William M. Long

The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.

To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S.E.M.) after the onset of shock, and 55 patients required vasopressor agents. Early in the hospital course, reversal of shock was more likely in patients who received corticosteroids than in those who did not. Four (19 per cent) of 21 methylprednisolone-treated, 7 (32 per cent) of 22 dexamethasone-treated, and none of 16 control patients had reversal of shock 24 hours after drug administration (corticosteroid groups vs. control group, P less than 0.05). Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal (P less than 0.05). At 133 hours after drug administration, 17 (40 per cent) of 43 corticosteroid-treated patients had died, and 11 (69 per cent) of 16 control patients had died (P less than 0.05). However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients.

Complement activation in septic shock patients.

To evaluate the status of the complement system and to determine the effects of corticosteroids on complement component levels in septic shock, C3, C4, and Factor B were measured in 42 patients with severe late septic shock. Serum levels of C4 and Factor B correlated with C3 levels (r = 0.48 and 0.64, respectively; p < .01) in patients in shock for more than 4 h, but only Factor B correlated with C3 (r = 0.85; p < .01) in patients in shock for 4 h or less. C3 and Factor B levels were significantly (p < .05) lower in patients who died (12,174 ± 1,524 CH50 U/ml and 14 ± 1 mg/dl, respectively) than in patients who survived (18,418 ± 2,833 CH50 U/ml and 21 ±2 mg/dl, respectively). Corticosteroids did not alter complement component levels.The alternative pathway appears to be activated early in septic shock, whereas the classical pathway is activated later. C3 and Factor B levels may predict survival of patients in septic shock. In this study, corticosteroids did not change the complement component levels of patients in late severe septic shock.

Bronchial circulation in asthma

Whereas the anatomical changes of the bronchial circulation in response to a wide variety of congenital and acquired cardiopulmonary diseases have been well described, little is known about its functional response. There is growing evidence that the bronchial circulation plays a major role in the pathophysiology of hyperreactive airway disease. The bronchial vascular system appears to be involved in mediator transport to and from target tissues in the airway wall, in the development of airway wall edema which may contribute to airflow obstruction, and in heat and water exchange in the tracheobronchial tree. Although our current understanding of these functions is rather sketchy, enough is known to outline the contributions of the bronchial, i.e. the systemic circulation to the mechanisms of bronchial asthma.

Mobilization of mucus by airway oscillations

The effects of high frequency asymmetric airway oscillations on mucus clearance were evaluated in excised tracheas of sheep, in an animal model of excessive mucus production, and in patients with bronchiectasis. Asymmetric high frequency ventilation (15 Hz) with expiratory biased flow profiles (expiratory peak‐flow > inspiratory peak‐flow) could move mucus droplets towards the pharynx in rigid and flexible tracheas by gas‐liquid interaction. In rigid tracheas the mucus was transported towards the periphery of the model lung if the oscillations were inspiratory biased. In very collapsible tracheas, however, even inspiratory biased oscillations moved the mucus cephalad. Parameters influencing direction and speed of mucus are airflow profile, peak‐flow, airway compliance and lung resistance. Gamma‐camera studies showed that in anesthetized dogs radiolabeled artificial mucus followed the direction of the bias during high frequency ventilation. In five human volunteers with bronchiectasis and excessive secretions the asymmetric airway oscillations were superimposed during spontaneous breathing using a mouthpiece. Airway wall vibrations following the pressure swings of the oscillator could be observed. During forced expiration inward bulging of the posterior membranes of trachea and bronchi occurred at the negative pressure phase of the oscillations. This event was associated with increased appearance of sputum in the central airways. We conclude that high frequency ventilation with asymmetric flow profiles applied via tube or mouthpiece might be an effective future treatment of mucostasis.