Audio Coursesby JellypodLesson 06 of 15
Overview
Dive into the evolving role of ketamine in managing refractory status epilepticus. We’ll explore its mechanism, evidence from recent studies, and how it fits into clinical protocols. Jeremy and Hamish discuss what makes ketamine unique and where it stands in the treatment landscape.
Jeremy: Welcome back to the TIME podcast. I’m Jeremy.
Hamish: And I’m Hamish. This is where we take topics that feel increasingly settled in practice — and deliberately unsettle them.
Jeremy: Today we’re talking about ketamine in status epilepticus. And I think it’s worth saying upfront: this is one of those topics where practice has moved faster than consensus, and probably faster than evidence.
Hamish: And not accidentally. Ketamine feels intuitive here. It feels pharmacologically elegant. It feels like the sort of drug that should work when everything else doesn’t.
Jeremy: Which makes it dangerous in a very particular way.
Hamish: Exactly. Because when something feels inevitable, we stop interrogating it. We stop asking whether we’re using it because it’s effective — or because it helps us do something in a moment of therapeutic exhaustion.
Jeremy: And status epilepticus is exactly that kind of clinical space. High stakes, time pressure, cognitive overload, and a deep discomfort with waiting.
Hamish: So this episode isn’t about whether ketamine is “good” or “bad.” It’s about how it entered this space, what the evidence actually supports, and what risks we take — clinically and systemically — when we treat biological plausibility as if it were proof.
Jeremy: We’re also not going to pretend this is theoretical. Many of you listening will have used ketamine in refractory seizures. Some of you will have seen it work. Some of you will have seen nothing change at all.
Hamish: And that lived experience matters — but it can also mislead us, especially when outcomes are driven more by aetiology and time than by the drug we most recently added.
Jeremy: So we’re going to be very explicit about what we know, what we think we know, and what we actually don’t know yet.
Hamish: And we’re going to allow disagreement. Because if everyone listening agrees with everything we say, then we’ve probably failed the purpose of this conversation.
Jeremy: This is not a protocol episode. It’s not a recommendation. It’s a systems-level, evidence-honest discussion about a drug that now sits uncomfortably between rescue therapy and emerging norm.
Jeremy: Before we get into physiology or outcomes, we need to talk about scope. Because ketamine in status epilepticus doesn’t just raise clinical questions — it raises governance questions.
Hamish: And that’s because this isn’t off-label use in the casual sense. This isn’t ketamine for analgesia, or sedation, or behavioural disturbance where off-label use is common, culturally accepted, and usually low consequence.
Jeremy: This is off-label use in a condition with high mortality, unclear attribution of benefit, and frequent overlap with anaesthetic-level care.
Hamish: Which immediately raises the question: who actually owns the decision when ketamine is started?
Jeremy: Because in theory, we say “the system” or “the team.” In reality, it’s often one clinician at two in the morning, with limited EEG access, a patient who’s already had multiple agents, and a clock that keeps moving.
Hamish: And what’s interesting is that ketamine often enters not as a planned step, but as a salvage manoeuvre. It’s used when the usual sequence has failed, or when haemodynamics make the usual sequence unsafe.
Jeremy: Which means it’s frequently introduced outside formal protocols — even in well-resourced centres — because protocols rarely keep pace with edge-case reality.
Hamish: That’s not a criticism. It’s a description of how medicine actually works. But it does matter for how we think about governance.
Jeremy: Because if a drug lives mostly in the “rescue” space, it also lives in a governance grey zone. Documentation is thinner. Intent is assumed rather than stated. And responsibility becomes diffuse.
Hamish: There’s also a subtle medico-legal tension here. When ketamine is added late in refractory SE, it’s often framed as “we had no other options.”
Jeremy: Which feels defensible — but only if the record makes clear why it was chosen, what it was intended to achieve, and what the plan was if it failed.
Hamish: And that’s where things sometimes fall down. Not because clinicians are careless, but because the system doesn’t give them time or cognitive space to be explicit.
Jeremy: Another governance issue is escalation drift. Once ketamine is started, the clinical posture often shifts — sometimes unconsciously — from active reassessment to watchful waiting.
Hamish: Yes. There’s a sense that we’ve now deployed the “big gun,” so the next step is to see if it works. That can delay EEG, delay reassessment of aetiology, or delay hard conversations about prognosis.
Jeremy: And to be clear, that’s not a ketamine problem per se. That’s a human factors problem — the way we psychologically anchor to interventions.
Hamish: It’s also worth naming that ketamine use in SE doesn’t sit neatly within any one specialty’s territory.
Jeremy: Emergency physicians initiate it. Intensivists continue it. Neurologists interpret its effects — sometimes hours later — through EEG.
Hamish: Which means ownership is distributed. And whenever ownership is distributed, accountability can become blurred unless it’s actively managed.
Jeremy: So when we talk about scope, what we’re really talking about is this: ketamine in status epilepticus is not just a pharmacological choice. It’s a system decision.
Hamish: A decision that crosses departmental boundaries, handovers, and documentation standards.
Jeremy: And if institutions are going to allow or tolerate its use — which many already do — then that decision needs to be visible, shared, and supported.
Hamish: Not hidden behind phrases like “used as per ICU advice” or “given in extremis,” which explain everything and nothing at the same time.
Jeremy: So as we move into the evidence, keep that lens in mind. Because the strength of the data matters — but so does the context in which the drug is actually deployed.
Hamish: Before we get any further into drugs, we need to talk about definitions — not because people don’t know them, but because in practice they don’t behave the way textbooks suggest.
Jeremy: Status epilepticus is defined as five minutes or more of continuous seizure activity, or recurrent seizures without return to baseline consciousness.
Hamish: That’s the clean definition. The messy reality is that by the time many patients reach us, they’re already pharmacologically altered, intubated, paralysed, or post-ictal — or all of the above.
Jeremy: Which makes the distinction between convulsive, non-convulsive, and no longer seizing far less obvious than we’d like to admit.
Hamish: And that’s where diagnostic drift creeps in.
Jeremy: We label someone as “still in status” because they haven’t woken up, or because there’s intermittent motor activity, or because we’re uncomfortable with how long it’s taking.
Hamish: Or the opposite happens — we assume seizure control because the convulsions have stopped, when in reality the patient has transitioned into non-convulsive status epilepticus.
Jeremy: Which is where EEG becomes critical — and also where systems start to show their cracks.
Hamish: EEG access is not uniform. In some centres, continuous EEG is available quickly. In others, it’s delayed by hours or only available during business hours.
Jeremy: And that inequity fundamentally changes how drugs like ketamine are interpreted.
Hamish: Because if you don’t have EEG, seizure cessation becomes a clinical impression rather than an objective endpoint.
Jeremy: Which means when ketamine is started and the patient stops moving, we can easily tell ourselves a story that seizures have resolved.
Hamish: Even when we don’t actually know.
Jeremy: Let’s make this concrete. Picture a patient with prolonged convulsive status epilepticus, multiple benzodiazepine doses, second-line therapy on board, now intubated in the ED.
Hamish: Ketamine is started because haemodynamics are fragile and further propofol feels risky.
Jeremy: The motor activity stops. The patient remains deeply unresponsive. ICU admission is delayed due to bed pressure.
Hamish: EEG doesn’t happen for another six hours.
Jeremy: When it does, it shows ongoing non-convulsive status.
Hamish: So was ketamine ineffective? Or was it partially effective? Or did it suppress motor manifestations while electrographic seizures continued?
Jeremy: We often can’t answer that — and yet we still document “seizures controlled.”
Hamish: That’s not a clinician failure. That’s a system limitation colliding with a drug that changes how seizures look.
Jeremy: Ketamine complicates clinical assessment because it alters consciousness, motor output, and autonomic tone — all the cues we normally rely on.
Hamish: Which increases cognitive load at exactly the moment when teams are already saturated.
Jeremy: And this matters when we later interpret observational studies. Many report “seizure cessation” without consistent EEG confirmation.
Hamish: So when we read that ketamine was associated with seizure resolution, we need to ask: resolution by what definition, and measured how?
Jeremy: Another subtle issue is category creep. Once a patient has failed multiple agents, there’s a tendency to label them as refractory — even if adequate dosing or timing is unclear.
Hamish: Which again inflates apparent success rates for late-line therapies.
Jeremy: So before we even talk about mechanisms or trials, we need to acknowledge that status epilepticus is diagnostically unstable terrain.
Hamish: And any drug introduced into that terrain — ketamine included — will inherit that uncertainty.
Jeremy: So let’s talk about the pharmacology — because this is often where the ketamine argument feels strongest.
Hamish: Yes. On paper, ketamine makes a lot of sense in prolonged status epilepticus.
Jeremy: The classic narrative is that sustained seizure activity leads to internalisation of GABA_A receptors, reducing the effectiveness of benzodiazepines, barbiturates, and propofol.
Hamish: At the same time, NMDA receptor expression and glutamatergic excitation increase — so the longer seizures persist, the more NMDA-mediated pathways dominate.
Jeremy: Ketamine, as a non-competitive NMDA antagonist, theoretically targets that shift.
Hamish: And if you stop the story there, it sounds compelling.
Jeremy: It does. But I think this is where we need to be careful about over-intellectualising bedside decisions.
Hamish: This is where we disagree a bit.
Jeremy: Good.
Hamish: Because while receptor-level models aren’t sufficient, they’re not irrelevant either. We do see diminishing returns from GABAergic agents over time.
Jeremy: I agree they’re not irrelevant. But I worry that the elegance of the theory gives us a false sense of precision in an environment that’s anything but precise.
Hamish: Explain that.
Jeremy: Because in the ICU — or the ED — patients in refractory status epilepticus aren’t experiencing isolated receptor shifts. They’re acidotic, hypoxic, inflamed, hypotensive, often septic or post-anoxic.
Hamish: So the pharmacodynamic environment is completely different from the models the theory comes from.
Jeremy: Exactly. And when we say “NMDA antagonism,” we’re often stacking ketamine on top of benzodiazepines, propofol, barbiturates, sometimes volatile agents.
Hamish: Which makes it hard to know what’s actually doing what.
Jeremy: Right. At that point, the question isn’t “does ketamine work?” It’s “what does adding another CNS-active agent change in this system?”
Hamish: But I’d push back slightly. The haemodynamic profile of ketamine isn’t theoretical — that is clinically observable.
Jeremy: That’s fair.
Hamish: In patients who are already vasopressor-dependent, ketamine often allows us to avoid escalating propofol or barbiturates further.
Jeremy: I agree with that observation. But I’d argue that haemodynamic stability is a means, not an outcome.
Hamish: True — but in status epilepticus, maintaining cerebral perfusion pressure is not trivial.
Jeremy: Absolutely. But here’s the uncomfortable question: are we sometimes choosing ketamine because it lets the numbers look better, even if we’re uncertain about seizure control?
Hamish: That’s uncomfortable, but probably true in some cases.
Jeremy: And that’s where cognitive load comes in. Ketamine reduces hypotension, which reduces alarms, which reduces the immediate sense of crisis.
Hamish: But it may also mask ongoing electrographic seizures if EEG isn’t immediately available.
Jeremy: Exactly. So a drug that feels stabilising can paradoxically delay recognition of treatment failure.
Hamish: Another layer here is neuroprotection. Ketamine is often described as potentially neuroprotective through reduction of glutamate-mediated excitotoxicity.
Jeremy: But that evidence is overwhelmingly preclinical.
Hamish: And we have to be honest about that. Animal models, in vitro data — not robust human outcome data.
Jeremy: So when ketamine is framed as “neuroprotective,” that’s aspirational language, not evidence-based language.
Hamish: Which doesn’t mean it’s wrong — just that it shouldn’t drive confidence beyond the data.
Jeremy: So where I land is this: ketamine’s pharmacology gives us permission to explore, not permission to assume benefit.
Hamish: And I’d add: it also gives us a responsibility to be explicit about why we’re choosing it in a given patient — haemodynamics, failure of GABAergic agents, or lack of alternatives — rather than relying on the elegance of the mechanism.
Jeremy: Because once mechanism becomes narrative, it stops being a hypothesis and starts being belief.
Hamish: When people talk about ketamine in status epilepticus, they often reach early for the Ket-Mid trial.
Jeremy: And that’s understandable. It’s one of the few randomised studies in this space, and it tells a story that clinicians want to hear.
Hamish: Just to recap briefly — Othman and colleagues, 2025. A single-centre randomised trial in paediatric generalised convulsive status epilepticus, comparing midazolam alone with midazolam plus ketamine.
Jeremy: They reported higher early seizure cessation rates in the ketamine group, fewer repeat benzodiazepine doses, and lower intubation rates.
Hamish: And importantly, no clear increase in adverse events.
Jeremy: On the surface, that’s compelling.
Hamish: But this is where we need to be very honest about why this trial resonates.
Jeremy: Because it validates a frustration clinicians already feel — that benzodiazepines lose effectiveness the longer seizures go on.
Hamish: And it offers a solution that feels pharmacologically coherent and operationally simple.
Jeremy: But the moment we start asking whether this should change adult practice, the cracks appear.
Hamish: First, it’s paediatric.
Jeremy: Second, it’s single centre.
Hamish: Third, the pre-hospital seizure durations were long, and the aetiology profile — with a high burden of infectious causes — is not representative of many adult ED populations.
Jeremy: And fourth, the comparator matters. This wasn’t ketamine versus another second-line agent. It was ketamine added to midazolam.
Hamish: So the trial doesn’t tell us whether ketamine is superior to standard second-line therapy. It tells us that adding another agent early may increase the chance of seizure cessation.
Jeremy: Which raises a more uncomfortable question: was ketamine the key variable — or was it simply escalation intensity?
Hamish: That’s an important distinction. Because if the benefit comes from faster, more aggressive escalation, then ketamine may be a proxy rather than the mechanism.
Jeremy: This is where I think we need to resist the urge to treat this as a “ketamine works” trial.
Hamish: I agree — but I also think it’s too dismissive to say it tells us nothing.
Jeremy: Go on.
Hamish: I think it tells us that waiting is harmful. That repeated benzodiazepine dosing without mechanistic diversification may be a losing strategy.
Jeremy: That’s fair. But that insight doesn’t necessarily mandate ketamine.
Hamish: No — it mandates earlier recognition of failure.
Jeremy: Exactly. And here’s where motivated reasoning creeps in. We see a trial that supports a drug we already like, and we credit the drug rather than the strategy.
Hamish: And the danger is that we over-generalise. We move from “this worked in paediatric convulsive SE in one setting” to “ketamine should be used earlier.”
Jeremy: Without accounting for adult physiology, comorbidities, or different seizure aetiologies.
Hamish: There’s also a subtle outcome problem. Reduced intubation rates sound unequivocally good.
Jeremy: But in status epilepticus, intubation is not always a failure — sometimes it’s a deliberate strategy.
Hamish: So avoiding intubation may reflect seizure control, or it may reflect clinician comfort — or risk tolerance.
Jeremy: Which again makes interpretation tricky.
Hamish: So where does that leave us?
Jeremy: For me, Ket-Mid is a proof-of-concept trial. It shows ketamine can augment benzodiazepines in some contexts.
Hamish: But it doesn’t justify early routine use in adult status epilepticus.
Jeremy: And it certainly doesn’t resolve the harder question of what to do after second-line failure.
Hamish: If anything, it highlights how desperate we are for trials that look like real adult practice.
Jeremy: And how careful we need to be about letting our hopes run ahead of the data.
Jeremy: If ketamine has a home in the literature, it’s here — refractory and super-refractory status epilepticus.
Hamish: And it’s worth saying upfront: this is where certainty largely disappears.
Jeremy: The most comprehensive synthesis we have is the 2024 systematic review by Adhikari and colleagues. Nineteen studies, 336 patients.
Hamish: Predominantly observational cohorts and case series, spanning both adult and paediatric populations.
Jeremy: And almost universally, ketamine is introduced late — after failure of multiple antiseizure medications and anaesthetic infusions.
Hamish: Which already sets the stage for interpretation problems.
Jeremy: Exactly. Because when a drug is introduced as a rescue therapy, any apparent success is immediately confounded by selection.
Hamish: The patients who survive long enough to receive ketamine are, by definition, different from those who don’t.
Jeremy: And that’s before we even talk about concurrent therapies — midazolam, propofol, barbiturates, sometimes volatile agents — all running in parallel.
Hamish: So when studies report seizure resolution rates of 50 to 90 percent, the first question has to be: resolution compared to what?
Jeremy: Compared to ongoing seizures under maximal polypharmacy? Compared to imminent withdrawal of care? Compared to nothing?
Hamish: This is where the phrase “associated with seizure cessation” needs to be handled very carefully.
Jeremy: Because association in this context doesn’t just lack causality — it lacks a stable comparator.
Hamish: There’s also enormous heterogeneity in how “seizure control” is defined.
Jeremy: Some studies rely on clinical cessation of motor activity.
Hamish: Others require EEG suppression.
Jeremy: Some accept reduced seizure burden rather than complete cessation.
Hamish: And many don’t specify duration — whether control was sustained, transient, or immediately relapsed.
Jeremy: Which means we’re often comparing apples, oranges, and brief moments of quiet.
Hamish: Another recurring theme in the literature is that earlier ketamine use appears to be associated with higher response rates.
Jeremy: This is where I think we need to be particularly cautious.
Hamish: Because “earlier” often just means “in patients who were less sick.”
Jeremy: Or patients with reversible aetiologies. Or patients with better physiological reserve.
Hamish: So we risk mistaking timing for efficacy.
Jeremy: Exactly. And this is a very seductive narrative — if only we’d used ketamine sooner, this would have gone differently.
Hamish: Which may be true in some cases. But the data don’t allow us to separate that from survivorship bias.
Jeremy: Let’s bring this into the real world with a scenario many listeners will recognise.
Hamish: A patient presents with prolonged convulsive status epilepticus. Multiple benzodiazepine doses, second-line therapy administered, intubated, ongoing haemodynamic instability.
Jeremy: Propofol is limited by hypotension. Barbiturates are considered but deferred due to concern about cardiovascular collapse.
Hamish: Ketamine is started. The motor seizures stop.
Jeremy: There’s relief in the room.
Hamish: But EEG isn’t immediately available. ICU transfer is delayed due to bed pressure.
Jeremy: Six hours later, EEG shows ongoing non-convulsive status epilepticus.
Hamish: At that point, ketamine is framed as having “failed.”
Jeremy: But what actually failed?
Hamish: Was it the drug? The timing? The lack of EEG? The system’s inability to escalate quickly?
Jeremy: Or was the underlying aetiology — say, hypoxic-ischaemic injury — always going to dominate the outcome?
Hamish: These cases illustrate how difficult it is to attribute success or failure to any single agent.
Jeremy: And they also highlight another issue: ketamine often changes how seizures look without necessarily stopping the underlying electrical activity.
Hamish: Which can buy time — but can also create false reassurance.
Jeremy: On safety, the literature is relatively reassuring.
Hamish: Serious adverse events clearly attributable to ketamine are uncommon.
Jeremy: Reported issues include hypersalivation, transient tachyarrhythmias, and reversible transaminitis.
Hamish: Importantly, mortality in these cohorts appears driven by disease severity rather than ketamine dose or duration.
Jeremy: That’s helpful — but it also means ketamine hasn’t convincingly moved the hardest endpoint.
Hamish: Which brings us to the most uncomfortable truth of all.
Jeremy: In refractory and super-refractory status epilepticus, most interventions look similar when the underlying pathology is catastrophic.
Hamish: Ketamine may reduce seizure burden. It may stabilise physiology. It may allow other therapies to continue.
Jeremy: But none of that guarantees meaningful neurological recovery.
Hamish: And yet, because ketamine sometimes coincides with improvement, it becomes part of the narrative of rescue.
Jeremy: Which is human. But dangerous if it hardens into belief.
Hamish: So where does that leave us?
Jeremy: It leaves us recognising that ketamine in RSE and SRSE is best understood as a supporting actor, not a protagonist.
Hamish: And that any confidence we have in its effectiveness should be proportional to the quality of the data — which remains limited.
Jeremy: One of the reasons ketamine generates so much quiet disagreement is that it doesn’t live neatly in any one clinical domain.
Hamish: It’s not an “ED drug” in the traditional sense, and it’s not an “ICU drug” in the way barbiturates or volatile agents are.
Jeremy: In reality, ketamine in status epilepticus lives at the interface — between emergency medicine, intensive care, and neurology.
Hamish: And that interface is where most system failures occur.
Jeremy: Because the ED is where refractory status epilepticus is first recognised, escalation decisions are made, and physiological instability is actively managed.
Hamish: But ICU is where prolonged infusions, EEG-guided titration, and definitive neurocritical care usually occur.
Jeremy: Ketamine often bridges that gap.
Hamish: Which means it’s frequently initiated in the ED, continued during transfer delays, and then reinterpreted hours later once EEG becomes available.
Jeremy: That creates a unique risk profile — not because ketamine is dangerous, but because ownership is fragmented.
Hamish: Who decides to start it?
Jeremy: Who decides whether it’s working?
Hamish: Who decides when to stop it?
Jeremy: And perhaps most importantly — who carries responsibility if outcomes are poor?
Hamish: These questions are rarely answered explicitly in the moment.
Jeremy: They’re answered implicitly, through habit, hierarchy, and bed availability.
Hamish: Let’s talk about bed availability, because it quietly shapes ketamine use more than any guideline ever has.
Jeremy: When ICU access is delayed, ED clinicians are forced to manage patients in a holding pattern.
Hamish: Ketamine can feel like a stabilising bridge — haemodynamics improve, motor seizures stop, the immediate chaos settles.
Jeremy: But that very stabilisation can reduce the perceived urgency of transfer.
Hamish: Which introduces a subtle moral hazard.
Jeremy: Yes. Ketamine may buy time — but it may also spend time.
Hamish: Time during which ongoing electrographic seizures continue unnoticed.
Jeremy: Time during which definitive EEG-guided management is delayed.
Hamish: This isn’t a criticism of ED practice. It’s a description of how systems behave under pressure.
Jeremy: And it raises an uncomfortable question: are we sometimes using ketamine to compensate for system constraints rather than clinical need?
Hamish: That’s a hard question, but an important one.
Jeremy: Another interface issue is handover.
Hamish: When ketamine is started in the ED, the rationale is often implicit — “we needed something haemodynamically tolerable.”
Jeremy: But if that rationale isn’t explicitly communicated, ICU teams may inherit a therapy without clear intent.
Hamish: Is ketamine being used as an anticonvulsant? As an anaesthetic-sparing agent? As a bridge to EEG?
Jeremy: Or simply because nothing else felt safe at the time?
Hamish: Without that clarity, continuation becomes default rather than deliberate.
Jeremy: And default continuation is one of the most common ways therapies outlive their usefulness.
Hamish: This is why framing ketamine as an ED-versus-ICU issue misses the point.
Jeremy: The real issue is whether there’s a shared mental model across departments.
Hamish: A shared understanding of when ketamine is considered, what success looks like, and what failure triggers escalation or reassessment.
Jeremy: And whether that model is robust enough to survive handovers at three in the morning.
Hamish: Because if it isn’t, ketamine risks becoming a holding pattern drug — something that feels active but delays resolution.
Jeremy: So ketamine isn’t an ED drug or an ICU drug.
Hamish: It’s a systems drug.
Jeremy: And systems drugs demand systems-level governance.
Hamish: When ketamine is discussed in refractory status epilepticus, it’s often framed in contrast to “traditional” anaesthetic agents — midazolam, propofol, and barbiturates.
Jeremy: And usually in a way that makes ketamine sound like the gentler option.
Hamish: Less hypotension. Lower vasopressor requirements. Less respiratory depression.
Jeremy: All of which are broadly supported by observational data.
Hamish: But this is where comparison gets slippery, because we’re rarely comparing like with like.
Jeremy: Exactly. Ketamine is often introduced because the patient has already declared themselves haemodynamically fragile.
Hamish: So the fact that ketamine is associated with less hypotension may say as much about patient selection as about pharmacology.
Jeremy: And even when that haemodynamic stability is real, we need to ask what problem we’re actually solving.
Hamish: Because maintaining blood pressure is not the same thing as improving neurological outcome.
Jeremy: This is where I think the “vasopressor-sparing” narrative becomes dangerous.
Hamish: Say more.
Jeremy: When we describe ketamine as vasopressor-sparing, we imply that avoiding vasopressors is inherently good.
Hamish: But vasopressors are not a moral failure. They’re a tool.
Jeremy: Exactly. Sometimes the right decision is to accept vasopressor support in order to deliver definitive seizure control.
Hamish: So if ketamine allows us to avoid vasopressors but at the cost of incomplete seizure suppression, that trade-off may not be favourable.
Jeremy: And yet, because haemodynamics are visible and EEG often isn’t, we can end up optimising what we can see.
Hamish: Blood pressure stabilises. Heart rate settles. Alarms quieten.
Jeremy: And cognitively, that feels like success.
Hamish: Even if electrographic seizures continue.
Jeremy: This is a classic cognitive load problem. We gravitate toward interventions that reduce noise, not necessarily those that improve outcomes.
Hamish: Another comparison that often comes up is tachyphylaxis.
Jeremy: Yes. Benzodiazepines and propofol clearly show diminishing effect over time.
Hamish: Ketamine doesn’t exhibit the same pattern, which is often framed as a major advantage.
Jeremy: But again, absence of tachyphylaxis doesn’t equate to superiority.
Hamish: It simply means the drug behaves differently.
Jeremy: And when ketamine is layered onto multiple other agents, the question becomes whether we’re adding efficacy — or just adding complexity.
Hamish: Complexity that increases sedation depth, prolongs ventilation, and complicates neurological prognostication.
Jeremy: Another subtle issue is EEG interpretation.
Hamish: Ketamine produces EEG patterns that are unfamiliar to many clinicians.
Jeremy: Which can create interpretive uncertainty — are we seeing treatment response, drug effect, or ongoing pathology?
Hamish: That uncertainty can delay escalation or de-escalation decisions.
Jeremy: So when we compare ketamine to barbiturates or propofol, we need to be very clear about what we’re optimising for.
Hamish: Is it haemodynamic stability? Seizure suppression? EEG clarity? Speed of decision-making?
Jeremy: Because different agents optimise different dimensions — and no agent optimises all of them.
Hamish: This is where I think ketamine risks becoming a compromise drug.
Jeremy: Meaning?
Hamish: A drug that feels like it splits the difference — not too hypotensive, not too suppressive — but may not decisively achieve any one goal.
Jeremy: That’s uncomfortable, but probably accurate in some cases.
Hamish: And again, this isn’t an argument against ketamine.
Jeremy: It’s an argument against unexamined comparisons.
Hamish: Because when we say “ketamine is better tolerated,” we need to finish the sentence: better tolerated for what purpose?
Jeremy: And by whom — the patient, the clinician, or the system?
Jeremy: This is probably the point in the episode where people start asking, “Alright — but what would I actually do on Monday morning?”
Hamish: And the honest answer is: there isn’t a clean algorithm waiting for you.
Jeremy: So instead of pretending there is, let’s talk about the real decisions leaders and senior clinicians are already making — often without naming them.
Hamish: The first question is about thresholds. Not drug choice — thresholds.
Jeremy: How long are you willing to tolerate ongoing seizures before escalating to anaesthetic-level care?
Hamish: And who gets to decide that threshold at two in the morning?
Jeremy: Because if that threshold is implicit rather than explicit, escalation becomes inconsistent — and retrospective justification becomes inevitable.
Hamish: The second question is about intent. When ketamine is started, what is it actually for?
Jeremy: Is it being used as an anticonvulsant of last resort?
Hamish: As a haemodynamically tolerable anaesthetic?
Jeremy: As a bridge while waiting for ICU, EEG, or senior review?
Hamish: Or — and this is uncomfortable — as a way to feel that something decisive has been done?
Jeremy: Those are very different intents. And if intent isn’t explicit, success and failure can’t be meaningfully judged.
Hamish: The third question is about ownership across time.
Jeremy: If ketamine is started in the ED and continued in ICU, who owns the reassessment?
Hamish: Who decides when the trial has failed?
Jeremy: And who carries responsibility if the patient deteriorates neurologically days later?
Hamish: Because distributed care without distributed accountability is one of the most common ways systems fail quietly.
Jeremy: The fourth question is about resource reality.
Hamish: EEG access, ICU beds, neurology availability — these are not uniform, and pretending they are doesn’t make better decisions.
Jeremy: So when ketamine is used to stabilise a patient while waiting for resources, that may be entirely appropriate.
Hamish: But leaders need to be honest about when ketamine is compensating for system delay rather than clinical need.
Jeremy: Because once a drug starts masking resource strain, the incentive to fix the strain weakens.
Hamish: That’s the moral hazard piece.
Jeremy: And the final question is about documentation and narrative.
Hamish: How do we write about ketamine use in a way that reflects uncertainty rather than certainty?
Jeremy: Because notes that say “seizures controlled” close doors that may still need to be open.
Hamish: Whereas notes that say “motor activity suppressed; EEG pending” preserve clinical honesty.
Jeremy: That’s not defensive documentation. That’s accurate documentation.
Hamish: So the Monday morning challenge isn’t to write a ketamine protocol.
Jeremy: It’s to decide whether your system tolerates ambiguity — and if so, whether it does so deliberately or accidentally.
Hamish: Because ketamine isn’t testing our pharmacology knowledge.
Jeremy: It’s testing our governance, our communication, and our willingness to sit with uncertainty.
Jeremy: When we step back from ketamine itself, what’s striking is how much weight this drug has taken on.
Hamish: Yes. Ketamine has become more than a medication. It’s become a symbol.
Jeremy: A symbol of escalation. Of seriousness. Of having reached the edge of conventional care.
Hamish: And that’s exactly why it deserves scrutiny.
Jeremy: Because when a drug starts to carry meaning beyond its evidence base, it begins to shape behaviour in ways we don’t always see.
Hamish: It shapes how long we wait. How hard we push. How comfortable we are sitting with uncertainty.
Jeremy: And how we tell the story of what happened afterward.
Hamish: One of the risks here is that ketamine becomes a kind of moral reassurance.
Jeremy: A way of saying — to ourselves, to families, to teams — that we did everything.
Hamish: Even when “everything” is poorly defined.
Jeremy: And the danger is not that ketamine is used.
Hamish: The danger is that its use allows us to stop asking harder questions.
Jeremy: Questions like: are we escalating because the evidence supports it — or because escalation feels safer than restraint?
Hamish: Are we acting in the patient’s interests — or in the system’s interests?
Jeremy: And are we honest about how much of what happens in refractory status epilepticus is driven by pathology we can’t reverse?
Hamish: There’s a temptation, especially in critical care, to equate action with virtue.
Jeremy: But sometimes good judgment looks like clarity rather than intensity.
Hamish: Clarity about goals. About limits. About uncertainty.
Jeremy: Ketamine doesn’t remove those responsibilities. If anything, it sharpens them.
Hamish: Because once a drug feels inevitable, it becomes harder to say no — and harder to explain why.
Jeremy: So perhaps the real question isn’t “Should we use ketamine in status epilepticus?”
Hamish: It’s “What do we need in place so that, when we do use it, we’re still thinking clearly?”
Jeremy: Clear intent. Clear handover. Clear reassessment.
Hamish: And clear acknowledgment that biology, evidence, and systems don’t always align neatly.
Jeremy: Ketamine may turn out to have a defined, evidence-supported role in the future.
Hamish: Or it may remain a useful but limited adjunct in a very narrow group of patients.
Jeremy: What matters now is that we don’t let confidence run ahead of data — or let systems quietly outsource judgment to a drug.
Hamish: Because in the end, ketamine doesn’t make decisions.
Jeremy: We do.
Jeremy: That brings us to the end of this episode of the TIME podcast.
Hamish: If there’s one thing we hope you take away, it’s not a position on ketamine — it’s a sharper awareness of how evidence, systems, and judgment interact when certainty is thin.
Jeremy: This podcast is produced by Clintix, the team behind the TIME podcast and a range of educational initiatives supporting clinicians across emergency medicine, intensive care, anaesthesia, and acute care more broadly.
Hamish: Clintix also develops Clintix Pro, an AI-powered study companion designed around Australian curricula and exams, helping trainees and clinicians focus their learning where it matters most.
Jeremy: As always, the goal of this podcast isn’t to tell you what to think — it’s to give you better questions to take back to your departments, your governance meetings, and your Monday mornings.
Hamish: Thanks for listening.
Jeremy: We’ll see you next time.
