Background. The purpose of this report is to describe our initial experience with a tiered-therapy, variable detection criteria, multiprogrammable antiarrhythmia device capable of antitachycardia pacing, cardioversion, and defibrillation in 50 cardiac arrest survivors. Methods and Results. An epicardial lead system was used in 35 patients. A transvenous lead system was used in 15 patients. The index arrhythmia leading to device implantation was ventricular fibrillation (VF) in 23 patients, ventricular tachycardia (VT) in 21 patients, and both VT and VF in six patients. Postoperatively, all 50 patients benefited from the additional functions available in the new device compared with a device capable only of high-energy termination of arrhythmias using a simple rate detection algorithm. Total patient survival over a mean follow-up period of 15±5 months was 96%, with no patient succumbing to sudden arrhythmic death, cardiac death, or surgical death. Nine patients (18%) avoided the need for a bradycardia pacemaker because of the device's backup bradycardia pacing function. A programmable tachycardia cycle length stability algorithm prevented inappropriate device intervention into atrial fibrillation in 11 patients (22%). Detection schema flexibility, antitachycardia pacing capabilities, and low-energy cardioversion options allowed the elimination or avoidance of antiarrhythmic drugs in 41 patients (82%). Device data storage facilitated troubleshooting and reprogramming of detection algorithms and therapeutic schema in all 50 patients. Finally, the ability to perform noninvasive programmed electrical stimulation obviated the need for invasive cardiac catheterization in 35 of 35 patients who required electrophysiological testing after device implantation. Conclusions. These findings indicate that a multiprogrammable antiarrhythmia device can provide a substantial advance in the treatment of patients with disabling or life-threatening ventricular arrhythmias by minimizing the use of painful shocks, reducing the need for antiarrhythmic drugs, lowering the incidence of inappropriate shocks, facilitating electrophysiological evaluation, and obviating the need for dual-device therapy. (Circulation 1992;85:1689-1698)

Implantable Defibrillators in Women. Clinical rhythm, heart disease, ejection fraction, defibrillation threshold, recurrent arrhythmias, and mortality were compared in 268 consecutive recipients (213 men and 55 women) of their first implantable cardioverter defibrillator for life‐threatening ventricular tachycardia or fibrillation. Women were younger than men, less likely to have structural heart disease, and more likely to have clinical ventricular fibrillation, a higher ejection fraction, and a lower defibrillation threshold. Complications of defibrillator placement were similar in both sexes. Unadjusted survival tended to be higher in women than in men (97% vs 90%, respectively, at 2 years, P = 0.08), largely due to fewer deaths from noncardiac causes or cardiac causes other than arrhythmia (P = 0.04). Women also tended to be at lower, albeit still substantial, risk for recurrent arrhythmias during follow‐up (37% vs 52% in men at 2 years, P = 0.11). After adjustment for baseline differences, overall survival, arrhythmia death‐free survival, nouarrhythmia death‐free survival, and frequency of recurrent arrhythmias were not found to be gender related. Despite their apparent “lower risk” status on initial presentation, women remained at substantial risk for recurrent arrhythmias. This underscores the need to avoid being unduly biased by the “appearance” of health in managing women with malignant arrhythmias. That survival and other clinical endpoints were all ultimately independent of gender emphasizes the importance of other clinical variables in assessing risk from ventricular tachyarrhythmias.

(Fitzgibbon) Acting Assistant Professor, Department of Anesthesiology, University of Washington, Seattle.(Rapp, Terman) Assistant Professor of Anesthesiology, University of Washington, Seattle.(Butler) Associate Professor of Anesthesiology, University of Washington, Seattle.(Dolack) Assistant Professor of Cardiology, University of Washington, Seattle.(DuPen) Pain Consultation Service, Department of Anesthesia, Swedish Hospital Medical Center, Seattle.(Ready) Professor of Anesthesiology; Director of Acute Pain Services, University of Washington, Seattle.Received from the Department of Anesthesiology, University of Washington, Seattle, Washington. Submitted for publication September 14, 1995. Accepted for publication November 28, 1995.Address reprint requests to Dr. Fitzgibbon: Department of Anesthesiology, Box 356540, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195.A small percentage of patients with cancer pain suffer from refractory pain despite aggressive therapy. [1]Intra-spinal administration of opioids and local anesthetic agents may be helpful in such settings, but their use may be limited by side effects such as motor block and hemodynamic instability. [2,3]Clonidine is a centrally acting alpha2-adrenergic agonist with established analgesic effects [4,5]and has synergistic effects with spinal opioids [6,7]and spinal local anesthetics. [8,9]Epidural clonidine produces analgesia by a spinal mechanism in patients after surgery and in those with cancer pain, [10]and it appears to be an effective treatment for severe cancer pain in patients for whom other treatments are ineffective. [11].Although the risk of acute withdrawal and rebound hypertension is well recognized with sudden cessation of systemically administered clonidine, [12]no such reports exist with regard to epidurally administered clonidine. We describe a case of acute withdrawal and rebound hypertension after abrupt cessation of epidural clonidine in a patient with intractable cancer pain.A 49-yr-old man was diagnosed with metastatic adenocarcinoma of the pancreas. The patient was normotensive and did not have a history of alcohol or other drug abuse. Despite chemotherapy with 5-fluorouracil and gencitabine, increased tumor growth resulted in complaints of upper abdominal pain radiating through to the back. Pain management was further complicated by complaints of diffuse abdominal pain and intermittent constipation associated with long-standing irritable bowel syndrome. Treatment with escalating doses of sustained-release and immediate-release morphine failed to control his pain and exacerbated his constipation. A neurolytic retrocrural celiac plexus block with 40 ml of 100% anhydrous alcohol produced only minimal relief of the pain. A temporary thoracic epidural catheter was inserted at the T8-T9 interspace, and a combination of 0.125% bupivacaine and 40 micro gram/ml morphine administered at 12 ml/h resulted in adequate pain control. One week later, a subcutaneously tunneled thoracic epidural catheter was inserted. The patient's pain was successfully managed at home with this regimen for 6 weeks. Because of complaints of increasing diffuse abdominal pain and postural hypotension, the patient was readmitted for evaluation and pain control. After epidurogram confirmation of catheter placement in the epidural space, incremental increases of both the bupivacaine and morphine concentrations failed to produce adequate pain control with unacceptable lower extremity motor impairment and postural hypotension. An epidural infusion of clonidine was added in a concentration of 10 micro gram/ml and commenced at 20 micro gram/h. This resulted in satisfactory pain control, enabling a rapid reduction in bupivacaine and morphine concentrations. Pain control was deemed adequate and postural hypotension eliminated with a combination of 0.1% bupivacaine and 50 micro gram/ml morphine at 12 ml/h and 10 micro gram/ml clonidine at 3 ml/h. After 2 weeks with this regimen, we noted progressive outward migration of the tunneled catheter. We decided to replace the catheter with a long-term implantable epidural device.Because of concerns for potential infection of the new device, before inserting it, we decided to remove the tunneled catheter and administer intravenous vancomycin for 24 h. The patient was given a hydromorphone patient-controlled analgesia device with a continuous infusion for pain control. In addition, a 0.2-mg clonidine transdermal patch was applied at the time of discontinuing the epidural infusion.Two hours after discontinuation of the epidural infusions, the patient was noted to be more agitated. A further 2 h later, he became progressively diaphoretic and tremulous. Blood pressure was increased from 140/80 to 220/110 mmHg, and heart rate was 170 beats/min. During this period, the patient complained of chest tightness. An electrocardiogram showed sinus tachycardia with new left bundle branch block. Nifedipine (10 mg) was given sublingually without significant effect on blood pressure control. A presumptive diagnosis of rebound hypertension after clonidine withdrawal was made when pain control was reported by the patient to be satisfactory. Five hours after the epidural infusions were discontinued, the patient received 0.1 mg oral clonidine. The patient was transferred to the intensive care unit for observation and blood pressure control. On arrival in intensive care unit, the patient's blood pressure and heart rate were 220/100 mmHg and 160 beats/min, respectively. In addition, the patient was noted to be profoundly agitated and profusely diaphoretic. A second dose of 0.1 mg oral clonidine was administered, and agitation was treated with small, intravenous incremental doses of midazolam to a total dose of 5 mg. Over the next 4 h, the blood pressure and heart rate gradually stabilized at 140/90 mmHg and 90 beats/min. The patient was discharged from the intensive care unit 14 h later with blood pressure stabilized at 140/80 mmHg and heart rate at 95 beats/min. A repeat electrocardiogram showed resolution of the left bundle branch block, and there were no new ST segment changes. Cardiac enzymes were normal. The clonidine transdermal patch was discontinued after the long-term epidural catheter was placed, and the patient recommenced epidural infusions of bupivacaine, morphine, and clonidine. The subsequent hospital course was uneventful, and the patient was discharged home with satisfactory pain control on a continuous epidural infusion of 0.1% bupivacaine and 40 micro gram/ml morphine at 12 ml/h and 10 micro gram/ml clonidine at 3 ml/h.The management of advanced cancer pain is sometimes difficult and may be improved by epidural infusion of varying combinations of local anesthetic, opioid, and clonidine. [11]Although epidural administration of clonidine is not approved by the Food and Drug Administration for long-term use in treating cancer pain, the drug may be used on a compassionate basis in individual cases. Approval for use was sought and obtained in this case. Clinical experience to date with intraspinal clonidine is largely based on postoperative analgesia studies, although Eisenach [11]reported on its long-term use in cancer pain. This and other clinical studies [13–15]suggest that intrathecal and epidural clonidine in combination with opioids is a suitable treatment for intractable cancer pain.The major side effects reported with the use of epidural clonidine are hypotension and sedation. [11]Clonidine decreases blood pressure after epidural administration by actions in the spinal cord [16]and brainstem [17]and in the periphery. [18]alpha2-Agonists decrease blood pressure by producing a "partial sympathectomy" as a result of direct inhibitory actions on preganglionic sympathetic neurons in the spinal cord. [16]Spread of the drug to the brainstem, by either rostral circulation in cerebrospinal fluid or systemic absorption, further diminishes sympathetic nervous system activity by actions at cardiovascular centers. [19–21]Sudden discontinuation of systemically administered clonidine may precipitate a withdrawal syndrome consisting of headache, apprehension, tremors, abdominal pain, sweating, and tachycardia, [12]accompanied or followed by a rapid rise in blood pressure. [22]The mechanism of rebound hypertension appears to involve an agonist-induced downregulation of normally sympatholytic alpha2receptors with resultant hyperresponsiveness of central noradrenergic pressor pathways after abrupt cessation of alpha2-agonist treatment. [23,24].To date, there are no reports of acute withdrawal or rebound hypertension associated with discontinuation of an epidural infusion of clonidine. It is unlikely that the hypertension observed in this case was attributable to discontinuation of the bupivacaine/morphine infusion because pain was adequately controlled at the time by the use of hydromorphone patient-controlled analgesia (boluses plus background infusion). Of interest in our case, acute withdrawal and rebound hypertension were observed within 4 h of stopping the epidural clonidine infusion. This is in direct contrast to the relatively delayed onset of 18–36 h of withdrawal commonly observed with cessation of systemic administration of the drug. We speculate that abrupt withdrawal of epidural clonidine resulted in a more rapid elimination of the drug from cerebrospinal fluid than systemically administered clonidine. This more rapid and earlier decline of cerebrospinal fluid drug level at both cardiovascular brainstem centers and at spinal cord preganglionic sympathetic neurons may account for the earlier withdrawal reaction and rebound hypertension observed with epidural clonidine discontinuation.Treatment recommendations for rebound hypertension and acute withdrawal after sudden cessation of oral or parenteral clonidine therapy include aggressive treatment of severe hypertension by intravenous bolus injection of phentolamine and reinstitution of oral clonidine therapy (0.1–0.2 mg followed by 0.1 mg hourly as needed up to a maximum of 0.5 mg). Clonidine therapy subsequently may be tapered over a number of days. [12,22]Although there are no guidelines for the management of similar problems with epidural use, the onset of oral clonidine may be too slow to adequately manage the withdrawal signs and symptoms, and intravenous administration of clonidine may be preferable. In our case, after initial blood pressure control, continuous monitoring of the electrocardiogram, close observation of blood pressure in the intensive care unit, and continued treatment of hypertension with oral clonidine until epidural therapy was reinstituted, proved satisfactory.Further research is required to investigate both the time when the problems of acute withdrawal and rebound hypertension become apparent on discontinuing therapy after continuous epidural infusion of clonidine and the most appropriate method to manage these problems. This case prompts the recommendation for cautious discontinuation and tapering of the clonidine dose if clonidine has been chronically administered.

The active can, unipolar right ventricular (RV)single lead system has been shown to be very effective for ventricular defibrillation using an RV+→ CAN–biphasic pulsing configuration. If this same RV+→ CAN–unipolar system could perform double-duty, providing atrial as well as ventricular defibrillation, it would broaden the role of current implantable cardioverter-defibrillators (ICDs). It would provide an atrial ICD without multiple shock electrodes, simultaneously providing backup protection for inadvertent induction of ventricular fibrillation (VF) following atrial defibrillation. The purpose of this study was to determine the RV+→ CAN–atrial defibrillation threshold at the time of ICD surgery for 10 VTNFpatients using the Medtronic 7219C ICD shell with a biphasic 65% tilt, 60 μF capacitance pulse delivered one minute following induction of AF. Initial pulse strength was 100 V and was incremented in 100 V steps every minute if atrial fibrillation persisted. The atrial defibrillation threshold data with the RV+→ CAN–system were 8.3 ± 4.1 joules, 511 ± 128 volts, and 58 ± 8 ohms. Although the RV+→ CAN–lead system does not provide atrial defibrillation at energies likely to be painless (e.g., <0.2 J), the safety and simplicity of this system has advantages that must be considered when compared to more complicated two and three lead elegtrode systems. If detection algorithms for AF, using near and far field electrogram analysis prove accurate, such a simple lead system may prove clinicallyviable.

Electrocardiographic (ECG) abnormalities are common following transthoracic defibrillation. ECG ST segment changes are especially problematic following defibrillation and may indicate ischemia or shock induced cardiac dysfunction after resuscitation. Biphasic defibrillation waveforms, compared to monophasic waveforms. diminish shock-induced cardiac dysfunction in laboratory preparations. This effect has not been validated in man. Therefore. we evaluated in a prospective. blinded fashion, the effect of biphasic and monophasic transthoracic defibrillation on the ECG ST segment in 30 consecutive patients during implantable cardioverter-defibrillator surgery. In each patient two low energy truncated biphasic transthoracic defibrillation shocks were compared to the standard 200 J monophasic damped sine wave shock traditionally employed in transthoracic defibrillators. Both biphasic shocks and the damped sine wave shock have previously demonstrated equal efficacies of 97%. Fifteen second bipolar ECG signals recorded across transthoracic defibrillation electrodes were digitized prior to ventricular fibrillation induction (baseline) and immediately after each defibrillation attempt. These signals were printed. and the STsegments analyzed in a blinded fashion by two reviewers. ST segment deflection (10 mm/mV) after therapy was compared to the baseline ST segment deflection for each of the dafibrillation waveforms used. Changes in the absolute value of the ST segment level were significantly greater with the 200 J damped sine waveform than with either biphasic waveform:WaveformECG ST segment change (mm)115 J Blphasic0.73 ± 0.62130 J Biphasic081 ± 0.24200 J Damped Sine2.10 ± 1.94**p < 0.0001 p < 0.0001 Transthoracic defibrillation with biphasic waveforms results in less post-shock ECG evidence of myocardial dysfunction (injury or ischemia) compared to the standard damped sine waveform without compromising defibrillation efficacy.

A trial fibrillation (AF) has been shown to be associated with prolonged hospital stay after open heart surgery. It has been difficult to establish whether AF is causally related to prolonged hospitalization or is simply a marker for more complicated patients. We identified 110 patients in sinus rhythm off antiarrhythmic medications prior to open heart surgery who developed at least 6 hours of AF after surgery and compared them to 96 randomly selected controls who did not develop AF.