Cardiac arrhythmias: drugs and devices.

This review focuses on the important role played by the various types of remedial therapy in the prevention and treatment of perioperative cardiac arrhythmias. It discusses the new concepts of arrhythmogenesis and pro-arrhythmia; the long QT interval syndrome; newer, more selective class 3 antiarrhythmic drugs; cardiac rhythm management devices; drugs or devices used as prophylaxis for postoperative atrial arrhythmias; intravenous amiodarone for destabilizing ventricular arrhythmias; and preoperative potassium imbalance.

The use of esmolol, nicardipine, or their combination to blunt hemodynamic changes after laryngoscopy and tracheal intubation.

UNLABELLED: Laryngoscopy and tracheal intubation (LTI) often provoke an undesirable increase in blood pressure (BP) and/or heart rate (HR). We tested the premise that nicardipine (NIC) and esmolol (ESM) in combination (COMB) would oppose both. Adult surgical patients received pretreatment (randomized) with IV bolus NIC 30 microg/kg (n = 31), ESM 1.0 mg/kg (n = 34), or COMB (one-half dose each, n = 32). Peak BP and HR after LTI were compared with controls (CONT; n = 35) with no pretreatment. Anesthetic induction was standardized: IV thiopental (5-7 mg/kg), fentanyl (1-2 microg/kg), and succinylcholine (1.5 mg/kg). Systolic (S), diastolic (D), and mean (M) BP and HR awake before pretreatment (baseline) were similar in all test groups. No patient was treated for hypotension, bradycardia, or tachycardia after pretreatment or anesthetic induction. Peak HR after LTI was increased versus baseline in CONT and all test groups, but did not differ from CONT among the test groups. Peak SBP and DBP increased versus baseline in CONT, and with ESM and NIC, but not COMB. Peak SBP, DBP, and MBP were increased with ESM versus COMB, and peak DBP with ESM versus NIC. Compared with no pretreatment before the IV induction of general anesthesia, the peak increase in BP after LTI is best blunted by the combination of nicardipine and ESM, compared with either drug alone. No single drug or combination in the doses tested opposed increased HR. IMPLICATIONS: Compared with no pretreatment before the IV induction of general anesthesia, the peak increase in blood pressure after laryngoscopy and tracheal intubation is best blunted by the combination of nicardipine and esmolol, compared with either drug alone. No single drug or combination in the doses tested opposed increased heart rate.

Comparison of a prototype esophageal oximetry probe with two conventional digital pulse oximetry monitors in aortocoronary bypass patients.

OBJECTIVE: Pulse oximetry (SpO2) is the non-invasive standard for monitoring arterial oxygen saturation in patients undergoing anesthesia, but is subject to external interference by motion artifact, peripheral vasoconstriction, and low cardiac output. We hypothesized that oximetry signals could be acquired from the esophagus when peripheral pulse oximetry is unobtainable. Therefore, we tested an esophageal stethoscope which incorporates transverse oximetry photodetectors and emitters in patients undergoing coronary bypass surgery. METHODS: Immediately after induction of general anesthesia in 10 coronary artery bypass (CABG) patients, Criticare and Nellcor digital probes were positioned on the left hand, concurrent with placement of an esophageal SpO2 probe. A computer recorded 5,910 matched oximetry signals every 15 sec during an average of 2.5 hrs. All SpO2 measurements were before, and immediately after non-pulsatile, hypothermic cardiopulmonary bypass. Data represent the percentage (median value [range]) of the total monitored time that a SpO2 value was displayed. RESULTS: The Nellcor (99.8%, range 6.5-100%) and Criticare (99.7%, range 36.6-100%) acquired and displayed saturation signals more frequently (p = 0.003) than the esophageal monitor (75.3%, range 42.1-95.8%). The two standard digital oximeters had a mean difference of 0.9%, with a standard deviation of the differences of 0.9. The esophageal probe had a mean difference of -5.2% and -4.8%, with standard deviation of differences of 8.0 and 7.7 (compared to the Nellcor and Criticare monitors, respectively). A second-generation prototype shielded from electrocautery interference was tested in an additional 4 patients. The shielded prototype displayed signals more frequently (96.7%, range 68.4-100%) than the original esophageal prototype. CONCLUSIONS: Digital pulse oximetry failure is common in CABG patients, probably because of marginal cardiac output and peripheral vasoconstriction associated with hypothermia. Our study could not confirm that esophageal technology, which utilizes the esophagus as a site of transflectance oximetry, was superior to conventional digital pulse oximetry.

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs.

UNLABELLED: Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. IMPLICATIONS: Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Perioperative ventricular dysrhythmias in patients with structural heart disease undergoing noncardiac surgery.

UNLABELLED: Noncardiac surgical patients with preoperative ventricular dysrhythmias and structural heart disease may be at increased risk of adverse cardiac outcome. We evaluated how anesthesia and surgery affect the course of ventricular dysrhythmias (premature ventricular beats [PVB] and repetitive forms of ventricular beats [RFVB]: couplets and nonsustained ventricular tachycardia) noted preoperatively in patients with structural heart disease and whether the frequency of ventricular dysrhythmias affects cardiac outcome. In a prospective study, 70 patients scheduled for noncardiac surgery with structural heart disease and RFVB on preoperative Holter electrocardiogram were continuously monitored intraoperatively and for 3 days postoperatively. Holter tracings were analyzed for rhythm, medians of total PVB and RFVB per hour. Preoperative RFVB recurred intraoperatively in 35% and postoperatively in 87% of patients. There was a significant intra- and postoperative decrease of total PVB per hour (P < 0.05) and RFVB per hour (P < 0.01). Frequency of ventricular dysrhythmias in the five patients suffering adverse outcome (unstable angina, n = 1; congestive heart failure, n = 4) did not significantly differ from those with good outcome. We conclude that in noncardiac surgical patients with structural heart disease and RFVB, the frequency of ventricular dysrhythmias is not associated with adverse cardiac outcome. IMPLICATIONS: Using continuous electrocardiogram monitoring, we investigated whether the frequency of perioperative ventricular dysrhythmias independently affects outcome in patients with structural heart disease undergoing noncardiac surgery. The incidence of perioperative dysrhythmia in patients with an adverse outcome (8%) did not differ from those with a good outcome.

Anesthetics and automaticity of dominant and latent pacemakers in chronically instrumented dogs. IV. Dysrhythmias after sinoatrial node excision.

BACKGROUND: Subsidiary atrial pacemakers assume control after sinoatrial (SA) node excision, and anesthetic-catecholamine interactions can produce severe bradycardia during isoflurane anesthesia. We hypothesized that epinephrine enhances atrial, atrioventricular junctional, and ventricular dysrhythmias after SA node excisions in dogs and that inhalation anesthetics would facilitate such dysrhythmias. METHODS: In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, at the His bundle, and along the sulcus terminalis. Site of the earliest atrial activation and incidences of nonatrial beats were determined in the conscious state, with methylatropine, with epinephrine, and during halothane, isoflurane, or enflurane anesthesia. RESULTS: After SA node excision, a stable, regular subsidiary atrial pacemaker rhythm resulted. Epinephrine and halothane shifted the site of earliest activation to more remote atrial sites. Epinephrine-induced ventricular escape was increased by all anesthetics tested, but atropine prevented ventricular escape. Epinephrine-induced His bundle (atrioventricular junctional) and premature ventricular beats were increased by halothane and enflurane. After SA node excision, ventricular escape occurred as a result of epinephrine-anesthetic interactions, especially during anesthesia with isoflurane. CONCLUSIONS: In dogs with excised SA nodes, anesthetic-catecholamine interaction facilitates ventricular escape, His bundle dysrhythmias, and premature ventricular beats. In addition, halothane and enflurane, more than isoflurane, facilitate ectopic ventricular tachydysrhythmias with epinephrine. Compared to intact dogs, dogs with excised SA nodes may be more susceptible to epinephrine anesthetic dysrhythmias. If findings can be extrapolated to humans, intrinsic SA node dysfunction may facilitate severe cardiac dysrhythmias with inhalation anesthetics and catecholamines.

Muscarinic and ganglionic blocking properties of atropine compounds in vivo and in vitro: time dependence and heart rate effects.

High doses (3 mg/kg) of methylatropine nitrate have been used in vivo to produce long-lasting muscarinic blockade during physiologic experiments. At these levels, the possibility exists that ganglionic blockade may also be responsible for some heart rate effects. Therefore, the effects of methylatropine nitrate (0.0012-2.4 mg.kg(-1)) and atropine sulfate (0.0036 - 0.060 mg.kg(1)) were evaluated in vivo using conscious dogs and in vitro using canine right atria and isolated stellate ganglia. The lowest doses of either agent given in vivo caused bradycardia, while intermediate doses induced excess tachycardia. High doses of methylatropine nitrate transiently decreased the heart rate, followed by slow recovery. In vitro using the canine right atria, neither drug caused pacemaker shifts nor directly altered the atrial rate, but postvagal tachycardia occurred with acetylcholine challenge and was prevented by metoprolol or 6-hydroxydopamine. In vitro studies using the canine stellate ganglia indicate that both agents depressed postganglionic compound action potentials at high doses. In conclusion, with high-dose methylatropine nitrate, ganglionic blockade yields the mechanism for a reduction of excess tachycardia as well as a likely explanation for opposing chronotropic effects in conscious and anesthetized dogs. In experimental studies where high doses of atropine compounds are used for long-term muscarinic blockade, it is possible that ganglionic blocking effects may also be produced.

Anesthetics and automaticity of dominant and latent atrial pacemakers in chronically instrumented dogs. III. Automaticity after sinoatrial node excision.

BACKGROUND: Management of patients with sinus node dysfunction must consider the stability of subsidiary pacemakers during anesthesia and treatment with antimuscarinic or sympathomimetic drugs. Baroreflex regulation of atrial pacemaker function is known to contribute to the interactions between inhalation anesthetics and catecholamines. Sinoatrial (SA) node excision can be a model for intrinsic SA node dysfunction. Subsidiary atrial pacemakers are expected to emerge after SA node excision, but they may respond differently to humoral and neural modulation. Isolated and combined effects of epinephrine and methylatropine should help characterize subsidiary pacemaker function during anesthesia with halothane, isoflurane, and enflurane. METHODS: In eight dogs, SA nodes were excised and epicardial electrodes implanted at the atrial appendages, the His bundle, and along the sulcus terminalis. Spontaneous pacemaker automaticity and subsidiary atrial pacemaker recovery time were measured in the conscious state, in the presence of methylatropine, with 1 and 2 micrograms.kg-1.min-1 epinephrine and during 1.25 and 2 MAC halothane, isoflurane, and enflurane. RESULTS: After SA node excision, a stable and regular subsidiary atrial pacemaker rhythm emerged. Each anesthetic prolonged subsidiary atrial pacemaker recovery times. This prolongation was greater in the presence of methylatropine. Without methylatropine, isoflurane and enflurane, but not halothane, further enhanced the baroreflex-mediated negative chronotropic effects of epinephrine, whereas with methylatropine, each anesthetic reduced the direct positive chronotropic effects of epinephrine. CONCLUSIONS: Halothane, isoflurane, and enflurane have significant depressant effects on the spontaneous and epinephrine-altered automaticity of subsidiary atrial pacemakers. Depression of subsidiary atrial pacemaker automaticity was most apparent in dogs with muscarinic blockade.

Anesthetics and automaticity of dominant and latent pacemakers in chronically instrumented dogs. I. Methodology, conscious state, and halothane anesthesia: comparison with and without muscarinic blockade during exposure to epinephrine.

BACKGROUND: Supraventricular dysrhythmias are common during anesthesia, but have been incompletely investigated. Mechanisms may involve altered automaticity of subsidiary pacemakers and participation of vagal reflexes. The following hypotheses were tested: (1) shifts from the sinoatrial (SA) node to subsidiary pacemakers require intact vagal reflexes and (2) halothane sensitizes the heart to epinephrine-induced atrial pacemaker shifts. METHODS: Epicardial electrodes were implanted in eight dogs on both atrial appendages, the right ventricle, along the sulcus terminalis, and at the His bundle. Weekly testing awake (control), awake with atropine methylnitrate, with 1 and 2 micrograms epinephrine.kg-1.min-1 (3 min-infusions), and under 1.25 and 2 MAC halothane was performed. Electrograms were analyzed for the site of earliest activation (SEA), which was scored 1-6 depending on the distance from the SA node, and expressed as the SEA value. RESULTS: In conscious dogs (control) and at 1.25 MAC halothane, epinephrine increased the SEA values (shifted activation from SA node) and blood pressure, and decreased heart rate; however, with atropine, SEA values were unaffected by epinephrine, although blood pressure and heart rate were elevated. At 2 MAC, atropine did not affect the epinephrine-induced increase in SEA values. Halothane increased SEA values when combined with 1 micrograms epinephrine.kg-1.min-1. CONCLUSIONS: Pacemaker shifts account for atrial dysrhythmias in the conscious state and during 1.25 MAC halothane with epinephrine, and require vagal participation. Halothane sensitizes the heart to epinephrine-induced atrial dysrhythmias. Atropine and halothane facilitate His bundle beats during exposure to epinephrine.

Anesthetics and automaticity of dominant and latent pacemakers in chronically instrumented dogs. II. Effects of enflurane and isoflurane during exposure to epinephrine with and without muscarinic blockade.

BACKGROUND: Atrial dysrhythmias precede ventricular dysrhythmias during epinephrine-anesthetic sensitization, and may be caused by an altered relationship between automaticity of primary and subsidiary pacemakers. The following hypotheses were tested: (1) epinephrine-induced pacemaker shifts with enflurane or isoflurane require intact vagal reflexes and (2) these anesthetics sensitize the atrial myocardium to epinephrine-induced dysrhythmias. METHODS: Eight dogs were instrumented for chronic electrophysiologic investigation, including electrodes at the SA node, atrial appendages, right ventricle, and His bundle, and along the sulcus terminalis. After conscious-state testing, dogs were anesthetized with isoflurane or enflurane and exposed to epinephrine, with or without atropine methylnitrate. Eight-channel ECG recordings were analyzed before and during epinephrine infusions. Atrial pacemakers were assigned values 1-6 with increasing distance from the SA node, normalized and expressed as the site of earliest activation value (SEA). RESULTS: Epinephrine increased SEA values during enflurane or isoflurane anesthesia. Atropine enhanced this increase during enflurane anesthesia, but abolished the increase during isoflurane anesthesia. Enflurane increased SEA values only when combined with atropine. Isoflurane did not increase SEA values under any test conditions. CONCLUSIONS: With enflurane, epinephrine-induced atrial pacemaker shifts in chronically instrumented dogs are caused by direct depression of SA node automaticity or a relative increase of automaticity in subsidiary atrial pacemakers. With isoflurane, pacemaker shifts are caused by reflex-induced vagal suppression of SA node automaticity and escape of latent pacemakers. Enflurane sensitizes the atrial myocardium to dysrhythmias when combined with muscarinic blockade; isoflurane does not sensitize the atrium.

Anesthetics and automaticity in latent pacemaker fibers. IV. Effects of isoflurane and epinephrine or norepinephrine on automaticity of dominant and subsidiary atrial pacemakers in the canine heart.

BACKGROUND: Anesthesia and surgery may be associated with atrioventricular junctional or ventricular rhythm disturbances. These may be caused by alteration of automaticity of primary and subsidiary pacemakers. METHODS: The direct effects of isoflurane, alone or in combination with epinephrine (E) and norepinephrine (NE), as well as single effects of E and NE, were examined on automaticity of primary and subsidiary atrial pacemakers (SAP) using a perfused canine right atrial preparation (n = 29). Preparations were perfused with oxygenated Krebs' solution at a constant perfusion pressure of 87 mmHg and a temperature of 36.5 +/- 0.5 degrees C. Delivered concentrations of isoflurane of 1.4 and 2.8% corresponded to measured perfusate concentrations of 315 +/- 7 and 617 +/- 16 microM in experiments with E (n = 14), and 316 +/- 10 and 610 +/- 26 microM in experiments with NE (n = 15). Epinephrine or NE perfusate concentrations were 2 and 5 micrograms/l or 5 and 10 micrograms/l, respectively. To determine the site of earliest activation, extracellular recordings were made from the SA node region and distal sites (approximately 1, 2, and 3 cm) along the sulcus terminalis, the previously reported locations of SAP. Sites of earliest activation shifts from SA node to SAP were scored 1, 2, or 3 depending on the distance from the control pacemaker. The summed shift scores (magnitude score) were normalized by dividing by the total number of preparations for each experimental condition. RESULTS: Exposure to isoflurane, NE, or E alone did not produce a significant increase in the incidence of pacemaker shifts or normalized pacemaker shift scores. Only the high dose of E significantly increased the incidence of pacemaker shifts and normalized shift scores. Dysrhythmogenic potential of E and NE tended to be greater after earlier exposure to isoflurane. Every combination of isoflurane with E or NE produced a significant increase in the incidence of pacemaker shifts and normalized shift scores. CONCLUSIONS: It was concluded that isoflurane with E or NE acts synergistically to increase dysrhythmic potential in the arterial tissue.

Transesophageal atrial pacing for intraoperative sinus bradycardia or AV junctional rhythm: feasibility as prophylaxis in 200 anesthetized adults and hemodynamic effects of treatment.

Sinus bradycardia (SB) or atrioventricular junctional rhythm (AVJR) may produce circulatory insufficiency in anesthetized surgical patients, especially those with cardiovascular disease. Chronotropic drugs have been the preferred initial treatment, except when epicardial pacing is available. Alternative methods include transvenous or transcutaneous pacing. Drugs may be ineffective or have undesirable effects. Transvenous pacing is time consuming and risky, and transcutaneous pacing is not universally applicable or effective. Transesophageal atrial pacing (TAP) lacks these disadvantages, but unavailability of equipment and unfamiliarity with the method has discouraged widespread use. Feasibility of TAP as prophylaxis for intraoperative SB or AVJR was tested with approved or investigational devices in 200 anesthetized surgical patients, not necessarily with cardiovascular disease or having cardiac surgery. Of these, 84 later had incidental SB < or = 60 beats/min, and 23 of these 84 had SB < or = 50 beats/min. Thirteen patients had AVJR (72 +/- 4 beats/min; mean +/- SEM). TAP at 80 beats/min for SB, or at a rate sufficient to overdrive AVJR, was effective initial treatment in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of transesophageal atrial pacing stethoscope in adult surgical patients under general anesthesia.

Sinus bradycardia (SB) and atrioventricular junctional rhythm (AVJR) commonly cause circulatory insufficiency in anesthetized surgical patients. Treatment is usually with drugs, which can be ineffective or have adverse effects. Cardiac pacing might be preferred, but the transvenous or epicardial routes are too invasive for routine use, and transcutaneous pacing fails to preserve atrial transport function. Transesophageal atrial pacing (TAP) lacks these disadvantages, yet unavailability of inexpensive products has prevented more widespread use. Therefore, a pacing esophageal stethoscope (PES) fabricated by addition of bipolar electrodes to disposable esophageal stethoscopes routinely used for intraoperative monitoring, was evaluated in 100 anesthetized adults. TAP thresholds (10-msec pulses) and hemodynamic effects of TAP as treatment for incidental SB (< or = 60 beats/min) or AVJR were determined. Minimum TAP thresholds (mean +/- standard error) in 48 males were 7.3 +/- 0.3 mA and in 51 females were 8.5 +/- 0.4 mA. Corresponding inferior alveolar ridge-to-electrode distances were 32.5 +/- 0.2 and 30.4 +/- 0.2 cm. For 48 patients with SB < or = 60 beats/min (54 +/- 1 beats/min), TAP (81 +/- 1 ppm) produced average 15, 11, and 14 mmHg increases in systolic, diastolic, and mean arterial pressure, respectively (P < 0.001). For 11 patients with AVJR (71 +/- 5 beats/min), TAP (92 +/- 3 ppm) produced average 23 and 15 mmHg increases in systolic and mean arterial pressure, respectively (P < 0.05). There were no apparent complications of TAP. TAP with a PES appears practical, safe, and effective for prophylaxis and treatment of SB or AVJR in anesthetized surgical patients.

Halothane, enflurane and isoflurane on abnormal automaticity and triggered rhythmic activity of Purkinje fibers from 24-hour-old infarcted canine hearts.

The effects of inhalation anesthetics halothane, enflurane, and isoflurane on spontaneous impulse initiation (automaticity) and triggered sustained rhythmic activity were examined in Purkinje fibers derived from normal (n = 38) and 24-h-old infarcted canine hearts (n = 27) to further understanding of their influence on the cellular mechanisms underlying generation of cardiac arrhythmias. Purkinje fibers from normal or infarcted hearts were superfused with modified Krebs' solution (37 degrees C) with or without epinephrine (2 or 15 microM) and equilibrated with a 97% O2-3% CO2 gas mixture (control). Transmembrane action potentials were recorded using conventional microelectrode techniques, and Purkinje fibers were exposed to anesthetic concentrations equivalent to 2.0 MAC. Normal Purkinje fibers were not spontaneously active unless exposed to epinephrine. All anesthetics (enflurane greater than halothane, isoflurane; P less than 0.05) increased automaticity of normal Purkinje fibers exposed to either epinephrine concentration. Partially depolarized Purkinje fibers from infarcted hearts were either spontaneously active or were quiescent. For ischemic fibers that beat spontaneously, abnormal automaticity was sustained (duration greater than 300 s) or periodic (duration less than 300 s). Sustained abnormal automaticity was elicited by epinephrine (15 microM) in some quiescent partially depolarized fibers. None of the anesthetics affected the rate of sustained abnormal automaticity, regardless of whether the induction of such automaticity required epinephrine, nor did anesthetics significantly affect the duration of trains of periodic abnormal automaticity. Finally, quiescent, partially depolarized Purkinje fibers were tested for triggered rhythmic activity during pacing at a cycle length of 800 ms.(ABSTRACT TRUNCATED AT 250 WORDS)