Postprandial Hypotension, Frailty and Post-Induction Hypotension in Older Patients Undergoing Noncardiac Surgery

Background and rationale:

Post-induction hypotension, occurring within the first 20 minutes after induction of general anesthesia or until surgical incision, is one of the most frequent periods of intraoperative hypotension and is common in older patients undergoing noncardiac surgery. Its severity and duration are associated with myocardial injury, acute kidney injury and other adverse postoperative outcomes, making preoperative identification of high-risk older patients clinically important. Age-related cardiovascular and autonomic changes, including reduced baroreflex sensitivity and diminished beta-adrenergic responsiveness, limit the ability to compensate for the sympatholytic and vasodilatory effects of anesthetic agents.

Postprandial hypotension is a frequent but under-recognized hemodynamic disorder in older adults, with a pooled prevalence of 40.5% in a recent meta-analysis, and is associated with syncope, falls, cardiovascular events and mortality. It reflects inadequate compensation for splanchnic blood pooling after a meal. Because maintaining blood pressure both after a meal and after anesthesia induction depends on adequate autonomic and cardiovascular reserve, the preoperative postprandial blood pressure response may serve as a simple, non-invasive marker of the capacity to tolerate the hemodynamic stress of anesthesia induction. Frailty, a syndrome of reduced physiological reserve across multiple systems, has been independently associated with post-induction hypotension in older surgical patients (odds ratio 2.73).

The relationship between postprandial and post-induction hypotension has been proposed in a recently published prospective cohort protocol, but clinical data remain limited. This study aims to evaluate the association between preoperative postprandial hypotension and post-induction hypotension in patients aged 65 years and older undergoing elective noncardiac surgery, to examine the relationship of frailty with both conditions, and to assess whether postprandial hypotension and frailty are independently associated with post-induction hypotension.

Data collection:

Demographic and clinical data will be recorded for all patients using standardized data collection forms, including age, sex, height, weight, body mass index, smoking status, hemoglobin level and routine preoperative biochemical laboratory values, ASA physical status, comorbidities (summarized using the Charlson Comorbidity Index) and regular medications. Antihypertensive treatments will be classified as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, diuretics and other antihypertensive drugs, and the time of the last dose will be recorded. All medications will be continued according to routine practice and will not be changed for the study. Preoperative fasting duration, partial bowel preparation, baseline hemodynamic values, Edmonton Frail Scale and APAIS scores, type of surgery, anesthetic induction drugs and doses, perioperative fluid and vasopressor requirements, postoperative intensive care unit admission, and intensive care unit and total hospital length of stay will also be recorded.

Preoperative assessments:

On the evening before surgery, the standard hospital evening menu served at the routine dinner time will be used as the test meal for the assessment of postprandial hypotension. According to the hospital nutrition unit, the energy content of the standard evening menus is similar across days; no additional meal will be provided and meal content or timing will not be altered for the study. Meal start and end times and the proportion of the meal consumed will be recorded.

Systolic, diastolic and mean arterial pressure and heart rate will be measured in the sitting position on the upper arm with an appropriately sized cuff before the evening meal and at 30, 60, 90 and 120 minutes after meal completion. Measurements will be performed with the automated device routinely used for vital sign monitoring on the ward, using the standard vital sign measurement method; only the timing and frequency of measurements are study-specific. Whether antihypertensive medications are taken on the evening of the measurements, their timing, and whether they coincide with the meal or the postprandial measurement period will be recorded; usual medication timing will not be changed for the study. Postprandial hypotension will be defined as a decrease in systolic blood pressure of ≥20 mmHg from the pre-meal value, or a fall to ≤90 mmHg when the pre-meal value is ≥100 mmHg, within 120 minutes after the meal. To ensure an adequate meal load, only patients who consume at least 70% of the meal will be included in the primary postprandial hypotension analysis; patients who consume less will complete all measurements, but their data will not be included in the primary analysis.

During the preoperative period, frailty will be assessed with the validated Turkish version of the Edmonton Frail Scale (11 items covering 9 domains; total score 0-17). On the day of surgery, in the preoperative holding area and before any premedication, preoperative anxiety will be assessed with the validated Turkish version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS; total anxiety score 4-20).

Intraoperative data collection:

Standard ASA monitoring, including electrocardiography, non-invasive arterial blood pressure, peripheral oxygen saturation and end-tidal carbon dioxide, will be applied in the operating room. With an appropriately sized cuff placed on the upper arm, after at least 3 minutes of rest in the supine position and before any sedative, opioid or anesthetic agent is administered, systolic, diastolic and mean arterial pressure, heart rate and peripheral oxygen saturation will be measured twice at 2-minute intervals, and the mean of the two measurements will be recorded as the baseline value. The baseline mean arterial pressure will be used as the reference value for defining post-induction hypotension. The amount of intravenous fluid given before induction and the time of the last antihypertensive dose will be recorded.

From the start of anesthesia induction until 20 minutes after induction or surgical incision, whichever occurs first, systolic, diastolic and mean arterial pressure and heart rate will be recorded at 2-minute intervals. Balanced crystalloid infusion will be administered before induction and throughout the study period according to routine clinical practice. Induction and maintenance agents, intravenous fluids and vasopressor/inotrope treatment will be chosen by the attending anesthesiologist according to routine practice; they will not be standardized by the investigators, and treatment of hypotension will not be delayed or modified for the study. The anesthetic and analgesic agents, neuromuscular blocking agents and premedication used, together with their doses and times of administration, will be recorded. If post-induction hypotension develops, the type, dose and timing of vasopressor or inotropic agents, fluid administration, changes in anesthetic or analgesic doses, position changes and other hemodynamic interventions will be recorded in detail.Recovery from post-induction hypotension will be defined as the return of mean arterial pressure to ≥65 mmHg and to \>70% of the pre-induction baseline value.

As far as possible, the anesthesia team will be blinded to the patients' postprandial hypotension status and frailty scores to reduce performance bias. However, any clinically significant preoperative finding requiring intervention will be communicated to the clinical team to ensure patient safety.

Statistical analysis:

A total of 200 patients will be enrolled, allowing for possible data loss, to provide adequate power for the primary analysis and a sufficient number of events for the prespecified multivariable model.

Continuous variables will be presented as mean ± standard deviation or median (interquartile range) according to their distribution, and categorical variables as numbers and percentages. Between-group comparisons will be performed using the independent samples t-test or Mann-Whitney U test for continuous variables and the Pearson chi-square or Fisher exact test for categorical variables. Correlations will be assessed using Pearson or Spearman correlation analysis, according to the data distribution. A two-sided p value \<0.05 will be considered statistically significant.

Primary analysis: The incidence of post-induction hypotension will be compared between patients with and without postprandial hypotension and reported as an odds ratio with 95% confidence interval. Multivariable logistic regression will be used to assess the independent association between postprandial hypotension and post-induction hypotension, adjusted for Edmonton Frail Scale score, age, history of hypertension and chronic beta-blocker use.

Sensitivity analyses: The APAIS total anxiety score will be added to the primary model as a continuous variable, and the primary analysis will be repeated after excluding patients receiving beta-blockers.

Secondary analyses:

• Frailty: Edmonton Frail Scale scores will be compared between patients with and without postprandial hypotension and with and without post-induction hypotension; the association of frailty with post-induction hypotension will be assessed using logistic regression.
• Magnitude of blood pressure decreases: The Edmonton Frail Scale score will be correlated with the maximum postprandial decrease in systolic blood pressure, the lowest mean arterial pressure and the maximum decrease in mean arterial pressure after induction. The maximum postprandial decrease in systolic blood pressure will also be correlated with the lowest mean arterial pressure and the maximum decrease in mean arterial pressure after induction, and its association with post-induction hypotension will be assessed using logistic regression.

Patients aged 65 years and older scheduled for elective noncardiac surgery under general anesthesia who meet the criteria for postprandial hypotension (a decrease in systolic blood pressure of ≥20 mmHg from the pre-meal value, or a fall to ≤90 mmHg when the pre-meal value is ≥100 mmHg, within 120 minutes after the routine hospital evening meal on the day before surgery).

Patients aged 65 years and older scheduled for elective noncardiac surgery under general anesthesia who do not meet the criteria for postprandial hypotension.

Time frame: Up to 20 minutes after induction of anesthesia

Description: Proportion of patients with mean arterial pressure \<65 mmHg and/or a ≥30% decrease from the pre-induction baseline mean arterial pressure (mean of two measurements), measured non-invasively at 2-minute intervals from induction until 20 minutes after induction or surgical incision, whichever occurs first.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery

Proportion of patients with a decrease in systolic blood pressure of ≥20 mmHg from the pre-meal value, or a fall to ≤90 mmHg when the pre-meal value is ≥100 mmHg.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery

Change in systolic blood pressure (mmHg) from the pre-meal value at 30, 60, 90 and 120 minutes after the meal.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery

Change in diastolic blood pressure (mmHg) from the pre-meal value at 30, 60, 90 and 120 minutes after the meal.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery

Change in mean arterial pressure (mmHg) from the pre-meal value at 30, 60, 90 and 120 minutes after the meal.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery

Change in heart rate (beats/min) from the pre-meal value at 30, 60, 90 and 120 minutes after the meal.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery

Maximum decrease in systolic blood pressure (mmHg) from the pre-meal value.

Time frame: Before and at 30, 60, 90 and 120 minutes after the evening meal on the day before surgery.

Maximum decrease in systolic blood pressure from the pre-meal value, expressed as a percentage of the pre-meal value (%).

Time frame: Up to 20 minutes after induction of anesthesia

Lowest mean arterial pressure (mmHg) recorded after induction of anesthesia.

Time frame: Up to 20 minutes after induction of anesthesia

Maximum decrease in mean arterial pressure (mmHg) from the pre-induction baseline value.

Time frame: Up to 20 minutes after induction of anesthesia

Maximum decrease in mean arterial pressure from the pre-induction baseline value, expressed as a percentage of the baseline value (%).

Time frame: Up to 20 minutes after induction of anesthesia

Change in systolic blood pressure (mmHg) from the pre-induction baseline value.

Time frame: Up to 20 minutes after induction of anesthesia

Change in diastolic blood pressure (mmHg) from the pre-induction baseline value.

Time frame: Up to 20 minutes after induction of anesthesia

Change in heart rate (beats/min) from the pre-induction baseline value.

Time frame: Up to 20 minutes after induction of anesthesia

Time (minutes) from the onset of post-induction hypotension until mean arterial pressure returns to ≥65 mmHg and to \>70% of the pre-induction baseline value.

Time frame: Up to 20 minutes after induction of anesthesia

Proportion of patients receiving at least one dose of a vasopressor or inotropic agent.

Time frame: Up to 20 minutes after induction of anesthesia

Proportion of patients requiring a second bolus or an additional vasopressor or inotropic agent.

Time frame: Up to 20 minutes after induction of anesthesia

Cumulative dose of ephedrine (mg) administered after induction of anesthesia.

Time frame: Up to 20 minutes after induction of anesthesia

Cumulative dose of norepinephrine (µg), including bolus and infusion doses, administered after induction of anesthesia.

Time frame: Day of surgery

Proportion of patients admitted to the intensive care unit after surgery

Time frame: Up to 30 days after surgery

Duration of intensive care unit stay (days).

Time frame: Up to 30 days after surgery

Duration of hospital stay after surgery (days).

Association of Preoperative Postprandial Hypotension and Frailty With Post-Induction Hypotension in Geriatric Patients Undergoing Noncardiac Surgery: A Prospective Observational Cohort Study