IMPORTANCE It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation. OBJECTIVETo determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands. INTERVENTIONSOn-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473). MAIN OUTCOMES AND MEASURESThe primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of −0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events. RESULTS Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, −0.00003 to ϱ). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, −15.5% [95% CI, −20.7% to −10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, −13.4% [95% CI, −18.4% to −8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, −4.1% [95% CI, −5.9% to −2.2%]; P < .001). CONCLUSIONS AND RELEVANCEAmong ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization.

This study suggests that a fixed dose of 1040 IU of F IX may be an effective way to rapidly counteract VKA therapy in our patient population and provides a basis for future research.

Animal tests are conducted in all fields of trauma research, but transferability of these data to humans is limited. For example, it is still unclear which animal species is most similar to humans in terms of physiology of blood coagulation. To improve transferability and raise awareness of the existing differences, we compared human coagulation to coagulation of different animals. Rotational thromboelastometry was used to analyse the blood of pigs, sheep, rabbits and dogs. Animal data were compared with human coagulation based on the number of significant differences of the test parameters and on a descriptive comparison of the extent of relative deviation of the single values. All animal species showed significant differences in coagulation properties when compared with humans. Coagulation parameters of dogs and sheep were on average most similar to humans. However, there is no animal which is most similar to humans concerning all aspects of coagulation. Differences in coagulation between humans and animals are significant. This must be taken into account when transferring animal test data to humans.

In patients with haematological malignancy admitted to the ICU, culture results are diverse. The combination of neutropenia and positive blood culture is associated with increased 28-day mortality. We suggest this could be of additional value when assessing mortality risk in this patient group.