Drug effects as a clock check¶
Infusion pumps, the rapid infuser and the cerebral oximeter share no waveform with the reference. Drug effects that follow infusions at plausible delays (propofol to BIS in about 2 minutes, fluid to CVP in about 30 s) bound their clocks to well within a minute of the recorder.
| Date | 2026-10-13 |
| Status | current |
| Methods | One event, two clocks |
| Techniques | Null controls |
| Devices | Infusion pumps, FMS rapid infuser, Invos, BIS monitor, SNUADC |
| Variables | Infusion pump rates and volumes, FMS rapid infuser, Invos regional oxygen saturation, BIS index |
Background¶
Physiology is a soft link: a drug's onset has a known range, not a known value, so it bounds a clock offset rather than measuring it. A response that comes before its cause would expose a clock error.
Data¶
1,529 cases (1,500 with Orchestra pumps, plus every FMS and Invos case). Every event type was also measured at random times with the same exclusions.
Results¶
| Event → response | Cases (events) | Responded (controls) | Latency p10 / p50 / p90 (s) | Verdict |
|---|---|---|---|---|
| Propofol start → BIS below 60 for 30 s | 497 (499) | 90% | 70 / 132 / 382; none ≤ 0 | Plausible |
| FMS flow over 100 mL/min → CVP rise ≥ 2 mmHg | 13 (67) | 84% (34%) | 3 / 32 / 129 | Plausible |
| FMS flow → MAP rise | 13 (68) | 90% (75%) | 2 / 34 / 136 | Weak |
| Remifentanil up → HR fall ≥ 3 bpm | 1,282 (1,691) | 93% (73%) | 26 / 110 / 274 | Weak |
| Phenylephrine or norepinephrine step → MAP rise | 27–32 | 63–71% (65–67%) | median 108–109 | Not distinguishable |
| Invos rSO2 against SpO₂ | 30–31 | median r 0.13 | — | Uninformative |
Discussion¶
Propofol to BIS is the strongest check: arm-brain circulation plus effect-site equilibration fits 1–3 minutes, and no response precedes its infusion. Vasopressor and remifentanil responses are matched too often at random times to test a clock, and Invos has no usable shared signal.
Worked examples¶
| Example | Side | Status | Summary |
|---|---|---|---|
| A cerebral autoregulation index from arterial pressure and cerebral oxygenation | time | planned | A moving correlation between mean arterial pressure and INVOS cerebral oxygenation, and how lag between the two devices changes it. |
| Time from a vasopressor bolus to the pressure response | both | planned | How quickly arterial pressure responds to a phenylephrine or ephedrine bolus, with the charted dose times' rounding taken into account. Not feasible in VitalDB, which records bolus totals but no bolus times; kept for a dataset that does. |