EDUCATIONALCOMPUTERSIMULATIONOF MALIGNANTHYPERTHERMIA Howard A. Schwid, MD, and Daniel O'Donnell, PhD

Schwid HA, O'Donnell D. Educational computer simulation of malignant hyperthermia. J Clin Monk 1992;8:201-208 ABSTRACT.An educational graphic simulator was developed to

provide an interactive learning environment to practice the diagnosis and treatment of malignant hyperthermia. The program incorporates a set of dynamically interacting models to present the physiologic changes associated with malignant hyperthermia and the simulated patient's response to management. Cardiovascular, respiratory, and temperature changes are presented through a graphic display of the operating room monitors. Mouse-driven input is used to manage the airway, control ventilation, manage cardiovascular and rhythm disturbances, and control fluids, electrolytes, and temperature. Medications, including dantrolene, antidysrhythmics, diuretics, and sodium bicarbonate, can be administered. Four simulated patients with different presentations of malignant hyperthermia are included to illustrate variations in the syndrome. Two of these patients are described in detail. KEYWORDS.Hyperthermia, malignant; dantrolene. Measure-

ment techniques: mathematics. Monitoring: temperature.

THE PROBLEM

From the Department of Anesthesiology, RN-10, University of Washington, Seattle, WA 98195. Received Dec 1, 1990, and in revised form Apr 11, 1990. Accepted for publication Sep 5, 1991. Address correspondence to Dr Schwid, Anesthesiology Service (112A), VA Medical Center, 1660 S Columbian Way, Seattle, WA 98108.

Malignant hyperthermia (MH) is a life-threatening emergency. When exposed to potent inhalation a g e n t s or succinylcholine, the susceptible patient undergoes a dramatic increase in metabolic rate, which causes increased 0 2 consumption and C O 2 production. Excessive heat production can lead to elevations o f temperature up to 46°C. The patient m a y also manifest cardiac dysrhythmias, severe hypertension, and cardiovascular collapse. Malignant hyperthermia is usually fatal if left untreated. Cardiac arrest can occur due to metabolic derangements, or the patient can experience later sequelae, such as disseminated intravascular coagulation, acute renal failure, and p u l m o n a r y edema. It is essential that a M H crisis be diagnosed and treated early, before c o m plications ensue. Malignant hyperthermia is a genetic disorder with an incidence o f approximately 1 per 12,000 pediatric anesthetic cases and 1 per 40,000 adult anesthetic cases [1]. Due to the low frequency o f this syndrome, most anesthesiologists will encounter very few patients with M H during a lifetime career. Most anesthesiologists will not be exposed to a case o f M H during their training or soon afterward. Reading about the syndrome or participating in continuing medical education courses m a y help prepare anesthesiologists for this emergency, but it is our premise that practicing the management on a simulator m a y significantly i m p r o v e training.

Copyright © 1992 by Little, Brown and Company

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202 Journal of Clinical Monitoring Vol 8 No 3 July 1992

RATIONALEFOR APPROACH

Simulators reproduce essential features of the original environment and have been shown to be highly effective training devices in many environments [2]. They are widely used in the aviation, military, and nuclear power fields, but few simulators have been developed for medical education. Full-scale simulators re-create the entire environment using physical devices that closely resemble the real environment, while graphic simulators use computer graphics to represent the functional equivalence o f the real environment. Graphic simulators operating on microcomputers are known as microsimulators [3] and have been shown to be effective training devices for radar [4], sonar [5], nuclear power [6], and weapons [7] systems. Although psychomotor skills are not possible on graphic simulators, the cognitive aspects can be well reproduced. In addition, the cost is substantially lower and accessibility much greater for microsimulators than for full-scale simulators. We therefore developed a microsimulator for problems in anesthesia, concentrating on the management of emergency situations, to be used by medical students, residents, and practicing anesthesiologists. The Anesthesia Simulator Consultant (ASC) is a computer program designed to assist teaching and testing patient management in anesthesiology. It can create a number of fundamental clinical anesthetic challenges. The ASC consists of a graphic presentation of the operating room monitors and a set of dynamically interacting mathematic models to predict the patient's response to management strategies. The program also includes a simulated consultant than can inform the anesthesiologist of the patient's condition and offer advice on treatment. This paper outlines the program for the clinical presentation of MH. The primary objectives of the M H simulator are to practice the recognition and treatment of the incident and differentiate M H from other clinical syndromes. The program provides a tutorial on the use of dantrolene in addition to presenting the cardiovascular, respiratory, physical, and laboratory disturbances associated with MH. Since M H is often unexpected, dantrolene may not be readily accessible in the clinical situation. In the simulator, dantrolene will not be immediately available unless it is ordered before the reaction occurs. This forces the anesthesiologist to practice the management of the severe metabolic and respiratory acidosis, hyperthermia, tachycardia, changes in blood pressure, and rhythm disturbances associated with severe MH. The essential features provided by the ASC are (1) a graphic user interface, (2) mathematic models and a finite-state machine, (3) a rule-based expert system, and

(4) an automated record-keeping system. The graphic interface with mouse-driven input was designed to be easy to use even by anesthesiologists with no computer experience. The essential clinical information is presented in text messages and on facsimiles of physiologic monitors on the computer screen. Predictions o f the simulated patient's condition are based on mathematic models of cardiovascular and respiratory physiology, pharmacokinetics, pharmacodynamics, fluid and electrolyte balance, and temperature. The models were adapted from previously developed physiologic models and are able to produce reasonable predictions in real-time on personal computers. A finite-state machine handles transitions from one state to another, such as from the pre-MH state, to the M H crisis state, to the post-MH crisis state. The combination o f the models and finite-state machine produces a robust, flexible system that provides the anesthesiologist almost unlimited management options during the simulation. Other educational programs that use decision trees constrain clinicians to follow branches and severely limit diagnostic and therapeutic decisions. Simulators, whether full-scale or graphic, only reproduce the events; they do not teach correct management. Typically, sessions in a simulator are followed by debriefing by an expert. To facilitate this process, the ASC includes an automated record-keeping system so that management decisions can be reviewed with an instructor or colleague. In addition, the rule-based expert system provides tutorials and management advice during the simulation. DESCRIPTIONOF SOLUTION

General Description of the Simulator The ASC program is written in Turbo Pascal 5.5 for IBM and compatible personal computers, including AT, 286, 386, and 486 models. The program requires 640 KBytes RAM, 1.5 MByte hard disk space, EGA or VGA graphics, and a mouse. The program operates in real time on computers with 10 MHz or faster microprocessor clock speed. It uses a graphic interface to present the current status of the simulated patient and to control case management. Mathematic physiologic and pharmacologic models and a finite-state machine predict the simulated patient's responses, For each simulated patient, the program reads a data file describing the cardiovascular and respiratory status, plus pharmacokinetic and pharmacodynamic parameters for each drug that can be administered. In addition, the data file contains several variables that describe the M H episode. These include the degree and duration of

Schwid and O'Donnell: Computer Simulation of Malignant Hyperthermia 203

skeletal muscle rigidity, the magnitude and onset rate for the increased metabolism, and the concentration of dantrolene required to normalize the metabolic rate. Once a triggering agent is administered, the mathematic models and finite-state machine predict physiologic changes associated with the incident. To improve differential diagnostic skills, the ASC also simulates several other clinical syndromes, such as pheochromocytoma and thyrotoxicosis, that could be confused with MH.

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The mathematic models used in the simulator have been previously described [8]. The cardiovascular model predicts the cardiac output and arterial, pulmonary, central venous, and pulmonary artery occlusion pressures given the intravascular volume, myocardial contractility, heart rate, systemic vascular resistance, and venous compliance. The time-varying elastance model of Suga and Sagawa [9] is coupled to a Windkessel model of the arterial system [10]. Baroreflexes increase heart rate during hypotension unless this reflex has been pharmacologically blunted. Myocardial oxygen balance is predicted using a model of myocardial oxygen supply and demand [11] based on the left ventricular pressurevolume area as described by Suga et al [12]. The respiratory model includes fresh gas flow from the anesthesia machine, transport through the circle system and airways, alveolar gas exchange, and metabolic consumption of oxygen and production of carbon dioxide. Anatomic and alveolar dead space and pulmonary shunt are included in the model to simulate pathologic situations [13]. Metabolic acidosis is simulated by reducing the concentration of bicarbonate if 0 2 delivery is inadequate to meet tissue metabolic requirements. In addition, control of spontaneous tidal volume and respiratory rate is affected by many drugs in the simulator and is represented by changing the respiratory rate, decreasing the slope of the COa response curve, and increasing the apneic threshold [14]. The pharmacokinetic model predicts the plasma concentrations for the 70 drugs included in the program. Each drug is represented by a two- or threecompartment model with central and peripheral compartments [15]. Parameters for volume of the central compartment, redistribution to and from the peripheral compartments, and elimination for each drug are included in the data files describing the simulated patients. Pharmacokinetic variability is incorporated by modifying these parameters for each simulated patient. The pharmacokinetic parameters used for dantrolene were taken from a report by Lerman et al [16].

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The pharmacodynamic model predicts the drug concentration in an effector compartment as described by Sheiner et al [17]. Each drug administered in the simulator may affect the level of consciousness, analgesia, neuromuscular blockade, or the cardiovascular or respiratory system. Dantrolene reverses the increased metabohc rate triggered in MH. A fluid and electrolyte model predicts intravascular volume, urine output, electrolytes, and hematocrit from volumes administered and lost during the case. A two-compartment model is used to describe potassium concentration. Clearance of potassium from the central compartment is in part determined by pH, catecholamines, and administered insulin. The temperature model used in the ASC is almost identical to the model developed by Stolwijk and Hardy to predict temperature response to environmental changes [18]. In this model, the human body is represented as three sets of cylinders, one each for the head, trunk, and extremities (Fig 1). Heat flows between these sets of cylinders solely by convection as transported by blood flow. The head, trunk, and extremities are further subdivided into two or more concentric solid cylinders representing skin, muscle, and deeper tissues. Heat

204 Journal of Clinical Monitoring Vol 8 No 3 July I992

flows between concentric cylinders by conduction and also by convection due to blood flow. The skin or outermost cylinder in each set exchanges heat with the environment by conduction, radiation, and evaporation. Ventilation provides heat exchange between the trunk core cylinder and the environment. Metabolism produces heat in each compartment, Thermoregulation is also described in the Stolwijk and Hardy model [18]. The body temperature is regulated through shivering, sweating, and changes in skin blood flow, which influence radiation losses. In our simulator, trunk core temperature is displayed on a temperature monitor. Body temperature can be manipulated by external means. For example, a warming blanket increases the ambient air temperature and modifies radiation losses from the skin. Heat can be added to the trunk core through ventilation by using a warm air humidifier. The blood temperature can be warmed or cooled with the introduction o f intravenous fluids o f the appropriate temperature. T o make this calculation, it was assumed that the intravenous fluid and blood reached equilibrium instantaneously. The model o f Stolwijk and Hardy also has been used to predict the response to immersion in cold water [19] and was used in the simulator to estimate the effect o f an ice bath. In the M H simulator, a gastric cylinder was added to the Stolwijk and Hardy model to allow an iced gastric larage to lower the temperature during a M H crisis. The thermal conductance coefficient was adjusted to achieve thermal equilbrium between the gastric cylinder and the trunk core cylinder in 20 minutes. Finite-State Machine

A finite-state machine is a mathematic device that consists o f a finite number o f events and a set o f factors that determine the transitions between the events [20]. The finite-state machine for M H was designed to produce the clinical manifestations o f M H as described by Rosenberg [21] and Sessler [1]. initially, the simulated patient is in the pre-trigger state and has a normal metabolic rate (Fig 2). O n exposure to succinylcholine or a potent inhalation agent, state transition occurs to the M H crisis state. In this state, the patient's metabolic rate increases, with increased 0 2 consumption, CO2 production, and heat production. The finite-state machine increases the metabolic heat production to the maxim u m rate over a period o f time, and the maximum level o f increased heat production is in part determined by the intensity and duration o f the triggering agent. The finite-state machine also controls a number o f patient responses. In the M H crisis state, skeletal muscle rigidity may be reported when the observation o f pa-

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Fig 2. Schematic diagram of the M H finite-state machine. Administration of succinylcholine or a potent inhalation agent changes the state fiom the pre-MH crisis state to the M H crisis state, with its increased metabolic rate, skin changes, and occasional skeletal muscle rigidity. Administration of the appropriate amount of dantrolene shifts the state to the post-MH crisis state and normalizes the metabolic rate.

tient movement is requested. Additionally, the anesthesiologist may be unable to open the patient's mouth to insert an oral airway or perform laryngoscopy. As the event progresses, the finite-state machine sets the skin appearance to mottled, as is often observed [22]. Administration o f an adequate dose o f dantrolene causes the finite-state machine to make the transition to the post-MH crisis state. The mathematic models predict the changes in the simulated patient's cardiovascular and respiratory condition as the metabolic rate normalizes. D y n a m i c Interaction o f Models

The key to realistic simulation o f M H is the dynamic response o f the cardiovascular, respiratory, pharmacologic, fluid and electrolyte, and temperature models. These models were integrated to allow the increased metabolic rate due to M H to lead to a characteristic interaction o f the physiologic models (Fig 3). The increased metabolic rate leads to increased heat production, and the temperature model predicts changes in temperature. The increased metabolism also causes increased 0 2 consumption and CO2 production by the tissues. The respiratory model computes the partial pressures o f 0 2 and CO2 in the mixed venous and arterial blood. Increased C O 2 production causes increased ventilatory requirements and can lead to an elevated Pat02. If the increase in metabolic rate exceeds the ability o f the cardiorespiratory system to supply oxygen, metabolic acidosis will result and the bicarbonate concentrafion will fall. In the integrated model, catecholamines are secreted in response to an elevated mixed venous CO2 as described by Gronert et al [23]. The cardiovascular model responds to the increased level o f catecholamines by increasing the heart rate and contractility and causing vasoconstriction, often leading to hypertension. In our

Schwid and O'Donnell: Computer Simulation of Malignant Hyperthermia 205

PHARMACOLOGI MODEL C Succinylcholins

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model, additional potassium is released from tissues at a rate proportional to the metabolic rate, and, as described by Rutberg et al, hyperkalemia may develop [24]. Rhythm disturbances may be predicted secondary to the excessive catecholamines, hyperkalemia, metabolic acidosis, and hypoxemia as controlled by the rhythm finite-state machine. Later in the acute crisis, extreme metabolic acidosis and dysrhythmias degrade myocardial performance, and the cardiovascular model may predict hypotension under these conditions. The educational simulator for MH was designed to improve recognition and treatment for the acute crisis only. Later sequelae such as disseminated intravascular coagulation and renal failure are not included. Four simulated patients are included in the MH simulator. Each is based on a well-described, published case report of a MH crisis [25-27]. These cases help demonstrate the ability of the simulator to display a variety of presentations of the syndrome. Simulations The anesthetic record of a 20-year-old patient who developed MH and was treated successfully is presented in Fig 4A [25]. The parameters of a simulated patient data file were set to reproduce this case. The cardiovascular and respiratory systems are normal, but on exposure to succinylcholine or potent inhalation agents the simulated patient develops mild rigidity and an eightfold increase in the metabolic rate. Thiopental and succinylcholine were administered to

the simulated patient, followed by oxygen, nitrous oxide, and halothane. The increased metabolic rate raised the CO2 production and increased the minute ventilation. Comparison of the anesthetic record for the real patient in the case report (Fig 4A) and the simulated patient (Fig 4B) show that both had large increases in respiratory rate and minute ventilation. Despite the hyperventilation, severe respiratory acidosis developed. The real patient developed increased heart rate and blood pressure. In the simulated patient, elevated mixed venous CO 2 caused the release of catecholamines, which leads to tachycardia and hypertension. Metabolic acidosis is predicted in the simulated patient despite increased cardiac output due to the greatly increased metabolic rate. The degree of metabolic acidosis observed in the simulated patient agrees with that observed in the real patient. The temperature changes were also similar for the real and simulated patients. Treatment was initiated less than 1 hour after induction. Halothane and nitrous oxide were discontinued and the real and simulated patients were ventilated with 100% 0 2. Sodium bicarbonate was administered to both patients. The patients were actively cooled with ice packs, rapid infusion of ice-cold saline, and iced lavage. Dantrolene (1 mg/kg) was administered twice. Recovery with treatment was similar for the real and simulated patients. The tachycardia decreased in approximately 30 minutes, but the hypertension persisted for hours. The temperature decreased, and both patients actually became hypothermic with the aggressive cooling regimen. The metabolic and respiratory acidosis resolved for both the real and simulated patients, while the respiratory rate and minute ventilation gradually normalized. The real patient developed decreased PaD2 due to pulmonary shunting, but this aspect was not included in the simulated patient. The second simulated patient is a 32-year-old woman undergoing a total abdominal hysterectomy [26]. During anesthesia with halothane and succinylcholine, the patient developed tachycardia, hypertension, and acidosis. Although the anesthetic was discontinued and active cooling measures were initiated, extreme hyperthermia developed. The patient subsequently became hypotensive, did not emerge from the anesthetic, and had a cardiac arrest several hours later. Parameters of the data file for this patient were adjusted to reproduce the case report. On exposure to halothane and succinylcholine, tachycardia and hypertension developed in the simulated patient (Fig 5). After approximately 90 minutes, myocardial depression occurred due to severe acidosis and caused decreased cardiac output and blood pressure. About 1 hour later, the combination of excessive catecholamines, hyperkalemia, and acidosis triggered a car-

206 Journal of Clinical Monitoring Vol 8 No 3 July I992

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diac arrest in the finite-state machine that controls cardiac r h y t h m o f the simulated patient. The simulated patient had a parallel course to the real patient, but the simulated patient died in less than 3 hours, while the real patient died in 18 hours. The onset and magnitude o f the increased metabolic rate were chosen for this simulated patient to make the reaction occur faster than in the case report. Acceleration of an event on a simulator m a y i m p r o v e training efficiency by presenting the case in less time than it actually occurred.

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Educational computer simulation of malignant hyperthermia.

An educational graphic simulator was developed to provide an interactive learning environment to practice the diagnosis and treatment of malignant hyp...
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