Regional intracoronary analgesia during percutaneous transluminal coronary angioplasty

Pain, 52 (1993) 93-99 0 1993 Elsevier Science

93 Publishers

B.V. All rights reserved

0304-3959/93/$06.00

PAIN 02204

Regional intracoronary

Thomas

Aversano,

analgesia during percutaneous coronary angioplasty

Gary D. Walford, Mark Midei, Paul Chew, Sidney 0. Gottlieb, Harlan Weisman, James L. Weiss and Jeffery A. Brinker

transluminal

Michael

N. Drossner,

Dir&ion of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD 21205 (USA) (Received

13 July 1992, revision

received

24 August

1992, accepted

28 August

1992)

The ischemic pain associated with balloon inflation during coronary angioplasty remains a signifiSummary cant source of procedural discomfort and sets a limit on the duration of percutaneous transluminal intravascular interventions. The present study examined whether intracoronary lidocaine reduced the pain of coronary angioplasty. Sixteen patients undergoing elective coronary angioplasty underwent three 90 set balloon inflations: the first with administration of no intracoronary agent, and the second and third with administration of one or the other of placebo or an equal volume of lidocaine (lo-16 mg). Placebo or lidocaine were randomized in administration sequence and were given just before balloon inflation. During the occlusions, pain was scored on an ordinal scale (0 = no pain; 10 = most severe pain). Lidocaine delayed the onset of pain (23 f 4 vs. 48 + 7 set, P < 0.005) and reduced its magnitude (at end-inflation: 7.8 f 1.3 vs. 3.2 f 1.3, P < 0.01). There were no significant hemodynamic or electrophysiologic effects in this group of patients, although atrioventricular conduction was delayed when lidocaine was administered into the epicardial coronary which had the atrioventricular node artery as a branch. Intracoronary analgesia with lidocaine is safe and effective in a select group of patients with normal ventricular function undergoing elective coronary angioplasty. Key words: Coronary angioplasty; Intracoronary

analgesia; Lidocaine; Ischemic pain

Introduction

Ischemic pain associated with balloon inflation during coronary angioplasty remains a significant source of procedural discomfort for many patients. The “need” for pain during coronary angioplasty is controversial. The traditional viewpoint is that pain during coronary angioplasty is important to the conduct of the procedure because it provides information about the presence of ischemia and about the viability of myocardial tissue in the territory of the angioplastied vessel. The alternative view, taken in this study, is that if a method can be developed that safely reduces or eliminates pain in those patients who experience pain during angioplasty, then this is a worthy goal. Correspondence to: Thomas Aversano, ogy, Johns Hopkins Medical Institutions, Street, Baltimore, MD 21205, USA.

M.D., Division of CardiolHalsted 500, 600 N. Wolfe

Furthermore, as progress in percutaneous transluminal vascular procedures continues, more complex manipulations may require a more prolonged duration of coronary artery occlusion. For this reason, an agent, such as lidocaine, which can produce regional anesthesia and regional cardioplegia, might be of potential utility. Recent advances in catheter technology have reduced, but not eliminated, the discomfort associated with coronary angioplasty using passive (Quigley et al. 19881 or active (Lehmann et al. 1987) blood perfusion systems or retrograde coronary sinus perfusion systems (Berland et al. 1990). Similarly, perfusion with oxygencarrying perfluorochemicals during balloon occlusion is of some benefit in reducing pain (Cowley et al. 1990). Each of these methods presumably works by providing oxygen to myocardium and limiting ischemia. Each method has significant limitations. Blood perfusion systems require catheters with large lumen size

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whose profiles may be too high to allow easy passage through severe or distal lesions. In addition, the guidewire must be removed from such systems to permit adequate flow and minimize hemolysis, potentially increasing the risk of vessel injury from catheter tip trauma or guidewire reinsertion. Perfusion with perfluorochemicals, while using standard catheters and allowing maintenance of the guidewire in place, must be prepared in advance and requires administration via a power injector. We hypothesized that intracoronary lidocaine could be used to reduce the pain associated with balloon inflation during coronary angioplasty. Since lidocaine blocks the sodium channel in neural and myocardial tissue, its potential pain-reducing effect could result from either a local anesthetic action or from a cardioplegic action, the latter reducing ischemia by reducing oxygen demand. Lidocaine can also be expected to have inhibitory effects on specialized cardiac conduction tissue. Because of the potential negative effects on cardiac conduction and contraction, this first study was undertaken in a highly selected group of patients undergoing elective coronary angioplasty. Our conclusion from these studies is that in the selected patient population studied here lidocaine was safe and effective in reducing the pain of coronary angioplasty with no significant adverse effects.

Methods Eligible patients were those undergoing elective coronary angioplasty at our institution between August 1988 and October 1989. Exclusion criteria are listed in Table 1. Patients with proximal lesions of the left anterior descending or right coronary arteries were excluded because of concern about inducing widespread left or right ventricular dysfunction if myocardium in either vascular distribution was rendered akinetic due to lidocaine’s potential cardioplegic effect. Similarly, patients with congestive heart failure were excluded. Patients with conduction system abnormalities were excluded hecause of concern that lidocaine might aggravate the abnormality. All patients signed informed consent. Routine pre-procedure medications included aspirin (at least 325 mg daily), a calcium channel antagonist, diazepam 10 mg and benedryl 50 mg orally. Ten

TABLE

1

STUDY

EXCLUSION

I. Conduction

2. 3. 4. 5. h. 7.

CRITERIA

(see text for details)

abnormality Bundle branch block Any degree atrioventricular node block Congestive heart failure Multivessel disease Left anterior descending coronary artery lesion proximal to first septal perforator and diagonal Right coronary artery lesion proximal to first major RV free wall branch Angiographically visible coronary collaterals lntraprocedural occlusion

thousand IU of sodium angioplasty procedure.

heparin

were administered

at the start of the

Pain scoring system An ordinal pain scoring system was used. Prior to the procedure. the angina history was reviewed with the patient. For prior angina1 episodes the patient was asked to grade the severity of his discomfort on a O-10 scale. with 0 heing no pain and 10 being the worst imaginahle pain. The patient was then asked to use these prior episodes as a reference from which to judge the severity of discomfort experienced during balloon inflation. He was told that not all patients have discomfort during coronary angioplasty. Lidocaine for intracoronary use was made by diluting 2 ml of 2% lidocaine (LyphoMed, Inc., Rosemont. IL) with 8 ml of lactated Ringer’s solution. This created a solution of 4 mg/ml of lidocaine. Placebo consisted of lactated Ringer’s solution. Routine guiding catheters and over-the-wire balloon angioplasty systems were used to permit injection through the distal lumen of the angioplasty catheter with the guidewire in place. Coronary angiography of the target lesion was performed after 50-200 kg of intracoronary nitroglycerin. Except for lidocaine or placebo, no additional sublingual, oral, intravenous or intracoronary drugs were administered during the course of this study. In the catheterization laboratory the following protocol was followed. The surface electrocardiogram lead thought to best represent the target vessel territory was selected from the 6 standard limb leads prior to the procedure and monitored throughout the procedure. After the dilatation system was placed across the lesion. the patient was asked if he had any discomfort before the first balloon inflation and to grade its severity. Heart rate, surface electrocardiogram and blood pressure were recorded. The balloon was then inflated for 90 set and the patient was asked to grade his discomfort on the previously described scale every IS set until balloon deflation. Immediately prior to the second balloon inflation a bolus of either placebo or lidocaine was administered through the dilatation catheter over a IS-30 set period while heart rate, blood pressure and surface electrocardiogram were recorded. The balloon was inflated a second time for 90 set and the dilatation catheter was flushed with approximately 1.5 ml of heparinized saline. Again, the patient rated his pain every IS sec. The identical procedure was followed for the third inflation, this time administering lidocaine or placebo, whichever had not heen given prior to the previous inflation. Time between intlations was always less than 60 sec. In 12 of Ih patients, lidocaine administration was double blinded: both the angioplaster who questioned the patient regarding symptoms and the patient were unaware of the sequence of drug administration. In 3 of 16 patients, only the patient was blinded to order of administration. In 12 patients a ?-dimensional echocardiogram was obtained during the procedure and in 9 of these the quality of the recording was adequate for analysis. Pre-angioplasty records were obtained in the catheterization laboratory, prior to instrumentation. Records were also obtained during each balloon inflation and then immediately following the procedure. Echocardiograms were read blindly by one of the investigators (J.L.W.). The area rendered dysfunctional during the first. control balloon inflation identified the region of interest for subsequent echocardiographic analysis. All echocardiograms were obtained in the short and long axis and four chamber views. Echocardiograms during inflation were recorded only in the short axis view. Regional function was described using a semiquantitative grading scale that has been described previously (Weiss et al. 19X1): 0, akinesis; I, hypokinesis: 2, normal wall motion; ~ 1. dyskinesis. Fractional grades were allowed. To determine if order m the inflation sequence influenced either the rate of development or magnitude of pain. 9 patients not en-

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rolled in this study but undergoing routine coronary angioplasty were asked to grade their pain on the previously described scoring system during each of three sequential 90 set balloon inflations.

Statistical analysis Since pain data were ordinal and non-continuous, non-parametric tests (Friedman 2-way ANOVA and Wilcoxon signed-rank) were used to test for significant differences. For these data, the median plus and minus the 95% confidence interval are reported. For hemodynamic and electrophysiologic data, a repeated measures analysis of variance was used in combination with a Bonferroni correction of the paired t test to detect differences between control, placebo and lidocaine inflations. For these data, the mean plus and minus the standard error of the mean are reported. A probability level less than or equal to 0.05 was considered significant.

TABLE

II

CHARACTERISTICS OF PATIENTS PROTOCOL (see text for details) Age Sex Vessel Angina Infarction Diabetes Hypertension Cholesterol Smoking Surgery

COMPLETING

STUDY

61 years (45-76) I2 males, 4 females 8 circumflex, 5 RCA, 2 LAD, 1 vein graft 11 unstable angina, 5 stable angina 6 previous infarction 3 adult onset diabetes mellitus 2 hypertension 8 cholesterol > 220 mg% IO current or former smokers 1 post-coronary artery bypass surgery

Hemodynamics

Results

Twenty-five patients were entered into the protocol and 16 completed the study. The reasons for withdrawal from the study included no pain during the procedure (4 patients), intraprocedural occlusion (1 patient), inability to cross lesion with an over-the-wire system (3 patients), and patient refusal in the catheterization laboratory (1 patient). Characteristics of patients who completed the protocol are listed in Table II. Of particular interest is that 3 patients had diabetes mellitus and 6 had previous subendocardial infarction in the target vessel territory. Most patients had either circumflex or right coronary artery angioplasty. This selection bias was due to entrance criteria that excluded patients with very proximal lesions of the left anterior descending coronary artery. An average of 14 mg (range lo-16 mg) of intracoronary lidocaine was administered to each patient.

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AORTIC PRESSURE