The Latest in Critical Care: November 26, 2025
"Permissive hypotension" in the OR; TOP trial for RBC transfusion; TXA for hemoptysis
I’m very grateful for each of you who have helped keep PulmCCM going through 2025. Wishing you all a safe and happy holiday season. —Matt
Intraoperative hypotension appears safer than we thought (PRETREAT and BP-CARES trials)
Intraoperative hypotension is associated with perioperative cardiovascular complications and organ dysfunction, like acute kidney injury. Numerous randomized and observational trials have demonstrated that intraoperative blood pressure could be effectively controlled, but most were not powered to analyze clinically meaningful outcomes. Thus, whether preventing hypotension also prevents complications has been unknown.
In INPRESS (JAMA 2017, n=292), patients treated within 10% of their preoperative blood pressure had dramatically lower rates of post-operative organ dysfunction (38% vs 52%).
In the larger and more recent PRETREAT trial (JAMA 2025), among 3,247 adults undergoing elective noncardiac surgery at two Dutch centers, intensive intraoperative blood pressure support (targeting a MAP of ≥70 mm Hg for low risk patients, ≥80 for intermediate risk, ≥90 for high-risk) did not improve postoperative disability at 6 months (the primary outcome) compared to usual care.
Nor was there any significant signal suggesting an increase in organ dysfunction among the relatively hypotensive patients. Twice as many patients in the intervention arm received vasopressors, but those receiving usual care had no significant increase in shock, acute kidney injury, stroke, or myocardial infarction. The trial was stopped short of its target enrollment of 5,000 patients due to statistical futility.
In the BP-CARES trial (JACC 2025)*, 1,500 patients undergoing major abdominal surgery were randomized to either intensive blood pressure management targeting intraoperative MAP ≥80 mm Hg or conventional management targeting intraoperative MAP ≥ 65 mm Hg (or higher for hypertensive patients). There was no reduction in cardiovascular events (the primary composite outcome) among the intensively treated patients (14.5% in the intensive strategy group vs. 13.6% in the conventional strategy group.
The new results agree with the POISE-3 trial (Annals Internal Medicine 2023), in which 3,742 patients undergoing noncardiac surgery at 110 hospitals in 22 countries had virtually identical rates (14% vs. 13.9%) of cardiovascular complications (a composite of vascular death, myocardial injury, stroke, and cardiac arrest) at 30 days post-op.
POISE-3 provided much of the power for a meta-analysis (BJA 2023) which also found that in 10 trials (n=9,359), which found that the lower-blood-pressure arms not only did not have increased mortality, but were surprisingly associated with a reduced rate of atrial fibrillation and shorter hospital stays.
There’s an intriguing connection with the recent hypothesis-generating discovery that lower blood pressure targets (so-called permissive hypotension) were associated with improved outcomes in critical illness:
Are usual vasopressor doses causing unrecognized harm?
Maintaining a mean arterial pressure (MAP) of 65 mm Hg has been advised for patients with sepsis and other forms of vasodilatory shock. In practice, treating teams often exceed this target by a significant margin, such as in patients with more severe organ failure or pre-existing hypertension. This strategy is likely pursued out of concern that lower MA…
It’s impossible to rule out heterogeneity of treatment effect in such studies, in which some patients hypothetically benefit from the intervention while others are harmed, resulting in a net neutral (no benefit) result that masks individual patients’ differing responses.
Kant et al. Proactive vs Reactive Treatment of Hypotension During Surgery: The PRETREAT Randomized Clinical Trial, JAMA 2025
Futier et al. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial, JAMA 2017
D’Amico F, Fominskiy EV, Turi S, et al. Intraoperative hypotension and postoperative outcomes: a meta-analysis of randomised trials. Br J Anaesth. 2023;131(5):823-831. doi:10.1016/j.bja.2023.08.026
Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery: An International Randomized Controlled Trial. Annals Internal Medicine 2023
Liberal vs. restrictive transfusion targets for higher-risk surgery (TOP trial)
Restrictive blood transfusion (e.g., targeting a hemoglobin level of 7 or 8 g/dL rather than 9 or 10 g/dL) has been generally recommended in most medical and surgical patients, including those with active upper GI bleeding or who are undergoing cardiac surgery.
Among 1,428 veterans undergoing major surgery and considered to be at high risk of postoperative cardiac events, those assigned to a transfusion target of hemoglobin ≥10 g/dL had similar rates of postoperative death or major ischemic events (the primary composite outcome) as those assigned to a target hemoglobin ≥7 g/dL (9.1% for ≥10 g/dL, 10.1% for ≥7 g/dL).
However, there was a concerning increase in cardiac complications in the restrictive group (9.9% vs 5.9%), including new-onset arrhythmias requiring treatment (4.3% vs 2.6%) and new or worsening heart failure (5.8% vs 4.0%).
Visually, the Kaplan-Meier curves separated early and favored a liberal transfusion strategy, especially for cardiac events.
The study was not powered to detect a small difference between groups; its power calculations and enrollment were based on the prediction of an implausibly high 7.5% absolute difference in the primary outcome between groups. Thus, its negative results were foreordained and the possibility of a false negative (type II error) appears significant.
Inhaled tranexamic acid for nonmassive hemoptysis?
Nebulized tranexamic acid was reported to have benefits in treating nonmassive hemoptysis in two small, single-center randomized trials conducted outside the U.S.
In Gopinath et al (Chest 2023), inhaled TXA (500 mg tid) reduced hemoptysis and the need for bronchial artery embolization in 68 randomized patients at a single center in New Delhi, India, compared to patients receiving IV TXA (500 mg tid).
In Wand et al (Chest 2018), significantly more patients randomized to inhaled TXA (500 mg tid) had resolution of hemoptysis by 5 days, at a single center in Tel Aviv, Israel.
There were no major adverse events attributed to the inhaled TXA.
These small single-center studies require replication before concluding TXA is beneficial in this context.
Another single-center trial of inhaled nebulized tranexamic acid is currently underway among 60 patients with pulmonary hemorrhage due to blood cancers at MD Anderson in Houston, Texas (NCT05053867).
Study Details | NCT05053867 | A Randomized Controlled Trial of Inhaled Tranexamic Acid for the Treatment of Pulmonary Hemorrhage in Cancer Patients | ClinicalTrials.gov
Mahalingam et al. Effectiveness of Inhalational Tranexamic Acid in Patients with Nonmassive Hemoptysis–A Systematic Review and Meta-Analysis | Lung 2025
Nebulized Tranexamic Acid in the Management of Hemoptysis: An Integrative Review - PubMed