pulsus alternans during halothane anesthesia in a dog

Veterinary Surgery, 22, 1, 79-84, 1993

Pulsus Alternans During Halothane Anesthesia in a Dog

JAMES E. BAILEY, DVM, WILLIAM W. MUlR 111, DVM, PHD, and ROMAN T. SKARDA, DMV, PHD

An adult dog with pyloric obstruction was anesthetized with thiamylal and halothane for surgical revision. When an ECG was attached, the QRS-complex rate was noted to differ dramatically from the peripheral pulse rate. A dorsal pedal arterial catheter was introduced, and direct arterial pressure measurements revealed a blood pressure waveform that alternated in amplitude. Blood pressure and ECG traces were recorded, and the condition was diagnosed as pulsus alternans. The inhalation anesthetic was changed to isoflurane, and the condition was resolved.

IRECT MONITORING OF arterial blood pressures and D pulse waveforms is becoming more common in veterinary practice. A number of abnormal arterial pulses can be detected, including hyperkinetic, hypokinetic, par- vus et tardus, dicrotic, anacrotic, bisferiens, paradoxic, bigeminal and alternating pulse^.^ The waveforms can provide information about the cardiovascular status of the individual. Pulsus alternans is a characteristic pattern in which the beats occur at regular intervals, but there is regular alternation of the amplitude of the arterial pressure wave. Detection of pulsus alternans may be indicative of ventricular dysfunction or failure.

Case Report

A 9-year-old, 28 kg spayed female black Labrador retriever was referred for chronic vomiting and signs of pyloric obstruction. Physical examination revealed pain on deep abdominal palpation but no other abnormalities. The heart rate was 80 beats/minute and the rhythm regular. A complete blood count and serum chemistry profile were within normal limits except for a mildly reduced nucleated cell count (5.8 X 109/L). A filling defect in the area of the pylorus could be seen on radiographs. Eval- uation of thoracic radiographs revealed no significant abnormalities except for mild cardiomegaly and mild microhepatia. Ultrasonography of the abdomen confirmed the microhepatia. Endoscopy, performed under general anesthesia, confirmed outflow obstruction and retention gastritis. Anesthesia was preceded by acepromazine se- dation (2 mg, intramuscularly), induced with thiamylal

(300 mg, intravenously [IV]), and maintained with halothane (2%) in oxygen, totaling 75 minutes for the gas- troscopy. Monitoring was limited to visualization of re- spiratory rate and mucous membrane color, palpation of peripheral pulse rate, and assessment of capillary refill time. No abnormalities were detected by these methods. Anesthesia and recovery were uneventful.

Abdominal exploration was performed the next day with the owner’s consent. Anesthesia was produced by administering 5 mg diazepam followed by 240 mg thiamylal IV. Orotracheal intubation was performed, and anesthesia was maintained using 2% halothane in oxygen. Electrocardiograph leads were attached before final prep- aration of the surgical site, and the concentration of halothane was reduced to 1.5%. The peripheral pulse rate, 1 10 beats per minute, and auscultated rhythm were not con- sistent with the ECG rate, 220 QRS complexes per minute (qpm), 45 minutes postinduction. A catheter was placed in the left dorsal pedal artery and attached to a blood pressure transducer before surgical draping. This catheter was also used for blood collection to determine arterial pH (pHa), arterial partial pressure of carbon dioxide (PaC02), and arterial partial pressure of oxygen (Pa02). The ECG and arterial blood pressure were observed si- multaneously and continuously on a multichannel physiologic monitor.* Recordings of ECG and arterial blood pressure were done independently, in series, on a single- channel physiologic recorder? within 15 seconds of each

* Type 870 monitor, Datascope Corp., Paramus, NJ. t 720 physiologic recorder, Datascope Corp., Saddle Brook, NJ.

From the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio. Reprint requests: James E. Bailey, DVM, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, The Ohio

State University, 1900 Coffey Road, Sisson Hall, Columbus, OH 43210-1089.

79

80 PULSUS ALTERNANS

Fig. 1. Lead II ECG and arterial blood pressure traces from a 9-year-old Labrador retriever with suspected pyloric obstruction. The heart rate (A) is 220 QRS complexes/min. The rhythm is sinus; however, the pulse rate (B) is 1 10 beatslmin. Arterial blood pressure is 185 mrn Hg systolic, 113 mm Hg diastolic, and 140 mm Hg mean. Note the P waves buried in the T waves, and the primary pulse wave (B, large arrow) with its associated reflected wave (B, small arrow) corresponding to every other electrical impulse. Sinus tachycardia and mechanical alternans. Paper speed 25 mm/s; calibration (.) = 1 mV.

other (Fig. 1). The heart rate was 220 beats/minute and the rhythm sinus. The P-waves appeared to be buried in the T-waves of the preceding QRS-complexes. Tall R- waves in lead I1 (calibration mark = 1 mV) were suggestive of left ventricular enlargement (R-wave > 2.5 to 3.0 mV in leads I1 and aVf).' The initial pulse rate was 110 beats per minute with systolic blood pressure measuring 185 mm Hg, diastolic measuring 1 13 mm Hg, and mean measuring 140 mm Hg. Comparison of the ECG R-R interval with the arterial pressure wave interval revealed that the second smaller wave (Fig. lB, small arrow) was associated with the taller primary wave (Fig. lB, large arrow) rather than the alternate electrical impulse. This association can also be seen in Figures 2B and 2C. The second smaller wave was considered to be a reflected wave associated with high pressures and observed in more peripheral arteries4 rather than a true alternate pressure wave. The pulse trace was characteristic of pulsus alternan~.',~

The blood gas analysis was interpreted as hypercapnia (pH 7.257, PaCOz 51.6 mm Hg, PaOz 388 mm Hg, bi- carbonate (HC03-) 23.2 mEq/L, total carbon dioxide (TCO,) 24 mEq/L, base excess -0.3 mEq/L), and inter- mittent mandatory ventilation ( 10 breaths per minute) was begun. The electromechanical abnormality described resolved within 10 minutes, only to return 4 minutes later.

In the first hour, lactated Ringer's solution was delivered at a rate of 18 mL/kg per hour. A packed cell volume (38%) and total protein (5.4 mg/dL) were measured 55 minutes postinduction. The fluid infusion rate was reduced to 10 mL/kg per hour for the duration of the procedure. Fentanyl, 0.05 mg, was administered IV (95 minutes postinduction) in an attempt to improve analgesia and slow heart rate. The electrical depolarization rate gradually slowed from 220 qpm to 170 qpm with no change in the electromechanical abnormality. Dopamine (2 pg/kg per minute, IV) was administered 120 minutes postinduction to support ventricular contractility. Arterial blood pressure increased from 164 mm Hg systolic, 105 mm Hg diastolic, and 115 mm Hg mean to 203 mm Hg systolic, 103 mm Hg diastolic, and 128 mm Hg mean. Heart rate and the electromechanical abnormality did not change during dopamine infusion; therefore, the infusion was discontinued 125 minutes postinduction.

The maintenance anesthetic was changed to isoflurane 137 minutes postinduction. The electromechanical abnormality changed within 2 minutes after initiating 2% isoflurane (Fig. 2). The sinus rate was 200 qpm with puisus alternans, but P-waves were more discernible. The ECG suggested left ventricular enlargement and right atrial enlargement (P-wave > 0.4 mV in leads 11, 111, and aVf).'

BAILEY, MUIR, AND SKARDA 81

Fig. 2. Lead II ECG and arterial blood pressure traces recorded when the anesthetic circuit was changed from 1.5% halothane to 2% isoflurane. The heart rate (A) is 200 QRS complexes/min, the rhythm is sinus and the P waves are discernible. The pulse rate (6) is 100 beats/rnin. The development of a detectable alternate beat can be seen in B (small arrow with star). This alternate beat develops into a palpable beat within 2 minutes (C, small arrow with star). Blood pressure was 174 mm Hg systolic, 114 mm Hg diastolic, and 127 mm Hg mean. Note the primary pulse wave (B and C, large arrow) with its associated reflected wave (6 and C, small arrow), corresponding to only every other electrical impulse. Paper speed 25 rnm/s; calibration ( . ) = 1 mV.

The second pulse wave gradually developed (Figs. 2B and 2C, small arrow with star) until no alternation in pulse was observed (Fig. 3). Within 5 minutes of introducing isoflurane, the pulsus alternans had resolved (Fig. 3). Halothane was reintroduced at 1.5% to verify that the electromechanical abnormality had not spontaneously resolved. The electromechanical abnormality returned within 3 minutes, and 2% isoflurane was resumed for the remainder of the procedure. Although the animal re- mained relatively tachycardiac (1 70 qpm), the pulse pressures no longer alternated. Recovery was uneventful. No follow-up cardiovascular investigations were performed.

Discussion

Pulsus alternans (mechanical alternans, ventricular alternans) refers to a condition in which the heart rate is regular, but the pulse pressure is alternately weak and

strong. Pulsus alternans is distinguished from pulsus bigeminus, in which an abnormal rhythm of a sequentially normal and then a premature or delayed depolarization gives rise to consecutively weak and strong pulse pres- ~ u r e . ~ . ~ Pulsus alternans can occur when there is myocardial compromise or, rarely, in the normal heart when heart rate is excessively f a~ t .~ ,~ , ’ Pulsus alternans has prognostic significance and is a valuable indicator of left ventricular dysfunction or fail~re.~,~,’ Total alternans, in which the weak beat is so small it is either undetectable or the aortic valve never opens, is relatively rare.234 Occasionally, pulsus alternans is accompanied by auscultatory or electrical al- tern an^.^,^-^

Since Traube’s characterization in 1872, many in- vestigators have postulated mechanisms for pulsus al- tern an^.^ Wiggers published three broad mechanistic views in 1949: “(a) all muscle fractions contract during large and small beats but to different extent, (b) all mus-

82 PULSUS ALTERNANS

Fig. 3. Lead II ECG and arterial blood pressure trace recorded 5 minutes after introduction of isoflurane 2% to the anesthetic circuit. The heart rate and pulse rate are both 170 per minute. Arterial blood pressure is 144 mm Hg systolic, 100 mm Hg diastolic, and 1 10 mm Hg mean. Paper speed 25 mm/s; calibration (. ) = 1 mV.

cle fractions contract to an equal degree but their phasic entry is slower in the case of the smaller beats, and (c) certain fractions fail to contract in alternate beats."' These views and subsequent studies focused on myo- genic and hemodynamic changes, suggesting a role for ventricular end-diastolic volumes, initial muscle fiber length, and baroreceptor reflexes in the genesis of pulsus alternam6 The role of in vivo hemodynamics waned, however, when an alternating contractile state was induced in isolated papillary muscle.' Three hypotheses proposed to explain mechanical alternans in the isolated cardiac muscle are: (a) changes in action potential duration, (b) incomplete relaxation (negative lusitropy) between contractions, and (c) altered calcium cycling by the sarcoplasmic reticulum. "J '

Recent work supports the cellular theory involving calcium and the sarcoplasmic reticulum."-' l Altered calcium cycling means altered release of calcium from the sarcoplasmic reticulum related to the rate at which calcium release processes reaccumulate calcium between myocardial contractions. A cycle is initiated in which calcium

accumulation in release sites is slowed, or not enough time is allowed for this accumulation. Less calcium is available for release in the ensuing contraction, producing a small calcium transient and a small contraction. This small contraction ends quickly, and calcium entry across the cell membrane is enhanced. There is greater accumulation of calcium in the release sites, bringing about a large calcium transient and resultant large contraction. This leaves a shorter time for restitution and inhibits calcium entry across the cell membrane such that the subsequent contraction is once again small. According to this mechanism, alternans develops from an altered rate at which calcium is recycled by the sarcoplasmic reticulum, leading to alternation in the size of the calcium transient and associated contraction.",ll

Halothane and isoflurane produce dose-dependent cardiovascular depression, seen clinically as arterial hypotension. The cardiovascular depressant effects of inhalation anesthetics have been well Halo- thane causes marked myocardial depres~ionl~- '~ that results in a 20% to 50% decrease in cardiac output at

BAILEY, MUIR, AND SKARDA 83

clinically relevant doses ( I .O to 1.5 MAC).$I4,I5 Isoflurane causes comparatively less change in cardiac output (up to 1.5 MAC), but, it has peripheral vasodilatory effects leading to hypotension.'3,14*16-'8 The myocardial depressant effects of halothane are more significant than those of isoflurane at equipotent doses, whereas the degree of hypotension produced by each is equivalent.

Halothane and isoflurane vary in their effects on conduction, isovolumetric relaxation, and calcium cycling. Halothane depresses the rate of phase 0 depolarization (Vmax) and action potential amplitude by decreasing the fast inward sodium current. 19,20 Halothane produces significant depression of conduction velocity in Purkinje fi- ben2' Isoflurane causes decreased conduction velocity in ventricular myocardium, but its effect is significantly less than that of halothane at equipotent concentrations." Relaxation of the ventricles (lusitropy), an active process, is significantly prolonged by halothane but not by isoflurane.21 The mechanism for this influence is debated, but it is probably produced by alterations in intracellular calcium cycling. Halothane, but not isoflurane, has direct effects on the function of the sarcoplasmic r e t i ~ u l u m , ~ ~ . ~ ~ causing an increased release of calcium from the sarcoplasmic reticulum whether or not the sarcoplasmic reticulum calcium pump is active, ultimately contributing to the reduction in sarcoplasmic reticulum calcium stores.24

Halothane shortens action potential duration, has negative lusitropic properties, and directly affects calcium release by the sarcoplasmic reticulum. Therefore, halothane can produce many of the effects postulated as mechanisms responsible for producing pulsus alternans. Isoflurane does not appear to share these properties. Alternation of intracellular free calcium concentration appears to underlie the mechanism of mechanical alternans. I' Halothane causes increased release of calcium from the sarcoplasmic reticulum that may lead to reduced calcium at release sites. Less calcium would then be available, producing a small calcium transient and a small contraction. This might initiate an altered state of calcium cycling. Alter- natively, the increased release of calcium from the sarcoplasmic reticulum caused by halothane may lead to elevated intracellular calcium concentrations, incomplete lusitropy, reduced end-diastolic volumes, reduced ejection volumes, and, ultimately, weak or absent pulses. Alternate incomplete relaxation might then initiate mechanical alternans. Halothane is used clinically on a regular basis and is only rarely associated with pulsus alternans; thus, it is unlikely that halothane is the sole initiator.

.$ MAC = minimum alveolar concentration of a gas anesthetic that prevents movement in 50% of animals upon application of a noxious stimulus. Represents the potency of an inhalation agent. Surgical planes of anesthesia in humans and animals are achieved at 1.2 to 1.5 times MAC.

Pulsus alternans can occur in the normal heart when heart rate is excessively One proposed mechanism for this observation involves the Frank-Starling Law of the heart that states that an increase in enddiastolic stretch of the ventricles results in increased stroke volume. When an alternating contractile state was induced in isolated papillary muscle, the theory shifted to incomplete relaxation as a cause of the a l t e rna t i~n .~~ Recent investigations in vivo seem to support a role for altered relaxation in the genesis of pulsus alternans.26 However, it is more likely that an alteration in calcium cycling is the explanation for mechanical alternans under high-frequency stimula- tion." In this case, the initial heart rate was high (220 qpm). However, the rate dropped to 170 qpm before introduction of isoflurane without eliminating pulsus alternans. Additionally, the heart rate had increased to 200 qpm as isoflurane was introduced and pulsus alternans did not return (Fig. 2). Tachycardia alone is not an explanation for the occurrence of pulsus alternans in this case.

Conclusion

A 9-year-old Labrador retriever exhibited pulsus alternans, which is frequently associated with ventricular failure. Although the existence of this phenomenon is well recognized, the mechanism for its genesis remains con- troversial. The most probable mechanism involves calcium cycling by the sarcoplasmic reticulum. Halothane alters calcium cycling by the sarcoplasmic reticulum and may contribute to the mechanism producing pulsus alternans. Changing the inhalation anesthetic from halothane to isoflurane may eliminate pulsus alternans.

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pulsus alternans during halothane anesthesia in a dog

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