AUTNEU-01668; No of Pages 5 Autonomic Neuroscience: Basic and Clinical xxx (2014) xxx–xxx
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Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient Muhammad Zaman Khan Assir a, Malik M. Faheem a,⁎, Jorge A. Brenes-Salazar b, Tariq Waseem a a b
Department of Medicine, Allama Iqbal Medical College/Jinnah Hospital, Lahore, Pakistan Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States
a r t i c l e
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Article history: Received 6 February 2014 Received in revised form 13 June 2014 Accepted 18 June 2014 Available online xxxx Keywords: Paradoxical respiratory sinus arrhythmia Retro-cardiac mass Empyema Bi-ventricular outflow tract obstruction Cardio-respiratory autonomic interplay
a b s t r a c t We report a case of paradoxical respiratory sinus arrhythmia (PRSA) caused by a retro-cardiac empyema in an ambulatory patient. The case describes the dynamics and deleterious impact of PRSA on cardio-respiratory cycle, its electrocardiographic, radiologic and echocardiographic findings. Furthermore, it discusses a probable mechanism of paradoxical respiratory sinus arrhythmia in the setting of a retrocardiac mass and suggests a need for physicians to check for the changes in ventilation perfusion mismatch and rise in physiological dead space in such patients. In conclusion, to the best of our knowledge, this is the first documented report of paradoxical respiratory sinus arrhythmia in an ambulatory, non-anesthetized spontaneously breathing patient. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Respiratory sinus arrhythmia (RSA) entails a complex interrelation of the nervous, cardiac and respiratory systems. The beat-to-beat fluctuation in heart frequency with reference to the change of phase of the respiratory cycle is represented on a surface EKG as a shortening of the R–R interval during inspiration and lengthening during expiration (Yasuma and Hayano, 2004). Notable previous studies suggest an active physiological benefit of RSA for efficacious gas exchange (Yasuma and Hayano, 2004). The reciprocity between heart rate and phase of respiration may have a direct benefit in conservation of energy by decreasing heart rate during periods of no substantial alveaolar exchange, phase of expiration and the end of perfusion (Hayano et al., 1996). Also an increased heart rate along with a higher right ventricular output during period of maximal ventilation serves to improve ventilation perfusion ratio and efficacious physiological dead space in ratio to tidal volume (Giardino et al., 2003; Yasuma and Hayano, 2004). Paradoxical respiratory sinus arrhythmia (PRSA), as opposed to RSA, shows an increase in the R–R interval during inspiration (inspiratory cardio-deceleration) and a decrease during expiration (expiratory cardio-acceleration). In spontaneously breathing subjects, temporal alignment of the heart beat with inspiratory onset is greatest for the
⁎ Corresponding author at: Department of Medicine 3, Allama Iqbal Medical College/ Jinnah Hospital, Lahore, Pakistan. Tel.: +92 321 732 3864. E-mail addresses:
[email protected] (M.Z.K. Assir),
[email protected] (M.M. Faheem),
[email protected] (J.A. Brenes-Salazar),
[email protected] (T. Waseem).
heart beat preceding inspiration (Larsen et al., 1999), and afterwards it follows a synchronized, and a unidirectional closely-knit pattern. In contrast, in animal models (Tzeng et al., 2005), the use of inspiratory positive pressure ventilation (IPPV) has shown to be able to reverse this relationship. A similar deviation from the normal physiological RSA has also been reported in anesthetized patients with nonspontaneous IPPV breathing (Larsen et al., 1999). Herein we report a case of paradoxical respiratory sinus arrhythmia in an ambulatory, non-anesthetized and spontaneously breathing patient, in the setting of a large, well circumscribed and compressive retro-cardiac empyema. 2. Case A 28-year old male farmer presented to our hospital with complaints of low-grade fever, non-productive cough, 20-pound weight loss and left-sided chest pain for 2 months.Initial assessment revealed a thin gentleman who did not appear toxic. Blood pressure was 115/ 80 mm Hg, pulse 90 beats per minute and regular, respiratory rate of 16/min, and O2 saturation 94%. Chest examination demonstrated a palpable thrill in the second left intercostal space (ICS), with a harsh grade 4/6 systolic ejection murmur best heard along the left parasternal border, radiating along the left clavicle. Heart rate spiked during expiration and slowed during inspiration. On clinical examination, the intensity of murmur and PRSA increased with expiration and decreased on deep inspiration, bending forward and in the left lateral decubitus position. His trachea showed a slight right-sided shift. Left hemi-thorax displayed reduced respiratory excursion, decreased tactile fremitus, dullness to percussion and
http://dx.doi.org/10.1016/j.autneu.2014.06.006 1566-0702/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: Assir, M.Z.K., et al., Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient, Auton. Neurosci. (2014), http://dx.doi.org/10.1016/j.autneu.2014.06.006
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M.Z.K. Assir et al. / Autonomic Neuroscience: Basic and Clinical xxx (2014) xxx–xxx
decreased intensity of breath sounds from the base to the 4th intercostal space posteriorly and increased tactile vocal fremitus, dull percussion note and bronchophony from the base up to the nipple anteriorly. General systemic, neurological and abdominal examination was unremarkable. Complete blood count and comprehensive metabolic panel were within normal limits. His ESR was 104 mm/1 h. His ECG corroborated the changes of heart rate during respiratory maneuvers (Fig. 1A–C), with an increased heart rate during expiration and restful breathing(RR interval 640 ms, heart rate 94/s) followed by deceleration during deep inspiration (RR interval 920 ms, heart rate 66/s). Chest X-ray (Fig. 2A, B) showed normal sized heart and a large circumscribed homogenous opacity along the left cardiac border with clearly appreciated cardiac silhouette. Lateral X-ray projection of the chest showed a large homogenous, well-demarcated posterior mediastinal shadow. Plain computed tomogram of the chest showed a large retro-cardiac empyema. Noted in particular was the mass location in posterior relation to left atrium and pulmonary vessels (Fig. 2C). Trans-thoracic echocardiography (Fig. 3A–D) revealed normal cardiac structure and valves. A cystic mass was found to be compressing against base of the heart, causing marked right ventricular outflow tract (RVOT) obstruction that was more pronounced during expiration and supine position. This RVOT obstruction was found to be markedly reduced during deep inspiration and in left lateral position. Some degree of left ventricular outflow tract (LVOT) obstruction was also noted. Ultrasound confirmed an 11 × 9 cm cystic mass with well demarcated walls containing thick debrinous material, with no loculations or daughter cysts. Aspiration yielded 600 ml of thick, debrinous purulent
fluid; analysis showed pH of 8.0, low glucose (2 mg/dl), high protein (5.16 g/dl) and markedly raised LDH content (11,000 U/l). No AFBs could be seen. Sputum was negative for AFB. Bacterial gram stains and culture were negative. Precordial examination after fluid aspiration was normal; the harsh systolic murmur disappeared. An EKG obtained 5 min after the procedure showed disappearance of PRSA. Restoration of normal RSA was observed on EKG obtained the next day. Patient was discharged on oral Clindamycin based on the provisional diagnosis of loculated empyema. He initially reported significant improvement, but complained of recurrence of his symptoms after 6–7 weeks. Examination revealed re-accumulation of fluid. He was referred to the thoracic surgeon, who performed a left thoracotomy with de-roofing of a loculated empyema. Operative findings included a well circumscribed empyema in proximity of a posterior segment of left lower lobe. Histopathology of the specimen suggested chronic inflammatory changes with no granulomas. The patient's post-operative course was uneventful. He was discharged home on day 7 and reported no recurrence of symptoms over one year of follow-up. 3. Discussion We have reported a case of paradoxical RSA in an ambulatory, spontaneously breathing human subject. Patient had a large left sided empyema that resulted in respiratory phase related dynamic bi-ventricular outflow tract obstruction and inspiratory cardio-deceleration. Normal, physiologic RSA entails a sophisticated interplay between parasympathetic outflow from cardio-respiratory centers in CNS and phase of
Fig. 1. Pre and post-intervention electrocardiogram. A–C is pre-intervention ECG showing an RR interval of 640 ms and heart rate of 94/min during restful breathing (A), cardiodeceleration during deep inspiration with an RR interval of 920 ms and a heart rate of 66/min (B) and an RR interval of 640 ms and a heart rate of 94/min during expiration (C). D and E were obtained 5 min after fluid aspiration and show no significant change in heart rate during deep inspiration (D) and expiration (E).
Please cite this article as: Assir, M.Z.K., et al., Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient, Auton. Neurosci. (2014), http://dx.doi.org/10.1016/j.autneu.2014.06.006
M.Z.K. Assir et al. / Autonomic Neuroscience: Basic and Clinical xxx (2014) xxx–xxx
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Fig. 2. Radiologic images of chest. Frontal (A) and lateral (B) X-ray projections of chest show a large retro-cardiac homogenous, well-demarcated posterior mediastinal mass. CT scan (C) shows a large retro-cardiac empyema. Note that the mass is located in posterior relation to left atrium and pulmonary vessels. Lateral X-ray of chest (D). Image obtained after fluid aspiration show resolution of empyema and an otherwise normal mediastinal, pulmonary and cardiac shadow.
respiration. The exact mechanism of RSA is not known. The current consensus is that RSA is mediated via multiple mechanisms. These include (a) the direct interaction between central cardiorespiratory centers within the brainstem, (b) pulmonary reflex pathways, (c) respiratory gating of central arterial baroreceptor afferent input, (d) an atrial reflex, and (e) oscillations in PaCO2 and pH in arterial blood (Daly, 1997). Whether the initial stimulus is triggered by the pulmonary inflation reflex or cardiac vagal outflow from the CNS respiratory centers, still remains open to debate. However, an objective analysis of parameters of pulmonary gas exchange (Tidal Volume (Vt), Respiratory Rate(RR), exhaled CO2(E.CO2), Exhaled O2 (E.O2) and Minute Ventilation (Vm),) demonstrates an enhanced tidal volume efficacy by decreasing the relative physiological dead space during each cycle of respiration. Inspiratory tachycardia and raised right ventricular blood outflow during inspiration—the period of maximal ventilation also favors a significant fall of intrapulmonary shunting and a mild increase in the overall consumption of oxygen during each respiratory cycle leading to an improved overall alveolar ventilation–capillary perfusion ratio. This leads to a new better energy efficient cardio-respiratory synchrony (Yasuma and Hayano, 2004; Hayano et al., 1996). An artificially introduced paradoxical respiratory sinus arrhythmia in anesthetized dog demonstrated a rise in physiological dead space, intrapulmonary shunting and a decline in oxygen saturation (Hayano et al., 1996). Reversal of normal RSA in our case was likely related to the large empyema thoracis and it resolved after successful surgical evacuation. One
of the proposed mechanisms of normal RSA is that respiratory fluctuations in normal individuals can stimulate the arterial and pulmonary parenchymal baroreceptors to produce reflex changes in the circulation. During inspiration, right sided blood flow is augmented; an effective decrease in intrathoracic pressure causes decreased stimulation of the pressure receptors, which in turn causes an increase in heart rate, potentially mediated by increased sympathetic drive. During expiration, when intrathoracic pressure increases, the increased stimulation of the baroreceptors results in a decreased heart rate to maximize gas exchange as discussed previously. In our patient, we hypothesize that during inspiration, the dynamic compressive effect of the purulent collection over the pulmonary parenchyma, major cardiac vessels and cardiac walls was able to generate increased pressure on key baroreceptors, simulating the conditions of the expiratory phase, and therefore, inducing inappropriate cardio-deceleration. This cyclical variation in BP is sensed by the arterial baroreceptors, which then modulate R–R interval and lead to a reflex response via RSA. Coordinated tempering in HR in cases of artificially induced respiratory phase mediated central hemodynamic changes has further supported the hypothesis .The ‘reversed’ RSA characterized by inspiratory cardio-decelaration has also been seen in heart transplant recipients and signifies the importance of intrinsic control of heart rate, a mechanism independent of vagal innervations (Bernardi et al., 1989). The changes or rate of changes in wall stretch have been proposed to modulate the heart rate in these circumstances. This ‘mechanical hypothesis’
Please cite this article as: Assir, M.Z.K., et al., Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient, Auton. Neurosci. (2014), http://dx.doi.org/10.1016/j.autneu.2014.06.006
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Fig. 3. Trans-thoracic echocardiogram. Long axis view of the heart (A) showing a large retrocardiac mass (measuring about 11 × 10 cm) compressing the left atrium. Parasternal short axis view (B) shows turbulence across RVOT and LVOT. The outflow obstruction is more in supine position (C) and less in left lateral position (D).
is supported by the observation of the ‘reversal’ of normal RSA in anesthetized humans during IPPV (Larsen et al., 1999). Positive pressure ventilation leads to a reversal of intrathoracic pressure, and therefore the transmural forces acting on the atrial myocardium will be reversed. From the viewpoint of the baroreceptors, mechanical lung expansion with positive intrathoracic pressure may mimic an increase in wall pressure, and decrease in heart rate during inspiration could be expected. However, the exact mechanism of reversal of RSA during IPPV is largely unknown. A large empyema in our case may have acted in a way similar to PPV resulting in paradoxical RSA. Ventricular outflow tract obstruction can result from intrinsic lesions (sub-valvular, valvular and supra-valvular) or external compression. The volume effect of a large retro-cardiac mediastinal mass may cause transient compression of vascular structures, such as the left atrium and pulmonary veins, resulting in obstruction of the transmitral flow leading to a decrease in cardiac output and hemodynamic instability (Ijsselmuiden et al., 2008). There are rare case reports of acquired pulmonary stenosis due to a mediastinal mass (Babcock et al., 1962). A large empyema in our case resulted in compression of left atrium and major blood vessels of the heart. This compression was posture and respiratory phase related and explains exaggeration of ejection systolic murmur during expiration and supine position. Echocardiographic findings also showed the dynamic respiratory phase related biventricular outflow obstruction. Empyemas have a tendency to recur. Drainage is recommended for patients with large (greater than or equal to half the hemithorax), loculated effusions, thickened pleura on contrast-enhanced CT scan, positive Gram stain or culture, or pH less than 7.20 (Porcel and Light, 2009). If pleural space drainage proves ineffective too, then videoassisted thoracic surgery should be instituted for resolution of empyema. In our patient, an initial effort of ultrasound guided drainage resulted in the recurrence. Taking into consideration the thickened pleura and loculations seen at recurrence, surgical excision was opted
and resulted in successful treatment of the empyema and reversion of PRSA back to an otherwise routine RSA. Further studies are needed to understand the effect of large thoracic masses on RSA and the exact mechanisms of paradoxical RSA.
4. Conclusion Paradoxical respiratory sinus arrhythmia [PRSA] is a unique variation of the normal physiological RSA that has been only rarely described before in artificially ventilated animals and humans and occasionally in heart transplant recipients. PRSA, however, has not been reported in non-transplant, spontaneously ventilated ambulatory human subjects and its presence should alert the clinician about the possibility of a compressive intrathoracic mass obstructing, and its potential subsequent effects on ventilation–perfusion ratio and rise in physiological dead space.
Competing interest Authors declare that they have no competing or conflicting interests and declare no financial disclosure.
Acknowledgment We are thankful to Dr. Irfan Bashir (MBBS, Department of Cardiology, Jinnah Hospital, Lahore. Pakistan) for performing the echocardiography. Informed consent Written informed consent was obtained from the patient for publication of his case report.
Please cite this article as: Assir, M.Z.K., et al., Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient, Auton. Neurosci. (2014), http://dx.doi.org/10.1016/j.autneu.2014.06.006
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Please cite this article as: Assir, M.Z.K., et al., Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient, Auton. Neurosci. (2014), http://dx.doi.org/10.1016/j.autneu.2014.06.006
