Services on Demand
Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.57 no.2 Campinas Mar./Apr. 2007
Severe hemodynamic instability during the use of isoflurane in a patient with idiopathic scoliosis. Case report*
Inestabilidad hemodinámica grave durante el uso de isoflurano en paciente portador de escoliosis idiopática. relato de caso
Adriano Bechara de Souza HobaikaI; Magda Lourenço Fernandes, TSAI; Cláudio Lopes CançadoI; Marcelo Luiz Souza PereiraII; Kléber Costa Castro Pires, TSAIII
da Santa Casa de Belo Horizonte
IIME3 do CET/SBA da Santa Casa de Belo Horizonte
IIIResponsável pelo CET/SBA da Santa Casa de Belo Horizonte
OBJECTIVES: Isoflurane is considered a safe inhalational anesthetic. It
has a low level of biotransformation, and low hepatic and renal toxicity. In
clinical concentrations, it has minimal negative inotropic effect, causes a
small reduction in systemic vascular resistance, and, rarely, can cause cardiac
arrhythmias. The objective of this report was to present a case of severe hemodynamic
instability in a patient with idiopathic scoliosis.
CASE REPORT: Male patient, 13 years old, ASA physical status I, with no prior history of allergy to medications, scheduled for surgical repair of idiopathic scoliosis. After anesthetic induction with fentanyl, midazolam, propofol, and atracurium, 1% isoflurane with 100% oxygen was initiated for anesthesia maintenance. After five minutes, the patient presented severe hypotension (MAP = 26 mmHg) associated with sinus tachycardia (HR = 166 bpm) that did not respond to the administration of vasopressors and fluids. Lung and heart auscultation, pulse oxymetry, capnography, nasopharyngeal temperature, and arterial blood gases did not change. The patient was treated for anaphylaxis and the surgery was cancelled. The clear temporal relationship between the administration of isoflurane and the symptoms suggested the diagnosis of cardiovascular intolerance to inhalational isoflurane. Two weeks later, total intravenous anesthesia was administered without complications.
CONCLUSIONS: There are no reports of severe hemodynamic instability caused by isoflurane in previously healthy individuals. Anaphylaxis, supraventricular tachycardia with hemodynamic consequences, and increased cardiac sensitivity to isoflurane are discussed as possible causes of the hemodynamic instability. Currently, there is evidence that isoflurane can interfere in the coupling-uncoupling system of myocardial contractility by reducing cytosolic Ca2+ and/or depressing the function of contractile proteins. The fundamental molecular mechanisms of this process remain to be elucidated. This report suggests that the administration of isoflurane was the cause of the hemodynamic changes; the patient probably developed an unusual cardiovascular sensitivity to the drug.
Key Words: ANESTHETICS, Volatile: Isoflurane; COMPLICATIONS: cardiac arrhythmias, hypotension; METABOLISM: calcium.
JUSTIFICATIVA Y OBJETIVOS:
El isoflurano se considera un anestésico de inhalación seguro.
Presenta un reducido grado de biotransformación, baja toxicidad hepática
y renal. En concentraciones clínicas presenta efecto inotrópico
negativo mínimo, disminución de la resistencia vascular sistémica
y raramente puede provocar arritmias cardíacas. El objetivo de este relato
fue presentar un caso de inestabilidad hemodinámica grave en paciente
portador de escoliosis idiopática.
RELATO DE CASO: Paciente del sexo masculino, 13 años, estado físico ASA I, sin antecedente de alergia a medicamentos, con consulta marcada para corrección quirúrgica de escoliosis idiopática. Después de la inducción de la anestesia con fentanil, midazolam, propofol y atracurio, isoflurano a 1%, en 100% de oxígeno se inició el mantenimiento. Cinco minutos después el paciente presentó hipotensión arterial grave (PAM = 26 mmHg) asociada a la taquicardia sinusal (FC = 166 bpm) que no respondió al uso de vasopresores e infusión de volumen. La ausculta pulmonar y precordial, oximetría, capnografía, temperatura nasofaríngea y gasometría arterial no tuvieron alteraciones. El paciente recibió tratamiento para anafilaxia y la intervención quirúrgica fue interrumpida. La clara relación temporal entre la administración de isoflurano y la incidencia de los síntomas sugirió un diagnóstico de intolerancia cardiovascular a la administración de inhalación de isoflurano. Dos semanas después, la anestesia venosa total se administró sin problemas.
CONCLUSIONES: No existen relatos de inestabilidad hemodinámica grave causada por isoflurano en pacientes previamente saludables. Anafilaxia, taquicardia supraventricular con repercusión hemodinámica y sensibilidad cardiaca aumentada al isoflurano son discutidas como posibles causas de la inestabilidad hemodinámica. Actualmente, existen evidencias de que el isoflurano pude interferir en el sistema de acoplamiento y desacoplamiento de la contratilidad miocárdica a través de la reducción del Ca2+ citosólico y/o deprimiendo la función de las proteínas contráctiles. Los mecanismos moleculares fundamentales de este proceso deben ser elucidados todavía. El relato sugiere que la administración del isoflurano fue la causa de las alteraciones hemodinámicas presentadas por el paciente y que este, probablemente, presentó una sensibilidad cardiovascular no común al fármaco.
Isoflurane is considered a safe inhalational anesthetic, and it can be used as part of general balanced anesthesia or as a single agent. Among its properties, we should mention the reduced level of biotransformation (0.2%), and low hepatic and renal toxicity. In clinical concentrations, up to two times the minimal alveolar concentration (MAC), it has minimal negative inotropic effect, decreases the systemic vascular resistance, and may decrease the mean arterial pressure with the reflex increase in heart rate. It practically does not sensitize the myocardium to catecholamines, having a minimal effect on the generation and conduction of the cardiac action potential. Cardiac arrhythmias associated with isoflurane are rare 1. Its influences on the coronary steal syndrome are controversial. The objective of this study was to report a case of severe hemodynamic instability in a patient with idiopathic scoliosis.
Male patient, 13 years old, 42 kg, ASA physical status I, with no prior history of allergy to medications, scheduled for surgical correction of idiopathic scoliosis. After venoclysis and monitoring (invasive blood pressure in the left radial artery, SpO2, PETCO2, cardioscope, gas analyzer, and nasopharyngeal temperature), anesthesia was induced with fentanyl (0.5 mg), midazolam (3 mg), propofol (130 mg), and atracurium (25 mg), the patient was intubated, and mechanical ventilation was set to maintain a PETCO2 close to 33 mmHg. Afterwards, 1% isoflurane with 100% oxygen was initiated. The patient was in the dorsal decubitus when, five minutes after induction, he developed severe hypotension (MAP = 26 mmHg) associated with sinus tachycardia (HR = 166 bpm). Patient had not received any antibiotics. Rapid IV infusion of crystalloid solution and ephedrine (10+10+10 mg) were administered without success. The inspired concentration of isoflurane (0.5%) was decreased, ethylephrine (2+2+2 mg) and 500 mL of hydroxyethyl starch were administered, without improvement of the patient's condition. There were no changes in lung and heart auscultation, pulse oximetry, capnography, nasopharyngeal temperature, and arterial blood gases. No dermatologic changes were observed. Since the patient might have developed a severe allergic reaction, hydrocortisone (300 mg), noradrenaline (1 µg.kg-1.min-1), and dobutamine (10 µg.kg-1.min-1) were administered with a slight improvement in MAP (36 mmHg) and increase in HR (180 bpm). The patient showed no significant improvement and was hemodynamically unstable, therefore, the surgery was cancelled and the patient transferred to the intensive care unit. Isoflurane administration was interrupted to allow the patient to regain consciousness; hemodynamic parameters improved at that time, and the infusion of adrenaline and dobutamine was discontinued. While awaiting the transference, isoflurane (0.5%) was restarted to keep the patient unconscious, and he developed severe hypotension and tachycardia. Isoflurane was once again discontinued, with improvement in hemodynamic parameters. The patient was removed to the ICU, where he did not present hemodynamic instability, being extubated one hour after his admission to the unit. Total CPK was normal. Due to the clear temporal relationship between the administration of isoflurane and the signs of hemodynamic instability, the diagnosis of cardiovascular intolerance to inhalational isoflurane seemed probable. The surgery was rescheduled for two weeks later, at which time total intravenous anesthesia with fentanyl, atracurium, and continuous infusion of propofol was administered without complications.
Despite being used for 150 years, the mechanism of action of inhalational anesthetics is still an enigma that molecular anesthesiology tries to explain. Among the possible mechanisms of action of isoflurane are: interference with cellular membranes, changing their volume and fluidity; blockade of ion channels; increased tonus in the GABAergic system; inhibition of excitatory neurotransmitters; cellular hyperpolarization with indirect repercussion in the autonomous nervous system; and, possibly, direct repercussion in the heart and blood vessels.
There are no reports of severe hemodynamic instability caused by isoflurane in previously healthy patients. Among the differential diagnosis that could explain this instability are: anaphylaxis, supraventricular tachycardia with hemodynamic repercussion, and increased cardiac sensitivity to isoflurane.
Anaphylaxis is a severe allergic reaction, more frequent in females, and in atopic patients who received anesthesia in the past. Among the most common changes in anaphylaxis are cardiovascular (73.6%) and cutaneous (69.6%) changes, and bronchospasm (44.2%) 2,3. Neuromuscular blockers and latex are the main trigger factors. Isoflurane has never been associated with allergic reactions, however, immune-mediated hepatitis can rarely occur. Our patient did not show any other symptoms besides cardiovascular changes that were reverted when isoflurane was discontinued, discarding the possibility of an allergic reaction.
Paroxysmal supravetricular tachycardia with hemodynamic repercussion could have been induced by isoflurane, but this agent does not interfere with cardiac conduction. An increased instability in the sinus node and Purkinje system could explain this event.
Another possibility would be the interference of isoflurane with the coupling-uncoupling of myocardial contractility.
There are essentially three important factors that determine the strength of the contraction of the cardiac muscle: the magnitude of the increase in cytosolic Ca++ after electrical excitation; the contractile response of the proteins to Ca++; and the length of the sarcomere in which the contractile proteins are activated. Therefore, there could be two possible mechanisms for the reduction in contractility induced by isoflurane: a reduction in the bioavailability of Ca++ or a reduction in the contractile response of the proteins 4.
Two systems are important for the increase in cytosolic Ca++: type L Ca++ channels that transport this ion from the extra- to the intracellular environment; and the ryanodyne receptors that release Ca++ from the sarcoplasmic reticulum.
Regarding the effects of volatile anesthetics on Ca++ availability, it is currently well established that these drugs decrease the amount of Ca++ released in the cytosol after electrical stimulation 5-9. This effect seems to be mediated by L type Ca++ channels. Volatile anesthetics also decrease the function of contractile proteins, regardless of the bioavailability of cytosolic Ca++ 10.
It has been known for some time that volatile anesthetics can impair the NADH mitochondrial oxidation system, inhibiting complex I (NADH: ubiquinone oxidoreductase) of the electron transport chain. Although studies in the past did not relate this inhibition to the reduction in inotropism, it is possible that the inhibition of the respiratory chain (energy store) decreases the cardiac reserve 11.
Minor interferences were related to other cellular components, such as ion channels, ion pumps, enzymes, and gap junctions. However, most of those studies related the effects to high concentrations of anesthetics, suggesting that volatile anesthetics could disturb lipid bilayers of the cell membrane, which could explain why these lipophilic agents would affect several molecular targets simultaneously 5.
However, the fundamental molecular mechanisms, by which those agents inhibit or stimulate several membrane proteins and depress the contractile apparatus, are still obscure.
This report suggests that the administration of isoflurane caused the hemodynamic changes in the patient and that he probably has an uncommon cardiovascular sensitivity to isoflurane, possibly mediated by systems that control the trafficking of Ca++ in the cytosol.
01. Tardelli MA, Munechika M, Iwata NM et al. Avaliação clínica do isoflurano. Rev Bras Anestesiol, 1988;38:277-281. [ Links ]
02. Hepner DL, Castells MC Anaphylaxis during the perioperative period. Anesth Analg, 2003;97:1381-1395. [ Links ]
03. Laxenaire MC, Mertes PM, Benabes B et al. Anaphylaxis during anaesthesia: results of a two-year survey in France. Br J Anaesth, 2001;87:549-558. [ Links ]
04. Hanley PJ, ter Keurs HEDJ, Cannell MB Excitation-contraction coupling in the heart and the negative inotropic action of volatile anesthetics. Anesthesiology, 2004;101:999-1014. [ Links ]
05. Hanley PJ, Loiselle DS Mechanisms of force inhibition by halothane and isoflurane in intact rat cardiac muscle. J Physiol, 1998;506:231-244. [ Links ]
06. Jiang Y, Julian FJ Effects of isoflurane on [Ca2+]i, SR Ca2+ content, and twitch force in intact trabeculae. Am J Physiol, 1998; 275:H1360-1369. [ Links ]
07. Davies LA, Gibson CN, Boyett MR et al. Effects of isoflurane, sevoflurane, and halothane on myofilament Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in rat ventricular myocytes. Anesthesiology, 2000;93:1034-1044. [ Links ]
08. Housmans PR, Wanek LA, Carton EG et al. Effects of halothane and isoflurane on the intracellular Ca2+ transient in ferret cardiac muscle. Anesthesiology, 2000;93:189-201. [ Links ]
09. Hannon JD, Cody MJ Effects of volatile anesthetics on sarcolemmal calcium transport and sarcoplasmic reticulum calcium content in isolated myocytes. Anesthesiology, 2002;96:1457-1464. [ Links ]
10. Bosnjak ZJ, Kampine JP Effects of halothane on transmembrane potentials, Ca2+ transients, and papillary muscle tension in the cat. Am J Physiol, 1986; 251:H374-381. [ Links ]
11. Hanley PJ, Ray J, Brandt U et al. Halothane, isoflurane and sevoflurane inhibit NADH: ubiquinone oxidoreductase (complex I) of cardiac mitochondria. J Physiol, 2002;544:687-693. [ Links ]
Dr. Adriano Bechara de Souza Hobaika
Rua Desembargador Jorge Fontana, 214/2502
30320-670 Belo Horizonte, MG
Submitted 26 de
abril de 2006
Accepted para publicação em 12 de dezembro de 2006
* Received from CET/SBA da Santa Casa de Belo Horizonte