Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill Invasively Ventilated Patients

The goal is to achieve the lowest possible respiratory rate (RR) according to a guideline in which the target RR is estimated by combining the baseline RR with the results of arterial blood gas analysis (ABG), determined by the highest acceptable partial pressure of carbon dioxide (PaCO2) of ≤ 8.5 kPa (64 mmHg) but limited by the lowest acceptable arterial pH (pHa) of \> 7.20. The RR is gradually decreased, in steps of 2 breaths every 10 minutes, based on continuous end-tidal CO2 monitoring. To ensure that the pHa does not fall below 7.20, following randomization, ABGs are repeated every hour until the target RR is reached, for at least 6 hours. Thereafter, blood gas analyses are repeated at least every 8 hours (at the start of every nursing shift). Down-titration of RR stops at a rate of 4 breaths per minute. This approach continues until the switch to spontaneous breathing. Of note, when the pHa is \> 7.50, this must first be decreased to ≤ 7.50 based on local protocol.

Following randomization, which should happen within 1 hour after start of ventilation in the ICU, the RR is set according to standard of care, based on continuous end-tidal CO2 monitoring, to target a normal PaCO2 (4.7-6.4 kPa or 35-48 mmHg) combined with a pHa within the range of 7.35 to 7.45. Following randomization, blood gas analyses are repeated every hour for at least 6 hours, and thereafter at least every 8 hours (at the start of every nursing shift). This approach continues until the weaning phase.