corporal na rotina terapêutica.

BACKGROUND: The lateral decubitus position leads to the greatest changes in regional pulmonary ventilation and is used in respiratory physical therapy routines. OBJECTIVES: To evaluate the influence of the lateral decubitus position on the pulmonary deposition of inhaled radioaerosol particles in young people and report the effects of the decubitus position on routine therapy. METHODS: Eight healthy male volunteers, mean age 23.6±2.5 years, were included in a randomized study in two phases. In the first phase, aerosol was inhaled for nine minutes in a randomly-selected lateral decubitus position and after an interval of 5 to 7 days, the second phase was conducted. Pulmonary scintigraphy was carried out by inhalation of 25 mCi of 99mTc-DTPA. Following inhalation, images were acquired with scintillation cameras and regions of interest (ROI) were investigated in the longitudinal and cross-sectional divisions of the lungs. Statistical analysis included a paired Student's t-test with a significance level of p<0.05. RESULTS: Inhalation in the right lateral decubitus position presented higher counts (p<0.04) in posterior ROI of the right lung than in the posterior ROI of the left lung. In the left lateral decubitus position, the count was higher in the left lung (p<0.02) than in the posterior ROI of the right lung. CONCLUSIONS: The deposition of aerosol particles during inhalation was position-dependent in the two phases of the study, which confirms the validity of technical and therapeutic resources based on the physiology of position-dependent ventilation and suggests that body positioning can be used to advantage in routine therapy.