Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients.

OBJECTIVES: The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD. METHODS: This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination. RESULTS: A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartile-range: 427-1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2-3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3-3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients 'ever colonized' with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization. CONCLUSIONS: COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142).

The effects of desflurane on splanchnic hemodynamics and oxygenation in the anesthetized pig.

This study was designed to investigate the effects of desflurane on systemic and splanchnic hemodynamics, O2 delivery and O2 uptake, tissue oxygenation (as monitored by surface PO2 electrodes), and hepatic oxygen-dependent intermediary metabolism (hepatic lactate uptake, intestinal lactate production, ketone-body ratio) in the pig. We studied 11 anesthetized (i.e., ketamine, flunitrazepam, vecuronium) and ventilated domestic pigs (17-23 kg). After instrumentation, desflurane was administered randomly at 0.5 minimum alveolar anesthetic concentration (MAC) (4.2 vol %) and 1.0 MAC (8.3 vol %). Desflurane caused dose-dependent decreases in heart rate, mean arterial blood pressure, and cardiac output. Hepatic arterial blood flow was not affected at 0.5 MAC but decreased at 1.0 MAC. In contrast, portal and superior mesenteric arterial blood flow decreased at 0.5 MAC but did not show any further significant decrease at 1.0 MAC. Total hepatic blood flow decreased dose-dependently. Although O2 deliveries of whole body, liver, and small intestine were markedly reduced at both concentrations, respective O2 uptakes did not change significantly. The decreases in O2 deliveries were reflected by moderate disturbances in hepatic and small intestinal surface PO2. No evidence for severe tissue hypoxia could be detected. Desflurane had no adverse effects on hepatic and small intestinal metabolic function. These data indicate that hepatic and small intestinal O2 reserve capacity is impaired by desflurane.

Different effects of early endotoxaemia on hepatic and small intestinal oxygenation in pigs.

OBJECTIVE: Study on simultaneous O2 supply/uptake relationships in liver and gut during endotoxaemia, to determine whether signs of dysoxia develop uniformly in the splanchnic region. DESIGN: Animal study to assess the early effects of endotoxaemia on oxygenation of both liver and small intestine. INTERVENTIONS: Eight anaesthetized pigs received a continuous portal venous infusion of lipopolysaccharide (0.5 microgram.kg-1.h-1) for 6 h. Systemic, pulmonary and splanchnic haemodynamics as well as systemic and splanchnic O2 supply/uptake relationships were determined. RESULTS: There was a multiphasic haemodynamic response pattern characterized by an early (within the 1st h) and a subsequent more prolonged phase (between the 2nd and 6th h) of decreases and recovery of hepatic arterial, portal venous and superior mesenteric arterial blood flows (electromagnetic flow probes) and splanchnic O2 deliveries. Unrelated to perfusion pressure and O2 delivery, there were early and sustained decreases in ileal mucosal surface partial pressure of oxygen (PO2) (multiwire PO2 electrode) and pH (tonometry). This was not reflected by ileal serosal surface PO2, O2 uptake and arteriomesenteric venous pH and partial pressure of carbon dioxide (PCO2) gradients. There was little evidence of concomitant hepatic dysoxia as evaluated by surface PO2. CONCLUSIONS: The study demonstrates early and sustained regional (mucosa) intestinal hypoxia with little evidence of simultaneous hepatic dysoxia during initial endotoxaemia.

Differential effects of dobutamine, dopamine, and noradrenaline on splanchnic haemodynamics and oxygenation in the pig.

Supranormal oxygen (O2) transport may benefit critically ill patients. Catecholamines are clinically employed for this purpose. However, their effects on splanchnic haemodynamics and oxygenation are now well defined. The effects of dobutamine (DOBU), dopamine (DOPA), and noradrenaline (NA) on splanchnic blood flows electromagnetic flow probes), O2 deliveries and uptakes (catheterisation of portal and hepatic veins) were studied in nine anaesthetised (ketamine/flunitrazepam), ventilated, paralysed, and laparotomised pigs. All three catecholamines (DOPA at 15 micrograms.kg-1.min-1, DOBU at 13 micrograms.kg-1.min-1, NA at 0.4 micrograms.kg-1.min-1) significantly (P < 0.05) increased cardiac output and systemic O2 delivery. Only DOPA increased small intestinal and total hepatic blood flows, and O2 deliveries, and decreased O2 extractions. The same parameters did not change during DOBU. During NA, total hepatic blood flow and O2 delivery decreased, and hepatic O2 extraction increased. During all three catecholamines, small intestinal and total hepatic O2 uptakes did not change significantly. Whereas hepatic arterial blood flow decreased during both DOPA and NE, portal venous flow increased during DOPA. These data suggest that in the experimental model used splanchnic O2 supply and O2 reserve capacity appear improved by DOPA, unaffected by DOBU, and impaired by NA.

Fluid removal with negative-pressure hydrostatic ultrafiltration using a partial vacuum.

Removal of excessive fluid with a negative-pressure hydrostatic ultrafiltration technique using a partial vacuum was performed successfully in eight patients. The technique appears to be a satisfactory means of fluid removal.