This document explains various details of the SimBioSys program. It is primarily intended for use as a reference.

Clinical Tools Ventilator

The SimBioSys Ventilator Tool is used to adjust the virtual patient’s mechanical ventilator. For example, you can increase or decrease the respiratory rate with the ventilator tool. Furthermore, you can observe the airway pressure, lung volume, and lung airflow waveforms using the ventilator tool.

Ventilator settings include: respiratory rate, tidal volume, FIO2 (fraction inspired oxygen), PEEP (positive end expiratory pressure), inspiratory pause, inspiratory flow rate and pressure alarm/pop off.

Clinical Tools Single Dose Infuser

Portions of this section and the next two sections were adapted from the SimBioSys help files and are Copyright 1995 Critical Concepts, Inc.

The pharmacokinetics of some drugs have been modified make the virtual patient respond to them more quickly than would a real patient. The designers of SimBioSys felt that accelerating drug action and decay times was justified on pedagogical grounds. See the SimBioSys manual for details on these modifications.

The following medications can be administered using the single dose infuser:

Albuterol

Albuterol is a selective beta 2 agonist.

Receptor Activity: Albuterol is an agonist at beta 2 adrenergic receptors.

Expected Physiological Effects: Albuterol is a long acting beta 2 agonist that is usually used as an inhalation bronchodilator. Significant absorption occurs, so that tachycardia accompanies application of albuterol to the airways.

Kinetics: Albuterol lasts at least 2 hours, and often 46 hours after administration. In SimBioSys, albuterol wears off a bit faster than it does in reality.

Method of Administration: Albuterol can be given orally, by metered dose inhaler, or by nebulization. The nebulization route is the commonest in the ICU, and is the only method of administration supported in SimBioSys..

Dosage: 0 to 2.5 mg. At 2.5 mg, the airway effects of albuterol should be near maximal. Above this level, additional doses have considerable incremental systemic absorption but little incremental effect on airway tone.

Atropine

Atropine is an inhibitor of parasympathetic activity.

Receptor Activity: Atropine is an antagonist of muscarinic acetylcholine receptors.

Expected Physiological Effects: Atropine is a vagolytic, in that is blocks the parasympathetic contribution to heart rate. Under normal situations, the parasympathetic system slows the heart rate substantially; with full muscarinic blockade the heart rate increases to about 100.

Kinetics: Atropine lasts roughly an hour after administration..

Method of Administration: Intravenous or intramuscular bolus doses may be given .

Dosage: 0 to 2 mg. At 2 mg, the autonomic effects of atropine should be near maximal. Above this level, additional doses have considerable incremental CNS effects but little incremental effect on vagal function.

Furosemide

Furosemide is a diuretic.

Units: mg

Usage: The user may administer this agent to effect increased urine output.

Pancuronium (Pavulon)

Pancuronium is a commonly used nondepolarizing muscle relaxant.

Units: mg/kg/hr (infusion rate)

Usage: Common uses of this pharmacologic agent include paralysis for the purposes of intubation and surgery, or to diminish oxygen consumption by skeletal muscle and/or control ventilation. These latter strategies are useful during resuscitation and stabilization of patients in shock or with acute respiratory failure.

Normal Range: The initial paralyzing dose is approximately .08 to .1 mg/kg with an effect lasting approximately 4060 minutes. Ongoing paralysis may be maintained with a dose of .025 mg/kg/hr given as intermittent bolus or by continuous infusion. Optimal dosing may be quite variable depending largely upon renal and hepatic clearance. Doses should be titrated to effect and periodically the drug should be discontinued to avoid accumulation.

Clinical Tools Continuous Infuser

The following medications and solutions can be administered using the continuous infuser:

Bicarbonate (alkali infusion)

Units: mEq/hr

Sodium bicarbonate infusion can be used to raise blood pH by elevating the strong ion difference (SID) in blood. When given clinically, (and its use is controversial in many circumstances), sodium bicarbonate produces a transient rise in carbon dioxide production, as some of the infused bicarbonate "buffers" the acid. That is, all of the infused sodium remains in the body, while some of the infused bicarbonate elevates the body bicarbonate load and the rest is exhaled as carbon dioxide. Bicarbonate infusions are often used to treat metabolic acidosis, although there remains considerable controversy over the wisdom of treating lactic and similar acidosis with bicarbonate infusion. A less controversial use of sodium bicarbonate infusion is in support of “permissive hypercapnia,” which is occasionally used in patients whom it is difficult to ventilate.

Normal Range: None at baseline, usually <25150 mEq/h when given therapeutically.

D5W Infusion (5% dextrose, i.e., glucose)

Units: ml/hour

D5W (5% dextrose, i.e., glucose) is a volume expander. D5W is isotonic and contains no electrolytes.

Dobutamine

Dobutamine is an inotropic agent.

Units: mg/kg/min.
This inotropic agent is usually titrated from 220 mcg/kg/min in the treatment of patients with severe ventricular dysfunction, such as congestive heart failure or cardiogenic shock.

Dopamine

Dopamine is an endogenous catecholamine that is released from the adrenal gland. When infused intravenously, it activates adrenergic and dopaminergic receptors. It has significant beta 1 activity at low doses, and at higher doses alpha 1 and alpha 2 activity predominates. It is used to provide inotropic support for the failing ventricle and to increase blood pressure.

Dosage: 0 to 20 mcg/kg/min

Epinephrine (adrenaline)

Epinephrine is an endogenous catecholamine that is released from the adrenal gland. When infused intravenously, it activates all adrenergic receptors.

Dosage: 0 to 2 mcg/kg/min

Esmolol

Esmolol is a beta blocker. When infused intravenously, it blocks binding of catecholamines to adrenergic receptors.

Receptor Activity: In fact, Esmolol blocks beta 1 receptors with considerable selectivity. In SimBioSys, it is treated as blocking both beta 1 and beta 2 receptors..

Expected Physiological Effects: Esmolol blocks the sympathetic contribution to heart rate and to cardiac contractility. Under normal situations, the sympathetic contribution to heart rate and contractility are modest; with full beta blockade the heart rate drops to 55, and cardiac output is minimally affected. In situations of increased sympathetic drive or adrenergic drug administration, effects will be more pronounced.

Kinetics: Esmolol has an elimination half life of approximately 8 minutes.

Method of Administration: Continuous intravenous infusion. In clinical reality, esmolol is given as an infusion following a loading dose. In SimBioSys, elimination is treated as instantaneous and no loading dose is used, so that blockade can be started or stopped more rapidly.

Dosage: 0 to 300 mcg/kg/min

Hemorrhage

Units: ml/hour

Hemorrhage is the rate of blood loss. The user may set this parameter to simulate hemorrhagic shock. Also see phlebotomy under the blood products infuser.

Hydrochloric Acid (acid infusion)

Units: mEq/hr

Hydrochloric acid can be used to lower blood pH by lowering the strong ion difference (SID) in blood. When given clinically (and its use is unusual), hydrochloric acid is diluted enough that it does not produce corrosive effects at the infusion site or damage to the formed elements in the blood. Metabolic alkalosis is only rarely treated by acid infusion; it is almost always appropriate and sufficient to seek, identify and correct the cause of the alkalosis.

Isoproterenol (Isuprel)

Isoproterenol is an artificial catecholamine that may be administered intravenously to critically ill patients.

Receptor Activity: Isoproterenol stimulates beta 1 receptors and beta 2 receptors very strongly, and has no effect on alpha receptor.

Expected Physiological Effects: This agent is a powerful chronotrope and a powerful inotrope. Because of the beta 2 effect there is also some vasodilation. Its administration will produce intense tachycardia, an increase in cardiac output, and a change in blood pressure that depends on the prior sympathetic state. It substantially increases cardiac workload and is considered to be too great a cardiac stressor for most clinical situations.

Kinetics: Isoproterenol is rapidly eliminated.

Method of Administration: Continuous intravenous infusion.

Dosage: 0 to 8 mcg/kg/min

Lactated Ringer’s

Units: ml/hour

Lactate Ringer’s is a volume expander. Lactated Ringer's contains 130 mEg/l Na+, 4 mEg/l K+, 3 mEg/l Ca++, 109 mEg/l Cl- and 28 mEg/l lactate and is isotonic.

Nitroprusside (Nipride)

Nitroprusside is a vasodilator.

This potent vasodilator is used to improve cardiac output in severe left ventricular systolic dysfunction (e.g., cardiogenic shock) or to acutely lower extreme elevations of blood pressure. It is typically titrated to a dose between .5 to 8 mg/kg/min.

Norepinephrine (levarterenol, Levophed, noradrenaline)

Norepinephrine, a naturally occurring catecholamine, may be administered intravenously to critically ill patients.

Receptor Activity: Norepinephrine stimulates alpha 1, alpha 2, and beta 1 receptors strongly, and beta 2 receptors very weakly..

Expected Physiological Effects: This agent is both an inotrope and vasoconstrictor, although the latter property tends to dominate in most clinical circumstances. Thus, norepinephrine will tend to increase the blood pressure, but often at the cost of a decrease in regional tissue bed perfusion (e.g., renal perfusion) due to vasoconstriction and with an increase in myocardial work. Infusion of norepinephrine into a normal individual will increase blood pressure dramatically.

Kinetics: Norepinephrine is rapidly eliminated.

Method of Administration: Continuous intravenous infusion.

Dosage: 0 to 2 mcg/kg/min

Phentolamine

Phentolamine is an alpha adrenergic receptor blocker.

Receptor Activity: Phentolamine blocks alpha 1 and alpha 2 receptors strongly, and has no effect on beta receptors.

Expected Physiological Effects: This agent is a vasodilator, by virtue of inhibiting alpha adrenergic receptors and sympathetic tone.

Kinetics: Phentolamine is eliminated over minutes, but still rapidly enough to justify continuous infusion. It can also be given as a single bolus injection in clinical practice, but not in SimBioSys.

Method of Administration: Continuous intravenous infusion. In SimBioSys, onset and withdrawal of its effects are treated as instantaneous to improve program responsiveness.

Dosage: 0 to 25 mcg/kg/min

Phenylphrine (NeoSynephrine)

Phenylephrine is an artificial catecholamine that may be administered intravenously to critically ill patients.

Receptor Activity: Phenylephrine stimulates alpha 1 receptors strongly, and has no effect on beta receptors.

Expected Physiological Effects: This agent is a powerful pressor, and is predicted to have some inotropic activity although this is not usually discussed. It is the closest drug to a pure pressor, that is a drug that selectively increases arterial resistance. It substantially increases cardiac workload and is considered to be too great a cardiac stressor for most clinical situations.

Kinetics: Phenylephrine is eliminated over minutes, more slowly than norepinephrine but still rapidly enough to justify continuous infusion. It can also be given as a single bolus injection in clinical practice, but not in SimBioSys.

Method of Administration: Continuous intravenous infusion. In SimBioSys, onset and withdrawal of its effects are treated as instantaneous to improve program responsiveness.

Dosage: 0 to 10 mcg/kg/min

Ritodrine

Ritodrine is an artificial catecholamine which may be infused in critically ill patients.

Receptor Activity: Ritodrine stimulates beta 2 receptors very strongly, and has very little effect on other receptors.

Expected Physiological Effects: This agent is a powerful chronotrope, tocolytic, and bronchodilator, and is essentially devoid of inotropic effects. Because of the beta 2 effect there is also some vasodilation. Its administration will produce intense tachycardia. It substantially increases cardiac workload and is considered to be too great a cardiac stressor for many clinical situations. In reality, it is used only as a tocolytic, because inhalation beta 2 agonists are generally preferable as bronchodilators. In SimBioSys, it can be used as a bronchodilator.

Kinetics: Ritodrine is eliminated more slowly than natural catecholamines although it is usually started as a continuous intravenous infusion. In SimBioSys, the effects are treated as if Ritodrine were instantaneously eliminated, to provide faster responses than could be seen with the real drug.

Method of Administration: Continuous intravenous infusion.

Dosage: 0 to 5 mcg/kg/min

Saline (0.9 N)

Units: ml/hour

Saline (0.9 N NaCl) is a volume expander. It contains 154 mEq/l NaCl and is isotonic.

Trimethaphan (Arfonad)

Trimethaphan is a ganglionic blocking agent.

Receptor Activity: Trimethaphan is a selective acetylcholine receptor blocker, and blocks cholinergic nerve transmission at both sympathetic and parasympathetic ganglia. Trimethaphan affects only nerve transmission, so does not reduce responsiveness to directacting vasodilators.

Expected Physiological Effects: This rapidly and reversibly blocks sympathetic and parasympathetic nerve transmission. It therefore has mild negative inotropic effects. Ordinarily heart rate will increase slightly because under normal situations the parasympathetic withdrawal has a greater effect than the sympathetic withdrawal. Under conditions of stress, the reverse is likely to be the case. In reality, trimethaphan also causes histamine release, occasionally producing initial hypotension, and this is not modeled in SimBioSys.

Kinetics: Trimethaphan is eliminated rapidly enough to require continuous infusion. In reality, its physiologic effects disappear over 520 minutes after stopping infusion.

Method of Administration: Continuous intravenous infusion. In SimBioSys, onset and withdrawal of its effects are treated as instantaneous to improve program responsiveness.

Dosage: 0 to 60 mcg/kg/min

Clinical Tools Blood Products Infuser

The following blood products can be administered using the blood products infuser:

Whole Blood
Packed Red Blood Cells (RBC)
Fresh Frozen Plasma (FFP)

The the blood products infuser can also be used to administer the following volume expanders:

Albumin, 5%
Albumin, 25%
Saline, 0.9 N (also can be administered using the continuous infuser)

Albumin is a colloid solution that is often used because it remains confined within the intravascular space to a much greater extent than saline or water. From a cardiovascular point of view, albumin infusion increases preload, and increases cardiac output, but at the price of relative hypervolemia. Albumin, 5% is isooncotic with plasma while albumin 25% is very hyperoncotic. Neither solution contains significant electrolytes.

Saline is a volume expander moves freely into the interstitial space but not the intercellular space..

The blood products infuser can also be used to simulate phlebotomies. Phlebotomies are therapeutic maneuvers in which blood is intentionally withdrawn to reduce circulatory volume. The user may set this parameter to induce hemorrhagic shock. Also see hemorrhage under the continuous infuser.

SimBioSys Viewer Variables

SimBioSys can predict and display the values of a wide rage of physiological variables. These variables are divided into categories based on the organ system to which they are related and their routine clinical availability. Values displayed in blue are inputs to the simulation and can be changed manually using appropriate tool bar choices. Value displayed in black are simulation outputs and therefore can not be changed manually.

Clinical cardiovascular variables include:

Arterial pressures (diastolic, mean, systolic and waveform)
Blood volume
Cardiac output
ECG waveforms (leads 1, 2 and 3)
Heart rate
PA pressure (mean)
PA wedge pressure
PVR
Pericardial properties (capacity, effusion, pressure and stiffness)
Pulse pressure
SVR
Stroke volume

Clinical lung and gas exchange variables include:

Aa PO2 difference
AV O2 content difference
Arterial bicarbonate concentration
Arterial pH
Body weight
CO2 production rate
Dead space, physiological
FRC
Hemoglobin concentration
Minute ventilation
O2 (delivery, extraction ratio and uptake)
PAO2
PEEP
PIO2
PaCO2
PaO2
PvCO2
PvO2
RQ
SaO2
Shunt, physiological
SvO2
Tidal volume
Venous pH

Clinical renal and fluid exchange variables include:

Fractional excretion of filtered sodium
GFR
Hematocrit
Plasma SID
Temperature
Urine (osmolality, output, volume, [Cl—], [K+], [Na+] and [protein]

Nonclinical cardiovascular variables include:

Arterial compliance
BP set point
Basal HR
Blood viscosity parameters
CVP waveform
LA (contraction function, functional fraction, P-V curves and mean pressure)
LV (contraction function, functional fraction and P-V curves)
Mean systemic pressure
Parasympathetic properties
Pleural pressure (mean and waveform)
Pulmonary artery properties
RA (contraction function, functional fraction and P-V curves)
RV (contraction function, functional fraction and P-V curves)
Systemic arterial properties
Sympathetic properties


Nonclinical lung and gas exchange variables include:

Barometric pressure
CaN2
Critical extraction ratio
Dead space (alveolar, anatomic and true)
H2O vapor pressure
Lactate production rate
Muscle VO2
O2 demand
Perfusion log standard deviation
Respiratory rate
Shunt (alveolar, anatomical and true)


Nonclinical renal and fluid exchange variables include:

Bladder volume
Glomerular (filtration coefficient and pressure)
Renal arteriole resistances (afferent and efferent)
Renal blood flow
Renal plasma flow

Automatic Control

The following parameters are normally controlled automatically in SimBioSys, but can be controlled manually if so desired:

LV Contractility
RV Contractility
LA Contractility
RA Contractility
Heart Rate
Systemic and Pulmonary Vein Compliance
Systemic Arterial Resistance
Pulmonary Arterial Resistance
Sympathetic Tone
Parasympathetic Tone
Shunt/Dead Space

Miscellaneous Technical Information

Some of this information is specific to MSOE's installation of SimBioSys.

Main program:

SBSPHYS.EXE

Default directory:

\SBSPHYS (on the k: drive on the A & P network).

Help Files:

SBS_PH.HLP - Physiology help.

SBS_PI.HLP - Interface help.

SBS_PT.HLP - Guided tour.

NOHIST.HLP - Default no case history screen.

Other Files:

*.CAS - Cases (physiological values).

*.DSK - Desktops (viewer collections).

*.INI - ASCII configuration files.

*.DLL - Dynamic link libraries.

*.BMP - Interface bit maps.

LWSDATA.DAT - ASCII EGC data file.

Critical Concepts, Inc. web page URL - http://www.laketech.com/CC_MAIN.HTML