The continuing quest to treat numbers, not patients (OPTRESS)

Might elderly patients, with a higher risk of undiagnosed hypertension and higher rates of vascular disease, require higher blood pressure targets in sepsis? Or might this just be yet another example of medicine doing harm in the quest of better numbers on a monitor?

The paper

Endo A, Yamakawa K, Tagami T, et al. Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial. Intensive Care Med. 2025 May;51(5):883-892. doi: 10.1007/s00134-025-07910-4. Epub 2025 May 13. PMID: 40358717

The Question

Does targeting a higher mean arterial pressure (MAP) (80–85 mmHg) improve outcomes in older patients with septic shock, compared to usual care (65–70 mmHg)?

The Methods

This is a pragmatic, open-label, multi-center RCT from 29 ICUs in Japan.

Patients

Adults aged ≥65 years admitted to the ICU with septic shock. Patients needed vasopressors but were excluded if already on them for ≥3 hours.

Intervention

Target MAP of 80-85 mmHg maintained for 72 hours or until vasopressors stopped. Early vasopressin use was protocolized to reduce catecholamine exposure (if a norepinephrine dose of ≥ 0.1 μg/kg/min was needed to achieve the target MAP, vasopressin was initiated, and the dose was increased to 0.04 U/min).

Comparison

Target MAP of 65-70 mmHg.

Outcome

Primary outcome: 90-day all-cause mortality.

The Results

The trial was stopped early due to harm detected at interim analysis. 516 patients were analyzed (of the 752 targeted by their somewhat delusional power calculation.) Mean age was 78 and 53% had chronic hypertension.

Although the MAP was statistically higher in the high target group, the overall differences are not overly impressive (which is expected).

Mortality at 90 days was:

• 39.3% in the high-MAP group
• 28.6% in the control group
  • ARR: 10.7% (95% CI 2.6 to 18.9)

Although none were statistically significant, all adverse events (arrhythmias, ischemia, and bleeding) were more frequent in the high-MAP group.

My thoughts

This is a valuable study targeting an interesting question (even if it is not all that relevant to the average emergency physician). Whenever we talk about lower MAP targets, the question of relative blood pressure always comes up. What about patients with higher baseline blood pressures? Should we be targeting higher values in those patients? (Of course, this study can’t identify baseline blood pressure, but instead uses age as a surrogate, much like we would clinically.)

The results of this study seem realistic to me. Aggressively targeting numbers in ICU patients always seems to increase adverse events, without clear benefit. So, overall, I buy this data, and will allow it to guide my practice, but it is of course far from perfect.

This is an open label study, and therefore very prone to bias. Overall, I would have expected that bias to push the data towards the null hypothesis, as clinicians who were concerned about lower blood pressures might add therapies more often in the low target group. We might get a hint at that bias considering the fact that the median MAP in the low target group actually falls within the high target range by 36 hours. Overall, it is very difficult to know the direction of the bias in an open label trial.

Of course, mortality is at least somewhat objective and resistant to bias. The bigger problem might be the small sample size. Although I said I believe the results, in that higher is not going to be better, I don’t believe that targeting a higher MAP results in a 10% increase in mortality. That kind of change in mortality is essentially unheard of. It hints that the results are either bias, or simply skewed by random change, magnified in a small study that was stopped early. 

Speaking of which, this study was designed to be far too small from the outset. Once again, power calculations in medicine are completely ascientific. They powered this trial based on the assumption that they would see an absolute decrease in mortality of 10%. That is a difference unheard of in modern medicine, and definitely not expected by simply changing MAP targets. I understand that these power calculations are made pragmatically, based on the number of patients they think they will actually be able to enrol, but that basically negates the entire purpose of doing the power calculation. We need to completely rethink about we design and fund studies in medicine, because if continue to run poorly designed studies, all we are going to get are bad results. 

Generalizability could also be a concern, if there happen to be differences in hypertension and its consequences between a Japanese population and your population, given that the participants in this study were 97% of Japanese ethnicity.

I have not done a deep dive on this topic, but there are prior studies looking at high and low MAP targets in SEPSIS. For example, SEPSISSPAM compared a MAP of 80-85 to a MAP of 65-70 in 776 patients in septic shock, and found no difference in 28 day mortality. (Asfar 2014) Consistency is a reassuring feature in science, even when the individual studies are imperfect. 

Bottom line

In this open-label RCT, targeting a higher MAP (80–85 mmHg) in older patients with septic shock appeared to cause harm, including an increased mortality. At this time, there is no role for routine high MAP targets, even in patients with chronic hypertension. Stick to a target of 65–70 mmHg and focus on clinical signs of good perfusion rather than chasing numbers.

Other FOAMed

Evidence based medicine is easy

The EBM bibliography

Evidence based medicine resources

EBM deep dives

References

Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Hervé F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014 Apr 24;370(17):1583-93. doi: 10.1056/NEJMoa1312173. Epub 2014 Mar 18. PMID: 24635770

Endo A, Yamakawa K, Tagami T, et al. Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial. Intensive Care Med. 2025 May;51(5):883-892. doi: 10.1007/s00134-025-07910-4. Epub 2025 May 13. PMID: 40358717