High Blood Pressure Target in Septic Shock: A Risky Bet for Older Patients?

The Big Question in Septic Shock

Hey there! Let’s dive into something pretty crucial in the world of critical care – how we manage blood pressure in folks battling septic shock, especially our older population. Septic shock, as you might know, is a really severe form of sepsis, where the body’s response to infection causes dangerously low blood pressure despite getting fluids. It’s a tough situation, and sadly, the mortality rate is quite high, even in places with top-notch healthcare.

Now, one of the key things doctors grapple with is finding the sweet spot for blood pressure. We need it high enough to get blood to all the vital organs, but not so high that we cause other problems. For years, there’s been a bit of a debate about the optimal target for Mean Arterial Pressure (MAP) in these patients. Some studies, mostly from Europe and North America, suggested that aiming for a higher MAP (like 80-85 mmHg) might not be all that helpful in general vasodilatory shock.

But here’s the twist: some previous research hinted that maybe, just maybe, a higher MAP target *could* be beneficial for patients with chronic hypertension. You know, the folks whose bodies are used to running at a higher pressure. Plus, how blood flow is regulated (that’s autoregulation for you science buffs!) can vary a lot depending on things like age, the specific disease, and how sick someone is. So, we really needed to look at different groups and regions.

Setting the Stage: The OPTPRESS Trial

This is where the OPTPRESS trial comes in. I was really interested to see this study because it tackled a few important gaps. First, it focused specifically on older patients (aged 65 and over) with septic shock. Second, it was conducted in Japan, a region that hasn’t been as represented in these kinds of trials, and where chronic hypertension is super common among older folks (like, 66.9% common!).

The researchers set up a multicentre, pragmatic, open-label, randomised controlled trial across 29 hospitals in Japan. They took patients who met the criteria for septic shock, were 65 or older, and were admitted to the ICU. They split them randomly into two groups: one aiming for a high MAP target (80-85 mmHg) and the other for a standard target (65-70 mmHg). This target was maintained for up to 72 hours or until they didn’t need vasopressors anymore.

They also did something a bit different – they used a protocol that included early, concomitant use of vasopressin alongside norepinephrine. The idea here was to potentially minimise some of the adverse effects that can come from high doses of catecholamines like norepinephrine.

Trial Details and Early Stop

The trial kicked off in July 2021 and was planned to enrol over 800 patients. However, things took an unexpected turn. Based on an interim analysis – basically, a check-in while the trial is still running – the results suggested that the high-target strategy wasn’t just *not* helping, but it might actually be causing harm. Because of this, the trial was stopped early in December 2023.

In the end, they included 518 patients in the analysis. About half were in the high-target group (258 patients) and half in the control group (260 patients). The patients were all Japanese, with a median age of 78. Common sources of infection were the abdomen, urinary tract, and lungs. The baseline characteristics were pretty similar between the two groups, including the history of chronic hypertension, which was present in just over half of the patients in both arms.

The study was pragmatic, meaning they tried to keep it as close to real-world practice as possible. Fluid resuscitation was left to the clinician’s judgment, not a strict 30 mL/kg rule, acknowledging concerns about excessive fluid in older adults. Patients who had already been on vasopressors for more than 3 hours before enrolment were excluded.

Randomisation was done centrally and stratified by age (<80 vs. ≥80) and history of chronic hypertension. While the treating physicians knew which group the patient was in (it was open-label), the statisticians analysing the data were kept in the dark until everything was locked down. This helps reduce bias in the analysis.

How the Targets Were Managed

The goal was to keep patients within their assigned MAP range for 72 hours. In the high-target group, if a patient had a potential vasopressor-related adverse event, the target could be lowered to 65 mmHg. After 72 hours, the MAP target was up to the doctor.

Blood pressure was mainly measured non-invasively on the arm, which makes sense for generalizability outside of just the most high-tech ICUs. The protocol encouraged early vasopressin use if norepinephrine doses went above a certain threshold (≥0.1 µg/kg/min), aiming to keep catecholamine doses lower.

Other aspects of care, like fluid volume, antibiotics, ventilation, RRT, and sedation, were largely left to the treating physician’s discretion, following standard guidelines where possible. This pragmatic approach reflects real-world ICU management.

The Not-So-Great News: Outcomes

Now, for the main findings. The primary outcome was all-cause mortality at 90 days after randomisation. And here’s the crucial part: 101 patients (39.3%) in the high-target group died compared to 74 patients (28.6%) in the control group. That’s a pretty significant difference, with a risk difference of 10.7% (95% confidence interval, 2.6–18.9). Basically, aiming for that higher MAP significantly increased the risk of death for these older patients.

Looking at secondary outcomes, it wasn’t much better for the high-target group. For instance, renal replacement therapy (RRT)-free days at 28 days were shorter in the high-target group (meaning they needed RRT for longer or died sooner). All the main safety outcomes, including arrhythmias, thromboembolism, ischemia not caused by clots, and bleeding requiring transfusions, happened more often in the high-target group.

Interestingly, they checked if having chronic hypertension made a difference, but no clinical benefits were seen for the high-MAP strategy in any subgroup, including those with known chronic hypertension. This goes against the idea that hypertensive patients might tolerate or benefit from a higher MAP target in this setting.

Why Did This Happen?

So, why did targeting a higher MAP seem harmful here? The study authors discussed a few possibilities. Even though they used vasopressin early to try and limit norepinephrine, the cumulative amount of vasopressors used was still higher in the high-target group. It’s possible that the risks associated with higher doses of vasopressors – like potential organ ischemia from excessive vasoconstriction – outweighed any potential benefit of the higher pressure, especially in older, more vulnerable patients.

While adverse events were more frequent in the high-target group, they didn’t see a difference in deaths specifically due to ischemic events, which is a bit counterintuitive if vasoconstriction was the main culprit. This suggests the picture might be more complex. Maybe it’s not just ischemia, but other effects of vasopressors, like potential immune system impacts (some studies suggest norepinephrine might suppress the immune system or promote bacterial growth in models).

They also looked at kidney function, as some previous studies hinted a higher MAP might help the kidneys in hypertensive patients. But in OPTPRESS, they didn’t see that benefit – RRT-free days were worse, and there was no improvement in major adverse kidney events. Differences in the study populations (age, kidney disease prevalence) might explain this.

Looking Ahead: Personalised Care?

This trial adds crucial evidence, especially from a population and region not heavily studied before. It reinforces the idea from other trials that higher MAP targets in vasodilatory shock aren’t universally beneficial and can be harmful, particularly in older adults.

The results also make you think about “personalised resuscitation.” Could we tailor blood pressure targets based on an individual patient’s pre-existing conditions, like their usual blood pressure or heart function? It makes sense in theory, and some studies in different settings (like surgery) show promise. But in the chaos of an emergency like septic shock, getting detailed information about a patient’s baseline can be tough, and many people have undiagnosed conditions.

The authors suggest future research should look into personalised haemodynamic management, perhaps using tools like echocardiography to assess heart function, to see if we can find the right target for the right patient.

A Few Caveats

Like any study, OPTPRESS had its limitations. It was open-label, meaning the doctors knew which group the patients were in. This could potentially influence how they managed care, although the primary outcome (death) is pretty objective. The randomisation process might not have been perfectly concealed in practice. Determining chronic hypertension status relied on available information at enrolment, which might not always be accurate in an emergency.

There wasn’t a super strict protocol for how to adjust vasopressors, which could lead to variations in how quickly targets were reached or how precisely MAP was controlled. The estimated mortality rate they used to plan the study size was higher than what they actually observed, which could affect the study’s power if it hadn’t been stopped early for harm.

Also, reporting of non-serious adverse events might have been incomplete, and detailed timing of events after the initial 72 hours wasn’t always available. Finally, being a single-country trial with ethnic homogeneity means we need to be a little cautious about applying these results directly to *all* older patients with septic shock everywhere, although the findings align with trends from other regions.

Wrapping It Up

So, what’s the takeaway from OPTPRESS? For older patients (65+) with septic shock, at least in this Japanese population, aiming for a high MAP (80-85 mmHg) was harmful compared to the standard 65-70 mmHg target. This was true even with a strategy designed to minimise catecholamine side effects and regardless of whether the patient had chronic hypertension.

It seems pretty clear from this study that pushing for a higher blood pressure target in this vulnerable group is a risky move. Until we get more evidence, perhaps from studies exploring truly personalised approaches, it seems wise to be really careful about using excessive vasopressors in older patients with septic shock and stick closer to the standard, lower MAP targets.

Source: Springer