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Biomedical Case Study 2
A Pharmacologic Scenario: Uptake and Distribution of Thiopental

N. Ty Smith , MD

This scenario allows the user to examine the uptake and distribution of thiopental. Feel free to try this scenario with other drugs, other doses of drugs, and supplemental doses of drugs.

A general description of the scenario is given. For a step-by-step description of how to set up this scenario in the Body Simulation software please see the Body Simulation Users' Manual.

Procedure:

Set up for a simple anesthetic case - a healthy young male having a lymph node biopsy for example. Select and IV line, a fluid, and drugs:

  • a 20cc THIOPENTAL syringe mixed to 25 mg/ml.
  • a 20cc SUCCINYLCHOLINE syringe mixed to 10 mg/ml.

Set up the Dynamic Time Plots to plot drugs for 8, 12, or 16 minutes as you prefer. Select THIOPENTAL concentrations to be plotted in the following compartments: Aorta, vena cava, myocardium, brain gray matter, kidney, liver, muscle, fat. Also, select THIOPENTAL masses to be plotted in at least the muscle and the fat.

Set up the anesthesia machine O2 flow at 5 lpm; place the mask on the patient, denitrogenate for 1 minute.

Inject the appropriate induction dose of thiopental. Ventilate the patient as required.

The following is a Dynamic Time Plot taken from the case.

Figure 1

Observations:

There are several interesting features of Figure 1. First, note that the recirculation of thiopental is evident in the concentration of thiopental in the vena cava plot (blue). Also, the concentrations of the drug in the tissue compartments follow the blood concentration. The effect differs between compartments of different mass and partition coefficient for thiopental. The tissue concentrations all lag the blood concentration, but it is possible to see that tissues that take up the agent more rapidly tend to "overshoot" the blood concentration (concentration of agent in the kidney (purple) is the most exaggerated case). All concentrations will eventually converge as they reach steady state in the body.

Note also that the mass of thiopental in the brain reaches a peak, and then begins to decrease after about the 2 minute mark. That is because the transfer of agent mass is in the direction of the concentration gradient. The 2 minute mark is about when the thiopental blood concentration drops below the brain concentration.

Finally, note that the mass of agent in the muscle and fat continue to increase even after 12 minutes. Again, this is due to the concentration gradients of muscle/blood and fat/blood. The majority of the thiopental is taken up into the muscle and fat.

Questions:

1. What is the role of fat in the rapid distribution of thiopental?

2. How about muscle?

3. How well do arterial (aortic) blood concentrations initially relate to those in the brain or myocardium? Does this change as a function of time?

4. Repeat this scenario by selecting the same patient, but with a blood volume of 4000 ml instead of 5000 ml. What happens to the distribution of thiopental? Why?

An Exercise:

Repeat the case with the same patient except perform a rapid hemorrhage scenario on the patient before starting (see the next section for an example of the scenario). Bleed the patient at a rate of 200 ml/min for 10 minutes. You should answer the following questions before starting the second case.

More Questions:

5. What do you anticipate will happen to the cardiovascular and respiratory systems in the low-volume situation? Why? - The initial mean arterial pressure was the same in both scenarios in this healthy young patient.

6. Repeat these two scenarios, this time either plotting cardiovascular and respiratory variables of your choice, or watching the variables on the Monitor screen. You may use the instructions in the "Rapid-hemorrhage Scenario" to set up the plot and implement the bleeding.

7. With which "patient" does thiopental have a greater impact on the cardiovascular system?

8. What should you do for a hypovolemic patient before injecting thiopental, if you use that agent at all in this situation?