REVIEW
Sedation for Electrophysiological Procedures STUART P. THOMAS, B.MED., PH.D., JAY THAKKAR, M.B.B.S., PRAMESH KOVOOR, M.B.B.S., PH.D., ARAVINDA THIAGALINGAM, M.B.B.S., PH.D., and DAVID L. ROSS, M.B.B.S. From the Department of Cardiology, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
Administration of intravenous sedation (IVS) has become an integral component of procedural cardiac electrophysiology. IVS is employed in diagnostic and ablation procedures for transcutaneous treatment of cardiac arrhythmias, electrical cardioversion of arrhythmias, and the insertion of implantable electronic devices including pacemakers, defibrillators, and loop recorders. Sedation is frequently performed by nursing staff under the supervision of the proceduralist and in the absence of specialist anesthesiologists. The sedation requirements vary depending on the nature of the procedure. A wide range of sedation techniques have been reported with sedation from the near fully conscious to levels approaching that of general anesthesia. This review examines the methods employed and outcomes associated with reported sedation techniques. There is a large experience with the combination of benzodiazepines and narcotics. These drugs have a broad therapeutic range and the advantage of readily available reversal agents. More recently, the use of propofol without serious adverse events has been reported. The results provide a guide regarding the expected outcomes of these approaches. The complication rate and need for emergency assistance is low in reported series where sedation is administered by nonspecialist anesthesiology staff. (PACE 2014; 37:781–790) arrhythmias, electrophysiology, sedation, anesthesia, atrial fibrillation, ablation, pacing, defibrillator, cardioversion, pulmonary vein isolation
The administration of sedation for cardiac procedures has become an integral part of the practice of cardiology. Sedation is commonly used for electrophysiological procedures, transesophageal echocardiography, and cardiac catheterization. The electrophysiological procedures for which sedation is employed include diagnostic and ablation procedures for cardiac arrhythmias, electrical cardioversion, and the insertion of implantable electronic devices including loop recorders, pacemakers, and defibrillators. The purpose of sedation for these procedures is to improve patient comfort. Sedation is frequently performed by specialized nurses under the supervision of the procedural cardiologist. The purpose of this review is to examine the agents used, methods, and safety of this approach.
Conflict of Interest: The authors have no conflicts of interest in relation to this manuscript. Address for reprints: Stuart P. Thomas, B.Med., Ph.D., Department of Cardiology, Westmead Hospital, Cnr Hawkesbury and Darcy Roads, Westmead, NSW 2145, Australia. Fax: 61 2 9845 8323; e-mail: [email protected] Received June 23, 2013; revised January 5, 2014; accepted January 7, 2014. doi: 10.1111/pace.12370
Sedation and anesthetic practices vary dramatically throughout the world. There is variation in the selection of patients for sedation or general anesthesia, the personnel administering sedation, the agents employed, and the technique for monitoring sedation. Deep levels of sedation are often administered in the absence of specialist anesthesiologists.1–4 The purpose of this review is to examine the evidence relating to the agents used, methods, and safety of sedation for cardiac electrophysiological procedures. We reviewed data supporting approaches to sedation in these cases. We identified manuscripts that evaluated use of sedation for cardiac electrophysiology procedures by searching the EMBASE and MEDLINE databases and the Cochrane library for publications from January 1970 to September 2013. The search design was conducted by two authors (JT and SPT). This search was supplemented by hand searching bibliographies of published studies and relevant review articles. The search terms: “sedation” or “anesthesia,” in combination with “electrophysiology,” “pacing,” “cardiac devices,” “cardioversion,” “catheter ablation,” or “pulmonary vein isolation” were used. We focused on clinical trials, case-control studies, cohort studies, case series, and expert
©2014 Wiley Periodicals, Inc. PACE, Vol. 37
June 2014
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THOMAS, ET AL.
consensus guidelines. We excluded individual case reports and editorials. Our initial screen yielded 13,789 manuscripts. Limiting our search to human studies in adults (>18 years) with publication in the English language reduced this to 1,084. In most cases, series of fewer than 50 patients were excluded. Title and abstract screening further reduced the number of manuscripts to those described in this review. Manuscripts not focusing on the process of sedation or anesthesia during electrophysiological procedures were excluded. Aims of Sedation and Advantages of General Anesthesia or Intravenous Sedation (IVS) The aims of sedation during cardiac procedures are to reduce patient discomfort and patient movement. Some shorter electrophysiological procedures may be performed with the patient awake or only lightly sedated. The pain associated with implantation of cardiac devices can usually be minimized by administration of local anesthesia. However, some electrophysiological procedures, including ablation of pain-sensitive sites and electrical cardioversion, require systemic analgesia. More complex electrophysiological procedures may have the additional demand of requiring the patient to remain relatively still. Some electrophysiological mapping systems employ sensors outside the body to determine catheter position in relation to that of the heart. These systems may partially compensate for patient movement but such compensation is imperfect. Ablation in the vicinity of critical structures, including the His-bundle, and procedures such as transeptal catheterization require the patient to be immobile to reduce the risk of complications. Assessing the Depth of Sedation The optimal level and technique for sedation depends on the nature of the procedure. For complex electrophysiological procedures, a wide range of practices are employed ranging from very light sedation to general anesthesia. The optimal level of sedation for electrophysiological procedures has not yet been definitively determined. The presence of pain during ablation may lead to movement, which makes the procedure more difficult. Such pain, however, may also alert the operator to a risk of complications. The use of muscle relaxants during general anesthesia may prevent phrenic nerve pacing, a technique used to avoid phrenic nerve injury. Deep sedation or anesthesia may delay the diagnosis of cerebrovascular events. However, these deeper levels of sedation reduce patient movement and may facilitate electrical cardioversion when required. Some anesthetic
782
Table I. Ramsay Sedation Scale Modified from Ramsay et al.5 Ramsay Sedation Scale (1) Patient is anxious and agitated or restless, or both. (2) Patient is cooperative, oriented, and tranquil. (3) Patient responds to commands only. (4) Patient exhibits brisk response to light glabellar tap or loud auditory stimulus. (5) Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus. (6) Patient exhibits no response.
agents reduce the inducibility of arrhythmias. This is a major consideration for studies that have a diagnostic component, including studies of ventricular tachycardia and supraventricular tachycardias. Agents that depress cardiac function may also be problematic during ablation of ventricular tachycardia. Ventricular tachycardia, well tolerated in the conscious patient, may cause hemodynamic collapse in patients under general anesthesia. Scales have been developed to allow estimation and standardization of the depth of sedation. Most authorities emphasize the continuum of sedation and acknowledge that divisions between levels of sedation may be arbitrary. Most sedation scales suggested for cardiac electrophysiological procedures are modifications of the Ramsey scale introduced to describe levels of sedation in the intensive care environment.5 The original scale relied on response to auditory stimulation or the glabellar tap (Table I). The first sedation scale for electrophysiological procedures was included in the 1998 Consensus Document of the North American Society for Pacing and Electrophysiology (Table II).6 A more recent scoring system is that of the American Society of Anesthesiologists,7 which also recommended a variation on the Observer’s Assessment of Alertness/Sedation developed by Chernik et al. (Table III).8 Pharmacological Agents, Doses, and Method of Administration Benzodiazepines The most common approach for sedation and pain relief during cardiac procedures is the use of benzodiazepines and narcotics either alone or in combination. The combination of these drugs provides analgesia, sedation, and amnesia. Local anesthetic is required in all cases.
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Table II. Spectrum of Sedation Modified from Bubien et al.6 Spectrum of Sedation (SEC): Scores: 2 = Present, 1 = Limited, 0 = Absent Responds Purposefully to Level
Consciousness
Light sedation IV Sedation (A) Sleepy (B) Sleep (C) Advanced sleep Deep sedation Gen. anesthesia
Near normal
Very depressed Unarousable
Verbal Stim.
Physical Stim.
Airway
Respiration
Total SED Score
2
2
2
2
8
1–2 0–1 0 0 0
2 1 1 0 0
2 2 1–2 0–1 0–1
2 1–2 1 0–1 0–1
7–8 4–6 3–4 0–2 0–2
Table III. Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia and Modified Observers Assessment of Alertness/Sedation (MOAA/S)7,8
Minimal Sedation (Anxiolysis)
Moderate Sedation/ Analgesia (Conscious Sedation)
Airway
Normal response to verbal stimulation Unaffected
Spontaneous ventilation
Unaffected
Purposefula response to verbal or tactile stimulation No intervention required Adequate
Cardiovascular function
Unaffected
Usually maintained
Responsiveness
MOAA/S Scorea 5 4 3 2 1 0 a Reflex
Deep Sedation/Analgesia
General Anesthesia
Purposefula response after repeated or painful stimulation
Unarousable, even with painful stimulus
Intervention may be required May be inadequate Usually maintained
Intervention often required Frequently inadequate May be impaired
Description Responds readily to name spoken in normal tone Lethargic response to name spoken in normal tone Responds after name called loudly or repeatedly Purposeful response to mild prodding or mild shaking Responds to trapezius squeeze (includes purposeful and reflexive withdrawal) No response to painful stimulation (trapezius squeeze)
ASA Continuum Minimal sedation Moderate sedation Moderate sedation Moderate sedation Deep sedation General anesthesia
withdrawal from a painful stimulus is not considered a purposeful response.
The most commonly studied benzodiazepines for sedation are diazepam and midazolam. These agents have a wide therapeutic range and can be reversed with flumazenil. They are metabolized in the liver and the metabolites are excreted by the kidneys. Midazolam has been used widely for sedation during electrophysiological procedures, usually in
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conjunction with other agents. The initial bolus and infusion doses depend on the doses of other agents, patient characteristics, and the target level of sedation. They are usually adjusted for weight and age, and other factors that may alter the drug metabolism or patient response. An initial bolus dose is usually in the range of 0.01–0.1 mg/kg.2,3,9–12 This may be followed by repeated
June 2014
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THOMAS, ET AL.
boluses or an infusion of up to 0.1 mg/kg/h. During long procedures, midazolam can cause restlessness that may be overcome by cessation of the drug and sedation with a different agent.13 When midazolam was used alone (after oral diazepam) to perform electrical cardioversion, a relatively high dose was required (5–12.5 mg).14–16 Diazepam has a longer half-life and is, therefore, less popular. External cardioversion has been described most commonly with doses of up to 30 mg.14,17 Pugh et al. described administration of diazepam with doses up to 100 mg (mean 27.2 mg).18
One patient receiving remifentanil experienced respiratory depression and muscular rigidity. Vomiting occurred in 10%. Morphine was used with midazolam by Kezerashvili et al.12 The mean dose ranged from 9.9 mg for diagnostic electrophysiological procedures to 14.6 mg for ablation procedures. These doses corresponded to an infusion rate of approximately 0.05 mg/min. The concurrent midazolam was administered at a similar dose. Other opioids that have been used for sedation include piritramid, meperidine, sulfentanil, alfentanil, and diamorphine.13,24
Narcotics Benzodiazepines have relatively poor analgesic properties and are frequently combined with narcotics. The most commonly described narcotics for cardiac sedation are fentanyl and morphine. Like benzodiazepines, narcotics have a wide therapeutic window. Their effect can be reversed by naloxone hydrochloride. With the exception of remifentanil, which is metabolized in the bloodstream, they are metabolized in the liver. Fentanyl is a relatively short-acting narcotic and the most commonly used in cardiac sedation. Like midazolam, with which it is frequently coadministered, it is often given as a bolus dose followed by an infusion. The bolus dose of fentanyl depends on patient characteristics and the use of other agents. Bolus doses are typically in the range of 10–50 mcg.3,4,9–11,19 The infusion dose described is in the range of 0.5–2.0 mcg/kg/h.2,9–11 Both doses may be adjusted for weight and age.10 The combination of midazolam and fentanyl does not have a significant adverse effect on arrhythmia inducibility.20 Remifentanil is a narcotic with a very short half-life. The drug has a time to peak effect of approximately 90 seconds and a half-life of 3–4 minutes. Remifentanil use has been described in complex electrophysiological studies combined with midazolam with doses of 0.06– 0.14 mcg/kg/min. Electrical cardioversion and epicardial access using a subxiphoid approach were reported using this combination.21 In another study, remifentanil reduced the dose of propofol or midazolam required to tolerate electrical cardioversion.22 Remifentanil may produce bradycardia and hypotension. Use of remifentanil in isolation with patient-controlled analgesia was described by Lena et al. in a nonrandomized comparison with infused propofol.23 Patients undergoing catheter ablation for atrial flutter were studied. Those receiving remifentanil experienced lower levels of sedation and had higher pain scores than those undergoing infused propofol sedation.
Propofol Propofol has the advantage of rapid onset and offset of action. It has a wide therapeutic range but may cause bradycardia, respiratory depression, or hypotension. Hypotension is common in elderly and dehydrated patients13 The use of propofol for cardiac procedures has recently been reported in several large series. Kottkamp described 650 patients undergoing ablation for atrial fibrillation.3 Propofol was used after a bolus of midazolam and fentanyl. The dose administered was initially 5 mg/kg/h and the mean dose was 399 mg/h. In another series of 1,000 consecutive patients described by Salukhe et al., propofol was also administered under the supervision of cardiologists.4 Fentanyl was administered simultaneously for analgesia. The propofol dose was a 44 ± 18 mg bolus followed by an infusion at a mean rate 390 ± 96 mg/h. Wutzler et al., reported the use of deep sedation or unconscious sedation with propofol and midazolam in a series of 316 patients undergoing catheter ablation for atrial fibrillation.24 A midazolam bolus dose of 0.05 mg/kg was used followed by 0.03 mg/kg maintenance infusion. A propafol infusion of 4 mg/kg/h was adjusted to maintain adequate sedation. The highest doses were used by Tang et al. An infusion of propofol beginning with 4 mg/kg/h was titrated to achieve analgesia and the absence of movement.9 The mean infusion rate was 8.0 ± 2.2 mg/kg/h.9
784
Expected Outcomes and Safety Benzodiazepine and Narcotic Combinations The largest experience with benzodiazepine/ narcotic combinations reported to date is that of Kezerashvili et al. In 9,558 cardiac procedures, of which a little over half were electrophysiological procedures, there were nine complications, six of which occurred in relation to the electrophysiological procedures.12 Two deaths occurred related to severe hypotension during and after device implantation and a third death occurred in a
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SEDATION FOR ELECTROPHYSIOLOGICAL PROCEDURES
75-year-old male patient who experienced pulseless electrical activity soon after a catheter ablation for atrial flutter. It is not clear whether sedation contributed to these deaths. In three cases, the patients could not be adequately sedated and it was not possible to complete the procedure without general anesthesia and intubation. Two other patients experienced transient hypotension (systolic below 60 mm Hg) and a third experienced an allergic reaction after administration of midazolam and morphine. These patients were resuscitated successfully. Kovoor et al. described a series of 1,344 patients who underwent electrophysiological procedures with midazolam and fentanyl sedation.10 There were no serious complications. In four cases, an anesthesiologist was called to convert to general anesthesia. These were due to restlessness in two cases, hypoventilation in one, and inadequate sedation in another. In 13 additional cases, an anesthesiologist was used for additional sedation during electrical cardioversion. Another study of 700 cases employing midazolam and fentanyl sedation from Pachulski et al. reported no deaths.11 Endotracheal intubation was never required. Mild hypoxemia (SaO2 > 80%, but < 90%) occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and oropharyngeal repositioning, increased oxygen concentration delivery, or intravenous naloxone administration (two cases, 0.3%). Reversible hypotension (systolic blood pressure < 90, but > 60 mm Hg) occurred in 14 patients (2.0%) and was corrected with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope infusion (four cases, 0.6%). No patient stay was prolonged due to sedation. In only five cases (0.7%) did patients have any recollection of the procedure, while in two cases (0.3%) they were specifically aware of pain. Geiger et al. described 536 consecutive procedures, the last 276 of which received deep sedation with a combination of midazolam and fentanyl.2 This was a mixed group undergoing pacing or electrophysiologial procedures. There were no serious complications. Fourteen patients required fluid boluses for systolic blood pressures falling below 90 mm Hg. One required cessation of fentanyl. Where deeper sedation was required for defibrillation testing, there was a higher rate of airway intervention. Fox et al.19 reported their experience with a combination of midazolam and diamorphine or fentanyl in 500 patients undergoing defibrillator implantation. There were no deaths and no patients required endotracheal intubation. One patient experienced apnea, which was treated successfully by flumazenil, a Guedel
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airway, and brief manual ventilation. Sedation was reversed in 7.6% of cases. In a smaller group of 53 patients, Natale et al. used a similar rate of sedation reversal (5.6%).36 Pain during and after ablation was identified as potential sources of patient dissatisfaction in a series of 101 catheter ablation procedures.25 This might be partially explained by the low sedation doses, limited to 10 mg of midazolam with 100 mcg fentanyl or 10 mg diamorphine. Propofol Where deep sedation with propofol was attempted for catheter ablation of atrial fibrillation, no major sedation-related complications were observed in a series of 650 patients.3 Endotracheal intubation or the assistance of an anesthesiologist was not required. Serious procedural complications included cardiac tamponade (n = 6), severe allergy to contrast media (n = 2), transient coronary air embolism (n = 1), and transient ischemic attack (n = 1). Fifteen percent of patients required an ephedrine bolus for hypotension. Eight patients (1.2%) required brief mask ventilation (
Sedation for Electrophysiological Procedures STUART P. THOMAS, B.MED., PH.D., JAY THAKKAR, M.B.B.S., PRAMESH KOVOOR, M.B.B.S., PH.D., ARAVINDA THIAGALINGAM, M.B.B.S., PH.D., and DAVID L. ROSS, M.B.B.S. From the Department of Cardiology, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
Administration of intravenous sedation (IVS) has become an integral component of procedural cardiac electrophysiology. IVS is employed in diagnostic and ablation procedures for transcutaneous treatment of cardiac arrhythmias, electrical cardioversion of arrhythmias, and the insertion of implantable electronic devices including pacemakers, defibrillators, and loop recorders. Sedation is frequently performed by nursing staff under the supervision of the proceduralist and in the absence of specialist anesthesiologists. The sedation requirements vary depending on the nature of the procedure. A wide range of sedation techniques have been reported with sedation from the near fully conscious to levels approaching that of general anesthesia. This review examines the methods employed and outcomes associated with reported sedation techniques. There is a large experience with the combination of benzodiazepines and narcotics. These drugs have a broad therapeutic range and the advantage of readily available reversal agents. More recently, the use of propofol without serious adverse events has been reported. The results provide a guide regarding the expected outcomes of these approaches. The complication rate and need for emergency assistance is low in reported series where sedation is administered by nonspecialist anesthesiology staff. (PACE 2014; 37:781–790) arrhythmias, electrophysiology, sedation, anesthesia, atrial fibrillation, ablation, pacing, defibrillator, cardioversion, pulmonary vein isolation
The administration of sedation for cardiac procedures has become an integral part of the practice of cardiology. Sedation is commonly used for electrophysiological procedures, transesophageal echocardiography, and cardiac catheterization. The electrophysiological procedures for which sedation is employed include diagnostic and ablation procedures for cardiac arrhythmias, electrical cardioversion, and the insertion of implantable electronic devices including loop recorders, pacemakers, and defibrillators. The purpose of sedation for these procedures is to improve patient comfort. Sedation is frequently performed by specialized nurses under the supervision of the procedural cardiologist. The purpose of this review is to examine the agents used, methods, and safety of this approach.
Conflict of Interest: The authors have no conflicts of interest in relation to this manuscript. Address for reprints: Stuart P. Thomas, B.Med., Ph.D., Department of Cardiology, Westmead Hospital, Cnr Hawkesbury and Darcy Roads, Westmead, NSW 2145, Australia. Fax: 61 2 9845 8323; e-mail: [email protected] Received June 23, 2013; revised January 5, 2014; accepted January 7, 2014. doi: 10.1111/pace.12370
Sedation and anesthetic practices vary dramatically throughout the world. There is variation in the selection of patients for sedation or general anesthesia, the personnel administering sedation, the agents employed, and the technique for monitoring sedation. Deep levels of sedation are often administered in the absence of specialist anesthesiologists.1–4 The purpose of this review is to examine the evidence relating to the agents used, methods, and safety of sedation for cardiac electrophysiological procedures. We reviewed data supporting approaches to sedation in these cases. We identified manuscripts that evaluated use of sedation for cardiac electrophysiology procedures by searching the EMBASE and MEDLINE databases and the Cochrane library for publications from January 1970 to September 2013. The search design was conducted by two authors (JT and SPT). This search was supplemented by hand searching bibliographies of published studies and relevant review articles. The search terms: “sedation” or “anesthesia,” in combination with “electrophysiology,” “pacing,” “cardiac devices,” “cardioversion,” “catheter ablation,” or “pulmonary vein isolation” were used. We focused on clinical trials, case-control studies, cohort studies, case series, and expert
©2014 Wiley Periodicals, Inc. PACE, Vol. 37
June 2014
781
THOMAS, ET AL.
consensus guidelines. We excluded individual case reports and editorials. Our initial screen yielded 13,789 manuscripts. Limiting our search to human studies in adults (>18 years) with publication in the English language reduced this to 1,084. In most cases, series of fewer than 50 patients were excluded. Title and abstract screening further reduced the number of manuscripts to those described in this review. Manuscripts not focusing on the process of sedation or anesthesia during electrophysiological procedures were excluded. Aims of Sedation and Advantages of General Anesthesia or Intravenous Sedation (IVS) The aims of sedation during cardiac procedures are to reduce patient discomfort and patient movement. Some shorter electrophysiological procedures may be performed with the patient awake or only lightly sedated. The pain associated with implantation of cardiac devices can usually be minimized by administration of local anesthesia. However, some electrophysiological procedures, including ablation of pain-sensitive sites and electrical cardioversion, require systemic analgesia. More complex electrophysiological procedures may have the additional demand of requiring the patient to remain relatively still. Some electrophysiological mapping systems employ sensors outside the body to determine catheter position in relation to that of the heart. These systems may partially compensate for patient movement but such compensation is imperfect. Ablation in the vicinity of critical structures, including the His-bundle, and procedures such as transeptal catheterization require the patient to be immobile to reduce the risk of complications. Assessing the Depth of Sedation The optimal level and technique for sedation depends on the nature of the procedure. For complex electrophysiological procedures, a wide range of practices are employed ranging from very light sedation to general anesthesia. The optimal level of sedation for electrophysiological procedures has not yet been definitively determined. The presence of pain during ablation may lead to movement, which makes the procedure more difficult. Such pain, however, may also alert the operator to a risk of complications. The use of muscle relaxants during general anesthesia may prevent phrenic nerve pacing, a technique used to avoid phrenic nerve injury. Deep sedation or anesthesia may delay the diagnosis of cerebrovascular events. However, these deeper levels of sedation reduce patient movement and may facilitate electrical cardioversion when required. Some anesthetic
782
Table I. Ramsay Sedation Scale Modified from Ramsay et al.5 Ramsay Sedation Scale (1) Patient is anxious and agitated or restless, or both. (2) Patient is cooperative, oriented, and tranquil. (3) Patient responds to commands only. (4) Patient exhibits brisk response to light glabellar tap or loud auditory stimulus. (5) Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus. (6) Patient exhibits no response.
agents reduce the inducibility of arrhythmias. This is a major consideration for studies that have a diagnostic component, including studies of ventricular tachycardia and supraventricular tachycardias. Agents that depress cardiac function may also be problematic during ablation of ventricular tachycardia. Ventricular tachycardia, well tolerated in the conscious patient, may cause hemodynamic collapse in patients under general anesthesia. Scales have been developed to allow estimation and standardization of the depth of sedation. Most authorities emphasize the continuum of sedation and acknowledge that divisions between levels of sedation may be arbitrary. Most sedation scales suggested for cardiac electrophysiological procedures are modifications of the Ramsey scale introduced to describe levels of sedation in the intensive care environment.5 The original scale relied on response to auditory stimulation or the glabellar tap (Table I). The first sedation scale for electrophysiological procedures was included in the 1998 Consensus Document of the North American Society for Pacing and Electrophysiology (Table II).6 A more recent scoring system is that of the American Society of Anesthesiologists,7 which also recommended a variation on the Observer’s Assessment of Alertness/Sedation developed by Chernik et al. (Table III).8 Pharmacological Agents, Doses, and Method of Administration Benzodiazepines The most common approach for sedation and pain relief during cardiac procedures is the use of benzodiazepines and narcotics either alone or in combination. The combination of these drugs provides analgesia, sedation, and amnesia. Local anesthetic is required in all cases.
June 2014
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SEDATION FOR ELECTROPHYSIOLOGICAL PROCEDURES
Table II. Spectrum of Sedation Modified from Bubien et al.6 Spectrum of Sedation (SEC): Scores: 2 = Present, 1 = Limited, 0 = Absent Responds Purposefully to Level
Consciousness
Light sedation IV Sedation (A) Sleepy (B) Sleep (C) Advanced sleep Deep sedation Gen. anesthesia
Near normal
Very depressed Unarousable
Verbal Stim.
Physical Stim.
Airway
Respiration
Total SED Score
2
2
2
2
8
1–2 0–1 0 0 0
2 1 1 0 0
2 2 1–2 0–1 0–1
2 1–2 1 0–1 0–1
7–8 4–6 3–4 0–2 0–2
Table III. Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia and Modified Observers Assessment of Alertness/Sedation (MOAA/S)7,8
Minimal Sedation (Anxiolysis)
Moderate Sedation/ Analgesia (Conscious Sedation)
Airway
Normal response to verbal stimulation Unaffected
Spontaneous ventilation
Unaffected
Purposefula response to verbal or tactile stimulation No intervention required Adequate
Cardiovascular function
Unaffected
Usually maintained
Responsiveness
MOAA/S Scorea 5 4 3 2 1 0 a Reflex
Deep Sedation/Analgesia
General Anesthesia
Purposefula response after repeated or painful stimulation
Unarousable, even with painful stimulus
Intervention may be required May be inadequate Usually maintained
Intervention often required Frequently inadequate May be impaired
Description Responds readily to name spoken in normal tone Lethargic response to name spoken in normal tone Responds after name called loudly or repeatedly Purposeful response to mild prodding or mild shaking Responds to trapezius squeeze (includes purposeful and reflexive withdrawal) No response to painful stimulation (trapezius squeeze)
ASA Continuum Minimal sedation Moderate sedation Moderate sedation Moderate sedation Deep sedation General anesthesia
withdrawal from a painful stimulus is not considered a purposeful response.
The most commonly studied benzodiazepines for sedation are diazepam and midazolam. These agents have a wide therapeutic range and can be reversed with flumazenil. They are metabolized in the liver and the metabolites are excreted by the kidneys. Midazolam has been used widely for sedation during electrophysiological procedures, usually in
PACE, Vol. 37
conjunction with other agents. The initial bolus and infusion doses depend on the doses of other agents, patient characteristics, and the target level of sedation. They are usually adjusted for weight and age, and other factors that may alter the drug metabolism or patient response. An initial bolus dose is usually in the range of 0.01–0.1 mg/kg.2,3,9–12 This may be followed by repeated
June 2014
783
THOMAS, ET AL.
boluses or an infusion of up to 0.1 mg/kg/h. During long procedures, midazolam can cause restlessness that may be overcome by cessation of the drug and sedation with a different agent.13 When midazolam was used alone (after oral diazepam) to perform electrical cardioversion, a relatively high dose was required (5–12.5 mg).14–16 Diazepam has a longer half-life and is, therefore, less popular. External cardioversion has been described most commonly with doses of up to 30 mg.14,17 Pugh et al. described administration of diazepam with doses up to 100 mg (mean 27.2 mg).18
One patient receiving remifentanil experienced respiratory depression and muscular rigidity. Vomiting occurred in 10%. Morphine was used with midazolam by Kezerashvili et al.12 The mean dose ranged from 9.9 mg for diagnostic electrophysiological procedures to 14.6 mg for ablation procedures. These doses corresponded to an infusion rate of approximately 0.05 mg/min. The concurrent midazolam was administered at a similar dose. Other opioids that have been used for sedation include piritramid, meperidine, sulfentanil, alfentanil, and diamorphine.13,24
Narcotics Benzodiazepines have relatively poor analgesic properties and are frequently combined with narcotics. The most commonly described narcotics for cardiac sedation are fentanyl and morphine. Like benzodiazepines, narcotics have a wide therapeutic window. Their effect can be reversed by naloxone hydrochloride. With the exception of remifentanil, which is metabolized in the bloodstream, they are metabolized in the liver. Fentanyl is a relatively short-acting narcotic and the most commonly used in cardiac sedation. Like midazolam, with which it is frequently coadministered, it is often given as a bolus dose followed by an infusion. The bolus dose of fentanyl depends on patient characteristics and the use of other agents. Bolus doses are typically in the range of 10–50 mcg.3,4,9–11,19 The infusion dose described is in the range of 0.5–2.0 mcg/kg/h.2,9–11 Both doses may be adjusted for weight and age.10 The combination of midazolam and fentanyl does not have a significant adverse effect on arrhythmia inducibility.20 Remifentanil is a narcotic with a very short half-life. The drug has a time to peak effect of approximately 90 seconds and a half-life of 3–4 minutes. Remifentanil use has been described in complex electrophysiological studies combined with midazolam with doses of 0.06– 0.14 mcg/kg/min. Electrical cardioversion and epicardial access using a subxiphoid approach were reported using this combination.21 In another study, remifentanil reduced the dose of propofol or midazolam required to tolerate electrical cardioversion.22 Remifentanil may produce bradycardia and hypotension. Use of remifentanil in isolation with patient-controlled analgesia was described by Lena et al. in a nonrandomized comparison with infused propofol.23 Patients undergoing catheter ablation for atrial flutter were studied. Those receiving remifentanil experienced lower levels of sedation and had higher pain scores than those undergoing infused propofol sedation.
Propofol Propofol has the advantage of rapid onset and offset of action. It has a wide therapeutic range but may cause bradycardia, respiratory depression, or hypotension. Hypotension is common in elderly and dehydrated patients13 The use of propofol for cardiac procedures has recently been reported in several large series. Kottkamp described 650 patients undergoing ablation for atrial fibrillation.3 Propofol was used after a bolus of midazolam and fentanyl. The dose administered was initially 5 mg/kg/h and the mean dose was 399 mg/h. In another series of 1,000 consecutive patients described by Salukhe et al., propofol was also administered under the supervision of cardiologists.4 Fentanyl was administered simultaneously for analgesia. The propofol dose was a 44 ± 18 mg bolus followed by an infusion at a mean rate 390 ± 96 mg/h. Wutzler et al., reported the use of deep sedation or unconscious sedation with propofol and midazolam in a series of 316 patients undergoing catheter ablation for atrial fibrillation.24 A midazolam bolus dose of 0.05 mg/kg was used followed by 0.03 mg/kg maintenance infusion. A propafol infusion of 4 mg/kg/h was adjusted to maintain adequate sedation. The highest doses were used by Tang et al. An infusion of propofol beginning with 4 mg/kg/h was titrated to achieve analgesia and the absence of movement.9 The mean infusion rate was 8.0 ± 2.2 mg/kg/h.9
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Expected Outcomes and Safety Benzodiazepine and Narcotic Combinations The largest experience with benzodiazepine/ narcotic combinations reported to date is that of Kezerashvili et al. In 9,558 cardiac procedures, of which a little over half were electrophysiological procedures, there were nine complications, six of which occurred in relation to the electrophysiological procedures.12 Two deaths occurred related to severe hypotension during and after device implantation and a third death occurred in a
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SEDATION FOR ELECTROPHYSIOLOGICAL PROCEDURES
75-year-old male patient who experienced pulseless electrical activity soon after a catheter ablation for atrial flutter. It is not clear whether sedation contributed to these deaths. In three cases, the patients could not be adequately sedated and it was not possible to complete the procedure without general anesthesia and intubation. Two other patients experienced transient hypotension (systolic below 60 mm Hg) and a third experienced an allergic reaction after administration of midazolam and morphine. These patients were resuscitated successfully. Kovoor et al. described a series of 1,344 patients who underwent electrophysiological procedures with midazolam and fentanyl sedation.10 There were no serious complications. In four cases, an anesthesiologist was called to convert to general anesthesia. These were due to restlessness in two cases, hypoventilation in one, and inadequate sedation in another. In 13 additional cases, an anesthesiologist was used for additional sedation during electrical cardioversion. Another study of 700 cases employing midazolam and fentanyl sedation from Pachulski et al. reported no deaths.11 Endotracheal intubation was never required. Mild hypoxemia (SaO2 > 80%, but < 90%) occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and oropharyngeal repositioning, increased oxygen concentration delivery, or intravenous naloxone administration (two cases, 0.3%). Reversible hypotension (systolic blood pressure < 90, but > 60 mm Hg) occurred in 14 patients (2.0%) and was corrected with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope infusion (four cases, 0.6%). No patient stay was prolonged due to sedation. In only five cases (0.7%) did patients have any recollection of the procedure, while in two cases (0.3%) they were specifically aware of pain. Geiger et al. described 536 consecutive procedures, the last 276 of which received deep sedation with a combination of midazolam and fentanyl.2 This was a mixed group undergoing pacing or electrophysiologial procedures. There were no serious complications. Fourteen patients required fluid boluses for systolic blood pressures falling below 90 mm Hg. One required cessation of fentanyl. Where deeper sedation was required for defibrillation testing, there was a higher rate of airway intervention. Fox et al.19 reported their experience with a combination of midazolam and diamorphine or fentanyl in 500 patients undergoing defibrillator implantation. There were no deaths and no patients required endotracheal intubation. One patient experienced apnea, which was treated successfully by flumazenil, a Guedel
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airway, and brief manual ventilation. Sedation was reversed in 7.6% of cases. In a smaller group of 53 patients, Natale et al. used a similar rate of sedation reversal (5.6%).36 Pain during and after ablation was identified as potential sources of patient dissatisfaction in a series of 101 catheter ablation procedures.25 This might be partially explained by the low sedation doses, limited to 10 mg of midazolam with 100 mcg fentanyl or 10 mg diamorphine. Propofol Where deep sedation with propofol was attempted for catheter ablation of atrial fibrillation, no major sedation-related complications were observed in a series of 650 patients.3 Endotracheal intubation or the assistance of an anesthesiologist was not required. Serious procedural complications included cardiac tamponade (n = 6), severe allergy to contrast media (n = 2), transient coronary air embolism (n = 1), and transient ischemic attack (n = 1). Fifteen percent of patients required an ephedrine bolus for hypotension. Eight patients (1.2%) required brief mask ventilation (
