Print version ISSN 0120-3347
Rev. colomb. anestesiol. vol.39 no.3 Bogotá July/Oct. 2011
Reporte de Caso
The Use of Dexmedetomidine (DXM) for Implanting a Cardiac Resynchronization Device: Is it Really Safe?
Luis Fernando Botero Posada*, Juan Miguel Arias Jiménez**, Juan Pablo Vasseur Arboleda**
* Neuroanestesiólogo, Clínica Las Américas-Instituto Neurológico de Antioquia, Departamento Anestesiología, Clínica Las Américas. Correspondencia: Carrera 80 Diagonal 75B No. 2A-80, Medellín, Colombia. Correo electrónico: firstname.lastname@example.org
Recibido: septiembre 15 de 2010. Enviado para modificaciones: abril 11 de 2011. Aceptado: mayo 18 de 2011.
Dexmedetomidine (DXM) is a selective 2-adrenoreceptor agonist acting over both the central and peripheral nervous system. Since it became available for medical application, DXM has been satisfactorily used for a broad spectrum of anesthetic procedures, ranging from sedation to interventions under general anesthesia. Its key advantages include its hemodynamic stability and minimal respiratory depression. This article provides a description of a successful cardiac resynchronization therapy implanting a biventricular pacemaker in a hemodynamically unstable patient under DXM and low-dose midazolam sedation.
Key Words: Dexmedetomidine, biological clocks, amiodarone, safety measures. (Source: MeSH, NLM).
Dexmedetomidine (DXM) is an alpha-2 receptor agonist with selectivity eight times higher than clonidine. It acts on the central nervous system by providing analgesia, sedation and anxiolysis, together with minimal respiratory and hemodynamic changes. Specifically, the effect obtained with DXM is due to its action over the α-2 postsynaptic receptors that increase the permeability to potassium ion through G proteins, which ultimately leads to cell hyperpolarization (1-3).
Being lipophilic, DXM has an average 6-minute alpha time and a beta clearance time of 2 hours, making it extremely attractive for short procedures that may even practiced as outpatient procedures. Some of its key systemic effects include high blood pressure (transient), hypotension and bradycardia; other less severe impacts are nausea and xerostomy that may hinder its use (3,4).
Following the FDA's approval of DXM in 1999, the drug has been used in a broad range of procedures requiring superficial sedation to profound anesthesia for major surgical procedures (3,4). The following is a successful case description of a cardiac resynchronization procedure implanting a cardiac device using sedation, in a patient with considerable limitation of his functional class.
This is a 71-year old Caucasian male patient with a history of ischemic dilated cardiomyopathy, who presented with clinical dyspnea, oppressive chest pain, and hemoptysis. The patient was admitted with a diagnosis of decompensated congestive heart failure. The patient had a history of three episodes of acute myocardial infarction, the last one 3 years ago, when he was managed with interventionist cardiology. NYHA functional class 3 and used to be a smoker.
In the light of the poor response to the initial medical management with ACE inhibitors and diuretics, the electrophysiology department scheduled the patient for the implantation of a biventricular pacemaker and cardiac resynchronization therapy.
The findings of the physical exam showed moderate respiratory distress and logorrhea; the patient says he can't tolerate decubitus because of dyspnea. The systolic blood pressure ranges between 80 and 90 mm Hg. There are no predictors of difficult airway, marked jugular ingurgitation with arrhythmic cardiac bruit and no murmur; the pulmonary auscultation indicated a decreased bilateral vesicular murmur. There was no peripheral edema and the patient had been receiving amiodarone infusion for transient episodes of ventricular tachycardia with pulse in the Holter monitor. The EKG revealed complete left branch block and a 15 % ejection fraction in the echocardiography in addition to grade III/IV mitral insufficiency.
In view of the patient's condition, the decision was made to start DXM sedation at a dose of 1 mcg/kg for 20 minutes, and then continue the infusion around 0.5 to 0.7 mcg/kg/hr, titrating according to the patient's status and hemodynamic stability.
Monitoring of vital signs included a 5-lead cardioscopy, non-invasive blood pressure, pulse oxymetry and constant medical evaluation. Oxygen was supplied through a nasal tube at a rate of 3 liters/minute. As a complement, midazolam was administered at a rate of 0.5 mg IV. Then the device was implanted under local anesthesia with 2 % lidocaine.
The patient maintained mean blood pressure levels close to the baseline. However, 15 minutes later the DMX infusion had to be tapered down because of sustained hypotension. Then 2 mg of IV ethylephrine were added. When the device was tested via induced ventricular fibrillation, an additional dose of 0,5 mg of IV midazolam was added. The patient was defibrillated and returned to normal ranges of sinus perfusion rate and QRS complex.
At the end, both the DXM and amiodarone infusions were stopped because the patient was hypotensive. The patient was then transferred to the recovery room and then to the Special Care Unit for monitored surveillance. The patient is calmed and stable and claims not to remember the defibrillation episode. No inotropic support or vasopressor was required until the next day when the patient was discharged.
DXM is a highly selective alpha-2A agonist that mainly affects the central nervous system leading to anxiolisis, analgesia and sedation, accompanied by a very stable hemodynamic profile. DMX has been used in multiple procedures and is currently accepted as a useful tool, not just for the anesthesiologist, but also for anyone able to provide sedation (1,2).
Traditionally, its mechanism of action has been described via G proteins that increase the potassium ion permeability in the cell, giving rise to hyperpolarizacion. Other effects have also been described, including calcium channels activation and increased Na/H+ exchange that eventually reduce the flow of neurotransmitters such as norepinephrine and serotonin into the brain cortex. Approximately 94 % of dexmedetomidine binds to serum proteins and its metabolism and excretion are through the liver and kidney, respectively (3,4). Despite having a stable hemodynamic profile, once the DMX infusion starts, it causes sustained bradycardia and hypotension that occasionally limits its use.
The initial high blood pressure may be due to the transient stimulus of alpha-1 receptors, particularly when administering boluses. Probably the key advantage of this drug is the absence of respiratory depression that very often hinders sedation with the traditional agents.
Though a drop in the tidal volume has been described, it is not clinically significant so it can be used liberally when no airway manipulation or constant awareness are needed. Its antinociceptive action is due to the stimulus of the Alpha-2A receptors in the spinal cord or in the locus ceruleus.
In addition to the above effects, there are other less frequent ones and probably not extensively studied; i.e., hormone secretion inhibition (insulin, ADH), decreased gastric secretion, lowering of intraocular pressure and more recently, neuroprotection (5, 6). It has also been found that there may be a reduction in the pulmonary vascular resistance and hence an improved gas exchange and less right ventricular work (6).
In the field of anesthesiology, it is clear that alpha-2 agonists lower the intraoperative anesthesia and analgesia requirements (7-9). In major cardiovascular surgeries, using DXM significantly lowered the concentration of the anesthetic gas used and the postoperative use of painkillers. (10,11). There is however some debate with regards to the interaction of DXM and neuromuscular relaxants because apparently DXM increases their serum concentration and further delays the normalization of neuromuscular conduction (7).
It is then advisable to exercise care with the use DXM and titrate the dose in hypovolemic, hemodynamically unstable patients with impaired renal function and specially with liver impairment. Care should also be used in elderly patients or in patients receiving other medications that may lower their blood pressure levels (amiodarone, calcium channel blockers, ACE inhibitors, direct vasodilators) (12).
Implanting a cardiac device is a high-risk procedure because the patient is subject to the occurrence of lethal arrhythmias such as ventricular fibrillation, whether induced or inadverted. DMX is apparently a safe drug that can be used as monotherapy or combined with other agents to obtain the sedation needed in these cases.
There are case reports in the literature describing cardiac arrest, apnea and even death associated to DXM (8,9,11). It is unclear whether there is a direct causal relationship to these adverse events, stressing the need to undertake additional studies that will provide guidance to doctors regarding the adoption of safety measures when using the agent. However, the available literature indicates that the pharma cokinetic and the pharmacodynamic characteristics of the drug provide a very reliable safety profile to consider its use. Moreover, DXM facilitate short procedures and ensures few hemodynamic changes that could place the life of the patient at risk.
The bradycardia and hypotension that may arise once the infusion begins are factors to be kept in mind to avoid the use of DXM in patients with these conditions. In these cases, there are no arrythmias or cardiovascular collapse, but there is hypotension, as expected with the concomitant use of amioradone (12). However, no additional critical events occurred as a result of the interaction of the two drugs and hypotension was easy to manage.
This case illustrates how useful DXM could be for borderline applications using sedation and analgesia, in addition to the stability provided in high-risk procedures. This is even more valid considering the effects on the pulmonary vasculature, gas exchange and the right ventricle (6).
1. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008;21:457-61.
2. Bekker AY, Basile J, Gold M, et al. Dexmedetomidine for Awake Carotid Endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol. 2004;16:126-35.
3. Bhana N, Goa K, McClellan KJ. Dexmedetomidine. Drugs. 2000;59:263-8.
4. Mato M, Pérez A, Otero J, et al. Dexmedetomidina, un fármaco prometedor. Rev Esp Anestesiol Reanim. 2002;49:407-20.
5. Rozet I. Anesthesia for functional neurosurgery: the role of dexmedetomidine. Curr Opin Anaesthesiol. 2008;21:537-43.
6. Wagner DS, Brummett CM. Dexmedetomidine: as safe as safe can be. Seminars in Anesthesia Perioperative Medicine and Pain. 2006;25:77-83.
7. Gurbet A, Basagan-Mogol E, Turker G, et al. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anesth. 2006;53:646-52.
8. Talke PO, Caldwell JE, Richardson CA, et al. The effects of dexmedetomidine on neuromuscular blockade in human volunteers. Anesth Analg. 1999;88:633-9.
9. Martin E, Ramsay G, Mantz J, et al: The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003;18:29-41.
10. Aantaa R, Jalonen J. Perioperative use of alpha2- adrenoceptor agonists and the cardiac patient. Eur J Anaesthesiol. 2006;23:361-72.
11. Ho AM, Chen S, Karmakar MK. Central apnoea after balanced general anaesthesia that included dexmedetomidine. Br J Anaesth. 2005;95:773-5.
12. Ingersoll-Weng E, Manecke G, Thistlethwaite P. Dexmedetomidine and cardiac arrest. Anesthesiology. 2004;100:738-9.
13. Shah AN, Koneru J, Nicoara A, et al. Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Pacing Clin Electrophysiol. 2007;30:1158-60.
1. Carollo DS, Nossaman BD, Ramadhyani U. Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008;21:457-61. [ Links ]
2. Bekker AY, Basile J, Gold M, et al. Dexmedetomidine for Awake Carotid Endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol. 2004;16:126-35. [ Links ]
3. Bhana N, Goa K, McClellan KJ. Dexmedetomidine. Drugs. 2000;59:263-8. [ Links ]
4. Mato M, Pérez A, Otero J, et al. Dexmedetomidina, un fármaco prometedor. Rev Esp Anestesiol Reanim. 2002;49:407-20. [ Links ]
5. Rozet I. Anesthesia for functional neurosurgery: the role of dexmedetomidine. Curr Opin Anaesthesiol. 2008;21:537-43. [ Links ]
6. Wagner DS, Brummett CM. Dexmedetomidine: as safe as safe can be. Seminars in Anesthesia Perioperative Medicine and Pain. 2006;25:77-83. [ Links ]
7. Gurbet A, Basagan-Mogol E, Turker G, et al. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anesth. 2006;53:646-52. [ Links ]
8. Talke PO, Caldwell JE, Richardson CA, et al. The effects of dexmedetomidine on neuromuscular blockade in human volunteers. Anesth Analg. 1999;88:633-9. [ Links ]
9. Martin E, Ramsay G, Mantz J, et al: The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003;18:29-41. [ Links ]
10. Aantaa R, Jalonen J. Perioperative use of alpha2- adrenoceptor agonists and the cardiac patient. Eur J Anaesthesiol. 2006;23:361-72. [ Links ]
11. Ho AM, Chen S, Karmakar MK. Central apnoea after balanced general anaesthesia that included dexmedetomidine. Br J Anaesth. 2005;95:773-5. [ Links ]
12. Ingersoll-Weng E, Manecke G, Thistlethwaite P. Dexmedetomidine and cardiac arrest. Anesthesiology. 2004;100:738-9. [ Links ]
13. Shah AN, Koneru J, Nicoara A, et al. Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Pacing Clin Electrophysiol. 2007;30:1158-60. [ Links ]