Rethinking Routine Preoperative Benzodiazepines: Better Brain Health or Unnecessary Anxiety?

Introduction

The Movement Is Not One Decision

Few perioperative habits have been reassessed as visibly as the automatic dose of midazolam before transport to the operating room. The change has been driven by a reasonable and important goal: reduce avoidable sedative exposure in older adults and other patients at risk for delirium, respiratory depression, falls, or delayed recovery. [1,11,12,18]

The problem is that the slogan “no benzodiazepines” is clinically imprecise. It can refer to at least five different decisions: whether to premedicate every patient, whether to give one short-acting dose to a selected patient, whether to use a benzodiazepine intraoperatively, whether to give repeated postoperative doses, and whether to continue a chronic home regimen. Those decisions carry different evidence, different risks, and different alternatives.

The Clinical Bottom Line

Remove the automatic default. Routine benzodiazepine premedication has not shown a consistent patient-centered benefit. [3,4,5]

Do not turn caution into prohibition. Contemporary older-adult guidance and recent delirium studies do not justify a categorical ban on a single short-acting perioperative dose. [1,2,6,7,8]

Protect chronic users from withdrawal. Abruptly withholding a regularly used benzodiazepine can cause delirium, seizures, and destabilization. [16,17]

What Routine Premedication Actually Delivers

Benzodiazepines can produce anxiolysis, sedation, and anterograde amnesia. Those effects are not interchangeable. A patient who remembers less has not necessarily experienced less fear. A calmer preinduction blood pressure is not the same outcome as better global recovery.

The I-PROMOTE trial randomized 616 adults ages 65 to 80 years to oral midazolam 3.75 mg or placebo before elective surgery. Global satisfaction was essentially identical between groups, including in prespecified groups with higher anxiety or frailty. Amnesia was more frequent with midazolam. Delirium was too uncommon for the study to provide a definitive safety answer. [3]

The earlier PremedX trial reached a similar patient-experience conclusion using oral lorazepam 2.5 mg in adults younger than 70 years. Lorazepam did not improve satisfaction and was associated with slower extubation and lower early cognitive recovery. Because lorazepam is longer acting than midazolam, however, this trial should not be used as a direct estimate of low-dose intravenous midazolam risk. [4]

A 2025 systematic review of randomized trials found no reliable improvement in postoperative pain or quality of recovery and uncertain effects on satisfaction. The included trials were heterogeneous in drug, dose, timing, procedure, and comparator. The broad message, nonetheless, is consistent: routine administration has not earned its place as a universal quality-of-care measure. [5]

Distinguishing Between Routine Use and Targeted Clinical Indications

The failure of routine premedication to improve an average satisfaction score does not prove that no selected patient benefits. Trials summarize populations. They do not erase the clinical relevance of severe needle phobia, trauma-related distress, panic, a prior awareness experience, or an awake procedure in which cooperation depends on tolerable anxiety.

The operational change should therefore shift from automatic administration to an explicit indication. Before medication is given, the team should identify the symptom or procedural goal, consider low-risk nonpharmacologic support, and decide whether the expected benefit outweighs the patient-specific risk.

Postoperative Delirium: What the Newer Evidence Changes

Older guidance often treated benzodiazepines as a single delirium-promoting class. That concern remains clinically important, especially with chronic use, postoperative exposure, long-acting drugs, and combinations with other sedatives. Newer perioperative evidence, however, does not show a consistent large delirium effect from one short-acting dose or from all intraoperative use. [1,2,8,9,10]

Summary of Recent Delirium Evidence

Evidence setting	Main finding	What it means
I-PROMOTE randomized trial, ages 65 to 80	Oral midazolam did not improve global satisfaction; delirium was rare and not a powered endpoint. [3]	Questions routine benefit more than it settles delirium safety.
B-Free cluster randomized cardiac-surgery trial	Delirium occurred in 14.0% during restricted periods and 14.9% during liberal periods; adjusted odds ratio 0.92, 95% CI 0.84 to 1.01, P = 0.07. [6]	Restricting intraoperative benzodiazepines alone did not significantly reduce delirium. It was a policy trial, not a premedication trial.
Prospective cohort of 5,663 older noncardiac patients	Delirium was 12.9% with midazolam and 12.7% without; adjusted risk ratio 1.09, 95% CI 0.91 to 1.33, P = 0.35. [7]	No significant association was detected, but observational confounding remains possible.
2023 systematic review and meta-analysis	Across randomized and observational studies, perioperative benzodiazepines were not associated with increased postoperative delirium. [8]	The pooled signal argues against a simple class-wide rule, but heterogeneity and certainty limitations matter.
BioCog older-adult cohort	Long-term use was associated with delirium; immediate preoperative use was not statistically associated. [9]	Chronic exposure should not be treated as equivalent to a single preoperative dose.
Older-adult postoperative medication cohort	Postoperative hospital benzodiazepine use was associated with delirium, adjusted hazard ratio 3.23, 95% CI 2.10 to 4.99. [10]	Repeated or postoperative exposure may be a more important target than one monitored preoperative dose; causality was not established.

Two additional older-adult cohorts also failed to detect a statistically significant association between immediate midazolam premedication and postoperative delirium. Both were nonrandomized and cannot prove safety. They do, however, reinforce the distinction between a short monitored exposure and a broader benzodiazepine burden. [13,14]

The B-Free result deserves especially careful interpretation. It tested institutional policies during cardiac surgery, not a patient-level decision about preoperative anxiolysis. The trial also had published corrections, including a later table correction, without an identified change to the primary delirium result. [6]

What the Delirium Evidence Can and Cannot Say

The newer evidence can say that a categorical claim is not supported: not every short-acting perioperative benzodiazepine exposure increases delirium.

The evidence cannot say that a benzodiazepine is harmless in every older patient, that dose and timing do not matter, or that a negative observational association proves absence of risk.

It also cannot say that withholding one dose prevents long-term cognitive decline. Most available evidence concerns delirium or short-term recovery, not durable brain-health outcomes.

Brain Health Is Bigger Than One Drug

Postoperative delirium is a multifactorial syndrome. Baseline cognitive impairment, frailty, sensory deprivation, acute illness, sleep disruption, pain, immobility, hypotension, infection, and medication burden can all contribute. Current ASA and ESAIC guidance therefore emphasizes risk identification and multicomponent prevention rather than a single-drug rule. [1,12]

A hospital can remove midazolam from the default order set and still fail at brain health if it does not screen cognition, return eyeglasses and hearing aids, maintain orientation, support sleep, mobilize early, treat pain appropriately, reconcile home medications, and recognize delirium promptly. [1,12]

Conversely, a carefully selected short-acting dose does not negate an otherwise strong delirium-prevention program. The medication decision belongs inside the bundle, not in place of the bundle.

When Avoidance Is Especially Sensible

The threshold for preoperative benzodiazepines should be higher when the likely benefit is small and vulnerability to sedation is high. The AGS Beers Criteria flag benzodiazepines because older adults have greater susceptibility to cognitive impairment, delirium, falls, fractures, and dependence. At the same time, the criteria recognize selected appropriate uses such as periprocedural anesthesia and withdrawal treatment. [11]

The midazolam label requires individualized dosing, reduced initial doses in older or debilitated adults, continuous respiratory and cardiac monitoring, and immediate access to airway-skilled personnel and resuscitation equipment. It also warns that opioids and other central nervous system depressants can produce profound sedation and respiratory depression when combined with benzodiazepines. [18]

A high threshold is particularly reasonable for patients with baseline cognitive impairment or prior delirium, frailty, recurrent falls, limited pulmonary reserve, obstructive sleep apnea, anticipated opioid exposure, multiple sedatives, prior prolonged emergence, or little demonstrable preoperative anxiety. These factors do not create an absolute contraindication. They do, however, narrow the margin for a nonessential sedative. [1,11,18]

Avoiding the Trap of Replacing One Reflex With Another

Avoiding a benzodiazepine does not automatically make another sedative a better choice. Diphenhydramine, anticholinergics, gabapentinoids, opioids, and other centrally active drugs carry their own risks. Substitution should be driven by a defined indication and evidence, not by a desire to keep the premedication ritual intact. [1,11]

Severe Anxiety and Patient-Centered Exceptions

Preoperative anxiety is not a trivial inconvenience. It can impair communication, complicate intravenous placement or regional procedures, increase physiologic stress, and make an already threatening experience less tolerable. A 2025 before-and-after deimplementation study found that removing routine oral midazolam was associated with higher preinduction blood pressure and heart rate. It was not associated with mortality and did not measure delirium. [15]

That study does not prove that midazolam improves outcomes. It does, however, warn against deimplementation without a replacement process. A no-routine policy should be paired with a quieter and more predictable preoperative environment, clear explanations, realistic timing information, preservation of hearing and vision aids, support persons when feasible, and rapid access to a clinician when anxiety is substantial.

When distress remains severe, an individualized benzodiazepine may be reasonable after considering age, cognition, respiratory reserve, coadministered sedatives, procedure requirements, and monitoring. The goal should be explicit, the dose individualized, and the effect reassessed rather than assumed. [1,2,18]

Chronic Benzodiazepine Users: The Dangerous Category Error

A patient who takes alprazolam, clonazepam, lorazepam, diazepam, or another benzodiazepine regularly is not equivalent to a benzodiazepine-naive patient being considered for optional premedication. Chronic exposure can produce physiologic dependence even when the medication is taken as prescribed. [16,17]

The 2025 joint benzodiazepine tapering guideline warns that rapid dose reduction or abrupt discontinuation can cause life-threatening withdrawal, including seizures and delirium. It explicitly distinguishes patients taking benzodiazepines regularly from those receiving brief treatment. The FDA class warning similarly directs clinicians to use a gradual, patient-specific taper rather than abrupt discontinuation. [16,17]

A preoperative “no benzo” rule must never function as an unplanned taper. Medication reconciliation should establish the drug, dose, schedule, last dose, duration of use, and likely dependence. If oral administration will be interrupted, the perioperative team should create a continuity or substitution plan and avoid both withdrawal and accidental duplicate dosing. [16,17,18]

Withdrawal treatment, seizure management, and alcohol withdrawal are separate clinical indications. They should not be constrained by a policy written to reduce optional anxiolytic premedication. [11,12,16]

A Practical Risk-Stratified Approach

Patient or setting	Default stance	Key safeguards
Mild anxiety, low sedative risk, routine elective surgery	Do not give a benzodiazepine automatically.	Explain the plan, minimize avoidable waiting, offer nonpharmacologic support, and reassess.
Older, frail, cognitively vulnerable, fall-prone, or high respiratory risk	Use a high threshold; avoid when the expected benefit is small.	Review opioids and other sedatives, use the lowest individualized dose if selected, and monitor continuously. [1,11,18]
Severe anxiety, needle phobia, trauma-related distress, prior awareness, or an awake procedure	Consider targeted treatment rather than a blanket prohibition.	Define the goal, discuss tradeoffs, individualize dose and timing, maintain monitoring, and document response. [1,2,18]
Regular home benzodiazepine use or likely physiologic dependence	Do not abruptly withhold or taper on the day of surgery without a plan.	Reconcile medication, prevent withdrawal, coordinate NPO-compatible continuity, and avoid duplicate sedative exposure. [16,17,18]
Suspected benzodiazepine or alcohol withdrawal, or seizure indication	Treat as a distinct urgent indication.	Use the appropriate withdrawal or seizure pathway; do not apply an optional-premedication prohibition. [11,12,16]
Postoperative agitation or insomnia in an older adult	Do not reflexively give repeated benzodiazepine doses.	Look for pain, hypoxia, retention, infection, sleep disruption, medication toxicity, and delirium; use nonpharmacologic measures first when appropriate. [10,12]

Five Essential Questions Before Administering a Preoperative Dose

1. What problem are we treating? Mild anticipatory worry, severe panic, needle phobia, procedural intolerance, or a chronic medication need are not the same indication.
2. What is the patient’s vulnerability? Consider age, cognition, frailty, falls, pulmonary reserve, sleep apnea, and prior delirium.
3. What else will depress the central nervous system? Review opioids, alcohol, sedating antihistamines, gabapentinoids, antipsychotics, and other anesthetic agents.
4. Can the goal be met without medication? Clear information, a calmer environment, sensory aids, support, and shorter waiting may be sufficient for many patients.
5. How will safety be maintained? Individualize dose and timing, monitor ventilation and circulation, avoid rapid stacking, and reassess the clinical effect. [18]

How Hospitals Should Implement a No-Routine Policy

The most defensible institutional policy is “no routine benzodiazepine premedication,” not “no benzodiazepines.” The difference should be visible in order sets, staff education, and quality metrics.

• Remove automatic orders while preserving an easily accessible, indication-based option.
• Require medication reconciliation that identifies chronic benzodiazepine use and withdrawal risk before a dose is omitted.
• Screen for actual anxiety and cognitive vulnerability rather than assuming either one from age alone.
• Build sedative-stacking alerts for opioids, other central nervous system depressants, sleep apnea, and reduced pulmonary reserve. [17,18]
• Measure outcomes that matter: untreated distress, rescue medication, delays, patient experience, delirium, prolonged recovery, respiratory events, and withdrawal complications.
• Audit exceptions clinically, not punitively. Appropriate treatment of severe anxiety, a chronic regimen, withdrawal, or a procedure-specific need should not be labeled policy failure.

A successful deimplementation program should reduce low-value exposure without making patients prove that they are anxious enough to deserve humane care. It should also prevent a chronic medication from disappearing at the exact moment physiologic stress increases.

Acknowledging the Limitations of the Current Evidence

The evidence base does not permit a simple class-wide verdict. Studies combine oral and intravenous routes, short- and long-acting drugs, preoperative and intraoperative timing, single doses and repeated exposure, and cardiac and noncardiac procedures. Delirium ascertainment and follow-up also vary.

Many high-risk patients are excluded from randomized trials, including those with severe cognitive impairment, chronic benzodiazepine use, emergency surgery, or substantial psychiatric comorbidity. Observational cohorts are larger and more representative but remain vulnerable to confounding by indication, clinician selection, and unmeasured illness severity. [3,6,7,9,10,13,14]

The outcome most often studied is postoperative delirium, not long-term cognition. It is therefore more accurate to say that categorical avoidance has not been shown necessary for delirium prevention than to say that benzodiazepines are brain-safe or that eliminating one dose improves durable brain health.

Future Directions and Unanswered Questions in Perioperative Benzodiazepine Research

The field needs patient-level randomized trials that isolate a clearly defined preoperative dose, enroll cognitively vulnerable and chronically treated patients safely, use standardized delirium assessment, and measure anxiety, patient experience, respiratory events, withdrawal, and longer-term cognition. A 2026 randomized spine-surgery protocol illustrates that more targeted evidence is being developed, but no results were available at this review date.

Implementation research is also needed. The relevant comparison is not simply midazolam versus no midazolam. It is an automatic-drug workflow versus a structured anxiety and brain-health workflow that includes screening, communication, nonpharmacologic support, medication continuity, and selective rescue treatment.

 

References

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