Overview
Low, Medium and High are bounded effect levels, not administered doses. The vascular model generally normalizes these levels to one-third, two-thirds and full effect. ERA, PDE5 inhibition and sotatercept instead use Off/On: On preserves the former Medium endpoint (two-thirds internal intensity). Finite positive values in older sessions select that same On endpoint, retaining numeric session compatibility. Multiple drugs can contribute to a shared resistance, filling or contractility term; their labels remain available in the paused intervention reference.
There is no general pharmacokinetic simulation. Infusion onset, renal clearance, accumulation, receptor saturation, changing electrolytes, lactate and toxicity are not predicted. Turning a control off restores the reference calculation rather than waiting for a biological half-life. For chronic PH therapies, this compares established-treatment endpoints; it does not represent clinical withdrawal or immediate onset/offset.
Families and coupled responses
| Family | Modeled action and important interactions |
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| Norepinephrine, phenylephrine, vasopressin | Raise systemic vascular tone. Higher pressure may accompany lower native output when LV afterload or RV delivery limits ejection. Phenylephrine has a pulmonary-load term; HOCM can benefit from increased afterload. |
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| Dobutamine, epinephrine, dopamine, milrinone | Increase contractile support with differing systemic/pulmonary tone effects. Fixed obstruction limits recruitment; dynamic obstruction, depletion or hypotension can reverse benefit. Epinephrine/dopamine use nonlinear dose-level tone terms. |
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| Isoproterenol, ephedrine, atropine | Alter rate and/or vascular tone through distinct pathways. Atropine improves selected vagal sinus/AV-node responses but is not a universal cure for distal block or vasodepression. |
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| Nitroglycerin, nitroprusside, amyl nitrite | Reduce vascular tone and/or filling. Depletion, external constraint and dynamic obstruction can worsen. Selected well-perfused high-afterload LV failure or AR can gain forward flow; this is not a blanket treatment rule. |
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| Inhaled nitric oxide, IV epoprostenol | Inhaled NO illustrates a rapid pulmonary response; IV epoprostenol illustrates an established titrated infusion with a moderately robust selected response. Both reduce elevated pulmonary resistance; systemic dilation is assigned to epoprostenol. Greater pulmonary return can increase wedge when the left heart cannot accept additional flow. |
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| ERA, PDE5 inhibition, selexipag, oral/SC treprostinil, sotatercept | ERA and PDE5 inhibition have distinct representative established-treatment effects. Selexipag and oral/SC treprostinil share the prostacyclin pathway with epoprostenol, with bounded overlap rather than independent full-strength stacking. Sotatercept represents a sustained follow-up endpoint around 24 weeks rather than an acute vasodilator response. Chronic PVR benefit is restricted to the selected precapillary or compatible elevated-PVR/low-wedge teaching phenotype; systemic loading can still change outside it. |
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| Fluids, furosemide | Change filling with phenotype-dependent forward response. Underfilled states may recruit flow; already congested/limited ventricles can gain pressure with little flow. No cumulative intake, urine output or bleeding balance is integrated. |
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| Metoprolol, digoxin | Rate/conduction changes are handled separately from negative or modest positive inotropy. Beta blockade opposes selected catecholamine effects; both can worsen protective bradycardia/escape or pre-excited AF scenarios. |
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How combined medications are resolved
Systemic resistance starts from the current vascular state and is multiplied by a combined drug factor. Pulmonary resistance receives a separate factor. Nominal flow receives a bounded, phenotype-specific multiplier; filling pressures receive preload and contractility contributions. The engine then resolves PA pressure, RV gradient and systemic pressure from the resulting flow/resistance.
Severe valve penalties use independent valve burdens. Mild disease does not inherit a full severe-stenosis penalty. A pulmonary vasodilator does not guarantee systemic improvement when severe MS, AS or LV failure constrains flow. Drug effects are not a list of independent fixed BP changes.
Pulmonary therapies: additive unloading and timing
The separate pulmonary-therapy module reduces elevated PVR and then the shared circulation solves mean PA pressure from PAWP + PVR × CO. It does not subtract fixed mmHg effects. The teaching reference is min(baseline PVR, 1.2 WU); only resistance above that reference is reduced. The 1.2-WU reference and every response strength are original synthetic choices, not a physiologic universal minimum or a fitted dose-response model.
On selects an illustrative excess-PVR reduction of 18.67% for an ERA, 16.67% for a PDE5 inhibitor and 20% for the sustained sotatercept endpoint (displayed here rounded; calculations retain precision). This is the former Medium endpoint, not a clinical dose or trial-calibrated response. The remaining graded agents retain full-intensity reductions of 48% for IV epoprostenol, 22% for selexipag, 24% for oral treprostinil, 42% for SC treprostinil and 40% for inhaled NO; their Low/Medium/High controls use one-third, two-thirds and full intensity. Independent pathway factors multiply the resistance that remains, providing additional unloading without adding absolute pressure reductions or forcing a negative PVR. The four IP-family contributions (epoprostenol, selexipag, oral treprostinil and SC treprostinil) share one bounded response: the strongest contribution first, with each weaker effect then multiplying the remaining fraction by (1 − 0.25 × effect). With two agents this preserves the previous stronger-plus-quarter-weaker calculation. This is not independent full-strength stacking. The route-specific coefficients are original teaching ranges, not dose equivalence, empirical route superiority or head-to-head efficacy estimates.
The systemic IP-family resistance fractions at full intensity are 20% for IV epoprostenol, 8% for selexipag, 9% for oral treprostinil and 18% for SC treprostinil, resolved with the same strongest-plus-residual rule. ERA and PDE5 inhibition use their On endpoint to subtract two-thirds of the internal 7% and 10% systemic factors respectively (about 4.67% and 6.67%). These are original coupled loading assumptions, not observed route-potency estimates. The selected left-return load is 4 × [shared IP(epoprostenol, 0.25 × selexipag, 0.30 × oral treprostinil, 0.85 × SC treprostinil) + NO + 0.4 × ERA + 0.3 × PDE5] × left-load limitation; chronic contributions first receive the phenotype scope guard. It illustrates filling-pressure loading and is not a prediction of pulmonary edema or clinical benefit.
The common model still handles milrinone, other vasoactive drugs, systemic resistance, ventricular reserve, valve obstruction and respiration. There is no second legacy NO/epoprostenol subtraction. Pulmonary afterload relief can recruit forward flow and reduce right filling pressure, with bounded recruitment up to 35%; rising flow can offset part of a PA-pressure fall. Pulmonary venous return can instead raise wedge in mitral/left-heart disease. Sotatercept has no direct acute systemic dilation term and only a small selected flow-recruitment contribution.
When a pulmonary therapy is active and pulmonic regurgitation is absent, PA pulse width equals baseline pulse width × CO/baseline CO × min(1, treated PVR/baseline PVR). This selected compliance response narrows the pulse as resistance falls while the pressure solver preserves mean PA = PAWP + PVR × CO. It does not impose a universal PAD ≥ mean PAWP floor: pre-existing MR/MS timing offsets retain their sign, and PR retains its separate diastolic-runoff behavior. The inverse PVR/compliance relationship provides physiological context, but RC time varies with wedge pressure and disease. This proportional scaling and its coefficients are original teaching assumptions, not a fitted or universally constant RC product.
ERA/PDE5/selexipag/oral treprostinil/SC treprostinil represent established treatment after initiation and titration; sotatercept uses a later follow-up response concept. Trial comparisons informed direction and broad relative scale only. These settings do not reproduce a particular trial average, predict individual benefit, model long-term toxicity or map to clinical doses. The optional 61-participant FREEDOM-EV RHC subset at 24 weeks supports the direction of oral treprostinil effects on CO, PVR and compliance, but did not show a significant mPAP change. It does not validate these response strengths or either four-drug preset. A DUE supports combining endothelin and PDE5 pathways; the phase-2 selexipag study and STELLAR/PULSAR supply later haemodynamic contexts. The stronger selected epoprostenol endpoint is a teaching range rather than the historical trial mean.
Chronic PVR benefit is enabled for selected precapillary disease or an elevated-PVR/low-wedge experiment without fixed pulmonary embolic obstruction, limiting left-heart loading or external constraint. This is not automated PAH diagnosis or a clinical treatment indication. Other states retain an explicit unmodeled-response note; systemic effects can still occur. PDE5 inhibition with nitrates is flagged as a clinically contraindicated selectable teaching combination. Never use the controls to guide clinical infusion interruption.
Dobutamine in hyperdynamic sepsis
An already high-output, vasodilated septic example has less additional flow reserve than a failing pump. Its dobutamine recruitment smoothly falls from the generic coefficient at 5 L/min to a 3% full-effect increment at 7 L/min or above; the 10% full-effect systemic resistance reduction remains. The full pipeline also includes rate, filling and other interventions. These thresholds and coefficients are synthetic teaching choices, not fitted clinical dose responses.
The default hyperdynamic septic example therefore develops lower diastolic and mean pressure, with only a modest flow increment. Concomitant pump dysfunction retains inotropic recruitment; obstruction and interacting drugs can change the response. Real BP may rise or fall depending on the balance between flow and vascular tone. There is no forced normalization or universal rule that dobutamine lowers BP.
The label describes reduced SVR and possible hypotension, as well as possible increases in rate and systolic BP. SSC 2026 reserves its suggested inotrope strategy for cardiac dysfunction with persistent hypoperfusion despite adequate fluid status and arterial pressure. The simulator is not making a treatment recommendation.
Selected response assumptions
The nitroprusside branch permits a monitored high-afterload LV-failure/AS example to improve flow when starting pressure is adequate and competing risk is absent. The AR branch can reduce modeled recirculation as forward flow improves. These branches represent selected study-informed directions; their numerical coefficients are original teaching choices.
All medication pages describe mechanism, route, example clinical dosing information, cautions and monitoring separately from simulator effect levels. Read the cited reference rather than translating a Low/Medium/High setting into a dose.
References & further reading
