Ketofol May Steady Blood Pressure During ERCP Sedation in Older Adults, Retrospective Study Finds

For older adults, an ERCP procedure is a double challenge: the endoscopic intervention itself, and the deep sedation required to tolerate it. A new retrospective cohort study from Düzce University Faculty of Medicine in Türkiye, published in BMC Geriatrics, examines which patients are most likely to experience dangerous drops in blood pressure during sedated ERCP and whether the choice of sedative cocktail makes a measurable difference. The answer, based on a decade of patient records, is that hemodynamic instability is strikingly common in this age group, and that a propofol-ketamine combination known as ketofol was associated with roughly half the odds of instability compared with propofol alone.

The research team, anesthesiologist Ali Ümit Eşbah and gastroenterologist Serkan Torun, analyzed records from patients aged 65 and older who underwent ERCP under deep sedation between 2015 and 2025. From that pool, 150 patients met the inclusion criteria. The study’s primary outcome, hemodynamic instability, was defined with clinical precision: either a drop of 30 percent or more in mean arterial pressure, the average pressure that drives blood through the body’s organs, or the need for vasopressor drugs to prop up failing circulation. This dual definition matters because it captures both the passive warning sign of a falling pressure curve and the active clinical response of an anesthesiologist reaching for rescue medication.

The headline finding is a frequency figure that should give clinicians pause: 46 of the 150 patients, or 30.7 percent, experienced hemodynamic instability during their procedure. Nearly one in three older adults in this cohort required either a substantial blood pressure intervention or vasopressor support. ERCP is already a demanding procedure for sedation teams because it is performed with the patient in a prone or semi-prone position, which restricts access to the airway and complicates monitoring. Combine that with the physiological vulnerabilities of advanced age, reduced cardiovascular reserve, blunted baroreceptor reflexes, and frequent comorbidities, and the sedation phase becomes one of the riskiest stretches of the entire procedure.

Using multivariable logistic regression, the researchers identified several independent predictors of instability. Advanced age itself increased risk, as did an American Society of Anesthesiologists physical status classification of III or IV, meaning severe systemic disease or life-threatening illness. Patients who arrived with a lower baseline mean arterial pressure were also more likely to cross the instability threshold, a finding that is intuitive but clinically actionable: the lower the starting point, the smaller the drop needed to reach the 30 percent reduction cutoff. Prolonged procedure duration emerged as a fourth predictor, likely reflecting both the cumulative cardiovascular stress of extended sedation and the fact that longer, more complex ERCPs tend to be performed in sicker patients.

The most provocative result concerns sedation strategy. Patients who received ketofol, a mixture of propofol and ketamine, had significantly lower odds of hemodynamic instability than those given propofol alone. The adjusted odds ratio was 0.50, with a 95 percent confidence interval of 0.25 to 0.99 and a p-value of 0.047. In plain terms, after accounting for other measured risk factors, the ketofol group’s odds of instability were about half those of the propofol-only group, and the result just crossed the conventional threshold for statistical significance.

The pharmacology behind this comparison is worth unpacking. Propofol is the workhorse of procedural sedation, prized for its rapid onset and quick offset, but it is a potent vasodilator and myocardial depressant. It lowers blood pressure partly by relaxing blood vessels and partly by blunting the sympathetic nervous system’s compensatory responses. Ketamine, by contrast, is a dissociative anesthetic that stimulates sympathetic outflow, typically raising heart rate and blood pressure. Blending the two is an attempt to have it both ways: propofol provides smooth hypnosis and amnesia while ketamine’s sympathomimetic activity counteracts propofol’s cardiovascular depression. The Düzce findings suggest that, in elderly ERCP patients, this counterbalancing may translate into a real reduction in clinically significant blood pressure crashes.

Because sedation strategy was not randomized, the researchers could not simply compare raw outcomes between groups; sicker patients may have been preferentially given one regimen over the other. To address this, they performed an inverse probability of treatment weighting analysis, or IPTW. This statistical technique reweights the two sedation groups as if treatment assignment had been random, based on each patient’s measured characteristics, thereby reducing the influence of confounding by indication. Under IPTW, the association held: the odds ratio for instability with ketofol was 0.55, with a 95 percent confidence interval of 0.31 to 0.98 and a p-value of 0.043. The consistency of the effect across two different analytical approaches strengthens the signal, even if it does not prove causation.

The authors are careful about the limits of their design, and that caution is warranted. As a retrospective, non-randomized study of 150 patients at a single center, residual confounding cannot be excluded. Unmeasured variables, such as the exact doses and titration patterns of sedatives, fluid management, the difficulty of individual cannulations, or subtle differences in patient physiology not captured in the chart, could all have influenced the results. The confidence intervals, while excluding unity, come close to it, and a finding with a p-value just under 0.05 in a modest sample should be treated as hypothesis-generating rather than practice-changing. A randomized controlled trial would be the definitive test of whether ketofol genuinely protects elderly patients or whether the association reflects selection of healthier patients for the combination regimen.

Still, the study fills a genuine gap. ERCP volumes are rising worldwide as populations age, and biliary disease remains one of the most common reasons older adults need urgent endoscopic intervention. Sedation-related hypotension in this population is not a trivial event: sustained low mean arterial pressure can compromise coronary and cerebral perfusion, precipitating myocardial injury or delirium in patients with little reserve to spare. Identifying who is at risk, the very old, the ASA III-IV patient, the one who starts with a marginal baseline pressure, and the one facing a long procedure, allows sedation teams to plan ahead with arterial line monitoring, preemptive fluid loading, or vasopressor availability.

The practical takeaway is twofold. First, hemodynamic instability during ERCP sedation in older adults is common enough, at roughly 31 percent in this cohort, that it should be anticipated rather than treated as a surprise. Second, the ketofol signal, replicated across multivariable regression and IPTW, gives anesthesiologists and gastroenterologists a concrete, testable option to weigh against propofol-only protocols in elderly patients. The study received no external funding, was approved by the Non-Interventional Clinical Research Ethics Committee of Düzce University, and is published open access. Whether ketofol’s apparent advantage survives the scrutiny of randomized trials remains to be seen, but for now it offers a data-driven starting point for a conversation that every sedation team caring for elderly ERCP patients should be having.

Subject of Research: Predictors of sedation-related hemodynamic instability during ERCP in older adults and the effect of ketofol versus propofol sedation

Article Title: Predictors of hemodynamic instability during ERCP sedation in older adults: impact of sedation strategy in a retrospective cohort

Article References: Eşbah, A. Ü., & Torun, S. (2026). Predictors of hemodynamic instability during ERCP sedation in older adults: impact of sedation strategy in a retrospective cohort. BMC Geriatrics. https://doi.org/10.1186/s12877-026-08405-7

Image Credits: AI Generated

DOI: 10.1186/s12877-026-08405-7

Keywords: ERCP, deep sedation, ketofol, propofol, ketamine, hemodynamic instability, older adults, geriatrics, anesthesiology, retrospective cohort, mean arterial pressure, vasopressors