W.J. Kim

Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy, etiological category of diffuse lung injury, and body position of the patient.

ObjectiveTo assess how the level of positive end-expiratory pressure (PEEP) (antiderecruitment strategy), etiological category of diffuse lung injury, and body position of the patient modify the effect of the alveolar recruitment maneuver (ARM) in acute respiratory distress syndrome (ARDS). DesignProspective clinical trial. SettingMedical intensive care unit at a tertiary hospital. PatientsForty-seven patients with early ARDS, including 19 patients from our preliminary study. InterventionFrom baseline ventilation at a tidal volume of 8 mL/kg and PEEP of 10 cm H2O, the ARM (a stepwise increase in the level of PEEP up to 30 cm H2O with a concomitant decrease in the magnitude of tidal volume down to 2 mL/kg) was given with (ARM + PEEP, n = 20) or without (ARM only, n = 19) subsequent increase of PEEP to 15 cm H2O. In eight other patients, PEEP was increased to 15 cm H2O without a preceding ARM (PEEP only). Measurements and ResultsIn all three groups, Pao2 was increased by the respective intervention (all p < .05). In the ARM-only group, Pao2 at 15 mins after intervention was lower than Pao2 immediate after intervention (p = .046). In the ARM + PEEP group, no such decrease in Pao2 was observed, and Pao2 at 15, 30, 45, and 60 mins after intervention was higher than in the ARM-only group (all p < .05). Compared with the PEEP-only group, Pao2 of the ARM + PEEP group was higher immediately after intervention and at the later time points (all p < .05). Compared with patients with ARDS associated with direct lung injury (pulmonary ARDS), patients with ARDS associated with indirect lung injury (extrapulmonary ARDS) showed a greater increase in Pao2 (27 ± 21% vs. 130 ± 112%;p = .002) and a greater decrease in radiologic scores (1.0 ± 2.4 vs. 3.4 ± 1.5;p = .005) after the ARM. The increase in Pao2 induced by the ARM was greater for patients in the supine position than for patients in the prone position (61 ± 82% vs. 21 ± 14%;p = .028). Consequently, Pao2 immediately after the ARM was similar in the two groups of patients in different positions. ConclusionsAfter the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.

The effects of hypothermia on endotoxin-primed lung.

BACKGROUND: Hypothermia may be effective for endotoxin-induced acute lung injury. In most studies, hypothermia was induced before the development of neutrophilic inflammation, which would be clinically irrelevant. We investigated whether hypothermia induced after the onset of such neutrophilic inflammation reduces acute lung injury. METHODS: In the first experiment, rats were allocated to one of four groups: intratracheal saline instillation/killed at 1 h (saline), intratracheal lipopolysaccharide (LPS) instillation/killed at 1 h (LPS-primed), intratracheal LPS instillation/killed at 6 h (LPS-NT), all under normothermia (NT) (37 ± 0.5°C) throughout study, and intratracheal LPS instillation/killed at 6 h with hypothermia (HT) (32 ± 0.5°C) for the last 5 h of study (LPS-HT). Lungs were lavaged for biochemical measurements. In the second experiment in 26 additional rats, we followed exactly the same protocol as described above for the saline group (n = 2), LPS-NT (n = 12), and LPS-HT (n = 12), and obtained a fresh pool of alveolar neutrophils to assess oxidative burst. RESULTS: Compared with the LPS-primed group, the neutrophil count, protein level, and lactate dehydrogenase activity in the bronchoalveolar lavage fluid, and myeloperoxidase activity of the lung were all higher in the LPS-NT group. Compared with this LPS-NT group, the neutrophil count, protein level, and lactate dehydrogenase activity in the bronchoalveolar lavage fluid, and microscopic scores for alveolar neutrophilic infiltration were all lower in the LPS-HT group. The stimulated production of hydrogen peroxide in neutrophils was lower in the LPS-HT group than in the LPS-NT group. CONCLUSION: Hypothermia, applied even after the onset of neutrophilic inflammation, was effective in reducing endotoxin-induced acute lung injury.

A possible role for CD8+ and non-CD8+ cell granzyme B in early small airway wall remodelling in centrilobular emphysema.

CD8+ cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease (COPD). CD8+ T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B‐positive cells in relation to CD8+ cells in the small airway walls of emphysema.

The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock.

Background/Aims Endogenous nitric oxide (NO) induces the peripheral vasodilation via the activation of guanylate cyclase in patients with septic shock. The purpose of this study was to assess the acute effects of methylene blue (MB), which is an inhibitor of guanylate cyclase, on the hemodynamics and on the production of pro-inflammatory cytokines and nitric oxide (NO) in patients with refractory septic shock. Methods Twenty consecutive patients with refractory septic shock, which was defined as shock refractory to a dopamine infusion of more than 20 µg/kg/min with the appropriate use of antibiotics and adequate volume replacement, received MB infusion of 1 mg/kg intravenously. The hemodynamic and respiratory variables were measured at baseline, 30, 60 and 120 min after an infusion of MB (1 mg/kg). The blood levels of NO, IL-1, IL-10 and TNF-α were measured at baseline, 30 and 120 min after MB infusion. Results The administration of MB induced an increase in the systemic vascular resistance (SVR) that resulted in an increase of the mean arterial pressure (MAP) in patients with refractory septic shock, and this was without a decrease in cardiac output. The administered MB induced an increase in pulmonary vascular resistance (PVR) that resulted in an increase of pulmonary arterial pressure (PAP), without any deterioration of gas exchange. However, the increases in SVR and PVR were not associated with the alteration of endogenous production of NO, IL-1, IL-10 and TNF-α. Conclusion MB transiently elevated the MAP by increasing the SVR without altering the endogenous productions of NO, IL-1, IL-10 and TNF-α during the study period in patients with refractory septic shock.